Devraj Sukul, M.D., from the University of Michigan in Ann Arbor, and colleagues characterized patient and hospital factors associated with CR participation after TAVR and examined which factors explain hospital-level variation in CR participation. The analysis included clinical and administrative claims data from 3,372 patients who underwent TAVR at 24 Michigan hospitals (Jan. 1, 2016, to June 30, 2020).

The researchers found that 30.6 percent participated in CR within 90 days after discharge. Patient factors negatively associated with CR participation included older age, Medicaid insurance, atrial fibrillation/flutter, dialysis use, and slower baseline five-minute walk times. CR participation after TAVR substantially varied by hospital, ranging from 5 to 60 percent. Hospital variation was not explained by patient case mix.

“With the continued growth of TAVR for the treatment of severe aortic stenosis and concomitant improvements in postprocedural outcomes due to periprocedural care innovations, including the use of moderate sedation and same-day discharge, we highlight an important gap in the postdischarge care of this ever-growing population of patients,” the authors write.

Several authors disclosed ties to industry.

Abstract/Full Text

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Researchers conducted parallel cohort studies using data from the UK (January 1998 to January 2020) and Ontario, Canada (April 2002 to September 2020). They sought to estimate the association between different patterns of oral corticosteroid prescribing and appropriate fracture prevention care among older adults with high cumulative exposure to oral corticosteroids due to relapsing-remitting conditions, such as eczema, asthma, and chronic obstructive pulmonary disease (COPD).

The UK study used deidentified primary care data from Clinical Practice Research Datalink GOLD, and the Ontario study used population-based primary and secondary care administrative data from ICES (previously Institute for Clinical Evaluative Sciences). The researchers evaluated data on patients with eczema, asthma, or COPD aged 66 years and older who exceeded the cumulative oral corticosteroid high-risk dose threshold of 450 mg of the prednisolone-equivalent dose within the previous 6 months. The analysis included 65,195 patients from the UK study (mean age, 75 [interquartile range {IQR}, 71-81] years; 50.6% men), and 28,674 patients from the Ontario study (mean age, 73 [IQR, 69-79] years; 59.5% men).

For the primary exposure, the researchers classified patients as either having low-intensity (90 days or longer to cross the risk threshold) or high-intensity (fewer than 90 days to cross the risk threshold) oral corticosteroid prescriptions. The primary outcome was prescriptions for fracture-prevention medications, which are recommended in guidelines for this population and include bisphosphonates, bazedoxifene, burosumab, raloxifene, and teriparatide.

In the UK study, 1 year after the index date, 8.9% of patients who had reached the risk threshold of a 450-mg prednisolone-equivalent dose had received fracture prevention care medication, with 10.7% receiving high-intensity oral corticosteroid prescriptions and 4.8% receiving low-intensity prescriptions (crude rates, 134 vs 57 per 1000 person-years; crude hazard ratio [HR], 2.34; 95% CI, 2.19-2.51; adjusted HR, 2.13; 95% CI, 1.99-2.29).

In the Ontario study, at 1 year after the index date, 6.1% of patients who had reached the risk threshold of a 450-mg prednisolone-equivalent dose had received fracture prevention care, with 6.4% receiving high-intensity oral corticosteroid prescriptions and 4.4% receiving low-intensity prescriptions (crude rates, 73 vs 48 per 1000 person-years, respectively; crude HR, 1.49; 95% CI, 1.29-1.72; adjusted HR, 1.47; 95% CI, 1.27-1.70).

In analyses with disease subgroups that compared patients with high-intensity vs low-intensity oral corticosteroid prescriptions, the highest HRs for being prescribed fracture prevention care were in patients with COPD (HR, 1.58; 95% CI, 1.30-1.91) and those with asthma (HR, 1.42; 95% CI, 1.07-1.88). No substantially increased risk was observed for patients with eczema (HR, 1.15; 95% CI, 0.89-1.50).

At the end of the UK study, 5.1% of patients who had reached the risk threshold with high-intensity oral corticosteroid prescriptions had experienced a major osteoporotic fracture, vs 4.7% with low-intensity prescriptions (crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15; adjusted HR, 1.12; 95% CI, 1.03-1.21).

At the end of the Ontario study, 10.3% of patients who had reached the risk threshold with high-intensity oral corticosteroid prescriptions had experienced a major osteoporotic fracture, vs 10.1% with low-intensity prescriptions (crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96; adjusted HR, 0.91; 95% CI, 0.73-1.12).

Among several limitations, the study lacked data regarding medication adherence. The UK study only included information about whether the prescription was written, and the Ontario study only included information about whether the prescription was filled. Additionally, other unmeasured confounders such as frailty may account for the association between oral corticosteroid prescribing patterns, receiving fracture prevention care, and experiencing fractures.

The researchers concluded, “These findings suggest missed opportunities to initiate fracture prevention for older people prescribed oral corticosteroids.” They added, “Clinicians, including dermatologists, respirologists, general practitioners, and internists, should be aware of recent cumulative oral corticosteroid dose, regardless of the prescribing pattern, and initiate fracture preventive care if indicated.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Kyndaron Reinier, Ph.D., M.P.H., from the Cedars-Sinai Health System in Los Angeles, and colleagues examined predictors of SCA risk among Hispanic or Latino individuals in the United States. A total of 1,468 adult SCA cases were ascertained from the Ventura Prediction of Sudden Death in Multi-Ethnic Communities study, and control participants were selected from 3,033 Hispanic or Latino participants at the San Diego site of the Hispanic Community Health Survey/Study of Latinos (HCHS/SOL). The analyses included 295 Hispanic or Latino SCA cases and 590 frequency-matched HCHS/SOL controls.

The researchers found that in models adjusted for age, sex, and other clinical variables, chronic kidney disease, heavy drinking, stroke, atrial fibrillation, coronary artery disease, heart failure, and diabetes were associated with SCA (odds ratios [95 percent confidence intervals], 7.3 [3.8 to 14.3], 4.5 [2.3 to 9.0], 3.1 [1.2 to 8.0], 3.7 [1.7 to 7.9], 2.9 [1.5 to 5.9], 2.5 [1.2 to 5.1], and 1.5 [1.0 to 2.3], respectively).

“These findings provide information that could be useful in designing public health and medical interventions to reduce SCA risk among Hispanic or Latino individuals,” the authors write. “Because of the strong association of kidney disease with SCA in our study, early identification and management of chronic kidney disease could reduce risk of SCA among Hispanic or Latino individuals.”

Abstract/Full Text

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Anees Bahji, M.D., from the University of Calgary, and colleagues examined the association between CUD and adverse CVD outcomes. The analysis included linked administrative health databases (2012 through 2019) from 29,764 matched pairs of individuals with and without CUD.

The researchers found that approximately 2.4 percent in the CUD group and 1.5 percent in the non-CUD group experienced an incident adverse CVD event (risk ratio, 1.57). There was a significant association observed between CUD and reduced time to an incident CVD event. There was greater risk seen for incident CVD among individuals without mental health comorbidity, those who had not used health care services in the previous six months, those who were not on prescription medications, and individuals who did not have comorbid conditions.

“This evidence suggests that cannabis use may place a healthier population at increased risk of major cardiovascular events,” the authors write. “As a result, our study points to the importance of educating our patients about the potential risks associated with cannabis use and CUD.”

Abstract/Full Text

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Recalls on digoxin tablets and devices used for the inflation and deflation of aortic balloons have been the focus of cardiology-related Food and Drug Administration (FDA) MedWatch safety alerts this summer. 

FDA Drug Recalls

Lanoxin^® (digoxin)¹ 

On August 31, 2023, the FDA announced a recall for digoxin tablets, manufactured by Marlex Pharmaceuticals, for incorrect labeling: certain lots of bottles labeled as digoxin 0.125 mg contain 0.25 mg, while other lots of bottles labeled as digoxin 0.25 mg contain 0.125 mg.

• Recalled lots:
  • Digoxin 0.125 mg tablet: lot number, E3810; NDC, 10135-0747-01; expiration, 2/2025
  • Digoxin 0.25 mg tablet: lot number, E3811; NDC, 10135-0748-01; expiration, 2/2025

Digoxin 0.25 mg tablets are white to off-white, circular, beveled, uncoated tablets scored between “N” and “202” on one side and plain on the other side. Digoxin 0.125 tablets are yellow, circular, beveled, uncoated tablets scored between “N” and “201” on one side and plain on the other side.

Digoxin is used to treat mild to moderate heart failure in adults, increase the contractility of the heart muscle in children, and control the resting ventricular rate in adults with chronic atrial fibrillation. 

Patients unaware of the labeling mistake who continue to take these pills can over- or underdose on digoxin. Patients who normally take digoxin 0.125 mg, but unknowingly take digoxin 0.25 mg can experience significant drug toxicity (eg, mental disorientation, dizziness, blurred vision, memory loss, and fainting) from the unintended overdose. Patients who take digoxin 0.25 mg, but unknowingly take digoxin 0.125 mg can experience abnormal heart rate and heart failure exacerbation due to the underdose. 

There are no active reports by Marlex Pharmaceuticals of adverse events linked to this recall. 

FDA Medical Devices Recalls

Update: Cardiosave Hybrid and Rescue Intra-aortic Balloon Pumps²

The FDA has classified 6 voluntary recalls for the Cardiosave Hybrid and Rescue Intra-Aortic Balloon Pump (IABP) devices manufactured by Getinge, Maquet, and Datascope, as class I, the most serious type of recall. 

Despite concerns revolving around device shutdowns and pump stop events related to the class 1 recalls, the FDA notes that “these devices may continue to be used to provide circulatory support when necessary.”

On August 31, 2023, the FDA provided an update on the recall. 

• Reasons for recall: 
  • Electrical failures in the power source path 
  • Failures in the printed circuit board assembly in the charging path
  • Device sitting in power cart incorrectly and unable to charge the batteries
  • Device unable to auto refill the helium to inflate the balloon
  • Sensitive high priority gas change alarms halting therapy until corrected or device replaced 
  • Internal device temperature exceeds a threshold of 80° C (176°F)

IABP devices are placed in the artery of the descending aorta to electromechanically inflate and deflate intra-aortic balloons and support the left ventricle through counter pulsation.  An interruption in therapy using an IABP can result in serious patient injury or death.

Due to ongoing device failures, the FDA recommends providers consider having additional charged IABP devices available to use in the event of device failure, and to review the recent urgent medical device correction notices from Getinge, Maquet, and Datascope. 

Impella RP Flex with SmartAssist³

The FDA issued a statement on the Abiomed voluntary recall for the Impella RP Flex with SmartAssist on August 17, 2023.

• Reason for recall:
  • Inadequate labeling of precautions for treating patients with a reduced anticoagulation clotting time. 

Patients with central venous lines and cardiac cannulas with systemic anticoagulation of less than 160 to 180 seconds are most at risk for blood clot formation or deposition when Impella RP Flex with SmartAssist catheters are used. 

The Impella RP Flex with SmartAssist System catheter is placed via the internal jugular vein and can be used up to 14 days in patients who develop acute right heart failure after left ventricular assist device implantation. The device pumps into the pulmonary artery to support the right ventricle. 

There have been 12 reported injuries related to this recall, but no reports of death. Impella RP Flex with SmartAssist can still be used with the caveat that providers maintain systemic anticoagulation between 160 to 180 seconds with central venous lines and consider the risk for blood clots on indwelling lines placed before the use of Impella RP Flex with SmartAssist System. For further information, physicians can refer to the recommendations in the “best practices pathway” on Figure 5.2 of the Instructions for Use.

Drug Safety-Related Labeling Changes 

Carospir^® (spironolactone)

CMP Pharma provided an update to spironolactone use in specific populations to include a recommendation against treatment of hypertension in pediatric patients. Prior to this update, recommendation for the use of spironolactone in pediatric patients was not established.

• Use in specific populations update:
  • Not established and not recommended for the treatment of hypertension in pediatric patients due to potential risks associated with the antiandrogenic, progestogenic, and estrogenic properties of spironolactone.

The oral suspension of spironolactone is indicated for the treatment of adults with New York Heart Association class III to IV heart failure and reduced ejection fraction, hypertension, or edema caused by cirrhosis. 

The post FDA Alerts: Cardiology Roundup, Summer 2023 appeared first on The Cardiology Advisor.

Elizabeth C. Lefferts, Ph.D., from Iowa State University in Ames, and colleagues conducted a 20-week, pilot e-health lifestyle walking intervention in 21 sedentary older adults with hypertension to examine the effectiveness of increasing daily steps by 3,000 steps/day for blood pressure control. The intervention was composed of two stages: Behavioral change assistance was provided during the first active phase (weeks 1 to 10) to help reach step goals, while the second self-maintenance phase included minimal assistance (weeks 11 to 20). Nineteen of the participants completed assessments at weeks 10 and 20.

The researchers found that participants significantly increased their average step count/day from 3,899 ± 2,198 at baseline to 6,512 ± 2,633 and 5,567 ± 2,587 at 10 and 20 weeks, respectively. Both systolic and diastolic blood pressure improved after 20 weeks (137 ± 10 to 130 ± 11 mm Hg and 81 ± 6 to 77 ± 6 mm Hg, respectively). In participants with and without antihypertensive medication, the response was consistent.

“It’s exciting that a simple lifestyle intervention can be just as effective as structured exercise and some medications,” Lefferts said in a statement.

Abstract/Full Text

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Zhengyu Yang, M.P.H., M.B.B.S., from Monash University in Melbourne, Australia, and colleagues examined lag-response associations and effect modifications of exposure to floods with the risks for all-cause, cardiovascular, and respiratory mortality in a time series study involving 761 communities in 35 countries or territories with at least one flood event. The analyses included 47.6 million all-cause deaths, 11.1 million cardiovascular deaths, and 4.9 million respiratory deaths.

The researchers found that mortality risks increased and persisted for up to 60 days (50 days for cardiovascular mortality) after a flooded day over the 761 communities. For all-cause, cardiovascular, and respiratory mortality, the cumulative relative risks were 1.021 (95 percent confidence interval [CI], 1.006 to 1.036), 1.026 (95 percent CI, 1.005 to 1.047), and 1.049 (95 percent CI, 1.008 to 1.092), respectively, with variation seen in these associations across countries or territories and regions. Climate type seemed to modify the flood-mortality associations; in addition, in low-income countries and in populations with a low human development index or high proportion of older people, the associations were stronger. Up to 0.10, 0.18, and 0.41 percent of all-cause deaths, cardiovascular deaths, and respiratory deaths, respectively, were attributed to floods in communities impacted by flood.

“Policy makers and health professionals should raise awareness of the increased mortality risk after floods to improve disaster response strategies and thereby reduce the number of avoidable deaths,” the authors write.

Abstract/Full Text

Editorial

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Influenza infections have been associated with higher rates of myocardial infarction (MI) and heart failure (HF). To mitigate this associated risk, the INVESTED (Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure; ClinicalTrials.gov Identifier: NCT02787044) trial investigated whether a high-dose influenza vaccine may lower cardiopulmonary event rates during influenza season.

The INVESTED study was a randomized, double-blind, active comparator trial conducted at 157 sites in the United States and Canada between 2016 and 2019. Patients (N=5260) with high-risk cardiovascular disease (CVD) who had been hospitalized in the past 12 months for MI or in the past 24 months for HF were randomly assigned to receive a high-dose trivalent (n=1548) or standard-dose quadrivalent (n=1546) influenza vaccine. In this secondary analysis of the INVESTED trial data, the primary outcome was to evaluate whether the high-dose vaccine was associated with decreased cardiopulmonary event risk.

The high- and standard-dose recipients had mean ages of 65 (SD, 13) and 67 (SD, 13) years, 74.4% and 74.8% were men, 73.0% and 71.8% were White, they had BMI of 31.9 (SD, 8.1) and 31.7 (SD, 7.7), and they had ejection fraction of 41% (SD, 17%) and 42% (SD, 16%), respectively.

When there was a 1% increase in influenza-like illness activity in the prior week, risk for the composite outcome of cardiopulmonary hospitalizations and all-cause mortality was increased (adjusted odds ratio [aOR], 1.14; 95% CI, 1.07-1.21; P <.001). Similarly, higher influenza-like illness activity associated with elevated risk for cardiopulmonary hospitalizations (aOR, 1.13; 95% CI, 1.06-1.21; P <.001) and cardiovascular hospitalizations (aOR, 1.12; 95% CI, 1.04-1.19; P =.001). Influenza activity was not significantly related to risk for pulmonary hospitalizations (aOR, 1.18; 95% CI, 0.99-1.40; P =.06) or all-cause mortality (aOR, 1.00; 95% CI, 0.88-1.13; P >.99).

Stratified by vaccine dose, the high-dose vaccine did not associate with decreased risk for the primary composite outcome relative to the standard dose (aOR, 1.07; 95% CI, 0.95-1.20; P =.25). Similarly, no trends were observed in months with typically high influenza activity (aOR, 1.09; 95% CI, 0.97-1.24; P =.15) or during weeks with high influenza-like illness activity (aOR, 0.88; 95% CI, 0.65-1.20; P =.43).

These findings may be limited, as patient-level influenza infection data were not collected in INVESTED.

 “…influenza activity was temporally associated with an increasing risk of [cardiopulmonary] events, yet a higher-dose influenza vaccine did not significantly reduce temporal CV risk,” the study authors wrote. “Other seasonal factors may also play a role in the higher rate of CV events associated with high rates of influenza.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Researchers conducted a systematic review and meta-analysis to evaluate the dose-response association of objectively measured step count metrics with all-cause mortality and incident CVD in the general population.

A literature search was performed in PubMed and EMBASE from inception to October 2022. Eligible studies quantified daily step count with objective step-counting methods, evaluated the associations between step count and all-cause mortality or incident fatal or nonfatal CVD, had a prospective cohort design, were peer reviewed and published online in English, and included adults aged 18 years or older without CVD at baseline.

The analysis included 12 studies: 11 studies assessed the association between step count and all-cause mortality (n=111,309; 60.8% women; mean age, 62.5±5.3 years), 4 studies assessed step count and incident CVD (n=85,261), and 4 assessed step cadence and all-cause mortality (n=102,191).

Overall, 4854 (4.4%) participants died during a median follow-up of 77.8 months, and 1224 individuals (1.4%) had CVD events during 72.9 months of follow-up.

Continuous dose-response analyses demonstrated nonlinear trends (P for nonlinearity <.001) for associations between step count vs all-cause mortality and incident CVD. Decreases in risk were statistically significant for the associations with all-cause mortality and CVD at 2517 steps/day (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.84-0.999) and 2735 steps/day (aHR, 0.89; 95% CI, 0.79-0.999), respectively.

For all-cause mortality and CVD, the minimal effective step count was 479 steps/day and 735 steps/day greater than the reference category for other cutoff points. Additional step count increases were associated with reduced mortality and CVD risk until 8763 steps/day (aHR, 0.40; 95% CI, 0.38-0.43) and 7126 steps/day (aHR, 0.49; 95% CI, 0.45-0.55), after which additional decreases in mortality and incident CVD risk were not statistically significant (16,000 vs 2,000 steps/day: aHRs, 0.35 [95% CI, 0.30-0.40] and 0.42 [95% CI, 0.33-0.53], respectively).

Cadences considered intermediate (median, 63 steps/min) and high (median, 88 steps/min) were associated with a decreased mortality risk (aHRs, 0.67 [95% CI, 0.56-0.80] and 0.62 [95% CI, 0.40-0.97]) compared with a low cadence (median, 29 steps/min). Further adjustments in step count reduced these associations for intermediate cadence (aHR, 0.78; 95% CI, 0.65-0.93) and high cadence (aHR, 0.79; 95% CI, 0.67-0.94).

Limitations of the study include the evaluation of daily step counts only at baseline and the inability to quantify the effects of reverse causation and other relevant factors that influence daily step count. In addition, only 4 studies assessed the additional effects of step cadence to total step count, and the findings may not apply to chronically diseased, older, and low-income populations.

“As health benefits of daily steps were similar between men and women and step count targets were independent of wear location and device, the integration of uniform daily step targets in future physical activity guidelines may be relevant from a public health perspective, as ‘every step counts,’” wrote the study authors.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The prospective study evaluated the efficacy of a multidisciplinary women’s heart clinic for controlling cardiovascular risk factors in women with hypertensive disorders of pregnancy (HDP; gestational hypertension and preeclampsia), gestational diabetes (GD), or small-for-gestational age (SGA) infants.

The women were aged 30 to 55 years; had given birth between January 1, 2013, and December 31, 2020; and were assessed at baseline and at 6 months after attending a WHC at 1 of 3 cardiovascular sites in Melbourne, Australia.

The participants were evaluated and managed in person or via telehealth by a cardiologist, cardiovascular nurse, and dietitian. The co-primary endpoints were the proportion of women who had blood pressure (BP) of less than 140/90 mm Hg (<130/80 mm Hg if known diabetes) and total cholesterol to high-density lipoprotein cholesterol ratio (TC:HDL-C) of less than 4.5.

A total of 156 women were enrolled from May 2021 to April 2022, and follow-up was completed in October 2022. Their mean age was 41.0±4.2 years, 68.6% were White, 23.1% had HDP only, 60.3% had GD only, 13.5% had HDP and GD, and 3.2% had an SGA infant. They had an average of 3.9 years from their last delivery.

The BP target was met by 69.2% of women at baseline and 80.5% at 6 months (P =.004). The TC:HDL-C ratio target was met by 80.6% of women at baseline and 83.7% at 6 months (P =.182).

Significant improvement was observed in secondary outcomes, including decreases in mean systolic BP (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P <.001), diastolic BP (-3.1 mm Hg; 95% CI, -4.4 to -1.8; P <.001), total cholesterol (-4.6 mg/dL; 95% CI, -9.1 to -0.2; P =.042), low-density lipoprotein cholesterol (-4.2 mg/dL; 95% CI, -8.2 to -0.2; P =.042), body mass index (-0.6 kg/m²; 95% CI, -0.8 to -0.3; P <.001), and waist circumference (-2.3 cm; 95% CI, -3.3 to -1.3; P <.001).

Significant increases were observed at 6 months in consumption of healthy fats and nuts, as well as a reduction in fast food intake. Physical activity increased significantly from 84.0% to 92.9% (P =.025).

Of the 131 patients who completed the surveys, 87.8% (95% CI, 82.2%-93.4%) responded that they were motivated to change their lifestyle after attending the WHC, and 91.6% (95% CI, 86.9%-96.4%) believed that the WHC was beneficial for their heart disease risk in addition to their usual general practice visits.

Among several limitations, the study was nonrandomized with no control comparator, and follow-up was 6 months owing to the COVID-19 pandemic. Also, a large proportion of women were assessed via telehealth, a high proportion had university degrees, most identified as White, and recruitment was from a hospital-based obstetric list.

“Our findings strongly support the benefit of female-specific cardiovascular health care services in risk factor control and healthy lifestyle adherence in women with past pregnancy-related conditions,” wrote the researchers.

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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With virtually no literature describing the effects of CPB on adult patients recently immunized against COVID-19, investigators aimed to assess how COVID-19 vaccination antibody concentrations might be affected by CPB in cardiac procedures.

They conducted a prospective observational monocentric clinical trial that included 77 adult participants aged older than 18 years who received a cardiac procedure requiring CPB between September 2021 and July 2022. All participants had received at least 1 dose of a COVID-19 vaccination series (complete vaccination series) prior to receiving their procedures. A pre-CPB measurement was taken of SARS-CoV-2 spike protein-specific antibody concentrations, and the measurement was repeated 24 hours following CPB (postoperative day 1) and again at 1 month following CPB.

Among the participants (median age, 67 [IQR, 61-70] years; 27.3% women; 89.6% White), 48.1% had hypertension, 44.2% were obese, 22.1% had diabetes, 10.4% were immunosuppressed, 2.6% were on dialysis before surgery, and 27.3% were current smokers. The majority of patients (50.6%) received the Pfizer-BioNTech vaccine, and 52.6% of all patients received a booster dose before surgery. Median time from last vaccine to surgery was 157 days (IQR, 46-221), and 18.2% of patients had prior history of COVID-19 infection.

Operative mortality occurred in 4 participants.

On postoperative day 1 (POD1), the investigators found mean antibody concentration significantly decreased relative to pre-CPB levels (-2091 AU/mL; P <.001). Subsequently, at the 1-month post-CPB measurement relative to the POD1 measurement, antibody concentration increased (2465 AU/mL; P =.015). The investigators found no significant difference between pre-CPB and the 1-month post-CPB concentrations (P =.983).

Postoperatively, 2 participants developed symptomatic COVID-19 pneumonia of which 1 case resulted in mortality. COVID-19 pneumonia diagnosis required a positive polymerase chain reaction test in addition to clinical and imaging findings consistent with viral pneumonia.

Diabetes was significantly associated with an increase in antibody concentration between pre-CPB and POD1 (2107 AU/mL; P =.040). However, no patient-reported characteristics were found to be significantly associated with changes in antibody concentration after applying the Hochberg sequential procedure for multiple comparisons.

Study limitations include the underpowered sample size and the lack of additional antibody measurements between the 24-hour post CPB and the 1-month post-CPB.

“COVID-19 vaccine antibody concentrations were significantly reduced in the short-term following CPB but returned to pre-CPB levels within 1 month,” the investigators wrote. “These findings suggest the need for heightened precautions in the perioperative period for cardiac surgery patients.”

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The retrospective secondary analysis used data from the National Health and Aging Trends Study (NHATS) to evaluate the association of multidimensional SDOH measures with HRQOL, advance care planning, and treatment preferences in older patients with heart disease.

The study population had self-reported heart disease and participated in a survey round that included a module titled End of Life Plans and Care. Latent class analysis was used to identify profiles of SDOH with similar categoric distributions among 12 SDOH indicators within the NHATS Economic and Social Consequences key concept area.

The cohort included 1202 participants with a history of heart disease. Their median age was 81 years, 57% were women, 70% were White non-Hispanic, 21% were Black non-Hispanic, and 10% were classified as other.

The high/medium-risk (22%) and low-risk (78%) SDOH profiles were identified after the high- and medium-risk profiles were combined. Individuals in the high/medium-risk SDOH profile reported receiving state Medicaid more frequently vs those in the low-risk SDOH profile (79.4% vs 0.3%, P <.001).

High-risk SDOH profile individuals were more likely to be women (P <.0001) and non-Hispanic Black or other (P <.0001) and less likely to be married/living with a partner (P <.0001). Participants in the high-risk SDOH profile were more likely to have fair or poor HRQOL (P <.0001) and less likely to have advance care planning (P <.0001). High-risk SDOH profile individuals were more likely to want life-prolonging treatment if needed (P <.0001).

In the multivariable adjusted multinomial logistic regression analysis after adjustment for age, sex, marital status, and race/ethnicity, high-risk SDOH profile individuals were more likely to report good HRQOL vs very good/excellent (odds ratio [OR], 1.62; 95% CI, 1.00-2.62; P =.05), fair HRQOL vs very good/excellent HRQoL (OR, 2.43; 95% CI, 1.50-3.91; P <.001), and poor HRQOL vs very good/excellent HRQoL (OR, 4.05; 95% CI, 2.29-7.16; P <.001). Participants who were more likely (with statistical significance P <.05) to have poor HRQOL vs those with very good/excellent HRQoL were women (OR, 1.63; 95% CI, 1.02-2.61) vs men and other race (OR, 3.84; 95% CI, 1.63-9.06) vs non-Hispanic White.

No significant association was observed between SDOH and treatment preferences (P =.344) in the adjusted regression, unlike the statistically significant association (P <.01) in the univariate analyses. Women (OR, 0.72; 95% CI, 0.53-0.97; P <.03) were less likely to request life-prolonging treatments compared with men, and non-Hispanic Black (OR, 4.02; 95% CI, 2.76-5.85; P <.001) individuals and other race/ethnicity individuals (OR, 1.68; 95% CI, 1.02-2.77; P <.04) were more likely to request life-prolonging treatments vs non-Hispanic White persons.

The researchers noted that their study is subject to survey errors, and the estimates may be biased. Also, analyses of specific subgroups may be limited owing to sample-size limitations, and the survey is based on self-reported responses.

“Findings from this study highlight opportunities to promote completion of advanced care planning and ensuring the understanding of treatment preferences in individuals with HD [heart disease] as recommended practice, particularly among individuals from racial and ethnic minority groups,” wrote the study authors.

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Cole B. Hirschfeld, M.D., from Weill Cornell Medicine and New York-Presbyterian Hospital in New York City, and colleagues collected data from 669 facilities in 107 countries, including 93 facilities in 34 U.S. states to examine the impact of the pandemic on diagnostic cardiovascular procedure volumes. For each diagnostic imaging modality, participants reported volumes used at their facility for March 2019 (baseline), April 2020, and April 2021.

The researchers found that U.S. and non-U.S. facilities had similar reductions in procedure volumes in April 2020 versus baseline (−66 and −71 percent, respectively). Compared with non-U.S. facilities, U.S. facilities reported greater return to baseline in April 2021 (4 versus −6 percent), but no difference was seen when comparing U.S. facilities with non-U.S. high-income country facilities (4 versus 0 percent). There were U.S. regional differences in return to baseline between the Midwest, Northeast, South, and West (11, 9, 1, and −7 percent, respectively), but none of the factors studied significantly predicted 2021 change from prepandemic baseline.

“To address potential excess morbidity and mortality rates from cardiovascular disease in economically disadvantaged regions, a multifaceted approach is necessary, which may include strategies such as increasing telehealth infrastructure, leveraging mobile clinics, and improving health care worker training to augment recovery of cardiovascular diagnostic procedures,” the authors write.

Several authors disclosed ties to industry.

Abstract/Full Text

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Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Harold Simmons Center for Kidney Disease Research and Epidemiology at the University of California Irvine, and colleagues examined baseline RKF in 39,623 patients as well as RKF decline over 6 months in a subset of 12,169 patients. They collected data on renal urea clearance and urine volume.

A significant trend toward higher cardiovascular and non-cardiovascular mortality risk was observed across low RKF categories, starting at a baseline renal urea clearance threshold (in mL/min/1.73m²) of less than 6, the investigators reported in Kidney International Reports. In subgroup analyses, non-cardiovascular death risk significantly increased 79%, 31%, and 22% when baseline renal urea clearance was less than 1.5, 1.5 to less than 3, and 3.0 to less than 4.5, respectively, compared with 6 or higher (reference). The risk for sudden cardiac death significantly increased 63% and 27% at renal urea clearances of less than 1.5 and1.5 to less than 3, respectively. The risk for other cardiovascular deaths significantly increased 59% at a renal urea clearance less than 1.5. The investigators adjusted for case-mix, ultrafiltration rate, and multiple laboratory values.

Adjustment for ultrafiltration rate slightly attenuated the association between low renal urea clearance and high cause-specific mortality, Dr Kalantar-Zadeh’s team reported. The highest serum potassium level reached did not explain the excess mortality.

The faster RKF declined, the greater the mortality risks. In case-mix adjusted analyses, the risk for sudden cardiac death, other cardiovascular mortality, and non-cardiovascular mortality significantly increased by 14%, 24%, and 19%, respectively, when renal urea clearance declined by 3.0 compared with 1.5 over 6 months.

The investigators used urine output as another measure of RKF. Mortality risk trended higher across urine volume categories lower than 900 mL/d. Faster decline in urine volume over 6 months correlated with increased risks for sudden cardiac death and non-cardiovascular mortality, respectively.

“Future clinical trials are warranted to demonstrate the benefits of interventions to preserve RKF, such as an incremental hemodialysis and/or emerging renoprotective pharmacotherapies, and whether these interventions improve high mortality in patients undergoing hemodialysis,” Dr Kalantar-Zadeh’s team wrote.

In an accompanying editorial, John T. Daugirdas, MD, of the University of Illinois College of Medicine in Chicago,  commented that the study provides “important and useful new insights.” He noted that infection-related mortality would have been a valuable addition.

“The exact mechanism whereby RKF is associated with a lower death risk remains incompletely defined, but it is most likely related to reduced serum levels of potential uremic toxins rather than to lower ultrafiltration rates or to lower incidence rates of severe hyperkalemia,” Daugirdas wrote. “Even small amounts of RKF can substantially lower serum levels of higher molecular weight toxins such as beta-2-microglobulin5 and protein-bound uremic toxins, which are not well removed by hemodialysis. Future exploration of the role of RKF and urine volume on hard outcomes should ideally include measurement of serum levels of such uremic toxins.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Gabriela Lima de Melo Ghisi, P.T., Ph.D., from the University of Toronto, and colleagues examined sex differences in CR barriers across all world regions. The Cardiac Rehabilitation Barriers Scale was administered to CR-indicated patients globally from October 2021 to March 2023 in a cross-sectional study. A total of 2,163 participants (42.3 percent women) from 16 countries were included in the analysis.

The researchers found that women did not report significantly greater total barriers overall but did report barriers in the Americans and Western Pacific, while men reported barriers in the Eastern Mediterranean. The greatest barriers for women were reported in the Western Pacific and Southeast Asian regions, with the greatest barrier in both regions being the lack of CR awareness. Significantly greater barriers were reported by women who were versus those who were not unemployed. Not knowing about CR, not being contacted by the program, cost, and finding exercise tiring or painful were the greatest barriers reported among nonenrolled referred women. The greatest barriers to session adherence were distance, transportation, and family responsibilities among enrolled women. Strategies for mitigation were rated as very helpful.

“Patients may have legitimate barriers to attending CR, but we recommend they discuss them with health care providers, as there are proven strategies to overcome them,” coauthor Sherry L. Grace, Ph.D., from York University in Toronto, said in a statement. “Please help spread the word that CR is available in most countries of the world and saves lives!”

Abstract/Full Text

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Stefano Piaserico, M.D., Ph.D., from the University of Padova in Italy, and colleagues examined the prevalence and predictors of CMD in a cohort of 448 patients with psoriasis without clinical cardiovascular disease. The participants underwent assessment of coronary microcirculation by transthoracic Doppler echocardiography.

The researchers found that 31.5 percent of the patients had CMD. Independent associations with CMD were seen for higher Psoriasis Area and Severity Index (PASI), longer disease duration, presence of psoriatic arthritis, and hypertension. The risk for CMD was increased 5.8 and 4.6 percent in association with an increase of 1 point of PASI and one year of psoriasis duration, respectively.

“Our findings extend the observations of earlier small studies by showing a high prevalence of coronary microvascular dysfunction in asymptomatic patients with severe psoriasis and by showing that the excess microvascular dysfunction is independently associated with the severity and duration of psoriasis,” the authors write.

Abstract/Full Text (subscription or payment may be required)

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Ann Marie Navar, M.D., Ph.D., from University of Texas Southwestern Medical Center in Dallas, and colleagues examined use of statins and other lipid-lowering therapy (LLT) and changes in low-density lipoprotein cholesterol (LDL-C) among patients with ASCVD. The analysis included electronic health record-derived data from outpatient visits for 322,153 patients with ASCVD (Cerner Real-World Data from 92 U.S. health systems 2017 through 2018).

The researchers found that 76.1 percent of patients were on statins, with only 39.4 percent on high-intensity statins. Compared with women, men were more likely to receive high-intensity statins (multivariable-adjusted odds ratio [OR], 1.34). Lower odds of statin use were seen with increasing age (OR, 0.79 per five-year increase at 60 years). Compared with patients with coronary heart disease, patients with peripheral artery disease (OR, 0.40) and cerebrovascular disease (OR, 0.75) had lower odds of using high-intensity statins. Most patients (61.3 percent) at baseline had elevated LDL-C (≥70 mg/dL), including 59.8 percent of those on low/moderate-intensity statins and 76.1 percent on no statin. At one year, only 45.3 percent achieved an LDL-C <70 mg/dL. Nonstatin LLT use was low. Among patients on no statin or low/moderate-intensity statin at baseline, at one year, 14.8 and 13.4 percent, respectively, were on high-intensity statins.

“Concerted efforts are needed to address therapeutic inertia for lipid management in patients with ASCVD,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

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Sam Parnia, M.D., Ph.D., from the New York University School of Medicine in New York City, and colleagues conducted a prospective 25-site study to examine consciousness and its underlying electrocortical biomarkers during CPR. Fifty-three (9.3 percent) of 567 patients with in-hospital cardiac arrest survived; 28 (52.8 percent) completed interviews to be examined for recall of awareness and cognitive experiences.

The researchers found that 11 patients (39.3 percent) reported cardiac arrest memories/perceptions suggestive of consciousness. Four categories of experiences were detailed: emergence from coma during CPR (CPR-induced consciousness; two patients [7.1 percent]) or during the postresuscitation period (two patients [7.1 percent]); dream-like experiences (three patients [10.7 percent]); and transcendent recalled experience of death (six patients [21.4 percent]). These categories were reinforced based on experiences of 126 community cardiac arrest survivors, and an additional one was added: delusions (misattribution of medical events). Normal electroencephalogram activity, consistent with consciousness, emerged as long as 35 to 60 minutes into CPR, despite marked cerebral ischemia.

“Our work found that the brain can show signs of electrical recovery long into ongoing CPR,” Parnia said in a statement. “This is the first large study to show that these recollections and brain wave changes may be signs of universal, shared elements of so-called near-death experiences.”

Abstract/Full Text

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The Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee voted in favor (9 “yes” to 3 “no”) that the benefits of patisiran outweigh its risks for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis.

The panel’s recommendation was based on efficacy and safety data that included results from the phase 3, placebo-controlled APOLLO-B study (ClinicalTrials.gov Identifier: NCT03997383), which included 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Study participants were randomly assigned to receive patisiran 0.3mg/kg or placebo intravenously every 3 weeks for 12 months.

Findings from the study showed that treatment with patisiran met the primary endpoint resulting in a statistically significant improvement from baseline in the 6-Minute Walk Test (6-MWT) at 12 months vs placebo. Moreover, the patisiran arm achieved a statistically significant and clinically meaningful improvement in health-related quality of life (measured by the Kansas City Cardiomyopathy Questionnaire [KCCQ-OSS]) compared with the placebo arm. 

While the panel supported the approval of patisiran, they expressed concerns over the design of the APOLLO-B trial. Specifically, they noted that the effects of patisiran were small and of questionable clinical meaningfulness, and were confined to patients not on background therapy with tafamidis. Moreover, the panel recommended the use of anchor-based methods to aid in the clinical meaningfulness of 6MWT or KCCQ-OSS.

Although not bound to the committee’s recommendations, the FDA does take them into consideration when making decisions on approval. A regulatory decision is expected by October 8, 2023.

Pushkal Garg, MD, Chief Medical Officer at Alnylam, commented: “The positive outcome of today’s meeting is supported by the efficacy and safety data observed in the APOLLO-B Phase 3 study, and is another step toward bringing patients with the cardiomyopathy of ATTR amyloidosis a novel treatment option that addresses the underlying cause of disease and has the potential to meaningfully benefit patients’ functional capacity and quality of life. We look forward to continuing to work with the FDA as they complete their review of our sNDA.”

Patisiran, a transthyretin-directed small interfering RNA, is currently approved under the brand name Onpattro for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

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The AHA’s Emergency Cardiovascular Care Committee reviewed data from1861 eligible patients (79.4% men) from the Hypothermia Versus Normothermia After Out-of-Hospital Cardiac Arrest (TT2M; ClinicalTrials.gov Identifier: NCT02908308) clinical trial who spontaneously regained circulatory function following an out-of-hospital cardiac arrest. Study participants underwent random assignment to temperature management with hypothermia (target temperature, 33°C) or normothermia (target temperature, 37°C ) for 28 hours, followed by gradual rewarming to 37°C. A total of 46% of individuals managed with normothermia received active temperature management due to a core temperature that approached 37.5°C.

There was no significance difference in the primary outcome of death between individuals managed with hypothermia and participants measured with normothermia (50% vs 48%; P = .37), the report shows. Moderate to severe disability was not significantly different between the groups (55% for both), and hemodynamically compromising arrhythmias occurred more frequently among individuals managed with hypothermia compared with normothermia (24% vs 16%; P < .001). There were not significant differences between the 2 cohorts for other adverse events.

The writing group confirmed that for unresponsive patients who spontaneously regained circulation following cardiac arrest, maintaining patient temperature at 37.5°C or less is a reasonable and evidence-based strategy. However, the team was unable to determine whether hypothermia management offered any additional benefits compared with normothermia. “In the absence of a clear nonsurvivable catastrophic brain injury resulting from [out-of-hospital cardiac arrest], strictly preventing fever with continuous temperature monitoring, providing comprehensive critical care support, and deploying multimodal evidence-based strategies for neuroprognostication at a minimum of 72 hours after normothermia remain essential for unresponsive post–cardiac arrest adult patients,” according to the researchers.

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Harman Yonis, M.D., from Nordsjællands Hospital in Hillerød, Denmark, and colleagues used the EuroQol Health Questionnaire (EQ index), 12-Item Short Form Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) to assess the health-related quality of life of 4,545 adult survivors of out-of-hospital cardiac arrest included in the Danish Cardiac Arrest Registry between June 1, 2001, and Aug. 31, 2019, who were alive in October 2020. The survey was completed by 56.1 percent of survivors, with a median follow-up of 5.5 years since their event.

The researchers found that the median EQ index score was 0.9 for both the shortest follow-up (zero to one year) and longest follow-up (>15 to 20 years) groups. The mean SF-12 physical and mental health scores were 43.3 and 52.9, respectively, for all responders. All three scores were similar to those from a general Danish reference population. Based on HADS scores, a low risk for anxiety was reported by 73.0 and 89.3 percent of the shortest and longest follow-up groups, respectively; these proportions were 79.7 and 87.5 percent, respectively, for symptoms of depression. In survivors across all follow-up periods, health-related quality of life was similar.

“These findings support resource allocation and efforts targeted to increasing survival after out-of-hospital cardiac arrest,” the authors write.

Several authors disclosed ties to the biopharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

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Increasing sensitivity of the cTnI assays has led to increasing evidence that elevated cTn concentrations are associated with adverse prognosis in multiple chronic conditions outside the context of type 1 myocardial infarction. Therefore, investigators sought to evaluate the relationship between cTnI concentration and medium-term mortality regardless of clinical indication for testing for cTnI.

They conducted a prospective observational study that included 20,000 consecutive in-hospital and outpatient patients from the original CHARIOT study (ClinicalTrials.gov Identifier: NCT03047785). CHARIOT included 20,000 unselected patients (unaware they were involved in a study as per study protocol) aged 18 years or older who received a blood test for any reason at the University Hospital Southampton NHS Foundation Trust from the end of June 2017 almost to the end of August 2017. Overall, patients had a median age of 61 (IQR, 43-74) years and 52.9% were women.

Overall, supervising clinicians requested cTnI assay in 1718 patients (8.6%). The assay was performed as part of the CHARIOT study in the remaining 18,282 patients with their first blood test, and the result was not released to the patient or their clinical team.

Researchers in the CHARIOT study used the Beckman Coulter Access AccuTnI+3 assay (Beckman Coulter, Brea, California, USA) which approaches the level of sensitivity required for a high sensitivity assay but does not meet criteria as defined by the International Federation of Clinical Chemistry.

Across a median of 809 days, 14.1% of patients died (median age, 77 years). Among those who died, 55.3% were men. Among the 1718 patients for whom cTnI assay was requested, 210 died (7.4% of the 2825 who died overall). The most common causes of death were malignancy (46.3%), cardiovascular mortality (12.8%), and old age (7.8%).

Patients with cTnI concentration above the upper limit of normal (ULN; manufacturer’s recommended upper limit; n=1085) experienced significantly higher mortality (45.3% vs 12.3%; P <.001 log rank). The log₁₀ cTnI concentration was independently associated with mortality in multivariable Cox regression analysis (hazard ratio, 1.76; 95% CI, 1.65-1.88). Regression analysis included sex, age, estimated glomerular filtration rate, clinical location (inpatient, outpatient, emergency department), and whether cTnI was requested by clinical team.

Study limitations include the lack of extensive demographic and comorbidity data that may include important variables known to affect cTn concentrations. Additionally, the assay used for testing as a high sensitivity assay does not meet the accepted qualifications as a true high sensitivity assay.

“In a cohort of 20,000 patients, the majority of whom had cTn testing performed without a clinical indication, a cTn concentration was independently associated with mortality out to a median of 809 days for both cardiovascular and non-cardiovascular causes,” the investigators wrote. “Landmark analysis demonstrated that this relationship was not driven purely by short-term mortality. In addition, those patients who had cTn requested for clinical reasons had a lower hazard mortality.”

Disclosure: This research was supported by Beckman Coulter. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Nóra Sydó, M.D., Ph.D., from Semmelweis University in Budapest, Hungary, and colleagues sought to identify specific causes of death and determine the prevalence of non-CV deaths in an exercise test referral population and to assess whether exercise test parameters predict non-CV as well as CV deaths. The analysis included nonimaging exercise tests from 13,382 patients (30 to 79 years; September 1993 to December 2010) with mortality determined through January 2016 via Mayo Clinic records and the Minnesota Death Index.

Researchers found that risk for non-CV death was significant for low functional aerobic capacity (hazard ratio, 1.42), abnormal heart rate recovery (hazard ratio, 1.36), and low chronotropic index (hazard ratio, 1.49). An abnormal exercise electrocardiogram (ECG) was not a significant risk. There was a stronger association observed between all exercise test abnormalities, including a composite exercise test score (EX_SCORE), and CV death versus non-CV death, except abnormal exercise ECG.

“Patients should be encouraged to increase physical activity if these prognostic parameters are abnormal, even in the absence of substantial ECG-based CV risk,” the authors write.

Abstract/Full Text

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Researchers assessed the global burden of CVD attributed to PM pollution with use of global burden of disease (GBD) data from the Institute for Health Metrics and Evaluation from 1990 to 2019. Years of life lost (YLLs), years lived with disability (YLDs), DALYs, and mortality were investigated in 204 countries, 21 GBD regions, and in sociodemographic index (SDI) quintiles.

In 2019, about 3.5 million (95% UI, 3.1 million-4.0 million) deaths from CVD attributed to PM occurred, with men accounting for 56.5% of deaths. Regarding the ASR of death, 44 deaths (95% UI, 38.9-49.4) were reported per 100,000. Globally, 8.9 million (95% UI, 7.9 million-9.9 million) DALYs were reported, with men accounting for 40.6%. Ambient PM and household air pollution from solid fuels had 2.5 million (95% UI, 2.0 million-2.9 million) and 1.1 million (95% UI, 0.7 million-1.5 million) CVD-attributed deaths, respectively.

The total number of deaths and DALYs attributable to PM pollution increased by about one-third from 1990 to 2019. All-age deaths increased from 2.6 million (95% UI, 2.3 million-2.9 million) in 1990 to 3.5 million (95% UI, 3.1 million-4.0 million) in 2019, with a higher increase in men (43.0%; 95% UI, 25.3%-61.5%) vs women (28.2%; 95% UI, 10.7%-48.0%).

A similar increasing pattern occurred with DALYs (6.8 million; 95% UI, 6.1 million-7.5 million) in 1990 vs 2019 (8.9 million; 95% UI, 7.9 million-9.9 million). YLLs increased from 6.4 million (95% UI, 5.7 million-7.1 million) to 8.2 million (95% UI, 7.3 million-9.2 million). A 73.1% (95% UI, 62.3%-83.6%) increase in YLDs occurred and was relatively similar in both sexes. For ASRs, a similar decrease of about 35% occurred for deaths, DALYs, and YLLs, although the age-standardized YLD of CVDs attributable to PM pollution had a small decrease (12.6%; 95% UI, 7.1%-18.3%).

Mortality related to ambient PM pollution increased by 121.9% (95% UI, 82.1%-181.2%), and DALYs and YLLs more than doubled from 1990 to 2019. YLDs increased by approximately 200.9% (95% UI, 146.4%-282.1%), with similar rates in women and men.

For PM pollution, decreasing trends were observed in ASR for all measures, especially for YLLs, deaths, and DALYs. All-ages numbers had increasing trends from 1990 to 2019.

The ASR of DALYs for CVD attributed to PM pollution decreased in most countries from 1990 to 2019. The PM-attributed CVD age-standardized YLLs/YLDs ratio for both sexes was 18.1 in 1990 and decreased to 13.2 in 2019.

The low-middle SDI region had the highest burden of YLLs/YLDs ratio caused by CVD attributed to PM pollution for men and women in 1990 and 2019.

Among several limitations, data for some countries may not be representative of the entire population of the region. Also, PM composition may vary over time and location, which can affect the spatial homogeneity assumption. Furthermore, cause-specific mortalities from different countries are heterogeneous, and no causal relationship can be deduced from the findings.

“The differences in the burden of CVD attributable to PM pollution among regions and between sexes can guide policy making to reduce the negative impacts of this environmental issue,” wrote study authors.

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Jordi de Batlle, Ph.D., from the Institut de Recerca Biomèdica de Lleida in Spain, and colleagues examined the impact of CPAP treatment on major CV events in a longitudinal observational study composed of all OSA patients terminating CPAP treatment in 2011 and propensity score-matched OSA patients continuing CPAP treatment (3,638 in each group). The researchers found that after adjustment by age, sex, and key comorbidities, CPAP continuators had a lower risk for CV death than terminators during a median follow-up of 4.5 years (hazard ratio, 0.66). Similar results were seen for CV hospitalizations and for a composite of CV deaths and hospitalizations (hazard ratios, 0.82 and 0.80, respectively).

Cliona O’Donnell, M.B.B.S., from St. Vincent’s University Hospital and University College Dublin, and colleagues examined the potential effect of CPAP versus glucagon-like peptide-1 (liraglutide)-mediated weight loss (LWR) on coronary artery plaque volumes in a proof-of-concept study. Thirty patients with moderate-to-severe OSA were randomly assigned to 24 weeks of CPAP, LWR, or a combination. The researchers observed a reduction in low-density coronary artery plaque volume with CPAP and with combination therapy, but not with LWR alone. There was a correlation seen for change in total plaque volume with change in time spent below 90 percent oxygen saturation.

“Although this is a pilot study, meaning we cannot draw firm conclusions, we found improvements in some early signs of cardiovascular disease with CPAP treatment,” O’Donnell said in a statement. “This should now be further evaluated in larger studies.”

Abstract – Batlle

Abstract – O’Donnell

More Information

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A team of researchers sought to build upon earlier research that documented considerable inequities in CVD incidence or mortality among Black and White cancer survivors, focusing mainly on survivors of 18 adult-onset cancers. They also sought to quantify the effect of potential mediators such as socioeconomic and clinical factors on mortality.

The researchers identified 1,287,124 non-Hispanic White and non-Hispanic Black survivors of malignant cancers diagnosed between the ages of 20 and 64 years during the 2007-2016 time period from 17 Surveillance, Epidemiology and End Results (SEER) registries. Data from 904,995 survivors with 18 cancer types met inclusion criteria for this analysis.

Proportional hazards models were used to examine associations between race and CVD mortality. Mediation analyses were performed to pinpoint more detail about the contributions of potential mediating factors, such as socioeconomic status factors (eg, health insurance, neighborhood socioeconomic status), as well as clinical factors (such as stage, surgery, and type of treatment).

After 43 months of median follow-up, 7683 (1.0%) White survivors and 3018 (1.9%) Black survivors died of CVDs. According to the analysis, CVD mortality rates were higher among survivors who lacked insurance or Medicaid coverage.

Specifically, Black survivors were less likely to have insurance or be Medicaid beneficiaries, and they were more likely to live in socioeconomically deprived neighborhoods than White survivors (48.8% vs 11.9%). Black survivors were also less likely than White survivors to have undergone surgery (40% vs 29.9%) and to have presented with distant-stage cancer (20.9% vs 16.4%).

A substantial proportion of racial inequities in cardiovascular mortality among US cancer survivors is relative to neighborhood socioeconomic environments, measured via census tract-level composite index, and health care access, measured via insurance status. These findings highlight the intersectionality of race, residential deprivation, and barriers to health care access as underlying pathways to inequities in survivorship, explained the researchers.

“A broader structural approach that improves the neighbourhood environment and equalizes access to care may offer effective solutions towards advancing cardiovascular health equity among cancer survivors,” they concluded.

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Laury Sellem, Ph.D., from Université Sorbonne Paris Nord, and colleagues examined the associations between exposure to food additive emulsifiers (i.e., total modified starches, lecithins, xanthan gum, pectins, monoglycerides and diglycerides of fatty acids, carrageenan, and guar gum) and the risk for CVD in a prospective cohort study involving 95,442 adults without prevalent CVD. Participants included a cohort from the French NutriNet-Santé study launched in 2009.

The researchers found that 1,995 incident CVD, 1,044 coronary heart disease, and 974 cerebrovascular disease events were diagnosed during a median follow-up of 7.4 years. Higher intake of celluloses (E460 and E468) was positively associated with elevated risks for CVD (hazard ratio, 1.05 per one standard deviation) and coronary heart disease (hazard ratio, 1.07). Higher risks for CVD and coronary heart disease were seen in association with higher cellulose E460 intake (hazard ratios, 1.05 and 1.07, respectively) and with higher intake of carboxymethylcellulose (E466; (azard ratios, 1.03 and 1.04, respectively). Higher risks for all outcomes were seen in association with higher intakes of monoglycerides and diglycerides of fatty acids (E471 and E472). An increased risk for coronary heart disease was seen in association with high intake of trisodium phosphate (E339; hazard ratio, 1.06).

“Results from this large prospective cohort suggest that additive emulsifiers may be associated with an increased risk of CVD,” the authors write. “Despite the moderate magnitude of the associations, these findings may have important public health implications given that these food additives are used ubiquitously in thousands of widely consumed ultra-processed food products.”

Abstract/Full Text

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In July 2023, the American Heart Association and the American College of Cardiology released an updated guideline on the management of chronic coronary disease (CCD), in collaboration with several other professional organizations.¹ The previous recommendations on the topic were published more than a decade ago.

“This guideline provides a much-needed update to the 2012 guideline on the management of stable ischemic heart disease, so there are a lot of changes,” said one of the guideline authors, Dave L Dixon, PharmD, the Nancy L and Ronald H McFarlane Professor of Pharmacy and professor of internal medicine in the division of cardiology at Virginia Commonwealth University in Richmond, Virginia, and member of the ACC Prevention of Cardiovascular Disease Council. 

Along with recommendations on new medication classes and updated recommendations on the use of beta blockers in patients with CCD, some of the most notable additions to the new guideline include “several concepts regarding the importance of social determinants of health and how we leverage a team-based approach to care” for this patient population, according to the lead author of the guideline, Salim S. Virani, MD, PhD, professor in the sections of cardiology and cardiovascular research at Baylor College of Medicine in Houston, Texas. Available evidence on the relationship between environmental exposures in patients with CCD are also discussed. 

Selected highlights from the new guideline are summarized below.

Multidisciplinary, Team-Based Approach

Patients with CCD should be seen for follow-ups at least once per year for assessment of symptoms, functional status, adherence to medications and lifestyle interventions, and complications of disease or treatments.

Long-term CCD management should be based on a patient-centered, multidisciplinary team-based approach that emphasizes shared decision-making between clinicians and patients (class of recommendation [COR], 1; level of evidence [LOE], A). This approach has been linked to improved health outcomes, patient self-efficacy, health-related quality of life (QOL), health service utilization, and management of atherosclerotic cardiovascular disease (ASCVD) risk factors in CCD patients.

To facilitate the shared decision-making process, the care team should routinely assess for social determinants of health (SDOH), which affect all aspects of CCD management (COR, 1; LOE, B-R).

“Routine SDOH screening in patients with CCD… should encompass assessment of mental health, psychosocial stressors, health literacy, sociocultural influences (language, religious affiliation, body image), financial strain, transportation, insurance status, barriers to adherence to a heart healthy diet (food security), neighborhood or environmental exposures, and viable options for regular physical activity and social support,” as explained in the guideline. “Based on identified barriers or needs, collaborative cardiovascular care teams can provide tangible and practical community-based resources and services to patients.”

Nonpharmacologic Strategies

Guidance on nonpharmacologic approaches to CCD management includes nutritional recommendations such as adherence to a diet emphasizing fruits and vegetables, legumes, nuts, whole grains, and lean proteins (COR, 1; LOE, B-R) and minimizing intake of saturated fat, sodium, refined carbohydrates, and processed meats (COR, 2a; LOE, B-NR).

In addition, consumption of trans fat, such as those found in certain baked goods and fried foods, should be avoided due to evidence linking trans fat to increased rates of morbidity and mortality in patients with CCD and the general population (COR, 3: Harm; LOE, B-NR).

The guideline also noted the lack of evidence supporting the use of dietary supplements such as omega-3 fatty acids, calcium, and vitamin D in reducing the risk of acute CV events (COR, 3: No benefit; LOE, B-NR).

Other recommendations in the area of nonpharmacologic strategies include regular assessment and cessation interventions for tobacco use, and guidance on minimizing alcohol intake to reduce CV mortality and all-cause death. 

In terms of physical activity, an exercise regimen consisting of at least 150 minutes of moderate-intensity aerobic activities or at least 75 minutes of higher-intensity aerobic activities per week is recommended to improve functional capacity, QOL, hospital admission rates, and mortality rates in patients with CCD who do not have contraindications to such a regimen (COR, 1; LOE, A).

In the absence of contraindications, strength training exercises on 2 or more days per week are also recommended (COR, 1; LOE, B-R), as well as non-exercise activities–such as gardening and taking walking breaks at work–to reduce sedentary time (COR, 2a; LOE, B-NR).

For eligible patients, cardiac rehab may reduce CV morbidity and mortality.

Minimization of environmental exposures, including ambient air pollution (COR, 2a; LOE, B-NR) as well as extreme temperatures and wildfire smoke (COR, 2b; LOE, B-NR), is recommended to reduce the risk of CV events in patients with CCD.

Pharmacologic Therapies

SGLT2 inhibitors and GLP-1 receptor agonists. The use of an SGLT2 inhibitor or a GLP-1 receptor agonist with proven CV benefit is recommended for patients with CCD and type 2 diabetes to reduce the risk for major adverse cardiac events (MACE; COR, 1; LOE, A).

Regardless of diabetes status, the use of an SGLT2 inhibitor is recommended for patients with CCD and heart failure with a left ventricular ejection fraction (LVEF) of 40% or less, to reduce the risk of CV death and hospitalization due to heart failure and improve QOL (COR, 1; LOE, A). The use of an SGLT2 inhibitor may also reduce heart failure hospitalizations and improve QOL in those with heart failure with an LVEF of more than 40%, regardless of diabetes status (COR, 2a; LOE, B-R).

Beta blockers. The use of beta blockers is recommended for patients with CCD and an LVEF of 40% or less, regardless of myocardial infarction (MI) history, to reduce the risk for future MACE (COR, 1; LOE, A).

The use of sustained release metoprolol succinate, carvedilol, or bisoprolol with titration to target doses is recommended over other beta blockers for patients with CCD and an LVEF of less than 50% (COR, 1; LOE, A).

In those who were previously initiated on beta blocker therapy after MI and with no history of or current LVEF of 50% or less, angina, uncontrolled hypertension, or arrhythmias, the guideline states that “it may be reasonable to reassess the indication for long-term ([more than] 1 year) use of beta blocker therapy for reducing MACE” (COR, 2b; LOE, B-NR).

As a new addition to the guideline, the use of beta blockers is not recommended for reducing MACE in patients without previous MI or LVEF of 50% or less or another primary indication for beta blocker therapy (COR, 3: No benefit; LOE, B-NR).

Antiplatelet therapy and oral anticoagulants. Other key updates in the new guideline include a “shift toward shorter durations for dual antiplatelet therapy in select patients,” Dr Dixon said.

Among the evidence supporting this shift, a meta-analysis of 10 RCTs with a combined total of 31,666 patients, a shorter duration of dual antiplatelet therapy (DAPT) was associated with lower all-cause mortality compared to a longer duration of DAPT after drug-eluting stent implantation.² While rates of mortality, MI, and stent thrombosis were similar between patients treated with DAPT for 6 months or less and those treated with 1-year DAPT, rates of major bleeding were lower in patients treated with DAPT for 6 months or less compared to 1 year.²

Another large meta-analysis found that short-term DAPT (less than 6 months) followed by P2Y12 inhibitor monotherapy was associated with a reduced risk for major bleeding compared to 12-month DAPT after drug-eluting stent implantation.³

“Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is low to moderate,” according to the guideline.

Dr Virani advised that clinicians review the guideline and determine “how their current practice patterns align with these recommendations, whether they need to make any changes and what evidence supports these changes, and then utilize the excellent resources available on the ACC and AHA websites.”^4,5

He noted that the recommendations can be implemented over time and suggested that clinicians initially focus on Class 1 and Class 3 recommendations—what should be done and what should be avoided, respectively—before aiming to incorporate recommendations of a lower class, such as 2a and 2b.

In sum, “This is an essential guideline for clinicians because it encompasses aspects of multiple guidelines into one to provide a comprehensive guide on managing patients with chronic coronary disease,” Dr Dixon stated.

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Ivy T. Ton, Pharm.D., from the Western University of Health Sciences in Pomona, California, and colleagues examined LCGPs’ coverage of evidence-based CVD medications in a cross-sectional study of 19 publicly available LCGPs in March and April 2023 in the United States. The proportion of LCGPs that offered evidence-based CVD medicines for six CVDs was examined according to four metrics (breadth, choice, high-quality evidence, and titratability).

The researchers found variation in the availability of CVD medication by program, drug, and CVD condition. Some of the programs had greater breadth and choice of coverage for most CVDs, while many had more focused coverage, and limited offerings were provided by others. Angiotensin-converting enzyme inhibitors, β-blockers, thiazides, and moderate-intensity statins were offered by nearly all LCGPs, while lower availability was seen for higher-cost or lower-use generics, including antiplatelets and antiarrhythmics. For atrial fibrillation and heart failure, core pharmacotherapy coverage and choices were limited, while for hypertension and hyperlipidemia, they were widely available.

“Medication coverage in LCGPs varies widely for core, evidence-based CVD medications in all CVD conditions investigated, with differences in medication coverage options and strengths by program and condition,” the authors write. “Health care professionals should consider medication availability and LCGP-specific characteristics when recommending their use.”

One author disclosed ties to the pharmaceutical industry and one to the medical device industry.

Abstract/Full Text (subscription or payment may be required)

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Investigators pooled data from the DELIVER and DAPA-HF trials involving 11,007 patients with heart failure and preserved, mildly reduced, or reduced ejection fraction. Of these, 347 patients (3.2%) had an eGFR that declined to less than 25 mL/min/1.73m² during the trials. The time to deterioration of kidney function was similar for patients randomly assigned to dapagliflozin or placebo: 120 vs 121 days.

The risk for the primary composite outcome of cardiovascular death or worsening heart failure was 87% higher for patients with vs without renal decline to less than 25 mL/min/1.73m², further reinforcing the adverse connection between heart failure and kidney disease, Scott D. Solomon, MD, of Harvard Medical School in Boston, Massachusetts, reported on behalf of his research team. The primary outcome occurred in 18.6 vs 10.2 per 100 person-years of the groups, respectively.

Dapagliflozin treatment vs placebo, however, was significantly associated with a 73% reduced risk of the primary outcome in patients with a persistent eGFR less than 25 mL/min/1.73m², which was greater than the 21% risk reduction observed in those without deterioration of kidney function to that level. In those with an eGFR decline to less than 25 mL/min/1.73m² at least once, the absolute risk reduction was higher among patients who experienced renal deterioration was 10.7 vs 2.4 per 100 person-years, respectively.

Approximately three-quarters of patients with eGFR decline to less than 25 mL/min/1.73m² remained on dapagliflozin or placebo, as randomly assigned. Rates of serious adverse events (AEs), renal AEs, AE leading to volume depletion, renal AE, and AE leading to drug discontinuation or interruption appeared lower than placebo among patients with renal deterioration to 25 mL/min/1.73m².

The safety of dapagliflozin appeared consistent, including among patients who remained on study drug after eGFR fell to below 25ml/min/1.73m², Dr Solomon reported.

The benefit-to-risk ratio may favor continued treatment with dapagliflozin in patients with heart failure and deterioration in kidney function below eGFR 25 mL/min/1.73m², he concluded.

He cautioned that current FDA labelling does not recommend initiation of dapagliflozin in patients with an eGFR less than 25 mL/min/1.73m².

Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.

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Researchers conducted a meta-analysis of randomized controlled trials (RCTs) that assessed the effect of statins on cardiotoxicity in cancer survivors treated with anthracyclines.

A search of relevant studies was performed in PubMed and Scopus from inception until May 3, 2023. Eligible studies were RCTs and included patients with any type of cancer who received anthracyclines as a chemotherapeutic agent and used statin therapy during cancer treatment. Muscle pain and serious adverse events were safety endpoints.

The analysis included 5 studies with 808 patients (401 in the statin-treated group and 407 in the placebo group), and the median follow-up was 10 months.

Patients who received statins had a decreased incidence of cardiotoxicity vs those who received placebo (risk ratio [RR], 0.52; 95% CI, 0.33-0.83; P =.01; I² = 0%). No significant difference in hospitalization for heart failure was observed between the groups during the follow-up (RR, 0.71; 95% CI, 0.26-1.93; P =.50; I² = 0%).

The statin-treated group had a greater mean left ventricular ejection fraction (LVEF) after anthracycline therapy (mean difference [MD], 1.88; 95% CI, 0.66-3.1; P <.01; I² = 57.3%). The statin group also had a more favorable change in LVEF (∆LVEF), with a P value near significance (MD, 2.38; 95% CI, -0.03 to 4.79; P =.05; I² = 99%). Severe heterogeneity was observed in the pooled analyses for LVEF and ∆LVEF.

No significant difference in safety endpoints was found between the statin-treated group and the control group (RR, 1.31 [95% CI, 0.78-2.20; P =.3; I² = 0%], and RR, 0.79 [95% CI, 0.37-1.67; P =.53; I² = 0%], respectively).

Meta-regression analysis showed a positive association between the magnitude of the statin-related protective effect and the cumulative dosage of anthracycline therapy for ∆LVEF and final LVEF (both P <.01).

Limitations of the study include variation in the definition of cardiotoxicity among the 5 included RCTs, and the pooled analysis is underpowered to detect significant differences in clinical endpoints and safety endpoints. In addition, cancer therapy-related cardiac dysfunction (CTRCD) is not uniform, and the included RCTs differed regarding study design, tumor type, cumulative anthracycline dose, imaging method, and follow-up duration.

“Statins represent a promise in mitigating CTRCD,” the researchers wrote. “Undoubtedly, larger RCTs with adequate follow-up are required to evaluate the impact of statins alone or in combination with the most recent guided-directed medical therapy (ie, sodium-glucose cotransporter 2 inhibitors) on prognosis in patients receiving anthracyclines therapy.”

Disclosure: One of the study authors declared an affiliation with a medical device company. Please see the original reference for a full list of authors’ disclosures.

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Zahra Raisi-Estabragh, M.D., Ph.D., from Queen Mary University in London, and colleagues examined trends and disparities in obesity-related cardiovascular mortality in the U.S. population between 1999 and 2020 using the Multiple Causes of Death database. Adults with primary cardiovascular death and obesity recorded as a contributing cause of death were identified.

The researchers found a threefold increase in age-adjusted mortality rates (AAMRs) from 1999 to 2020 in an analysis of 281,135 obesity-related cardiovascular deaths, from 2.2 to 6.6 per 100,000 population. The highest AAMRs were seen for Black individuals, whereas the greatest temporal increase in AAMRs was seen for American Indian and Alaska Native individuals (+415 percent). The most common primary cause of death was ischemic heart disease, followed by hypertensive disease, which was most common among Black individuals (31 percent). Among Black individuals, women had higher AAMRs than men, while men had a greater proportion of obesity-related cardiovascular mortality cases and higher AAMRs across all other racial groups. Greater AAMRs were seen in urban versus rural settings for Black individuals, whereas the opposite was true for other races.

“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors write.

Abstract/Full Text

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Researchers assessed patients with Omicron-associated COVID-19 to determine factors related to the highest proportion of cases and to assess these factors’ prognostic value. Toward that end, the researchers analyzed data from 714 outpatients and inpatients, aged 15 to 97 years, who were infected with the Omicron variant in Chongqing, China, from December 20, 2022, to January 20, 2023. All patients had a positive nucleic acid or antigen test result and were included in 3 components of the study.

The first study component evaluated the incidence proportions of Omicron-associated pneumonia.All 714 patients infected with the Omicron variant were included and were stratified into 2 groups, either the pneumonia or the nonpneumonia group. The second study component assessed the prognosis of 186 hospitalized patients with pneumonia, and the third component analyzed laboratory indices in the 186 inpatients.

Of the 714 patients infected with the Omicron variant, 313 presented with pneumonia (43.8%). Among those with pneumonia, 84 patients were older than 80 years of age, and 180 were male. In the 401 patients without pneumonia, 117 were aged 30 to 39 years, and 240 were female.

The incidence proportions of pneumonia were greatest in patients who had cardiovascular disease (82.4% of the basic diseases of the cardiovascular system [BDCS] subset) or kidney disease (92.3% of the kidney disease subset). Patients with lung cancer (35.7% of the lung cancer subset) had a lower incidence proportion.

Older patients, men (vs women: odds ratio [OR], 1.66; 95% CI, 1.14-2.41), patients in the BDCS subset (vs healthy patients: OR, 2.01; 95% CI, 1.04-3.87), and patients with kidney disease (vs healthy patients: OR, 10.95; 95% CI, 1.19-101.14) were associated with significantly increased odds of pneumonia, according to binary logistic regression. Lung cancer was associated with marginally lower odds for pneumonia (vs healthy patients: OR, 0.38; 95% CI, 0.16-0.89).

Participants who had thrombosis frequently had a hospital stay greater than 14 days (hazard ratio [HR], 159.83; 95% CI, 6.86-3722.23), and those with a pleural effusion often remained more than 7 days (HR, 50.87; 95% CI, 3.87-668.06). Participants with basic diseases of the respiratory system had an increased mortality risk vs those without (HR, 5.88; 95% CI, 1.09-31.83).

Use of Paxlovid (HR, 0.32; 95% CI, 0.13-0.80) and immunoglobulins (HR, 0.24; 95% CI, 0.09-0.66) was associated with a significantly decreased mortality risk.

Participants with noninvasive ventilation and mechanical ventilation had an increased number of neutrophils (OR, 1.22; 95% CI, 1.12-1.34) and myoglobin (OR, 1.00; 95% CI,1.00-1.01) vs those with routine oxygen inhalation, but a lower number of lymphocytes (OR, 0.43; 95% CI, 0.22-0.87) and partial pressure of oxygen (OR, 0.98; 95% CI, 0.97-0.99).

The researchers noted that they were unable to classify the basic diseases more accurately owing to the limited number of participants.

“This study helps us to identify the incidence proportions for pneumonia to protect the susceptible population and helps us to optimize treatment programs to improve the prognosis of patients,” concluded the investigators.

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Kyndaron Reinier, Ph.D., from Cedars-Sinai Health System in Los Angeles, and colleagues estimated the strength of the association between symptoms and imminent SCA in a case-control study. The analysis included a discovery cohort of participant data from emergency medical services reports for adults (aged 18 to 85 years) with witnessed SCA between Feb. 1, 2015, and Jan. 31, 2021, and an inclusion symptom (411 participants) and control participants with similar symptoms but without SCA (1,185 participants), as well as a separate replication cohort (427 participants), all identified from two U.S. community-based studies of patients.

The researchers found that in the discovery cohort, patients with SCA were more likely to have dyspnea (41 versus 22 percent; P < 0.0001), chest pain (33 versus 25 percent; P = 0.0022), diaphoresis (12 versus 8 percent; P = 0.0059), and seizure-like activity (11 versus 7 percent; P = 0.011) compared with controls. Men with SCA were more likely to have chest pain (odds ratio [OR], 2.2), dyspnea (OR, 2.2), and diaphoresis (OR, 1.7), while in women, only dyspnea was significantly associated with SCA (OR, 2.9). In a separate replication population, findings were mostly consistent, although among men, diaphoresis was not associated with SCA.

“Harnessing warning symptoms to perform effective triage for those who need to make a 911 call could lead to early intervention and prevention of imminent death,” coauthor Sumeet Chugh, M.D., also from Cedars-Sinai Health System in Los Angeles, said in a statement.

Abstract/Full Text

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David Gaist, Ph.D., from Odense University Hospital in Denmark, and colleagues examined the risk for any stroke, ischemic stroke (IS), and recurrent ICH associated with statin use among ICH survivors. The researchers used data from the Danish Stroke Registry for patients aged 50 years and older with a first-ever ICH between January 2003 and December 2021 who survived for >30 days. Three nested case-control analyses were conducted for any stroke, IS, and recurrent ICH. Statin use on or before the date of subsequent stroke or equivalent date in matched controls was the primary exposure.

A total of 1,959 patients with any stroke were matched to 7,400 controls; 1,073 patients with IS were matched to 4,035 controls; and 984 patients with recurrent ICH were matched to 3,755 controls. The researchers found that statin exposure was associated with a lower risk for any stroke and IS (adjusted odds ratios, 0.88 and 0.79), but was not associated with the risk for recurrent ICH.

“The results of our study are good news for people taking statins who have had a bleeding stroke,” Gaist said in a statement. “While we did find a lower risk of having another stroke, it is important to note that when looking at the data more closely, that lower risk was for ischemic stroke. Still, we found no increased risk for bleeding stroke.”

Several authors disclosed ties to the biopharmaceutical industry, including Novo Nordisk, which funded the study.

Abstract/Full Text (subscription or payment may be required)

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The FARAPULSE Pulsed Field Ablation (PFA) System is a nonthermal treatment that delivers microsecond high-voltage electrical fields to selectively ablate heart tissue and potentially limit damage to tissues outside the myocardium. The randomized, single-blind, noninferiority ADVENT trial (ClinicalTrials.gov Identifier: NCT04612244) evaluated the efficacy and safety of PFA in 607 patients with paroxysmal AF. Study participants were assigned 1:1 to undergo PFA or standard-of-care ablation (either radiofrequency or cryoablation).

At 1 year, results showed that 73.3% (n=204) and 71.3% (n=194) of those who underwent PFA and thermal ablation, respectively, met the primary endpoint achieving freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, −5.2 to 9.2; posterior probability of noninferiority, >0.999).

The study also met the primary composite safety endpoint, defined as acute and chronic device- and procedure-related serious adverse events within 7 days of the procedure, with a comparably low adverse event rate of 2.1% (6 events) in the PFA arm and 1.5% (4 events) in the thermal arm. Moreover, the PFA arm demonstrated superiority to the thermal arm with significantly less post-ablation narrowing of the pulmonary veins at 3 months (0.9% vs 12%, respectively).

The ablation time was also shorter with the PFA System compared to thermal; 29.2 minutes (standard deviation [SD] 14.3 minutes) vs 50.0 minutes (SD 24.6 minutes), respectively.

Kenneth Stein, MD, senior vice president and global chief medical officer of Boston Scientific said, “The performance of the FARAPULSE PFA System in this trial is an encouraging sign of the potential utilization of the device in the US and we look forward to further studying the system for the treatment of patients with persistent AF in the ADVANTAGE AF clinical trial, which began enrollment earlier this year.”

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Previous studies show that CPAP usage can improve cardiovascular events and metabolic components in patients with OSA, but its effects on patients with concomitant CAD were not known. Researchers therefore conducted a systematic review and meta-analysis to investigate the effects of CPAP therapy on cardiovascular events in adults with moderate to severe OSA with CAD.

The reviewers searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception through December 20, 2021, for randomized controlled trials (RCTs) and observational studies comparing CPAP with usual care in patients with moderate to severe OSA and CAD. Primary outcomes were MACE, all-cause mortality, acute coronary syndrome (ACS), heart failure readmission, repeat revascularization, and arrhythmia.

A total of 14 studies of patients with OSA and CAD (average age, 54 to 71 years; 77% to 96% male) were identified for analysis. In those studies, 9 to 1346 patients received CPAP, with 22 to 1341 patients included in the control groups. Follow-up ranged from 12 to 86 months for MACE outcomes.

In the 11 studies (n=5410) reporting on the association of CPAP with MACE, CPAP treatment was associated with a risk ratio (RR) of 0.87 (95% CI, 0.78-0.98; P =.02). In the 8 studies (n=5034) reporting on the association of CPAP with all-cause and cardiovascular death, CPAP was associated with a 23% reduction in all-cause and cardiovascular death risk.

In the 6 studies (n=4591) evaluating the association between CPAP and repeat revascularization, CPAP was not associated with repeat revascularization incidence, although a subgroup analysis showed a lower risk of repeat revascularization with the usage of 4 hours CPAP or more per night, with a risk ratio of 0.56 (95% CI, 0.34-0.92; P =.02). Usage of less than 4 hours per night did not significantly reduce the risk of repeat revascularization (RR, 1.15; 95% CI, 0.92-1.40; P =.23).

Three studies (n=2445) showed that CPAP therapy was associated with systolic and diastolic blood pressure improvements. One study also showed that CPAP use of approximately 5 hours per night over 3 months was associated with improved glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA IR) in patients with OSA and CAD who were not diabetic.

With respect to limitations, the researchers noted that most studies involved nonsleepy patients with OSA, who have a better prognosis than symptomatic patients. In addition, the MACE definition differed across studies and the average follow-up time was 4 years.

Researchers concluded, “CPAP usage in patients with moderate to severe OSA and concomitant CAD was associated with a reduced risk of MACE and all-cause death. The better CPAP use exceeding 4h/night may add more benefits on MACE, repeat revascularization, and blood pressure.”

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Investigators assessed the effects of GC dose and duration of treatment on the risk for MACE among patients with RA.

A population-based retrospective cohort study was conducted, including adult patients without MACE who were diagnosed with RA from 2006 to 2015. Data were taken from a city-wide database in Hong-Kong. Patient follow-up continued until 2018. 

The main study outcome of interest was initial incidence of MACE, defined as a composite of myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, and mortality. Daily GC dose and duration of use were calculated; to account for differences in anti-inflammatory effects among the types of GCs used, doses were converted into prednisolone-equivalents.

A total of 12,233 patients with RA were included in the analysis, accounting for 105,825 patient-years of follow-up (mean follow-up duration, 8.7 years).

Of these patients, 860 (7%) developed MACE during the study period, corresponding to an incidence rate of 8.13 per 1000 person-years.  

After controlling for confounding factors, compared with receiving no GC treatment, receiving a daily prednisolone dose of at least 5 mg doubled the risk for MACE according to both erythrocyte sedimentation rate (ESR; hazard ratio [HR], 2.02; 95% CI, 1.72-2.37; P <.001) and C-reactive protein (CRP; HR ,1.87; 95% CI, 1.60-2.18; P <.001) models.

Risk for incident MACE was increased by 7% per month among patients receiving a daily prednisolone dose of at least 5 mg.

However, compared with receiving no GC treatment, receiving a daily prednisolone dose of less than 5 mg did not appear to effect MACE risk (ESR model: HR, 0.83; 95% CI, 0.60-1.14; CRP model: HR, 0.84; 95% CI, 0.62-1.15).

Study limitations included an absence of analysis of validated Disease Activity Scores and traditional CV risk factors, such as obesity, exercise, and family history. The observational nature of the study introduced the risk of channeling bias and prevented causality from being proven. Finally, GCs can affect MACE risk directly and indirectly by increasing inflammation, thereby resulting in treatment confounder feedback.

The study authors concluded, “We advocate to use systemic GC judiciously in RA, balancing the risks and benefits, and to discontinue or taper to prednisolone <5 mg daily as soon as possible.”

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To determine whether pitavastatin use prevents atherosclerotic CVD events in persons with HIV infection at low to moderate risk for CVD, researchers performed a phase 3 randomized trial. The primary outcome was major adverse cardiovascular event incidence, including cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina, among others, measured via time-to-event analysis. Patients included in the analysis were aged between 40 and 75 years and receiving stable antiretroviral therapy.

Patients (N=7769) were randomly assigned 1:1 to receive either oral pitavastatin calcium (4 mg daily) or identical placebo. The median patient age was 50 (IQR, 45-55) years, 65.2% identified as non-White, 31.1% were women, and the median screening low-density lipoprotein (LDL) cholesterol level was 108 mg/dL.

Major adverse cardiovascular event incidence was significantly lower among patients in the pitavastatin vs placebo group (4.81 vs 7.32 per 1000 person-years; hazard ratio [HR], 0.65; 95% CI, 0.48-0.90; P =.002). Overall, myocardial infarction occurred in 63 patients.

Patients in the pitavastatin vs placebo group also had significantly lower composite incidence of major adverse cardiovascular events or all-cause mortality (9.18 vs 11.63 per 1000 person-years; HR, 0.79; 95% CI, 0.65-0.96). Both mortality due to non-CVD causes and nonfatal heart failure events occurred at similar rates between the groups.

After 12 months, patients in the pitavastatin group experienced a significant reduction in median LDL cholesterol levels (from 107 to 74 mg/dL), whereas those in the placebo group experienced a marginal decrease (from 106 to 105 mg/dL).

The incidence of nonfatal severe adverse event was similar between the groups. However, patients in the pitavastatin group were more likely to develop diabetes (incidence rate ratio, 1.35; 95% CI, 1.09-1.66). Overall, pitavastatin had an acceptable safety profile.

Limitations of this study include the lack of comparison between pitavastatin and other statins or alternative LDL cholesterol-lowering strategies.

The researchers noted that “The trial was stopped early after we found that participants in the pitavastatin group had a lower incidence of major adverse cardiovascular events than those in the placebo…”

Disclosure: This research was supported by Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. Please see the original reference for a full list of disclosures.

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SARS-CoV-2, the virus that causes COVID-19 infection, damages the lungs, impairing gas exchange and depriving the body of oxygen. It also has significant cardiovascular effects, particularly in patients with preexisting cardiovascular disease (CVD). The reduced oxygen supply to the heart muscle causes inflammation, tissue damage, and arrhythmias and decreases cardiac output. Infection and inflammation further impair cardiac biochemical and fibrinogen pathways and diminish cardiac muscle integrity, leading to myocardial injury and dysfunction while also increasing the metabolic demand on many organs, including the heart.

Heart damage caused by COVID-19 without other causes is referred to as myocardial infarction type 2.¹ It is diagnosed using cardiac biomarker measurements, such as high-sensitivity cardiac troponin l (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment is based on increasing knowledge of the SARS-CoV-2 life cycle and its association with host cells and involves preventing exposure, diminishing viral proliferation, and attenuating inflammatory responses. Educating patients on available treatment options, including potential side effects and complications, is important.

Cardiovascular Complications of COVID-19

COVID-19 induces a range of negative cardiac effects, such as hypoxic respiratory failure and hypoxemia leading to hypoxia-induced myocardial injury (3%–33%), microvascular injury, venous thromboembolism (23%–27%), causing small vessel ischemia, and pulmonary embolism, which can result in acute right ventricular failure [33%–47%], and left ventricular dysfunction (10%–41%).² Other cardiac complications of COVID-19 include arrhythmias (9%–17%), (eg, atrial and ventricular fibrillation), ventricular tachyarrhythmia, myocarditis, acute myocardial injury, and venous thromboembolism.

Preexisting CVD increases the risk for these complications. In a New York City area analysis of 5700 patients hospitalized with COVID-19, the most common comorbidities were hypertension (57%), obesity (42%), and diabetes (34%).³ In a meta-analysis of 6 studies on cardiometabolic comorbidities of COVID-19 in China (N=1527;), the most common cooccurring diseases were hypertension (17.1%), cardia-cerebrovascular disease (16.4%), and diabetes (9.7%).⁴ Cardiovascular diseases — hypertension, in particular — are also associated with the highest morbidity rate (10.5%) after the development of COVID-19.³ Other comorbidities, such as chronic pulmonary disease, diabetes, and cancer, increase mortality as well.

Regardless of the presence of preexisting conditions, severe inflammation of the heart muscle can cause life-threatening myocarditis.¹ Case studies show that COVID-19 viral infection injures cardiomyocytes, leading to acute myocardial injury in 8% patients.⁴ Acute cardiac injury, as shown by elevated cTnI levels, occurs in 8% to 62% of patients hospitalized with COVID-19 and is associated with greater severity, the need for mechanical ventilation, and death.² In Wuhan, China, 5 of the first 41 patients diagnosed with COVID-19 had elevated cTnI levels (>28 pg/mL).³

Hospitalized patients with COVID-19 frequently present with acute cardiac compromise, as demonstrated by acute heart failure (3%-33%), ventricular dysfunction (right, 33%-47%; left, 10%-41%; biventricular, 3%-15%), venous thromboembolism (23%-27%), cardiogenic shock (9%-17%), arrhythmias (9%-17%), myocardial ischemia or infarction (0.9%-11%), stress cardiomyopathy (2%-5.6%), and arterial thrombosis secondary to viral-mediated coagulopathy.² In a recent report on 138 individuals hospitalized with COVID-19, arrhythmias were the second most common serious complication after acute respiratory distress syndrome, occurring in 16.7% of patients.³ Arrhythmias were present in 44% of patients who required treatment in the intensive care unit (ICU) and 7% of those who did not.³

Even in the absence of COVID-19-related lung damage and after the acute phase of illness has resolved, healthy adults can experience cardiac problems.¹ Such extrapulmonary manifestations can have long-term consequences.²

Pathophysiology

The inflammatory response to infection interferes with cardiac biochemical pathways, diminishes the integrity of cardiac muscle, and initiates abnormal clotting cascades, leading to myocardial injury and dysfunction.

SARS-CoV-2 enters host cells via a viral spike protein and angiotensin-converting enzyme 2 (ACE2) receptors.¹ ACE2 has broad expression in the heart, lungs, gastrointestinal system, and kidneys and is vital in the neurohumoral management of the cardiovascular system. It regulates the renin-angiotensin-aldosterone system, which converts angiotensin II, a vasoconstrictor and proinflammatory mediator that can damage the capillary endothelium, to angiotensin, a vasodilator. As the virus binds with and down-regulates ACE2 to infiltrate cardiac myocytes and alveolar epithelial cells, levels of angiotensin II increase, causing lung and heart injury.¹

The inflammatory response disrupts the coagulation cascade, leading to coagulopathy, disseminated intravascular coagulation (DIC), and the formation of pulmonary and cardiovascular emboli.⁵ Initially, this is evidenced by elevated levels of D-dimer and fibrinogen/fibrin degradation products and abnormalities in coagulopathy parameters. In DIC, micro-clots form in the blood and can become lodged in the lungs, arteries, other blood vessels, or extremities, leading to complications. DIC also interferes with the body’s ability to dissolve the clots and depletes platelets and clotting factors, presenting challenges in patients with bleeding problems.

Diagnosis

Cardiac injury is measured by cTnl and NT-proBNP levels. The significant relationship between these biomarkers demonstrates the close association of inflammation and myocardial stress. Elevated cTnl is a predictive marker for COVID-19, regardless of the presence of pre-existing CVD. Myocardial injury also confirms the presence of more severe systemic inflammation, further demonstrated by increased levels of other biomarkers, such as leukocyte counts, procalcitonin, creatine kinase, and myoglobin.¹

Cardiac injury is strongly associated with worse COVID-19 outcomes, as evidenced by a trend toward rising serial cTnl and NT-proBNP measurements in individuals with poor clinical outcomes vs those who recover. A recent review demonstrated a significant difference in in-hospital mortality rates for patients who had increased cTnI levels compared with those who did not (51.2% vs 4.5%, respectively).¹ Another review showed elevated cTnl levels in few survivors of uncomplicated COVID-19 (1%-20%),  many severely ill patients (46%-100%), and nearly all ICU-level patients and non-survivors.² Autopsies have revealed evidence of COVID-19-associated lymphocytic myocarditis (14%-40%), , small vessel thrombosis (19%), focal pericarditis (19%), endocardial thrombosis (14%), and right ventricular strain (19%).²

COVID-19 is responsible for progressive systemic inflammation leading to respiratory distress, sepsis, multiorgan failure, and death. Studies to date demonstrate a delay between symptom onset and myocardial damage; therefore, cardiac magnetic resonance imaging (MRI) is used to detect typical signals of acute myocardial injury. The gold standard diagnostic test, endomyocardial biopsy (EMB), identifies myocyte necrosis and mononuclear cell infiltrates with viral causes; myocarditis can also have other autoimmune-mediated causes. Biopsy studies in European patients with acute myocarditis, for example, found viral etiology in 37.8% to 77.4% of cases. Evidence describing myocardial injury in COVID-19 is scarce and based on individual case studies, highlighting the need for systematic assessment.³

Treatment Options

Treatments for COVID-19 have been developed, but the illness remains incurable.¹ Preventive and therapeutic strategies are based on the sequence of pathogenic events and increasing understanding of the SARS-CoV-2 life cycle. The overarching goal is the prevention of COVID-19 via social distancing, mask wearing, and vaccination. Recent randomized trials for the mRNA vaccine have “reported ≈95% efficacy with very low incidence of serious adverse events demonstrated across race, ethnicity, and age groups.”² However, long-term safety and durability, as well as efficiency in different populations, remain key research topics.

The next steps in treatment are inhibiting viral proliferation and impeding inflammatory responses in the body. This involves 3 subclasses of therapies: repurposed previously approved therapeutics, biologics, and small-molecule therapeutics. Prevention of virus–host cell receptor binding is a common approach to decreasing virus proliferation and involves targeting the COVID-19 spike protein or ACE2. This has been achieved using a lipopeptide to negate cell–cell fusion via the spike protein, to disrupt the spread of the virus into airway epithelial cells.² Other entry inhibitors have been repurposed from existing therapeutics, such as clemastine, trimeprazine, amiodarone, bosutinib, flupenthixol, toremifene, and azelastine.² In emergent situations, antiviral treatment with remdesivir, nirmatrelvir-ritonavir, or molnupiravir  may diminish the severity of COVID-19 complications, but these medications must be administered soon after symptom onset to be effective: 7 days for remdesivir and 5 days for nirmatrelvir-ritonavir and molnupiravir.⁶ In addition, steroids, hydroxychloroquine, i.v. immunoglobins, and active mechanical life support have been used to treat COVID-19.

Finally, organ-specific therapies are used to improve complications, such as a prothrombotic state, acute kidney injury, or stroke syndromes. Continuous heparin infusion along with additional anticoagulation therapy can inhibit microvascular injury and thrombosis, preventing small-vessel ischemia, pulmonary embolism, or stroke syndromes. Continuous renal replacement therapy filters blood and removes waste, allowing the kidneys to recover from acute injury. Extracorporeal membrane oxygenation provides cardiac and respiratory support when the lungs are unable to provide adequate gas exchange or perfusion. Even with these advanced processes and devices, outcomes are bleak for those requiring such strategies.

Education

The long-term cardiac consequences of COVID-19-associated myocardial injury include evidence of myocardial fibrosis or myocarditis in 9% to 78% of patients after acute COVID-19 infection.² Although evidence-based recommendations for post-COVID-19 follow-up evaluations are lacking, patients with cardiac involvement should receive close monitoring every 1 to 3 months, including 12-lead and Doppler echocardiograms.³ Continued monitoring and cardiac plans, including medication regimens, scheduled follow-up visits, referrals, and upcoming procedures, should be in place for any patient with cardiac complications of COVID-19. Patients should receive education about this to support adherence.

Health care providers also require ongoing education on the appropriate management of COVID-19 and its complications. For example, some physicians prescribe the antibiotic azithromycin to decrease the severity of the virus. Unfortunately, azithromycin is known to cause QT prolongation, which can lead to torsades de pointe and serious arrhythmias and increase the risk for sudden death. The use of other medications, including chloroquine and hydroxychloroquine, has been suggested; however not enough clinical data exist to support this approach. If these agents are prescribed, recipients should be monitored for QT prolongation and other adverse effects.¹

Limitations

Because of the lack of long-term research on COVID-19, current studies may be limited by inclusion bias or small cohorts. Information based on early population exposure and untested medications and methods has likely evolved. Other factors affecting study applicability include the finite nature of hospital resources, including staffing, and uneven access to testing kits and treatment, which initially limited the categories of people tested. In addition, asymptomatic individuals who have been inoculated may not seek testing or treatment. These realities contribute to the challenge of assessing the true occurrence, prevalence, and mortality of COVID-19.³

Conclusion

The mechanisms underlying COVID-19-related myocardial injury remain unclear, with questions around systemic vs local reactions and the initiation of ischemic vs inflammatory processes yet to be answered. However, clinical evidence indicates that COVID-19 negatively affects the cardiac system. Similarly, other acute viral infections are well documented to cause cardiac injury and acute myocarditis.³ Preexisting cardiac diseases such as hypertension and CVD increase the risk for COVID-19-related complications; and comorbidities such as obesity, pulmonary diseases, and diabetes increase the complexity of the illness and are associated with worse clinical outcomes.

Treatment involves prevention of the virus via vaccination and social distancing and medications to decrease the absorption and spread of COVID-19 throughout the body. Education on the effects of current medication therapies and monitoring of cardiac function after recovery are important for the long-term management of this illness.

Seva McKee, RN, BSN, practices in the cardiac catheterization laboratory and is working on her doctor of nursing practice degree at the University of North Florida in Jacksonville.

References

1. Soumya RS, Unni TG, Raghu KG. Impact of COVID-19 on the cardiovascular system: a review of available reports. Cardiovasc Drugs Ther. Published online September 14, 2020. doi: 10.1007/s10557-020-07073-y

2. Chung MK, Zidar DA, Bristow MR, et al. COVID-19 and cardiovascular disease: from bench to bedside. Circ Res. Published online April 16, 2021. doi: 10.1161/CIRCRESAHA.121.317997

3. Guzik TJ, Mohiddin SA, Dimarco A, et. al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. Published online April 30, 2020. doi: 10.1093/cvr/cvaa106

4. Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. Published online March 11, 2020. doi:10.1007/s00392-020-01626-9

5. Srivastava S, Garg I, Bansal A, Kumar B. COVID-19 infection and thrombosis. Clin Chim Acta. Published online July 24, 2020. doi: 10.1016/j.cca.2020.07.046

6. Centers for Disease Control and Prevention. COVID-19 treatments and medications. Updated May 26, 2023. Accessed July 19, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/treatments-for-severe-illness.html

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Shuxiao Shi, from Shanghai Jiao Tong University School of Medicine, and colleagues examined the prevalence of lifestyle risk factors and cardiometabolic diseases among adults aged 18 to 44 years from the National Health and Nutrition Examination Survey, 2011 to 2018. The age-standardized prevalence of lifestyle risk factors and cardiometabolic diseases was estimated overall and by demographic and social risk factors.

Data were included for 10,405 participants (median age, 30.3 years). The researchers found that the prevalence of lifestyle factors varied from 16.3 to 49.3 percent for excessive drinking and poor diet quality, respectively. Cardiometabolic disease prevalence varied from 4.3 percent for diabetes to 37.3 percent for dyslipidemia. The prevalence of having two or more lifestyle risk factors and two or more cardiometabolic diseases was 45.2 and 22.0 percent, respectively. After adjustment for social risk factors and lifestyle factors, racial and ethnic disparities in many cardiometabolic diseases persisted but were attenuated.

“Given that cardiometabolic diseases are largely preventable and lifestyle behaviors are theoretically modifiable, devising effective and targeted interventions to improve cardiometabolic health in young adults would deliver long-term health benefits,” coauthor Nannan Feng, Ph.D., also of Shanghai Jiao Tong University School of Medicine, said in a statement.

Abstract/Full Text

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Andrew O. Agbaje, M.D., M.P.H., from the University of Eastern Finland in Kuopio, and colleagues examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) with left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD) in a cohort of 1,856 adolescents (mean age, 17.7 years) followed for seven years.

The researchers found that the prevalence of LVH increased from 3.6 to 7.2 percent and that of LVDD increased from 11.1 to 16.3 percent during follow-up. In the total cohort, males, those with overweight/obesity, and normotensive individuals, high cfPWV progression was associated with worsening increased LV filling pressure E/e’ wave ratio (hiLVFP). Similarly, in the total cohort, females, and individuals with normal weight, high cfPWV progression was associated with worsening hiLVFP. In the total cohort and those with overweight/obesity and elevated blood pressure/hypertension, high cIMT progression was associated with worsening LVH. In the total cohort, there was no association for cfPWV or cIMT progression with worsening increased relative wall thickness (hiRWT). Higher baseline cfPWV was associated with future LV mass indexed for height^2.7 (LVMI^2.7), RWT, LVD function E/A wave ratio, and LV filling pressure E/e’ wave ratio in cross-lagged models. The direct associations of cumulative cfPWV with cumulative LVMI^2.7 were mediated by cumulative increased systolic blood pressure and insulin resistance (34.3 and 15.1 percent mediation, respectively).

“Experimental and clinical intervention studies are urgently needed on comprehensive approaches to treating and reversing arterial stiffness from adolescence,” Agbaje said in a statement. “At least, targeting blood pressure and insulin resistance leaves the problem half-solved.”

Abstract/Full Text

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Maleesa M. Pathirana, Ph.D., from University of Adelaide in Australia, and colleagues used three-year follow-up data from 160 women-child dyads participating in the Screening Tests to Predict Poor Outcomes of Pregnancy study. Differences in cardiometabolic health were compared between mothers who breastfed for at least six months and their children versus those who did not.

The researchers found that women who breastfed for at least six months had significantly lower maternal body mass index (BMI), systolic blood pressure (BP), diastolic BP, mean arterial pressure, central systolic BP, and central diastolic BP versus those who did not. Results were similar even after adjusting for BMI and socioeconomic index in early pregnancy, prenatal smoking, and maternal age in early pregnancy. Significantly lower maternal systolic and diastolic BPs, serum insulin and triglycerides, and higher high-density lipoprotein cholesterol were seen among women who had one or more pregnancy complications during the index pregnancy (i.e., preeclampsia, gestational hypertension, delivery of a small-for-gestational-age infant, delivery of a preterm infant, and/or gestational diabetes mellitus) and who breastfed for at least six months. Anthropometric and hemodynamic variables were similar among children regardless of breastfeeding duration.

“It may be beneficial to provide interventions that support breastfeeding in disadvantaged women with pregnancy complications to reduce their risk of cardiovascular disease,” the authors write.

Abstract/Full Text

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Théo Pezel, M.D., from Université Paris Cité, and colleagues examined the prevalence of recreational drug use and its association with in-hospital major adverse events (MAEs) in patients admitted to the ICCU. All patients admitted to the ICCU in 39 French centers from April 7 to 22, 2021, underwent systematic screening for recreational drugs performed by prospective urinary testing.

The researchers found that 11 percent of 1,499 consecutive patients had a positive test for recreational drugs (cannabis, 9.1 percent; opioids, 2.1 percent; cocaine, 1.7 percent; amphetamines, 0.7 percent; 3,4-methylened ioxymethamphetamine [MDMA], 0.6 percent). Recreational drug use was declared by 57 percent of these patients. Those using recreational drugs had a higher rate of MAEs (13 versus 3 percent). After adjustment for comorbidities, recreational drugs were associated with a higher rate of in-hospital MAEs (odds ratio, 8.84). Cannabis, cocaine, and MDMA, assessed separately, were independently associated with in-hospital MAEs, after adjustment. Twenty-eight percent of positive patients had multiple drug detection, which was associated with even higher incidence of MAEs (odds ratio, 12.7).

“The detection of recreational drug use was a strong and robust independent predictor of MAE,” the authors write. “Multiple recreational drugs users had the worst in-hospital prognosis, with a doubling of MAE risk, compared with single-drug users.”

Abstract/Full Text

Editorial

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Menopause often includes a range of unpleasant symptoms, like hot flashes, night sweats, sleep disturbances, and mood changes. Unfortunately, the change of life also brings a higher risk for heart disease. Estrogen therapy mitigates these effects, but not for every patient. In addition, some forms of estrogen come with more significant risks than others.

The Women’s Health Initiative (WHI) shed light on the pitfalls of aggressive menopause hormone therapy, particularly in older women with cardiovascular histories.¹ As a result, today’s physicians have more considerations to weigh before selecting the best treatment options.

Quantifying the Risks

Health care providers can reduce potential upticks in cardiovascular events by choosing the route of estrogen administration carefully. Although preferred by many patients, oral estrogen is associated with a 19% higher risk for hypertension than vaginal creams or suppositories and a 14% higher hypertension risk than transdermal estrogen creams.² Fortunately, these different forms of estrogen are equally effective, so providers can educate patients on choosing their safest option.¹

Cerebral stroke rates do not increase for women receiving menopause hormone therapy who are aged younger than 60 years or within 10 years of starting menopause.³ However, menopause hormone therapy does raise the risk for ischemic stroke, but not hemorrhagic stroke, in women aged over 60 years. As a result, experts advise transdermal administration and lower-dose menopause hormone therapy to mitigate this risk while still supplying patients with the benefits of estrogen therapy.

After age 60 years, the risk for venous thromboembolism increases for all women. Additional risk factors include BMI, history of thromboembolism, and genetic factors, particularly the factor V Leiden mutation.³ Menopause hormone therapy almost doubles the risk for venous thromboembolism in women aged 60 years and older, particularly during the first year of treatment. By increasing thrombin activity and downregulating plasmin activity, oral estrogen increases risk for thromboembolism for at-risk groups. Adding progesterone to estrogen therapy increases this risk more than estrogen alone.

There’s a marked discrepancy between the risk for coronary artery disease (CAD) and menopause hormone therapy for women of different age groups. While some studies suggest a preventative effect in those under the age of 60 (28% reduction), studies that included older patients showed no primary prevention and a 50% to 80% higher risk for CAD during the first year of treatment, which declined as treatment continued. Researchers concluded that menopause hormone therapy initiated within 10 years of menopause is associated with a 48% reduction in cardiovascular mortality.³ However, the reasons for initiating menopause hormone therapy should not be solely for CAD prevention.³

Studies on estrogen-only therapy show that conjugated equine estrogen promotes hypertension more than estradiol. In addition, longer durations and higher doses of estrogen increase hypertension risk.⁴ One of the most common complaints of menopause is vasomotor symptoms, including hot flashes. Low-dose menopause hormone therapy is similarly effective for this symptom as standard doses.³ An individualized and conservative approach to treatment during and after menopause should guide decisions about the proper duration, dosage, and administration of menopause hormone therapy. It all starts with appropriate screening.

Screening for the Right Menopause Treatments

When initiated during the first 10 years of menopause, menopause hormone therapy helps prevent diabetes, metabolic syndrome, and cardiovascular disease. It can also lower the risk for colon cancer and, potentially, Alzheimer’s.¹ However, certain patients may be risking cardiovascular events by using menopause hormone therapy. Therefore, some absolute contraindications to menopause hormone therapy related to the cardiovascular system include congenital coagulation disorders, acute myocardial infarction, acute stroke, and unstable hypertension.¹

Physicians must conduct a thorough examination before prescribing menopause hormone therapy. Aside from assessing the indications and contraindications, prescribers should evaluate alcohol and smoking history, along with significant family history (particularly for cardiovascular disease and venous thromboembolism).³ Lipid tests, blood pressure, height and weight, thyroid function tests, and blood glucose screenings can also help identify cardiovascular risk factors. Additionally, customized tests may be necessary for individual risk factors.

Follow-ups every 1 to 2 years can help catch any concerning changes and allow for adjustments. Instructing patients to monitor their health between appointments (such as by taking periodic blood pressure readings at home) can be a proactive and collaborative approach to managing risk.

According to a 2022 article in Global Health Journal, “To reduce the risk of venous thromboembolism and stroke, transdermal estradiol (gels, patches,) should be used, in free combination with progesterone or dydrogesterone as ‘golden standard’ in patients with increased risk.”¹ Because the liver doesn’t process transdermal estrogen, it is more suitable for women with diabetes, high blood pressure, and other cardiovascular risk factors.³ Ultimately, hormone therapy should be prescribed with adjunct therapies and lifestyle changes based on the severity and frequency of menopause symptoms to improve quality of life and minimize potential harm.³

Alternative Therapies to Consider

The ideal candidate for menopause hormone therapy is aged 60 years or younger, are 10 years or less from the onset of menopause, and otherwise healthy with no history of cardiovascular disease.⁵ This period is frequently called the “window of opportunity” for menopause hormone therapy. However, as any practicing physician knows, ideal patients are rare. Postmenopausal women need solutions to manage their symptoms, even if their age or medical history makes menopause hormone therapy too risky. As women live longer and obesity rates continue rising, heart health becomes an even more critical consideration for postmenopausal patients.⁶

Aside from recommending a non-oral route for estrogen administration, physicians can mitigate cardiovascular risks by exploring different options, including non-hormone-derived drugs and herbal supplements.¹ For instance, vasomotor menopause symptoms may improve with off-label use of citalopram, clonidine, desvenlafaxine, escitalopram, gabapentin, opipramol, paroxetine, and venlafaxine.

Tibolone is a combined steroid and derivative of 19-nortestosterone.³ After transformation in the liver and stomach, tibolone has characteristics of androgen, progesterone, and an estrogen metabolite. Tibolone is a selective tissue estrogen activity regulator because it reduces estrogen activity in the breast tissue, making it a safer option for those with a breast cancer risk or history. It helps with menopausal symptoms, including headache, libido, insomnia, osteopenia, hot flashes, urinary symptoms, and vaginal dryness. Tibolone also lowers total cholesterol and does not appear to increase the risk for venous thromboembolism or CAD in at-risk patients aged older than 60 years. However, older patients may still have a higher stroke risk.

The herbal product black cohosh (Cimicifuga racemosa) also helps through the activation of the serotonin transmitter system.¹ But health care professionals should be aware of the potential contamination of some preparations, which may warrant liver function monitoring with long-term use. Finally, other forms of Chinese Traditional Medicine, including acupuncture, may be effective menopause management tools in patients contraindicated for menopause hormone therapy.

Encouraging Successful Lifestyle Changes

It is no secret that regular exercise is essential, especially with aging. Encouraging patients to engage in consistent physical activity may improve both their postmenopausal symptoms and cardiovascular risk.⁶ Studies show that women who exercise regularly don’t experience the same age-related resting metabolic rate decline as their sedentary counterparts.⁶ In addition, weight loss interventions lower the incidence of hot flashes.⁶

Social support and accountability can make all the difference in a patient’s success with lifestyle interventions. Thinking beyond traditional one-to-one patient-provider counseling sessions offers opportunities for better outcomes, especially in patients for whom menopause hormone therapy is contraindicated. Therefore, group nutrition classes, walking programs, or stress management clinics are some additional ways beyond menopause hormone therapy for doctors to treat patients and promote heart health and well-being during menopause.

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Researchers used inpatient data—patient characteristics, treatments, and outcomes— from the SWEDEHEART registry and outpatient data—comorbidities, blood pressure, medications, smoking, and lifestyle variables—from the SWEDEHEART Cardiac Rehabilitation registry to compare the association between levels of pain severity 1 year after MI and all-cause mortality. 

They included 18,376 patients (mean age, 62.0 years; 75.5% men) who had been diagnosed with MI at hospital admission and followed for 1 year after hospital discharge. A follow-up questionnaire was completed by the patients at 12-month follow-up which included a self-reported pain assessment entailing 3 levels of pain severity statements: “I have no pain or discomfort,” “I have moderate pain or discomfort,” or “I have extreme pain or discomfort.” The Cox proportional hazards regression model (adjusted for many variables such as age, sex, and smoking status) was utilized to assess the association between all-cause mortality and pain experienced 12 months after hospital stay.

There were a total of 1067 deaths up to 8.5 years after the 12-month follow-up. Of these deaths, 104 were associated with patients who reported extreme pain 12 months after discharge (12.5% of n=834), followed by 543 deaths with moderate pain (7.7% of n=7025), and 420 deaths with no pain (4.0% of n=10517). The hazard ratio (HR) was higher in patients who reported extreme pain 12 months after discharge than those who reported moderate pain (extreme pain, 2.06; 95% CI, 1.63-2.60; vs moderate pain, 1.35; 95% CI, 1.18-1.55; P <.0001).

A sensitivity analysis that utilized the same model—but only adjusted for age and sex—compared all available pain data (n=40963) to the population in the analysis (n=18376). The HR for moderate pain and extreme pain was found to be 1.71 and 3.04, respectively (P <.0001).

Of note, researchers further assessed the all-cause mortality from 1 year after MI by comparing the risk for pain categories with the risk for smoking using Kaplan-Meier curves. The C-statistics for pain were higher than for smoking (pain, 0.60 vs smoking, 0.55), denoting that pain is a stronger indicator of all-cause mortality risk from 1 year after MI than smoking.  

 “Pain 1 year after MI is highly prevalent, and its effect on mortality 1 year after MI was found to be more pronounced than the effect of the more well-known risk factor, smoking,” the researchers wrote.

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Brian Stamm, M.D., from the University of Michigan in Ann Arbor, and colleagues examined door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and identified factors associated with these times in a retrospective study. Patients with ischemic or hemorrhagic stroke transferred from the emergency department at registry-affiliated hospitals to other acute care hospitals between January 2019 through December 2021 were included in the analysis. Of the 108,913 patients transferred from 1,925 hospitals, 67,235 and 41,678 had acute ischemic and hemorrhagic stroke, respectively.

The researchers found that the median door-in-door-out time was 174 minutes; 27.3 percent of patients had a door-in-door-out time of ≤120 minutes. Age 80 years or older, female sex, non-Hispanic Black race, and Hispanic ethnicity were factors significantly associated with longer median times. Emergency medical services prenotification, National Institutes of Health Stroke Scale score >12, and patients with acute ischemic stroke eligible for endovascular therapy were significantly associated with shorter median door-in-door-out times. Female sex, Black race, and Hispanic ethnicity were associated with significantly higher door-in-door-out times among patients with acute ischemic stroke eligible for endovascular therapy.

“Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives,” the authors write.

Abstract/Full Text (subscription or payment may be required)

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Aron Onerup, M.D., Ph.D., from the University of Gothenburg in Sweden, and colleagues examined associations between cardiorespiratory fitness and incidence of site-specific cancer using data from 1.078 million men who underwent military conscription (1968 to 2005) with a mean follow-up of 33 years.

The researchers found that higher cardiorespiratory fitness was linearly associated with a lower risk for developing cancer in the head and neck (hazard ratio [HR], 0.81), esophagus (HR, 0.61), stomach (HR, 0.79), pancreas (HR, 0.88), liver (HR, 0.60), colon (HR, 0.82), kidney (HR, 0.80), and lung (HR, 0.58). Higher cardiorespiratory fitness was associated with higher risk for being diagnosed with prostate cancer (HR, 1.07) and malignant skin cancer (HR, 1.31).

“Our study suggests that cardiorespiratory fitness is linearly associated with a lower hazard of developing most of the site-specific cancers assessed here, some of which have not previously been reported in relation to cardiorespiratory fitness or physical activity,” the authors write. “These results strengthen the incentive for promoting interventions aimed at increasing cardiorespiratory fitness in youth.”

Abstract/Full Text

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Lingering uncertainty regarding the effectiveness of varying COVID-19 therapies has resulted in major worldwide differences in practice guidelines. Study authors therefore reported on findings involving remdesivir antiviral activity from the PLATCOV trial (ClinicalTrials.gov Identifier: NCT05041907), an ongoing phase 2 open-label randomized controlled pharmacometric platform trial.

Adults aged 18 to 50 years (mean age, 30.1 years) with early symptomatic COVID-19 (symptoms for <4 days) who had been previously healthy were included in the study; all had an oxygen saturation of at least 96% and were unimpeded in their activities of daily living. The primary outcome measure was the rate of viral clearance among patients using remdesivir.

The modified intention-to-treat population included 131 patients, 67 receiving remdesivir and 64 randomly assigned to receive ivermectin, casirivimab/imdevimab, favipiravir, nitazoxanide, fluoxetine, molnupiravir, or nirmatrelvir/ritonavir. Remdesivir was administered in an intravenous infusion for 60 minutes in an initial adult dose of 200 mg, followed by 100 mg once daily for 4 days. All participants received standard symptomatic treatment.

Each participant had a median of 18 sample swabs taken to measure viral density in the first 8 days, resulting in a total of 2356 quantitative polymerase chain reaction (qPCR) analyses; 86% of these swabs were above the lower limit of detection.

Clearance of oropharyngeal virus in patients randomized to remdesivir was 42% faster compared with the control arm (95% CI, 18%-73%; probability of >12.5% acceleration: 0.99). The median estimate of viral clearance half-lives under the linear model was 12.8 (range, 4.8-50.0) hours for the remdesivir group and 18.0 (range, 3.6-46.7) hours for the control group.

Oropharyngeal swabbing and treatments were well-tolerated. In the control arm, 3 serious adverse events (AEs) occurred vs 1 in the remdesivir arm. In addition, 2 patients in the control group and 1 in the remdesivir group had asymptomatic increased creatinine phosphokinase level (>10 times ULN) owing to COVID-19-related skeletal muscle damage. No treatment-related serious AEs occurred.

Among several limitations, the researchers intentionally assessed the COVID-19 antiviral interventions in low-risk adults with high viral burdens in order to optimize the comparative assessment of the different drugs, thus excluding elderly and other individuals with a higher risk for disease progression. Other limitations include the open-label design and a lack of statistical significance in the time to symptom resolution and time to fever clearance.

“Remdesivir continues to have a role in the treatment of COVID-19 for certain populations,” stated the investigators. “The simple pharmacometric methodology presented demonstrates the in vivo antiviral efficacy of remdesivir and is readily performed anywhere where accurate qPCR viral quantitation can be performed.”

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Mahsa Moradi, Ph.D., from Tehran University of Medical Sciences in Iran, and colleagues examined the global burden of cardiovascular diseases attributed to PM from 1990 to 2019 using the Global Burden of Disease study 2019. DALYs, years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM were investigated.

The researchers found the same declining trend for all burden measures’ age-standardized rates for PM; the highest decline was seen for deaths (−36.7 percent). There was a 31 percent increase in all-age DALYs, reaching 8.9 million in 2019, with YLLs contributing the most (8.2 million). Higher deaths, DALYs, and YLLs were higher for men despite lower years lived with disability versus women in 2019. An 8.1 percent increase was seen in the age-standardized rate of DALYs for ambient PM. However, during the study period, there was a 65.4 percent decrease in household air pollution from solid fuels. In 2019, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDs ratio for PM pollution, respectively.

“The declines in deaths may be considered positive news, as they indicate improvements in health care, air pollution control measures, and access to treatment,” senior author Farshad Farzadfar, M.D., M.P.H., D.Sc., also of the Tehran University of Medical Sciences, said in a statement. “However, the increase in disability-adjusted life years suggests that although fewer people were dying from cardiovascular disease, more people were living with disability.”

Abstract/Full Text

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