Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study

Area of Science:

• Cardiovascular Medicine
• Molecular Biology
• Biomarker Discovery

Background:

• Coronary heart disease is a leading cause of death globally, with increasing prevalence.
• Accurate risk prediction tools and novel biomarkers are crucial for managing cardiovascular disease.
• Current risk assessment models may benefit from enhanced predictive capabilities.

Purpose of the Study:

• To evaluate the predictive utility of circulating microRNAs (miRs) for future fatal acute myocardial infarction (AMI) in healthy individuals.
• To identify specific miRs associated with AMI risk.
• To assess gender-specific differences in miR-associated AMI risk.

Main Methods:

• A prospective nested case-control study involving 112 healthy participants (40-70 years) with a 10-year follow-up for fatal AMI.
• Quantification of 179 miRs in serum using real-time polymerase chain reaction.
• Validation of candidate miRs in an independent cohort of 100 healthy individuals.

Main Results:

• Twelve miRs showed differential expression between cases and controls in the derivation cohort, with 10 validated in the independent cohort.
• Specific miRs, miR-424-5p and miR-26a-5p, were associated with AMI risk exclusively in men and women, respectively.
• A panel of 5 miRs (miR-106a-5p, miR-424-5p, let-7g-5p, miR-144-3p, miR-660-5p) achieved 77.6% correct classification and significantly improved the AUC from 0.72 to 0.91 when added to the Framingham Risk Score.

Conclusions:

• Several circulating miRs are significantly associated with the risk of future fatal AMI in healthy individuals.
• Gender-specific associations between certain miRs and AMI risk were identified.
• A panel of five miRs offers a promising tool to enhance the prediction of AMI risk, particularly when combined with existing risk scores.