LDL subfractions are associated with incident cardiovascular disease in the Malmö Prevention Project Study

After assessing the risk for cardiovascular disease (CVD) based on traditional risk factors, decisions concerning lipid lowering therapy might remain uncertain. To investigate whether lipoprotein subfraction levels could aid these decisions, we assessed the association between lipoprotein subfractions and CVD, after adjustment for traditional risk factors including standard lipids.

Using a case-cohort design, participants were randomly drawn from the Malmö Prevention Project (MPP), a population-based prospective study of 18,240 participants, and supplemented with additional incident CVD events (5764 participants, 1784 CVD events).

Low density lipoprotein particle number (LDL-P) and individual subfractions ranging in size from very-small to large were associated with CVD (continuous p value (p_cont) < 0.001) while adjusting for age, sex, hypertension, smoking, and diabetes. After further adjustment for LDL-C, HDL-C, and triglycerides, very small LDL subfraction (b) (LDL-VS (b)) remained associated with CVD (HR = 1.23, 95% CI, 1.06 to 1.43 for top vs. bottom quartile, p_cont = 0.03). Among participants with low/intermediate risk [without diabetes and with LDL-C <3.36 mmol/L (<130 mg/dL)], the fully adjusted HR for LDL-small (top vs. bottom quartile) was 1.48 (95% CI 1.02 to 2.17, p_cont = 0.03). Among those with very-high risk (>20% 10-year risk of CVD), LDL-VS(a) and LDL-VS(b) were associated with CVD in fully adjusted models (HR = 1.37, 95% CI 1.12 to 1.67 and HR = 1.28, 95% CI 1.07 to 1.53, respectively, p_cont≤0.03).

Smaller LDL particles are associated with incident CVD independently of traditional risk factors, including standard lipids, in participants with low/intermediate and very-high risk, who might benefit from improved risk assessment.