Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort

Amy B. Karger, Brian T. Steffen, Sarah O. Nomura, Weihua Guan, Parveen K. Garg, Moyses Szklo, Matthew J. Budoff, Michael Y. Tsai

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background: While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results: MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions: To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration: Unique identifier: NCT00005487.

Original languageEnglish (US)
Article numbere013934
JournalJournal of the American Heart Association
Issue number3
StatePublished - Feb 4 2020

Bibliographical note

Funding Information:
This research was supported by contracts HHSN268201500003I, 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, N01‐HC‐95169 and R01 HL071739 from the National Heart, Lung, and Blood Institute, and by grants UL1‐TR‐000040, UL1‐TR‐001079, and UL1‐TR‐001420 from the National Center for Advancing Translational Sciences. This publication was developed under the Science to Achieve Results research assistance agreements, No. RD831697 (MESA Air) and RD‐83830001 (MESA Air Next Stage), awarded by the US Environmental Protection Agency. It has not been formally reviewed by the Environmental Protection Agency. The views expressed in this document are solely those of the authors and the Environmental Protection Agency does not endorse any products or commercial services mentioned in this publication.

Publisher Copyright:
© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.


  • calcification progression
  • cardiovascular disease
  • homocysteine
  • vascular calcification


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