Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Study

The Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) was undertaken in men with known coronary heart disease (CHD), a low HDL cholesterol, a low LDL cholesterol, and a broad range of triglyceride values. This multicenter, placebo-controlled study demonstrated that therapy with gemfibrozil significantly reduced the incidence of nonfatal myocardial infarction (MI) and CHD death (1)

• randomised blinded, placebo controlled trial. There was a median follow-up of 5.1 years
  
  
• the study group were men (<74 years) with a history of ischaemic heart disease. The men had no serious comorbidity. The study recruits had an HDL cholesterol <= 1.0 mmol/l (<= 40 mg/dl) and an LDL cholesterol <= 3.6 mmol/l (<= 140 mg/dl). Also they had a triglyceride level < 3.4 mmol/l (<300 mg/dl)
  
  
• patients were allocated to gemfibrozil 1200mg/d (1264) or to placebo
  
  
• the study revealed that gemfibrozil reduced the risk for non-fatal myocardial infarction and death from coronary artery disease
  • therapy with gemfibrozil in patients HDL-C and coronary disease reduced cardiovascular events by 22% compared with placebo

This study is important because it shows treatment benefits for patients with low HDL cholesterol levels as well as LDL cholesterol levels below current guidelines for treatment.

Insulin resistance:

In VA-HIT there was a high percentage of subjects with diabetes and features of insulin resistance with a high BMI, high waist circumference, and increased fasting concentrations of plasma insulin

• in this study, the 5-year rate of a new cardiovascular event was highest in subjects with lowest levels of HDL cholesterol, in those with highest levels of triglycerides, and in those with diabetes or with hyperinsulinemia
  • although a low HDL cholesterol and high triglycerides are frequently found with insulin resistance with or without type 2 diabetes, there is no evidence that the risk of a cardiovascular event associated with this dyslipidemia is modified by the presence of insulin resistance
  • in VA-HIT the occurrence of a new cardiovascular event and the benefit of fibrate therapy was much less dependent on levels of HDL cholesterol or triglycerides than on the presence or absence of insulin resistance (the homeostasis model assessment of insulin resistance (2) (HOMA-IR) was used in this trial)
  • analysis of this trial data revealed that in men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level (3)

Reference:

• 1) NEJM 1999;341: 410-18.
• 2) Robins SJ et al. Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003 May;26(5):1513-7
• 3) Rubins HB et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med. 2002 Dec 9-23;162(22):2597-604.