Author + information
- Received September 5, 2019
- Accepted September 9, 2019
- Published online November 25, 2019.
- Michael C. Honigberg, MD, MPPa,b,c,
- Seyedeh Maryam Zekavat, BSc,d,
- Krishna Aragam, MD, MSa,b,c,
- Derek Klarin, MDb,e,
- Deepak L. Bhatt, MD, MPHf,
- Nandita S. Scott, MDa,
- Gina M. Peloso, PhDg and
- Pradeep Natarajan, MD, MMSca,b,c,∗ (, )@pnatarajanmd
- aCardiology Division and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
- cCardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
- dYale University School of Medicine, New Haven, Connecticut
- eDepartment of Surgery, Massachusetts General Hospital, Boston, Massachusetts
- fCardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- gDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Pradeep Natarajan, Massachusetts General Hospital, 185 Cambridge Street, CPZN 3.184, Boston, Massachusetts 02114.
Background History of a hypertensive disorder of pregnancy (HDP) among women may be useful to refine atherosclerotic cardiovascular disease risk assessments. However, future risk of diverse cardiovascular conditions in asymptomatic middle-aged women with prior HDP remains unknown.
Objectives The purpose of this study was to examine the long-term incidence of diverse cardiovascular conditions among middle-aged women with and without prior HDP.
Methods Women in the prospective, observational UK Biobank age 40 to 69 years who reported ≥1 live birth were included. Noninvasive arterial stiffness measurement was performed in a subset of women. Cox models were fitted to associate HDP with incident cardiovascular diseases. Causal mediation analyses estimated the contribution of conventional risk factors to observed associations.
Results Of 220,024 women included, 2,808 (1.3%) had prior HDP. The mean age at baseline was 57.4 ± 7.8 years, and women were followed for median 7 years (interquartile range: 6.3 to 7.7 years). Women with HDP had elevated arterial stiffness indexes and greater prevalence of chronic hypertension compared with women without HDP. Overall, 7.0 versus 5.3 age-adjusted incident cardiovascular conditions occurred per 1,000 women-years for women with versus without prior HDP, respectively (p = 0.001). In analysis of time-to-first incident cardiovascular diagnosis, prior HDP was associated with a hazard ratio (HR) of 1.3 (95% CI: 1.04 to 1.60; p = 0.02). HDP was associated with greater incidence of CAD (HR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001), heart failure (HR: 1.7; 95% CI: 1.04 to 2.60; p = 0.03), aortic stenosis (HR: 2.9; 95% CI: 1.5 to 5.4; p < 0.001), and mitral regurgitation (HR: 5.0; 95% CI: 1.5 to 17.1; p = 0.01). In causal mediation analyses, chronic hypertension explained 64% of HDP’s association with CAD and 49% of HDP’s association with heart failure.
Conclusions Hypertensive disorders of pregnancy are associated with accelerated cardiovascular aging and more diverse cardiovascular conditions than previously appreciated, including valvular heart disease. Cardiovascular risk after HDP is largely but incompletely mediated by development of chronic hypertension.
- cardiovascular epidemiology
- hypertension in pregnancy
- women’s health
Dr. Honigberg is supported by the National Institutes of Health (T32HL094301-07). Dr. Bhatt has served on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as Chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA CART Research and Publications Committee; has served on data monitoring committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi- Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as Deputy Editor of Clinical Cardiology; has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as Site Co-Investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; is a Trustee of the American College of Cardiology; and has performed unfunded Research for FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Drs. Peloso and Natarajan are supported by a grant from the National Heart, Lung, and Blood Institute (R01HL142711). Dr. Natarajan is supported by a Hassenfeld Scholar Award from the Massachusetts General Hospital, a grant from Fondation Leducq (TNE-18CVD04), and National Heart, Lung, and Blood Institute grants (R01HL148565, R01HL148050); has received grant support from Amgen, Apple, and Boston Scientific; and has served as a scientific advisor to Apple and Blackstone Life Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This research has been conducted using the UK Biobank Resource under Application Number 7089.
- Received September 5, 2019.
- Accepted September 9, 2019.
- 2019 American College of Cardiology Foundation
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