The goal of this research is to assess the safety of commonly used medications in relation to the risk of incident atrial fibrillation (AF), and to assess the association of several genetic polymorphisms with stroke risk after AF onset. Several lines of evidence suggest that both beta-blockers and ACE inhibitors may prevent or inhibit the atrial electrical remodeling that allows AF to become established and maintained. Withdrawal of these medications may be associated with increased risk of AF in individuals at risk. Genetic polymorphisms that promote thrombosis are associated with an increased risk of venous thrombosis, and in some studies, with arterial thrombosis including stroke or myocardial infarction. Although several recently published trials indicate that warfarin or aspirin treatment of patients with AF decreases the risk of stroke, little is known about the risk of stroke as a complication of AF in relation to genetic variants that affect clotting. ? ? The proposed project will build on successful population-based studies of myocardial infarction and stroke at Group Health Cooperative (GHC), a large non-profit health maintenance organization. Detailed information from the GHC computerized pharmacy database on the timing of medication use among approximately 1500 incident AF cases and 1750 controls with medically treated hypertension will permit us to assess the risk of incident AF associated with the use or recent stopping of beta-blockers or ACE inhibitors. This project will collect DNA samples on a population-based inception cohort of approximately 855 AF patients, and will examine the risk of stroke in relation to genetic variants known to affect coagulation. ? ? The main tasks of the proposed project are: 1) identification of cases with incident AF and controls; 2) review of outpatient and inpatient medical records to assess eligibility and collect information on risk factors and medical history; 3) classification of medication use over time; 4) for AF patients, telephone interview and collection of blood samples; 5) blood specimen processing, DNA extraction, and genotyping; and 6) data analysis of the associations of medication use and genotype with AF onset and stroke complications. This project will contribute important information about drug safety and will incorporate advances in molecular biology to study AF and its complications, problems of considerable public health importance in the elderly.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL068986-03
Application #
6761909
Study Section
Special Emphasis Panel (ZRG1-SNEM-5 (02))
Program Officer
Jaquish, Cashell E
Project Start
2002-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$589,677
Indirect Cost
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Choi, Seung Hoan; Weng, Lu-Chen; Roselli, Carolina et al. (2018) Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation. JAMA 320:2354-2364
Prins, Bram P; Mead, Timothy J; Brody, Jennifer A et al. (2018) Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6. Genome Biol 19:87
Lindström, Sara; Germain, Marine; Crous-Bou, Marta et al. (2017) Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet 136:897-902
Ehlert, Alexa N; Heckbert, Susan R; Wiggins, Kerri L et al. (2017) Administrative billing codes accurately identified occurrence of electrical cardioversion and ablation/maze procedures in a prospective cohort study of atrial fibrillation patients. Clin Cardiol 40:1227-1230
Maloney, James P; Branchford, Brian R; Brodsky, Gary L et al. (2017) The ENTPD1 promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk. FASEB J 31:2771-2784
Harrington, L B; Marck, B T; Wiggins, K L et al. (2017) Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women. J Thromb Haemost 15:80-90
Postmus, Iris; Warren, Helen R; Trompet, Stella et al. (2016) Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. J Med Genet 53:835-845
Jensen, Richard A; Sim, Xueling; Smith, Albert Vernon et al. (2016) Novel Genetic Loci Associated With Retinal Microvascular Diameter. Circ Cardiovasc Genet 9:45-54
Smith, N L; Harrington, L B; Blondon, M et al. (2016) The association of statin therapy with the risk of recurrent venous thrombosis. J Thromb Haemost 14:1384-92
Floyd, James S; Wiggins, Kerri L; Christiansen, Mark et al. (2016) Case-control study of oral glucose-lowering drugs in combination with long-acting insulin and the risks of incident myocardial infarction and incident stroke. Pharmacoepidemiol Drug Saf 25:151-60

Showing the most recent 10 out of 79 publications