Abstract

This application represents a competing continuation of a project originally designed to assess whether calcium-channel blockers, given as anti-hypertensive therapy to patients with hypertension, increase the risk of myocardial infarction (MI). Based on the results of the secondary-prevention clinical trials, the study hypothesized an adverse effect. In the study, calcium-channel blockers were associated with a 57% increased risk of myocardial infarction in patients with high blood pressure (relative risk [RR] = 1.57, 95% confidence interval [CI] = 1.21 - 2.04). Pilot-study data also suggest an adverse effect of calcium-channel blockers on the outcome of stroke (RR = 2.56, 95% CI = 0.88-7.49). In this competing continuation, it is proposed to determine: 1) whether calcium-channel blockers increase the risk of stroke among hypertensive patients; and 2) whether individual calcium-channel blocking agents representing the three major subclasses increase the risks of MI and of the combined endpoint of MI and stroke in patients with high blood pressure. The setting is Group Health Cooperative (GHC). The investigators will use the GHC computerized files to identify all treated hypertensive patients, aged 30 to 79 yrs., with incident MI or stroke during July 1989-Dec 1998. Population-based controls with treated hypertension will be sampled from the GHC enrollment files. Data collection will include review of the ambulatory medical record and telephone interviews of consenting cases and controls (or proxies). The GHC computerized pharmacy records will serve as the primary source of information about the use of calcium-channel blockers. Frequency matching will control for the potential confounding effects of age, gender and year of presentation, and data analysis will involve restriction, stratification, and logistic regression. This study will have 80% power to detect a relative risk of 1.66 for the association between stroke and calcium- channel blockers. For individual calcium-channel blocking agents, the study will have 74-94% power to detect RRs in the range of 1.4-1.5 for MI and 72-91% power to detect RRs in the range of 1.3-1.4 for the combined endpoint of MI plus stroke.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043201-06
Application #
2430683
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1991-09-30
Project End
2000-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

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
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
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
Harrington, Laura B; Weiss, Noel S; Wiggins, Kerri L et al. (2016) Prior hysterectomy and oophorectomy and incident venous thrombosis risk among postmenopausal women: a population-based, case-control study. Menopause 23:143-9
Harrington, Laura B; Wiggins, Kerri L; Sitlani, Colleen M et al. (2016) The association of F11 genetic variants with the risk of incident venous thrombosis among women, by statin use. Thromb Haemost 115:682-4
Germain, Marine; Chasman, Daniel I; de Haan, Hugoline et al. (2015) Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. Am J Hum Genet 96:532-42
Smith, Nicholas L; Blondon, Marc; Wiggins, Kerri L et al. (2014) Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med 174:25-31
Blondon, M; van Hylckama Vlieg, A; Wiggins, K L et al. (2014) Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers. J Thromb Haemost 12:879-86

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