Associations of Long-Term and Early Adult Atherosclerosis Risk Factors With Aortic and Mitral Valve Calcium
Open accessAbstract
Objectives To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification.Background Traditional atherosclerosis risk factors have been associated with aortic and mitral valve calcium in cross-sectional studies, but long-term prospective data are lacking.Methods This was a prospective, community-based cohort study with 27-year follow-up (median follow-up 26.9 years; range 23.1 to 29.6 years). Participants from the Framingham Offspring Study (n = 1,323, enrolled between 1971 and 1975, mean age at enrollment 34 +/- 9 years; 52% women) underwent cardiac multidetector computed tomography assessment between 2002 and 2005. Associations between the long-term average of each cardiovascular risk factor and valve calcium were estimated using logistic regression.Results Aortic valve calcium was present in 39% of participants and mitral valve calcium in 20%. In multivariable models, the odds ratio for aortic valve calcium associated with every SD increment in long-term mean total cholesterol was 1.74 (p < 0.0001); with every SD increment in high-density lipoprotein cholesterol, it was 0.77 (p = 0.002); and with every 9 cigarettes smoked per day, it was 1.23 (p = 0.002). Associations of similar magnitude were seen for mitral valve calcium. The mean of 3 serum C-reactive protein measurements was associated with mitral valve calcium (odds ratio: 1.29 per SD increment in C-reactive protein levels; p = 0.002). A higher Framingham risk score in early adulthood (40 years age or younger) was associated with increased prevalence and severity of aortic valve calcium measured 3 decades later.Conclusions Exposure to multiple atherosclerotic risk factors starting in early to mid-adulthood is associated with aortic and mitral valve calcium. Studies evaluating early risk factor modification to reduce the burden of valve disease are warranted.
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Robust translational data suggest that apolipoprotein B-containing lipoproteins, including Lp(a), are causal for aortic stenosis.
“This result is concordant with robust translational data suggesting that apolipoprotein B-containing lipoproteins, including Lp(a), are causal for AS7,37,38.”
From Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction (2026) · cites this paper as [38]
The AORTIC VALVE CALCIUM discussion reports an association between long-term cholesterol levels and aortic valve calcium, and the MITRAL VALVE CALCIUM discussion describes experimental evidence that lipids contribute to early valvular calcification (page numbers unavailable). The paper does not establish that apolipoprotein B-containing lipoproteins, specifically Lp(a), cause clinical aortic stenosis; it also notes that lipid-lowering trials have generally been disappointing. (LLM, conf=0.84)
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Self-citationPolymorphism Rs10455872 at The Lipoprotein(A) Gene Locus Enhances the Risk of Aortic Valve Disease
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- Authors
- Thanassoulis, G., Massaro, J. M., Cury, R., Manders, E., Benjamin, E. J., Vasan, R. S., Cupple, L. A., Hoffmann, U., O'Donnell, C. J., & Kathiresan, S.
- Affiliations
- Boston University (US)
- Harvard University (US)
- Framingham Heart Study (US)
- Broad Institute (US)
- Corresponding author
- Kathiresan, Sekar
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 55
- Issue
- 22
- Pages
- 2491-2498
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC3042249
- OpenAlex
- W1986883175
- Cited by
- 114
- References
- 44
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 5 · 2022: 18 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 11 · 2014: 9 · 2013: 5 · 2012: 3
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195)
- Canadian Institute of Health Research
- Fonds de Recherche en Santé du Québec
- Astellas Pharma
- Pfizer
- GE Healthcare
- American College of Cardiology Foundation/Merck Adult Cardiology Research
- GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease
- Alnylam Pharmaceuticals
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- aortic valve calcification, mitral valve calcification, valve calcification, atherosclerosis risk factors, total cholesterol, HDL cholesterol, smoking, C-reactive protein, Framingham risk score, early adulthood, Framingham Offspring Study
- MeSH terms
- Adult, Aged, Aortic Valve, Calcinosis, Calcium, Female, Follow-Up Studies, Heart Valve Diseases, Humans, Male, Middle Aged, Mitral Valve, Probability, Prospective Studies, Severity of Illness Index, Time Factors, Cohort Studies, Incidence, Multivariate Analysis, Confidence Intervals, Odds Ratio, Age Distribution, Sex Distribution, Disease Progression, Risk Assessment, Atherosclerosis
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