Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses' Health Study: A Prospective, Observational Study

Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses' Health Study: A Prospective, Observational Study

From Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.

Abstract

Background: The Heart and Estrogen/progestin Replacement Study (HERS) was the first randomized clinical trial of combined hormone therapy and secondary prevention of coronary events. The trial had overall null results but reported an unexpected increased risk for recurrent events in the initial year, followed by a decrease during the final years.

Objective: To provide additional data on a time trend in risk for recurrent heart disease.

Design: A prospective, observational cohort study of secondary prevention of coronary heart disease.

Setting: Nurses' Health Study.

Patients: 2489 postmenopausal women with previous myocardial infarction or documented atherosclerosis; 213 cases of recurrent nonfatal myocardial infarction or coronary death were identified from 1976 through 1996.

Measurements: Information on hormone status and on recurrent disease was collected by using biennial questionnaires. Multivariable-adjusted relative risks and 95% CIs were calculated from logistic regression models.

Results: A trend of decreasing risk for recurrent major coronary heart disease events with increasing duration of hormone use was observed (P for trend = 0.002). For short-term current users, the multivariate-adjusted relative risk for major coronary heart disease was 1.25 (95% CI, 0.78 to 2.00) compared with never-users. However, after longer-term hormone use, the rate of second events was lower in current users than in never-users (relative risk, 0.38 [CI, 0.22 to 0.66]). No clear differences emerged between users of estrogen alone and users of estrogen combined with progestin. Overall, with up to 20 years of follow-up, the relative risk for a second event among current users of hormone therapy was 0.65 (CI, 0.45 to 0.95) compared with never-users.

Conclusions: The risk for recurrent major coronary events seems to increase among short-term hormone users with previous coronary disease but to decrease with longer-term use.

Article and Author Information

Acknowledgment: The authors thank Drs. Frank Speizer and Graham Colditz for their support.
Grant Support: By grants CA40356 and HL34594 from the National Institutes of Health. Dr. Grodstein is partially supported by grant AG13482 from the National Institute of Aging and a New Scholars Award from the Ellison Medical Foundation.
Requests for Single Reprints: Francine Grodstein, ScD, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115.
Current Author Addresses: Dr. Grodstein: Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115.
Dr. Manson: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215.
Dr. Stampfer: Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115.
Author Contributions: Conception and design: F. Grodstein, J.E. Manson, M.J. Stampfer.
Analysis and interpretation of the data: F. Grodstein, J.E. Manson, M.J. Stampfer.
Drafting of the article: F. Grodstein.
Critical revision of the article for important intellectual content: J.E. Manson, M.J. Stampfer.
Final approval of the article: F. Grodstein, J.E. Manson, M.J. Stampfer.
Statistical expertise: F. Grodstein, M.J. Stampfer.
Obtaining of funding: J.E. Manson.
Administrative, technical, or logistic support: F. Grodstein, J.E. Manson, M.J. Stampfer.
Collection and assembly of data: F. Grodstein, J.E. Manson.