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IntroductionCoronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC™) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC cardiac chambers for prediction of incident heart failure (HF).MethodsWe applied AI-CAC to 5750 CAC scans of asymptomatic individuals (52% female, White 40%, Black 26%, Hispanic 22% Chinese 12%) free of known cardiovascular disease at the MESA baseline examination (2000-2002). We used the 15-year outcomes data and compared the time-dependent area under the curve (AUC) of AI-CAC volumetry versus NT-proBNP, Agatston score, and 9 known clinical risk factors (age, gender, diabetes, current smoking, hypertension medication, systolic and diastolic blood pressure, LDL, HDL for predicting incident HF over 15 years.ResultsOver 15 years of follow-up, 256 HF events accrued. The time-dependent AUC [95% CI] at 15 years for predicting HF with AI-CAC all chambers volumetry (0.86 [0.82,0.91]) was significantly higher than NT-proBNP (0.74 [0.69, 0.77]) and Agatston score (0.71 [0.68, 0.78]) (p ​

PurposeSouth Asian (SA) persons have increased risks for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). We examined whether the association of DM with subclinical atherosclerosis assessed by coronary artery calcium (CAC) differs in SA versus other ethnic groups.MethodsWe studied adults from the Multi-Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America studies without ASCVD. CAC was examined among those normoglycemic, pre-DM and DM. Logistic regression examined pre-DM and DM with the odds of any CAC > 0 and CAC ≥ 100.ResultsAmong 7562 participants, CAC > 0 and CAC ≥ 100 in those with DM was highest in non-Hispanic White (NHW) (80% and 48%) and SA (72% and 41%) persons. Adjusted Ln (CAC + 1) was highest in NHW (3.68 ± 0.21) and SA (3.60 ± 0.23) (p < .01) DM patients. SA and NHW adults with DM (vs normoglycemic) had highest odds of CAC > 0 (2.13 and 2.27, respectively, p < .01). For CAC ≥ 100, SA and Chinese adults had the highest odds (2.28 and 2.27, respectively, p < .01). Fasting glucose and glycated hemoglobin were most strongly associated with CAC among SA.ConclusionsDiabetes mellitus most strongly relates to any CAC in SA and NHW adults and CAC ≥ 100 in SA and Chinese adults, helping to explain the relation of DM with ASCVD in these populations.

Purpose of reviewReferral to nutrition care providers in the USA such as registered dietitian nutritionists (RDNs) for medical nutrition therapy (MNT) remains low. We summarize research on the effectiveness of MNT provided by dietitians versus usual care in the management of adults with dyslipidemia. Improvements in lipids/lipoproteins were examined. If reported, blood pressure (BP), fasting blood glucose (FBG) glycated hemoglobin (A1c), body mass index (BMI), and cost outcomes were also examined.Recent findingsThe synthesis of three systematic reviews included thirty randomized controlled trials. Multiple MNT visits (3-6) provided by dietitians, compared with usual care, resulted in significant improvements in total cholesterol (mean range: - 4.64 to - 20.84 mg/dl), low-density lipoprotein cholesterol (mean range: - 1.55 to - 11.56 mg/dl), triglycerides (mean range: - 15.9 to - 32.55 mg/dl), SBP (mean range: - 4.7 to - 8.76 mm Hg), BMI (mean: - 0.4 kg/m2), and A1c (- 0.38%). Cost savings from MNT were attributed to a decrease in medication costs and improved quality of life years (QALY). Multiple MNT visits provided by dietitians compared with usual care improved lipids/lipoproteins, BP, A1c, weight status, and QALY with significant cost savings in adults with dyslipidemia and justify a universal nutrition policy for equitable access to MNT.

ObjectiveElevated lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease (ASCVD) and has no approved pharmacotherapies. Limited real-world data exists on the proportion of patients with available Lp(a) test results, characteristics of these patients, and their use of lipid lowering therapies (LLTs) for secondary prevention (SP) and primary prevention (PP) of ASCVD.MethodsPatients with measured Lp(a) receiving LLTs for SP or PP of ASCVD were identified in the Optum Clinformatics® Data Mart database. Lp(a) distribution and LLT utilization including persistence and adherence were assessed. Logistic regression was used to assess the association between Lp(a) levels and low-density lipoprotein cholesterol (LDL-C) levels after index LLT, adjusting for baseline characteristics.ResultsOverall, 2154 SP and 7179 PP patients met eligibility criteria. Of patients with available laboratory data, only 0.7% (SP) and 0.6% (PP) had Lp(a) test results. In the SP cohort, Lp(a) levels ≥125 nmol/L and ≥175 nmol/L were 26.4% and 17.6%, respectively, and the mean (SD) Lp(a) levels (overall SP cohort 90.4 [97.9] nmol/L) were highest in Black patients (123.4 [117.4]; p

Real-world data on lipid levels and treatment among adults with diabetes mellitus (DM) are relatively limited. We studied lipid levels and treatment status in patients with DM across cardiovascular disease (CVD) risk groups and sociodemographic factors. In the All of Us Research Program, we categorized DM as (1) moderate risk (≤1 CVD risk factor), (2) high risk (≥2 CVD risk factors), and (3) DM with atherosclerotic CVD (ASCVD). We examined the use of statin and non-statin therapy as well as LDL-C and triglyceride levels. We studied 81,332 participants with DM, which included 22.3% non-Hispanic Black and 17.2% Hispanic. A total of 31.1% had ≤1 DM risk factor, 30.3% had ≥2 DM risk factors, and 38.6% of participants had DM with ASCVD. Only 18.2% of those with DM and ASCVD were on high-intensity statins. Overall, 5.1% were using ezetimibe and 0.6% PCSK9 inhibitors. Among those with DM and ASCVD, only 21.1% had LDL-C < 70 mg/dL. Overall, 1.9% of participants with triglycerides ≥ 150 mg/dL were on icosapent ethyl. Those with DM and ASCVD were more likely to be on high-intensity statins, ezetimibe, and icosapent ethyl. Guideline-recommended use of high-intensity statins and non-statin therapy among our higher risk DM patients is lacking, with LDL-C inadequately controlled.

Purpose of reviewCoronary artery calcium (CAC) is an important measure of subclinical atherosclerosis and strongly predicts atherosclerotic cardiovascular disease (ASCVD) outcomes. The purpose of this review is to discuss the key studies that have helped to establish its role as an important screening tool and its place in preventive cardiology.Recent findingsEpidemiologic studies document a strong relation of age, race/ethnicity, and risk factors with the prevalence and extent of CAC. Large-scale registry and prospective investigations show CAC to be the strongest subclinical disease predictor of ASCVD outcomes, with higher CAC scores associated with successively higher risks and those with a CAC score of 0 having a long-term "warranty" against having events. Moreover, CAC is associated with greater initiation of preventive health behaviors and therapy. Current US guidelines utilize CAC to inform the treatment decision for statin therapy. Further study is underway to document whether CAC screening will ultimately improve clinical outcomes. CAC is well established as the most important subclinical cardiovascular disease measure for prediction of future ASCVD outcomes and can be used for informing the treatment decision for preventive therapies.

BackgroundPrior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown.MethodsCohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD.ResultsAfter 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4-10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48-5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37-3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83-12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22-11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33-8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66-8.59; p

Although cardiovascular disease risk factors relate to COVID-19, the association of estimated atherosclerotic cardiovascular disease (ASCVD) risk with severe COVID-19 is not established. We examined the relation of the pooled-cohort ASCVD risk score to severe COVID-19 among 28,646 subjects from the National COVID Cohort Collaborative database who had positive SARS-CoV-2 test results from April 1, 2020 to April 1, 2021. In addition, 10-year ASCVD risk scores were calculated, and subjects were stratified into low-risk (=20%) groups. Severe COVID-19 outcomes (including death, remdesivir treatment, COVID-19 pneumonia, acute respiratory distress syndrome, and mechanical ventilation) occurring during follow-up were examined individually and as a composite in relation to ASCVD risk group across race and gender. Multiple logistic regression, adjusted for age, gender, and race, examined the relation of ASCVD risk group to the odds of severe COVID-19 outcomes. Our subjects had a mean age of 59.4 years; 14% were black and 57% were female. ASCVD risk group was directly related to severe COVID-19 prevalence. The adjusted odds ratio of the severe composite COVID-19 outcome by risk group (vs the low-risk group) was 1.8 (95% confidence interval 1.5 to 2.2) for the borderline-risk, 2.7 (2.3 to 3.2) for the intermediate-risk, and 4.6 (3.7 to 5.6) for the high-risk group. Black men and black women in the high-risk group showed higher severe COVID-19 prevalence compared with nonblack men and nonblack women. Prevalence of severe COVID-19 outcomes was similar in intermediate-risk black men and high-risk nonblack men (approximately 12%). In conclusion, although further research is needed, the 10-year ASCVD risk score in adults ages 40 to 79 years may be used to identify those who are at highest risk for COVID-19 complications and for whom more intensive treatment may be warranted.

AimsStatin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.Methods and resultsWe searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P 4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

ObjectiveTo explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs.MethodsWe derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59.ResultsWe estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion).ConclusionsTreating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

BackgroundBreast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD.MethodsA cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD.ResultsTwenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status.ConclusionsOur results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

BackgroundAtherosclerotic cardiovascular diseases (ASCVD) including myocardial infarction, stroke and peripheral arterial disease continue to be major causes of premature death, disability and healthcare expenditure globally. Preventing the accumulation of cholesterol-containing atherogenic lipoproteins in the vessel wall is central to any healthcare strategy to prevent ASCVD. Advances in current concepts about reducing cumulative exposure to apolipoprotein B (apo B) cholesterol-containing lipoproteins and the emergence of novel therapies provide new opportunities to better prevent ASCVD. The present update of the World Heart Federation Cholesterol Roadmap provides a conceptual framework for the development of national policies and health systems approaches, so that potential roadblocks to cholesterol management and thus ASCVD prevention can be overcome.MethodsThrough a review of published guidelines and research papers since 2017, and consultation with a committee composed of experts in clinical management of dyslipidaemias and health systems research in low-and-middle income countries (LMICs), this Roadmap identifies (1) key principles to effective ASCVD prevention (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMICs; and (4) potential strategies for overcoming these.ResultsReducing the future burden of ASCVD will require diverse approaches throughout the life-course. These include: a greater focus on primordial prevention; availability of affordable cholesterol testing; availability of universal cholesterol screening for inherited dyslipidaemias; risk stratification moving beyond 10-year risk to look at lifetime risk with adequate risk estimators; wider availability of affordable cholesterol-lowering therapies which should include statins as essential medications globally; use of adequate doses of potent statin regimens; and combination therapies with ezetimibe or other therapies in order to attain and maintain robust reductions in LDL-C in those at highest risk. Continuing efforts are needed on health literacy for both the public and healthcare providers, utilising multi-disciplinary teams in healthcare and applications that quantify both ASCVD risk and benefits of treatment as well as increased adherence to therapies.ConclusionsThe adverse effects of LDL-cholesterol and apo B containing lipoprotein exposure are cumulative and result in ASCVD. These are preventable by implementation of different strategies, aimed at efficiently tackling atherosclerosis at different stages throughout the human life-course. Preventive strategies should therefore be updated to implement health policy, lifestyle changes and when needed pharmacotherapies earlier with investment in, and a shift in focus towards, early preventive strategies that preserve cardiovascular health rather than treat the consequences of ASCVD.

BackgroundCoronary artery calcium (CAC) density is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD) risk. We examined this relation in those with diabetes mellitus (DM) or metabolic syndrome (MetS).MethodsWe studied 3,818 participants with non-zero CAC scores from the Multiethnic Study of Atherosclerosis and classified them as DM, MetS (without DM) or neither DM/MetS. Risk factor-adjusted CAC density was calculated and examined in relation to incident CHD and CVD events over a median follow-up of 15 years among these three disease groups.ResultsAdjusted CAC density was 2.54, 2.61 and 2.69 among those with DM, MetS or neither DM/MetS. Hazard ratios (HRs) for CHD per 1 SD increase of CAC density was 0.91 (95% CI: 0.72-1.16), 0.70 (95% CI: 0.56-0.87) and 0.79 (95% CI: 0.66-0.95) for those with DM, MetS or neither DM/MetS groups and were 0.77 (95% CI: 0.64-0.94), 0.83 (95% CI: 0.70-0.99) and 0.82 (95% CI: 0.71-0.95) for CVD, respectively. Adjustment for CAC density increased the HRs of CAC volume for CHD/CVD events. Compared to prediction models with or without single CAC measures, c-statistics of models with CAC volume and density were the highest ranging 0.67-0.72.ConclusionCAC density is lower among patients with DM or MetS than those with neither DM/MetS and is inversely associated with future CHD/CVD risk among them. Including CAC density in risk assessment among those with MetS may improve prediction of CHD and CVD.

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines. Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009-2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing. Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times. Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

Lipoprotein(a) is an underrecognized, but significant genetic risk factor for atherosclerotic cardiovascular disease (ASCVD), shown to be causal from data from prospective epidemiologic studies, Mendelian randomization, and genome wide association studies [...].

BackgroundWe sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.MethodsThis was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)

BackgroundObesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated.MethodsWe included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women's Health Initiative. Normal weight was defined as a body mass index ≥18.5 and

[This corrects the article DOI: 10.1016/j.ajpc.2020.100010.].

AimIn statin-treated persons with atherosclerotic cardiovascular disease (ASCVD) the further ASCVD risk that diabetes mellitus (DM) adds is not well-quantified. We examined this residual risk for initial and total recurrent ASCVD events.MethodsWe studied 3271 patients with ASCVD on statin therapy in the AIM-HIGH clinical trial cohort. Cox regression and the Prentice, Williams, and Peterson model examined the excess risk of initial and total recurrent ASCVD events associated with DM over a 3- year mean follow-up. Predictors of first and total ASCVD events in those with and without DM were also examined.ResultsOf our cohort with ASCVD on statin therapy 40% also had DM. Those with vs. without DM were older, were less likely to be male or white. They had higher systolic blood pressure, lower HDL-C, LDL-C, lipoprotein (a), but higher triglycerides and BMI (all p

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p

Background and aimsWe sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects.MethodsWe studied 1069 subjects (age 58.2 ± 8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation.ResultsAt 14.5 ± 2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p = 0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p

Heterozygous familial hypercholesterolemia (HeFH) creates elevated low-density lipoprotein cholesterol (LDL-C), causing premature atherosclerotic cardiovascular disease (ASCVD). Guidelines recommend cascade screening relatives and starting statin therapy at 8-10 years old, but adherence to these recommendations is low. Our purpose was to measure self-reported physician practices for cascade screening and treatment initiation for HeFH using a survey of 500 primary care physicians and 500 cardiologists: 54% "always" cascade screen relatives of an individual with FH, but 68% would screen individuals with "strong family history of high cholesterol or premature ASCVD", and 74% would screen a child of a patient with HeFH. The most likely age respondents would start statins was 18-29 years, with few willing to prescribe to a pediatric male (17%) or female (14%). Physicians who reported previously diagnosing a patient with HeFH were more likely to prescribe to a pediatric patient with HeFH, either male (OR = 1.34, 95% CI = 0.99-1.81) or female (OR = 1.31, 95% CI = 0.99-1.72). Many physicians do not cascade screen and are less likely to screen individuals with family history of known HeFH compared to "high cholesterol or premature ASCVD". Most expressed willingness to screen pediatric patients, but few would start treatment at recommended ages. Further education is needed to improve diagnosis and treatment of HeFH.

Globally, nearly 500 million adults currently have diabetes, which is expected to increase to approximately 700 million by 2040. Cardiovascular diseases (CVD), including coronary heart disease, stroke, heart failure, and peripheral arterial disease, are the principal causes of death in persons with diabetes. Key to the prevention of CVD is optimization of associated risk factors. However, few persons with diabetes are at recommended targets for key CVD risk factors including low-density lipoprotein cholesterol (LDL-C), blood pressure, glycated hemoglobin, nonsmoking status, and body mass index. While lifestyle management forms the basis for the prevention and control of these risk factors, newer and existing pharmacologic approaches are available to optimize the potential for CVD risk reduction, particularly for the management of lipids, blood pressure, and blood glucose. For higher-risk patients, antiplatelet therapy is recommended. Medication for blood pressure, statins, and most recently, icosapent ethyl, have evidence for reducing CVD events in persons with diabetes. Newer medications for diabetes, including sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists, also reduce CVD and SGLT2 inhibitors in particular also reduce progression of kidney disease and reduce heart failure hospitalizations (HFHs). Most importantly, a multidisciplinary team is required to address the polypharmaceutical options to best reduce CVD risks persons with diabetes. Key words: diabetes, cardiovascular disease, risk assessment, risk factors, statins, SGLT2 inhibitors, GLP1 receptor agonists A l'echelle mondiale, pres de 500 millions d'adultes sont actuellement atteints de diabete, nombre que l'on s'attend a voir augmenter jusqu'a environ 700 millions d'ici 2040. Les maladies cardiovasculaires (MCV), y compris la coronaropathie, l'AVC, l'insuffisance cardiaque et la maladie arterielle peripherique representent les principales causes de deces chez les personnes atteintes de diabete. La cle de la prevention des MCV est l'optimisation des facteurs de risque associes. Toutefois, l'etat de peu de personnes atteintes de diabete correspond aux cibles cles recommandees pour les facteurs de risque des MCV, y compris le cholesterol lie aux LDL, la tension arterielle, l'HbA1c, l'etat sans tabagisme et l'indice de masse corporelle. Bien que la prise en charge des habitudes de vie constitue le fondement de la prevention et de la maitrise de ces facteurs de risque, certaines approches therapeutiques nouvelles ou utilisees actuellement sont disponibles en vue d'optimiser une eventuelle reduction du risque de MCV, en particulier pour la prise en charge des lipides, de la tension arterielle et de la glycemie. Le traitement antiplaquettaire est recommande pour les patients exposes a un risque accru. Les antihypertenseurs, les statines et tres recemment l'icosapent ethyle se sont avere entrainer une diminution du nombre d'evenements CV chez les personnes atteintes de diabete. Les nouveaux medicaments contre le diabete, y compris les inhibiteurs du SGLT2 et les agonistes des recepteurs du GLP-1 entrainent aussi une diminution de la frequence des MCV. Les inhibiteurs du SGLT2 en particulier entrainent aussi une attenuation de l'evolution de l'insuffisance renale de meme qu'une diminution du nombre d'hospitalisations liees a l'insuffisance cardiaque. Le plus important est de remettre a une equipe multidisciplinaire la responsabilite d'aborder les options therapeutiques en vue de faire decroitre le risque CV le plus possible chez les personnes atteintes de diabete. [Traduit par la Redaction] Mots-cles : diabete, maladies cardiovasculaires, evaluation du risque, facteurs de risque, statines, inhibiteurs du SGLT2, agoniste des recepteurs du GLP1, Introduction Diabetes mellitus (DM), in particular type 2 DM, continues to be a global epidemic with nearly 500 million adults currently with DM, expected to increase to 700 million over [...]

Despite statin therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) still suffer from ASCVD events. Predictors of residual ASCVD risk are not well-delineated. We aimed to develop an ASCVD risk prediction model for patients with previous ASCVD on statin use. We utilized statin-treated patients with ASCVD from the AIM-HIGH trial cohort. A 5-year risk score for subsequent ASCVD events with known ASCVD was developed using Cox regression, including potential risk factors with age, sex, and race forced in the model. Internal discrimination and calibration were evaluated. We included 3,271 patients with ASCVD (85.4% male, mean age 63.6 years, 65% on moderate- and 24% on high-intensity statin) with complete risk factor data and mean follow-up of 4.18 years. Overall, the estimated 5-year ASCVD risk was 21.1%: 10.2% of patients had a 5-year risk of >30%, and 38.8% had risk of between 20% and 30%. In the model, male sex, hemoglobin A1c, alcohol use (inversely), family history of cardiovascular disease, homocysteine, history of carotid artery disease, and lipoprotein(a) best predicted residual ASCVD risk. Niacin treatment status did not enter the model. A C-statistic of 0.59 was obtained, with the Greenwood-Nam-D'Agostino test showing excellent calibration. We developed a risk prediction risk model for predicting 5-year residual ASCVD risk in statin-treated patients with known ASCVD that may help in identifying such persons at the highest risk of recurrent events. Validation in larger samples with patients on high-intensity statin is needed.