ACC/AHA Guidelines for Cardiovascular Disease Prevention and Cholesterol Management: Implications of New Therapeutic Agents

In 2014 the American College of Cardiology/American Heart Association issued four new guidelines for cardiovascular disease prevention that focused on cardiovascular risk assessment, lifestyle management, obesity management, and blood cholesterol management. The development of an atherosclerotic cardiovascular disease risk calculator formed the basis of the risk assessment guideline, and the lifestyle management guideline focused on recommending an evidence-based dietary pattern. The blood cholesterol management guideline specifically identified four groups of patients shown to benefit from moderate-intensity or high-intensity statin therapy from previous clinical trials and abandoned the use of specific low-density lipoprotein (LDL) cholesterol (LDL-C) goal levels on the basis of the lack of clinical trial evidence. The recommendations for treatment with moderate-intensity or high-intensity statin therapy are based on rigorous evidence from randomized clinical trials. Guidance has since been provided for the use of nonstatin therapies, including cholesterol absorption inhibitor and proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapy when adequate reduction of LDL-C levels is not achieved with maximally tolerated statin therapy. The recent development and application of these therapies have resulted in remarkable reductions in LDL-C levels that are well tolerated, and preliminary outcome data are promising in showing substantial atherosclerotic cardiovascular disease event reductions beyond statin therapy

Interpreting the Findings From the Recent PCSK9 Monoclonal Antibody Cardiovascular Outcomes Trials

The recent development of monoclonal antibodies targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9), e.g., PCSK9 inhibitors has revolutionized the landscape of lipid management. Many clinical trials assessing this class have demonstrated remarkable and consistent reductions in low-density lipoprotein-cholesterol. Moreover, the GLAGOV trial demonstrated the efficacy of evolocumab, when added to statin therapy, in reducing the progression of atherosclerosis measured by serial intravascular ultrasound, with the first suggestion of continued benefit down to LDL-C levels of 0.5 mmol/L (20 mg/dL). This trial was followed by the FOURIER Cardiovascular Outcomes trial in more than 27,000 patients with stable atherosclerotic cardiovascular disease (ASCVD) where evolocumab reduced the primary endpoint of atherosclerotic events by 15%, without significant safety differences between treatment groups. Furthermore, subgroup analyses suggested greater benefits seen in those with longer exposure to evolocumab recent acute coronary syndrome, multiple myocardial infarctions, multivessel coronary artery disease, peripheral arterial disease, as well as the subgroup who achieved very low low-density lipoprotein-cholesterol levels of below 0.3 mmol/L (10 mg/dL). Moreover, the EBBINGHAUS substudy demonstrated no differences in objectively measured cognitive function between treatment groups. The SPIRE 2 trial evaluating bococizumab in high-risk patients with baseline LDL-C ≥2.6 mmol/L (100 mg/dL) demonstrated significant atherosclerotic risk reduction, but the trial and further development of the drug was prematurely discontinued due to substantial attenuation of the LDL-C effect over time due to the development of neutralizing antibodies. Finally, the ODYSSEY Cardiovascular Outcomes trial testing alirocumab in subjects with recent (<1 year) acute coronary syndrome demonstrated a 15% relative risk reduction in the primary composite outcome, as well as a significant reduction in total mortality. Greater benefits were noted in those whose LDL-C at baseline was 2.6 mmol/L (100 mg/dL) or greater. These trials collectively demonstrate the added efficacy of PCSK9 inhibitors over moderate and high-intensity statin therapy for unprecedented low-density lipoprotein-cholesterol reduction and incremental ASCVD risk reduction

Prevalence of United States adults with triglycerides ≥ 135 mg/dL: NHANES 2007–2014

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Association of lung function with coronary heart disease and cardiovascular disease outcomes in elderly: The Rancho Bernardo study

SummaryIntroductionLung function is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD). We evaluated the prospective association of reduced lung function by spirometry and CHD or CVD events in older community-dwelling adults.MethodsWe studied 1548 participants (mean age 73.6 ± 9.2 years, 42% males) from the Rancho Bernardo Study using age, sex, and risk-factor adjusted Cox regression to assess pulmonary function (FEV1, FVC, and FEV1/FVC ratio) as a predictor of CHD and CVD events followed for up to 22 years.ResultsOf CVD risk factors, older age, male sex, current/past smoking, physical exercise (<3× a week), and prevalent CVD predicted an increased risk of CHD and CVD. Higher FEV1 and FVC were each associated with a decreased risk of CHD [HR 0.80 (0.73–0.88) for both FEV1 and FVC, per SD, p < 0.01] and CVD [HR 0.82 (0.74–0.91) for both FEV1 and FVC, per SD, p < 0.01]. Those in the lowest quartiles of FEV1 and FVC had hazard ratios of 1.68 (1.33–2.13) and 1.55 (1.21–2.00) respectively for CHD and 1.74 (1.34–2.25) and 1.49 (1.13–1.96) respectively for CVD (all p < 0.01, relative to those in the highest quartile). Similar findings were observed for CHD and CVD mortality. Sex- and age-stratified analyses showed the strongest associations for CHD and CVD events in women and in the oldest participants.ConclusionsFEV1 and FVC are inversely associated with risk of future CHD and CVD events in older community-dwelling adults and may add to CVD risk stratification in the elderly

Twenty-Five Year Secular Trends in Lipids and Modifiable Risk Factors in a Population-Based Biracial Cohort: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2011

BACKGROUND: Cross-sectional analyses suggest that total and low-density lipoprotein cholesterol (LDL-c) trends that had been declining are now reversing. We examined longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine secular trends in total cholesterol, LDL-c, high-density lipoprotein cholesterol (HDL-c), and triglycerides over 25 years. We also assessed whether modifiable lifestyle factors (body mass index, physical activity, alcohol consumption, smoking, and lipid-lowering medications) are associated with these trends. METHODS AND RESULTS: CARDIA recruited 5115 black and white men and women ages 18 to 30 years from 4 US communities in 1985-1986, and re-examined them 5, 10, 15, 20, and 25 years later. Secular trends, modeled as age-matched time trends, were estimated using repeated-measures regression stratified on race and sex. Total cholesterol and LDL-c initially decreased approximately 5 to 8 mg/dL between visits before plateauing and moving toward adverse trends in all groups, except black women, by year 25. HDL-c showed an upward secular trend of 1 to 3 mg/dL between visits starting at year 15 in all groups; triglyceride trends were largely flat. Obesity and use of lipid-lowering medications, which both increased over follow-up, had strong independent, but opposite, associations with lipid trends over time. In aggregate, associations of modifiable lifestyle factors counterbalanced one another, minimally influencing secular trends. CONCLUSIONS: Over 25 years, initially favorable trends in total cholesterol and LDL-c have leveled off and may be reversing, persisting after control for modifiable risk factors. Factors such as dietary changes over 25 years and poor adherence to medications are candidates for additional investigation

Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BackgroundAlthough the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis.Methods and resultsThe Multi-Ethnic Study of Atherosclerosis is a population-based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline and follow-up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2&nbsp;years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182 participants developed incident HF. CAC progression of 10&nbsp;units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P=0.03) and LV end systolic volume (β=0.12; P=0.006) after excluding participants with any coronary heart disease.ConclusionsCAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow-up exam independent of overt coronary heart disease

Risk factor control and adherence to treatment in patients with coronary heart disease in the Republic of Srpska, Bosnia and Herzegovina in 2005–2006

Introduction: European treatment guidelines in persons with known coronary heart disease (CHD) focus on adherence to antiplatelet therapy, beta-blockers, ACE/ARBs, and lipid-lowering agents, with goals for blood pressure (BP) of &lt; 140/90 mm Hg and LDL cholesterol of &lt; 3.0 mmol/l. Data on adherence to these measures in Eastern Europe are limited. Material and methods: The Third Republic of Srpska, Bosnia and Herzegovina, Coronary Prevention Study (ROSCOPS III) was conducted in 2005-2006 at 10 primary heath care centres in 601 patients (36% female, mean age 55 years) with CHD including acute myocardial infarction or ischaemia, coronary artery bypass graft, or angioplasty who were examined and interviewed at least 6 months after the event. We examined the proportion of subjects on recommended treatments and at goal for BP, LDL-C, and non-smoking. Results: The proportion of subjects on recommended treatments included 61% for beta-blockers, 79% for ACE/ARBs, 63% for lipid-lowering agents and 74% for antiplatelet therapy. Only 30% of subjects were on all four of these treatments. 59% of subjects had BP at goal of &lt; 140/90 mm Hg and 33% were controlled to &lt; 130/80 mm Hg, 41% for LDL-C, and 88% were non-smokers. Improvements were seen in lipid-lowering and ACE/ARB drug use and non-smoking status from an earlier survey (ROSCOPS II) in 2002-2003. Conclusions: Our data show, despite improvement over recent years, that many persons with CHD in the Republic of Srpska, Bosnia and Herzegovina are neither on recommended treatments nor at target for BP and/or LDL-C. Improved efforts targeted at both physicians and patients to address these issues are needed

Relationship of Metabolic Syndrome With Incident Aortic Valve Calcium and Aortic Valve Calcium Progression: The Multi-Ethnic Study of Atherosclerosis (MESA)*

ObjectiveMetabolic syndrome (MetS) has been associated with increased prevalence of aortic valve calcium (AVC) and with increased progression of aortic stenosis. The purpose of this study was to determine whether MetS is associated with increased risks for the development of new ("incident") AVC or for progression of established AVC as assessed by CT.Research design and methodsThe relationships of MetS or its components as well as of diabetes to risks for incident AVC or AVC progression were studied among participants with CT scans performed at baseline and at either year 2 or year 3 examinations in the Multi-Ethnic Study of Atherosclerosis (MESA).ResultsOf 5,723 MESA participants meeting criteria for inclusion, 1,674 had MetS by Adult Treatment Panel III criteria, whereas 761 had diabetes. Among the 5,123 participants without baseline AVC, risks for incident AVC, adjusted for time between scans, age, sex, race/ethnicity, LDL cholesterol, lipid-lowering medications, and smoking, were increased significantly for MetS (odds ratio [OR] 1.67 [95% CI 1.21-2.31]) or diabetes (2.06 [1.39-3.06]). In addition, there was an increase in incident AVC risk with increasing number of MetS components. Similar results were found using the International Diabetes Federation MetS criteria. Among the 600 participants (10.5%) with baseline AVC, neither MetS nor diabetes was associated with AVC progression.ConclusionsIn the MESA cohort, MetS was associated with a significant increase in incident ("new") AVC, raising the possibility that MetS may be a potential therapeutic target to prevent AVC development