Abstract
Introduction: It is unclear if individuals with very low mean low-density lipoprotein cholesterol (LDL-C) during midlife experience significant absolute risk (AR) for coronary heart disease (CHD). Hypothesis: Individuals with LDL-C ≤80mg/dL from ages 20-60 years (y) do not develop significant AR for CHD over 30 y of follow-up. Methods: Our objective was to quantify and compare the 30-year AR for fatal or nonfatal CHD from index ages 20-40 y and 40-60 y in participants (ppts) with LDL-C ≤80, 81-130, and >130 mg/dL using data from the Lifetime Risk Pooling Project. We included ppts who were free from lipid lowering medications and CHD at baseline. Mean LDL-C was an average of multiple (2-5) fasting LDL-C measurements within 10 years prior to the baseline age. We used a modified Kaplan Meier analysis, adjusted for competing risks of death, to quantify the 30-year CHD AR by LDL-C strata. Results: 3,781 men and 4,995 women were followed for a combined 110,431 person*years and experienced 778 events. Among all ppts, tobacco use ranged from 20-40% and hypertension prevalence ranged from 13-40%. Non-lipid risk factor profiles were generally more favorable in the low-LDL-C strata. At index ages 20-40, men and women with LDL-C ≤80mg/dL did not experience risk for CHD over 20 and 25 years, respectively (Figure). A similar pattern was seen in the LDL-C 80-130mg/dL strata. At index ages 40-60, men and women with LDL-C ≤80mg/dL experienced no risk for CHD for 5 to 15 years, respectively. However, both sex groups saw a gradual increase in risk up to 13.7% (95% confidence interval [CI] 1.9-25.4%) for men and 5.2% (95% CI 2.0-8.4%) for women at year 30 of follow-up. Conclusion: Young ppts with LDL-C ≤80mg/dL had very low CHD risks across midlife despite significant risk factor burden. At older ages, ppts with low LDL-C develop modest AR for CHD suggesting adverse lipid changes over time or alternative mediators of CHD in this age group.
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