Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk

J Am Coll Cardiol. 2020 Sep 29;76(13):1507-1516. doi: 10.1016/j.jacc.2020.07.059.

Abstract

Background: Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.

Objectives: Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.

Methods: This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The 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.

Results: During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).

Conclusions: Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.

Keywords: CARDIA; cardiovascular disease; cholesterol lowering; coronary heart disease; low-density lipoprotein; preventive cardiology.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Cholesterol, LDL / blood*
  • Female
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Prospective Studies
  • United States / epidemiology
  • Young Adult

Substances

  • Cholesterol, LDL