Serial measurement of circulating cardiovascular-enriched microRNAs in patients with ischaemic heart disease – a five-year longitudinal study

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Abstract
Patients with ischaemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. MicroRNAs (miRNAs), small non-coding RNAs involved in physiological and pathological processes, are released into circulation and remain stable. In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Fifty-three new IHD patients participated in a five-year study with regular echocardiography, blood tests and follow-ups at 12-month intervals, with 25 followed up at five years. Serial echocardiography revealed a pattern towards worsening diastolic function over the follow-up period. RT-PCR analysis was conducted on four cardiovascular-enriched circulating miRNAs: miR-1, miR-126, miR-132 and miR-34a. Among these, only miR-1 and miR-126 showed statistically significant down-regulation starting from 24 months onwards. Linear mixed models, adjusted for body mass index and HbA1c changes, indicated significant associations between fold changes in miR-1 and miR-34a with cardiac function changes. Results from this first-ever five-year follow-up study have identified a possible link between cardiovascular-enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a foundation for prognostic tests for IHD and laying the foundation for further studies in larger populations. It is noteworthy that a significant dropout of participants may have impacted the statistical power in our study.

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