Clinical study
Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: the strong heart study

https://doi.org/10.1016/S0735-1097(02)02534-2Get rights and content
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Abstract

Objectives

The goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM).

Background

Cardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications.

Methods

We sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years.

Results

In multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype.

Conclusions

This study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient.

Abbreviations

BP
blood pressure
BMI
body mass index
CI
confidence intervals
CVD
cardiovascular disease
DM
diabetes mellitus
HDL
high-density lipoprotein
Hp 1-1
individuals who are homozygous for the 1 allele
Hp 2-2
individuals who are homozygous for the 2 allele
Hp 2-1
individuals who are heterozygous at the haptoglobin locus
LCAT
lecithin-cholesterol acyl transferase
LDL
low-density lipoprotein
SHS
Strong Heart Study

Cited by (0)

Supported by NHLBI RO1 HL-66195, the Kennedy Leigh Trust (A.P.L.), and cooperative grants for Strong Heart (NHLBI U01-HL-41642, 41652, 41654).