Serum non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and the risk of sudden cardiac death: findings from a prospective cohort study

BACKGROUND AND AIMS: The non-high-density lipoprotein cholesterol-to-HDL-C ratio (NHHR), calculated as non-high-density lipoprotein cholesterol (non-HDL-C) divided by HDL-C, is a novel lipid index reflecting the balance between atherogenic and anti-atherogenic lipoproteins. This study evaluated and compared the associations and predictive utility of NHHR, non-HDL-C, and HDL-C for sudden cardiac death (SCD). METHODS AND RESULTS: Serum lipoprotein concentrations were measured at baseline in 2575 men aged 42-61 years from the Finnish Kuopio Ischemic Heart Disease prospective cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression. During a median follow-up of 27.8 years, 294 SCD events occurred. In multivariable-adjusted analyses, NHHR and non-HDL-C showed positive linear dose-response associations with SCD risk, whereas HDL-C demonstrated an inverse association. The adjusted HR (95% CI) per 1 SD increase was 1.68 (1.30-2.17) for NHHR and 2.40 (1.54-3.73) for non-HDL-C. Comparing extreme quartiles, the HR (95% CI) was 2.23 (1.55-3.21) for NHHR and 2.04 (1.44-2.89) for non-HDL-C. For HDL-C, the HR (95% CI) per 1 SD decrease was 2.33 (1.33-4.07) and 1.63 (1.13-2.34) comparing bottom vs top quartiles. Addition of NHHR to a model with established risk factors significantly improved discrimination (ΔC-index = 0.0079; p = .037), whereas improvements with non-HDL-C and HDL-C were not significant. CONCLUSION: In middle-aged and older men, elevated NHHR is associated with an increased risk of SCD, independently of several cardiovascular risk factors and consistent with a dose-response relationship. NHHR is a stronger predictor of SCD risk compared to non-HDL-C and HDL-C.