Insulin resistance and the relationship of a dyslipidemia to coronary heart disease: the Framingham Heart Study

Abstract

Objective: The goal of this study was to examine the effect of insulin resistance (IR) in subjects without diabetes on the relationship of a dyslipidemia with high triglycerides and low high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease (CHD).

Methods and results: Lower and higher fasting plasma HDL-C and triglyceride concentrations (defined at the study population median) and presence or absence of IR (defined by upper quartile Homeostatic Model Assessment values) were related to the development of myocardial infarction or CHD death in Framingham Heart Study participants without diabetes or a history of CHD (n=2910) attending the 1991 to 1995 examination. During follow-up (mean, 14 years), 128 participants experienced an incident CHD event. With Kaplan-Meier plots, the incidence of CHD was significantly greater with than without IR at either the lowest HDL-C or the highest triglycerides (P<0.001). In multivariable Cox models adjusted for major CHD risk factors, including waist circumference, only subgroups with IR had a significantly higher incidence of CHD. Compared with a reference group without IR and with higher-than-median HDL-C or lower-than-median triglycerides, the hazard ratio (HR) for incident events was significant with only IR and a lower HDL-C (HR 2.83, P<0.001) or higher triglycerides (HR 2.50, P<0.001). These findings were similar in men and women.

Conclusions: In this community-based sample exclusive of diabetes, incident CHD risk associated with plasma HDL-C or triglycerides was significantly increased only in the presence of IR.

Fig 1

The prevalence of insulin resistance (IR) by the 4^th quartile of HOMA-IR is shown across quartiles of fasting plasma HDL-C and across quartiles of fasting plasma triglycerides for men and women. Darker shaded bars represent the percentage of men and lighter-shaded bars the percentage of women with IR at each quartile division. Values at the base of each quartile division show the concentration range of HDL-C or triglycerides for that quartile.

Fig 2

Unadjusted Kaplan-Meier curves, showing the cumulative incidence of CHD events in the entire study sample (N=2910) with and without insulin resistance (IR) and with lower or higher values of fasting plasma HDL-C) (panel A) and lower or higher values of plasma triglycerides (TG) (panel B). Insulin resistance was defined in the entire study group without diabetes by the upper quartile of HOMA-IR values. Lower or higher values of plasma HDL-C and triglycerides were defined at the median plasma concentration of these values for the combined study group of men and women (i.e., at 49 mg/dL for HDL-C and at 112 mg/dL for triglycerides). Mean HDL-C and triglyceride values for each of these subgroups (with and without IR) are shown for each curve within parenthesis.

Fig 2

Unadjusted Kaplan-Meier curves, showing the cumulative incidence of CHD events in the entire study sample (N=2910) with and without insulin resistance (IR) and with lower or higher values of fasting plasma HDL-C) (panel A) and lower or higher values of plasma triglycerides (TG) (panel B). Insulin resistance was defined in the entire study group without diabetes by the upper quartile of HOMA-IR values. Lower or higher values of plasma HDL-C and triglycerides were defined at the median plasma concentration of these values for the combined study group of men and women (i.e., at 49 mg/dL for HDL-C and at 112 mg/dL for triglycerides). Mean HDL-C and triglyceride values for each of these subgroups (with and without IR) are shown for each curve within parenthesis.