Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.

Importance: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease. Objective: To identify proteins in the circulation associated with HDPs. Design, Setting, and Participants: Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023. Exposures: Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs). Main Outcomes and Measures: Gestational hypertension and preeclampsia. Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins. Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

Risk Factors, Imaging Findings, and Sex Differences in Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is increasingly being recognized. However, data supporting diagnosis and management are scarce. We analyze a contemporary and comprehensive SCAD registry to advance the understanding of SCAD risk factors, angiographic appearance, and gender differences. This is a retrospective analysis of a prospectively populated database of SCAD patients seen at the Massachusetts General Hospital (MGH) between June 2013 and October 2017. Core laboratory analysis of both coronary angiograms and computerized tomographic (CT) angiography of the extracoronary vessels was performed. Of the 113 patients, 87% were female and mean age was 47 ± 10 years. Traditional cardiovascular risk factors including hypertension, hyperlipidemia, and smoking were present in 27%, 14%, and 22% of patients. Among females, 14%, 8%, and 9% had a history of gestational hypertension, pre-eclampsia, and gestational diabetes, respectively. Fifteen percent had used fertility treatment and 47% of postmenopausal women had used hormone replacement therapy. Angiography showed multivessel SCAD in 42%, severe coronary artery tortuosity in 59%, and extracoronary vascular abnormalities in 100% of patients with complete CT angiographic imaging. Gender differences revealed a self-reported depression and anxiety prevalence of 20% and 32%, respectively, in women compared with 0% in men. Type 1 SCAD was more commonly diagnosed in men than women (71% vs 29%, p <0.01). In conclusion, we highlight under-recognized features of SCAD including (1) relation with pregnancy complications and exposure to hormonal therapy; (2) diffuse, multivessel process in tortuous coronaries on a background of extracoronary arterial abnormalities; and (3) gender differences highlighting the role of mental health as well as potential underdiagnoses in men.

Effect of atrial septal mobility on transcatheter closure of interatrial communications.

BACKGROUND: Transcatheter techniques have evolved as alternatives to surgical closure of interatrial communications due to its less invasive nature and low morbidity. The technique may be limited by the inability to deploy the device and, thus, may be complicated by significant residual shunting. Mobile or redundant septal tissue has been implicated as a possible cause of unsuccessful closure. METHODS: To determine if atrial septal hypermobility precludes successful transcatheter device closure of interatrial communications, 69 patients (mean age 46.4 +/- 17.5 years [male:female ratio 34:35]) with periprocedural transesophageal echocardiograms were reviewed. Septal excursion was defined as the maximal transit of the interatrial septum between either side of the plane connecting the superior and inferior attachment points. Unsuccessful closure was defined as subsequent cardiac surgery to close the defect, inability to deploy the device, recurrent attempts at closure, device malalignment, residual shunting greater than mild in degree on follow-up transthoracic study, and procedural complications. RESULTS: Reasons for closure were the following: embolic events (n = 48); platypnea/orthodeoxia (n = 15); atrial septal defect with right ventricular dilatation and paroxysmal atrial tachycardia (n = 2); atrial septal defect (n = 3); and prophylactic patent foramen ovale closure in a scuba diver (n = 1). Successful closure occurred in 76% of patients (n = 53). Compared with those patients with successful transcatheter closure, the mean septal excursion in patients with failed closure was 0.66 +/- 0.56 cm versus 0.76 +/- 0.47 cm (P = not significant [NS]). CONCLUSION: Our results do not support the concern that exaggerated septal mobility compromises successful device closure of interatrial communications.

Mitral valve replacement for restenosis after repeat percutaneous mitral valvuloplasty.

Percutaneous mitral valvuloplasty (PMV) produces good results for symptomatic mitral stenosis or restenosis if valve morphology is suitable. However, complications such as atrial septal defect have severe hemodynamic effects, and repeat PMV is not always appropriate. The patient in this case had already undergone multiple PMVs and was a candidate for valve replacement.