The TG-HDL-C ratio is associated with incident MACE in normoglycemic individuals without diabetes: findings from a Swedish population-based cohort

Introduction The triglyceride to high density lipoprotein cholesterol ratio (TG-HDL-C ratio) has emerged as a clinically available proxy for insulin resistance (IR). It has also been found to be independently associated with the development of major adverse cardiovascular events (MACE). Despite intense research on the subject, prospective cohort studies in European general populations are sparse. Also, few studies have taken abdominal obesity into account. Finally, from a clinical perspective, markers of IR and future MACE risk would be of specific interest among individuals without obvious IR in the form of diabetes or elevated fasting glucose. Purpose To examine the fasting TG-HDL-C ratio in relation to prospective MACE amongst normoglycemic non-diabetics from a Swedish general-population. Methods Individuals from a population-based cohort in southeast Sweden (n=6870; data collected 2012-2015) with baseline clinical and questionnaire data along with fasting glucose and lipid panels were enrolled. Participants with known diabetes (n=241) and/or high fasting glucose levels (≥6.1 mmol/L) (n=839) were excluded. The development of myocardial infarction, PCI, CABG, ischemic stroke and cardiovascular death was recorded during follow-up and used in a composite MACE endpoint based on ICD-10 codes from Swedish registers. Uni- and multivariable Cox regression models were used. TG-HDL-C ratios were analyzed as log-transformed Z-scores and in quartiles. Results At baseline, the study cohort consisted of 5601 normoglycemic non-diabetics with available TG-HDL-C ratios. Apparent from TG-HDL-C ratio quartile comparison (Table 1), individuals with higher TG-HDL-C ratio were more often men, smokers and users of antihypertensive and lipid-lowering medication (p<0.001 for all). This group also exhibited a more adverse risk-profile, with higher waist-hip-ratio, blood pressure, glucose and lipid levels (p<0.001 for all). During a median follow-up of 9.8 (IQR 1.6) years, 209 individuals developed MACE. In univariable analysis, higher TG-HDL-C ratio was generally associated with MACE, mainly driven by an association in the highest quartile (HR=3.18, 95% CI=2.06-4.90, p<0.001). With stepwise introduction of covariates (Table 2) in the multivariable models, the association was attenuated but remained significant in the final model for the highest quartile when compared to quartile 1-3 (HR=1.41, 95% CI=1.03-1.94, p=0.031). Conclusions Higher fasting TG-HDL-C ratio is associated with incident MACE in a Swedish population-based cohort without diabetes or hyperglycemia. The relationship seems independent of traditional cardiovascular risk factors including waist-hip-ratio as a measure of abdominal obesity. The findings propose the TG-HDL-C ratio as a potential indicator of MACE risk among individuals without overt IR. Future studies should evaluate if this translates into added clinical value beyond traditional risk prediction tools.