Introduction: Insulin resistance (IR), a metabolic dysregulation predictive of various clinical sequelae, is reportedly associated with the risk of coronary heart disease (CHD). The invasive nature of direct measures of IR limits their use in clinical practice and population research, motivating the need for a suitable tool to signal the presence of IR. Its correlation with insulin action, simplicity, and wide availability of standardization in its assay properties, promotes the ratio of fasting plasma triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C). However, there is no consensus for TG/HDL-C ratio thresholds to index IR, whether the ratio relates to IR in African Americans, nor the ratio’s ability to predict coronary heart disease (CHD) risk.
Objectives: To: 1) optimize race and gender-specific TG/HDL-C ratio cut-points indicative of IR in white and African American males and females; 2) compare cardio-metabolic profiles of the dichotomies created by these cut-points within each race-gender subgroup; and 3) estimate associations of IR indexed by the TG/HDL-C ratio with incident CHD by race and gender.
Methods: Data from 10,031 white and 3,076 African American non-diabetic participants aged 45-64 years in the population-based ARIC Study were examined. Race and gender-specific TG/HDL-C ratio cut-points with optimal performance against the upper quartile of fasting insulin were calculated at baseline (1987-1989) using Youden indices. Cardio-metabolic profiles were compared by IR categories in each race-gender subgroup. Competing risk (of death) Cox models, adjusted for age, hypertension, cigarette smoking, BMI, and LDL-C, were fit by race and gender to quantify the risk of incident CHD events by 2012 independently attributed to IR. Incident CHD events were ascertained from cohort examinations, follow-up of hospital admissions and fatal events records, and classified according to a standardized protocol.
Results: A total of 1,886 (18%) and 429 (14%) validated CHD events accrued by 2012 in whites and African Americans, respectively. Optimized values of the TG/HDL-C ratio thresholds to index IR were ≥3.4 for white males, ≥2.3 for white females, ≥2.2 for African American males, and ≥1.8 for African American females. Applying these thresholds, individuals denoted as having IR had noticeably poorer cardio-metabolic risk profiles than those not having IR in each race-gender subgroup. IR, as defined by the above cut-points, was associated with the following adjusted hazard ratios (95% confidence intervals) of incident CHD by 2012: 1.35 (1.21, 1.52) in white males; 1.52, (1.27, 1.83) in white females; 1.69 (1.28, 2.22) in African American males; and 1.44 (1.08, 1.92) in African American females.
Conclusion: The TG/HDL-C ratio, a clinically useful indicator of IR, independently predicts coronary heart disease in non-diabetic white and African American men and women.