RESUMEN
A fair number of epidemiological studies suggest that age at menarche (AAM) is associated with depression, but the reported effect sizes are small, and there is evidence of residual confounding. Moreover, previous Mendelian randomization (MR) studies to avoid inferential problems inherent to epidemiological studies have provided mixed findings. To clarify the causal relationship between age at menarche and broadly defined depression risk, we used 360 genome-wide significantly AAM-related single-nucleotide polymorphisms (SNPs) as instrumental variable and data from the latest GWAS for the broadly defined depression risk on 807,553 individuals (246,363 cases and 561,190 controls). Multiple methods to account for heterogeneity of the instrumental variable (penalized weighted median, MR Lasso, and contamination mixture method), systematic and idiosyncratic pleiotropy (MR RAPS), and horizontal pleiotropy (MR PRESSO and multivariable MR using three methods) were used. Body mass index, education attainment, and total white blood count were considered pleiotropic phenotypes in the multivariable MR analysis. In the univariable [inverse-variance weighted (IVW): OR = 0.96, 95% confidence interval = 0.94-0.98, p = 0.0003] and multivariable MR analysis (IVW: OR = 0.96, 95% confidence interval = 0.94-0.99, p = 0.007), there was a significant causal effect of AAM on depression risk. Thus, the present study supports conclusions from previous epidemiological studies implicating AAM in depression without the pitfalls of residual confounding and reverse causation. Considering the adverse consequences of an earlier AAM on mental health, this finding should foster efforts to address risk factors that promote an earlier AAM.
RESUMEN
BACKGROUND: Recent studies identified total atrial conduction time (TACT) as an independent and powerful predictor of new-onset atrial fibrillation (AF). The purpose of this study was to assess the association between the degree of atrial fibrosis, TACT, and frequency of postoperative atrial fibrillation (POAF) among patients undergoing cardiac surgery. METHODS AND RESULTS: Sixty patients in sinus rhythm (mean ± SD age 66 ± 10 years; 22% women) and without a history of AF undergoing cardiac surgery were prospectively enrolled. TACT was measured preoperatively in the left atrium by tissue-Doppler Imaging (PA-TDI interval). Holter-ECG/telemetry was used to screen for POAF throughout 10 days after cardiac surgery. Right atrial appendages (RAA) were obtained in 33 patients during surgery; atrial fibrosis was assessed by visual quantification (% area of positive van Gieson elastic staining). POAF occurred in 23 patients (38%). Fibrosis extent of RAA was higher in patients with POAF as compared to those without (27.5 ± 1.93 vs 15.8 ± 0.81% area; mean ± SEM; P < 0.001). PA-TDI interval was longer in patients with POAF versus patients who maintained in sinus rhythm (152.1 ± 3.0 vs 120.8 ± 1.8 milliseconds; P < 0.001) and correlated with the degree of atrial fibrosis (r = 0.73; P < 0.01). At the cut-off value of 133 milliseconds, TACT sensitivity and specificity related to POAF were 100% and 86%, respectively. CONCLUSION: PA-TDI interval is useful to identify patients at risk for POAF undergoing cardiac surgery and correlates with the degree of atrial fibrosis.