Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, particles, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC.

We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6814).

After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC, as was higher CETP mass. Neither small nor medium HDL-P, apoC3-containing HDL-C, or CETP activity were significantly associated with AVC incidence/progression in the main analyses. When included together, a significant association was observed only for HDL-C, but not for HDL-P. In exploratory analyses, inverse associations for HDL-C, HDL-P, large HDL-P, and apocC3-lacking HDL with AVC incidence/progression were more pronounced for adults ≥65 years, men, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups.

In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.