Objectives The goal of this study was to systematically review the peripartum cardiomyopathy (PPCM) literature and determine the prevalence of preeclampsia (PE) in women with PPCM. Secondary analyses included evaluation of the prevalence of hypertensive disorders, multiple gestations, and multiparity. Background PPCM is a significant cause of maternal and infant morbidity and mortality worldwide, yet its etiology remains unknown. PE is often cited as a risk factor for the development of PPCM, and recent research suggests that PE and PPCM share mechanisms that contribute to their pathobiology. No comprehensive evaluation of the relationship between PE and PPCM exists. Methods A systematic predetermined search strategy was performed in multiple databases to identify studies describing ≥3 women with PPCM. Prevalence rates of PE, hypertension, multiple gestations, and multiparity were pooled. Results Data from 22 studies (979 patients) were included in this analysis. The pooled prevalence of 22% (95% confidence interval [CI] 16 to 28) was more than quadruple the 5% average worldwide background rate of PE in pregnancy (p < 0.001). There were no geographic or racial differences detected in the prevalence of PE in women with PPCM. The rates of hypertension during pregnancy (37% [95% CI 29 to 45) and multiple gestations (9% [95% CI 7 to 11]) were also elevated. Conclusions The prevalence of PE, hypertensive disorders, and multiple gestations in women with PPCM is markedly higher than that in the general population. These findings support the concept of a shared pathogenesis between PE and PPCM and highlight the need for awareness of the overlap between these 2 diseases.

Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.

Background--Obesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comparisons of the associations of obesity with each of these CVD subtypes, particularly regarding the extent to which they are unexplained by traditional CVD mediators.Methods and Results--We followed 13 730 participants in the Atherosclerosis Risk in Communities (ARIC) study who had a body mass index ≥18.5 and no CVD at baseline (visit 1, 1987-1989). We compared the association of higher body mass index with incident HF, CHD, and stroke before and after adjusting for traditional CVD mediators (including systolic blood pressure, diabetes mellitus, and lipid measures). Over a median follow-up of 23 years, there were 2235 HF events, 1653 CHD events, and 986 strokes. After adjustment for demographics, smoking, physical activity, and alcohol intake, higher body mass index had the strongest association with incident HF among CVD subtypes, with hazard ratios for severe obesity (body mass index ≥35 versus normal weight) of 3.74 (95% CI 3.24-4.31) for HF, 2.00 (95% CI 1.67-2.40) for CHD, and 1.75 (95% CI 1.40-2.20) for stroke (P<0.0001 for comparisons of HF versus CHD or stroke). Further adjustment for traditional mediators fully explained the association of higher body mass index with CHD and stroke but not with HF (hazard ratio 2.27, 95% CI 1.94-2.64).Conclusions--The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors. Weight management is likely critical for optimal HF prevention, and nontraditional pathways linking obesity to HF need to be elucidated. ( J Am Heart Assoc. 2016;5:e003921 doi: 10.1161/JAHA.116.003921) Key Words: coronary heart disease • epidemiology • heart failure • obesity • stroke O besity is a common risk factor for several subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, and heart failure (HF) [1][2][3][4] ; however, increasing evidence suggests that obesity leads to various subtypes of CVD through multiple distinct pathways. Some traditional risk factors, including hypertension, diabetes mellitus, and dyslipidemia, are established as mediators between obesity and atherosclerotic vascular disease. Although weight management is a fundamental component of CVD prevention, the majority of persons with obesity in the general population do not achieve sufficient and sustained weight loss. [5][6][7][8] Consequently, there is great emphasis on controlling the traditional CVD risk factors resulting from obesity as a strategy for reducing cardiovascular risk. Nevertheless, uniform approaches to the control of cardiovascular risk factors may not have the same impact on the likelihood of developing different subtypes of CVD. In this context, data conflict regarding whether the relationships of obesity with CHD and stroke are independent of established CVD mediators. Several prospective studies [9]...

Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder. During development, ureters migrate by an unknown mechanism from their initial integration site in the Wolffian ducts up to the base of the bladder in a process that we call ureter maturation. Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret. Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-) mutant mice are probably caused by a failure of this process. Our studies indicate that formation of the trigonal wedge may be essential for correct insertion of the distal ureters into the bladder, and that these events are mediated by the vitamin A and Ret signaling pathways.