Reproductive Risk Factors and Coronary Heart Disease in the Women's Health Initiative Observational Study

Nisha I Parikh; Rebecca P Jeppson; Jeffrey S Berger; Charles B Eaton; Candyce H Kroenke; Erin S LeBlanc; Cora E Lewis; Eric B Loucks; Donna R Parker; Eileen Rillamas-Sun; Kelli K Ryckman; Molly E Waring; Robert S Schenken; Karen C Johnson; Anna-Karin Edstedt-Bonamy; Matthew A Allison; Barbara V Howard

doi:10.1161/CIRCULATIONAHA.115.017854

Reproductive Risk Factors and Coronary Heart Disease in the Women's Health Initiative Observational Study

Circulation. 2016 May 31;133(22):2149-58. doi: 10.1161/CIRCULATIONAHA.115.017854. Epub 2016 Apr 19.

Authors

Nisha I Parikh¹, Rebecca P Jeppson², Jeffrey S Berger², Charles B Eaton², Candyce H Kroenke², Erin S LeBlanc², Cora E Lewis², Eric B Loucks², Donna R Parker², Eileen Rillamas-Sun², Kelli K Ryckman², Molly E Waring², Robert S Schenken², Karen C Johnson², Anna-Karin Edstedt-Bonamy², Matthew A Allison², Barbara V Howard²

Affiliations

¹ From Division of Cardiology, University of California San Francisco (N.I.P.); Fred Hutchinson Cancer Research Center, Seattle, WA (R.P.J., K.K.R.); Cardiology, Hematology, Vascular Surgery, NYU School of Medicine, New York (J.S.B.); Departments of Family Medicine and Epidemiology, Brown University, Providence, RI (C.B.E., D.R.P.); Kaiser Permanente Division of Research, Oakland, CA (C.H.K.); Kaiser Permanente Center for Health Research, Portland, OR (E.S.L.); University of Alabama at Birmingham (C.E.L.); Department of Epidemiology, Brown University School of Public Health, Providence, RI (E.B.L.); Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket (D.R.P.); Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (E.R.-S.); Division of Epidemiology of Chronic Diseases and Vulnerable Populations, Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester (M.E.W.); Department of Obstetrics and Gynecology, The University of Texas Health Science Center, San Antonio (R.S.S.); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (K.C.J.); Unit for Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden (A.-K.E.-B.); Department of Family Medicine, USCD, La Jolla, CA (M.A.A.); MedStar Health Research Institute, Hyattsville, MD (B.V.H.); and Georgetown University Center for Clinical and Translational Science, Washington, DC (B.V.H.). parikh.nisha@gmail.com.
² From Division of Cardiology, University of California San Francisco (N.I.P.); Fred Hutchinson Cancer Research Center, Seattle, WA (R.P.J., K.K.R.); Cardiology, Hematology, Vascular Surgery, NYU School of Medicine, New York (J.S.B.); Departments of Family Medicine and Epidemiology, Brown University, Providence, RI (C.B.E., D.R.P.); Kaiser Permanente Division of Research, Oakland, CA (C.H.K.); Kaiser Permanente Center for Health Research, Portland, OR (E.S.L.); University of Alabama at Birmingham (C.E.L.); Department of Epidemiology, Brown University School of Public Health, Providence, RI (E.B.L.); Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket (D.R.P.); Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (E.R.-S.); Division of Epidemiology of Chronic Diseases and Vulnerable Populations, Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester (M.E.W.); Department of Obstetrics and Gynecology, The University of Texas Health Science Center, San Antonio (R.S.S.); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (K.C.J.); Unit for Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden (A.-K.E.-B.); Department of Family Medicine, USCD, La Jolla, CA (M.A.A.); MedStar Health Research Institute, Hyattsville, MD (B.V.H.); and Georgetown University Center for Clinical and Translational Science, Washington, DC (B.V.H.).

Abstract

Background: Reproductive factors provide an early window into a woman's coronary heart disease (CHD) risk; however, their contribution to CHD risk stratification is uncertain.

Methods and results: In the Women's Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C statistic, net reclassification index (or net reclassification index with risk categories of <5%, 5 to <10%, and ≥10% 10-year risk of CHD), and integrated discriminatory index were assessed. Among 72 982 women (CHD events, n=4607; median follow-up,12.0 [interquartile range, 8.3-13.7] years; mean [standard deviation] age, 63.2 [7.2] years), an age-adjusted reproductive risk factor model had a C statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C statistic increased from 0.726 to 0.730; integrated discriminatory index, 0.0013; P<0.0001). Net reclassification for women with events was not improved (net reclassification index events, 0.007; P=0.18); and, for women without events, net reclassification was marginally improved (net reclassification index nonevents, 0.002; P=0.04) CONCLUSIONS: Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination, and do not materially improve net reclassification.

Keywords: coronary disease; reproductive history; risk adjustment; spontaneous abortion; women.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Coronary Artery Disease / diagnosis*
Coronary Artery Disease / epidemiology*
Female
Humans
Longitudinal Studies
Middle Aged
Pregnancy
Pregnancy Rate* / trends
Reproduction*
Risk Factors
Women's Health*
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding