Abstract Background Pulmonary hypertension complicates the clinical course of extremely preterm infants and is associated with bronchopulmonary dysplasia ( BPD ). However, prevalence, risk factors, and outcome of pulmonary hypertension in these infants are insufficiently known. This systematic review and meta‐analysis aims to provide an up‐to‐date overview of available data on prevalence, risk factors, and outcome of pulmonary hypertension and to identify current knowledge gaps. Methods Medline, EMBASE , and the Cochrane Library databases were searched in July 2017. Two authors reviewed titles/abstracts and full‐texts. Eligible studies reported prevalence, patient characteristics or mortality of infants with/without pulmonary hypertension. Studies were excluded if they did not include extremely preterm infants. Only similar study samples (selected infants with BPD or infants both with/without BPD ) were compared in the meta‐analyses. Results Of 1829 unique articles identified, 25 were eligible for inclusion. Pulmonary hypertension was observed in infants with BPD (20%, 95% confidence interval [CI] 14, 25), but also in those without BPD (2%, 95% CI 0, 8). Infants with severe BPD were most at risk of pulmonary hypertension (risk ratio [RR] 2.7, 95% CI 1.7, 4.2). Infants with pulmonary hypertension were more at risk of mortality (RR 4.7, 95% CI 2.7, 8.3). Conclusions Pulmonary hypertension occurs in particularly in infants with severe BPD , and increases risk of mortality. Due to selected study populations, heterogeneous pulmonary hypertension‐definitions and poorly reported timing of pulmonary hypertension assessments, however, data available in current reports are insufficient to allow accurate assessment of true prevalence, risk factors, and time‐related outcome. Prospective studies, with standardised methodology and follow‐up are needed to determine these factors.
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
Prolonged Frozen Storage of Urine Samples, Jacoline W. Brinkman, Dick de Zeeuw, Jacko J. Duker, Ronald T. Gansevoort, Ido P. Kema, Hans L. Hillege, Paul E. de Jong, and Stephan J.L. Bakker (Departments of 1 Clinical Pharmacology, 2 Internal Medicine, and 3 Pathology and Laboratory Medicine, and the 4 Trial and Coordination Center, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands; * address correspondence to this author at: University of Groningen and University Medical Center Groningen, Department of Internal Medicine, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands; fax 31-50-3639069, e-mail s.j.l.bakker@int.umcg.nl)
Microalbuminuria (MA) is an important early sign of diabetic nephropathy. Hyperfiltration and impaired filtration in relation to albuminuria has been well investigated in diabetic subjects. This study tested the hypothesis that an increased urinary albumin excretion (UAE) is associated with renal functional abnormalities also in nondiabetic subjects. The relation between UAE and creatinine clearances (Ccr) in 7728 nondiabetic subjects was studied. Subjects were divided in four groups according to UAE (mg/24 h): 0 to 15 (control), 15 to 30 (high-normal albuminuria [HNA]), 30 to 300 (MA), >300 (macroalbuminuria). An elevated filtration and a diminished filtration were defined as a Ccr exceeding or below 2x the SD of the control group corrected for age and gender. Ccr followed a parabolic trend, with a higher Ccr in the HNA as compared with control and a lower Ccr in the MA and macroalbuminuria group as compared with HNA. With each increasing UAE level, male sex, age, body mass index, minimal waist circumference, systolic and diastolic BP, plasma glucose, and a positive family history for diabetes all followed a significant linear increasing trend (P < 0.001). After adjustment for age, gender, body mass index, plasma glucose, a positive family history for diabetes, systolic and diastolic BP, antihypertensive medication, and smoking in a multivariate analysis, HNA and MA were independently associated with an elevated filtration (RR 1.8 [95% confidence interval, 1.30 to 2.51] and 1.7 [1.17 to 2. 45]). Macroalbuminuria was independently associated with a diminished filtration (4.3 [range, 1.97 to 9.36]). In conclusion, an elevated UAE might be an important and early sign for progressive renal function loss in a nondiabetic population.
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