Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine ( P <0.001) and sodium nitroprusside ( P <0.05), but greater benefit from vitamin C ( P <0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P =0.001), the effect of vitamin C ( P =0.001), and age ( P =0.016) remained independent predictors of cardiovascular events. Conclusions Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.

Aim: Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants. Methods: A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3-5 days after birth. DNA-methylation was analyzed in leucocytes. Results: Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methyla-

No abstract

BackgroundBirth by cesarean section is associated with increased risks of immune disorders. We tested whether establishment of immune function at birth relates to mode of delivery, taking other maternal and infant characteristics into account.Methods and findingsUsing a prospectively collected database, we retrieved information on maternal and infant characteristics of 6,014 singleton infants delivered from February to April 2014 in Stockholm, Sweden, with gestational age ≥35 weeks, Apgar scores ≥7, and without congenital malformations or any neonatal morbidity. We linked our data to blood levels of T-cell receptor excision circles (TREC) and κ-deleting recombination excision circles (KREC), determined as part of a neonatal screening program for immune-deficiencies, and representing quantities of newly formed T- and B-lymphocytes. Multivariate logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for participants having TREC and KREC levels in the lowest quintile. Multivariate models were adjusted for postnatal age at blood sampling, and included perinatal (mode of delivery, infant sex, gestational age, and birth weight for gestational age), and maternal characteristics (age, parity, BMI, smoking, diabetes, and hypertensive disease).Low TREC was associated with cesarean section before labor (adjusted OR:1.32 [95% CI 1.08–1.62]), male infant sex (aOR:1.60 [1.41–1.83]), preterm birth at 35–36 weeks of gestation (aOR:1.89 [1.21–2.96]) and small for gestational age (aOR:1.67 [1.00–2.79]). Low KREC was associated with male sex (aOR:1.32 [1.15–1.50]), postterm birth at ≥42 weeks (aOR:1.43 [1.13–1.82]) and small for gestational age (aOR:2.89 [1.78–4.69]). Maternal characteristics showed no consistent associations with neonatal levels of either TREC or KREC.ConclusionCesarean section before labor was associated with lower T-lymphocyte formation, irrespective of maternal characteristics, pregnancy, and neonatal risk factors. The significance of a reduced birth-related surge in lymphocyte formation for future immune function and health remains to be investigated.