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Tag: CVD

Aggressively Lowering LDL-C Reduces Cardiovascular Risk

Cardiovascular disease (CVD) is the leading cause of death in the United States, affecting more than 92 million people, with 45 million more being at an increased risk for developing CVD within 10 years. Elevated low-density lipoprotein cholesterol (LDL-C) is one of the key risk factors for CVD and several studies have shown that lowering LDL-C is one of the most important aspects of primary and secondary CVD prevention.

However, how much we should lower LDL-C to convey a cardiovascular benefit is not clear. The concept of “treat to target” is constantly evolving to “lower is better”, which has spun a growing debate in the clinical community, partly because we don’t agree about the specific target LDL-C levels that are also safe. The approval of new non-statin therapies that aggressively lower LDL-C, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, has invigorated the debate about specific LDL-C targets, with many experts advocating for achieving very low levels of LDL-C (below 50 mg/dL and in some cases, ≤20 mg/dL) early in the treatment regimen in order to maximize cardiovascular benefits.

A recent meta-analysis published in JAMA Cardiology explored the efficacy and safety of additional lowering of LDL-C in patients with very low baseline LDL-C (70 mg/dL or less) in reducing cardiovascular adverse events. In this study, the authors report that aggressive LDL-C lowering further decreases the risk for major cardiovascular events, measured by a composite score of coronary heart death, myocardial infarction, ischemic stroke, or coronary revascularization. For patients treated with statins, the overall risk reduction per 1-mmol/L (38.7 mg/dL) LDL-C reduction was 22%, whether for non-statin therapies (ezetimibe, evolocumab, and anacetrapib) the risk reduction for CV events was 21% per 1-mmol/L LDL-C reduction. LDL-C lowering was also shown to be safe and did not lead to an increase in serious adverse events, including myalgias, myositis, elevated levels of aminotransferases, new-onset diabetes, hemorrhagic stroke or cancer.

This study demonstrated that lowering LDL-C to levels as low as 21 mg/dL conveys additional cardiovascular benefits without increasing adverse events. These are encouraging data about the role of aggressive LDL-C lowering in cardiovascular prevention, but additional long-term studies may be required to further ensure the safety of this approach.

Reference:
Sabatine, Marc S., et al. “Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels: A Meta-analysis.” JAMA Cardiology (2018).

Coronary Artery Calcium as a Predictor of ASCVD Risk

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the US, and prevention of ASCVD is a public health priority in order to minimize its impacts on morbidity and mortality. Global CVD risk assessment is an integrated approach to evaluate the total risk of developing CVD over a given period (usually 10 years) based on several risk factors, including age, male sex, hypertension, diabetes mellitus, dyslipidemia, smoking, family history, overweight and obesity. These risk factors have been incorporated in several algorithms for the primary prevention of CVD, including the Pooled Cohort Equation (PCE) developed by American College of Cardiology (ACC) and American Heart Association (AHA). However, despite the development of several algorithms for risk assessments aimed to prevent CVD events, the overall disease burden has increased. CVD events can occur even in individuals that do not have risk factors, and the dependence of CVD risk assessment on the presence or absence of conventional risk factors may not allow for accurate risk prediction, given the fact that CVD is multi-factorial and progresses in a continuum.

As a result, novel risk assessment methods, including coronary artery calcium (CAC) score, may be necessary to improve ASCVD risk prediction and to better guide treatment options. The utility of the CAC score in preventing CVD risk in asymptomatic individuals has been demonstrated in several results from the Multi-Ethnic Study of Atherosclerosis (MESA), a study designed to evaluate the characteristics of subclinical atherosclerosis and risk factors for ASCVD progression. However, most of the outcomes of these studies have evaluated coronary heart disease (CHD) with short to intermediate follow-ups.

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