Anna E Bortnick1,2, Petra Buzkova3, James D Otvos4, Majken K Jensen5,6, Michael Y Tsai7, Matthew J Budoff8, Rachel H Mackey9,10, Samar R El Khoudary9, Elda Favari11, Ryung S Kim12, Carlos J Rodriguez1,12, George Thanassoulis13, Jorge R Kizer14,15. 1. Department of Medicine, Division of Cardiology (A.E.B., C.J.R.), Albert Einstein College of Medicine, Bronx NY. 2. Division of Geriatrics (A.E.B.), Albert Einstein College of Medicine, Bronx NY. 3. Department of Biostatistics, University of Washington, Seattle (P.B.). 4. Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC (J.D.O.). 5. Department of Nutrition (M.K.J.), Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 6. Channing Division of Network Medicine, Department of Medicine (M.K.J.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 7. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.). 8. Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA (M.J.B.). 9. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (R.H.M., S.R.E.K.). 10. Premier Applied Sciences, Inc, Charlotte, NC (R.H.M.). 11. Department of Food and Drug, University of Parma, Italy (E.F.). 12. Department of Epidemiology and Population Health (R.S.K., C.J.R.), Albert Einstein College of Medicine, Bronx NY. 13. Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal' Canada (G.T.). 14. Cardiology Section, San Francisco VA Health Care System, CA (J.R.K.). 15. Departments of Medicine, Epidemiology and Biostatistics, University of California' San Francisco (J.R.K.).
Abstract
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.
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.
Entities:
Keywords:
cardiovascular disease; cholesterol; cholesteryl ester transfer protein; incidence; lipoprotein
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