Cumulative Exposure to Elevated LDL-C and Future Risk for CVD Events

LDL cholesterol test results
LDL cholesterol test results
The cumulative number of years an individual is exposed to elevated levels of LDL-C may predict the risk for future CVD events.

The cumulative number of years an individual is exposed to elevated levels of low-density lipoprotein cholesterol (LDL-C) may predict the risk for future cardiovascular disease (CVD) events, according to a study published in the Journal of the American College of Cardiology.

In this study, the data of 4958 asymptomatic adults (mean age, 24.9±3.7 years) who were enrolled between 1985 and 1986 in the multicenter, longitudinal Coronary Artery Risk Development in Young Adults study ( Identifier: NCT00005130) were analyzed. The study’s primary outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure (HF) hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.

The time course of accumulation of LDL-C before age 40 years was examined in relation to the occurrence of CVD events after this landmark age. A total of 275 participants experienced an incident CVD event during a median follow-up period of 16 years (range, 0.2-26.3 years) after the landmark age. Events included 134 coronary heart disease events, 78 strokes, 27 congestive HF events, and 38 CVD-attributable deaths. On average, patients who survived these events were 55.8±.36 years. The median age at the first CVD event was 49.4 years (range, 40-60 years).

The cumulative LDL-C exposure before age 40 years, as assessed with the area under the LDL-C curve for the 18 to 40 years of age period, yielded a mean of 2520.6±577.7 mg/dl x years (ie, average yearly LDL-C exposure: 114.6±26.3 mg/dl).

After adjusting for sex, race, and traditional CVD risk factors, variables significantly associated with CVD event risk included the area under LDL-C vs age curve (hazard ratio [HR], 1.053 per 100 mg/dl x years; P <.0001) and the time course of area accumulation (HR, 0.797 per mg/dl/year; P =.045).

A limitation of the study was the inclusion of a relatively young participant population.

 “[These results underscore] the importance of optimal LDL-C control starting early in life, because lower LDL-C later, even when low enough to result in the same area at a landmark age, does not fully reverse risk acquired earlier,” noted the study authors.


Domanski MJ, Tian X, Wu CO, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2020;76(13):1507-1516. doi:10.1016/j.jacc.2020.07.059