ImportanceHypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias.ObjectiveTo investigate the association of HDPs with multiple cardiovascular diseases.Design, Setting, and ParticipantsA genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release).ExposuresUncorrelated (r2<0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia.Main Outcomes and MeasuresGenetic association estimates for outcomes were extracted from genome-wide association studies of 122 733 cases for coronary artery disease, 34 217 cases for ischemic stroke, 47 309 cases for heart failure, and 60 620 cases for atrial fibrillation.ResultsGenetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio [OR], 1.24; 95% CI, 1.08-1.43; P = .002); this association was evident for both gestational hypertension (OR, 1.08; 95% CI, 1.00-1.17; P = .04) and preeclampsia/eclampsia (OR, 1.06; 95% CI, 1.01-1.12; P = .03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27; 95% CI, 1.12-1.44; P = 2.87 × 10−4). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24; direct effect OR, 1.10; 95% CI, 1.02-1.08; P = .02) and type 2 diabetes (total effect OR, 1.24; direct effect OR, 1.16; 95% CI, 1.04-1.29; P = .008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97; 95% CI, 0.76-1.23; P = .79) or atrial fibrillation (OR, 1.11; 95% CI, 0.65-1.88; P = .71).Conclusions and RelevanceThe findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease.

Gynecomastia is defined as a palpable enlargement of the male breast, secondary to an increase in the glandular and stromal breast tissue. Gynecomastia is encountered in up to 80% of Klinefelter syndrome cases. The pathophysiology involves testosterone/estrogen imbalance. This review article will further explore the pathophysiology of gynecomastia along with the different lines of management.

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Background Hypertensive disorders in pregnancy are major causes of maternal and foetal morbidity and have also been associated with long-term maternal risk of cardiovascular diseases. Whilst many retrospective and prospective cohort studies have explored this relationship, it is difficult to make causal inferences from observational studies due to potential residual confounding and bias. Leveraging genetic data predisposing to exposures and outcomes in instrumental variable analysis, Mendelian randomisation (MR) can provide valuable information for causal inference. The aim of this study is to use MR to investigate the relationship between hypertensive disorders in pregnancy and cardiovascular diseases. Methods Uncorrelated single nucleotide polymorphisms (SNPs) were selected as instrumental variables from the FinnGen consortium summary statistics for the exposures of any hypertensive disorder in pregnancy, and its two subgroups of gestational hypertension, and pre-eclampsia or eclampsia. Genetic association estimates for outcomes were extracted from GWAS studies of 122,733 for coronary artery disease, 34,217 cases for ischaemic stroke, 47,309 cases for heart failure and 60,620 cases for atrial fibrillation. All studies included patients predominantly of European ancestry. Primary analysis was conducted using inverse-variance weighted MR. Results Hypertensive disorders in pregnancy were associated with increased risk of coronary artery disease (odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08–1.43; p=0.002); and this association was evident for both gestational hypertension (OR= 1.08; 95% CI: 1.00–1.17; p=0.040) and pre- or eclampsia (OR=1.06; 95% CI: 1.01–1.12; p=0.030). Hypertensive disorders in pregnancy were also associated with increased risk of ischaemic stroke (OR=1.27; 95% CI: 1.12–1.44; p=2.87x10–4). Neither gestational hypertension nor pre-eclampsia were independently associated with increased risk of ischaemic stroke, though effect estimates were consistent in direction. No associations were noted between the three hypertensive disorders in pregnancy and the outcomes of heart failure or atrial fibrillation. Conclusions Our findings provide genetic evidence that supports a likely causal association between hypertension in pregnancy and increased risk of coronary artery disease and stroke. This is consistent with observational evidence and supports the classification of hypertensive disorders in pregnancy as risk factors for cardiovascular disease. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council GEPSI 946647 for EAWSBritish Heart Foundation RG/16/3/32175 for FSN