Key result
A 13-allele genetic risk score is linked to ~127% greater risk of developing NICM.
Why the study?
Common genetic variants have been linked to an increased risk of non-ischaemic cardiomyopathy, but their significance in a general population had not been evaluated.
Does a genetic risk score based on 13 NICM risk alleles predict LV dysfunction and the development of non-ischaemic cardiomyopathy in the general population?
Cohort (n=1,897)
Does a genetic risk score based on 13 NICM risk alleles predict LV dysfunction and the development of non-ischaemic cardiomyopathy in the general population?
Answers are grounded in this paper and cite their sources.
A genetic risk score based on 13 common variants correlates with echocardiographic changes and the long-term development of non-ischaemic cardiomyopathy in the general population.
AIMS: Common genetic variants have been linked to an increased risk of non-ischaemic cardiomyopathy (NICM). The primary objective of this study was to evaluate the significance of these variants in a general population. METHODS AND RESULTS: Thirteen NICM risk alleles, previously validated by meta-analyses of case-control genetic association studies, were used to determine genetic risk (GR) in a large, unselected cohort (n = 1897) of Olmsted County residents aged >45 years. Clinical and echocardiographic data, with biomarkers, were correlated with this NICM-GR over a median of 16 years of follow-up (interquartile range [IQR] 15-17). There were no significant differences between the study population quartiles, based on NICM-GR, in terms of age (median 61.6 [IQR 53.6-70.4]), sex (48% male), and cardiovascular risk factors. A significant correlation was detected by specific linear-regression models between NICM-GR and left ventricular (LV) ejection-fraction (beta [standard error]: -2.68 [0.68], p < 0.001), LV end-systolic-diameter (0.22 [0.06], p < 0.001), and LV end-diastolic-diameter (0.14 [0.06], p = 0.01). During follow-up, 46 subjects developed NICM. Using a 3:1 matched-cohort of non-NICM versus NICM patients, linear-regression analysis found a significant correlation between NICM-GR and NICM development (odds ratio 2.27, 95% confidence interval 1.06-4.85, p = 0.03). There was no significant association between these variants and heart failure biomarkers (aldosterone, natriuretic peptides, ST2, galectin-3). CONCLUSIONS: The NICM-GR correlates with LV function and dimension, and subsequent development of NICM in the general population. The lack of correlation of these variants with cardiovascular risk factors and the renin-angiotensin-aldosterone axis or natriuretic peptides suggest different biological mechanisms involved. These findings support the need to explore newer pathophysiologic pathways in the development of NICM.
No takes yet. Share an insight, caveat, or question.
Paldino et al. (2025) conducted a cohort in Non-ischaemic cardiomyopathy (n=1,897). NICM genetic risk score (13 risk alleles) vs. Lower genetic risk was evaluated on Development of non-ischaemic cardiomyopathy (OR 2.27, 95% CI 1.06-4.85, p=0.03). A 13-allele genetic risk score was associated with the development of non-ischaemic cardiomyopathy in the general population.
Synapse has enriched 10 related papers. Consider them for comparative context: