Abstract 15005: Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank

Introduction: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We sought to characterize the association between alcohol intake and incident AF and determine whether the effect of alcohol is modified by inherited predisposition to AF. Methods: We analyzed UK Biobank participants without prevalent AF and with complete alcohol consumption, genomic, and clinical data collected between 2006-2010. Exposures included alcohol consumption (stratified by an acceptable range of ≤98 grams/week for women or ≤196 grams/week for men and analyzed as a continuous variable) and an AF polygenic risk score (PRS). Cox proportional hazard models were adjusted for established AF risk factors. The cumulative incidence of AF was assessed at 5 years. Results: Among 376,776 participants (47.5% male, mean age 56.9 years), 6,293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio [HR] 1.10; 95% CI 1.05-1.16 for intake above an acceptable range; HR 1.04 per 100 grams/week; 95% CI 1.02-1.06). An AF PRS was associated with AF (HR 1.38 per standard deviation [SD]; 95% CI 1.35-1.41). In models including both alcohol intake and the AF PRS, each remained associated with AF. The 5-year cumulative incidence of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI 2.07-2.59), compared to 0.69% (95% CI 0.58-0.80) for those with alcohol intake within acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with risk of incident AF across a range of polygenic predisposition to AF. Preventive counseling regarding alcohol intake may reduce the risk of AF regardless of the degree of risk conferred by inherited predisposition.

А. Cramer. Pathologisch-anatomischer Befund in einem acutem Fall der Paranoiagruppe. (Archiv fur Psychiatric . Bd. 29, Heft. 1. pg. 1—24)

The author describes a case of acute hallucinatory insanity that developed 10 days after the fall from the horse (and there were no direct consequences) and after repeated excesses in potu. The patient, a completely healthy 24-year-old man, without an inherited predisposition, died a week after the illness.

Ernst Beyer. Ueber eine Form der acuten Verworrenheit im klimakterischen Alter. (Archiv f. Psych. Bd. 29. Heft. pg. 182—210)

On the basis of seven observations, the author describes a form of acute illusionary insanity, which deserves a special name, because it develops after a prolonged depressive period, without any depleting reasons for the body, in the absence of an inherited predisposition during Climacterium.

SSRIs as Risk Reduction for Cardiovascular Disease in Patients with Schizophrenia

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A systematic review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, LDL and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, further studies are needed to establish the impact of SSRIs on CV risk in SCZ.

Population Screening for Inherited Predisposition to Breast and Ovarian Cancer

The discovery of genes underlying inherited predisposition to breast and ovarian cancer has revolutionized the ability to identify women at high risk for these diseases before they become affected. Women who are carriers of deleterious variants in these genes can undertake surveillance and prevention measures that have been shown to reduce morbidity and mortality. However, under current strategies, the vast majority of women carriers remain undetected until they become affected. In this review, we show that universal testing, particularly of the BRCA1 and BRCA2 genes, fulfills classical disease screening criteria. This is especially true for BRCA1 and BRCA2 in Ashkenazi Jews but is translatable to all populations and may include additional genes. Utilizing genetic information for large-scale precision prevention requires a paradigmatic shift in health-care delivery. To address this need, we propose a direct-to-patient model, which is increasingly pertinent for fulfilling the promise of utilizing personal genomic information for disease prevention.