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Introduction. Some groups of Asian Americans, especially Asian Indians, experience higher rates of atherosclerotic cardiovascular disease (ASCVD) compared with other groups in the U.S. Barriers in accessing medical care partly may explain this higher risk as a result of delayed screening for cardiovascular risk factors and timely initiation of preventive treatment. Methods. Cross-sectional data were utilized from the 2006 to 2015 National Health Interview Survey (NHIS). Barriers to accessing medical care included no place to seek medical care when needed, no healthcare coverage, no care due to cost, delayed care due to cost, inability to afford medication, or not seeing a doctor in the past 12 months. Results. The study sample consisted of 18,150 Asian individuals, of whom 20.5% were Asian Indian, 20.5% were Chinese, 23.4% were Filipino, and 35.6% were classified as “Other Asians”. The mean (standard error) age was 43.8 (0.21) years and 53% were women. Among participants with history of hypertension, diabetes mellitus, or ASCVD (prevalence = 25%), Asian Indians were more likely to report delayed care due to cost (2.58 (1.14,5.85)), while Other Asians were more likely to report no care due to cost (2.43 (1.09,5.44)) or delayed care due to cost (2.35 (1.14,4.86)), compared with Chinese. Results among Filipinos were not statistically significant. Conclusions. Among Asians living in the U.S. with cardiovascular risk factors or ASCVD, Asian Indians and Other Asians are more likely to report delayed care or no care due to cost compared with Chinese.

South Asians account for around 25% of the global population and are the fastest-growing ethnicity in the US. This population has an increasing burden of atherosclerotic cardiovascular disease (ASCVD) which is also seen in the diaspora. Current risk prediction equations underestimate this risk and consider the South Asian ethnicity as a risk-enhancer among those with borderline-intermediate risk. In this review, we discuss why the South Asian population is at a higher risk of ASCVD and strategies to mitigate this increased risk.

Purpose of review Summarize and examine the epidemiology, etiologies, risk factors, and treatment of stroke among young adults and highlight the importance of early recognition, treatment, and primordial prevention of risk factors that lead to stroke. Recent findings Incidence of stroke, predominantly ischemic, among young adults has increased over the past two decades. This parallels an increase in traditional risk factors such as hypertension, diabetes, and use of tobacco, and use of illicit substances among young stroke patients. Compared to older patients, there is a much higher proportion of intracerebral and subarachnoid hemorrhage in young adults. The cause of ischemic stroke in young adults is also more diverse compared to older adults with 1/3rd classified as stroke of undetermined etiology due to inadequate effort or time spent on investigating these diverse and rare etiologies. Young premature Atherosclerotic Cardiovascular Disease patients have suboptimal secondary prevention care compared to older patients with lower use of antiplatelets and statin therapy and lower adherence to statins. Summary Among young patients, time-critical diagnosis and management remain challenging, due to atypical stroke presentations, vast etiologies, statin hesitancy, and provider clinical inertia. Early recognition and aggressive risk profile modification along with primary and secondary prevention therapy optimization are imperative to reduce the burden of stroke among young adults and save potential disability-adjusted life years.

Background Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk. Objectives This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories. Methods Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors. Results There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to Conclusions Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low‐density‐lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US‐based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P =0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m 2 versus 29±6 kg/m 2 ; P P P P =0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P =0.004) and other lipid‐lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60–1.49; P =0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid‐lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Summarize and examine the epidemiology, etiologies, risk factors, and treatment of stroke among young adults and highlight the importance of early recognition, treatment, and primordial prevention of risk factors that lead to stroke.Incidence of stroke, predominantly ischemic, among young adults has increased over the past two decades. This parallels an increase in traditional risk factors such as hypertension, diabetes, and use of tobacco, and use of illicit substances among young stroke patients. Compared to older patients, there is a much higher proportion of intracerebral and subarachnoid hemorrhage in young adults. The cause of ischemic stroke in young adults is also more diverse compared to older adults with 1/3rd classified as stroke of undetermined etiology due to inadequate effort or time spent on investigating these diverse and rare etiologies. Young premature Atherosclerotic Cardiovascular Disease patients have suboptimal secondary prevention care compared to older patients with lower use of antiplatelets and statin therapy and lower adherence to statins.Among young patients, time-critical diagnosis and management remain challenging, due to atypical stroke presentations, vast etiologies, statin hesitancy, and provider clinical inertia. Early recognition and aggressive risk profile modification along with primary and secondary prevention therapy optimization are imperative to reduce the burden of stroke among young adults and save potential disability-adjusted life years.

Purpose of Review This review highlights late-breaking science presented at the Virtual American College of Cardiology Scientific Sessions 2021 that demonstrated advancements in preventative cardiology and introduced novel therapeutic modalities for the management of chronic kidney disease, heart failure, and COVID-19. Recent Findings The studies reviewed include clinical trials that assessed the use of dapagliflozin in patients with respiratory failure due to COVID-19 (DARE-19 trial); evinacumab for patients with severe hypertriglyceridemia and pancreatitis; effect of genotype-guided oral P2y12 inhibitors vs conventional clopidogrel on long-term ischemic outcomes after percutaneous coronary intervention (TAILOR-PCI trial); anticoagulation in patients hospitalized with COVID-19 (ACTION trial); atorvastatin vs placebo in patients with COVID-19 admitted to the ICU (INSPIRATION-S trial); rehabilitation therapy in older acute heart failure patients (REHAB-HF trial); and aspirin dosing: a patient-centric trial assessing benefits and long-term effectiveness (ADAPTABLE trial). In addition, we review the results of the American College of Cardiology Global Heart Attack Initiative (GHATI). Finally, we discuss the secondary analysis of the STRENGTH trial assessing the association of achieved levels of omega-3 fatty acid levels and major cardiovascular outcomes. Summary The studies presented at the virtual American College of Cardiology Scientific Session 2021 represent remarkable contributions in the field of cardiovascular disease and prevention.

Individuals with atherosclerotic cardiovascular disease (ASCVD) often have a high burden of comorbidities. Social determinants of health (SDOH) may complicate adherence to treatment in these patients. This study assessed the association of comorbidities and SDOH among individuals with ASCVD. Cross-sectional data from the 2016 to 2019 Behavioral Risk Factor Surveillance System, a nationally representative US telephone-based survey of adults ages ≥18 years, were used. Cardiovascular comorbidities included hypertension, hyperlipidemia, diabetes mellitus, current cigarette smoking, and chronic kidney disease. Non-cardiovascular comorbidities included chronic obstructive pulmonary disease, asthma, arthritis, cancer, and depression. SDOH associated with being at or above the 75

Background Non-vitamin K oral anticoagulants (NOACs) have emerged as alternatives to vitamin K antagonists in select situations. For left atrial (LA) appendage thrombus in nonvalvular atrial fibrillation (AF) or flutter, guidelines recommend oral anticoagulation (OAC) for at least 3 weeks prior to reassessment. Data comparing NOACs to warfarin in this scenario are scarce. Methods A retrospective study identified subjects with nonvalvular AF or flutter who were: a) noted to have LA thrombus detected on transesophageal echocardiography (TEE), b) previously not receiving long-term OAC; and c) evaluated for resolution of LA thrombus by follow-up TEE between 3 weeks to less than 1 year of the initial TEE. Results The study included 45 subjects with mean age 63.2 years, 69% male, 78% white race/ethnicity, 42% paroxysmal, and mean CHA2 DS2 -VASc score 3.4 ± 1.7. All LA thrombi were confined to the appendage. OAC received included apixaban (3), dabigatran (13), rivaroxaban (6), and warfarin (23), The median follow-up time to repeat TEE was 67 (interquartile range, 49-96) days. LA appendage thrombus resolution rates were 76% for the entire cohort, 77% for NOACs, and 74% for warfarin. In univariable logistic regression analysis, LA appendage thrombus resolution was similar for NOACs when compared to warfarin (odds ratio, 1.20; 95% confidence interval, 0.31-4.69; P = .79). Conclusions In patients nonvalvular AF or flutter who were OAC naive at the time of diagnosis with LA appendage thrombus, complete resolution was similar between NOACs and warfarin.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The “American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update” is a summary document (updated yearly) regarding CVD risk factors. This “ASPC Top Ten CVD Risk Factors 2021 Update” summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the “ASPC Top Ten CVD Risk Factors 2021 Update” to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Lipids and lipoproteins are the target of many novel therapeutics and are an area with great potential for the prevention and treatment of cardiovascular disease (CVD). Reduction of low-density lipoprotein cholesterol has been the mainstay of reducing the burden of CVD, however, several other atherogenic particles have more recently come into the spotlight as potential avenues for primary and/or secondary prevention of CVD. These include triglycerides, high sensitivity C-reactive protein, apolipoprotein A, apolipoprotein C3 and lipoprotein(a). In this review, we showcase novel therapeutics to target lipid and cardiovascular risk reduction that are either in development or that have recently been approved for use. We discuss the mechanisms of action, data from clinical trials and expected effects of each therapy based on the current body of literature.

Background Recent literature has shown an association between atherosclerotic cardiovascular disease and inflammatory bowel disease, potentially mediated through chronic inflammatory pathways. However, there is a paucity of data demonstrating this relationship among young patients with premature atherosclerotic cardiovascular disease. Methods Using data from the nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed the association between extremely premature and premature atherosclerotic cardiovascular disease (age at diagnosis: ≤40 years and ≤55 years, respectively) and inflammatory bowel disease. Patients were compared with age-matched controls without atherosclerotic cardiovascular disease. Multivariable regression models adjusted for traditional risk factors. Results We identified 147,600 patients and 9485 patients with premature and extremely premature atherosclerotic cardiovascular disease, respectively. Compared with controls, there was a higher prevalence of overall inflammatory bowel disease among premature (0.96% vs 0.84%; odds ratio [OR] 1.14; 95% confidence interval [CI], 1.08-1.21) and extremely premature (1.36% vs 0.75%; OR 1.82; 95% CI, 1.52-2.17) patients. After adjustment, these associations attenuated in both premature and extremely premature groups (OR 1.07; 95% CI, 1.00-1.14 and OR 1.61; 95% CI, 1.34-1.94, respectively). Conclusion Inflammatory bowel disease is associated with higher odds of extremely premature atherosclerotic cardiovascular disease, especially for those age ≤40 years. With increasing age, this risk is attenuated by traditional cardiometabolic factors such as obesity, hypertension, diabetes, smoking, and dyslipidemia. Prospective studies are needed to assess the role of early intervention to decrease cardiovascular risk among young patients with inflammatory bowel disease.

Purpose Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. Methods We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. Results Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. Conclusion Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

Aims Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study. Methods and results In 6359 participants (mean age 75.8 ± 5.3 years) followed for ASCVD events [coronary heart disease (CHD) or ischaemic stroke] up to 6 years, associations between LDL-TG, RLP-C, apoC-III, and ANGPTL3 and ASCVD events were assessed using Cox regression. With adjustment for age, sex, and race, RLP-C, LDL-TG, apoC-III, and ANGPTL3 (as continuous variables) were significantly associated with CHD. However, after adjustment for traditional risk factors and lipid-lowering medications, only LDL-TG and ANGPTL3 were significantly associated with ASCVD events [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.25–2.37 per log unit increase in LDL-TG; HR 1.63, 95% CI 1.17–2.28 per log unit increase in ANGPTL3]. Conclusions In older adults, LDL-TG, RLP-C, apoC-III, and ANGPTL3 were associated with CHD events in minimally adjusted models; LDL-TG and ANGPTL3 remained independent predictors of ASCVD events with further adjustment. Future studies should assess potential benefit of lowering hepatic apoC-III or ANGPTL3 expression in patients with elevated triglyceride-rich lipoproteins.

Purpose of the Review This review highlights late-breaking science presented at the American Heart Association Scientific Session 2020 that demonstrated advancements in preventative cardiology and introduced novel treatment approaches for the management of chronic kidney disease, type 2 diabetes, and/or heart failure. Recent Findings The studies reviewed include clinical trials that assessed the use of omecamtiv in the treatment of heart failure with reduced heart failure (GALACTIC-HF); effects of sotagliflozin in patients with diabetes and recent heart failure exacerbation; cardiovascular outcomes with the use of omega-3 carboxylic acids in patients with high vascular risk and atherogenic dyslipidemia (STRENGTH) and omega-3 fatty acids in elderly patients with recent myocardial infarction (OMEMI); efficacy and safety of evinacumab in patients with refractory hypercholesterolemia; and the use of coronary computed tomography angiography for the assessment of suspected acute coronary syndrome. In addition, we review the results of the International Polycaps Study (TIPS-3) on the use of a polypill for the primary prevention of cardiovascular disease in intermediate-risk people. Finally, we discuss the SAMSON trial—a three-arm-N-of-1 trial—to identify the root cause of the symptoms contributing to patient nonadherence to statin therapy. Summary The studies presented at the American Heart Association Scientific Session 2020 represent remarkable contributions in the field of cardiovascular disease and prevention.

Detection of subclinical atherosclerosis through noninvasive imaging such as ultrasound and magnetic resonance imaging (MRI) can improve cardiovascular risk stratification beyond that based on traditional cardiovascular risk factors. Ultrasound-based measures such as carotid intima-media thickness (CIMT) and presence of plaque (carotid, iliofemoral) have been evaluated and shown to have associations with cardiovascular events. However, given issues with reproducibility and other potential errors related to assessment of CIMT, there is currently a greater focus on use of carotid artery plaque measurement for cardiovascular risk assessment. The Mannheim consensus defined plaque as a focal structure or thickening (1) that is at least 50% greater than the thickness of its surrounding vessel, or (2) encroaches into the arterial lumen by at least 0.5 mm, or (3) demonstrates a CIMT greater than 1.5 mm. Several methods of plaque quantification including plaque score, plaque area, and 3D ultrasound-based plaque volume have been shown to predict cardiovascular outcomes. Additional efforts in characterizing plaque also continue to be evaluated. Carotid MRI is an important diagnostic tool not only to identify plaque burden but also to characterize plaque components including a thin fibrous cap, lipid-rich necrotic core, calcification, and intraplaque hemorrhage. It demonstrates moderate to excellent correlation of different plaque characteristics with histology. Clinical data on the value of MRI in risk prediction are starting to emerge. Numerous prospective and retrospective studies have shown MRI-derived measures of plaque characteristic and burden can identify those at higher risk for future cardiovascular events. At the current time, coronary calcium scoring is the recommended imaging approach in cardiovascular risk stratification. However, as technology continues to advance, the value of ultrasound and MRI in cardiovascular risk stratification will likely increase.

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin–angiotensin–aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro–B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in the United States, leading to one in four deaths. The role of inherited susceptibility to CVD is well established, from rare monogenic disorders to polygenic traits. For many of these conditions, guidelines exist for medical interventions and other preventative care that can improve outcomes and quality of life. Methods: We developed a comprehensive genetic screen, "HeartCare", consisting of a 158 gene panel evaluating 1) Mendelian conditions including cardiomyopathies, aortopathies, arrhythmias, and dyslipidemias, 2) a coronary artery disease polygenic risk score (PRS), 3) variants in the LPA gene encoding Lipoprotein(a) that are an independent risk factor for atherosclerotic CVD events, and 4) pharmacogenetic (PGx) variants contributing to simvastatin-induced myopathy and warfarin metabolism. After sequencing in a CAP/CLIA certified laboratory, results were returned to the ordering physician after a multi-disciplinary sign-out conference and uploaded to the EMR. Results: As of June 2020, 678 individuals had completed testing with a 31% overall positive rate for Mendelian genes, elevated polygenic risk, and LPA risk alleles (excluding PGx). Of these, 8.1% had a positive finding for a Mendelian condition, the majority (60%) being dyslipidemias (e.g., FH), followed by 25% cardiomyopathies (e.g., HCM, DCM, ARVC) and 6% aortopathies (e.g., Marfan, Loeys-Dietz). Approximately 20% of individuals carried an LPA risk allele, and 9.3% belonged to the high-risk group according to their PRS. Approximately half had a PGx finding related to simvastatin and/or warfarin metabolism. Nearly one in five individuals had a finding with direct clinical care impact, including referral to specialists, imaging, laboratory studies, therapies/procedures (e.g., PCSK9i, ICD). Conclusions: To our knowledge, this is the first test of its kind assaying four distinct categories of genetic variation related to cardiovascular health. Our results demonstrate that comprehensive testing can be routinely used to identify individuals who may benefit from interventions to improve survival, reduce morbidity, and enhance quality of life.

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population

Introduction: Black men and women are at higher risk for atherosclerotic cardiovascular disease (ASCVD) and when diagnosed, have greater morbidity and mortality as compared to individuals from European ancestry (EA). In patients with familial hypercholesterolemia (FH), it remains unknown whether Black patients have similarly increased risk for ASCVD. Hypothesis: To characterize the prevalence of ASCVD and to determine the strongest predictors of ASCVD in Black FH patients compared to EAs. Methods: The prevalence of ASCVD in 173 Black adult patients with FH followed in US-based lipid clinics was assessed retrospectively through a multicenter. A multivariate logistic regression model was used to determine the strongest predictors of ASCVD. Covariates included age, sex, diabetes mellitus, hypertension, and current smoking. ASCVD was defined as coronary, peripheral, and cerebrovascular events including angina, myocardial infarction, coronary angioplasty, peripheral arterial surgery, claudication, peripheral angioplasty, transient ischemic attack, stroke, and carotid endarterectomy. Results: Baseline characteristics of the 173 Black adult patients compared to EAs are shown in table 1. Black patients with FH were more likely to have higher BMI, hypertension, diabetes and to be current smokers. The prevalence of ASCVD in Black patients with FH was 38% compared to 30% in EAs, an absolute difference of 8% (p=0.047). The strongest predictors of ASCVD in Black patients with FH were hypertension and current smoking (table 2). Conclusions: Black patients with FH have a significantly higher prevalence of ASCVD when compared to EAs with FH. The strongest predictors of ASCVD in Black patients with FH were hypertension and current smoking. Aggressive primary prevention strategies specifically focused on the management of hypertension and smoking cessation should be tested for impact on the cardiovascular risk profile of Black patients with FH.

Introduction: Clinical trials suggest that low-saturated fat diet (LSFD) may reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with hypertriglyceridemia (HTG). Monocytes play crucial roles in atherogenesis. Hypothesis: LSFD vs high-saturated fat diet (HSFD) improves monocyte phenotypes, thereby reducing ASCVD risk, in subjects with HTG. Methods: Subjects with HTG and metabolic syndrome (MetS, n=19) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) plus a breakfast on day 5, separated by a 4- to 6-week washout period. Blood was drawn on day 1 fasting before the diets and 3 times on day 5 (fasting before the breakfast and 4 and 6 hours postprandial) for measurement of lipid profile and analyses of monocyte phenotypes by flow cytometry and monocyte adhesion by a lab-on-a-chip microfluidic assay. Results: On day 5, LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride and LDL-triglyceride and fasting and postprandial total cholesterol, LDL-cholesterol, and small dense LDL-cholesterol. Compared to HSFD, LSFD reduced fasting and postprandial intracellular lipid accumulation in classical and intermediate monocytes examined by nile red staining and indicated by side scatter value of flow cytometric analysis. LSFD versus HSFD also reduced ex vivo uptake of oxidized LDL by classical monocytes at 4 hours postprandially and by intermediate monocytes in fasting state. Surface levels of molecules involved in monocyte adhesion/migration, including CD11c, CD81, and CCR2, were lower on monocytes with LSFD than with HSFD. Consistently, LSFD compared to HSFD reduced monocyte adhesion to VCAM-1. Intracellular levels of cytokines such as IL-1β, TNFα, and IL-6 in monocytes showed no difference between the two diets. Conclusions: In subjects with HTG and MetS, short-term LSFD compared to HSFD reduces monocyte intracellular lipid accumulation and improves monocyte phenotypes with reductions in monocyte adhesion and oxidized LDL uptake. These findings highlight the importance of diet composition in monocyte phenotypes and possibly atherosclerosis risks in patients with HTG and MetS.

Introduction: Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study Methods: We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score 3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors. Results: Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50). Conclusions: In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.

Purpose of Review The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the 2020 European Society of Cardiology (ESC) Congress—The Digital Experience. Recent Findings The studies reviewed include clinical trials on novel RNA interference-based lipid-lowering therapies AKCEA-APOCIII-LRx and vupanorsen (AKCEA-ANGPTL3-LRx); the EVAPORATE trial assessing the effects of icosapent ethyl on coronary plaque volume progression; the LoDoCo2 trial evaluating the efficacy of low-dose colchicine in cardiovascular disease risk reduction among patients with chronic coronary artery disease; as well as the EMPEROR-Reduced trial evaluating cardiovascular and renal outcomes with empagliflozin in patients with heart failure and reduced ejection fraction. In addition, we review the BPLTTC analysis on blood pressure treatment across blood pressure levels and CVD status and discuss findings from the BRACE CORONA study that examined continuing versus suspending angiotensin-converting enzyme inhibitor or angiotensin receptor blockers in patients on these antihypertensive medications who were hospitalized with COVID-19 infection. Summary The studies presented at the 2020 digital ESC Congress highlight the continuing advancements in the field of CVD prevention.

Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to 300 or 300 pg/ml, compared with NT-proBNP 100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of 100 pg/ml and SBP of 140 to 149 mm Hg.Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

This review focuses on recent evidence examining the role triglycerides (TG) and triglyceride-enriched lipoproteins (TGRL) play in atherosclerotic cardiovascular disease (ASCVD). It also provides a succinct overview of current and future TG-lowering therapies for ASCVD risk reduction. Epidemiological and Mendelian randomization studies have consistently shown that TGRL are strongly associated with ASCVD. REDUCE-IT demonstrated cardiovascular benefit with icosapent ethyl in high-risk patients with hypertriglyceridemia on statin therapy. Polymorphisms in APOC3 and ANGPTL3 are associated with ASCVD and use of RNA-interfering therapies to target these proteins has shown TG lowering in early phase trials. TG and TGRL are causally associated with ASCVD. Lifestyle modifications and statin therapy can lower TG/TGRL and are considered first-line treatment for hypertriglyceridemia. Icosapent ethyl has been shown to reduce residual ASCVD risk in high-risk patients on maximally tolerated statins. Ongoing clinical trials will better define optimal therapy for patients on statins with residual hypertriglyceridemia.

Background Accumulation of lipoprotein X (LpX) in blood can cause severe hypercholesterolemia and cutaneous xanthomas. Monocytes sensitively sense lipid changes in circulation and contribute to inflammation. However, how monocytes respond to LpX is undefined. Objective We examined the phenotype of monocytes from a patient, who had LpX, severe hypercholesterolemia, and extensive cutaneous xanthomas, and effects of semiselective plasmapheresis therapy (SPPT). Method Fluorescence-activated cell sorting and adhesion assays were used to examine monocyte phenotype and ex vivo oxidized low-density lipoprotein uptake and adhesion in the patient before and after treatment with SPPT. Effects of plasma from the patient on the phenotype and adhesion of monocytes from a healthy participant were determined. Results SPPT improved hypercholesterolemia and cutaneous xanthomas. Before treatment, the patient had lower frequency of nonclassical monocytes but higher frequency of intermediate monocytes than the control participant. Before treatment, monocytes from the patient with LpX showed more intracellular lipid accumulation, alterations in several cell surface markers and intracellular cytokines, as well as enhanced oxidized low-density lipoprotein uptake and reduced adhesion compared with control. After SPPT, the phenotypes of monocytes from the patient with LpX were similar to control monocytes. Incubation with plasma from the patient before treatment as compared with plasma from the control participant or the patient after treatment increased CD11c expression and adhesion of monocytes from a healthy participant. Conclusion LpX-induced hypercholesterolemia increased lipid accumulation and altered the phenotype of monocytes, which may contribute to cutaneous xanthoma development. Removal of LpX by SPPT reduced lipid accumulation and improved monocyte phenotype, likely contributing to xanthoma resolution.

BACKGROUND Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and

Background: Implantable cardioverter-defibrillators (ICDs) are indicated in patients with left ventricular ejection fraction ≤35%, but many eligible patients do not receive this therapy. In this cluster randomized trial, we investigated the impact of a best practice alert (BPA) through the electronic health records on the rates of electrophysiology referrals, ICD implantations, and all-cause mortality in severe cardiomyopathy patients. Methods and Results: Providers in the Heart and Vascular Institute (n=106) and in General Internal Medicine (n=89) were randomized to receive or not receive a BPA recommending consideration for ICD implantation. Patients belonging to the BPA and no BPA groups of providers were followed to the end points of electrophysiology referrals, ICD implantations, and all-cause mortality. Between 2013 and 2015, patients with reduced left ventricular ejection fraction were managed by 93 providers in the BPA (n=997 patients) and 102 providers in the no BPA (n=909 patients) groups. Patients in the 2 groups had comparable baseline characteristics. After a median follow-up of 36 months, 638 (33%) patients were referred to electrophysiology, 536 (27%) received an ICD, and 445 (23%) died. Patients in the BPA group were more likely to be referred to electrophysiology (hazard ratio=1.23; P =0.026), to receive ICD therapy (hazard ratio=1.35; P =0.006), and exhibited a trend towards slightly lower mortality (hazard ratio=0.85; P =0.091). Conclusions: Delivering a BPA through the electronic health record recommending to providers consideration of ICD implantation when the left ventricular ejection fraction is ≤35% improves the rates of electrophysiology referrals and ICD therapy in patients with severe left ventricular dysfunction.