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

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

Journal article

Open access

Peer reviewed

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, …

Circulation (New York, N.Y.), Vol.133(22), pp.2149-2158

05/31/2016

DOI: 10.1161/CIRCULATIONAHA.115.017854

PMCID: PMC4889516

PMID: 27143682

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Abstract

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

Pregnancy

Reproduction

Women's Health

Humans

Middle Aged

Risk Factors

Young Adult

Coronary Artery Disease - diagnosis

Adult

Female

Aged

Coronary Artery Disease - epidemiology

Longitudinal Studies

Pregnancy Rate - trends

Details

Title: Subtitle: Reproductive Risk Factors and Coronary Heart Disease in the Women's Health Initiative Observational Study
Creators: Nisha I Parikh - University of California San Francisco Medical Center
Rebecca P Jeppson - Fred Hutch Cancer Center
Jeffrey S Berger - New York University School of Medicine
Charles B Eaton - Brown University
Candyce H Kroenke - Kaiser Permanente Division of Research
Erin S LeBlanc - Kaiser Permanente Center for Health Research
Cora E Lewis - University of Alabama at Birmingham
Eric B Loucks - Brown University
Donna R Parker - Brown University
Eileen Rillamas-Sun - University of Iowa
Kelli K Ryckman - Fred Hutch Cancer Center
Molly E Waring - University of Massachusetts Chan Medical School
Robert S Schenken - The University of Texas Health Science Center at San Antonio
Karen C Johnson - University of Tennessee Health Science Center
Anna-Karin Edstedt-Bonamy - Karolinska Institutet
Matthew A Allison - University of California San Diego
Barbara V Howard - Georgetown University
Resource Type: Journal article
Publication Details: Circulation (New York, N.Y.), Vol.133(22), pp.2149-2158
DOI: 10.1161/CIRCULATIONAHA.115.017854
PMID: 27143682
PMCID: PMC4889516
NLM abbreviation: Circulation
ISSN: 0009-7322
eISSN: 1524-4539
Publisher: Lippincott Williams & Wilkins; United States
Grant note: HHSN268201100002I / NHLBI NIH HHS UL1 TR001453 / NCATS NIH HHS HHSN268201100001C / WHI NIH HHS HHSN268201100004I / NHLBI NIH HHS U54 MD007584 / NIMHD NIH HHS L30 HL097670 / NHLBI NIH HHS HHSN268201100004C / WHI NIH HHS HHSN268201100046C / NHLBI NIH HHS American Heart Association-American Stroke Association P30 DK079626 / NIDDK NIH HHS HHSN268201100002C / WHI NIH HHS KL2 TR000160 / NCATS NIH HHS HHSN268201100001I / NHLBI NIH HHS UL1 TR001409 / NCATS NIH HHS U01 HL105268 / NHLBI NIH HHS HHSN268201100003C / WHI NIH HHS R21 HL115398 / NHLBI NIH HHS
Language: English
Date published: 05/31/2016
Academic Unit: Stead Family Department of Pediatrics; Epidemiology
Record Identifier: 9983995134502771

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