Abstract | CONTEXT: OBJECTIVES: DESIGN, SETTING, AND PARTICIPANTS: Population-based case-control study of patients enrolled in a health maintenance organization, treated pharmacologically for hypertension, and genotyped as homozygous carriers of the adducin wild-type genotype or carriers of 1 or 2 copies of the Trp460 variant allele. Cases had a first nonfatal MI (n = 206) or stroke (n = 117) between January 1995 and December 1998. Controls (n = 715) were a stratified random sample of pharmacologically treated hypertensive patients who were matched to MI cases by age, sex, and calendar year. MAIN OUTCOME MEASURE: Risk of the combined outcome of first nonfatal MI or stroke. RESULTS: The adducin variant was present in more than one third of the participants. Among the 653 carriers of the adducin wild-type genotype, diuretic therapy was not associated with the risk of MI or stroke (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.78-1.52). Among the 385 carriers of the adducin variant allele, diuretic therapy was associated with a lower risk of the combined outcome of MI and stroke than other antihypertensive therapies (OR, 0.49; 95% CI, 0.32-0.77). The OR in carriers of the adducin variant was less than half of the OR in carriers of the wild-type genotype (P =.005). The case-control synergy index (SI) was 0.45 (95% CI, 0.26-0.79) for the combined outcome of MI and stroke. The point estimates of the diuretic- adducin interaction were similar in separate analyses of MI (SI, 0.41; 95% CI, 0.21-0.80) and stroke (SI, 0.53; 95% CI, 0.24-1.19). The diuretic- adducin interaction was not confounded by traditional cardiovascular risk factors, was specific to diuretic therapy but not present for other major antihypertensive drug classes, and did not differ substantially between subgroups defined by age, sex, race, diabetes, and history of cardiovascular disease. CONCLUSIONS:
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Authors | Bruce M Psaty, Nicholas L Smith, Susan R Heckbert, Hans L Vos, Rozenn N Lemaitre, Alexander P Reiner, David S Siscovick, Joshua Bis, Thomas Lumley, W T Longstreth Jr, Frits R Rosendaal |
Journal | JAMA
(JAMA)
Vol. 287
Issue 13
Pg. 1680-9
(Apr 03 2002)
ISSN: 0098-7484 [Print] United States |
PMID | 11926892
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antihypertensive Agents
- Calmodulin-Binding Proteins
- Diuretics
- adducin
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Topics |
- Aged
- Antihypertensive Agents
(therapeutic use)
- Calmodulin-Binding Proteins
(genetics)
- Case-Control Studies
- Diuretics
(therapeutic use)
- Female
- Genotype
- Humans
- Hypertension
(drug therapy, genetics)
- Male
- Middle Aged
- Myocardial Infarction
(epidemiology)
- Risk
- Stroke
(epidemiology)
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