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CLINICAL STUDY

Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes

the strong heart study

Andrew P. Levy, MD, PhD, FACC^*,*, Irit Hochberg, MD^*, Kathleen Jablonski, PhD, Helaine E. Resnick, PhD, Elisa T. Lee, PhD, Lyle Best, MD and Barbara V. Howard, PhD

^* Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;
MedStar Research Institute and Washington Hospital Center, Washington, DC, USA
Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Missouri Breaks Industries Research Inc., Timber Lake, South Dakota, USA

Manuscript received April 25, 2002; revised manuscript received July 31, 2002, accepted August 26, 2002.

^* Reprint requests and correspondence: Dr. Andrew Levy, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, POB 9649, Haifa 31096, Israel.
alevy{at}tx.technion.ac.il

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 and Acronyms   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

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