Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study

Abstract

Background: Dyslipidemia causes coronary heart disease in middle-aged and elderly adults, but the consequences of lipid exposure during young adulthood are unclear.

Objective: To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age.

Design: Prospective cohort study.

Setting: 4 cities in the United States.

Participants: 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in Young Adults) study.

Measurements: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study; these measurements were then related to coronary calcium scores assessed later in life (45 years [SD, 4]).

Results: 2824 participants (87%) had nonoptimal levels of LDL cholesterol (>or=2.59 mmol/L [>or=100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60 mg/dL]), or triglycerides (>or=1.70 mmol/L [>or=150 mg/dL]) during young adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001). The association was similar across race and sex and strongly graded, with odds ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of 3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of 4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other coronary risk factors. Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinically abnormal lipid levels were excluded.

Limitation: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome.

Conclusion: Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later.

Primary funding source: National Heart, Lung, and Blood Institute.

Figure 1. Coronary calcium score distribution in middle age with increasing exposure to lipids before age 35 years

Cumulative exposure to each lipid (LDL cholesterol, HDL cholesterol and triglycerides) is estimated via integrated lipid trajectory analysis (see Methods), and expressed as a time-averaged value. The association with coronary calcium score category is significant in all cases (p<.001). Ten persons with a positive coronary calcium scan but an unknown coronary calcium score were excluded from this analysis.

Figure 2. Prevalence of coronary calcium by lipid exposure before age 35 years, stratified by race and sex

Cumulative exposure to each lipid (LDL cholesterol, HDL cholesterol and triglycerides) is estimated via integrated lipid trajectory analysis (see Methods), and expressed as a time-averaged value. Numbers in bars are subgroup sample sizes; no bar with fewer than 20 participants is shown (n is shown in parentheses for these). P-values represent trend for increasing odds of calcification by category.