A Promising Biomarker for Predicting Cardiovascular Risk in Asymptomatic Familial Hypercholesterolemia Patients From The SAFEHEART Study
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Background
Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a markedly increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Genetic and molecular factors, including microRNAs (miRNAs), may serve as biomarkers to improve disease risk prediction. miRNAs are key regulators of biological processes involved in cardiovascular pathology. This study aimed to identify miRNAs that, combined with clinical variables, enhance ASCVD prediction in asymptomatic FH patients from the SAFEHEART cohort.
Methods
A total of 400 subjects diagnosed with FH were included. Coronary calcium score (Agatston score) was measured by computed tomography and stratified into three risk categories (0–99, 100–299, >300). Circulating plasma miRNA levels were quantified using the OpenArray platform. Statistical analyses characterized baseline features and assessed predictive performance using ROC curve analysis. Functional enrichment was explored through the MIENTURNET database.
Results
Individuals carrying the null allele for the LDL-R gene showed significantly higher plasma miR-1 levels than those carrying the defective allele (p=0.042). Likewise, subjects with an Agatston score of 0–99 exhibited higher miR-1 levels than those with scores >300 (p=0.025). A predictive model based on clinical variables including age, sex, hypertension, smoking, BMI, LDL burden, and lipoprotein(a) achieved an AUC of 0.846 for ASCVD prediction. Incorporating miR-1 increased the AUC to 0.878, representing a statistically significant improvement (DeLong test, p=0.005).
Conclusions
miR-1 emerged as a promising biomarker for ASCVD risk prediction in FH patients. When integrated with conventional clinical variables, miR-1 improved the model’s predictive accuracy. These findings suggest that miR-1 could serve as a useful molecular marker for enhanced cardiovascular risk stratification in asymptomatic individuals with familial hypercholesterolemia.
