Yi-Xin Wang1, Lidia Mínguez-Alarcón2,3, Audrey J Gaskins4, Liang Wang5, Ming Ding1, Stacey A Missmer6, Janet W Rich-Edwards3,7,8, JoAnn E Manson8,9, Jorge E Chavarro1,3,8. 1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Building II, 3rd Floor, Room # 322, 655 Huntington Avenue, Boston, MA 02115, USA. 2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA. 3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Ave, Boston, MA, USA. 4. Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta, GA 30322, USA. 5. Department of Public Health, Robbins College of Health and Human Sciences, Baylor University, One Bear Place #97343 Waco, TX 76798, USA. 6. Department of Obstetrics and Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, 400 Monroe Ave NW, Grand Rapids, MI 49503, USA. 7. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 02120, USA. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Building II, 3rd Floor, Room # 331, 655 Huntington Avenue, Boston, MA 02115, USA. 9. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02115, USA.
Abstract
AIMS: The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. METHODS AND RESULTS: We followed 95 465 ever-gravid women participating in the Nurses' Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10-1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07-1.35) and stroke (HR 1.23; 95% CI 1.04-1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06-1.31) for 1 and 1.34 (95% CI 1.13-1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21-1.62) for age ≤23 years, 1.25 (95% CI 1.09-1.43) for age 24-29 years, and 1.03 (95% CI 0.88-1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained <1.80% of the association between PL and CVD. CONCLUSION: PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. METHODS AND RESULTS: We followed 95 465 ever-gravid women participating in the Nurses' Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10-1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07-1.35) and stroke (HR 1.23; 95% CI 1.04-1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06-1.31) for 1 and 1.34 (95% CI 1.13-1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21-1.62) for age ≤23 years, 1.25 (95% CI 1.09-1.43) for age 24-29 years, and 1.03 (95% CI 0.88-1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained <1.80% of the association between PL and CVD. CONCLUSION: PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders. Published on behalf of the European Society of Cardiology. All rights reserved.
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