Sofia Klingberg1, Hilde K Brekke2, Anna Winkvist3, Gunnar Engström4, Bo Hedblad4, Isabel Drake5. 1. Department of Public Health and Community Medicine, Section for Epidemiology and Social Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: sofia.klingberg@gu.se. 2. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. 3. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 4. Cardiovascular Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. 5. Diabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Abstract
BACKGROUND: High parity has been suggested to increase risk of maternal cardiovascular disease independent of body mass index measured after childbearing. Pregnancy is, however, associated with persistent weight gain and metabolic changes that, independent of parity, increase the risk of cardiovascular disease. It could therefore be questioned if high parity independently increases the risk of cardiovascular disease or if this association may be confounded, mediated, or modified by other parity-related factors. OBJECTIVE: We sought to investigate the association between parity and risk of cardiovascular disease, and secondary outcomes in terms of myocardial infarction and cerebral infarction, with particular focus on potential mediation by anthropometric measures and effect modification by lactation. STUDY DESIGN: We used data from 16,515 female participants (age 44.5-73.6 years) of the population-based Malmö Diet and Cancer Study with baseline examination from 1991 through 1996. The Malmö Diet and Cancer Study was followed up throughout 2010, with a median follow-up of 15.8 years. We used Cox proportional hazards model to examine the association between parity and cardiovascular disease. RESULTS: Adjusted for age and other potential confounders, grand multiparous women (≥5 children) had an increased risk of cardiovascular disease (hazard ratio, 1.60; 95% confidence interval, 1.20-2.14), myocardial infarction (hazard ratio, 1.68; 95% confidence interval, 1.15-2.45), and cerebral infarction (hazard ratio, 1.74; 95% confidence interval, 1.18-2.58) compared to women with 2 children. Additional adjustment for baseline body mass index and weight change since age 20 years attenuated the risk, but the increased risk for cardiovascular disease (hazard ratio, 1.38; 95% confidence interval, 1.02-1.87) and myocardial infarction (hazard ratio, 1.53; 95% confidence interval, 1.04-2.26) in grand multiparous women remained significant. Models stratified by lactation time showed that risk was only raised in grand multiparous women who had a mean lactation time of <4 mo/child. In sensitivity analyses excluding women with a history of diabetes at baseline, risk estimates for grand multiparous women became nonsignificant in the full model. CONCLUSION: Part of the increased risk of cardiovascular disease and myocardial infarction in grand multiparous women seems to be mediated by weight gain and potentially by higher likelihood of type 2 diabetes mellitus. Lactation may modify the increased risk of grand multiparity in that longer duration might offset the cardiovascular disease risk.
BACKGROUND: High parity has been suggested to increase risk of maternal cardiovascular disease independent of body mass index measured after childbearing. Pregnancy is, however, associated with persistent weight gain and metabolic changes that, independent of parity, increase the risk of cardiovascular disease. It could therefore be questioned if high parity independently increases the risk of cardiovascular disease or if this association may be confounded, mediated, or modified by other parity-related factors. OBJECTIVE: We sought to investigate the association between parity and risk of cardiovascular disease, and secondary outcomes in terms of myocardial infarction and cerebral infarction, with particular focus on potential mediation by anthropometric measures and effect modification by lactation. STUDY DESIGN: We used data from 16,515 female participants (age 44.5-73.6 years) of the population-based Malmö Diet and Cancer Study with baseline examination from 1991 through 1996. The Malmö Diet and Cancer Study was followed up throughout 2010, with a median follow-up of 15.8 years. We used Cox proportional hazards model to examine the association between parity and cardiovascular disease. RESULTS: Adjusted for age and other potential confounders, grand multiparous women (≥5 children) had an increased risk of cardiovascular disease (hazard ratio, 1.60; 95% confidence interval, 1.20-2.14), myocardial infarction (hazard ratio, 1.68; 95% confidence interval, 1.15-2.45), and cerebral infarction (hazard ratio, 1.74; 95% confidence interval, 1.18-2.58) compared to women with 2 children. Additional adjustment for baseline body mass index and weight change since age 20 years attenuated the risk, but the increased risk for cardiovascular disease (hazard ratio, 1.38; 95% confidence interval, 1.02-1.87) and myocardial infarction (hazard ratio, 1.53; 95% confidence interval, 1.04-2.26) in grand multiparous women remained significant. Models stratified by lactation time showed that risk was only raised in grand multiparous women who had a mean lactation time of <4 mo/child. In sensitivity analyses excluding women with a history of diabetes at baseline, risk estimates for grand multiparous women became nonsignificant in the full model. CONCLUSION: Part of the increased risk of cardiovascular disease and myocardial infarction in grand multiparous women seems to be mediated by weight gain and potentially by higher likelihood of type 2 diabetes mellitus. Lactation may modify the increased risk of grand multiparity in that longer duration might offset the cardiovascular disease risk.
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