Citations

Introduction: Higher body mass index (BMI) is an independent risk factor for incident atrial fibrillation (AF). However, its impact on management strategies and clinical outcomes among patients with prevalent AF is unclear. Methods: The study cohort included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry from June 2010 through August 2011. Participants with BMI > 18.5 kg/m2 were stratified into normal (18.5 - 25 kg/m2), overweight (25 - 30 kg/m2), Class I obese (30 - 35 kg/m2), Class II obese (35 - 40 kg/m2), and Class III obese (>40 kg/m2) categories. Unadjusted and adjusted Cox frailty models were constructed to assess the categorical and continuous association of BMI with AF progression, mortality, and incidence of thromboembolic events. Results: We evaluated 9,606 patients with AF (mean age: 74 + 11 years; 42% women) from 174 US ORBIT participating practices. Patients in the higher BMI categories were younger and had a higher prevalence of comorbidities such as diabetes, hypertension, and obstructive sleep apnea. AF symptom burden was greatest among patients in extreme BMI categories. Proportional use of anticoagulation, antiarrhythmic drugs, and invasive rhythm control strategies was significantly greater among patients in higher BMI categories. Rates for mortality and stroke/non-CNS embolism decreased in a near linear fashion across successively higher BMI categories (P<0.001; Table). After multivariable adjustment, higher BMI categories were associated with lower risk for mortality (p = 0.0002), with the lowest risk observed among overweight patients [Hazard Ratio (HR) (95% CI): 0.65 (0.54 - 0.79) ref. group: normal weight]. For every 5-kg/m2 increase in BMI, the odds of risk-adjusted mortality were 6% lower [HR (95% CI): 0.94 (0.89 - 0.98)]. In contrast, the association between BMI and risk for stroke/non-CNS embolism was significant on unadjusted analysis (P <0.001) but attenuated after adjustment for risk factors (P = 0.78; Table). No significant association was observed between BMI and AF progression rates in either unadjusted (P = 0.35) or adjusted analyses (P = 0.17). Conclusion: Among patients with AF, higher BMI was associated with a greater use of anticoagulation, rhythm control strategies, and lower mortality risk.

Abstract Coronary artery disease (CAD) is a leading cause of death, yet its genetic determinants are not fully elucidated. We report a multi-ethnic genome-wide association study of CAD involving nearly a quarter of a million cases, incorporating the largest cohorts to date of Whites, Blacks, and Hispanics from the Million Veteran Program with existing studies including CARDIoGRAMplusC4D, UK Biobank, and Biobank Japan. We verify substantial and nearly equivalent heritability of CAD across multiple ancestral groups, discover 107 novel loci including the first nine on the X-chromosome, identify the first eight genome-wide significant loci among Blacks and Hispanics, and demonstrate that two common haplotypes are largely responsible for the risk stratification at the well-known 9p21 locus in most populations except those of African origin where both haplotypes are virtually absent. We identify 15 loci for angiographically derived burden of coronary atherosclerosis, which robustly overlap with the strongest and earliest loci reported to date for clinical CAD. Phenome-wide association analyses of novel loci and externally validated polygenic risk scores (PRS) augment signals from the insulin resistance cluster of risk factors and consequences, extend previously established pleiotropic associations of loci with traditional risk factors to include smoking and family history, and confirm a substantially reduced transferability of existing PRS to Blacks. Downstream integrative genomic analyses reinforce the critical role of endothelial, fibroblast, and smooth muscle cells within the coronary vessel wall in CAD susceptibility. Our study highlights the value of a multi-ethnic design in efficiently characterizing the genetic architecture of CAD across all human populations.

Abstract Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face‐to‐face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference.