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Background The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline recommends using 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk to guide decisions to initiate antihypertensive medication. Methods We included adults aged 40-79 years from the National Health and Nutrition Examination Survey 2013-2018 (n = 8803). We computed 10-year predicted ASCVD risk using the Pooled Cohort risk equations. Clinical CVD was self-reported. Analyses were conducted overall and among those with stage 1 hypertension, defined by a mean SBP of 130-139 mmHg or DBP of 80-89 mmHg. In subgroups defined by diabetes, chronic kidney disease (CKD), and age at least 65 years, we estimated the proportion of United States adults with high ASCVD risk (i.e. 10-year predicted ASCVD risk ≥10% or clinical CVD) and estimated age-adjusted probability of having high ASCVD risk. Results Among United States adults, an estimated 72.3, 64.5, and 83.9 of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. Among United States adults with stage 1 hypertension, an estimated 55, 36.7, and 72.6% of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. The probability of having high ASCVD risk increased with age and exceeded 50% for United States adults with diabetes and CKD at ages 52 and 57 years, respectively. For those with stage 1 hypertension, these ages were 55 and 64 years, respectively. Conclusion Most United States adults with diabetes, CKD, or age at least 65 years had high ASCVD risk. However, many with stage 1 hypertension did not.

Purpose of review To highlight mechanisms of elevated risk of atherosclerotic cardiovascular disease (ASCVD) among people living with HIV (PLWH), discuss therapeutic strategies, and opportunities for primary prevention. Recent findings HIV-associated ASCVD risk is likely multifactorial and due to HIV-specific factors and traditional risk factors even in the setting of treated and suppressed HIV disease. Although a growing body of evidence suggests that inflammation and immune activation are key drivers of atherogenesis, therapies designed to lower inflammation including colchicine and low-dose methotrexate have not improved secondary cardiovascular endpoints among PLWH. Statins continue to be the mainstay of management of hyperlipidemia in HIV, but the impact of newer lipid therapies including proprotein convertase subtilisin/kexin type 9 inhibitors on ASCVD risk among PLWH is under investigation. Aside from the factors mentioned above, healthcare disparities are particularly prominent among PLWH and thus likely contribute to increased ASCVD risk. Summary Our understanding of mechanisms of elevated ASCVD risk in HIV continues to evolve, and the optimal treatment for CVD in HIV aside from targeting traditional risk factors remains unknown. Future studies including novel therapies to lower inflammation, control of risk factors, and implementation science are needed to ascertain optimal ways to treat and prevent ASCVD among PLWH.

Purpose of review Elevated levels of triglycerides, independent of low-density lipoprotein cholesterol (LDL-C) levels and statin therapy, are associated with heightened cardiovascular risk. Recent findings Mixed omega-3 fatty acid formulations, which contain varying amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), lower triglycerides levels but trial results with omega-3 fatty acids combinations have generally been neutral for cardiovascular outcomes. In contrast, the REDUCE-IT trial with icosapent ethyl (IPE), a highly purified ethyl ester of EPA, demonstrated reduced cardiovascular risk in individuals with established atherosclerotic cardiovascular disease or diabetes with at least one additional risk factor, despite having relatively well controlled LDL-C levels but triglycerides at least 135 mg/dl while on statin therapy. IPE offers an important new avenue for cardiovascular risk management in statin-treated individuals with elevated triglycerides. Summary This review summarizes the results from outcome trials conducted with omega-3 fatty acids, differentiating between those with combinations of EPA/DHA and those with pure EPA, as well as imaging and preclinical data that help explain the different cardiovascular efficacy observed. A list of frequently asked questions with evidence-based responses is provided to assist our colleagues and their patients in the shared-decision process when considering if IPE is appropriate for cardiovascular risk reduction.

The menopause transition is associated with adverse changes to the lipid profile. Although there are no specific treatment guidelines for women, current evidence supports the use of statin therapy in women with 1) established clinical atherosclerotic cardiovascular disease (ASCVD); 2) primary hypercholesterolemia, with low-density lipoprotein cholesterol of 190 mg/dL (4.9 mmol/L) or higher; 3) diabetes mellitus regardless of ASCVD risk category (ages 40-75 y); and 4) for primary prevention of ASCVD in women at high risk (10-y risk, ≥20%) or intermediate risk (10-y risk, ≥7.5-20%) with the presence of guideline-derived risk enhancers (age 40-75 y) such as premature menopause or a history of preeclampsia.

Purpose of review To summarize types of dyslipidemia frequently encountered during childhood and adolescence, with a focus on screening, diagnosis, and management. Recent findings It is important that screening for atherosclerotic cardiovascular disease (ASCVD) begin in childhood. Genetic testing allows for increased awareness of dyslipidemia and more targeted intervention. Pharmacologic treatment of pediatric dyslipidemias has a good safety profile and can reduce adult ASCVD risk. Summary Much of what is known about pediatric dyslipidemia has been extrapolated from adult data, but recently, there have been increasing investigations within the pediatric population to better guide diagnosis and management of these disorders.

Supplemental Digital Content is available in the text., Background: In patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes. Methods: VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial), a double-blind, placebo-controlled trial, randomly assigned patients with type 2 diabetes mellitus and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF/CV death, overall and stratified by prespecified characteristics. Cox proportional hazards modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF/CV death events. Results: A total of 8246 patients were randomly assigned to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pretrial ejection fraction (EF) available, including n=959 with EF ≤45%. Ertugliflozin did not significantly reduce first HHF/CV death (hazard ratio [HR], 0.88 [95% CI, 0.75–1.03]). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70 [95% CI, 0.54–0.90]; P=0.006). Previous HF did not modify this effect (HF: HR, 0.63 [95% CI, 0.44–0.90]; no HF: HR, 0.79 [95% CI, 0.54–1.15]; P interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF ≤45% versus preserved EF >45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF ≤45% (HR, 0.48 [95% CI, 0.30–0.76]) versus EF >45% (HR, 0.86 [95% CI, 0.58–1.29]). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in 3 populations: baseline estimated glomerular filtration rate

Background: Lipid-lowering recommendations for prevention of atherosclerotic cardiovascular disease rely principally on estimated 10-year risk. We sought to determine the optimal time for initiation of lipid lowering in younger adults as a function of expected 30-year benefit. Methods: Data from 3148 National Health and Nutrition Examination Survey (2009–2016) participants, age 30 to 59 years, not eligible for lipid-lowering treatment recommendation under the most recent US guidelines, were analyzed. We estimated the absolute and relative impact of lipid lowering as a function of age, age at initiation, and non–high-density lipoprotein cholesterol (HDL-C) level on the expected rates of atherosclerotic cardiovascular disease over the succeeding 30 years. We modeled expected risk reductions based on shorter-term effects observed in statin trials (model A) and longer-term benefits based on Mendelian randomization studies (model B). Results: In both models, potential reductions in predicted 30-year atherosclerotic cardiovascular disease risk were greater with older age and higher non–HDL-C level. Immediate initiation of lipid lowering (ie, treatment for 30 years) in 40- to 49-year-old patients with non–HDL-C ≥160 mg/dL would be expected to reduce their average predicted 30-year risk of 17.1% to 11.6% (model A; absolute risk reduction [ARR], 5.5%) or 6.5% (model B; ARR 10.6%). Delaying lipid lowering by 10 years (treatment for 20 years) would result in residual 30-year risk of 12.7% (A; ARR 4.4) or 9.9% (B; ARR 7.2%) and delaying by 20 years (treatment for 10 years) would lead to expected mean residual risk of 14.6% (A; ARR 2.6%) or 13.9% (B; ARR 3.2%). The slope of the achieved ARR as a function of delay in treatment was also higher with older age and higher non–HDL-C level. Conclusions: Substantial reduction in expected atherosclerotic cardiovascular disease risk in the next 30 years is achievable by intensive lipid lowering in individuals in their 40s and 50s with non–HDL-C ≥160 mg/dL. For many, the question of when to start lipid lowering might be more relevant than whether to start lipid lowering.

OBJECTIVES: The AHA/ACC-2017 hypertension guideline recommends an age-independent target blood pressure (BP) of less than 130/80 mmHg. In an elderly cohort without established cardiovascular disease (CVD) at baseline, we determined the impact of this guideline on the prevalence of hypertension and associated CVD risk. METHODS: Nineteen thousand, one hundred and fourteen participants aged at least 65 years from the ASPirin in Reducing Events in the Elderly (ASPREE) study were grouped by baseline BP: ‘pre-2017 hypertensive’ (BP ≥140/90 mmHg and/or on antihypertensive drugs); ‘reclassified hypertensive’ (normotensive by pre-2017 guidelines; hypertensive by AHA/ACC-2017 guideline), and ‘normotensive’ (BP

Purpose of review Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD. Recent findings The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15-20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) reduce LDL-C by 50-60% and reduce the risk of ASCVD events. However, these agents require self-administration by subcutaneous injection every 2-4 weeks. The PCSK9 synthesis inhibitor, inclisiran, is administered approximately 6 monthly and may be more suitable for widespread use, although outcome trials are awaited. These PCSK9 targeting therapies require no dose adjustment in CKD and have no drug interactions. Summary Statins and ezetimibe are safe and reduce ASCVD risk in CKD populations. PCSK9 targeting agents may be useful in high-risk CKD patients, including those with prior ASCVD.

Atherosclerotic cardiovascular disease (ASCVD), the buildup of plaque within the arterial walls, contributes to acute coronary syndrome, angina, stroke, transient ischemic attack, and peripheral arterial disease. This second article in a series about the most commonly billed diagnoses in primary care describes the pathophysiologic processes of ASCVD as well as how the clinical manifestations and treatments are linked to the pathogenesis of the disease.

PURPOSE OF REVIEW: Cholesterol on Low-Density Lipoproteins (LDL-C) is one of the main drivers of atherosclerotic cardiovascular disease (ASCVD) and hence its measurement is critical in the management of patients at risk. Although LDL-C has routinely been either calculated by the Friedewald equation or measured with direct assays, these methods have limitations, particularly for patients with dyslipidaemias, low LDL-C and hypertriglyceridaemia. The focus of this review will be recent advances in the measurement of LDL for ASCVD risk management. RECENT FINDINGS: We first describe the recent recommendations on how LDL-C is used in ASCVD risk assessment and management. We then review the current approaches to the measurement of LDL-C and recent developments on new more accurate equations for calculating LDL-C. Finally, we present new and emerging LDL assays that may be superior to LDL-C for risk assessment, such as LDL particle number and small dense LDL-C, as well as several LDL-based lipid tests in early development. SUMMARY: LDL-C is valuable in ASCVD risk management but recent improvements in its measurement and the development of other LDL related tests may further improve its value.

Purpose of review Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy trials, many of which provide a unique opportunity to further reduce low-density lipoprotein cholesterol (LDL-C) levels and ASCVD risk on top of statin therapy, and in doing so further decrease the number of future major adverse cardiovascular events. Recent findings Although statin therapy has been the mainstay of treatment for lowering LDL-C levels for many years, many individuals require additional or alternative options for further reducing their risk. Trials on previously studied therapies, such as PCSK9 inhibitors, and new therapies, including inclisiran, bempedoic acid and icosapent ethyl demonstrate significant potential for further lowering of LDL-C levels and risk for events on top of maximally tolerated statin therapy with favourable side effect profiles. Summary As therapies for ASCVD prevention continue to emerge, clinicians will need to identify the appropriate treatment for individuals based on their estimated risk and risk-enhancing factors. When statin therapy is either not sufficient or patients do not tolerate adequate statin therapy, relying on newer therapies, such as PCSK9-inhibitors, inclisiran, bempedoic acid and icosapent ethyl, will be critical to maximize risk factor profiles to reduce adverse outcomes.

Background: Medication nonadherence is associated with worse outcomes in patients with atherosclerotic cardiovascular disease (ASCVD), a group who requires long-term therapy for secondary prevention. It is important to understand to what extent drug costs, which are potentially actionable factors, contribute to medication nonadherence. Methods: In a nationally representative survey of US adults in the National Health Interview Survey (2013–2017), we identified individuals ≥18 years with a reported history of ASCVD. Participants were considered to have experienced cost-related nonadherence (CRN) if in the preceding 12 months they reported skipping doses to save money, taking less medication to save money, or delaying filling a prescription to save money. We used survey analysis to obtain national estimates. Results: Of the 14 279 surveyed individuals with ASCVD, a weighted 12.6% (or 2.2 million [95% CI, 2.1–2.4]) experienced CRN, including 8.6% or 1.5 million missing doses, 8.8% or 1.6 million taking lower than prescribed doses, and 10.5% or 1.9 million intentionally delaying a medication fill to save costs. Age 1 in 5 reporting CRN in these subgroups. Survey respondents with CRN compared with those without CRN had 10.8-fold higher odds of requesting low-cost medications and 8.9-fold higher odds of using alternative, nonprescription, therapies. Conclusions: One in 8 patients with ASCVD reports nonadherence to medications because of cost. The removal of financial barriers to accessing medications, particularly among vulnerable patient groups, may help improve adherence to essential therapy to reduce ASCVD morbidity and mortality.

PURPOSE OF REVIEW: Determine if evidence supports interventions to prevent development of atherosclerosis and atherosclerotic cardiovascular disease (ASCVD) events and death. RECENT FINDINGS: An extensive body of evidence supports the fundamental causal role of apoB lipoproteins in the development of atherosclerosis. Recent epidemiologic studies have shown that LDL-C and non-HDL-C levels in early adults are associated with accelerated subclinical atherosclerosis and an excess of atherosclerotic cardiovascular events later in life. Animal and human data have shown that intensive LDL-C lowering can regress earlier stages of atherosclerosis. SUMMARY: The next research priority is evaluating the impact of lowering LDL-C earlier in life to regress early atherosclerosis, followed by trials to demonstrate this approach will eradicate later-life ASCVD events and death. This approach of curing atherosclerosis will likely be the most effective strategy for reducing the huge global burden of atherosclerosis.

Purpose of review:\ud Cardiovascular disease prevention trials of lipid lowering with statins have shown unexpected long-term benefits after the formal randomized treatment stopped. This finding needs further exploration because it raises the possibility that the trajectory of the disease can be modified.\ud Recent findings:\ud Extended follow up data are now available from further major primary prevention studies and from meta-analyses of the legacy effect of statin trials. New outcome studies have been proposed and launched to test the ability of early intervention to slow or regress atherosclerosis.\ud Summary:\ud Legacy effects are apparent in trials of LDL lowering in hypercholesterolemic and hypertensive patient cohorts. Over follow up periods of decades, both cardiovascular mortality and all-cause mortality are reduced in individuals who received 3 to 5 years of statin therapy. The phenomenon is observed also in studies of intensive glycemic control suggesting that it is possible to impact plaque development with long-term beneficial consequences. Novel strategies for primary prevention are being devised that include the early use of both prolonged-moderate and short-term aggressive LDL lowering.

Residual risk for atherosclerotic cardiovascular disease (ASCVD) persists even among patients with optimal low-density lipoprotein cholesterol (LDL-C) levels. Randomized trials attempting to modulate other lipids beyond LDL-C have failed to demonstrate significant reductions in ischemic events.Mounting evidence suggests that triglyceride elevation is an independent risk factor for ASCVD. Though trials of triglyceride-lowering therapy in the statin era have failed to provide protection from ASCVD events, subgroup analyses have revealed that those with the highest triglycerides at time of enrollment appeared to receive the greatest clinical benefit. REDUCE-IT was a trial that enrolled patients with high triglycerides despite having goal LDL-C levels on statin therapy. Treatment with icosapent ethyl, a highly purified omega-3 fatty acid (OM3FA), eicosapentaenoic acid ethyl ester, provided a 25% relative risk reduction for the primary composite cardiovascular endpoint (hazard ratio 0.75, 95% CI 0.68--0.83; P = 0.00000001), as well as a 30% relative risk reduction in total ischemic events (P = 0.00000000036).Icosapent ethyl was rigorously shown to decrease residual risk for cardiovascular events, though the benefits seen were likely because of mechanisms beyond mere triglyceride lowering. Clinical application of icosapent ethyl in this cohort of patients with residual risk is urgently needed.

Background Patients with risk factors or established atherosclerotic cardiovascular disease remain at high‐risk for ischemic events. Triglyceride levels may play a causal role. Methods and Results We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low‐density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all‐cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88–172 mg/dL) and 116 mg/dL (interquartile range, 84–164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89–0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05–1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92–0.97) and higher risk of all‐cause hospitalization (HR, 1.03; 95% CI, 1.01–1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05–1.24). Conclusions In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.

Background: Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing. Methods: PRSs were developed using least absolute shrinkage and selection operator regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines. Results: In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90–0.92) and 0.74 (95% CI, 0.73–0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the European Society of Cardiology/European Atherosclerosis Society lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate. Conclusions: A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.

Background: Current American College of Cardiology/American Heart Association guidelines recommend using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk to guide statin therapy for primary prevention. Real-world data on adherence and consequences of nonadherence to the guidelines in primary are limited. We investigated the guideline-directed statin intensity (GDSI) and associated outcomes in a large health care system, stratified by ASCVD risk. Methods: Statin prescription in patients without coronary artery disease, peripheral vascular disease, or ischemic stroke were evaluated within a large health care network (2013–2017) using electronic medical health records. Patient categories constructed by the 10-year ASCVD risk were borderline (5%–7.4%), intermediate (7.5%–19.9%), or high (≥20%). The GDSI (before time of first event) was defined as none or any intensity for borderline, and at least moderate for intermediate and high-risk groups. Mean (±SD) time to start/change to GDSI from first interaction in health care and incident rates (per 1000 person-years) for each outcome were calculated. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Results: Among 282 298 patients (mean age ≈50 years), 29 134 (10.3%), 63 299 (22.4%), and 26 687 (9.5%) were categorized as borderline, intermediate, and high risk, respectively. Among intermediate and high-risk categories, 27 358 (43%) and 8300 (31%) patients did not receive any statin, respectively. Only 17 519 (65.6%) high-risk patients who were prescribed a statin received GDSI. The mean time to GDSI was ≈2 years among the intermediate and high-risk groups. At a median follow-up of 6 years, there was a graded increase in risk of ASCVD events in intermediate risk (hazard ratio=1.15 [1.07–1.24]) and high risk (hazard ratio=1.27 [1.17–1.37]) when comparing no statin use with GDSI therapy. Similarly, mortality risk among intermediate and high-risk groups was higher in no statin use versus GDSI. Conclusions: In a real-world primary prevention cohort, over one-third of statin-eligible patients were not prescribed statin therapy. Among those receiving a statin, mean time to GDSI was ≈2 years. The consequences of nonadherence to guidelines are illustrated by greater incident ASCVD and mortality events. Further research can develop and optimize health care system strategies for primary prevention.

Background Atherosclerotic cardiovascular disease (ASCVD) results in high out‐of‐pocket healthcare expenditures predisposing to food insecurity. However, the burden and determinants of food insecurity in this population are unknown. Methods and Results Using 2013 to 2018 National Health Interview Survey data, we evaluated the prevalence and sociodemographic determinants of food insecurity among adults with ASCVD in the United States. ASCVD was defined as self‐reported diagnosis of coronary heart disease or stroke. Food security was measured using the 10‐item US Adult Food Security Survey Module. Of the 190 113 study participants aged 18 years or older, 18 442 (adjusted prevalence 8.2%) had ASCVD, representing ≈20 million US adults annually. Among adults with ASCVD, 2968 or 14.6% (weighted ≈2.9 million US adults annually) reported food insecurity compared with 9.1% among those without ASCVD ( P Conclusion About 1 in 7 US adults with ASCVD experience food insecurity, with more than 1 in 2 adults reporting food insecurity among the most vulnerable sociodemographic subgroups. There is an urgent need to address the barriers related to food security in this population.

Background Because of an increasing number and complexity of treatment options for lipid‐lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision‐making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid‐lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low‐density lipoprotein cholesterol (LDL‐C) control (LDL‐C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low‐Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid‐lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL‐C level, and 69% did not know their LDL‐C goal. Patients on PCSK9 inhibitors (versus LDL‐C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient‐reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid‐lowering medications, current LDL‐C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision‐making and treatment adherence. Registration URL: https://www.clinicaltrials.org ; Unique identifier: NCT02993120.

Supplemental Digital Content is available in the text., Background: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to the risk of peripheral artery disease (PAD) have not been well defined. We leveraged large-scale genetic association data to investigate the effects of circulating lipoprotein-related traits on PAD risk. Methods: Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the mendelian randomization bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B (ApoB) lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified with transcriptome-wide association studies. Results: ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability, 0.86; P=0.003) and CAD (marginal inclusion probability, 0.92; P=0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (odds ratio,0.87 per 1-SD decrease in ApoB [95% CI, 0.84–0.91]; P=9×10−10) and CAD (odds ratio,0.66 [95% CI, 0.63–0.69]; P=4×10−73), with a stronger predicted effect of ApoB lowering on CAD (ratio of effects, 3.09 [95% CI, 2.29–4.60]; P

Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long‐term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001–2002) and underwent ultrasound imaging at follow‐up (2013–2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10‐year atherosclerotic cardiovascular disease risk Conclusions Nearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium‐phosphate homeostasis and low sodium intake were associated with long‐term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Background: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study. Methods: We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation in ANGPTL3 protein levels, and accordingly the correlation with the plasma lipidome. Results: In a variance components framework, we identified that variation in ANGPTL3 was significantly heritable (h 2 =0.33, P =1.31×10 −16 ). To explore the genetic basis of this heritability, we conducted a genome-wide linkage scan and identified significant linkage (logarithm of odds =6.18) to a locus on chromosome 1 at 90 centimorgans, corresponding to the ANGPTL3 gene location. In the genomes of 23 individuals from a single pedigree, we identified a loss-of-function variant, rs398122988 (N121Kfs*2), in ANGPTL3 , that was significantly associated with lower ANGPTL3 levels (β=−1.69 SD units, P =3.367×10 −13 ), and accounted for the linkage signal at this locus. Given the known role of ANGPTL3 as an inhibitor of endothelial and lipoprotein lipase, we explored the association of ANGPTL3 protein levels and rs398122988 with the plasma lipidome and related phenotypes, identifying novel associations with phosphatidylinositols. Conclusions: Variation in ANGPTL3 protein levels is heritable and under significant genetic control. Both ANGPTL3 levels and loss-of-function variants in ANGPTL3 have significant associations with the plasma lipidome. These findings further our understanding of ANGPTL3 as a therapeutic target for atherosclerotic cardiovascular disease.

Introduction: The United States has a growing population of transgender adolescents aged 12-21y presenting for medical transition via gender affirming hormone therapy (HT). Transgender people do not identify with their sex assigned at birth while cisgender people do. HT involves estrogen for trans females, those who identify as female, and testosterone for trans males, those who identify as male. Initiation of HT is beginning in adolescence and is a lifelong commitment for many transgender individuals. Little is known about how HT affects ASCVD risk factors in transgender adolescents. Studies of cisgender adults show cardioprotective effects of estrogen, and an estimated 37% of normal-weight cis gender adolescents have at least 1 ASCVD risk factor; but little investigation exists for transgender people, especially adolescents. Although some studies involving the transgender population have reproducible results, few include adolescents and comparison to acceptable ASCVD risk factor profiles. Guidelines for transgender health recommend laboratory assessment before starting HT and annually. This study expands on current knowledge and informs clinical practice by comparing ASCVD risk biomarkers of transgender adolescents taking HT to acceptable clinical values for adolescents. Hypothesis: Estrogen therapy for trans females will ameliorate ASCVD risk factors while testosterone therapy for trans males will worsen ASCVD risk factors. Methods: Retrospective chart review identified 300 transgender patients receiving HT at an academic adolescent medicine gender clinic. Of those 300, 50 trans female and 50 trans male were randomly selected for evaluation of ASCVD risk parameters at baseline and 1 year after initiating HT. ASCVD risk factors were compared to the International Diabetes Federation guidelines for metabolic syndrome. Parameters included lipids, glucose, and blood pressure. BMI ≥30 was used as proxy for obesity. Results: At baseline, at least one abnormal value was found for 50% (n=25, of these 5 had obesity) of trans females and 66% (n=33, of these 13 had obesity) of trans males. At 1 year, at least one abnormal value was found for 30% (n=15) of trans females and 70% (n=35) of trans males. At baseline, 50% (n=25) of trans females and 82% (n=41) of trans males, and at 1 year 20% (n=10) of trans females and 48% (24) of trans males had all parameters measured. Paired t-tests (α=.05) showed no significant change in ASCVD risk factors for trans females, and significant decrease in HDL and significant increase in BMI for trans males after 1 year of HT. Conclusions: The prevalence of having at least 1 ASCVD risk factor is greater among transgender adolescents than normal weight cisgender adolescents. HT may worsen HDL and BMI for trans males. We recommend baseline parameters for all and follow up and lab surveillance for patients with abnormal baseline parameters.

Background: Atherosclerotic cardiovascular disease and its risk factors are increasing globally. We estimated global and regional mean levels of systolic blood pressure (SBP) for the Global Burden of Disease (GBD) 2019 study. Methods: Mean SBP in mm Hg was estimated by age (adults >25 years), sex, location and year using all available population-based health surveys and studies that systematically measured brachial blood pressure. Estimates were produced using a Bayesian statistical model, spatiotemporal Gaussian process regression, which produces a smoothed time series from 1990 to 2019, borrowing strength over space and time, then aggregates to GBD regions. Each point in the figure represents age- and sex-specific mean SBP for one of 21 GBD regions, color coded by the 7 GBD super regions; black triangles denote global mean SBP. We report 95% uncertainty intervals in brackets. Results: Globally, mean SBP increased with age, peaking at 75-84 years, followed by a plateau and slight decline amongst oldest adults. In adults >60 in 1990 and >70 in 2019, females had higher SBP than males globally; this difference declined over time. In 1990, mean SBP was highest among females in Central Europe aged 60-64 (150 [147- 154]) and High-income Asia Pacific aged 80-84 (150 [147 - 152]), and in males aged 80-84 in Western Europe (150 [147-152]) and High-income Asia Pacific (148 [146 - 150]). By 2019, mean SBP was highest among adults aged 80-84 in Western and Southern Sub-Saharan Africa for both females (150 [136 - 164]; 149 [142 - 156], respectively), and males (145 [140 - 150]; 144 [136 - 153], respectively). Conclusions: SBP increased globally with age and was higher in older women than men. The 5-year age group with highest estimated SBP shifted over time from parts of Europe and High-income Asia Pacific to parts of Sub-Saharan Africa. Elevated SBP remains a major health risk for the world’s population, suggesting a need for increased investments in understanding its etiologies and how to treat and eventually prevent it as a cause of disease.

Introduction: A significant proportion of persons with metabolic syndrome, prediabetes, or type 2 diabetes do not develop atherosclerotic cardiovascular disease (ASCVD). Discordantly normal apolipoprotein B (ApoB) relative to elevated LDL-cholesterol (LDL-C) may help to explain underlying heterogeneity in ASCVD risk among these individuals. Hypothesis: We hypothesized that discordantly normal ApoB (> 100 mg/dL) would be associated with a lower atherosclerosis burden among individuals with metabolic disorders. Methods: There were 331 Bogalusa Heart Study participants with metabolic syndrome (n=107), prediabetes (n=291), or type 2 diabetes (n=34) and LDL-C > 100 who were free of carotid plaque at baseline (2001-02) and underwent carotid ultrasound at follow-up (2013-16). Carotid plaque was defined as a focal wall thickening >1.5 mm. Modified Poisson regression with robust error variance estimated the long-term absence of plaque for normal ApoB after adjusting for established risk factors. Results: Participants were on average 36.3 years old at baseline, 202 (61.0%) were women, and 93 (29.9%) were African American. Overall, LDL-C explained 42.3% of the variability in ApoB as the lipoprotein markers were only modestly correlated (r=0.65). Participants with ApoB > 90 (74.6% versus 57.4%, p=0.001, Figure ). In multivariable modeling, persons with ApoB Conclusions: More than half of persons with metabolic disorders and elevated LDL-C had normal ApoB with a lower burden of carotid atherosclerosis over 13 years follow-up. ApoB better represents the atherogenic lipid burden among persons with metabolic disorders compared to LDL-C and may be especially helpful for persons with the pattern of high triglycerides and low HDL-cholesterol.

Background: The Dietary Approaches to Stop Hypertension (DASH) diet is known to reduce cardiovascular disease (CVD) risk factors, but its effects on 10-year CVD risk based on the pooled cohort estimating equation has not been reported. Objective: To determine the effects of adopting the DASH diet on 10-year atherosclerotic cardiovascular disease (ASCVD) risk compared to a typical American (control) diet or a diet rich fruit and vegetables (F/V), but otherwise similar to control. Methods: The DASH trial was a 3-arm, parallel-group, randomized controlled feeding trial of 459 adults aged 22 to 75 years without CVD and not taking anti-hypertensive or diabetes medications. These participants were randomized to a control diet, a F/V diet, or the DASH diet for 8 weeks. Weight was kept constant. Blood pressure (BP) and lipids were measured at baseline and at 8-weeks to compare 10-year ASCVD risk scores across dietary assignments. Comparisons were performed via linear regression adjusted for baseline ASCVD risk score. Results: The mean age of participants was 45 years; 49% were women, 60% were black, and 10% were current smokers. Mean systolic BP was 131.3±10.8 mm Hg, mean LDL cholesterol was 121±32 mg/dL, and mean HDL cholesterol was 48±14 mg/dL. Both DASH and F/V diets shifted the distribution of ASCVD risk scores downward compared to the control diet ( Figure, Panel A ). Compared to the control diet, the DASH and F/V diets reduced 10-year ASCVD risk by 10.0% (95% CI: -17.7, -1.5; P = 0.02) and 11.7% (95% CI: -19.3, -3.3; P = 0.007) respectively ( Figure, Panel B ). There was no difference between the DASH and F/V diets (-1.9%; 95% CI: -10.3, 7.4; P = 0.68). Conclusions: Compared to the control diet, the DASH and F/V diets reduced 10-year ASCVD risk, while the DASH and F/V had similar effects.

Introduction: Early differentiation of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease (ASCVD) risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque in young adults. Hypothesis: Calcium and phosphate are found in excess in atherosclerotic lesions, therefore we hypothesized that mineral markers may help to explain residual heterogeneity in arterial aging phenotypes beyond traditional ASCVD risk factors. Methods: We included 508 participants from the Bogalusa Heart Study without clinical ASCVD who were free of carotid plaque at baseline (2001-02) and underwent ultrasound at follow-up (2013-16). Modified Poisson regression estimated the persistent absence of carotid plaque over 12.8 years. Results: Participants were on average 36.2 years old at baseline, 64% were women, and 29% were African American. Although a majority (97%) of participants had a 10-year ASCVD risk Figure ). Beyond younger age (RR=1.20, 95% CI: 1.07-1.36, per 10 years) and a total cholesterol-HDL-cholesterol ratio Conclusions: Lower calcium-phosphate homeostasis and low sodium intake independently associated with long-term absence of carotid plaque. However, nearly one-third of young adults with a relatively low burden of traditional risk factors developed premature atherosclerosis. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Introduction: The coronary artery calcium (CAC) score is a strong predictor of atherosclerotic cardiovascular disease (ASCVD) events. Current clinical practice guidelines recommend using a CAC score of 100 or age-, sex-, and race-specific 75 th percentile as thresholds of high risk for guiding preventive therapy for ASCVD. On the low end of the spectrum, zero CAC attracts attention as a potent negative predictor of ASCVD and may be used to “de-risk” individuals who may safely defer aggressive preventive therapy. However, due to sparse data on CAC in the age 75+ population, the value of these CAC thresholds in older adults is uncertain. Objective: To understand the distribution of CAC (75 th percentile, CAC 100, and zero CAC) in adults aged 75+. Methods: We assessed 2,303 ARIC Visit 7 (2018-2019) participants age 75+ years without clinical coronary heart disease (CHD) who underwent CAC scanning (median age 80 years, 39% males). Demographic-specific percentiles of the CAC distribution across age were estimated nonparametrically with pooled residual ranking and locally weighted regressions. Results: Male-white and male-black participants had lower prevalence of zero CAC than female-white and female-black participants (4% and 10% versus 13% and 16%, respectively). CAC scores tended to increase with age across race and sex strata but appeared to peak at an old age threshold (between age~85-95) ( Figure ). Regardless of age, sex, and race, a majority of individuals in this age range had CAC >100 ( Figure , green 50 th percentile line exceeds red dashed CAC 100 line at most ages). Conclusions: In the largest US cohort of community-dwelling adults aged 75+ free of clinical CHD with CAC data, the prevalence of zero CAC was approximately 4-16%. We also confirmed a general age-dependent increase in CAC. Using CAC >100 as a threshold for high ASCVD risk would categorize the majority of older adults age 75+ as high risk. Alternatively, our demographic-specific CAC percentiles may be a valuable tool for interpreting CAC in the age 75+ population.

Background: In the 2018 AHA/ACC Cholesterol guideline, risk stratification is an essential element. The use of a Pooled Cohort Equation (PCE) is recommended for individuals without atherosclerotic cardiovascular disease (ASCVD), and the new dichotomous classification of very high-risk vs. high-risk has been introduced for patients with ASCVD. These distinct risk stratification systems mainly rely on traditional risk factors, raising the possibility that a single model can predict major adverse cardiovascular events (MACEs) in persons with and without ASCVD. Methods: We studied 11,335 ARIC participants with (n=885) and without (n=10,450) a history of ASCVD (myocardial infarction, ischemic stroke, and symptomatic peripheral artery disease) at baseline (1996-98). We modeled factors in the PCE and the new classification for ASCVD patients (Figure legend) in a single CVD prediction model. We examined their associations with MACEs (myocardial infarction, stroke, and heart failure) using Cox models and evaluated the discrimination and calibration for a single model including those factors. Results: During a median follow-up of 18.4 years, there were 3,658 MACEs (3,105 in participants without ASCVD). In general, the factors in the PCE and the risk classification system for ASCVD patients were associated similarly with MACEs regardless of baseline ASCVD status, although age and systolic blood pressure showed significant interactions. A single model with these predictors and the relevant interaction terms showed good calibration and discrimination for those with and without ASCVD (c-statistic=0.729 and 0.704, respectively) (Figure). Conclusion: A single CVD prediction model performed well in persons with and without ASCVD. This approach will provide a specific predicted risk to ASCVD patients (instead of dichotomy of very high vs. high risk) and eliminate a practice gap between primary vs. secondary prevention due to different risk prediction tools.

Background Aging leads to increased visceral adipose tissue (VAT) and reduced skeletal muscle density. To which extent these are associated with the risk of stroke, myocardial infarction (MI), and all‐cause mortality in older adults is unknown. Methods and Results A total of 3294 70‐year‐old individuals (49.6% women) underwent a health examination in Umeå, Sweden, during 2012 to 2018. VAT and muscle density were measured using dual‐energy x‐ray absorptiometry and peripheral quantitative computed tomography. Cases of stroke, MI, and all‐cause mortality were collected through national registers. Cox regressions were used to calculate hazard ratios (HRs) and 95% CIs per SD greater VAT and per SD lower muscle density. During a mean follow‐up of 3.6 years, there were 108 cases of stroke or MI, and 97 deaths. Greater VAT (adjusted HR [aHR], 1.56; 95% CI, 1.09–2.22), but not lower muscle density (aHR, 1.14; 95% CI, 0.97–1.34), was associated with increased risk of stroke or MI. Neither VAT (aHR, 0.95; 95% CI, 0.65–1.41) nor muscle density (aHR, 1.11; 95% CI, 0.92–1.34) was associated with all‐cause mortality. The association of VAT with stroke or MI was only significant in men (aHR, 1.86; 95% CI, 1.19–2.91) but not women (aHR, 0.60; 95% CI, 0.25–1.42) (P interaction=0.038). Conclusions With the limitation of being an observational study, these findings suggest that VAT is an important obesity‐related predictor of cardiovascular risk in 70‐year‐old men, and by implication, that decreasing VAT may potentially reduce their risk of cardiovascular disease.

Globally, the proportion of older people living with HIV (PLWH) is growing and the burden of noncommunicable diseases, including cardiac and renal disease, is increasing. There are few studies of renal disease and cardiac risk in older PLWH. This study investigates the relationship between albuminuria and cardiac risk as estimated by the Atherosclerotic Cardiovascular Disease 10-year risk calculator. We report that albuminuria is associated with a higher Atherosclerotic Cardiovascular Disease risk score in both diabetic and nondiabetic older PLWH.

Aspirin is the cornerstone of the antithrombotic management of patients with established atherosclerotic cardiovascular disease, but major guidelines provide conflicting recommendations for its use in primary prevention. Findings from recent randomized trials totaling >47 000 patients called into question the net clinical benefits of aspirin in primary prevention for 3 key populations: patients with diabetes mellitus, community-dwelling elderly individuals, and patients without diabetes mellitus who are at intermediate risk for atherosclerotic events. In the context of increasing emphasis on the use of other treatments for primary prevention in patients with moderate-high future risk of developing atherosclerotic cardiovascular disease, the efficacy and safety of aspirin for primary prevention has become uncertain. Key unresolved questions regarding the role of aspirin in primary prevention include the optimal drug formulation, dosing schedule, weight-based dose selection, and interplay between sex and treatment response. In the current era, most patients without established atherosclerotic cardiovascular disease should not be prescribed aspirin. Rather, aggressive management of comorbidities tailored to the expected cardiovascular risk needs to be emphasized. In this context, informed shared decision making between clinicians and patients regarding the use of aspirin for primary prevention of cardiovascular events is a suitable and laudable approach. In this article, we revisit the role of aspirin for the primary prevention of cardiovascular diseases by critically reviewing the key scientific literature, highlight key areas of uncertainties for future research, and propose a decisional framework for clinicians to support prescription of aspirin in primary prevention.

Background: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C–lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. Methods: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. Results: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50–0.86; P =0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37–0.98; P =0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18–0.79; P =0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. Conclusions: LDL-C–lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp . Unique identifier: UMIN000001988.

Objective: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis. Here, we experimentally investigated whether HIV expression is sufficient to accelerate atherosclerosis and evaluated the role of caspase-1 activation in monocytes/macrophages in HIV ASCVD. Approach and Results: We crossed a well-characterized HIV mouse model, Tg26 mice, which transgenically expresses HIV-1, with ApoE −/− mice to promote atherogenic conditions ( Tg26 +/− / ApoE −/− ). Tg26 +/− /ApoE −/− have accelerated atherosclerosis with increased caspase-1 pathway activation in inflammatory monocytes and atherosclerotic vasculature compared with ApoE −/− . Using a well-characterized cohort of people with HIV and tissue-banked aortic plaques, we documented that serum IL (interleukin)-18 was higher in people with HIV compared with non–HIV-infected controls, and in patients with plaques, IL-18 levels correlated with monocyte/macrophage activation markers and noncalcified inflammatory plaques. In autopsy-derived aortic plaques, caspase-1+ cells and CD (clusters of differentiation) 163+ macrophages correlated. Conclusions: These data demonstrate that expression of HIV is sufficient to accelerate atherogenesis. Further, it highlights the importance of caspase-1 and monocyte/macrophage activation in HIV atherogenesis and the potential of Tg26 +/− /ApoE −/− as a tool for mechanistic studies of HIV ASCVD.

Atherosclerotic cardiovascular disease remains a worldwide epidemic and one of the leading causes of death nowadays. Vessel wall imaging can be used to understand the development and progression of atherosclerosis, but it is rarely done because of the high cost. We recently identified the Osteoarthritis Initiative, a large prospective cohort study of knee osteoarthritis, which might serve as a valuable source for atherosclerosis research with its serial knee magnetic resonance imaging data. We have found that these images are suitable for vessel wall image analysis of the lower extremity arteries. Here, we will introduce the Osteoarthritis Initiative data set and explain why it could be used for cardiovascular research purposes. Also, we will briefly comment on peripheral artery atherosclerosis as it is covered in the Osteoarthritis Initiative image data set and review the use of vessel wall imaging for studying atherosclerosis. We think data mining of imaging studies, not originally designed on cardiovascular research, can not only maximize the value of the imaging data set but also boost our understanding of atherosclerosis.

With the incidence and impact of atherosclerotic cardiovascular disease and its clinical manifestations still rising, therapeutic options that target the causal mechanisms of this disorder are highly desired. Since the CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) has demonstrated that lowering inflammation can be beneficial, focusing on mechanisms underlying inflammation, for example, leukocyte recruitment, is feasible. Being key orchestrators of leukocyte trafficking, chemokines have not lost their attractiveness as therapeutic targets, despite the difficult road to drug approval thus far. Still, innovative therapeutic approaches are being developed, paving the road towards the first chemokine-based therapeutic against inflammation. In this overview, recent developments for chemokines and for the chemokine-like factor MIF (macrophage migration inhibitory factor) will be discussed.

If undiagnosed and untreated, familial hypercholesterolemia can lead to serious cardiac complications, such as premature atherosclerotic cardiovascular disease. NPs should be familiar with the clinical presentation of this inherited metabolic disease to diagnose patients as early as possible and promptly begin treatment that may include lifestyle changes, statin therapy, and/or nonstatin therapy.

Purpose To investigate whether selected carotid computed tomography angiography (CTA) quantitative features can predict 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. Methods One hundred seventeen patients with calculated ASCVD risk scores were considered. A semiautomated imaging analysis software was used to segment and quantify plaque features. Eighty patients were randomly selected to build models using 14 imaging variables and the calculated ASCVD risk score as the end point (continuous and binarized). The remaining 37 patients were used as the test set to generate predicted ASCVD scores. The predicted and observed ASCVD risk scores were compared to assess properties of the predictive model. Results Nine of 14 CTA imaging variables were included in a model that considered the plaque features in a continuous fashion (model 1) and 6 in a model that considered the plaque features dichotomized (model 2). The predicted ASCVD risk scores were 18.87% ± 13.26% and 18.39% ± 11.6%, respectively. There were strong correlations between the observed ASCVD and the predicted ASCVDs, with r = 0.736 for model 1 and r = 0.657 for model 2. The mean biases between observed ASCVD and predicted ASCVDs were -1.954% ± 10.88% and -1.466% ± 12.04%, respectively. Conclusions Selected quantitative imaging carotid features extracted from the semiautomated carotid artery analysis can predict the ASCVD risk scores.

Background: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. Methods: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. Results: Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei . Conclusions: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. Clinical Trial Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.

Background: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non–high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort. Methods: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk ( Results: In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C Conclusions: In a low 10-year risk cohort with long-term follow-up, LDL-C and non–HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms.

Background: Coronary artery calcium (CAC) is a powerful novel risk indicator for atherosclerotic cardiovascular disease (ASCVD). Currently, there is no available ASCVD risk prediction tool that integrates traditional risk factors and CAC. Methods: To develop a CAC ASCVD risk tool for younger individuals in the general population, subjects aged 40 to 65 without prior cardiovascular disease from 3 population-based cohorts were included. Cox proportional hazards models were developed incorporating age, sex, systolic blood pressure, total and high-density lipoprotein cholesterol, smoking, diabetes mellitus, hypertension treatment, family history of myocardial infarction, high-sensitivity C-reactive protein, and CAC scores (Astro-CHARM model [Astronaut Cardiovascular Health and Risk Modification]) as dependent variables and ASCVD (nonfatal/fatal myocardial infarction or stroke) as the outcome. Model performance was assessed internally, and validated externally in a fourth cohort. Results: The derivation study comprised 7382 individuals with a mean age 51 years, 45% women, and 55% nonwhite. The median CAC was 0 (25th, 75th [0,9]), and 304 ASCVD events occurred in a median 10.9 years of follow-up. The c-statistic was 0.784 for the risk factor model, and 0.817 for Astro-CHARM ( P P 2 , 13.2; P =0.16) in the validation cohort (n=2057; 55 events). A mobile application and web-based tool were developed to facilitate clinical application of this tool ( www.AstroCHARM.org ). Conclusion: The Astro-CHARM tool is the first integrated ASCVD risk calculator to incorporate risk factors, including high-sensitivity C-reactive protein and family history, and CAC data. It improves risk prediction in comparison with traditional risk factor equations and could be useful in risk-based decision making for cardiovascular disease prevention in the middle-aged general population.

Elevated triglycerides are independently associated with increased atherosclerotic cardiovascular disease risk. Hypertriglyceridemia is often a polygenic condition that can be affected by numerous interventions. Primary care NPs are well positioned to appropriately evaluate and manage hypertriglyceridemia, improving overall health outcomes.

Introduction: Statins significantly reduce the risk of fatal and non-fatal cardiovascular events in patients with atherosclerotic cardiovascular disease and other high-risk conditions. Current guidelines strongly recommend the use of statins in all eligible patients after an ischaemic stroke, but some patient groups (e.g. elderly, female) still miss out, suggesting more evidence of benefit is still needed. Aim: To investigate the effect of statins on one-year mortality outcomes in ischaemic stroke survivors. Methods: This retrospective study linked routinely collected health data from the Scottish Stroke Care Audit (SSCA), the Prescribing Information System (PIS) and the Scottish Morbidity Record (SMR) 01 and mortality data from the National Records of Scotland (NRS). The study population included patients from January 2010 to December 2015 who survived an ischaemic stroke. Statin therapy was defined as at least one statin prescription within six months of the stroke event (yes/no) and data modelled to analyse the effect on mortality outcomes up to one year. Data were analysed using Cox proportional hazards in SPSS version 25. Results: The study population included 24 499 patients discharged from hospital to their usual place of residence within thirty days after an incident ischaemic stroke and who survived to six months. Statins were prescribed to 21 356 (87.2%) within the first six months in the community setting. Patients on a statin were more likely to be younger [median age 71.2 (IQR 61.1 to 79.5) versus 73.2 (IQR 55.5 to 83.2) years] and male (53.7% versus 46.3%) but had similar Charlson Comorbidity Index scores compared with patients not prescribed a statin. Post stroke statin therapy significantly reduced the risk of death [HR 0.49 (95% confidence interval 0.41 to 0.59)] when adjusted for age, sex, prior statin therapy and baseline stroke severity. Separate analysis also revealed similar benefits regardless of age and sex. Conclusion: Post-stroke statin therapy was associated with a reduced risk of death within one year even accounting for age, sex or comorbidities. This reinforces the benefit of current guideline implementation.

Background Evidence‐based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence‐based therapies on, or covering, the index date ±30 days: high‐intensity statin, angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence‐based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high‐intensity statin, 53.1% were using an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence‐based therapies, and 37.4% were on none of them. Over a 12‐month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence‐based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Conclusions Alarming gaps exist in the contemporary use of evidence‐based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.

Background Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality among women, with younger women being disproportionately affected by traditional cardiovascular risk factors such as dyslipidemia. Despite recommendations for lipid screening in early adulthood and the risks associated with maternal dyslipidemia during pregnancy, many younger women lack access to and utilization of early screening. Accordingly, our objective was to assess the prevalence of and disparities in lipid screening and awareness of high cholesterol as an atherosclerotic cardiovascular disease risk factor among pregnant women receiving prenatal care. Methods and Results We invited 234 pregnant women receiving prenatal care at 1 of 3 clinics affiliated with the University of Pennsylvania Health System to complete our survey. A total of 200 pregnant women (86% response rate) completed the survey. Overall, 59% of pregnant women (mean age 32.2 [±5.7] years) self‐reported a previous lipid screening and 79% of women were aware of high cholesterol as an atherosclerotic cardiovascular disease risk factor. Stratified by racial/ethnic subgroups, non‐Hispanic Black women were less likely to report a prior screening (43% versus 67%, P =0.022) and had lower levels of awareness (66% versus 92%, P P =0.043). Those seeing an obstetrician/gynecologist for usual care were less likely to report a prior lipid screening compared with those seeing a primary care physician (29% versus 63%, P =0.007). Conclusions Significant racial/ethnic disparities persist in lipid screening and risk factor awareness among pregnant women. Prenatal care may represent an opportunity to enhance access to and uptake of screening among younger women and reduce variations in accessing preventive care services.

Background: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy. Methods: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient surveys. Poisson regression models evaluated associations between risk estimates, statin use, and willingness to take prevention therapy. Results: Overall, there was no correlation between patients’ estimates of their 10-year CVD risk and calculated 10-year risk (ρ=−0.01, P correlation =0.46), regardless of age, sex, race, or socioeconomic status. The majority (72.2%) overestimated their 10-year CVD risk relative to the pooled cohorts equation (mean perceived 33.3% versus mean calculated 17.1%, P difference P P =0.18) but was associated with willingness to consider future prevention therapy ( P Conclusions: When asked, most patients overestimate their 10-year risk but hold an optimistic bias of their risk relative to age-, race-, and sex-matched peers. Providing accurate absolute risk assessments to patients without proper context may paradoxically decrease many patients’ perceived risk of CVD, thereby disincentivizing initiation of CVD risk reduction therapy.