Haptoglobin Phenotype Is Associated With High-Density Lipoprotein-Bound Hemoglobin Content and Coronary Endothelial Dysfunction in Patients With Mild Nonobstructive Coronary Artery Disease.

Objective- Coronary endothelial dysfunction (ED) is an early stage of atherosclerosis and is associated with impaired high-density lipoprotein (HDL) function. A functional polymorphism at the haptoglobin (Hp) gene locus (rs72294371) has been associated with marked differences in HDL structure and function. We sought to determine whether Hp phenotype was associated with coronary ED and whether the amount of hemoglobin (Hb) tethered to HDL via Hp was Hp-type dependent and associated with ED. Approach and Results- Microvascular and epicardial coronary endothelial function was assessed in 338 individuals with nonobstructive coronary artery disease. Microvascular ED was defined as <50% change in coronary blood flow and epicardial ED as ≥20% decrease in coronary artery diameter after intracoronary acetylcholine infusion. The amount of Hb bound to HDL was measured by ELISA after HDL purification from plasma samples using immune-affinity chromatography. One hundred and seventy of the individuals in this study (50.3%) were diagnosed with microvascular ED, 143 (42.3%) with epicardial ED, and 67 (19.7%) had diabetes mellitus (DM). Hp phenotype was significantly associated with microvascular ( P=0.01) and epicardial ED ( P=0.04) among DM individuals. There was a significant and inverse correlation between the amount of HDL-bound Hb and change in coronary blood flow (r=-0.40; P<0.0001) and in coronary artery diameter (r=-0.44; P<0.0001) in response to acetylcholine infusion. Hb content of HDL was significantly increased in individuals with Hp 2-2 and DM. In a logistic regression model, Hp 2-2 phenotype was associated with microvascular ED (odds ratio, 1.9; P=0.03) and the amount of HDL-bound Hb was an independent predictor of both microvascular (odds ratio, 4.6 for each 1-SD increase; P<0.0001) and epicardial (odds ratio, 2.2; P<0.0001) ED. Conclusions- Hp phenotype is significantly associated with coronary ED in DM individuals. This association is likely related to increased Hb tethering to HDL via Hp 2-2 in DM.

The 'immunologic theory' of preeclampsia revisited: a lesson from donor oocyte gestations.

OBJECTIVE: To determine the prevalence of placental complications in patients conceived through donor versus autologous oocytes. STUDY DESIGN: A retrospective cohort study including 2 groups of patients who conceived through in vitro fertilization using: (1) donor oocyte (n = 139) and (2) autologous oocyte (n = 126). Only singleton gestations were included. The rate of placental complications including preeclampsia, gestational hypertension, and intrauterine growth restriction was compared between these 2 groups. RESULTS: The women who conceived using donor oocytes were older compared with women who conceived using autologous oocytes (median maternal age 45 vs 41, P < .01). The rate of hypertensive diseases of pregnancy including gestational hypertension and preeclampsia was significantly higher in ovum donor recipients compared with women conceived with autologous oocytes (25% vs 10%, P < .01). Similarly, the rate of intrauterine growth restriction was also higher among patients conceived through oocyte donation although it did not reach statistical significance (9.3% vs 4%, P = .08). When maternal age was restricted to ≤45 years, the rate of hypertensive diseases of pregnancy remained significantly higher among ovum donor compared with autologous oocyte recipients (22% vs 10%, P = .02). Adjustment for maternal age, gravidity, parity, and chronic hypertension revealed that oocyte donation was independently associated with higher rate of hypertensive diseases of pregnancy (P = .01). CONCLUSION: Patients conceived through oocyte donation have an increased risk for placental complications of pregnancy. These findings support the 'immunologic theory' suggesting that immunologic intolerance between the mother and the fetus may play an important role in the pathogenesis of preeclampsia.