Cardiovascular
Serum Metabolomics and the Risk of Ischemic Heart Disease Death: Evidence from the Golestan Cohort Study Mahdi Nalini* Mahdi Nalini Nalini Nalini Nalini Nalini Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Background: Established cardiovascular risk factors do not fully explain the burden of atherosclerotic cardiovascular disease. We evaluated associations between 250 serum metabolomic measures and ischemic heart disease (IHD) mortality to identify prediagnostic biomarkers.
Methods: We conducted a case-cohort nested within the population-based Golestan Cohort Study (n = 50,045; ages 40–75 years; 58% women; enrollment 2004–2008) in northeastern Iran. Metabolites were quantified using nuclear magnetic resonance spectroscopy by Nightingale. After excluding participants with prior cardiovascular events, the analysis included 387 IHD deaths and 458 subcohort noncases. Associations were estimated between standardized (z-score) biomarker measures and IHD death through 2018 using Cox regression models with age as the time scale and stratified/adjusted for sex, residence, ethnicity, education, wealth, physical activity, fruit and vegetable intake, tobacco smoking, opium use, obesity, hypertension, and diabetes. Bonferroni correction was applied for multiple testing.
Results: The mean (SD) age at baseline was 57.5 (9.5) years, and the median follow-up was 9.1 years. An increased risk of death from IHD was associated with higher apolipoprotein B-to-A1 ratio [HR, 1.49; 95% CI, 1.19–1.86; P=0.0006], large-size high-density lipoprotein free cholesterol (% of total lipids) [1.44; 1.15–1.80; 0.0017], tyrosine [1.40; 1.13–1.72; 0.0019], and creatinine [1.54; 1.17–2.03; 0.0021], whereas albumin [0.75; 0.62–0.89; 0.0012] and medium-size high-density lipoprotein cholesteryl ester [0.74; 0.62–0.90; 0.0021] were inversely associated. Additional adjustment for routine blood lipids did not materially change these associations.
Conclusion: Specific biomarkers—including lipoprotein subclass composition, tyrosine, albumin, and creatinine—were independently associated with death from IHD, highlighting their potential value in risk assessment beyond traditional cardiovascular risk factors.