Association of parity with the prevalence of hypertension in Japan: The Tohoku Medical Megabank Community-based cohort study.

Hongxin Wang contributed to the study conception, statistical analysis, data interpretation, and manuscript drafting. Noriyuki Iwama and Masatoshi Saito contributed to the study conception, data interpretation, and manuscript revision. Keiichi Yuwaki, You Nakamichi, Hirotaka Hamada, Hasumi Tomita, Kazuma Tagami, Rie Kudo, Natsumi Kumagai, and Hirohito Metoki contributed to manuscript revision. Naoki Nakaya, Atsushi Hozawa, Shinichi Kuriyama, and Nobuo Yaegashi contributed to data acquisition, data interpretation, and manuscript revision. All authors approved the final version of the manuscript.

Written informed consent was obtained from all the participants.

Figure  1 comprises a flowchart depicting participant screening and selection in this study. Among the 40 712 women who participated in the type 1 survey of the TMM CommCohort Study who met the inclusion criteria, the following were excluded due to: missing data on history of conception ( N  = 2101), parity ( N  = 600), clinical history of HDP ( N  = 3757), menopause ( N  = 1761), current BW ( N  = 7), or BW at age 20 ( N  = 1898) or improbable data on menopausal status ( N  = 55) and breastfeeding ( N  = 3). Finally, 30 530 women (6700 premenopausal and 23 830 postmenopausal women) were eligible for inclusion in the analysis undertaken. Flowchart of the screening and enrollment procedures of this study. Table  1 presents the characteristics of the premenopausal women stratified by parity. The average age in this study was 41.2 years, and 12.3% and 5.0% of premenopausal women had hypertension and a history of HDP. Increased parity was associated with higher age, prevalence of hypertension, and estimated 1‐day NaCl intake, as well as higher proportions of breastfeeding experience, hormone replacement therapy, history of HDP, and residence in Iwate Prefecture. The proportion of those with current obesity was higher among participants with parity ≥4, compared to participants with other parities. The proportions of unmarried and divorced women were high in women with parity of 0 and 1, respectively. The proportion of high levels of education decreased as parity increased. Characteristics of premenopausal women stratified by parity. All ( N  = 6700) a 0 ( N  = 1609) a 1 ( N  = 1130) a 2 ( N  = 2485) a 3 ( N  = 1206) a ≥4 ( N  = 270) a Continuous and categorical variables are shown as the mean (standard deviation) and frequency (proportion), respectively. Table  2 presents the characteristics of the postmenopausal women stratified by parity. The average age in this study was 63.9 years, and 41.6% and 4.9% of postmenopausal women had hypertension and a history of HDP, respectively. The mean value of current BMI and proportion of current obesity, as well as the prevalence of hypertension and T2DM, among postmenopausal women increased with parity. In contrast, the proportions of family history of hypertension and T2DM decreased with parity. The proportions of unmarried and divorced women were high in nulliparous women and those with single parity, whereas the proportion of those with a high level of education was high in the group of nulliparous women. Characteristics of postmenopausal women stratified by parity. All ( N  = 23 830) a 0 ( N  = 1658) a 1 ( N  = 2110) a 2 ( N  = 11 580) a 3 ( N  = 7248) a ≥4 ( N  = 1234) a Continuous and categorical variables are shown as the mean (standard deviation) and frequency (proportion), respectively. The results of the association between parity and hypertension prevalence in premenopausal multiparous women are presented in Figure  2 . Although women with a parity of 2 had lower odds for the prevalence of hypertension, the results were not statistically significant. There was no significant graded linear association of parity with the prevalence of hypertension in models 1, 2, and 3 ( p ‐value for trend: .54, .44, and .35 in models 1, 2, and 3, respectively) or in Model 4 ( p ‐value for trend: .66). In models 5 and 6, no significant linear association of parity with the prevalence of hypertension was observed ( p ‐value for trend: .69 and .76, respectively). In models 5 and 6, BMI at age 20 and current BMI were significantly associated with the prevalence of hypertension (adjusted odds ratio [OR] per 1‐SD increase in BMI at age 20 and current BMI: 1.432 [95% confidence interval [CI]: 1.302−1.574] and 1.560 [95% CI:1.469−1.657]), respectively. Associations of parity with the prevalence of hypertension in premenopausal multiparous women. A history of HDP exhibited a significant association with an increased prevalence of hypertension (adjusted OR: 1.670 [95% CI: 1.443−1.934]) in model 4. History of HDP remained as a risk factor for hypertension even after the adjustment for BMI at age 20 or current BMI (adjusted OR: 1.588 [95% CI: 1.369−1.842] in model 5 and adjusted OR: 1.469 [95% CI: 1.260−1.713] in model 6). Figure  3 indicates the results for the association of parity with hypertension prevalence in postmenopausal multiparous women. In models 1, 2, and 3, a significant linear association of parity with the prevalence of hypertension was observed ( p ‐values for trend: .0036, <.0001, and .0004 in models 1, 2, and 3, respectively) and persisted in Model 4 ( p ‐value for trend: .0003). In Model 5, the association of parity with the prevalence of hypertension was attenuated as compared to the results of Model 4 ( p ‐value for trend: .0011). BMI at age 20 was associated with increasing odds of the prevalence of hypertension (adjusted OR per 1‐SD increase in BMI at age 20: 1.103 [95% CI:1.070−1.138]). In Model 6, the linear graded association between parity and the prevalence of hypertension diminished ( p ‐value for trend: .55). The adjusted OR for a parity of 2 was 1.060 (95% CI: 1.006−1.117). Furthermore, the current BMI was significantly related to an increasing risk of the prevalence of hypertension (adjusted OR per 1‐SD increase in current BMI: 1.546 [95% CI: 1.510−1.584]). Associations of parity with the prevalence of hypertension in postmenopausal multiparous women. A history of HDP was significantly associated with increased odds of the prevalence of hypertension (adjusted OR: 1.388 [95% CI: 1.299−1.483]) in model 4. A history of HDP remained a risk factor for hypertension even after adjusting for BMI at age 20 or current BMI (adjusted OR: 1.379 [95% CI: 1.291−1.473] in model 5 and adjusted OR: 1.318 [95% CI: 1.231−1.411] in model 6). The results of the association between parity and the prevalence of hypertension in all premenopausal women are presented in Figure S1 and Supporting Material. The results of the association of parity with the prevalence of hypertension in all postmenopausal women are shown in Figure S2 and Supporting Material.

This study does not involve a clinical trial.

This cross‐sectional study utilized data from the type 1 survey of the Tohoku Medical Megabank Community‐based Cohort Study (TMM CommCohort Study)—a prospective cohort study that has been conducted in the Miyagi and Iwate prefectures of Japan since 2013. The TMM CommCohort Study was undertaken, as described previously, 20 , 21 to contribute to the recovery efforts and address medical concerns in the aftermath of the Great East Japan Earthquake (GEJE) and the associated tsunami in 2011, which caused severe damage along the Pacific coast of the Tohoku region. The TMM CommCohort Study recruited both men and women. However, the present study included only women who met the following criteria: (1) age ≥20 and <75 years and residing in the Miyagi or Iwate prefectures between May 2013 and March 2016, when the baseline survey of the TMM CommCohort Study was conducted, and (2) provided written informed consent to participate in the study during the municipal health checkup. This study was approved by the Institutional Review Board of the Tohoku University School of Medicine (approval numbers: 2021‐1‐608, 2022‐1‐069, and 2022‐1‐216). A total of 40 712 women who met the inclusion criteria were included in this study. Menopause is a known risk factor for hypertension 9 , 10 and the fertility potential differs based on menopausal status. Therefore, we stratified the study participants into premenopausal and postmenopausal participants. We obtained information on the number of children through self‐reported questionnaires. Parity, identified as the exposure of interest in this study, was defined as the number of children and categorized as nulliparous (i.e., parity = 0), 1, 2, 3, and ≥4. Neither the number of stillbirths nor multiple pregnancies was collected in this study. The outcome in this study was hypertension. The medical information of the participants was collected using self‐reported questionnaires. Blood pressure was measured by a nurse or qualified staff at the municipal health checkup venues. It was measured using an automated blood pressure monitor 22 with the participant in a seated position. The participants were diagnosed with hypertension if any of the following criteria were met: (1) participants who, in the self‐reported questionnaire, answered “yes” to the question of whether they had hypertension; (2) participants who reported that they were “under treatment for hypertension” in the self‐reported questionnaire on lifestyle diseases; (3) participants whose measured systolic blood pressure at the municipal health checkup venues was ≥140 mmHg; and (4) participants whose measured diastolic blood pressure was ≥90 mmHg. 22 , 23 Data on blood pressure measured during prenatal check‐ups were obtained, and a clinical history of HDP was obtained using the self‐reported questionnaire in response to the question, “Have you ever experienced hypertensive disorders of pregnancy or toxemia?” 22 Premenopausal and postmenopausal women were identified based on their responses in the self‐reported questionnaire when asked about their current menstrual status and selected one of the three options: “I have menstruation,” “Menstruation is disappearing,” and “No menstruation for more than a year.” Women who selected one of the first two options were classified as premenopausal, whereas those who selected the third option were classified as postmenopausal. Details of the data collection for the remaining study variables are described in the Supplementary Material . After we stratified participants into two subgroups (i.e., premenopausal and postmenopausal women) according to their menopausal status, subgroup‐specific statistical analyses were performed. Continuous variables are expressed as the mean (standard deviation [SD]) or median (interquartile range), as appropriate, whereas the categorical variables are presented as the frequency (proportion). The differences in characteristics between participants who were analyzed and those who were excluded owing to missing data or clinically improbable data were evaluated using the student's t ‐test or chi‐square test. Considering the possibility that nulliparous women may have a medical or socioeconomic background that forced them not to give birth or may have chosen not to deliver due to their preferences, there may exist differences in the characteristics of nulliparous and multiparous women. Therefore, we first performed analyses in multiparous women (i.e., nulliparous women were excluded) while setting participants with a single parity as the reference category in both premenopausal and postmenopausal women. The linear trend association of parity with the prevalence of hypertension was calculated using the Cochran–Armitage test. Multiple logistic regression models were created to investigate the association between parity and prevalence of hypertension. Model 1 was adjusted for age. Model 2 was additionally adjusted for height, physical activity, marital status, smoking status, alcohol drinking, own birth weight, highest educational level, family history of HDP, family history of hypertension, family history of type 2 diabetes mellitus (T2DM), oral contraceptive use, hormone replacement therapy, glomerulonephritis, thyroid disease, 24 endometriosis, mental disease, menstrual cycle, age at menarche (<15 or ≥15 years), sleeping time, nap time, year of participation in the study, prefecture (Miyagi or Iwate), number of relocations after the GEJE, breastfeeding experience, and age at last delivery (<35 or ≥35 years). When postmenopausal women were analyzed, menopausal age (age at menopause <40 years or ≥40 years) was further included in Model 2. Model 3 was adjusted for all variables adjusted in Model 2, as well as the γ‐GTP (<50 or ≥50 IU) based on a previous study 25 , 26 and estimated 24‐hour sodium chloride (NaCl) and potassium (K) intakes, which were calculated according to previously reported methods. 27 , 28 In addition to the variables in Model 3, Model 4 was adjusted for HDP and gestational diabetes mellitus (GDM). As parity is associated with obesity, 29 , 30 Model 5 was adjusted for BMI at age 20, per 1‐SD increase, in addition to the variables in Model 4. Model 6 was adjusted for the current BMI, per 1‐SD increase, in addition to the variables in model 4. Furthermore, the linear trend in the association of parity with T2DM prevalence was tested in each model. Next, the association between parity and the prevalence of hypertension was investigated in all women (i.e., nulliparous and multiparous women) in both premenopausal and postmenopausal women. Women with single parity were the reference category. Model 1 was adjusted for age. Model 2 was adjusted for the covariates we previously mentioned, except for breastfeeding experience and age at last delivery (<35 or ≥35 years). Model 3 was adjusted additionally for γ‐GTP (<50 or ≥50 IU) 25 , 26 and estimated 24‐h NaCl and K intakes. 27 , 28 Model 4 was adjusted for BMI at age 20, per 1‐SD increase, in addition to the covariates in Model 3. Furthermore, Model 5 was adjusted for the current BMI per 1‐SD increase in addition to the covariates in Model 3. No strong multicollinearity was observed. Multiple imputation using the Markov‐chain Monte Carlo simulation was used to deal with missing data for several covariates. A dependent variable (i.e., hypertension) and all covariates were used to create the imputation model. After creating 20 datasets by multiple imputation, each data set was evaluated separately, and the results were combined eventually. We analyzed the participants’ characteristics using the gtsummary package of R version 4.1.1. 31 Other statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, North Carolina, USA).

This is the first study to examine the association of parity with the prevalence of hypertension, considering a clinical history of HDP and current menstrual status in Japan. In postmenopausal women, an increase in parity was associated with a higher risk of hypertension when the current BMI was not adjusted; however, the association attenuated after adjusting for the current BMI. Although statistical significance in the association of women with a parity of 2 with the prevalence of hypertension remained, the very small point estimate of the adjusted OR would not be clinically relevant in our study. These findings align with those of the study by Xu and colleagues, 14 which showed that women with a parity of 4 and ≥5 had a higher risk of hypertension than those with a parity of zero or one, and the association diminished after adjusting for BMI and waist circumference. However, our study contradicted the study by Moazzeni and colleagues, 13 which found that women with parity of 3 had a higher risk of hypertension than those with a parity of 2 even after adjusting for BMI. The average age was 43.64 years in Moazzeni's study, and differences in ethnicity, lifestyle, and study design could have led to different results from our results. 13 On the other hand, Jang reported that parity was associated with a decreasing risk of hypertension in postmenopausal women in Korea. 11 Differences in covariates, study design, lifestyle including intake of salt in eating habits, and number of participants might produce different results from those of our study. It is crucial to consider potential mechanisms that underlie the association between parity and hypertension. Postmenopausal status has been reported to be associated with a 60% increased risk of metabolic syndrome, 32 and hypertension associated with metabolic syndrome has more severe cardiovascular risk and low response to therapy. Metabolic syndrome induces systemic endothelial dysfunction and chronic inflammation, causing cardiac and cerebrovascular events. 33 In postmenopausal women, a higher parity may increase insulin resistance, which could be attributed to prolonged cumulative exposure to insulin resistance due to decreased insulin sensitivity during pregnancy and elevated estrogen levels. 34 Insulin resistance, reported to be independently associated with an exacerbated risk of hypertension, plays a central role in the development of hypertension through affecting the function of pancreatic β‐cells responsible for glucose homeostasis, 35 , 36 decreasing urinary excretion of sodium and increasing plasma norepinephrine levels and plasma renin activity. 37 BMI is reported to be the most effective anthropometric indicator to identify insulin resistance. 38 In this study, the association between parity and hypertension attenuated after adjusting for current BMI, indicating the importance of body weight management. In premenopausal women, increased parity was not significantly associated with the prevalence of hypertension in our study. The mean age of premenopausal women was lower than that of postmenopausal women, which could explain the observed lower prevalence of hypertension in premenopausal women than that in postmenopausal women. Additionally, the potential for future childbirths in premenopausal women may not reflect their lifetime parity count accurately. Liu reported no association of parity with hypertension in China, 39 whereas Chen reported a linear trend association between parity and hypertension among Danish premenopausal women. 40 The incidence of hypertension was 3.8% in the Danish study compared to 12.3% in our study; this difference in the incidence of hypertension limits the comparison of the two studies. Furthermore, women who participated in the Danish study had a higher socio‐occupational status and a higher possibility of being healthier than women in the overall Danish population, limiting the generalizability of the results. 40 Another cohort study in Japan reported a positive association between parity and hypertension before adjusting for BMI, which disappeared after adjusting for BMI in postmenopausal women. 19 However, this study also found that parity generally had a protective effect on hypertension in premenopausal women, 19 which contrasts with our findings. Several factors, including age of participants, especially the age of premenopausal women, education level, and covariate adjustments, may have contributed to these different results. Furthermore, our study was conducted in the Tohoku region of Japan, which experienced the GEJE, while the previous Japanese study was mainly performed in West Japan. Natural disasters have been linked to long‐term adverse impact on cardiometabolic risk, 41 possibly due to post‐disaster relocations and changes in living environments. Differences in the participants’ geographic locations and exposure to natural disasters may also explain the discrepancy between the previous study results and our findings. Women with a history of HDP were 3.7 times more likely to develop hypertension than those with normotensive pregnancies in a meta‐analysis. 42 Similarly, in our study, a history of HDP was significantly associated with the prevalence of hypertension in both premenopausal and postmenopausal women. Even after adjusting for current BMI, a clinical history of HDP remained a risk factor for hypertension prevalence in both premenopausal and postmenopausal women, underscoring the importance of HDP prevention. Establishing evidence for reducing the risk of preterm preeclampsia, a subtype of HDP, through interventions such as low‐dose aspirin oral use during pregnancy, is a necessary consideration in Japan. 43 Although GDM was reported to be associated with hypertension, 44 a history of GDM was not associated with hypertension in our study. As GDM was diagnosed according to the Japan Society of Obstetrics and Gynecology criteria from 1984, women who gave birth before 1984 could not be diagnosed with GDM. 45 Therefore, more women with hypertension could have been diagnosed with GDM. Although HDP was more likely to be an accompanying co‐morbidity in women with GDM, 46 GDM itself may not be directly associated with hypertension. Thus, preventing HDP in women with GDM could be of crucial importance in preventing hypertension. The strengths of our study are the large sample size and various covariates, including medical history, lifestyle habits, psychiatric history, and social factors. However, some limitations need to be acknowledged. The study design does not allow for the examination of the timing of hypertension risk over time. Furthermore, the study relied on self‐reported information, which may introduce recall bias and affect the accuracy of the results. Premenopausal women might remember the history of past pregnancies more accurately due to recent experiences than postmenopausal women. However, according to a previous study, the number of children written in self‐reported questionnaires is almost identical to the number of children in medical records; thus, this limitation was not considered to have an important impact on the results of this study. 47 Additionally, our study did not collect data on multiple pregnancies, which could be relevant to the association between parity and hypertension. As HDP was not defined until 1982 in Japan, 48 women who gave birth before 1982 could not be diagnosed with HDP, causing an underestimation of HDP in this study. The historical changes in defining HDP and GDM may potentially affect the comparisons of the associations of HDP and GDM with hypertension prevalence between premenopausal and postmenopausal women. Considering the limited prior research on this topic in Japan, this study provides valuable preliminary evidence into the association between parity and hypertension, taking into account the history of HDP. However, further prospective studies with larger sample sizes and longitudinal follow‐up are needed to confirm these findings and investigate the potential mechanisms underlying this association. Additionally, studies considering other relevant factors such as economic factors and genetic predisposition would contribute to a more comprehensive understanding of the relationship between parity and hypertension in the Japanese population. In conclusion, parity is associated with an increased risk of hypertension in postmenopausal women, although the association attenuated after adjusting for current BMI. Therefore, in postmenopausal women, by maintaining an appropriate body weight, parity would no longer influence the risk for hypertension. A clinical history of HDP is a risk factor for hypertension in both pre‐ and postmenopausal women. Therefore, continuous surveillance and preventive measures for hypertension should be provided for women with HDP.

This study is an original work, containing no content from other sources.

Hypertension is a leading risk factor for cardiovascular disease, stroke, and renal disease and affects millions of people worldwide. 1 , 2 , 3 Globally, more than 30% of adults aged 30−79 years have been diagnosed with hypertension, 4 , 5 whereas, in Japan, more than 60% of women aged 60 years or more have hypertension. 6 Risk factors for hypertension include obesity, excessive salt intake, lack of exercise, excessive drinking, and family history of hypertension. 7 , 8 Moreover, menopause is one of the risk factors for hypertension in women. 9 , 10 Despite inconsistent findings, parity—defined as the number of live births—has been associated with hypertension. 11 , 12 , 13 , 14 Pregnancy can significantly affect a woman's cardiovascular health, and hypertensive disorders of pregnancy (HDP) increase the risk of later‐life chronic hypertension. 15 A graded association between parity, particularly grand multiparity, and hypertension has been reported, although some studies showed either no or an inverse association. Among Iranian women, parity of three or more conferred a higher risk of incident hypertension than parity of two. 16 A study conducted in Korea showed that parity was negatively associated with hypertension in postmenopausal women. 11 Notable variations have been observed in the prevalence of hypertension among different ethnic groups. 4 , 17 Japanese women, compared to their Western counterparts, tend to have significantly lower BMI and different lifestyles, 18 suggesting that the association between parity and hypertension may differ between Japanese women and those from other countries. Although one previous study in Japan examined the association between parity and hypertension, 19 no prior studies have explored the relationship while considering the clinical history of HDP, a specific risk factor for hypertension in women. Therefore, this study aimed to clarify the association between parity and the prevalence of hypertension, with consideration of HDP.

Noriyuki Iwama, Nobuo Yaegashi, and Masatoshi Saito are members of Women's Health Care Medical Science, Tohoku University Graduate School of Medicine. Employment: You Nakamichi and Keiichi Yuwaki (Dai‐ichi Life Insurance Company, Limited, which had no involvement in the statistical analysis, interpretation of results, manuscript writing, or decision to submit the manuscript for publication). The remaining authors have nothing to declare.

Supporting information Click here for additional data file. Supporting information Click here for additional data file. Supporting information Click here for additional data file.