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Review of the US and European literature indicates that most patients at high risk for atherosclerotic cardiovascular disease (ASCVD are not treated with high-intensity statins, despite strong clinical-trial evidence of maximal statin benefit. High-intensity statins are recommended for 2 categories of patients: those with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD. Most patients with ASCVD are candidates for high-intensity statins, with a goal for low-density lipoprotein cholesterol reduction of 50% or greater. A subgroup of patients with ASCVD are at very high risk and can benefit by the addition of nonstatin drugs (ezetimibe with or without bile acid sequestrant or bempedoic acid and/or a proprotein convertase subtilisin/kexin type 9 inhibitor). High-risk primary prevention patients are those with severe hypercholesterolemia, diabetes with associated risk factors, and patients aged 40 to 75 years with a 10-year risk for ASCVD of 20% or greater. In patients with a 10-year risk of 7.5% to less than 20%, coronary artery calcium scoring is an option; if the coronary artery calcium score is 300 or more Agatston units, the patient can be up-classified to high risk. If high-intensity statin treatment is not tolerated in high-risk patients, a reasonable approach is to combine a moderate-intensity statin with ezetimibe. In very high-risk patients, proprotein convertase subtilisin/kexin type 9 inhibitors lower low-density lipoprotein cholesterol levels substantially and hence reduce risk as well.

Purpose This review describes the considerations for the design and implementation of a hybrid cardiac rehabilitation (HYCR) program, a patient-individualized combination of facility-based cardiac rehabilitation (FBCR) with virtual cardiac rehabilitation (CR) and/or remote CR. Review methods To help meet the goal of the Millions Hearts Initiative to increase CR participation to 70% by 2022, a targeted review of the literature was conducted to identify studies pertinent to the practical design and implementation of an HYCR program. Areas focused upon included the current use of HYCR, exercise programming considerations (eligibility and safety, exercise prescription, and patient monitoring), program assessments and outcomes, patient education, step-by-step instructions for billing and insurance reimbursement, patient and provider engagement strategies, and special considerations. Summary A FBCR is the first choice for patient participation in CR, as it is supported by an extensive evidence base demonstrating effectiveness in decreasing cardiac and overall mortality, as well as improving functional capacity and quality of life. However, to attain the CR participation rate goal of 70% set by the Million Hearts Initiative, CR programming will need to be expanded beyond the confines of FBCR. In particular, HYCR programs will be necessary to supplement FBCR and will be particularly useful for the many patients with geographic or work-related barriers to participation in an FBCR program. Research is ongoing and needed to develop optimal programming for HYCR.

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (

Ty J. Gluckman, MD, FACC, Chair Niti R. Aggarwal, MD, FACC Nicole M. Bhave, MD, FACC Gregory J. Dehmer, MD, MACC Olivia N. Gilbert, MD, MSc, FACC Chayakrit Krittanawong, MD Dharam J. Kumbhani, MD, SM, FACC Andrea L. Price, CPHQ, RCIS, AACC Javier A. Sala-Mercado, MD, PhD David E.

Million Hearts and partners have been committed to raising national cardiac rehabilitation participation rates to a goal of 70%. Quality improvement tools, resources, and surveillance models have been developed in support. Efforts to enhance research programs and collaborative initiatives have created momentum to accelerate implementation of new care models.

Dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, have been shown to improve cardiac health. Intermittent fasting is another type of popular dietary pattern that is based on timed periods of fasting. Two different regimens are alternative day fasting and time-restricted eating. Although there are no large, randomized control trials examining the relationship between intermittent fasting and cardiovascular outcomes, current human studies that suggest this diet could reduce the risk for cardiovascular disease with improvement in weight control, hypertension, dyslipidemia, and diabetes. Intermittent fasting may exert its effects through multiple pathways, including reducing oxidative stress, optimization of circadian rhythms, and ketogenesis. This review evaluates current literature regarding the potential cardiovascular benefits of intermittent fasting and proposes directions for future research.

Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group.Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression.246 individuals (mean age = 63 ± 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ± 27 mg/dL). Age65 years (RR = 2.17, 95%CI = 1.49-3.23), female sex (RR = 2.10, 95%CI = 1.42-3.10), and no diabetes (RR = 2.22, 95%CI = 1.18-4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10-0.66).Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.

Aspirin use in the prevention of cardiovascular events has been a mainstay of treatment for decades. However, the use of aspirin in primary prevention of atherosclerotic cardiovascular disease has recently come under scrutiny. Several recent studies have evaluated the use of aspirin in primary prevention and the results suggest that in many patients the risks may outweigh the benefits. Closer examination of these trials suggests that the use of aspirin therapy for primary prevention may have a role but likely needs a more tailored approach and that caution is needed in prescribing aspirin for primary prevention. In conclusion, in this article we review the evolving evidence for aspirin in the primary prevention of atherosclerotic cardiovascular disease.

Background: South Asians are at a significantly increased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), are diagnosed at relatively younger ages, and exhibit more severe disease phenotypes as compared with other ethnic groups. The pathophysiological mechanisms underlying T2D and CVD risk in South Asians are multifactorial and intricately related. Method: A narrative review of the pathophysiology of excess risk of T2D and CVD in South Asians. Result: T2D and CVD have shared risk factors that encompass biological factors (early life influences, impaired glucose metabolism, and adverse body composition) as well as behavioral and environmental risk factors (diet, sedentary behavior, tobacco use, and social determinants of health). Genetics and epigenetics also play a role in explaining the increased risk of T2D and CVD among South Asians. Additionally, South Asians harbor several lipid abnormalities including high concentration of small-dense low-density lipoprotein (LDL) particles, elevated triglycerides, low high-density lipoprotein (HDL)- cholesterol levels, dysfunctional HDL particles, and elevated lipoprotein(a) that predispose them to CVD. Conclusion: In this comprehensive review, we have discussed risk factors that provide insights into the pathophysiology of excess risk of T2D and CVD in South Asians.

This article describes the October 2020 proceedings of the Million Hearts Cardiac Rehabilitation Think Tank: Accelerating New Care Models, convened with representatives from professional organizations, cardiac rehabilitation (CR) programs, academic institutions, federal agencies, payers, and patient representative groups. As CR delivery evolves, terminology is evolving to reflect not where activities occur (eg, center, home) but how CR is delivered: in-person synchronous, synchronous with real-time audiovisual communication (virtual), or asynchronous (remote). Patients and CR staff may interact through ≥1 delivery modes. Though new models may change how CR is delivered and who can access CR, new models should not change what is delivered—a multidisciplinary program addressing CR core components. During the coronavirus disease 2019 (COVID-19) public health emergency, Medicare issued waivers to allow virtual CR; it is unclear whether these waivers will become permanent policy post-public health emergency. Given CR underuse and disparities in delivery, new models must equitably address patient and health system contributors to disparities. Strategies for implementing new CR care models address safety, exercise prescription, monitoring, and education. The available evidence supports the efficacy and safety of new CR care models. Still, additional research should study diverse populations, impact on patient-centered outcomes, effect on long-term outcomes and health care utilization, and implementation in diverse settings. CR is evolving to include in-person synchronous, virtual, and remote modes of delivery; there is significant enthusiasm for implementing new care models and learning how new care models can broaden access to CR, improve patient outcomes, and address health inequities.

Although significant progress has been made to reduce the global burden of cardiovascular disease, efforts have focused primarily on treatment of manifest disease rather than on prevention of events. An enormous opportunity exists to transition focus from intervention to providing equal attention to prevention of cardiovascular disease. The nascent specialty of "preventive cardiology" is emerging from the background of long-established services such as lipid, diabetes, hypertension, and general cardiology clinics. It is incumbent on the cardiology community to invest in cardiovascular prevention because past gains are threatened with the rising tide of obesity and diabetes. Now is the time to establish a dedicated preventive cardiology subspecialty to train the clinicians of the future. This American College of Cardiology Council Perspective aims to define the need for preventive cardiology as a unique subspecialty, broaches controversies, provides a structure for future training and education, and identifies possible paths forward to professional certification.

The decline in cardiovascular (CV) mortality over the last 50 years can be largely attributed to advances in preventive care [(1)][1]. Despite these improvements, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide [(1)][1]. Recent advances in

PCSK9 inhibitors are potent low-density lipoprotein cholesterol-lowering medications. There is a lack of data regarding safety and efficacy of PCSK9 inhibitors in cardiac transplant patients. In this case series, we provide data supporting the low-density lipoprotein-lowering efficacy and short-term safety of PCSK9 inhibitors in three cardiac transplant patients.

The measurement of high-density lipoprotein cholesterol is highly utilized by clinicians to help predict cardiovascular risk, but this measure is not causally associated with atherosclerotic cardiovascular disease events. The use of Mendelian randomization studies has led to a change in investigative attention from the high-density lipoprotein cholesterol concentration to its physiological functions. High-density lipoprotein plays key roles in important pathways related to the development of atherosclerotic disease including reverse cholesterol transport, oxidation and inflammation, and endothelial function as well as in other physiological systems including immune system modulation, cellular apoptosis, and endothelial progenitor cell homeostasis. The identification of dysfunctional high-density lipoprotein may better predict future cardiovascular events compared to numerical high-density lipoprotein cholesterol and aid in enhanced clinical risk stratification. The emergence of discrete physiological measurements of high-density lipoprotein, such as cholesterol efflux capacity and the high-density lipoprotein inflammatory index, may provide an opportunity for clinical application in the future. However, the validity of these measurements and their commercial availability remain barriers to a realistic transition to clinical medicine.

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.

Despite historical evidence suggesting an inverse association between HDL cholesterol (HDL-C) and adverse cardiovascular events, pharmacological efforts to increase HDL-C and improve outcomes have not been successful. Recently, a U-shaped association between HDL-C and adverse events has been demonstrated in several population cohorts, further complicating our understanding of the clinical significance of HDL. Potential explanations for this finding include genetic mutations linked to very high HDL-C, impaired HDL function at high HDL-C levels, and residual confounding. However, our understanding of this association remains premature and needs further investigation.

James L. Januzzi, Jr, MD, FACC, Chair Tariq Ahmad, MD, MPH, FACC Brendan Everett, MD, FACC William Hucker, MD, PHD Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela B. Morris, MD, FACC Robert N. Piana, MD, FACC Sunil V. Rao, MD, FACC Marielle Scherrer-Crosbie, MD, PhD

Supplemental Digital Content is available in the text., Objective: The underlying pathobiology of the paradoxical relationship between obesity and adverse outcomes in coronary artery disease (CAD) is unclear. Our objective was to determine the association between obesity and circulating progenitor cell (CPC) counts—a measure of intrinsic regenerative capacity—in asymptomatic individuals and patients with CAD and its impact on the obesity paradox. Approach and Results: CPCs were enumerated by flow cytometry as CD45med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 years of age; 28% obese) and 1277 patients with CAD (66 years of age; 39% obese). The association between obesity and CPCs was analyzed using linear regression models. The association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-year follow-up in patients with CAD was studied using Cox models. Obesity was independently associated with 16% to 34% higher CPC counts (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated by systemic inflammation, insulin resistance, or secretion but partly attenuated by cardiorespiratory fitness and body composition. In patients with CAD, obesity was associated with 8% to 12% higher CPC counts and 30% lower risk of adverse outcomes. Compared with nonobese patients, only obese patients with high CPC counts (CD34+ cells ≥median, 1806 cells/mL) were at a lower risk (hazard ratio, 0.52 [95% CI, 0.31–0.88]), whereas those with low counts (

Background: Absence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear. Methods: Multi-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use. Results: Among these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1–12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04–2.66]; and 1.48 [95% CI, 1.01–2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18–1.54]; and 1.37 [95% CI, 1.21–1.54]), respectively. Conclusions: The presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.

We aimed to evaluate if a shorter course of DAPT followed by P2Y12 inhibitor monotherapy is as effective as a 12-month course with fewer bleeding events. PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials of ACS patients comparing dual antiplatelet therapy (DAPT) for 1 to 3 months followed by a P2Y12 inhibitor to 12-month DAPT. Quality assessment was performed with the Cochrane Collaboration risk of bias assessment tool. Five randomized clinical trials were included, with a total of 18,046 participants. Antiplatelet strategies were aspirin and P2Y12 inhibitor for 12 months compared with aspirin and P2Y12 inhibitor for 1 to 3 months followed by P212 inhibitor alone. Patients randomized to 1 to 3 months of DAPT followed by P2Y12 inhibitor monotherapy had lower rates of major bleeding (1.42% vs 2.53%; OR 0.53; 95% CI 0.42-0.67; p0.001; I

Although statin therapy is a primary treatment to prevent cardiac allograft vasculopathy (CAV), its use may be delayed due to pharmacologic interactions in the early post-transplant period among heart transplant (HT) recipients with hepatitis C virus positive (HCV+) donors. Further examination of the possible benefits of early, nonstatin lipid-lowering therapies (LLT), such as PCSK9 inhibitors (PCSK9i), among this specific subset of transplant recipients is therefore becoming increasingly important. We report a 60-year-old man who received a HT from a HCV+ donor for end-stage ischemic cardiomyopathy. In the early post-transplant period, there was concern for drug-drug interactions between statin, immunosuppressant, and direct acting antiviral (DAA) therapy. In addition, prior to transplant, he reported statin-associated muscle symptoms in response to multiple statins, which persisted despite attempts to re-challenge and use an every-other-day dosing strategy. Therefore, the patient was started on PCSK9i therapy after transplantation and while receiving curative DAA therapy for HCV. As the number of HT recipients of HCV+ donors continue to rise, investigation into the safety and benefits of early use of PCSK9i for the reduction of CAV and improved cardiovascular and mortality outcomes should be pursued.

Before the coronavirus disease 2019 (COVID-19) pandemic, use of telehealth services had been limited in cardiovascular care. Potential benefits of telehealth include improved access to care, more efficient care management, reduced costs, the ability to assess patients within their homes while involving key caretakers in medical decisions, maintaining social distance, and increased patient satisfaction. Challenges include changes in payment models, issues with data security and privacy, potential depersonalization of the patient-clinician relationship, limitations in the use of digital health technologies, and the potential impact on disparities, including socioeconomic, gender, and age-related issues and access to technology and broadband. Implementation and expansion of telehealth from a policy and reimbursement practice standpoint are filled with difficult decisions, yet addressing these are critical to the future of health care.

The metabolic syndrome (MetS) is a constellation of comorbid derangements that increase the risk for both type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Diabetes may be preventable in many individuals with the MetS through the implementation of lifestyle and behavioral preventive strategies including dietary approaches. Several dietary patterns demonstrate efficacy in those living with the MetS to prevent progression to diabetes and reduce the risk of CVD.

Cardiac rehabilitation is a key component of secondary prevention for patients who have undergone coronary artery bypass graft surgery. Cardiac rehabilitation is a comprehensive, multidisciplinary, long-term provision of medical evaluation, prescriptive exercise, cardiac risk factor modification, and education. Not only does cardiac rehabilitation reduce cardiovascular mortality and hospital readmissions, but it also improves the functional status and quality of life for patients. Despite the strong evidence and recommendation for referral to and utilization of cardiac rehabilitation early in the postoperative period, it remains underutilized, especially in the elderly and women.

Cardiovascular mortality declined in the United States from 1980 to 2000 due to advancements predominately in prevention, in addition to therapies/technology. Unfortunately, the rise in obesity and diabetes has in part been responsible for halting this progress resulting in a concerning increase in cardiovascular mortality, particularly in younger individuals. Compared to other industrialized countries, the United States provides low-value care in a healthcare system which is disease focused, but is inadequate at promoting health. Herein, we discuss the importance of promoting health as well as the “three buckets of prevention”: (1) traditional clinical prevention, (2) innovative clinical prevention, and (3) community-wide prevention. These “buckets” provide a useful framework to discuss the challenges and opportunities for cardiovascular preventive specialists to improve the care of their patients, as well as the populations they serve.

Background Sex differences in the trends for control of cardiovascular disease (CVD) risk factors have been described, but temporal trends in the age at which CVD and its risk factors are diagnosed and sex‐specific differences in these trends are unknown. Methods and Results We used the Medical Expenditure Panel Survey 2008 to 2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease, or stroke, and who reported the age when these conditions were diagnosed, were included. We included 100 709 participants (50.2% women), representing 91.9 million US adults with above conditions. For coronary heart disease and hypercholesterolemia, mean age at diagnosis was 1.06 and 0.92 years older for women, compared with men, respectively (both P P P P =0.03), it increased by 0.22 years for men ( P =0.02). Conclusions The trend in decreasing age at diagnosis for CVD and its risk factors in the United States appears to be more pronounced among women. While earlier identification of CVD risk factors may provide opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD earlier in life, and sex‐specific interventions may be needed.

Untreated hypertension may contribute to increased atherosclerotic cardiovascular disease (ASCVD) risk in South Asians (SA). We assessed HTN prevalence among untreated adults free of baseline ASCVD from the MASALA & MESA studies. The proportion of participants who received discordant recommendations regarding antihypertensive pharmacotherapy use by the 2017-ACC/AHA and JNC7 Guidelines across CAC score categories in each race/ethnic group was calculated. Compared with untreated MESA participants (n=3896), untreated SA (n=445) were younger (55±8 versus 59±10 years), had higher DBP (73±10 versus 70±10mmHg), total cholesterol (199±34 versus 196±34mg/dL), statin use (16% versus 9%) and CAC=0 prevalence (69% versus 58%), with fewer current smokers (3% versus 15%) and lower 10-year-ASCVD-risk (6.4% versus 9.9%) (all p100 and thus may be better at informing hypertension management in American South Asians.

Introduction: Although data up to 2016 suggests that mortality from cardiovascular disease (CVD) in the US appears to be on a decreasing trend, there is evidence of stagnation in progress among young adults, especially women. Sex differences in the trends for control of CVD risk factors have been described, but the temporal trends in the age at which CVD and its risk factors are diagnosed in the US, and whether there are sex-specific differences in these trends is unknown. Methods: We used the Medical Expenditure Panel Survey (MEPS) 2008-2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease (CHD) or stroke and reported the age at which these conditions were diagnosed were included. The trend in the age at diagnosis was calculated from the annual change overall and by sex, using a linear regression model. Results: There were 100,709 participants (50.2% women), representing 91.9 million US adults with the above disease conditions. The mean age at diagnosis of CVD risk factors has decreased over time, with steeper declines among women [(Hypercholesterolemia: women - annual decrease of 0.31 years, men-annual decrease of 0.24 years, all Ps Conclusion: The decreasing trend in the age at diagnosis for CVD and its risk factors in the US appears to be more pronounced among women. While earlier identification of CVD risk factors may provide an opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD at the earliest opportunity and sex-specific interventions may be needed.

Background PCSK9 inhibitors were approved by the Food and Drug Administration in 2015 to lower low-density lipoprotein cholesterol (LDL-C) levels. In the years following, additional research findings, changes in national guideline recommendations, and price reductions have occurred. Objective The goal of the study is to describe the characteristics and trends in PCSK9 inhibitor prescription fills and price, from initial FDA approval in Quarter 3 2015 through Quarter 4 2019, at the national and state levels. Methods Cross-sectional study of fills obtained using the IQVIA National Prescription Audit®, Extended Insights, New to Brand, and Regional databases. Prescription fills included injections that provided cholesterol-lowering therapy from 14 to 90 days for the two PCSK9 inhibitors: alirocumab (75 mg/mL and 150 mg/mL) or evolocumab (140 mg/mL and 420 mg/3.5 mL). Quarterly prescription fills obtained nationally for Quarter 3 2015 through Quarter 4 2019, by sex, age, and state during 2019. Results Over the time period examined, 2.75 million PCSK9 inhibitor prescriptions were filled nationally (alirocumab: 38%; evolocumab: 62%), and the average retail price per fill (unadjusted $US) from retail pharmacies decreased by 40% from $1502 to $896 per fill. Year-over-year percent change in new PCSK9 inhibitor users increased throughout the observation period, with 9611 new alirocumab users and 25,381 new evolocumab users in Q4 2019. PCSK9 inhibitor fill rates ranged from 5.6 per 1000 in the Northeast to 3.4 per 1000 in the West in 2019, with the highest rate per 1000 in Louisiana (9.1), and lowest in Wyoming (1.3). Conclusions PCSK9 inhibitor prescriptions have increased nationally since 2015, coinciding with additional evidence supporting their use for LDL-C lowering and cardiovascular event reduction. Although the retail price has decreased since introduction, cost and delivery mode likely continue as barriers.

Objective Patients with CAD have substantial residual risk of mortality, and whether hitherto unknown small-molecule metabolites and metabolic pathways contribute to this risk is unclear. We sought to determine the predictive value of plasma metabolomic profiling in patients with CAD. Approach and results Untargeted high-resolution plasma metabolomic profiling of subjects undergoing coronary angiography was performed using liquid chromatography/mass spectrometry. Metabolic features and pathways associated with mortality were identified in 454 subjects using metabolome-wide association studies and Mummichog, respectively, and validated in 322 subjects. A metabolomic risk score comprising of log-transformed HR estimates of metabolites that associated with mortality and passed LASSO regression was created and its performance validated. In 776 subjects (66.8 years, 64% male, 17% Black), 433 and 357 features associated with mortality (FDR-adjusted q

Background: Coronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear. Methods: White, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested. Results: Among 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P Conclusions: In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

Cardiovascular disease remains one of the most prevalent and preventable chronic conditions worldwide. Diet modification is the foundation of cardiovascular disease prevention. Several dietary approaches have emerged to promote better cardiovascular health. The rapid dissemination of anecdotal and observational data through the internet and social media has caused confusion amongst providers and patients. The aim of this comprehensive review is to present objective insights into 2 of today's most popular fad diets: ketogenic diet and intermittent fasting. We will evaluate the performance of these diets based on their impact on cardiovascular risk factors.

Premature atherosclerotic peripheral artery disease (PAD) of the lower extremities is characterized by disease diagnosis before the age of 50 years. The global prevalence of premature PAD has increased, and the disease is often underdiagnosed given heterogenous patient symptoms. Traditional cardiovascular risk factors like smoking, diabetes, hypertension, and hyperlipidemia as well as non-traditional risk factors like elevated lipoprotein(a), family history of PAD, hypercoagulability, and systemic inflammation are associated with premature PAD. Patients with premature PAD tend to have an aggressive vascular disease process, a high burden of cardiovascular risk factors, and other concomitant atherosclerotic vascular diseases like coronary artery disease. Prevention of cardiovascular events, improvement of symptoms and functional status, and prevention of adverse limb events are the main goals of patient management. In this review, we discuss the epidemiology, risk factors, clinical evaluation, and management of patients with premature PAD.

Background Women have higher circulating levels of soluble urokinase‐type plasminogen activator receptor (suPAR), and elevated suPAR is associated with cardiovascular risk. The independent association of sex with suPAR and the impact of sex on its association with cardiovascular risk are unknown. Methods and Results Plasma suPAR was measured using ELISA in 2 cohorts of 666 asymptomatic individuals (49 years, 65% women) and 4184 patients with coronary artery disease (63 years, 37% women). Independent association of sex with suPAR was studied using linear regression models adjusted for demographics, risk factors, and visceral adiposity in asymptomatic participants. Impact of sex on association of suPAR with all‐cause mortality was studied in patients with coronary artery disease using multivariable‐adjusted Cox models. Sex‐specific suPAR cutoffs for predicting all‐cause mortality were calculated. Asymptomatic women had 10% higher suPAR compared with men after adjusting for confounders, and visceral adiposity partly accounted for this association. Over a median follow‐up of 5.2 years, 795 deaths were recorded in patients with coronary artery disease. Log 2 ‐transformed suPAR was independently associated with mortality (hazard ratio per 1‐SD 1.72, 95% CI 1.60–1.85) and an interaction with sex was noted ( P =0.005). Association of suPAR with mortality was slightly weaker in women (hazard ratio 1.61, 95% CI 1.41–1.83) compared with men (hazard ratio 1.83, 95% CI 1.67–2.00). However, using sex‐specific suPAR cut‐offs (4392 pg/mL for women and 3187 pg/mL for men), a similar mortality incidence was observed for both sexes (38.5% and 35.5%, respectively, P =0.3). Conclusions Women have 10% higher plasma suPAR levels compared with men. Elevated sex‐specific plasma suPAR levels are equally predictive of risk of adverse events in both sexes.

Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and Results A total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD 34 + and CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of Ex MI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with Ex MI had a significant decrease in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (−18%, P =0.01) after stress that was inversely correlated with the magnitude of ischemia ( r =−0.19, P =0.003). In contrast, patients without Ex MI had an increase in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (14.7%, P =0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P PC counts in those with Ex MI ( P =0.03), suggesting a greater decrease in PC s in those with a greater change in stromal‐derived factor‐1α level with exercise. Conclusions Ex MI is associated with a significant decrease in circulating levels of CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PC s to the ischemic myocardium. The physiologic consequences of this uptake of PC s and their therapeutic implications need further investigation.

This review highlights selected cardiovascular disease (CVD) prevention studies presented at the 2019 American Heart Association (AHA) Scientific Sessions. Several important cardiovascular prevention studies were presented at the 2019 AHA Scientific Sessions. Results from the Colchicine Cardiovascular Outcomes Trial (COLCOT) showed that low-dose colchicine reduces the risk of recurrent CVD events among patients with recent myocardial infarction. A prospective analysis from the UK Biobank cohort demonstrated that the increased CVD risk associated with clonal hematopoiesis of indeterminate potential is mitigated by a common disruptive mutation in the IL6R gene that suppresses the pro-inflammatory IL-1β/IL-6 pathway. The Treat Stroke to Target trial demonstrated that reducing low-density lipoprotein cholesterol to

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the developed world. The economic impact of the epidemic is expected to total more than $800 billion by 2030. Low-cost interventions such as meditation and mindfulness, physical activity, and improvement in dietary habits are of particular interest in curbing the impact of CVD. The chapter will review the evidence for these interventions in primary and secondary prevention of CVD.

Atherosclerotic cardiovascular disease (ASCVD) and its associated economic burden are increasing globally. Although cardiac rehabilitation is a vital component of secondary prevention with proven benefits, it is underutilized due to numerous barriers, especially in resource-limited settings. New care models for delivery of comprehensive prevention programs such as community-based, home-based, and "hybrid" models implementing m-health, e-health, and telemedicine need to be adopted. Such new care models should be offered to all patients with established ASCVD (coronary, cerebral, and peripheral) and additionally to those at high risk of developing ASCVD with multiple risk factors for panvascular prevention.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Cardiovascular disease remains the leading cause of death worldwide with coronary atherosclerotic heart disease being the largest contributor. The mechanisms behind the presence and progression of atherosclerosis remain an area of intense scientific focus. Immune dysregulation and inflammation are key contributors to the development of an atherosclerotic plaque and its progression to acute coronary syndromes. Increased circulating levels of biomarkers of systemic inflammation including hsCRP are correlated with a higher cardiovascular risk. Targeting specific inflammatory pathways implicated in atherosclerotic plaque formation is an exciting area of ongoing research. Target specific therapies directed at pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and CCL2 have demonstrated slowing in the progression of atherosclerosis in animal models and improved cardiovascular outcomes in human subjects. Most notably, treatment with the monoclonal antibody canakinumab, which directly targets and neutralizes IL-1β, was recently shown to be associated with reduced risk of adverse cardiovascular events compared to placebo in a randomized, placebo-controlled trial. Several other therapies including colchicine, methotrexate and leukotriene inhibitors demonstrate the potential for lowering cardiovascular risk through immunomodulation, though further studies are needed. Understanding the role of inflammation in atherosclerosis and the development of targeted immunotherapies continues to be an evolving area of research that is rapidly becoming clinically relevant for the 21st century cardiac patient.

Metabolic equivalents, or METs, are routinely employed as a guide to exercise training and activity prescription and to categorize cardiorespiratory fitness (CRF). There are, however, inherent limitations to the concept, as well as common misapplications. CRF and the patient's capacity for physical activity are often overestimated and underestimated, respectively. Moreover, frequently cited fitness thresholds associated with the highest and lowest mortality rates may be misleading, as these are influenced by several factors, including age and gender. The conventional assumption that 1 MET = 3.5 mL O-2/kg/min has been challenged in numerous studies that indicate a significant overestimation of actual resting energy expenditure in some populations, including coronary patients, the morbidly obese, and individuals taking beta-blockers. These data have implications for classifying relative energy expenditure at submaximal and peak exercise. Heart rate may be used to approximate activity METs, resulting in a promising new fitness metric termed the "personal activity intelligence" or PAI score. Despite some limitations, the MET concept provides a useful method to quantitate CRF and define a repertoire of physical activities that are likely to be safe and therapeutic. In conclusion, for previously inactive adults, moderate-to vigorous physical activity, which corresponds to >= 3 METs, may increase MET capacity and decrease the risk of future cardiac events. (C) 2017 Elsevier Inc. All rights reserved.

Type 2 diabetes mellitus (DM) is a significant cause of premature complications and mortality in patients with cardiovascular disease (CVD). In addition to lifestyle modifications, conventional treatment of DM consists of oral hypoglycemic agents, insulin sensitizers, and subcutaneous insulin. In diabetic individuals with or at risk for CVD, aspirin and statin therapy reduce CVD morbidity and mortality. Several natural or herbal supplements have shown potential benefit in patients with CVD and DM. We provide an overview of the current guidelines for treatment of DM and CVD. We then review the literature to describe the efficacy of natural approaches to CVD risk reduction in diabetic patients, with a focus on physical activity, dietary modification, and natural/herbal supplements. Activity and diet improve cardiovascular outcomes in patients with CVD and DM. Natural and herbal supplements have potential for benefit but require further research to determine their efficacy and safety.

Background Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited. Objective Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (E h GSH) and cysteine will be associated with prevalent and incident AF. Methods Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level. Results For each 10% increase in E h GSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1–1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3–2.7; P = .004) when the median was used as a cutoff. The E h GSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3–12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1–2.7; P = .03). Each 10% increase in E h GSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1–1.7; P = .01). Conclusion Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.