Low Levels of Atherogenic Lipoproteins & Incident Atherosclerotic Cardiovascular Disease: A Pooled Cohort Primary Prevention Study.

BACKGROUND Elevated atherogenic lipoproteins increase risk of atherosclerotic cardiovascular disease (ASCVD), though long-term risk for adults without ASCVD who have low-normal levels has not been well described.

METHODS This study used pooled data from 16,384 individuals in three population-based prospective cohorts. At baseline all participants were without ASCVD and were not taking lipid-lowering therapy. We evaluated ASCVD events by baseline LDL-C, non-HDL-C and apoB, including low-normal values. ASCVD risk was assessed using multivariable Cox proportional hazards.

RESULTS The study cohort had a mean age of 52 (SD 18) years with 56.5% women, 64.7% of White race and 35.3% of Black race. Over a median follow-up of 18.8 years, unadjusted ASCVD event incidence was similar for adults with baseline LDL-C <70 mg/dL and 70-99 mg/dL, and higher with LDL-C ≥100 mg/dL; trends were similar for non-HDL-C and apoB categories. Compared to having baseline LDL-C 70-99 mg/dL, LDL-C <70 mg/dL was associated with similar ASCVD risk (adjusted HR 1.16 [95% CI 0.90-1.50]) and LDL-C ≥130 mg/dL was associated with higher risk (adjusted HR 1.31 [95% CI 1.14-1.50]) after multivariable adjustment; adults with non-HDL-C ≥160 mg/dL or apoB ≥90 mg/dL also had higher risk after multivariable adjustment.

CONCLUSIONS Among adults without ASCVD not taking lipid-lowering therapy at baseline, ASCVD risk for adults with low-normal and high-normal LDL-C, non-HDL-C and apoB was similar, and their risk remained less than in adults with elevated lipoproteins. These findings emphasize the importance of achieving normal atherogenic lipoprotein levels for primary prevention of ASCVD from early adulthood through middle age.