An individual's risk of future cardiovascular events may depend both on cumulative exposure to LDL-C concentration and, independently, on the time course of LDL-C accumulation, according to a study published Sept. 21 in the Journal of the American College of Cardiology.

Michael J. Domanski, MD, FACC, and Valentin Fuster, MD, PhD, MACC, et al., developed a risk model to determine risk of future cardiovascular events that looks at the area under the LDL-C curve vs. age curve and the time course of area accumulation. The researchers used data of 4,958 asymptomatic adults ages 18 to 30 years who were enrolled in the CARDIA study between 1985 and 1986 to test the model. Age 40 was used as the beginning of follow up for cardiovascular events. The primary outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention or cardiovascular death.

The mean age of surviving participants was 55.8 years (range, 46.5-66.3 years). In a median of 16 years of follow up after age 40 years, 275 participants experienced an incident cardiovascular event. After adjusting for sex, race and risk factors, both the area under the LDL-C curve vs. age curve (hazard ratio [HR], 1.053; p<0.0001 per 100 mg/dL x years) and the time course of area accumulation, or slope of LDL-C curve, (HR, 0.797 per mg/dL/year; p=0.045) were significantly associated with risk of a cardiovascular disease event.

The median age of the first cardiovascular event was 49.4 years (range, 40-60 years), and the rate of cardiovascular events was 3.1% at age 50 and 7.8% at age 60.

According to the researchers, the study suggests that incident cardiovascular event risk depends on prior exposure to LDL-C and time course of area accumulation. The findings "suggest that clinical trials of lowering LDL-C in young, even teenage, populations might show a major reduction in [cardiovascular disease] incidence compared to risk reduction started later," they note. They conclude that the "same area accumulated at younger age, compared to older age, resulted in greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life."

The "unresolved tension raised by this study is that while elevated LDL-C early in life is prognostically important, the ultimate trial to prove that early treatment is superior to our current strategy is impossible to perform, at least with conventional approaches," Michael D. Shapiro, DO, MCR, FACC, and Deepak L. Bhatt, MD, MPH, FACC, write in an accompanying editorial comment. They add that "perhaps the most important issues to focus upon" include the amount of evidence needed to initiate long-term lipid-lowering treatment in young individuals with hypercholesterolemia and whether society has "the appetite to start low-intensity therapy in large swaths of young, healthy individuals even if robust randomized trial evidence does not support this approach."

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Interventions and Vascular Medicine

Keywords: Ischemic Attack, Transient, Risk Factors, Hypercholesterolemia, Cardiovascular Diseases, Cholesterol, LDL, Peripheral Arterial Disease, Incidence, Appetite, Follow-Up Studies, Stroke, Coronary Disease, Myocardial Revascularization, Cardiology, Hospitalization, Risk Reduction Behavior

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