The Role of Haptoglobin Polymorphism in Cardiovascular Disease in the Setting of Diabetes.

Shmuel Somer,Andrew P Levy

doi:10.3390/ijms22010287

Abstract

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with diabetes mellitus (DM). Preclinical models have suggested that excessive oxidative stress and hyperglycemia are directly responsible for this pathological association. However, numerous clinical trials involving the administration of high doses of the antioxidant vitamin E or attempts at strict glycemic control have failed to show a significant reduction of CVD in DM patients. We describe here a possible explanation for the failure of these trials, that being their lack of proper patient selection. The haptoglobin (Hp) genotype is a major determinant of the risk of CVD in the setting of DM. Treatment of individuals with the high-risk Hp genotype with antioxidants or aggressive glycemic control has shown benefit in several small studies. These studies suggest a precision medicine-based approach to preventing diabetes complications. This approach would have a profound effect on the costs of diabetes care and could dramatically reduce morbidity from diabetes.

Highlights

Diabetes Mellitus (DM) patients are at increased risk for the development of cardiovascular disease (CVD) [1]
We aim to discuss all published interventional studies assessing the ability of vitamin E or aggressive glycemic control to reduce the risk of CVD in patients with the
Prevention Evaluation (HOPE) study assessed the effects of angiotensin-converting enzyme (ACE) inhibition and vitamin E on incident cardiovascular disease (CV death, stroke, and non-fatal myocardial infarction (MI)) [14]

Summary

Introduction

Diabetes Mellitus (DM) patients are at increased risk for the development of cardiovascular disease (CVD) [1]. Virtually all of these studies using the antioxidant vitamin E or strict glycemic control have shown a lack of improvement but even suggested harm to those DM patients who received these interventions [6]. One possible explanation for the failure of these studies may be the lack of proper patient selection in determining who would receive these interventions [3,7]. We are proposing that with the correct selection of patients with the haptoglobin (Hp) genotype, these therapies could potentially reduce the risk of CVD in the setting of DM. We aim to discuss all published interventional studies assessing the ability of vitamin E or aggressive glycemic control to reduce the risk of CVD in patients with the

Studies Assessing CVD in Relation to the Haptoglobin Genotype

Mechanism by Which the Hp Genotype May Impact the Risk of CVD

Vitamin E Treatment Provides Protection against CVD in DM Patients with the

Limitations and Future