High-Density Lipoprotein and Long-Term Incidence and Progression of Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis

Anna E. Bortnick, Petra Buzkova, James D. Otvos, Majken K. Jensen, Michael Y. Tsai, Matthew J. Budoff, Rachel H. MacKey, Samar R. El Khoudary, Elda Favari, Ryung S. Kim, Carlos J. Rodriguez, George Thanassoulis, Jorge R. Kizer

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background: 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, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. Methods: 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=6784). Results: 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. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1272-1282
Number of pages11
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number10
StatePublished - Oct 1 2022

Bibliographical note

Funding Information:
Funding for this study, was in part, from an American Heart Association Mentored and Clinical Population Research Award 17MCPRP33630098 and the Montefiore Medical Center Division of Cardiology (Dr Bortnick). Dr Bortnick is also supported by a K23 HL146982 from the National Heart, Lung and Blood Institute (NHLBI). Dr Kizer is supported by a K24 HL135493 from the NHLBI. This research was supported by R01 HL071739 and MESA (Multi-Ethnic Study of Atherosclerosis) was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-RR-025005 from National Center for Research Resources.

Publisher Copyright:
© 2022 Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.


  • cardiovascular disease
  • cholesterol
  • cholesteryl ester transfer protein
  • incidence
  • lipoprotein


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