Relationships Between Reproductive History and Mortality From Cardiovascular Diseases Among Japanese Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study

Tanigawa, Kanami; Ikehara, Satoyo; Kimura, Takashi; Imano, Hironori; Muraki, Isao; Shirai, Kokoro; Tamakoshi, Akiko; Iso, Hiroyasu

doi:10.2188/jea.je20190020

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Epidemiological data of thousands of healthy individuals indicate that multiparous women have an elevated risk for cardiovascular disease ( Ness et al, 1993 ; Sanghavi et al, 2016 ; Kim et al, 2018 ; Oliver-Williams et al, 2019 ; Tanigawa et al, 2019 ) and stroke ( Qureshi et al, 1997 ). Given our findings, we hypothesized that multiple pregnancies increase cardiovascular disease risk due to repeated, yet transitory decrease in the concentration of the mineralization inhibitor, inorganic pyrophosphate.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, in meta-analyses of ∼20,000 participants from 7 studies and ∼150,000 participants from 24 studies, elevated alkaline phosphatase activity was associated with increased cardiovascular disease mortality, especially in young patients (<55 years of age) ( Li et al, 2014 ; Rahmani et al, 2019 ). On the other hand, several epidemiological studies established that multiparous women also have increased risk for developing cardiovascular disease decade(s) after their pregnancies ( Sanghavi et al, 2016 ; Kim et al, 2018 ; Oliver-Williams et al, 2019 ; Tanigawa et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent epidemiological studies demonstrated that multiparous women have an increased risk for developing cardiovascular disease manifesting decade(s) after their pregnancies ( Sanghavi et al, 2016 ; Kim et al, 2018 ; Oliver-Williams et al, 2019 ; Tanigawa et al, 2019 ). The molecular mechanism underlying this severe health-care problem is still elusive.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Veiga-López

Sethuraman

Navasiolava

et al. 2020

Front. Cell Dev. Biol.

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Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum in sheep and at term in humans and demonstrated its shortage in pregnancy, mirroring alkaline phosphatase activity. Next, we tested whether multiparity is associated with increased vascular calcification in pseudoxanthoma elasticum patients, characterized by low intrinsic plasma pyrophosphate levels. We demonstrated that these patients had increased vascular calcification when they give birth multiple times. We propose that transient shortages of pyrophosphate during repeated pregnancies might contribute to vascular calcification and multiparity-associated cardiovascular disease risk threatening hundreds of millions of healthy women worldwide. Future trials are needed to assess if gestational pyrophosphate supplementation might be a suitable prophylactic treatment to mitigate maternal cardiovascular disease risk in multiparous women.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Veiga-López

Sethuraman

Navasiolava

et al. 2020

Front. Cell Dev. Biol.

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“…The number of children was self-reported on a questionnaire administered at entry and was categorized as 0, 1, 2, and ≥ 3. In a Japanese survey from 2015, couples with more than four children are only accounted for 3.3% of the whole sample 9) ; thus, we divided women into four groups to avoid extreme differences in the number of subjects between groups. Demographic information including age at first birth, age at last birth, age at menopause, educational level, history of hypertensive disorders of pregnancy (HDP), and smoking status were also determined by selfreport.…”

Section: Variable Definitionsmentioning

confidence: 99%

Number of Children and Risk of Cardiovascular Disease in Japanese Women: Findings from the Tohoku Medical Megabank

Egawa

Kanda

Ohtsu

et al. 2023

JAT

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Aim: Cardiovascular disease (CVD) is the second largest cause of death in Japanese women. Pregnancy and childbirth are events that put a strain on the cardiovascular system. When postpartum weight retention is insufficient, weight gain due to fat deposition during pregnancy might lead to obesity. Thus, we examined the effects of body mass index (BMI) in middle and older ages and the number of children on CVD and metabolic disorders. Methods: From the Tohoku Medical Megabank database, we used data from 32,000 women aged ≥ 50 years. This database contains obstetrical history, medical history, and laboratory data obtained once from 2013 to 2015. Results: The mean age of participants was 64.2 years, and 47.7% of women had two children. Compared with nulliparous women, those who had a higher number of children had higher BMI and systolic blood pressure. The prevalence of CVD was highest in obese class I (30 kg/m 2 ≤ BMI) women with three or more children and the prevalence of hypertension was high in pre-obese (25 kg/m 2 ≤ BMI ＜30 kg/m 2 ) and obese class I women with children. Conversely, the prevalence of diabetes and proportion of women whose HbA1c values were ＞6.5% was highest in obese class I women with no children. Conclusion: In this study, we found that not only BMI but also the number of children influenced the health status of middle- and older-aged women, suggesting the importance of childbirth history in the health management of women.

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“…Women with two children were at the lowest point of developing CVD, while women with more children were more likely to develop various types of CVD ( 11 , 12 ), including coronary heart disease (CHD) ( 13 , 14 ), ischemic heart disease ( 15 ), stroke ( 16 , 17 ), and carotid atherosclerosis ( 18 ). The number of children and CVD mortality was U-shaped ( 19 ). However, after adjusting for other factors, there was uncertainty about whether this positive correlation was still significant or not.…”

Section: Introductionmentioning

confidence: 99%

Fertility Histories and Heart Disease in Later Life in China

Pang

Wang

et al. 2022

Front. Public Health

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PurposeBased on life course theories, health among older people is driven by a continuous and cumulative process that develops over the life course. To better understand the aging process, it is important to assess associations between parity and heart disease in older people of China.MethodThe associations between heart disease prevalence and number of births, number of boys or girls ever born were evaluated among 5,990 samples (mean age 64.1 years) using the Probit regression model based on the data from China Health and Retirement Longitudinal Study (CHARLS) conducted in 2013 and 2018. The model was adjusted only for rural or urban residents, and multivariate regression models were run separately by gender.ResultsOur results showed that more than three children or more than two boys ever born were associated with a higher risk of heart disease. However, the number of girls ever born had no significant effect on heart disease in the elderly. We further analyzed the group difference between urban and rural residents using the regression model. More than three children or more than two boys ever born were associated with a high risk of heart disease in rural areas. Compared to urban residents, rural residents were more likely to be suffering from heart disease due to high parity. When considering the digender difference the paper found that more than three children ever born were associated with a high risk of heart disease in the female group. Late age at the time of giving birth for the first time was associated with a poorer risk level of heart disease in the rural residents, because the phenomenon of early childbearing was serious in the rural residents. But after considering the impact on the physical health of using chronic diseases, the first birth and the last birth both increased the risk of heart disease.ConclusionsSome policy implications were being put forward. Firstly, parents who were ready to give birth should be aware of the possible health loss of high parity. Postpartum nutrition supplements and chronic disease prevention were suggested to prevent heart disease in later life. Secondly, the elderly in rural areas should pay more attention to heart diseases. Participating in more daily exercise and physical examinations was a good choice to reduce the risk of heart disease. Thirdly, women who give birth prematurely have a higher risk of CVD. Based on our results, age at entry to parenthood was closely related to the risk of heart disease in later life.

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Relationships Between Reproductive History and Mortality From Cardiovascular Diseases Among Japanese Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study

Cited by 7 publications

References 32 publications

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity to Cardiovascular Disease Risk

Number of Children and Risk of Cardiovascular Disease in Japanese Women: Findings from the Tohoku Medical Megabank

Fertility Histories and Heart Disease in Later Life in China

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