Abstract
Background: Patients with ischemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. Currently available tests are either not sensitive enough to detect early changes or not easily incorporated into routine clinical practice. MicroRNAs (miRNAs), small non-coding RNAs involved in both physiological and pathological processes, are released into circulation and remain stable.
Research Question: 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.
Methods: Fifty-four new IHD patients joined a 5-year study, providing informed consent for regular echocardiography, blood tests and follow-ups at 12-month intervals. Plasma RNA was extracted and RT-PCR analysis used to assess expression of cardiovascular-enriched miR-1, miR-126, miR-132, and miR-34a.
Results: Serial echocardiography analysis showed the development of diastolic dysfunction in the participants starting from 48 months (E/e’-10.7±4.3 vs 9.7±3.6 at baseline, P<0.04). RT-PCR analysis revealed significant downregulation of miR-1 and miR-126 starting from 24 months of follow-up (P<0.03 vs. baseline). Associations between each miRNA and each cardiac function measure were examined using linear mixed models without and with adjustment for changes in BMI and HbA1c during the same period. None of the lagged models found statistically significant associations (all p ≥ 0.126). From the concurrent models, two miRNA were associated with cardiac function: miR-1 and MV E Vel in the unadjusted (p = 0.045) and adjusted models (slope = -0.004, 95% CI -0.007 to -0.000, p = 0.026) models and miR-34a and FS(%) in the adjusted model only (slope = -0.151, 95% CI -0.301 to -0.001, p = 0.048).
Conclusion: Results from this first-ever five-year follow-up study have identified a link between cardiovascular enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a knowledge platform for prognostic tests for IHD and laying the foundation for further studies in larger population size.