Bempedoic Acid in Secondary Prevention.

•Bempedoic acid has been shown to reduce major adverse cardiovascular outcomes in patients unable to take statins due to statin-associated side effects.•Analysis of CLEAR Outcomes trial data reveals possible differences in baseline characteristics between the primary and secondary prevention subgroups.•Further research is needed to optimize use of bempedoic acid and clarify its impact on cardiovascular outcomes in diverse patient populations.

Rising mortality related to cardiovascular disease and prostate cancer amongst older men across the United States.

OBJECTIVE: There is a significant association between cardiovascular diseases (CVD) and prostate cancer (PCa), leading to high mortality. This study evaluates the trends in mortality associated with CVDs and PCa among older (≥ 65 years) men in the United States (US). METHODS: This analysis utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). The analysis of Multiple Cause of Death Files was carried out from 1999 to 2019 to identify fatalities with CVD and PCa listed as either contributory or underlying causes of death. Crude and age-adjusted mortality rates (AAMRs) per 100,000 populations for variables such as year, race and ethnicity, and geographic regions were determined. To assess annual percent change (APC), a Joinpoint regression program was employed. RESULTS: Overall AAMR was 54.3 in 1999 and 34.6 in 2019. After a decline in AAMR from 1999 to 2015, an alarming rise in mortality was observed until 2019. Mortality rates were highest among Non-Hispanic (NH) Black and African American men (74.9). Geographically, the highest mortalities were witnessed in the West (46.4) and non-metropolitan areas (44.6). States with AAMRs ranking in the 90th percentile were Nebraska, California, North Dakota, the District of Columbia, and Mississippi. CONCLUSION: After decreasing death rates associated with CVD and PCa from 1999 to 2015, a reversal in the trend was observed from 2015 to 2019. Addressing this increase in death rates, especially among the vulnerable population, requires focused attention and targeted strategies to implement necessary safeguards in the upcoming years.

Ongoing and future clinical trials of device therapies for patients with heart failure.

Heart failure continues to pose a significant burden in terms of morbidity, mortality, and healthcare costs worldwide despite the implementation of guideline-directed medical therapy. Addressing this challenge and improving clinical outcomes for this patient population remains an urgent priority. Recognizing the limitations in current medical approaches and exploring strategies to overcome these limitations are crucial steps toward improving future outcomes. Various device-based interventions, such as Cardiac Resynchronization Therapy devices and Left Ventricular Assist Devices, have demonstrated notable benefits for individuals with heart failure. Our review is aimed at summarizing the ongoing research into new device therapies for heart failure, emphasizing their potential to overcome the current challenges in treatment. By utilizing Clinicaltrials.gov, an online repository, we conducted a comprehensive search for trials investigating emerging device therapies for patients dealing with heart failure.

Relationship between race, income-level, and Cardiovascular Disease.

AIM: To study the prevalence of cardiovascular disease (CVD) and associated risk factors among different races/ethnicities across different income groups. METHODS: This retrospective analysis included data from the National Health and Nutrition Examination Survey from 2005-2018. Adults >20 years who identified as non-Hispanic (NH) White, NH Black, or Hispanic were included. Family income-to-poverty ratio (PIR) was calculated by dividing family income by poverty guidelines specific to the survey year and divided into four quartiles. Weighted logistic regression was performed to estimate adjusted odds ratios to determine association of race/ethnicity and CVD in each PIR quartile. Models were adjusted for age, sex, race, health insurance, marital status, citizenship status, education level, and PIR. RESULTS: We included 31,884 adults that corresponded to ∼191.3 million weighted, nationally representative participants. Of these, 8,009, 7,967, 7,944, and 7,964 participants belonged to 1st, 2nd, 3rd, and 4th quartiles, respectively. The prevalence of diabetes mellitus (DM), hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke decreased with each successive PIR quartile. NH Black participants had higher prevalence odds of DM, hypertension, obesity, CHF, and stroke compared to NH White participants. The difference in prevalence odds between NH White adults and NH Black adults was greater for obesity (p-interaction=0.002), DM (p-interaction=0.027), and stroke (p-interaction=0.053) in the 4th PIR quartile (highest income) compared to the 1st PIR quartile (lowest income). CONCLUSION: Racial and ethnic disparities in the risk of CVD persists across income levels, with a greater difference in prevalence of select CVD and risk factors between NH Black and NH White participants in the highest income quartile compared to the lowest income quartile.

Suicide-related mortality in cardiovascular disease in the United States from 1999 to 2019.

INTRODUCTION: Research has shown chronic diseases can be associated with suicide but there is limited data on suicide in cardiovascular disease (CVD). Given the substantial psychosocial, financial, quality of life, and health impact of CVD, we aimed to study suicide-related mortality in CVD. METHODS: We used Center for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) to access Multiple Cause of Death data from 1999 to 2019. Suicide and CVD related deaths in patients ≥ 25 years were identified. Proportionate suicide-related mortality (PSrM) was calculated as suicide-related deaths (listed with CVD) divided by all CVD-related deaths (irrespective of suicide) and reported as PSrM per 100,000 CVD-related deaths. Joinpoint regression was used to examine trend changes using annual percentage change (APC) overall and by sex, race/ethnicity, disease subtype, and age. RESULTS: Overall, PSrM in CVD increased from 62.8 in 1999 to 90.5 in 2019. The PSrM increased from 1999 to 2002 with an associated APC of 6.2 (95 % CI, 0.0 to 12.7), remained stable from 2002 to 2005, increased from 2005 to 2013 with an APC of 4.8 (95 % CI, 3.4 to 6.3), and decreased from 2013 to 2019 with an APC of -2.1 (95 % CI, -3.6 to -0.5). Among racial/ethnic groups, PSrM was highest in non-hispanic (NH) White (103.8), then Hispanic or Latino (63.6), and then NH Black or African American individuals (29.2). PSrM was highest in the 25-39 years age group (858), then 40-54 years (382.8), 55-69 years (146.2), 70-84 years (55.9), and then 85+ (17). PSrM initially increased in men with APC (3.1 until 2013), women (4.1 until 2014), NH White individuals (3.9 until 2013), Hispanic or Latino (3.5 until 2014), ages 40-54 years (2.9 until 2013), 55-69 years (6.0 until 2013), then stabilized or decreased. AAMR increased in NH Black or AA individuals APC (1.0) and 25-39 years APC (1.4) from 1999 to 2019. CONCLUSION: PSrM in CVD peaked in the early 2010s, with varying differences across sex, racial/ethnic, and age groups. Further research is needed to understand disparities and develop preventive strategies.

Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

Ongoing and Future Clinical Trials of Pharmacotherapy for Heart Failure.

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world.We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review.

Sex-Based Differences in Patients With Left Ventricular-Assisted Devices and Strokes.

Background: Sex-based differences in clinical outcomes among patients with stroke related to left ventricular assist devices (LVADs) are not well described. Objectives: In this study, the authors examined differences in clinical characteristics and outcomes in men and women who had a stroke during LVAD hospitalization. Methods: The National Inpatient Sample from 2010 and 2019 was used to identify patients with stroke during LVAD hospitalization. Outcomes of interest include inpatient mortality and clinical complications among men vs women. Weighted logistic regression was used to determine the association of sex and outcomes. Adjustments were made for age and the Elixhauser comorbidity index. Results: In total, 35,820 patients underwent LVAD implantation (77% men), and 6.12% (n = 2,192) of patients experienced stroke. Women who had stroke were younger than men who had stroke (mean age in women was 51 years vs men 59 years, P < 0.001). Men with strokes had a higher burden of comorbidities than women. While there were no differences in the odds of ischemic stroke, women had higher odds of hemorrhagic stroke compared to men (OR: 1.49 [95% CI: 1.02-2.18]). Mortality in patients with LVAD who had stroke was significantly higher than in those without stroke. Between 2010 and 2019, stroke rates significantly increased among men, while the trend remained variable among women. Conclusions: In this national cohort, men had a higher comorbidity burden and had worsening stroke trends over the last decade compared to women. Women had fewer LVAD implants and a higher incidence of hemorrhagic stroke. Understanding the factors that contribute to sex-related outcome disparities among LVAD stroke patients is crucial in addressing these diverging trends.

Has mortality in the United States returned to pre-pandemic levels? An analysis of provisional 2023 data.

BACKGROUND: The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown. METHODS AND RESULTS: The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels. CONCLUSION: Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. RECENT FINDINGS: The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumption with the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2 years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Brief report: Effect of cardiac multi-morbidity on COVID hospitalization outcomes.

BACKGROUND: The COVID-19 pandemic has stretched healthcare resources thin and led to significant morbidity and mortality. There have been no studies utilizing national data to investigate the role of cardiac risk factors on outcomes of COVID hospitalizations. The aim of this study was to examine the effect of cardiac multimorbidity on healthcare utilization and outcomes among COVID hospitalizations during the first year of the pandemic. METHODS: Using the national inpatient sample (NIS), we identified all adult hospital admissions with a primary diagnosis of COVID in 2020, using International Classification of Diseases, Tenth Revision, Clinical Modification codes (ICD010-CM). Coronary artery disease, diabetes mellitus, heart failure, peripheral vascular disease, previous stroke, and atrial fibrillation were then identified as cardiac comorbidities using ICD-10-CM codes. Multivariable logistic regression was used to evaluate the effect of cardiac multimorbidity on mortality and mechanical ventilation. RESULTS: We identified 1,005,040 primary COVID admissions in 2020. Of these admissions, 216,545 (20.6%) had CAD, 413,195 (39.4%) had DM, 176,780 (16.8%) had HF, 159,700 (15.2%) had AF, 30735 (2.9%) had PVD, and 25,155 (2.4%) had a previous stroke. When stratified by number of comorbidities, 428390 (40.8%) had 0 comorbidities, 354960 (33.8%) had 1, 161225 (15.4%) had 2, and 105465 (10.0%) had 3+ comorbidities. COVID hospitalizations with higher cardiac multimorbidity had higher mortality rates (p<0.001) higher MV rates (p<0.001). In our multivariable regression, these associations remained with increasing odds for mortality with each stepwise increase in cardiac multimorbidity (1: OR 1.48 (1.45-1.50); 2: OR 2.13 (2.09-2.17); 3+: OR 2.43 (2.38-2.48), p<0.001, all). CONCLUSIONS: Our study is the first national examination of the impact of cardiac comorbidities on COVID outcomes. A higher number of cardiac comorbidities was associated with significantly higher rates of MV and in-hospital mortality, independent of age. Future, more granular, and longitudinal studies are needed to further examine these associations.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: Focused review highlighting ten select studies presented at the 2023 American Heart Association (AHA) Scientific Sessions. RECENT FINDINGS: Included studies assessed semaglutide and cardiovascular outcomes in overweight or obese patients without diabetes (SELECT); dapagliflozin in patients with acute myocardial infarction without diabetes (DAPA-MI); effects of dietary sodium on systolic blood pressure in middle-aged individuals (CARDIA-SSBP); long-term blood pressure control after hypertensive pregnancy with physician guided self-management (POP-HT); effect and safety of zilebesiran, an RNA interference therapy, for sustained blood pressure reduction (KARDIA-1); recaticimab add-on therapy in patients with non-familial hypercholesterolemia and mixed hyperlipidemia (REMAIN-2); efficacy and safety of lepodisiran an extended duration short-interfering RNA targeting lipoprotein(a); safety and pharmacodynamic effects of an investigational DNA base editing medicine that inactivates the PCSK9 gene and lowers LDL cholesterol (VERVE-101); automated referral to centralized pharmacy services for evidence-based statin initiation in high-risk patients; and effects of intensive blood pressure lowering in reducing risk of cardiovascular events (ESPRIT). Research presented at the 2023 AHA Scientific Sessions emphasized innovative strategies in cardiovascular disease prevention and management.

Sex differences in heart transplantation - analysis of the national inpatient sample 2012-2019.

INTRODUCTION: Advanced heart failure therapies and heart transplantation (HT) have been underutilized in women. Therefore, we aimed to explore the clinical characteristics and outcomes of HT by sex. METHODS: We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2012 and 2019. International Classification of Disease (ICD) procedure codes were used to identify those who underwent HT. RESULTS: A total of 20,180 HT hospitalizations were identified from 2012-2019. Among them, 28 % were female. Women undergoing HT were younger (mean age 51 vs. 54.5 years, p<0.001). HT hospitalizations among men were more likely to have atrial fibrillation, diabetes, hypertension, renal failure, dyslipidemia, smoking, and ischemic heart disease. HT hospitalizations among women were more likely to have hypothyroidism and valvular heart disease. HT hospitalizations in women were associated with no significant difference in risk of in-hospital mortality (adjusted odds ratio [OR] 0.82; 95 % confidence interval [CI] 0.58-1.16, p=0.271), no significant difference in length of stay or inflation-adjusted cost. Men were more likely to develop acute kidney injury during HT hospitalization (69.2 % vs. 59.7 %, adjusted OR 0.71, 95 % CI 0.61-0.83, p<0.001). CONCLUSIONS: HT utilization is lower in women. However, most major in-hospital outcomes for HT are similar between the sexes. Further studies are need to explore the causes of lower rates of HT in women.

Disparities in heart failure between White, Black, and Hispanic young adults: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of heart failure (HF) is increasing among young adults in the United States with pervasive racial and ethnic differences in this population. OBJECTIVE: To evaluate contemporary associations between race and ethnicity, clinical comorbidities, and outcomes among young to middle-aged adults with HF. METHODS: A retrospective analysis was performed using the National Health and Nutrition Examination Survey. All participants with a self-report of HF aged 20-64 years from 2005 to 2018 were included and stratified by race and ethnicity [non-Hispanic (NH) Whites, NH Blacks, and Hispanics]. Data on baseline characteristics including age, sex, marital status, citizenship, education level, body mass index, insurance, waist circumference, cigarette smoking, marijuana use, and relevant clinical comorbidities were included. Weighted logistic regression was performed to estimate adjusted odds ratios (aOR) to determine the association of race and ethnicity with HF. Cox proportional-hazards models were used to assess the association of race and ethnicity with all-cause and cardiac mortality. RESULTS: A total of 1,940,447 young to middle-aged adults had self-reported HF between 2005 and 2018, of whom 61% were NH White, 40% were NH Black, and 22% were Hispanic. When compared with NH White adults, NH Black adults had higher odds of HF adjusted for age, sex, insurance status, marital status, education level, citizenship status, and clinical comorbidities (adjusted aOR 2.63, 95% CI: 1.71-4.05, p < 0.001). There was no significant difference in the odds of HF between Hispanic and NH White adults (aOR 1.18, 95% CI: 0.64-2.18, p = 0.585). NH Black adults had higher mean systolic and diastolic blood pressure, and a comparable or lower burden of cardiovascular and non-cardiovascular clinical comorbidities compared with NH White and Hispanic adults. No statistical significance was noted by race and ethnicity for all-cause and cardiac mortality during a follow-up of 5 years. CONCLUSION: NH Black young to middle-aged adults were more likely to have HF which may be related to higher blood pressure given the largely similar burden of clinically relevant comorbidities compared with other racial and ethnic groups.

Racial and ethnic disparities in cardiovascular disease - analysis across major US national databases.

BACKGROUND: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US. METHODS: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, and American Commission for Graduate Medical Education data to evaluate CVD-related disparities among Non-Hispanic (NH) White, NH Black and Hispanic populations. RESULTS: The prevalence of most CVDs and associated risk factors was higher in NH Black adults compared to NH White adults, except for dyslipidemia and ischemic heart disease (IHD). Statins were underutilized in IHD in NH Black and Hispanic patients. Hospitalizations for HF and stroke were higher among Black patients compared to White patients. All-cause, CVD, heart failure, acute myocardial infarction, IHD, diabetes mellitus, hypertension and cerebrovascular disease related mortality was highest in NH Black or African American individuals. The number of NH Black and Hispanic trainees in adult general CVD fellowship programs was disproportionately lower than NH White trainees. CONCLUSION: Racial disparities are pervasive across the spectrum of CVDs with NH Black adults at a significant disadvantage compared to NH White adults for most CVDs.