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Context Coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. Objective To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. Design, Setting and Participants CACS was measured by computed tomography on 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded for the primary analysis. Five-year risk estimates for incident CHD were categorized as 0-<3%, 3-<10%, and ≥10% using Cox proportional hazards models. Model 1 used age, gender, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement (NRI) and compared the distribution of risk using Model 2 versus Model 1. Main Outcome Measures Incident CHD events Results Over 5.8 years median follow-up, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared to Model 1 (NRI=0.25, 95% confidence interval 0.16-0.34, P<0.001). With Model 1, 69% of the cohort was classified in the highest or lowest risk categories, compared to 77% with Model 2. An additional 23% of those who experienced events were reclassified to high risk, and an additional 13% without events were reclassified to low risk using Model 2. Conclusions In the MESA cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

Background: The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published. Methods: We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1 000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke. Results: The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84–0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73–0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79–0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes. Conclusions: In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.

IMPORTANCE Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor.OBJECTIVE To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control.

clinicaltrials.gov Identifier: NCT02462824.

Background The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested. Objectives We assessed the predictive accuracy and improvement in reclassification gained by the addition of coronary artery calcium (CAC) score, ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP), and family history (FH) of ASCVD to the PCE in participants of the MESA (Multi Ethnic Study of Atherosclerosis). Methods The PCE was calibrated (cPCE) and used for this analysis. Cox proportional hazard model, Harrell's C-statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke. Results Of 6,814 MESA participants not on statins at baseline, 5,185 had complete data and were included in this analysis. Mean age was 61years; 53.1% were women, 9.8% diabetic, and 13.6% current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC modestly improved the Harrell's C-statistic (0.74 vs. 0.76; p = 0.04) while ABI, hsCRP, and FH showed no improvement in Harrell's C-statistic when added to the cPCE. Conclusions CAC, ABI, and FH are independent predictors of ASCVD events. CAC modestly improved the discriminative ability of the cPCE best compared with other nontraditional risk markers.

The elimination of specific dietary cholesterol target recommendations in recent guidelines has raised questions about its role with respect to cardiovascular disease. This advisory was developed after a review of human studies on the relationship of dietary cholesterol with blood lipids, lipoproteins, and cardiovascular disease risk to address questions about the relevance of dietary cholesterol guidance for heart health. Evidence from observational studies conducted in several countries generally does not indicate a significant association with cardiovascular disease risk. Although meta-analyses of intervention studies differ in their findings, most associate intakes of cholesterol that exceed current average levels with elevated total or low-density lipoprotein cholesterol concentrations. Dietary guidance should focus on healthy dietary patterns (eg, Mediterranean-style and DASH [Dietary Approaches to Stop Hypertension]–style diets) that are inherently relatively low in cholesterol with typical levels similar to the current US intake. These patterns emphasize fruits, vegetables, whole grains, low-fat or fat-free dairy products, lean protein sources, nuts, seeds, and liquid vegetable oils. A recommendation that gives a specific dietary cholesterol target within the context of food-based advice is challenging for clinicians and consumers to implement; hence, guidance focused on dietary patterns is more likely to improve diet quality and to promote cardiovascular health.

clinicaltrials.gov Identifier: NCT01408901.