Background: Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. Objective: We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. Methods: A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. Results: Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27). Conclusions: In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.
Bibliographical noteFunding Information:
Supported by National Heart, Lung, and Blood Institute (NHLBI) of the NIH award T32HL007779 (to MRR). The Atherosclerosis Risk in Communities Study has been funded in whole or in part with federal funds from the NHLBI, NIH, Department of Health and Human Services, under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. CMR was supported by National Institute of Diabetes and Digestive and Kidney Diseases mentored research scientist development award K01 DK107782 and NHLBI grant R21 HL143089.
Copyright © 2019 The Author(s).
- circulating magnesium
- cohort study
- coronary artery disease
- observational prospective studies