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.

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.

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.

Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.

Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics.

Global burden of cardiovascular disease attributable to smoking, 1990-2019: an analysis of the 2019 Global Burden of Disease Study.

AIMS: This study aims to investigate the trends in the global cardiovascular disease (CVD) burden attributable to smoking from 1990 to 2019. METHODS AND RESULTS: Global Burden of Disease Study 2019 was used to analyse the burden of CVD attributable to smoking (i.e. ischaemic heart disease, peripheral artery disease, stroke, atrial fibrillation and flutter, and aortic aneurysm). Age-standardized mortality rates (ASMRs) per 100 000 and age-standardized disability-adjusted life year rates (ASDRs) per 100 000, as well as an estimated annual percentage change (EAPC) in ASMR and ASDR, were determined by age, sex, year, socio-demographic index (SDI), regions, and countries or territories. The global ASMR of smoking-attributed CVD decreased from 57.16/100 000 [95% uncertainty interval (UI) 54.46-59.97] in 1990 to 33.03/100 000 (95% UI 30.43-35.51) in 2019 [EAPC -0.42 (95% UI -0.47 to -0.38)]. Similarly, the ASDR of smoking-attributed CVD decreased between 1990 and 2019. All CVD subcategories showed a decline in death burden between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women. Significant geographic and regional variations existed such that Eastern Europe had the highest ASMR and Andean Latin America had the lowest ASMR in 2019. In 2019, the ASMR of smoking-attributed CVD was lowest in high SDI regions. CONCLUSION: Smoking-attributed CVD morbidity and mortality are declining globally, but significant variation persists, indicating a need for targeted interventions to reduce smoking-related CVD burden.

The burden of cardiovascular disease (CVD) attributed to smoking declined worldwide between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women in 2019. There were significant variations between different countries and regions such that Eastern Europe had the highest death rate and Andean Latin America had the lowest death rate in 2019. Also, countries with high socio-economic status had lower death rates from smoking-attributed CVD. This highlights the need for targeted interventions to reduce the burden of smoking-attributed CVD.The overall age-adjusted deaths from CVD attributed to smoking declined from 57.16/100 000 in 1990 to 33.03/100 000 in 2019.In 2019, ischaemic heart disease was the leading cause of smoking-attributed CVD deaths.

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.