https://orcid.org/0000-0002-0122-2356
Abstract
Objective
This study aimed to examine the association between severity of menopausal symptoms and cardiovascular disease (CVD) risk among middle-aged Chinese women.
Methods
A cross-sectional study recruited 9679 women aged 40–70 years from three socioeconomic regions of China in 2018. Menopausal symptoms were assessed by the modified Kupperman Menopausal Index (KMI). The severity of individual symptoms was classified as none (0 points), mild (1 points) and moderate-to-severe symptoms (2–3 points), and overall menopausal symptoms were classified as none (<15 points), mild (15–24 points) or moderate-to-severe (≥25 points) according to the sum score of the KMI. Logistic regression models were used to examine associations of the severity of menopausal symptoms with CVD risk.
Results
A total of 5.6% of participants reported being diagnosed with CVD. Overall menopausal symptoms were more common in women aged 60–70 years than in women aged 40–59 years. After multiple adjustment, mild (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.64–2.61) and moderate-to-severe (OR = 2.64, 95% CI: 1.92–3.63) overall menopausal symptoms were associated with increased risk of CVD compared with no symptoms. Significant positive associations between the severity of individual menopausal symptoms and CVD risk were observed for all 13 items.
Conclusion
The severity of menopausal symptoms was positively associated with CVD risk in middle-aged Chinese women.
Introduction
Cardiovascular disease (CVD) has been the leading cause of death and is one of the most common causes of disability-adjusted life-years lost in women globally [Citation1]. CVD risk factors specific to women include early menarche, adverse pregnancies (e.g. stillbirth, miscarriage, gestational diabetes mellitus and pre-eclampsia) and early menopause [Citation2, Citation3]. It is reported that women are more likely to develop CVD events later in life than men, with a distinct increase in CVD risk during midlife that is a time coinciding with the menopause transition [Citation4]. The menopause transition has been considered a period of increasing CVD risk, probably due to distinct patterns of changes in endogenous sex hormones and adverse alterations in lipids, lipoproteins and body composition, and indices of vascular health [Citation5]. However, the relationship between menopausal symptoms and CVD risk has not been fully understood.
Recently, data from the Women’s Health Initiative Observational Cohort based on a majority of white women (85.8%) found that the severity of specific individual menopausal symptoms, including night sweats, waking up several times at night, joint pain or stiffness, heart racing or skipping beats, dizziness, feeling tired, forgetfulness, mood swings, restlessness or fidgeting and difficulty concentrating, was each significantly associated with total CVD [Citation6]. Additionally, the Study of Women’s Health Across the Nation conducted at seven US sites also reported that frequent and persistent vasomotor symptoms were associated with increased risk of later CVD events [Citation7]. Another retrospective cross-sectional analysis of a relative sample size demonstrated that menopausal symptoms assessed by the Greene Climacteric Scale, composed of anxiety, depression, somatic symptoms, vasomotor symptoms and sexuality, correlated with biochemical risk factors for CVD and atherosclerosis [Citation8]. Previous studies are mainly based on western populations, and evidence on Asian populations is still lacking.
Furthermore, previous studies mostly focused on the relationship between vasomotor symptoms, depression and CVD risk, while the association of menopausal symptoms as a whole with the risk of CVD has not been fully delineated. Nowadays, several validated menopausal symptom scales have been developed and used in epidemiological studies to comprehensively evaluate the presence and severity of menopausal symptoms, such as the modified Kupperman Menopausal Index (KMI). The KMI not only assesses the overall score of 13 individual menopausal symptoms, but also rates the severity of individual and overall menopausal symptoms, which could explore more information on menopausal symptoms and CVD risk. Therefore, the objective of this study was to examine the association between the presence and severity of menopausal symptoms, evaluated by the modified KMI, and CVD risk in middle-aged Chinese women.
Methods
Study design and participants
The National Survey of Women’s Health, a cross-sectional, community-based study, was conducted in three socioeconomic regions of China: eastern (Jiangsu and Shandong provinces), central (Anhui and Hunan provinces) and western (Shanxi and Sichuan provinces). The study design has been described in detail elsewhere [Citation9, Citation10]. Briefly, one urban area and one rural area of the six provinces were selected as investigation sites, and women aged 10–70 years were recruited using a multi-stage stratified random cluster sampling at all investigation sites. Face-to-face interviews were performed to gather information on demographic characteristics, lifestyle factors, medical history and menopausal symptoms (only obtained in women aged 40–70 years) using a structured questionnaire. Among the 11,013 participants aged 40–70 years, the present analysis was restricted to 9679 participants. Participants meeting the following criteria were excluded: incomplete data collection for menopausal symptoms (n = 160) or CVD (n = 162); women who took estrogen in the past 6 months (n = 80); and women who were in menopause due to surgical removal of both ovaries or medical termination of both ovarian functions, such as chemotherapy or radiotherapy (n = 46) [Citation11]. The study was approved by the Ethical Review Committee of the Chinese Center for Disease Control and Prevention, and written informed consent was acquired from all participants.
Assessment of CVD
Consistent with previous studies, the occurrence of CVD was assessed by the following question: ‘Have you been told by a doctor that you have been diagnosed with a stroke or cardiac events (such as heart attack, coronary heart disease, congestive heart failure, angina or other heart problems)?’ Women who answered ‘yes’ to this question were defined as having CVD [Citation12].
Assessment of menopausal symptoms
The Chinese version of the modified KMI, which has been widely utilized in epidemiological studies based on Chinese populations, was used to assess the severity and intensity of menopause symptoms [Citation10, Citation13]. According to the recommendations from the Chinese Obstetrics and Gynecology, the modified KMI contains 13 items in four domains as follows: vasomotor (hot flashes), psychological (mood swing and depression), somatic (paresthesia, insomnia, dizziness, fatigue, arthralgia and myalgia, headache, palpitations and skin formication) and urogenital (sexual problems and urinary tract infection) [Citation11, Citation14]. A 4-point scale was used to evaluate the severity of each symptom: no symptoms (0 points), mild symptoms (1 point), moderate symptoms (2 points) and severe symptoms (3 points). The item ‘hot flashes’ was weighted with a factor of four, the items ‘mood swing’, ‘paresthesia’, ‘insomnia’, ‘sexual problems’ and ‘urinary tract infection’ were weighted a factor of two and all other items were weighted with a factor of one. The sum score of the modified KMI could be subdivided into three groups: no (total KMI score <15 points), mild (total KMI score 15–24 points) and moderate-to-severe (total KMI score ≥25 points) menopausal symptoms [Citation11]. Cronbach’s α was 0.87 in the present study.
Assessment of covariates
The interviewer-administered structured questionnaire was utilized to gather the information from all participants, as well as anthropometric parameters including height and weight. Covariates included age, residence, education, employment status, average monthly household income, marital status, nulliparity, menopausal status, drinking, smoking, physical activity, body mass index (BMI), diabetes mellitus, hypertension and dyslipidemia. According to the 2011 Stages of Reproductive Aging Workshop +10 criteria [Citation15], menopausal status was categorized into: reproductive stage, defined as regular menstruation or subtle changes in menstrual cycle characteristics; perimenopause, defined as the beginning of a persistent difference of 7 days in the length of consecutive cycles or the last menstruation having occurred for no more than 12 months; and postmenopause, defined as the end of the 12-month period of amenorrhea. BMI was calculated as the weight in kilograms divided by the square of height measured in meters. Diabetes mellitus, hypertension and dyslipidemia were ascertained by the participants’ report of disease diagnosis.
Statistical analysis
Demographic characteristics were expressed as number and frequency distribution for categorical variables based on CVD diagnosis, or as median and interquartile range for skewed continuous variables, and the chi-square test or rank-sum text was used to compare the differences, respectively. Univariate and multivariate logistic regression models were performed to examine the associations of menopausal symptoms with CVD risk. In the multivariate models, we adjusted for age, residence, education, employment status, average monthly household income, marital status, nulliparity, menopausal status, drinking, smoking, physical activity, BMI, diabetes mellitus, hypertension and dyslipidemia. The no menopausal symptom group was treated as the reference group. A subgroup analysis based on 10-year age (40–49 years, 50–59 years, 60–70 years) was further performed to evaluate whether the association between menopausal symptoms was different in different age groups. Analyses were conducted using SAS software version 9.4 (SAS Institute, Cary, NC, USA) for all analyses, and a 0.05 level was used to declare significant differences (two-sided).
Results
Among the 9679 women aged 40–70 years, the mean age was 51.8 years and 5.6% (547/9679) of participants reported being diagnosed with CVD. The prevalence of CVD was 3.9% (300/7763), 11.4% (161/1410) and 17.0% (86/506) in women reporting no, mild and moderate-to-severe menopausal symptoms, respectively. presents the demographic characteristics of study participants according to the diagnosis of CVD. Women diagnosed with CVD were more likely to be older, and to have a lower level of education and average monthly household income, higher BMI and a higher prevalence of diabetes mellitus, hypertension and dyslipidemia than those who did not report having CVD (all p < 0.001), and were less likely to be married and drink (both p < 0.001).
Table 1. Characteristics of participants by cardiovascular disease (CVD) status.
presents the prevalence of menopausal symptoms regarding whether the participants were diagnosed with CVD. Generally, mild symptoms tended to be more common, while moderate-to-severe symptoms were less prevalent. For instance, 14.6% experienced mild overall menopausal symptoms, whereas 5.2% experienced moderate-to-severe overall menopausal symptoms; and 39.7% reported mild insomnia that was the most common symptom in the whole population, while 8.1% reported moderate-to-severe insomnia. Women diagnosed with CVD tended to have a higher likelihood of mild and moderate-to-severe symptoms than those without CVD (all p < 0.05). Among women with CVD, the three most prevalent symptoms were insomnia (mild 43.0%, moderate-to-severe 22.3%), arthralgia and myalgia (mild 34.4%, moderate-to-severe 30.3%) and dizziness (mild 43.3%, moderate-to-severe 17.2%). In contrast, the three most common symptoms were insomnia (mild 39.5%, moderate-to-severe 7.2%), fatigue (mild 33.9%, moderate-to-severe 7.0%) and headache (mild 30.5%, moderate-to-severe 6.0%) in women without CVD.
Table 2. Menopausal symptoms of participants by cardiovascular disease (CVD) status.
shows the prevalence of menopausal symptoms by age group (40–49 years, 50–59 years and 60–70 years). Overall menopausal symptoms were more common in older women (60–70 years) than younger women (40–59 years, p < 0.01). A total of 20.5% and 9.0% experienced mild and moderate-to-severe overall symptoms among women aged 60–70 years, respectively, whereas only 10.8% and 3.4% experienced mild and moderate-to-severe overall symptoms among women aged 40–49 years, respectively. Hot flashes were more prevalent among women aged 50–59 years. Mood swing, most somatic symptoms (insomnia, fatigue, dizziness, arthralgia and myalgia, headache, palpitations and skin formication) and urogenital symptoms (sexual problems and urinary tract infection) were more common among older women (60–70 years).
shows the prevalence of menopausal symptoms by menopausal status (reproductive stage, perimenopause and postmenopause). Overall menopausal symptoms were more prevalent in perimenopause and postmenopause than women in the reproductive stage (p < 0.001). A total of 18.7% and 7.3% reported mild and moderate-to-severe overall symptoms among postmenopausal women, respectively, whereas only 7.5% and 2.0% experienced mild and moderate-to-severe overall symptoms among women in the reproductive stage, respectively. Mood swing, depression, paresthesia and urinary tract infection were more common among perimenopausal women, whereas most somatic symptoms (insomnia, dizziness, arthralgia and myalgia, headache, palpitations and skin formication) and sexual problems were more prevalent among postmenopausal women.
The associations of menopausal symptoms with CVD risk are presented in . After adjustment for potential confounders, mild (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.64–2.61) and moderate-to-severe (OR = 2.64, 95% CI: 1.92–3.63) overall menopausal symptoms were associated with increased likelihood of CVD, when compared to the group who did not report having menopausal symptoms. Significant positive associations between the severity of individual menopausal symptoms and CVD risk were observed for all 13 items. The largest adjusted ORs corresponded to mild palpitations (OR = 2.69, 95% CI: 2.15–3.36), followed by skin formication (OR = 1.96, 95% CI: 1.50–2.55) and arthralgia and myalgia (OR = 1.86, 95% CI: 1.48–2.34), compared with no symptoms. Moderate-to-severe symptoms of palpitations were associated with a 6.87-fold risk of CVD compared with no symptoms (OR = 6.87, 95% CI: 5.14–9.19), followed by urinary tract infection (OR = 3.05, 95% CI: 1.91–4.88) and arthralgia and myalgia (OR = 3.03, 95% CI: 2.34–3.91).
Table 3. Associations between menopausal symptoms and cardiovascular disease.
Discussion
In this study, we examined associations between the severity of menopausal symptoms assessed by the modified KMI and CVD risk in 9679 middle-aged women from six provinces of China. The results demonstrated that mild and moderate-to-severe overall menopausal symptoms were associated with an increased risk of CVD. We also found that the severity of individual menopausal symptoms including vasomotor, somatic, psychological and urogenital domains was also positively associated with CVD risk. In addition, we observed that overall and most individual menopausal symptoms, except for vasomotor symptoms, were more prevalent in older than younger women. We also found that psychological symptoms were more common in perimenopausal than postmenopausal women, while somatic symptoms were more prevalent in postmenopausal than perimenopausal women.
One important finding of this study is that the severity of overall menopausal symptoms was positively associated with CVD risk. Evidence from previous studies about the relationship between overall menopausal symptoms and CVD risk remains scarce, especially in Asian populations. Consistent with our findings, a previous observational cohort study of US women also reported that the severity of the vasomotor, somatic and cognitive-affective menopausal symptoms was significantly associated with total CVD risk [Citation5]. Similarly, the menopausal symptoms in this study also comprised symptoms of vasomotor, somatic, psychological and urogenital domains, and our results suggested that the severity of all these individual symptoms was also positively associated with CVD risk. The biological mechanisms underlying the link between menopause and CVD risk may partly due to decreases in estrogen levels [Citation16], while increases in traditional cardiovascular risk factors, such as changes in lipid profiles and indices of vascular health, during the time of menopause may also contribute to higher risk of CVD [Citation5]. Future large-scale prospective studies are needed to confirm the association between overall menopausal symptoms and CVD risk among Asian populations.
In addition, we found that mild and moderate-to-severe palpitations were associated with 2.69-fold and 6.87-fold increased risk of CVD compared with no symptoms, respectively. Consistent with our results, a longitudinal study of US women also reported mild and moderate/severe heart racing or skipping beats were associated with a 15% and 39% higher risk of CVD [Citation17]. Palpitations, highly prevalent among women during the menopause transition, may reflect women’s cardiovascular health [Citation17]. In contrast, a cross-sectional study of Japanese women suggested that palpitations were correlated with systolic blood pressure, but not with other cardiovascular parameters such as cardio-ankle vascular index, ankle–brachial pressure index and arrhythmia [Citation18]. However, this Japanese study only enrolled 394 women who attended the menopause clinic, and did not validate using a wider population.
In this study, insomnia was the most prevalent symptom reported by the participants who were diagnosed with and without CVD, and we found that mild and moderate-to-severe insomnia was associated with 19% and 150% increase on CVD risk, respectively. In line with our results, a recent meta-analysis including nine observational studies indicated a significant association between insomnia and higher incidence of myocardial infarction, one of the important subtypes of CVD, in the female population [Citation16]. Another cross-sectional study of South Korean midlife women also revealed a significant link between insomnia and CVD risk factors including total and low-density lipoprotein cholesterol levels [Citation19]. The potential pathogenetic mechanisms for the relationship between insomnia and CVD may partly because of dysregulation of the hypothalamic–pituitary axis, increased systemic inflammation and atherogenesis, abnormal modulation of the autonomic nervous system and elevated sympathetic nervous system activity [Citation20, Citation21].
Arthralgia and myalgia are the second most prevalent symptoms among women diagnosed with CVD in this study, and mild and moderate-to-severe arthralgia and myalgia were associated with 1.86-fold and 3.03-fold higher odds of CVD risk, respectively. A prospective cohort study of middle-aged UK women also indicated that women experiencing knee pain was associated with higher risk of CVD-specific mortality [Citation22]. Literature focusing on the relationship between arthralgia and myalgia and CVD risk remains limited. Several studies examined the association between osteoarthritis, characterized by pain, stiffness, swelling, deformity and reduced function of joints, and CVD risk. A meta-analysis of 15 studies revealed that osteoarthritis was a significant risk factor for CVD [Citation23], and another meta-analysis suggested a potential causal relationship between osteoarthritis and risk of coronary heart disease, heart failure and stroke [Citation24]. Additionally, several epidemiological studies reported the significant association of hand osteoarthritis with an increased risk of atherosclerosis and coronary heart disease [Citation25, Citation26]. There is growing evidence that osteoarthritis and CVD share many similar risk factors (e.g. age, reduced physical activity and obesity) and molecular mechanisms (e.g. oxidative stress and low-grade systemic inflammation) [Citation27].
This study also observed a significant association between vasomotor symptoms and an increased CVD risk, particularly among women aged 50–59 years. The relationship between vasomotor symptoms and CVD risk was widely investigated in western female populations. In line with our findings, a previous study pooled six prospective studies of western women and showed that greater severity of vasomotor symptoms was associated with higher risk of CVD [Citation28]. Another prospective cohort study conducted in 3083 US women also suggested that frequent and persistent vasomotor symptoms were associated with increased risk of CVD events [Citation7]. Contrary to our findings, a cross-sectional study based on Chinese postmenopausal women in Hong Kong reported that vasomotor symptoms were associated with several cardiovascular risk factors including low-density lipoprotein cholesterol and total cholesterol, but were not associated with CVD risk [Citation29], which might be partly due to a small sample size and a convenience sample used in the Hong Kong study.
Our findings may have some public health implications, as these results indicated that menopausal symptoms were associated with an increased risk of CVD, which reflected that women with CVD were more likely to be bothered by a variety of physical and psychological symptoms related to menopause. This finding emphasizes the importance of managing menopausal symptoms for women with CVD to relieve their physical and psychological symptoms and enhance their quality of life. Furthermore, our results indicated that the overall and most individual menopausal symptoms were more prevalent in older (60–70 years) than younger women (40–59 years), whereas vasomotor symptoms were more common among women aged 50–59 years. In addition, we found that psychological symptoms were more common in perimenopausal than postmenopausal women, while somatic symptoms were more prevalent in postmenopausal than perimenopausal women. These results suggested that women of different ages and menopausal status should pay attention to different menopausal symptoms based on the epidemiological characteristics of menopausal symptoms. Moreover, targeted interventions and strategies of management and treatment of menopausal symptoms were required for women of different ages and menopausal status, so as to contribute to prevention and control of CVD among middle-aged women.
The main strengths of this study include a relatively large sample size and adjustment for potential confounders. This study has several limitations. First, due to the nature of cross-sectional studies, this study cannot determine the direction of causality between menopausal symptoms and CVD risk. Second, this study used a self-reported diagnosis of CVD to examine the occurrence of CVD, and lacked confirmation from treating physicians. Finally, we only utilized the modified KMI to assess menopausal symptoms, and did not confirm them using other valid scales.
Conclusion
In summary, this study found that mild and moderate-to-severe overall menopausal symptoms were associated with an increased risk of CVD. Moreover, we also found that the severity of individual menopausal symptoms including vasomotor, somatic, psychological and urogenital domains was also positively associated with CVD risk. We observed that the overall and most individual menopausal symptoms, except for vasomotor symptoms, were more prevalent in older than younger women. Further large-scale prospective observational studies are needed to validate the relationship between the severity of menopausal symptoms and CVD risk among Asian populations.
Supplemental Material
Download MS Word (48.1 KB)Acknowledgements
The authors thank all participants and investigators who made it possible to complete this research project.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
- Woodward M. Cardiovascular Disease and the Female Disadvantage. Int J Environ Res Public Health. 2019;16(7):1165. doi: 10.3390/ijerph16071165.
- Peters SA, Woodward M. Women’s reproductive factors and incident cardiovascular disease in the UK Biobank. Heart. 2018;104(13):1069–1075. doi: 10.1136/heartjnl-2017-312289.
- Tobias DK, Stuart JJ, Li S, et al. Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women. JAMA Intern Med. 2017;177(12):1735–1742. doi: 10.1001/jamainternmed.2017.2790.
- Kannel WB, Hjortland MC, McNamara PM, et al. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med. 1976;85(4):447–452. doi: 10.7326/0003-4819-85-4-447.
- Aw PY, Pang XZ, Wee CF, et al. Co-prevalence and incidence of myocardial infarction and/or stroke in patients with depression and/or anxiety: a systematic review and meta-analysis. J Psychosom Res. 2023;165:111141. doi: 10.1016/j.jpsychores.2022.111141.
- Nudy M, Aragaki AK, Jiang X, et al. The severity of individual menopausal symptoms, cardiovascular disease, and all-cause mortality in the Women’s Health Initiative Observational Cohort. Menopause. 2022;29(12):1365–1374. doi: 10.1097/GME.0000000000002089.
- Thurston RC, Aslanidou Vlachos HE, Derby CA, et al. Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN. J Am Heart Assoc. 2021;10(3):e017416. doi: 10.1161/JAHA.120.017416.
- Cagnacci A, Cannoletta M, Palma F, et al. Menopausal symptoms and risk factors for cardiovascular disease in postmenopause. Climacteric. 2012;15(2):157–162. doi: 10.3109/13697137.2011.617852.
- Wang X, Wang L, Di J, et al. Prevalence and risk factors for menopausal symptoms in middle-aged Chinese women: a community-based cross-sectional study. Menopause. 2021;28(11):1271–1278. doi: 10.1097/GME.0000000000001850.
- Wang XY, Wang LH, Di JL, et al. Association of menopausal status and symptoms with depressive symptoms in middle-aged Chinese women. Climacteric. 2022;25(5):453–459. doi: 10.1080/13697137.2021.1998435.
- Cao Z. Chinese Obstetrics and Gynecology. Beijing, People’s Republic of China People’s Medical Publishing House; 2014. :.
- Li H, Zheng D, Li Z, et al. Association of depressive symptoms with incident cardiovascular diseases in middle-aged and older Chinese adults. JAMA Netw Open. 2019;2(12):e1916591. doi: 10.1001/jamanetworkopen.2019.16591.
- Tao M, Shao H, Li C, et al. Correlation between the modified Kupperman Index and the Menopause Rating Scale in Chinese women. Patient Prefer Adherence. 2013;7:223–229. doi: 10.2147/PPA.S42852.
- Li L, Wu J, Pu D, et al. Factors associated with the age of natural menopause and menopausal symptoms in Chinese women. Maturitas. 2012;73(4):354–360. doi: 10.1016/j.maturitas.2012.09.008.
- Harlow SD, Gass M, Hall JE, et al. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Climacteric. 2012;15(2):105–114. doi: 10.3109/13697137.2011.650656.
- Dean YE, Shebl MA, Rouzan SS, et al. Association between insomnia and the incidence of myocardial infarction: a systematic review and meta-analysis. Clin Cardiol. 2023;46(4):376–385. doi: 10.1002/clc.23984.
- Carpenter JS, Cortés YI, Tisdale JE, et al. Palpitations across the menopause transition in SWAN: trajectories, characteristics, and associations with subclinical cardiovascular disease. Menopause. 2023;30(1):18–27. doi: 10.1097/GME.0000000000002082.
- Enomoto H, Terauchi M, Odai T, et al. Independent association of palpitation with vasomotor symptoms and anxiety in middle-aged women. Menopause. 2021;28(7):741–747. doi: 10.1097/GME.0000000000001776.
- Ham OK, Kim J, Lee BG, et al. Behavioral characteristics and cardiovascular disease risks associated with insomnia and sleep quality among middle-aged women in South Korea. Res Nurs Health. 2017;40(3):206–217. doi: 10.1002/nur.21792.
- Javaheri S, Redline S. Insomnia and risk of cardiovascular disease. Chest. 2017;152(2):435–444. doi: 10.1016/j.chest.2017.01.026.
- Castro-Diehl C, Diez Roux AV, Redline S, et al. Association of sleep duration and quality with alterations in the hypothalamic-pituitary adrenocortical axis: the Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Endocrinol Metab. 2015;100(8):3149–3158. doi: 10.1210/jc.2015-1198.
- Kluzek S, Sanchez-Santos MT, Leyland KM, et al. Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women. Ann Rheum Dis. 2016;75(10):1749–1756. doi: 10.1136/annrheumdis-2015-208056.
- Wang H, Bai J, He B, et al. Osteoarthritis and the risk of cardiovascular disease: a meta-analysis of observational studies. Sci Rep. 2016;6(1):39672. doi: 10.1038/srep39672.
- Wang Z, Kang C, Xu P, et al. Osteoarthritis and cardiovascular disease: a Mendelian randomization study. Front Cardiovasc Med. 2022;9:1025063. doi: 10.3389/fcvm.2022.1025063.
- Jonsson H, Helgadottir GP, Aspelund T, et al. Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study. Ann Rheum Dis. 2009;68(11):1696–1700. doi: 10.1136/ard.2008.096289.
- Haugen IK, Ramachandran VS, Misra D, et al. Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham heart study. Ann Rheum Dis. 2015;74(1):74–81. doi: 10.1136/annrheumdis-2013-203789.
- Vaiciuleviciute R, Bironaite D, Uzieliene I, et al. Cardiovascular drugs and osteoarthritis: effects of targeting ion channels. Cells. 2021;10(10):2572. doi: 10.3390/cells10102572.
- Zhu D, Chung HF, Dobson AJ, et al. Vasomotor menopausal symptoms and risk of cardiovascular disease: a pooled analysis of six prospective studies. Am J Obstet Gynecol. 2020;223(6):898.e1–898.e16. doi: 10.1016/j.ajog.2020.06.039.
- Chair SY, Lo SWS, Cheung HY, et al. Vasomotor symptoms, cardiovascular risk factors, and cardiovascular disease risk among Chinese postmenopausal women in Hong Kong. Women Health. 2022;62(7):621–632. doi: 10.1080/03630242.2022.2100034.