Key result
Baseline circulating miR-126 is linked to ~2.7-fold higher risk of incident myocardial infarction.
Why the study?
Circulating microRNAs are emerging as potential biomarkers, but their association with incident myocardial infarction and cellular origin remain to be explored.
Are baseline levels of specific circulating microRNAs associated with the risk of incident myocardial infarction?
Cohort (n=820)
Are baseline levels of specific circulating microRNAs associated with the risk of incident myocardial infarction?
Hazard Ratio: 2.69 (95% CI 1.45–5.01)
p-value: p=0.002
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“many studies are simply underpowered (too low numbers of patients) and/or do not use appropriate controls matched for potentially confounding factors such as age, sex, medication, and comorbidities. Also, there is little comparison of miRNAs to reference biomarkers.”
Specific circulating microRNAs, including miR-126, miR-223, and miR-197, are significantly associated with the future risk of myocardial infarction and appear to be predominantly platelet-derived.
OBJECTIVES: This study sought to explore the association between baseline levels of microRNAs (miRNAs) (1995) and incident myocardial infarction (1995 to 2005) in the Bruneck cohort and determine their cellular origin. BACKGROUND: Circulating miRNAs are emerging as potential biomarkers. We previously identified an miRNA signature for type 2 diabetes in the general population. METHODS: A total of 19 candidate miRNAs were quantified by real-time polymerase chain reactions in 820 participants. RESULTS: In multivariable Cox regression analysis, 3 miRNAs were consistently and significantly related to incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio: 2.69 [95% confidence interval: 1.45 to 5.01], p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio: 0.47 [95% confidence interval: 0.29 to 0.75], p = 0.002, and 0.56 [95% confidence interval: 0.32 to 0.96], p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 min, 1 h, 5 h, 2 days, and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified 6 distinct miRNA clusters. One cluster included all miRNAs associated with the risk of future myocardial infarction. It was characterized by early (1 h) and sustained activation (7 days) post-ischemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets. CONCLUSIONS: In subjects with subsequent myocardial infarction, differential co-expression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature.
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Zampetaki et al. (2012) conducted a cohort in Myocardial Infarction (n=820). Baseline circulating microRNAs (miR-126, miR-223, miR-197) was evaluated on Incident myocardial infarction (HR 2.69, 95% CI 1.45 to 5.01, p=0.002). Baseline circulating miR-126 was positively associated with incident myocardial infarction (HR 2.69; 95% CI 1.45-5.01), whereas miR-223 and miR-197 were inversely associated.
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