• J. Intern. Med. · Apr 2023

    Plasma methylmalonic acid predicts risk of acute myocardial infarction and mortality in patients with coronary heart disease: A prospective 2-cohort study.

    • Indu Dhar, Vegard Lysne, Arve Ulvik, SvingenGard F TGFTDepartment of Heart Disease, Haukeland University Hospital, Bergen, Norway., Eva R Pedersen, Espen Ø Bjørnestad, Thomas Olsen, Robert Borsholm, Johnny Laupsa-Borge, Per M Ueland, Grethe S Tell, Rolf K Berge, Gunnar Mellgren, Kaare H Bønaa, and Ottar K Nygård.
    • Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway.
    • J. Intern. Med. 2023 Apr 1; 293 (4): 508519508-519.

    BackgroundElevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs).ObjectivesWe examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality.Methods And ResultsUsing Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n = 4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n = 3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3-11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09-1.28), 1.25 (1.18-1.33), and 1.28 (1.17-1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10-1.28), 1.22 (1.14-1.31), and 1.30 (1.19-1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers.ConclusionsElevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.© 2023 The Association for the Publication of the Journal of Internal Medicine.

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