Circulating Metabolic Markers, MI, and Stroke Subtypes

Study Questions:

What are the associations between plasma metabolic markers (i.e., lipids, lipoprotein particles, and circulating metabolites) with risks of incident myocardial infarction (MI), ischemic stroke, and intracerebral hemorrhage (ICH)?


Data from a large prospective cohort, the China Kadoorie Biobank, were used for the present nested case-control study. Cases included 912 MI events, 1,146 ischemic stroke events, and 1,138 intracerebral hemorrhage events. A total of 1,466 controls were matched by age, sex, and residence area wherever possible. Both cases and controls were between the ages of 30-79 years, had no clinical coronary heart disease, or stroke/transient ischemic attack and were not on statin therapy at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers in baseline plasma samples.


Very-low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and ischemic stroke. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with intracerebral hemorrhage. Cholesterol in large HDL was inversely associated with MI and ischemic stroke (odds ratios [ORs], 0.79 and 0.88), whereas cholesterol in small HDL was not (ORs, 0.99 and 1.06). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for ischemic stroke. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all three diseases. The 225 metabolic markers showed concordant associations between MI and ischemic stroke, but not with intracerebral hemorrhage.


The authors concluded that lipoproteins and lipids showed similar associations with MI and ischemic stroke, but not with intracerebral hemorrhage. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several nonlipid-related metabolites were associated with all three diseases.


This large case-control study suggests that MI and ischemic stroke risk is associated with lipoprotein and lipid profiles, but not intracerebral hemorrhage, while inflammation is associated with all three events.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins

Keywords: Cerebral Hemorrhage, Cholesterol, Cholesterol, HDL, Docosahexaenoic Acids, Dyslipidemias, Glucose, Inflammation, Ketone Bodies, Lipoproteins, HDL, Lipoproteins, LDL, Magnetic Resonance Spectroscopy, Metabolic Syndrome X, Myocardial Infarction, Primary Prevention, Risk, Stroke, Triglycerides

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