Article

Haptoglobin Polymorphism Predicts 30-Day Mortality and Heart Failure in Patients With Diabetes and Acute Myocardial Infarction

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel
Diabetes (Impact Factor: 8.1). 10/2005; 54(9):2802-6. DOI: 10.2337/diabetes.54.9.2802
Source: PubMed

ABSTRACT

Patients with diabetes presenting with acute myocardial infarction (AMI) have an increased rate of death and heart failure. Patients with diabetes homozygous for the haptoglobin (Hp) 1 allele (Hp 1-1) develop fewer vascular complications. We tested the hypothesis that Hp type is related to the outcome of patients with diabetes presenting with AMI. We prospectively assessed the relationship between Hp type and 30-day mortality and heart failure in 1,437 patients with AMI (506 with diabetes). Multivariate logistic regression identified a significant interaction between Hp type and diabetes status on these outcome measures. Hp type was not related to outcome among patients without diabetes. In contrast, Hp 1-1 was associated with a strong protective effect with regard to the primary end point of death (OR 0.14, P = 0.015) and for death and heart failure (OR 0.35; 95% CI 0.15-0.86, P = 0.018) among patients with diabetes. Finally, among patients with diabetes, Hp 1-1 was associated with smaller infarct size. This study demonstrates that in patients with diabetes and AMI, the Hp type is an important determinant of clinical outcome and infarct size.

Full-text

Available from: Simcha Meisel, Nov 29, 2015
  • Source
    • "Low levels of vitamin are associated with increased incidence of diabetes (Hope and Hope, 2005). Individuals with diabetes have low level of antioxidant; on the other hand, people with diabetes need more antioxidant requirements due to increase in free radical's production with increase in serum glucose concentration (Suleiman et al., 2005). When vitamin E therapy was given to diabetic rats has remarkable effect in reduction of lipid peroxidase and elevation of catalase, GPx and glutathione-s-transferase and these finding along with its reduction of malonaldehyde level in liver, brain and myocardial homogenate confirm known effect of vitamin E (Halim and Mukhopadhyay, 2006). "
    [Show abstract] [Hide abstract] ABSTRACT: Oxidative stress and reactive oxygen species (ROS) have been documented subsist to the pathogenesis of many diseases including diabetes mellitus. The strength of both parameters could be estimated by measuring oxidative stress marker thiobarbituric acid reactive substances (TBARS), its related parameters and the antioxidants glutathione peroxidase and superoxide dismutase (SOD) in plasma of DM patients. Lipid peroxidation was measured as TBARS and presented as malondialdehyde, total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (Tg), the antioxidants (vitamin A (β-carotene), vitamin E, vitamin C, glutathione peroxidase (GPx) and superoxide dismutase) levels. The results showed that these parameters, commonly, were declined appreciably in diabetic individuals as compared to the healthy individuals. In most cases, age and gender were appeared to involve in having greater values of diabetes marker. Further, increased level of lipid peroxidation and random behaviour of antioxidant potential also associated with Diabetes. For that reason these biomarkers might be of great important to diagnosis DNA damages of diabetic patients.
    Full-text · Article · Mar 2015 · Pakistan journal of pharmaceutical sciences
  • Source
    • "Furthermore, it has been shown that within smokers, ferroxidase and HDL-C concentrations were significantly lower inHp2-2 than in Hp2-1 and Hp1-1 , whereas total cholesterol and LDL-C concentrations were significantly higher among the Hp2-2 smokers. Contrarily, other studies that investigated the combined effect of smoking and Hp genotypes in predisposing to cardiovascular status found no association between the Hp genotypes and the prevalence of coronary heart disease (De Bacquer et al. 2001; Roguin et al. 2001; Suleiman et al. 2005). Obesity had been considered a risk factor for coronary heart disease, so we have found that Hp2-2 increases the risk of SCS (OR 1.98, 95% CI 1.109–4.86; "
    [Show abstract] [Hide abstract] ABSTRACT: Haptoglobin (Hp) polymorphism generates three common human genotypes (Hp1-1, Hp2-1, and Hp2-2), having functional differences, related to the risk of development of cardiovascular diseases. These functions are a consequence of hemoglobin binding that leads to the synthesis of an antioxidant like ferritin. We explored the association of Hp polymorphism with significant coronary stenosis (SCS) and its severity within 400 Tunisian patients, using genotyping, biochemical parameters, and the Gensini score. After adjustments for age and gender, Hp2-2 was associated with the highest ferritin but the lowest Hp concentrations. After adjustments for confounding parameters, the OR of SCS associated with Hp2-2 was 1.74 (95% CI 1.18-2.58; p = 0.005). This effect was enhanced within diabetics (OR 1.90, 95% CI 1.11-3.24; p = 0.018), obese subjects (OR 1.98, 95% CI 1.10-4.86; p = 0.034), and smokers (OR 4.17, 95% CI 1.54-1.29; p = 0.005). The Hp2-2 genotype is associated with an increase in SCS especially in diabetics, the obese, and smokers.
    Preview · Article · Feb 2014 · Biochemical Genetics
  • Source
    • "More recent investigations employing native Hp:Hb ligand appeared to suggest poor or even lack of dependence on CD163 for IL-6 or IL-10 signalling pathways, depending on the type of polymorphic haptoglobin variant employed [17] [18]. Since the haptoglobin 2 allele is linked to a host of adverse clinical cardiovascular events, [19] [20] [21] [22] [23] it is important to understand Hp genotype-dependent disease mechanisms in CD163 + macrophages in greater detail, to guide informed interdictions in vulnerable individuals. Here we have examined IL-10 signalling pathways during scavenging of polymorphic Hp2-2:Hb versus Hp1-1:Hb complexes in CD163 + human monocyte-derived macrophages. "
    [Show abstract] [Hide abstract] ABSTRACT: Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes ( P < 0.05 ) . Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.
    Full-text · Article · Apr 2013
Show more