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Background Non-statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non-statin LLT remain incompletely described. Hypothesis The guideline-recommended statin intensity remains underutilized in patients treated with and without non-statin LLT. Methods The PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non-statin LLT. Results Among 7720 patients, 1930 (25.0%) were treated with a non-statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin treatment occurred in 73.7%, of which 45.4% were dosed under the guideline-recommended intensity. Compared with patients on statin alone, patients receiving both a statin and non-statin LLT (n = 1423) were more likely to be male, white race and to perceive themselves as higher risk of ASCVD compared with their peers (38.5% vs. 34.9%, p = .047). Only 27.4% of patients treated with non-statin LLT alone perceived themselves at higher risk. Most (75.7%) patients treated with a non-statin LLT alone reported never being treated with a statin, despite ASCVD in 30.8% of these patients. Among those previously treated with a statin, 59.3% reported being willing to try a statin again. Conclusions Non-statin LLT is used in one in four patients with or at risk for ASCVD; its use is frequently in place of statin therapy or in the absence of guideline-recommended statin intensity. More work is needed to establish statins as first line therapy.

Background and aims Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics. Methods We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007–12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models. Results Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03–0.08). Conclusions The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics.

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs. with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk.

Triglyceride (TG) levels encompass several lipoproteins that have been implicated in atherogenic pathways. Whether TG levels independently associate with cardiovascular disease both overall and, in particular among patients with established coronary artery disease (CAD) and type 2 diabetes (T2DM), remains controversial. Data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was used to evaluate patients with T2DM and CAD. Cox proportional hazards models were used to determine the association between TG levels and outcomes. Stepwise adjustment was performed for demographics, clinical factors, lipid profile and statin treatment. The primary composite outcome was time to CV death, myocardial infarction (MI), or stroke and secondary outcome was CV death. Among 2,307 patients with T2DM and CAD, the mean (±SD) TG levels were 181 (±136) with a median (Q1-Q3) 148mg/dL (104-219). Overall, 51% of patients had TG150 mg/dL, 18% 150-199 mg/dL, 28% 200-499 mg/dL and 3% ≥500 mg/dL. Participants with elevated TG levels (≥150 mg/dL) were younger (61 vs 63 years, p0.001), had higher BMI (32 vs 30 kg/m

Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mendelian Randomization studies, have demonstrated that increasing Lp(a) levels are associated with increased risk of heart disease, including atherosclerotic cardiovascular disease and calcific aortic stenosis. The risk associated with elevations in Lp(a) appears to be independent of other lipid markers. While the current treatment options for elevated Lp(a) are limited, promising new therapies are under development, leading to renewed interest in Lp(a). This review provides an overview of the biology and epidemiology of Lp(a), available outcome studies, and insights into future therapies.

Background/objectives Elevated low-density lipoprotein cholesterol (LDL-C) in early adulthood is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). The strength of the association between LDL-C and ASCVD among older adults, however, is less understood. Design We examined individual-level cohort data from the National Institutes of Health Pooled Cohorts (Framingham Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study), which prospectively measured CVD risk factors and incident disease. Setting Prospective cohort study. Participants Adults, aged 75 years or older, free of ASCVD. Measurements We evaluated the associations between LDL-C and incident ASCVD (stroke, myocardial infarction, and cardiovascular death) in unadjusted analysis and in multivariable-adjusted Cox proportional hazards models. We assessed 5-year Kaplan-Meier ASCVD event rates in patients with and without hyperlipidemia (LDL-C ≥130 mg/dL or on lipid-lowering medications), stratified by the number of other risk factors, including smoking, diabetes, and hypertension. Results We included 2667 adults, aged 75 years or older (59% female), free of ASCVD; median age was 78 years, with median LDL-C of 117 mg/dL. In both unadjusted and adjusted analyses, there was no association between LDL-C and ASCVD (adjusted hazard ratio = 1.022; 95% confidence interval = 0.998-1.046; P = .07). Among adults without other risk factors (free of smoking, diabetes, and hypertension), event rates were similar between those with and without hyperlipidemia (Kaplan-Meier rates = 5.8% and 7.0%, respectively). Among adults with one or two or more other risk factors, the presence of hyperlipidemia was also not associated with 5-year CVD event rates (Kaplan-Meier rates = 12.8% vs 15.0% [P = .44] for one other risk factor and 21.9% vs 24.0% [P = .59] for two or more other risk factors). Conclusion Among a well-characterized cohort, LDL-C was not associated with CVD risk among adults aged 75 years or older, even in the presence of other risk factors. J Am Geriatr Soc 67:2560-2567, 2019.

Background Extended elevations of non–high-density lipoprotein cholesterol (non–HDL-C) across a lifespan are associated with increased risk of cardiovascular disease (CVD). However, optimal testing intervals to identify individuals with high lipid-related CVD risk are unknown. Objectives This study determined the extent to which lipid levels in young adulthood predict future lipid trajectories and associated long-term CVD risk. Methods A sample of 2,516 Framingham Offspring study participants 25 to 40 years of age free of CVD and diabetes had their non–HDL-C progression modeled over 8 study examinations (mean follow-up 32.6 years) using group-based methods. CVD risk based on 25 to 30 years of follow-up was evaluated using Kaplan-Meier analyses for those with mean non–HDL-C ≥160 mg/dl (“high”) and Results The trajectories of the lipid levels were generally stable over the 30-year life course; mean non–HDL-C measured in young adulthood were highly predictive of levels later in life. Individuals could be reliably assigned to high and low non–HDL-C groups based on 2 measurements collected between 25 to 40 years of age. Overall, 80% of those with non–HDL-C ≥160 mg/dl at the first 2 exams remained in the high group on subsequent 25-year testing, whereas 88% of those with non–HDL-C Conclusions Most adults with elevated non–HDL-C early in life continue to have high non–HDL-C over their life course, leading to significantly increased risk of CVD. The results demonstrate that early lipid monitoring before 40 years of age would identify a majority of those with a high likelihood for lifetime elevated lipid levels who also have a high long-term risk for CVD. This information could facilitate informed patient–provider discussion about the potential benefits of preventive lipid-lowering efforts during the early midlife period.

Supplemental Digital Content is available in the text., Background: To optimize preventive strategies for coronary heart disease (CHD), it is essential to understand and appropriately quantify the contribution of its key risk factors. Our objective was to compare the associations of key modifiable CHD risk factors—specifically lipids, systolic blood pressure (SBP), diabetes mellitus, and smoking—with incident CHD events based on their prognostic performance, attributable risk fractions, and treatment benefits, overall and by age. Methods: Pooled participant-level data from 4 observational cohort studies sponsored by the National Heart, Lung, and Blood Institute were used to create a cohort of 22 626 individuals aged 45 to 84 years who were initially free of cardiovascular disease. Individuals were followed for 10 years from baseline evaluation for incident CHD. Proportional hazards regression was used to estimate metrics of prognostic model performance (likelihood ratio, C index, net reclassification, discrimination slope), hazard ratios, and population attributable fractions for SBP, non–high-density lipoprotein cholesterol (non–HDL-C), diabetes mellitus, and smoking. Expected absolute risk reductions for antihypertensive and lipid-lowering treatment were assessed. Results: Age, sex, and race capture 63% to 80% of the prognostic performance of cardiovascular risk models. In contrast, adding either SBP, non–HDL-C, diabetes mellitus, or smoking to a model with other risk factors increases the C index by only 0.004 to 0.013. However, primordial prevention could have a substantial effect as demonstrated by population attributable fractions of 28% for SBP≥130 mm Hg and 17% for non–HDL-C≥130 mg/dL. Similarly, lowering the SBP of all individuals to

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors represent a promising class of lipid‐lowering therapy, although their use has been limited by cost concerns. Methods and Results A retrospective cohort study was conducted using a nationwide commercial claims database comprising patients with atherosclerotic cardiovascular disease (ASCVD), aged 18 to 64 years. We identified the number of patients with ASCVD started on a PCSK9 inhibitor from the dates of US Food and Drug Administration approval in quarter 3 2015 through quarter 2 2019. Secondary objectives identified the proportions of patients started on a PCSK9 inhibitor in various ASCVD risk groups based on statin use and baseline low‐density lipoprotein cholesterol. We identified 126 419 patients with ASCVD on either PCSK9 inhibitor or statin therapy. Among these patients, 1168 (0.9%) filled a prescription for a PCSK9 inhibitor. The number of patients initiating a PCSK9 inhibitor increased from 2 patients in quarter 3 2015 to 119 patients in quarter 2 2019, corresponding to an increase from 0.05% to 2.5% of patients with ASCVD already on statins who started PCSK9 inhibitor therapy. Of patients with ASCVD with high adherence to a high‐intensity statin, 13 643 had low‐density lipoprotein cholesterol ≥70 mg/dL, and in this subgroup, 119 (0.9%) patients initiated a PCSK9 inhibitor. Conclusions Few patients started PCSK9 inhibitors from 2015 through mid‐2019, despite increasing trial evidence of efficacy, guidelines recommending PCSK9 inhibitors in high‐risk patients with ASCVD, and price reductions during this period. The magnitude of price reductions may not yet be sufficient to influence use management strategies aimed to limit PCSK9 inhibitor use.

Background Statin associated side effects (SASE) are a leading cause of statin discontinuation. Objective We evaluated patient, provider, and facility characteristics associated with SASEs and whether these characteristics impact statin utilization. Methods Patients with atherosclerotic cardiovascular disease (ASCVD) receiving care across the Veterans Affairs healthcare system from October 1, 2014 to September 30, 2015 were included. Multivariable logistic regression analyses were performed to determine (a) factors associated with SASE and (b) factors associated with statin use in those with SASE. Results Our cohort included 1,225,576 patients with ASCVD. Of these, 171,189 (13.7%) had at least 1 reported SASE since year 2000. The most significant odds for SASEs were observed with female sex (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.36, 1.45), White race (OR 1.43, 95% CI 1.41, 1.45), hypertension (OR 1.37, 95% CI 1.33, 1.41) and ischemic heart disease (IHD: OR 1.45, 95% CI 1.43, 1.47). Lower odds were noted with care at a teaching facility (OR 0.89, 95% CI 0.88, 0.90). Factors most associated with being on a statin among patients with SASE included having diabetes (OR 1.18, 95% CI 1.15, 1.20), IHD (OR 1.39, 95% CI 1.35, 1.43) and a higher number of cardiology visits (OR 1.08, 95% CI 1.07, 1.09), while female sex was associated with lower odds (OR 0.65, 95% CI 0.61, 0.69). Conclusion There are significant disparities in statin use by sex, ASCVD type, and comorbidities among secondary prevention patients with SASE, which represent areas for improvement in optimizing statin utilization.

BackgroundInfluenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease.Methods and ResultsWe searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [P=0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [PPP=0.12]) compared with control.ConclusionsData from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.

Objective This study aimed to investigate the association between cumulative exposure to chronic stressors and the incidence of myocardial infarction (MI) in US older adults. Methods Nationally representative prospective cohort data of adults 45 years and older (n = 15,109) were used to investigate the association between the cumulative number of chronic stressors and the incidence of MI in US older adults. Proportional hazards models adjusted for confounding risk factors and differences by sex, race/ethnicity, and history of MI were assessed. Results The median age of participants was 65 years, 714 (4.7%) had a prior MI, and 557 (3.7%) had an MI during follow-up. Approximately 84% of participants reported at least one chronic stressor at baseline, and more than half reported two or more stressors. Multivariable models showed that risks of MI increased incrementally from one chronic stressor (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.20-1.37) to four or more chronic stressors (HR = 2.71, 95% CI = 2.08-3.53) compared with those who reported no stressors. These risks were only partly reduced after adjustments for multiple demographic, socioeconomic, psychosocial, behavioral, and clinical risk factors. In adults who had a prior MI (p value for interaction = .038), we found that risks of a recurrent event increased substantially from one chronic stressor (HR = 1.30, 95% CI = 1.09-1.54) to four or more chronic stressors (HR = 2.85, 95% CI = 1.43-5.69). Conclusions Chronic life stressors are significant independent risk factors for cardiovascular events in US older adults. The risks associated with multiple chronic stressors were especially high in adults with a previous MI.

Background Half the global burden of cardiovascular disease (CVD) is concentrated in the Asia‐Pacific (APAC) region. Hypothesis Suboptimal control of low‐density lipoprotein cholesterol (LDL‐C) may play a large role in the burden of CVD in APAC and non‐Western countries. Methods The Acute Coronary Syndrome Management (ACOSYM) registry is a multinational, multicenter, prospective observational registry designed to evaluate LDL‐C control in patients within 6 months after hospitalization following an acute coronary syndrome (ACS) event across nine countries. Results Overall, 1581 patients were enrolled, of whom 1567 patients met the eligibility criteria; 80.3% of the eligible patients were men, 46.1% had ST‐elevation myocardial infarction, and 39.5% had non‐ST‐elevation myocardial infarction. Most (1245; 79.5%) patients were discharged on a high‐intensity statin. During the follow‐up, only 992 (63.3%) patients had at least one LDL‐C measurement; of these, 52.9% had persistently elevated LDL‐C (>70 mg/dl). The patients not discharged on a high‐dose statin were more likely (OR 3.2; 95% CI 2.1–4.8) to have an LDL‐C above the 70 mg/dl LDL‐C target compared with those who were discharged on a high‐dose statin. Conclusion Our real‐world registry found that a third or more of post‐ACS patients did not have a repeat LDL‐C follow‐up measurement. In those with an LDL‐C follow‐up measurement, more than half (52.9%) were not achieving a

Introduction: Influenza infection is associated with increased morbidity and mortality in patients with cardiovascular disease (CVD). We assessed the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with CVD. Hypothesis: Influenza vaccination in those with CVD is associated with a reduction in mortality and major adverse cardiovascular events (MACE). Methods: We searched PubMed, EMBASE, and Cochrane library through January 2020 for randomized-controlled trials (RCTs) and observational studies assessing effects of influenza vaccine on mortality and cardiovascular outcomes in patients with CVD. Estimates were reported as random effects risk ratios (RR) with 95% confidence intervals (CI). Analyses were stratified by study design into RCT and observational studies. Results: Overall, 16 studies (n=237,058) encompassing 4 RCTs (n=1,667) and 12 observational studies (n=235,391) were included. The mean age was 69.2±7.01; 36.6% were female, 65.1% had hypertension, 31.1% had diabetes, and 23.4% were smokers. The median follow-up duration was 19.5 (IQR, 12, 43.3) months. Influenza vaccine was associated with a lower risk of all-cause mortality (RR, 0.72 [95% CI, 0.59-0.89], pFigure 1A ), cardiovascular mortality (RR, 0.82 [95% CI, 0.80-0.84], pFigure 1B ), though the association with myocardial infarction was not statistically significant (RR, 0.73 [95% CI, 0.50-1.07]; p=0.10). These finding were consistent across randomized and observational studies. Conclusions: This meta-analysis suggests that both randomized and observational data support the use of influenza vaccine in adults with CVD to reduce mortality and MACE events. Efforts to improve utilization of influenza vaccine in this population should continue to reap survival benefits.

This review compares representation of older adults in interventional cardiovascular disease studies in the US before and after implementation of the National Institutes of Health’s Inclusion Across the Lifespan Policy.

Objective To identify the prevalence, treatment, and low-density lipoprotein cholesterol (LDL-C) control of individuals with LDL-C ≥190 ​mg/dL in contemporary clinical practice. Methods We included adults (age ≥18 years) with LDL-C ≥190 ​mg/dL, at least one LDL-C level drawn from 255 health systems participating in Cerner HealthFacts database (2000–2017, n ​= ​4,623,851), and a detailed examination within Duke University Health System (DUHS, 2015–2017, n ​= ​267,710). Factors associated with LDL-C control were evaluated using multivariable logistic regression modeling. Results The cross-sectional prevalence of LDL-C ≥190 ​mg/dL was 3.0% in Cerner (n ​= ​139,539/4,623,851) and 2.9% at DUHS (n ​= ​7728/267,710); among these, rates of repeat LDL-C measurement within 13 months were low: 27.9% (n ​= ​38,960) in Cerner, 54.5% (n ​= ​4211) at DUHS. Of patients with follow-up LDL-C levels, 23.6% in Cerner had a 50% of greater reduction in LDL-C, 18.3% achieved an LDL-C, Highlights • Large numbers of U.S. adults with extremely high LDL-C.oCan be identified using available EHR dataoOften have no follow-up lipid measurementoAre not treated with recommended lipid-lowering therapiesoDo not achieve guideline-recommended LDL-C reduction goals

The 2018 cholesterol guidelines of the American Heart Association and the American College of Cardiology (AHA/ACC) changed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) eligibility criteria for primary prevention to include multiple risk enhancers and novel intensive lipid-lowering therapies for secondary prevention.This study sought to determine how guideline changes affected identification for preventive therapy in young adults with premature myocardial infarction (MI).The study identified adults presenting with first MI at Duke University Medical Center in Durham, North Carolina. Statin therapy eligibility was determined using the 2013 ACC/AHA and 2018 AHA/ACC guidelines criteria. The study also determined potential eligibility for intensive lipid-lowering therapies (very high risk) under the 2018 AHA/ACC guidelines, by assessing the composite of all-cause death, recurrent MI, or stroke rates in adults considered "very high risk" versus not.Among 6,639 patients with MI, 41% were 55 years of age ("younger"), 35% were 55 to 65 years of age ("middle-aged"), and 24% were 66 to 75 years of age ("older"). Younger adults were more frequently smokers (52% vs. 38% vs. 22%, respectively) and obese (42% vs. 34% vs. 31%, respectively), with metabolic syndrome (21% vs. 19% vs. 17%, respectively) and higher low-density lipoprotein cholesterol (117 vs. 107 vs. 103 mg/dl, respectively) (p trend 0.01 for all). Pre-MI, fewer younger adults met guideline indications for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) therapy than middle-aged and older adults. The 2018 guideline identified fewer younger adults eligible for statin therapy at the time of their MI than the 2013 guideline (46.4% vs. 56.7%; p 0.01). Younger patients less frequently met very high-risk criteria for intensive secondary prevention lipid-lowering therapy (28.3% vs. 40.0% vs. 81.4%, respectively; p 0.01). Over a median 8 years of follow-up, very high-risk criteria were associated with increased risk of major adverse cardiovascular events in individuals 55 years of age (hazard ratio: 2.09; 95% confidence interval: 1.82 to 2.41; p 0.001), as was the case in older age groups (p interaction = 0.54).Most younger patients with premature MI are not identified as statin candidates before their event on the basis of the 2018 guidelines, and most patients with premature MI are not recommended for intensive post-MI lipid management.

Importance Determining blood pressure (BP) patterns in young adulthood that are associated with cardiovascular disease (CVD) events in later life may help to identify young adults who have an increased risk for CVD. Objective To determine whether the long-term variability of BP across clinical visits and the rate of change in BP from young adulthood to midlife are associated with CVD and all-cause mortality by middle age, independently of mean BP during young adulthood and a single BP in midlife. Design, Setting, and Participants This prospective cohort study included a community-based sample of 3394 African American and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, enrolled from March 1985 through June 1986. Patterns of systolic BP (SBP) were evaluated with measurements at year 0 (baseline) and 2, 5, 7, and 10 years after baseline. Visit-to-visit SBP variability was estimated as BP variability independent of the mean (VIM). Data were collected from March 1985 through August 2015 and analyzed from June through October 2019. Main Outcomes and Measures Cardiovascular disease and all-cause mortality experienced through August 2015 were adjudicated. The associations of each SBP pattern with CVD events and all-cause mortality were determined using Cox proportional hazards regression models. Results At year 10, the mean (SD) age of the 3394 participants was 35.1 (3.6) years; 1557 (45.9%) were African American; 1892 (55.7%) were women; and 103 (3.0%) were taking antihypertensive medication. During a median follow-up of 20.0 (interquartile range, 19.4-20.2) years, 162 CVD events and 181 deaths occurred. When all BP pattern measurements were entered into the same model including a single SBP measurement at the year 10 examination, the hazard ratios for CVD events for each 1-SD increase in SBP measures were 1.25 (95% CI, 0.90-1.74) for mean SBP, 1.23 (95% CI, 1.07-1.43) for VIM SBP, and 0.99 (95% CI, 0.81-1.26) for annual change of SBP. The VIM for SBP was the only BP pattern associated with all-cause mortality (hazard ratio, 1.24; 95% CI, 1.09-1.41). Conclusions and Relevance The results of this study suggest that the assessment of visit-to-visit SBP variability may help identify young adults at increased risk for CVD and all-cause mortality later in life.

IMPORTANCE: Lipid management typically focuses on levels of low-density lipoprotein cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). However, animal models and genetic studies suggest that the atherogenic particle subpopulations (LDL and very-low-density lipoprotein [VLDL]) are both important and that the number of particles is more predictive of cardiac events than their lipid content. OBJECTIVE: To determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)–containing lipoproteins. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 (10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the clinical trials. Two populations were studied in this analysis: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment. EXPOSURES: ApoB, non–high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG. MAIN OUTCOME AND MEASURES: The primary study outcome was incident myocardial infarction (MI). RESULTS: Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis, 9647 (24%) were female, and the median (IQR) age was 63 (56.2-69.0) years. In the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI, 1.15-1.40; P

Background The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline recommends statin treatment based on patients' predicted atherosclerotic cardiovascular disease (ASCVD) risk. Whether clinician-reported guideline adoption translates to implementation into practice is unknown. Objectives We aimed to compare clinician lipid management in hypothetical scenarios versus observed practice. Methods The PALM Registry asked 774 clinicians how they would treat 4 hypothetical scenarios of primary prevention patients with: (1) diabetes; (2) high 10-year ASCVD risk (≥7.5%) with high low-density lipoprotein cholesterol (LDL-C; ≥130 mg/dL); (3) low 10-year ASCVD risk ( Results In primary prevention scenarios, 85% of clinicians reported they would prescribe a statin to a diabetic patient and 93% to a high-risk/high LDL-C patient (both indicated by guidelines), while 40% would prescribe statins to a low-risk/high LDL-C patient. In clinical practice, statin prescription rates were 68% for diabetic patients, 40% for high-risk/high LDL-C patients, and 50% for low-risk/high LDL-C patients. Agreement between hypothetical and observed practice was 64%, 39%, and 52% for patients with diabetes, high-risk/high LDL-C, and low-risk/high LDL-C, respectively. Among patients with persistently high LDL-C despite high-intensity statin treatment, 55% of providers reported they would add a non-statin lipid-lowering medication, while only 22% of patients were so treated. Conclusions While the majority of clinicians report adoption of the 2013 ACC/AHA guideline recommendations, observed lipid management decisions in practice are frequently discordant.

The latest cholesterol guidelines have shifted focus from achieving low-density lipoprotein cholesterol (LDL-C) targets toward statin use and intensity guided by atherosclerotic cardiovascular disease (ASCVD) risk.Statin use and intensity were evaluated in 5,905 statin-eligible primary or secondary prevention patients from 138 PALM Registry practices.Overall, 74.7% of eligible adults were on statins; only 42.4% were on guideline-recommended intensity. Relative to primary prevention patients, ASCVD patients were more likely to be on a statin (83.6% vs 63.4%, P.0001) and guideline-recommended intensity (47.3% vs 36.0%, P.0001). Men were more likely than women to be prescribed recommended intensity for primary (odds ratio [OR] 1.87, 95% CI 1.49-2.34) and secondary (OR 1.47, 95% CI 1.26-1.70) prevention. In primary prevention, increasing age, diabetes, obesity, hypertension, and lower 10-year ASCVD risk were associated with increased odds of receiving recommended intensity. Among ASCVD patients, those with coronary artery disease were more likely to be on recommended intensity than cerebrovascular or peripheral vascular disease patients (OR 1.71, 95% CI 1.41-2.09), as were those seen by cardiologists (OR 1.43, 95% CI 1.12-1.83). Median LDL-C levels were highest among patients not on statins (124.0 mg/dL) and slightly higher among those on lower-than-recommended intensity compared with recommended-therapy recipients (88.0 and 84.0 mg/dL, respectively; P≤.0001).In routine contemporary practice, 1 in 4 guideline-eligible patients was not on a statin; less than half were on the recommended statin intensity. Untreated and undertreated patients had significantly higher LDL-C levels than those receiving guideline-directed statin treatment.

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan–Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91–1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02–1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function.

Long-term exposure to stress has been linked to multiple behavioral and biological responses that are detrimental to cardiovascular health, but the association between chronic stress and risks for acute myocardial infarction (MI) remains unknown. We examined the association between exposure to chronic stress and MI incidence from 2006 to 2016 using data from a nationally-representative prospective cohort study of adults aged 45 and older (n=15,109). Chronic stressors included ongoing issues related to personal health, social relationships, financial strain, housing, and caregiving responsibilities. Cox proportional hazards models were used to examine the association between the number of chronic stressors and MI while adjusting for confounding risk factors. More than half of the respondents reported ≥2 chronic stressors at baseline. Risks for MI increased incrementally from 1 chronic stressor (HR=1.28; 95% CI, 1.20-1.37) to ≥4 chronic stressors (HR = 2.71; 95% CI, 2.08-3.53) compared with those who reported no stressors. These risks were partly attenuated after adjustments for socioeconomic, psychosocial, behavioral, and clinical risk factors. The impact of chronic stressors was especially pronounced among adults with a history of MI (P value for interaction=.032). In adults with a prior MI, risks for a recurrent MI increased substantially from 1 chronic stressor (HR=1.31; 95% CI, 1.10-1.55) to ≥4 chronic stressors (HR = 2.92; 95% CI, 1.47-5.82) compared to those with no stressors. Chronic stress is a significant risk factor for acute coronary events in U.S. adults. More research is required to further understand the psychosocial, behavioral, and biological mechanisms underlying this association.

BACKGROUND: The ACC/AHA guidelines for primary prevention rely on the Pooled Cohort Risk Equations (PCE) risk estimates of atherosclerotic cardiovascular disease (ASCVD) to guide treatment decisions. In light of the PCE being derived in younger populations, their accuracy in older adults is uncertain. OBJECTIVE: To evaluate the predictive accuracy and calibration of the PCE in older individuals. DESIGN AND SETTING: We estimated CVD predicted and observed risk among individuals from four large prospective cohort studies: Cardiovascular Health Study, Multiethnic Study of Atherosclerosis, Framingham Original, and Framingham Offspring. PARTICIPANTS: 12,527 overall individuals without ASCVD, including 9864 individuals aged 40–74 years and 2663 aged ≥75 years. MEASUREMENTS: We examined the operating characteristics of the PCE to estimate 5-year risk of stroke, MI, and CHD death overall and by age and sex strata. The associations between individual components of the PCE and cardiovascular events by age group (≥75 vs 40–74 years) were also evaluated. RESULTS: The PCE had low discrimination for 5-year ASCVD risk in older (≥75 years) (c-statistic = 0.62, 95% CI 0.60–0.65) vs. younger (40–74 years) adults (c-statistic = 0.75, 95% CI 0.73–0.76). Calibration of the PCE was suboptimal in both older and younger adults, overestimating risk in the highest risk groups. Performance of the PCE in older adults was similarly poor when stratified by sex and age ≥ 80 years. LIMITATIONS: Since the PCE were derived from similar cohorts, though using different age groups and exams, this analysis likely overestimates the performance of the PCE. CONCLUSION: The performance of the PCE for ASCVD risk estimation in older adults is suboptimal; new models to effectively risk-stratify older adults are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05361-4) contains supplementary material, which is available to authorized users.

BACKGROUND: Trapping of apoB lipoprotein particles within the arterial wall initiates and drives the atherosclerotic process from beginning to end. Very low-density lipoprotein particles (VLDL) contain most of the triglyceride in plasma whereas low-density lipoprotein particles (LDL) particles contain most of the cholesterol. Smaller numbers of chylomicron and Lp(a) particles are also present in plasma. All these particles have one molecule of apoB. Therefore, plasma apoB equals the total number of apoB particles. Because the lipid content of apoB particles is variable, plasma triglyceride and cholesterol are not always accurate-measures of the number of apoB particles. THE CHOLESTEROL MODEL OF ATHEROSCLEROSIS: The conventional model of atherosclerosis presumes that the mass of cholesterol within VLDL and LDL particles is the principal determinant of the mass of cholesterol that will be deposited within the arterial wall and will drive atherogenesis. But cholesterol can only enter the arterial wall within apoB particles and the mass of cholesterol that will be deposited is determined by the rate at which apoB particles are trapped within the arterial wall rather than passing harmless through. THE APOB PARTICLE MODEL OF ATHEROGENESIS: The number of apoB particles that enter and are trapped within the arterial wall is determined primarily by the number of apoB particles within the arterial lumen. However, once within the arterial wall, smaller cholesterol-depleted apoB particles have a greater tendency to be trapped than larger cholesterol-enriched apoB particles because they bind more avidly to the glycosaminoglycans within the subintimal space of the arterial wall. If so, a cholesterol-enriched particle would deposit more cholesterol than a cholesterol-depleted apoB particle. By contrast, more smaller apoB particles that enter the arterial wall will be trapped than larger apoB particles. The net result is, with the exceptions of the abnormal chylomicron remnants in type III hyperlipoproteinemia and Lp(a), all apoB particles are equally atherogenic. ApoB, therefore, unifies, amplifies, and simplifies the information from the conventional lipid markers as to the atherogenic risk attributable to the apoB lipoproteins.

Background Elevated triglycerides (TGs) are associated with increased risk of cardiovascular disease (CVD), but the best way to both measure TGs and assess TG-related risk remains unknown. Objective The objective of the study was to evaluate the association between TGs and CVD and determine whether the average of a series of TG measurements is more predictive of CVD risk than a single TG measurement. Methods We examined 15,792 study participants, aged 40–65 years, free of CVD from the Atherosclerosis Risk in Communities and Framingham Offspring studies, using fasting TG measurements across multiple examinations over time. With up to 10 years of follow-up, we assessed time-to-first CVD event, as well as a composite of myocardial infarction, stroke, or cardiovascular death. Results Compared with a single TG measurement, average TGs over time had greater discrimination for CVD risk (C-statistic, 0.60 vs 0.57). Risk for CVD increased as average TGs rose until an inflection point of ~100 mg/dL in men and ~200 mg/dL in women, above which this risk association plateaued. The relationship between average TGs and CVD remained statistically significant in multivariable modeling adjusting for low-density lipoprotein cholesterol, and interactions were found by sex and high-density lipoprotein cholesterol level. Conclusions The average of several TG readings provides incremental improvements for the prediction of CVD relative to a single TG measurement. Regardless of the method of measurement, higher TGs were associated with increased CVD risk, even at levels previously considered “optimal” (

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease ( CAD ) versus cerebrovascular disease (Ce VD ) versus both CAD and Ce VD ( CAD &Ce VD ). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with Ce VD only (n=403), CAD only (n=2202), and Ce VD & CAD (n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with Ce VD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45–0.81) than those with CAD only. Individuals with Ce VD only were also less likely to achieve low‐density lipoprotein cholesterol dL (59.2% versus 69.7%; adjusted odds ratio 0.79, 95% CI 0.64–0.99) than individuals with CAD alone. There were no significant differences in the use of any statin therapy or guideline‐recommended statin intensity between individuals with CAD &Ce VD and those with CAD only. Conclusions Despite lack of significant differences in patient‐perceived cardiovascular risk or statin beliefs, patients with Ce VD were significantly less likely to receive higher intensity statin or achieve low‐density lipoprotein cholesterol dL than those with CAD only.

Muscle-related events, including less severe muscle complaints without a clear pharmacological relationship to the treatment, may hamper compliance with lipid-lowering therapy and increase the risk of drug discontinuation ([1][1]). In IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy

Background: While hypertriglyceridemia is a known risk factor for developing CVD, whether it poses residual risk in patients with type 2 diabetes mellitus (T2DM) and established CVD is under-studied. Methods: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, we examined 2,307 patients with T2DM and CVD to determine the association of baseline fasting triglyceride (TG) levels with MACE (time to CV death, myocardial infarction (MI), or stroke) or CV death over a mean follow-up of 5.0 years. Results: At baseline, the mean fasting TG was 181 mg/dl with a median (Q1, Q3) of 148 (104, 219) mg/dl. Overall, 49.3% had TG≥ 150 mg/dl (N=1,167). Compared with those with TG Conclusions: In this analysis of patients with T2DM and known CVD, TGs were relatively high and were associated with CV outcomes, but not when other risk factors were taken into account. Thus, while TGs are clearly a marker of those with residual high risk for CV events in T2DM, whether they specifically need to be lowered awaits well conducted clinical trials. Disclosure N. Pagidipati: Research Support; Self; Amarin Corporation, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Regenerative Medical Solutions, Sanofi. A. Navar: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Amarin Corporation, Amgen Inc., Regeneron Pharmaceuticals, Sanofi. H. Mulder: None. D.M. Wojdyla: None. S. Philip: Employee; Self; Amarin Corporation. Stock/Shareholder; Self; Amarin Corporation. C.B. Granowitz: Employee; Self; Amarin Pharma Inc. Stock/Shareholder; Self; Amarin Pharma Inc. Funding Amarin Corporation

Background Trials have demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective as an adjunct to statin therapy, but access and cost issues have limited their use in community practice. Objective The aim of the study was to better understand patients' experiences when trying to obtain, fill, and use PCSK9 inhibitor therapy in community practice. Methods We conducted a patient survey to evaluate patient experiences with PCSK9 inhibitors including medication initiation, indication for treatment, insurance approval status, medication persistence, and reason for discontinuation. The survey was emailed to 4740 adults who used a patient access support program. Results Overall, 1327 of 4740 adults completed the survey (28.0% response rate). Of those, 75.0% were aged >60 years, 52.8% were male, and 92.4% were White. At the time of PCSK9 inhibitor prescription, 70.2% were not on a statin (with 84.4% of those not on a statin reporting statin intolerance). Overall, 74.6% of patients found the drug approval process to be "somewhat" or "very" burdensome. Among n = 1216 patients who initiated treatment, 33.7% discontinued by the time of the survey, with 50.0% taking the drug for 1 to 6 months. Patient out-of-pocket costs were the leading reported reason for discontinuation. Conclusions Most PCSK9 inhibitor users in community practice were not on a statin, presumably because of statin intolerance. The drug approval process and costs continue to be strong reasons for lower initiation of PCSK9 agents, as well as higher discontinuation rates.

BACKGROUND: Adherence to guideline-recommended statin recommendations in the United States (U.S.) is suboptimal. Patients’ likelihood to be treated according to guidelines may vary by the practice in which they are treated. METHODS: Variation in the use of statin therapy in 5,445 patients, with known or at high risk for atherosclerotic cardiovascular disease (ASCVD) and meeting a statin treatment indication, was examined across 74 U.S. Patient and Provider Assessment of Lipid Management (PALM) Registry clinics. Multivariable generalized linear mixed modeling was used to determine the median odds ratio (MOR) for statin use and 2013 American College of Cardiology/American Heart Association guideline-recommended statin intensity by practice. MOR quantifies between-practice variation by comparing the odds of receiving guideline-recommended statin treatment in a patient from a randomly selected practice with a similar patient from another random practice. Risk-adjusted low-density lipoprotein cholesterol (LDL-C) control (

Background: Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials. Methods and Results: We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8–85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%–51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2–8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P =0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates. Conclusions: Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.

Guideline implementation requires clinician knowledge but may be influenced by pre-existing beliefs and biases. We assessed the association of these clinician factors with lipid management following the release of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. In the PALM registry, 774 clinicians completed a survey to assess their knowledge of the 2013 American College of Cardiology/American Heart Association guidelines, belief in statin benefit, and statin safety concerns. The association of these factors with statin use, statin dosing, and low-density lipoprotein cholesterol (LDL-C) levels were assessed in the 6,839 patients treated by these clinicians between May and November 2015. Overall, 63.9% of clinicians responded to at least 3 out of 4 hypothetical scenarios in concordance with guideline recommendations (good tested knowledge), 88.4% reported belief in statin benefit, and 15.4% raised concerns about statin safety. Belief in statin benefit was more prevalent among cardiologists, who represented 48.8% of the clinicians surveyed, and concerns regarding statin safety were higher among noncardiologists and clinicians in an academic setting. Guideline knowledge was not associated with a difference in statin use (74.1% vs 73.8%, p = 0.84) and achievement of LDL-C level100 mg/dl (54.7% vs 52.4%, p = 0.07). However, patients treated by clinicians who reported belief in statin benefit were more likely to receive guideline-recommended statin intensity (41.9% vs 36.9%, p = 0.03), whereas patients treated by clinicians expressing statin safety concerns were less likely receive statins of at least guideline-recommended intensity (36.8% vs 42.5%, p = 0.001) and to achieve an LDL-C100 mg/dl (44.1% vs 56.1%, p0.001); the latter persisted after multivariable adjustment (odds ratio 0.75, 95% confidence interval 0.63 to 0.89). In conclusion, clinician beliefs regarding benefits and risks of statins were significantly associated with guideline adherence and patients' achieved LDL-C levels, whereas clinician knowledge of guideline recommendations was not.

Background The 2013 American College of Cardiology/American Heart Association Cholesterol Treatment Guideline increased the number of primary prevention patients eligible for statin therapy, yet uptake of these guidelines has been modest. Little is known of how primary care provider ( PCP ) beliefs influence statin prescription. Methods and Results We surveyed 164 PCP s from a community‐based North Carolina network in 2017 about statin therapy. We evaluated statin initiation among the PCP s’ statin‐eligible patients between 2014 and 2015 without a previous prescription. Seventy‐two PCP s (43.9%) completed the survey. The median estimate of the relative risk reduction for high‐intensity statins was 45% (interquartile range, 25%–50%). A minority of providers (27.8%) believed statins caused diabetes mellitus, and only 16.7% reported always/very often discussing this with patients. Most PCPs (97.2%) believed that statins cause myopathy, and 72.3% reported always/very often discussing this with patients. Most (77.7%) reported always/very often using the 10‐year atherosclerotic cardiovascular disease risk calculator, although many reported that in most cases other risk factors or patient preferences influenced prescribing (59.8% and 43.1%, respectively). Of 6172 statin‐eligible patients, 22.3% received a prescription for a moderate‐ or high‐intensity statin at follow‐up. Providers reporting greater reliance on risk factors beyond atherosclerotic cardiovascular disease risk were less likely to prescribe statins. Conclusions Although beliefs and approaches to statin discussions vary among community PCP s, new prescription rates are low and minimally associated with those beliefs. These results highlight the complexity of increasing statin prescriptions for primary prevention and suggest that strategies to facilitate standardized discussions and to address external influences on patient beliefs warrant future study.

This report presents findings of an ad hoc working group assembled by the National Heart, Lung, and Blood Institute (NHLBI) to assess research needs to improve prevention, treatment, and control of hypertension among African Americans. Non-Hispanic Blacks (African American and Black will be used for US and international studies, respectively) tend to have an earlier onset, higher prevalence, and disproportionately high risk of complications for hypertension compared with non-Hispanic Whites and Mexican Americans.1 Surveys identify substantial variation in mean blood pressure (BP) among populations of African origin.2 In high-income countries, including the United States, mean BP and prevalence of hypertension are higher in adults self-described,3–6 observer reported,7,8 or otherwise identified9,10 as being black or having darker skin color.11 However, the relationship between African origin and BP is absent or only minimally apparent in reports from middle-income countries.12–14 Research to clarify reasons for this variability may contribute to understanding of hypertension-related racial disparities in the United States. In US National Health and Nutrition Examination Survey (NHANES) reports, crude and age-adjusted prevalence of hypertension (systolic BP [SBP] ≥140 mm Hg, diastolic BP ≥90 mm Hg, or taking antihypertensive medication) in adults has remained fairly constant at ≈30% since 1999 to 2000.3,4 The corresponding prevalence estimate for African Americans is ≈40% and has also remained reasonably stable. In African Americans, hypertension awareness and treatment rates are higher but control rates lower compared with non-Hispanic Whites (85.7% versus 82.7% for awareness, 77.4% versus 76.7% for treatment, and 49.5% versus 53.9% for control in NHANES 2011–2012).4 The lower prevalence of BP control is present despite use of more BP-lowering medications, including thiazide diuretics.15 This contrasts with clinical trial experience, where differences in BP control rates by race/ethnicity …

Background Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. Methods We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Results Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Conclusions Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations.

IMPORTANCE: Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. OBJECTIVE: To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. INTERVENTIONS: Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. MAIN OUTCOMES AND MEASURES: Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. RESULTS: Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P

GlycA, a measure of glycosylated proteins, is a novel biomarker of chronic sub-clinical inflammation. Its association with premature coronary artery disease (CAD) is unknown. GlycA data from the PROMISE trial were compared to incident cardiovascular (CV) events (death, myocardial infarction or

The 2018 American Heart Association/American College of Cardiology cholesterol guideline changed statin eligibility criteria for primary prevention to include multiple new risk “enhancers”. Whether this improved identification of young adults at risk for premature CVD compared with the prior

Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low‐density lipoprotein cholesterol ( LDL ‐C) to identify untreated patients with LDL ‐C ≥190 mg/dL, assess lipid‐lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL ‐C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL ‐C levels measured in the 2 years before enrollment. Patients without chart‐documented LDL ‐C levels were more often women, nonwhite, uninsured, and non–college graduates (all P P =0.0034), a high‐intensity statin (21.5% versus 24.3%; P =0.016), nonstatin lipid‐lowering therapy (24.8% versus 27.3%; P =0.037), and had higher core laboratory LDL ‐C levels at enrollment (median 97 versus 92 mg/dL; P LDL ‐C testing. Of 166 individuals with core laboratory LDL ‐C levels ≥190 mg/dL, 36.1% had no LDL ‐C measurement in the prior 2 years, and 57.2% were not on a statin at the time of enrollment. Conclusions In routine clinical practice, LDL ‐C testing is associated with higher‐intensity lipid‐lowering treatment and lower achieved LDL ‐C levels.

African American individuals face higher atherosclerotic cardiovascular disease risk than white individuals; reasons for these differences, including potential differences in patient beliefs regarding preventive care, remain unknown.To evaluate differences in statin use between white and African American patients and identify the potential causes for any observed differences.Using the 2015 Patient and Provider Assessment of Lipid Management (PALM) Registry data, we compared statin use and dosing between African American and white outpatient adults who were potentially eligible for primary or secondary prevention statins. A total of 138 US community health care practices contributed to the data. Data analysis was conducted from March 2017 to May 2018.Primary outcomes were use and dosing of statin therapy according to the 2013 American College of Cardiology/American Heart Association guideline by African American or white race. Secondary outcomes included lipid levels and patient-reported beliefs. Poisson regression was used to evaluate the association between race and statin undertreatment, a category combining people who were not taking a statin or those taking a dose intensity lower than recommended.A total of 5689 patients (806 [14.2%] African American) in the PALM registry were eligible for statin therapy. African American individuals were less likely than white individuals to be treated with a statin (570/807 [70.6%] vs 3654/4883 [74.8%]; P = .02). Among those treated, African American patients were less likely than white patients to receive a statin at guideline-recommended intensity (269 [33.3%] vs 2145 [43.9%], respectively; P .001; relative risk, 1.07 [95% CI, 1.00-1.15]; P = .05, after adjustment for demographic and clinical factors). The median (interquartile range) low-density lipoprotein cholesterol levels of patients receiving treatment were higher among African American than white individuals (97.0 [76.0-121.0] mg/dL vs 85.0 [68.0-105.0] mg/dL; P .001). African American individuals were less likely than white individuals to believe statins were safe (292 [36.2%] vs 2800 [57.3%]; P .001) or effective (564 [70.0%] vs 3635 [74.4%]; P = .008) and were less likely to trust their clinician (663 [82.3%] vs 4579 [93.8%]; P .001). Group differences in statin undertreatment were not significant after adjusting for demographic, clinical, and clinician factors, socioeconomic status, and patient beliefs (final adjusted relative risk, 1.03 [95% CI 0.96-1.11]; P = .35).African American individuals were less likely to receive guideline-recommended statin therapy. Demographic, clinical, socioeconomic, belief-related, and clinician differences contributed to observed differences and represent potential targets for intervention.

Background New cholesterol guidelines emphasize 10-year risk of cardiovascular disease (CVD) to identify adults eligible for statin therapy as primary prevention. Whether these CVD risk thresholds should be individualized by age and sex has not been explored. Objectives This study evaluated the potential impact of incorporating age- and sex-specific CVD risk thresholds into current cholesterol guidelines. Methods Using data from the Framingham Offspring Study, this study assessed current treatment recommendations among age- and sex-specific groups in 3,685 participants free of CVD. Then, it evaluated how varying age- and sex-specific 10-year CVD risk thresholds for statin treatment affect the sensitivity and specificity for incident 10-year CVD events. Results Basing statin therapy recommendations on a 10-year fixed risk threshold of 7.5% results in lower statin consideration among women than men (63% vs. 33%; p Conclusions Cholesterol treatment recommendations could be improved by using individualized age- and sex-specific CVD risk thresholds.

Background— Many young adults with moderate hyperlipidemia do not meet statin treatment criteria under the new American Heart Association/American College of Cardiology cholesterol guidelines because they focus on 10-year cardiovascular risk. We evaluated the association between years of exposure to hypercholesterolemia in early adulthood and future coronary heart disease (CHD) risk. Methods and Results— We examined Framingham Offspring Cohort data to identify adults without incident cardiovascular disease to 55 years of age (n=1478), and explored the association between duration of moderate hyperlipidemia (non–high-density lipoprotein cholesterol≥160 mg/dL) in early adulthood and subsequent CHD. At median 15-year follow-up, CHD rates were significantly elevated among adults with prolonged hyperlipidemia exposure by 55 years of age: 4.4% for those with no exposure, 8.1% for those with 1 to 10 years of exposure, and 16.5% for those with 11 to 20 years of exposure ( P Conclusions— Cumulative exposure to hyperlipidemia in young adulthood increases the subsequent risk of CHD in a dose-dependent fashion. Adults with prolonged exposure to even moderate elevations in non–high-density lipoprotein cholesterol have elevated risk for future CHD and may benefit from more aggressive primary prevention.