Preventive cardiology
Usefulness of the Triglyceride–High-Density Lipoprotein Versus the Cholesterol–High-Density Lipoprotein Ratio for Predicting Insulin Resistance and Cardiometabolic Risk (from the Framingham Offspring Cohort)

https://doi.org/10.1016/j.amjcard.2007.09.109Get rights and content

Increased triglycerides (TG) and decreased high-density lipoprotein (HDL) cholesterol are key metabolic abnormalities in patients with insulin resistance (IR) states, including diabetes mellitus. The TG/HDL cholesterol ratio was advocated as a simple clinical indicator of IR, but studies yielded inconsistent results. The total cholesterol/HDL cholesterol ratio was widely used to assess lipid atherogenesis, but its utility for assessing IR or its associated coronary heart disease (CHD) risk was unknown. TG/HDL cholesterol and total cholesterol/HDL cholesterol ratios were related to IR (top quartile of the homeostasis model assessment-IR) in 3,014 patients (mean age 54 years; 55% women). Logistic regression was used to construct receiver-operator characteristic curves for predicting IR, with lipid ratios as predictors. Multivariable Cox regression was used to evaluate whether adjusting for lipid ratios attenuated the association of IR with CHD. Cross sectionally, age- and gender-adjusted correlations of IR were 0.46 with TG/HDL cholesterol ratio and 0.38 with total/HDL cholesterol ratio. IR prevalence increased across tertiles of lipid ratios (p <0.0001). The area under the receiver-operator characteristic curves for predicting IR with TG/HDL cholesterol ratio was 0.745, slightly higher than that for total/HDL cholesterol ratio (0.707; p <0.001 for comparison). On follow-up (mean 6.4 years), 112 patients experienced initial CHD events. IR was associated with CHD risk (multivariable-adjusted hazards ratio 2.71, 95% confidence interval 1.79 to 4.11), which remained significant even after adjustment for lipid ratios. In conclusion, our observations suggested that the TG/HDL cholesterol ratio was an imperfect surrogate for IR and its associated CHD risk, and it was only slightly better than the total/HDL cholesterol ratio for this purpose.

Section snippets

Methods

The Framingham Offspring Study was initiated in 1971, and the design and selection criteria were described previously.1 Subjects who attended the examination cycle 5 (1991 to 1995) were eligible for the present study (n = 3,799). At each quadrennial examination, offspring cohort subjects underwent a routine medical history, physical examination that included blood pressure measurement and anthropometry, and blood sampling (after an overnight fast). We excluded 785 subjects because of age <20

Results

Baseline characteristics of our study sample (overall and according to presence vs absence of IR) are listed in Table 1. Subjects with IR were older and more likely to be men and weigh more and had higher blood pressure and greater prevalence of hypertension. TG was higher and HDL cholesterol was lower in those with IR, resulting in higher TG/HDL cholesterol ratios. Total/HDL cholesterol ratio was also higher in subjects with IR.

Age- and gender-adjusted correlations among lipid variables are

Discussion

Our principal findings are threefold. First, cross-sectional analyses suggested that of the several candidate lipid markers evaluated, TG/HDL cholesterol ratio was the best correlate of IR. However, performance of this ratio for predicting IR was only fair, reflected by the area under the curve of 0.745. Second, longitudinal analyses showed that even after adjustment for lipid variables (including TG/HDL cholesterol ratio), IR was significantly and strongly associated with CHD risk. These

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1

Dr. Vasan was supported by Contracts N01-HC-25195 and 2K24 HL04334 from the National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, Maryland.

2

Dr. Kannel was supported by the Visiting Scientist Program, which is supported by Astra Zeneca, Waltham, Massachusetts.

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