Background-Users of typical antipsychotics have increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice.

In this trans-ethnic multi-omic study we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenome, and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in GWASs of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically-predicted gene expression of 840 genes in 45 tissues, and murine renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Purpose Bleeding complications are a serious adverse effect of medications that prevent abnormal blood clotting. To facilitate epidemiologic investigations of bleeding complications, we developed and validated an automated database case definition for bleeding-related hospitalizations. Methods The case definition utilized information from an in-progress retrospective cohort study of warfarin-related bleeding in Tennessee Medicaid enrollees 30 years of age or older. It identified inpatient stays during the study period of January 1990 through December 2005 with diagnoses and/or procedures that indicated a current episode of bleeding. The definition was validated by medical record review for a sample of 236 hospitalizations. Results We reviewed 186 hospitalizations that had medical records with sufficient information for adjudication. Of these, 165 (89% [95% CI, 83%-92%]) were clinically confirmed bleeding-related hospitalizations. An additional 19 hospitalizations (10% [7%-15%]) were adjudicated as possibly bleeding-related. Of the 165 clinically confirmed bleeding-related hospitalizations, the automated database and clinical definitions had concordant anatomical sites (gastrointestinal, cerebral, genitourinary, other) for 163 (99% [96%-100%]). For those hospitalizations with sufficient information to distinguish between upper/lower gastrointestinal bleeding, the concordance was 89%(76%-96%) for upper gastrointestinal sites and 91%(77%-97%) for lower gastrointestinal sites. Conclusion A case definition for bleeding-related hospitalizations suitable for automated databases had a positive predictive value of between 89% and 99% and could distinguish specific bleeding sites.

Objective. To compare the prevalence and severity of coronary-artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls.Methods. Electron-beam computed tomography was used to measure the extent of coronary-artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronaryartery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary-artery calcification.Results. Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0-358.8) compared with those with early disease (median 0, IQR 0-42.6) and controls (median 0, IQR 0-19.2) (P ‫؍‬ 0.001). Coronary-artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P ‫؍‬ 0.016) The OR for the likelihood of having more severe coronary-artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P ‫؍‬ 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P ‫؍‬ 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P ‫؍‬ 0.05) were associated with more severe coronary-artery calcification after adjustment for age and sex.Conclusion. The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.

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