Prevalence of cardiovascular risk factors in non-menopausal and postmenopausal inpatients with type 2 diabetes mellitus in China

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity worldwide [1]. The prevalence of CVD in China has increased rapidly since 2010, with stroke and ischemic heart disease accounting for most deaths [2] and is the first cause of death in Chinese women. However, in previous studies, compared to non-menopausal women, the incidence of CVD among postmenopausal women was found to be higher [3, 4]. The association between menopausal transition and the incidence of CVD is well known. For example, the increase in CVD risk is related to significant hormonal changes, especially estrogen deprivation at the time of menopause [4]. A decrease in oestradiol levels can lead to metabolic disorders, such as dyslipidemia, hypertension and increased central adiposity, which are considered to be cardiovascular risk factors [4‐6].

As is well known, diabetes mellitus is a significant risk factor for developing CVD. The major pathological basis of CVD begins with endothelial damage or dysfunction [7, 8]. A review has suggested that the female sex hormone estrogen mediates the relative protection of premenopausal women against cardiovascular disease, compared with age-matched men [9]. However, these protective effects are absent in women with diabetes [10, 11]. Among diabetic patients, high glucose promotes the increase of reactive oxygen species formation, which may neutralize the vasorelaxant and anti-inflammatory effects of NO [12]. In hyperglycemia, the estrogen receptors α to estrogen receptors β ratio declined with the decreased secretion of estrogen modulation on endothelial estrogen receptor expression, which may lead to vascular injury [13]. Diabetes also changes the vascular tissue at the molecular level by enhancing oxidative stress and pro-inflammatory response, as well as advancing glycation end products and protein Kinase C activation, which together promote the development of CVD [14]. In addition, among menopausal patients, age at menopause, time since menopause, and total reproductive years (i.e., the duration between menarche and menopause) may determine the duration and level of exposure to endogenous estrogen [15, 16]. Therefore, the risk of CVD among postmenopausal women with diabetics is higher. These findings are primarily based on studies conducted in Western populations. The relationship between the risk of CVD and menopause has been widely studied in China. Wu et al. [17] demonstrated that during a median follow-up period of 11.2 years, 246 out of 31,955 died from diabetes. In a Kailuan study, diabetic participants only accounted for 2.5% of all deaths [18]. A study by Gallagher et al. selected patients from among textile workers, but information on their diabetes status was not available [19]. These studies sampled the general population, but there is no research that has focused on diabetic patients in China [1, 17‐19]. Therefore, the aim of the present study was to investigate the prevalence of CVD risk factors and assess the 10-year risk of CVD using the Framingham Risk Score (FRS) on 569 non-menopausal and postmenopausal women with type 2 diabetes mellitus in China.

The findings of the present study indicate that the incidence of dyslipidemia, hypertension, overweight or obesity and NAFLD is high. All these indicators are considered to be conventional cardiovascular risk factors. The association between these factors and cardiovascular disease is well known [21, 24‐26]. The prevalence of dyslipidemia, hypertension, overweight or obesity and NAFLD in diabetic patients was found to be 36.2, 38.1, 56.6 and 58.2%, respectively, in the current study, which is higher than the rates reported of Ma et al. [27], Bachir Cherif et al. [28], Echouffo-Tcheugui et al. [29] and Younossi et al. [30]. The total prevalence in their studies were found to be 13.1, 31.6, 44.5 and 25.24%, respectively. The explanation for these differences may be due to differences among sample populations. In our study, subjects were recruited from among inpatients who had suffered from diabetes under critical conditions. The participants of the other studies were selected from a community dwelling or were outpatients, and most of them were healthy. In the current study, except for hypoglycemic agents, the usage rate of antihypertensive agents, lipid modulators and antithrombotic drugs was low. According to the guidelines for T2DM, health care professionals should promptly detect T2DM patients with hypertension, dyslipidemia and NAFLD, and provide early treatment measures, such as antihypertensive agents, lipid modulators and aspirin [21]. However, the treatment status of these Chinese T2DM inpatients was not ideal. In addition, the target goals for the control of blood glucose, blood pressure and blood lipids was only 1.2%, which is significantly lower than the 5.6% reported among type 2 diabetic outpatients [31]. Thus, achieving adequate control of risk factors for cardiovascular disease in patients with type 2 diabetes remains a clinical challenge [31]. For diabetic patients, complications may include dyslipidemia, hypertension, overweight or obesity, NAFLD. Therefore, healthcare professionals should not only focus on helping patients monitor their plasma glucose levels, but also intervene to achieve control of blood pressure and serum lipid.

We found that a higher risk of CVD was observed among diabetic patients who have experienced menopause, compared with non-menopausal women. The related factors are LDL-C and FPG levels. Two studies have shown that menopause has a marked effect on the circulation levels of lipids and lipoproteins, with an especially significant increase in LDL-C levels [32, 33]. Previous studies have examined the association between FPG, 2hPG and CVD risk in a community [18, 34, 35]. These studies have reported significant results, which are consistent with our findings. Shen et al. also indicate that postmenopausal women show significant association with worse glycemic control, including FPG levels, which is independently associated with 10-year cardiovascular risk [36, 37]. Additionally, diabetes is associated with chronic inflammation, which is characterized by the release of excess pro-inflammatory cytokines, abrupt levels of acute-phase proteins, and other mediators, which are integral to the severity of cardiovascular disorders [38‐40]. Menopause complicated with diabetes is an independent predictor of cardiovascular disease. Our study shows that the waist-to-hip-ratio is a protective factor for 10-year risk of CVD. In a study conducted on five hundred postmenopausal women study, truncal obesity with a waist-hip ratio > 0.8 was found in 68% of females, which does not indicate the association between waist-to-hip ratio and 10-year risk of CVD [41]. This is an urgent matter for healthcare providers to assist these patients in establishing a good lifestyle, in order to maintain a proper waist-to-hip ratio.

Furthermore, as the period of time since menopause increases, the CVD risk also increases. In a Chinese population study, compared to women who had been menopausal for less than 1 year, those with elapsed time since menopause of 2–3 years had higher coronary heart disease prevalence, and higher TG levels [42]. Cho et al. also determined that 10 to 14 years after menopause, postmenopausal women show an increased risk of high TG [43]. Additionally, time since menopause may related to some conventional CVD risk factors, such as metabolic syndrome or obesity [40, 43]. But a review has shown that there is no meaningful relationship that has emerged between time since menopause and CVD risk factors [44]. Further, a study of the relationship between time since menopause and CVD risk or relevant diseases is needed to explain the biological mechanisms.

This study has several limitations. First, although this is the first study to report that cardiovascular risk factors of menopausal women with type 2 diabetes mellitus, the study used a hospital-based cohort of a Chinese population, indicating that the study sample was from a single hospital. We cannot assume that our findings can be generalize to other groups. Second, the study population was hospitalized patients, which may have introduced a selection bias. In addition, there was also a memory bias in the study, especially when we asked some questions about reproductive factors, such as menstrual days, menstrual cycle, menopausal age, complications, and treatment regimen, subjects had to recall what had happened in the past, which is not the best method. Third, the lack of a non-diabetic age-matched control group was also a limitation of this study. Fourth, due to the observational nature of the study, the mechanisms proposed to explain the association between higher risk of CVD, menopausal status and FPG are merely speculative. Indeed, no tests of sex hormones have been performed. Finally, an analysis of the difference in autoantibody positivity between the non-menopause group and the menopause groups was not conducted, which is a shortcoming of this study.

In conclusion, among women with type 2 diabetes mellitus in China, the prevalence of cardiovascular risk factors are high. Although there is overwhelming evidence to indicate that achieving adequate control of blood pressure and lipids can significantly delay or prevent the onset of CVD, successful accomplishment of recommended therapeutic goals is a huge challenge. In diabetic females, except for menopausal state and time since menopause being uncontrollable factors, LDL-C, FPG and waist-to-hip ratio were found to be controllable factors. The clinical management of diabetes needs change. In addition to monitoring plasma glucose, interventions to improve blood pressure, serum lipids and lifestyle are needed. These women are currently too young to have experienced CVD events, therefore, the continued follow-up of these women needs to be conducted.