Triglyceride to High-Density Lipoprotein Cholesterol (TG/HDL-C) ratio as a Marker of Subclinical Coronary Atherosclerosis and Hepatic Steatosis in Familial Hypercholesterolaemia

OBJECTIVE: Features of the cardiometabolic syndrome are prevalent in patients with familial hypercholesterolaemia (FH). Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a surrogate marker of insulin resistance, may be a robust predictor of cardiac events in the general population. We explored the association between TG/HDL-C ratio and high-risk coronary artery plaque (HRP) and hepatic steatosis (HS) in asymptomatic patients with FH.

METHODS: We conducted a cross-sectional study of 290 patients (mean age 49 years, 44% male) who underwent computed tomography coronary angiography (CTCA) for cardiovascular risk assessment. HRP and HS were assessed from CTCA, and TG/HDL-C ratio derived from the fasting lipid panel collected around time of scanning. Associations was assessed using binary logistic and Kaplan-Meier analysis.

RESULTS: TG/HDL-C ratio was significantly associated with HRP (OR: 1.27; 95% CI: 1.04-1.56; p=0.020) and HS (OR: 1.71; 95% CI: 1.17-2.51; p=0.005) after adjusting for age, body mass index, smoking and coronary calcium score. TG/HDL-C ratio was associated with HRP in patients treated with lipid-lowering medications (p=0.042) and inclusion in a predictive model outperformed the FH-Risk-Score (AUROC 0.74 vs 0.63, p=0.004). An elevated TG/HDL-C ratio predicted myocardial infarction or coronary revascularisation over a median follow-up of 91 months with 10 cardiac events recorded (p=0.043). TG/HDL-C ratio was strongly positively correlated (p <0.001 for all) with markers of cardiometabolic dysfunction: lipid accumulation product (r=0.81), visceral adiposity index (r=0.96) and triglyceride-glucose index (r=0.91).

CONCLUSIONS: TG/HDL-C ratio was strongly associated with HRP, HS and cardiac events in patients with FH treated with long-term cholesterol-lowering therapy.