Abstract Objective A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population. Methods A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI. Results Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertension was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59–0.79, P < 0.001) and obese individuals (OR 0.51; 95% CI 0.38–0.70, P < 0.001). Conclusion In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.
Introduction Hypertension, characterized by chronically elevated blood pressure (BP) above 140/90 mmHg, is a major public health problem affecting more than 1 billion people worldwide (1, 2). Despite multiple methods to prevent and manage high blood pressure, the global incidence and prevalence of hypertension continues to increase significantly (3). Convincing evidence demonstrated that hypertension, untreated or uncontrolled, is a crucial contributor to cardiovascular disease, stroke, and chronic kidney diseases (2). Consequently, hypertension is the leading cause of mortality and disability globally, which results in a huge health burden (4). Startlingly, more than half of individuals with elevated BP were unaware of their hypertensive status in numerous surveys, partly owing to hypertension rarely showing symptoms in the early stages (3, 4, 5). Hence, hypertension is a silent killer. Previous research has demonstrated that intra-abdominal visceral deposition of adipose tissue, which characterizes upper-body obesity, plays a significant role in the development of hypertension (6, 7). Conversely, subjects with lower-body obesity exhibited a favorable metabolic profile (8). Due to the advantages of simplicity, convenience, harmlessness, and low cost, anthropometric measurements, especially circumferences, are useful options for estimating fat distribution and body composition, particularly in large-scale population-based studies. Certain circumferences have shown good performance in evaluating nutritional status, assessing obesity, screening for ectopic lipid deposits, and identifying decline of muscle mass (9, 10, 11). Moreover, some abnormal circumferences are marks of increased risk of certain diseases (12). For instance, a small thigh circumference was associated with greater risk of diabetes (13), cardiovascular diseases, and total mortality (14) in both men and women. Additionally, it is well established that waist circumference is positively correlated with blood pressure (15) and that a high waist–thigh circumference ratio is a risk factor for hypertension (16). Data indicate that thigh circumference may be an indicator of hypertension. To date, however, evidence from large-scale populations about the association between thigh circumference and hypertension is scarce. The aim of the present study was to examine the relationship between thigh circumference and blood pressure.
Methods Study population The study is a part of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) study, which was a community-based cross-sectional study conducted among 259,657 Chinese individuals aged 40 years and older, from 2011 to 2012 (17). The study design and methods have been described previously in detail (17, 18, 19). The data presented in this study are based on the baseline survey of subsamples from the Chongming District in Shanghai, China. A total of 9930 eligible subjects participated in the research. The individuals with data missing for thigh circumference, blood pressure (BP), and metabolic variables were excluded. The final model included 9520 subjects (3095 men and 6425 women). Data collection A standardized questionnaire was used by certified medical workers to gather essential information, including sex, age, smoking and alcohol consumption habits, physical activity, education status, and previous medical history. Anthropometric measurements were performed by trained physicians using standard protocols. Thigh circumference was measured directly below the gluteal fold of the thigh. The final thigh circumference is the average value of left thigh circumference and right thigh circumference. BP was measured with an automated electronic device (OMRON Model1 Plus; Omron Company, Kyoto, Japan) after the subjects sat down and rested quietly for >5 min. BP measurements were taken three times and the mean was recorded as the BP result. Overweight was defined as 24 kg/m2 ≤ BMI < 28 kg/m2 and obesity was defined as BMI ≥ 28 kg/m2. Biochemical measurements Peripheral venous blood samples were collected after 10 h of overnight fasting. Plasma glucose level was assessed by the glucose oxidase method (ADVIA-1650 Chemistry System, Bayer). Triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol were measured by an automatic analyzer (Hitachi 7080). Fasting insulin was assessed by RIA (Linco Research). Insulin resistance was evaluated by the homeostasis model of assessment for insulin resistance (HOMA-IR). Definition of hypertension Hypertension was defined as a systolic blood pressure (SBP) ≥ 140 mmHg, a diastolic blood pressure (DBP) ≥ 90 mmHg, or current use of antihypertensive medications (20). Statistical analysis Normally distributed continuous variables were presented as means ± s.d., and variables with skewed distribution were reported as medians (interquartile range) and log transformed to approximate normality before analysis. Categorical variables were described by percentage (%). P values were calculated by Student’s t-test (for continuous parametric variables) or nonparametric Mann–Whitney U test (for continuous nonparametric variables) and by Chi-squared tests for categorical variables. Multiple linear regression analyses were used to assess the association between thigh circumference and metabolic features. Multivariate logistic regression models were applied to estimate the odds ratios (ORs) for hypertension. Potential confounding variables including age, gender, smoking, alcohol drinking, physical activity, educational status, C-reactive protein (CRP), adiponectin, BMI, and HOMA-IR were controlled in the regression models. Data management and statistical analysis were performed with SPSS software (version 23.0). The significance level was set at P < 0.05, and P values were provided for two-sided tests. Ethics statement The study protocol was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Written informed consent was obtained from all participants.
Discussion In this study, we found that large thigh circumference is significantly associated with lower prevalence of hypertension in overweight and obese individuals, independent of age, BMI, and waist circumference. Moreover, thigh circumference is negatively correlated with both SBP and DBP. Differences in body fat distribution patterns have long been linked to certain metabolic disease risks (21, 22). Previous studies have reported that upper-body and lower-body fat have opposite (harmful vs beneficial) correlations with long-term blood pressure and the risk of developing diabetes (23). Advanced and accurate measuring techniques such as dual-energy X-ray absorptiometry and CT are often used to assess body fat and muscle distribution. However, these sophisticated, time-consuming, and costly techniques are not always feasible, particularly in large-scale population studies. Due to convenience, harmlessness, and low cost, simple anthropometric measurements, such as waist circumferences, are often preferable. Large waist circumference is a proxy of abnormal accumulation of visceral fat along with adverse metabolism (15, 24). Conversely, large thigh circumference is considered to be protective for diabetes and cardiovascular disease, and a small thigh circumference seems to be associated with an increased risk of developing heart disease (14, 25). There are two likely causes for the hypertensive risk difference between different thigh circumference groups. On the one hand, a small thigh circumference may involve low subcutaneous thigh fat. Several studies reported that, independently of high abdominal fat, low subcutaneous thigh fat contributed to adverse lipid and glucose metabolism, while high subcutaneous thigh fat was associated with favourable lipid and glucose metabolism (26). It is established that thigh subcutaneous adipose is negatively associated with fasting glucose, post load glucose, and HOMA-IR (27, 28). Moreover, greater thigh-fat deposition exhibited a more favorable metabolic profile including lower triglycerides and LDL-c (26), and thigh adipocytes were resistant to epinephrine-stimulated lipolysis, presumably due to an increase in alpha-adrenergic receptors (29). Therefore, the adverse glucose and lipid metabolism that mediates vascular dysfunction may link low thigh circumference to increased risk of elevated blood pressure. On the other hand, small thigh circumference may indicate a low thigh skeletal muscle mass, which is closely associated with increased risk factors for hypertension and diabetes (30, 31). Clear evidence demonstrated that obese individuals with sarcopenia have a higher risk of hypertension than patients with obesity or sarcopenia alone (31, 32). Obesity increases the risk of hypertension, a decline in thigh skeletal muscle mass increases this risk further. This may partially explain why we only found a stronger correlation of small thigh circumference and increased risk of developing hypertension in overweight and obese subjects. Additionally, skeletal muscle is the predominant site for insulin-stimulated glucose uptake, a lower thigh skeletal muscle mass may induce or promote dysfunctional glucose metabolism. The major strength of this study is that the analysis is performed in different BMI classifications. Many potential covariates were considered in the analysis to minimize the impact of confusing risk factors. However, there are several potential limitations to consider in this study. First, we could not quantify the thigh muscle mass, intermuscular adipose tissue, and subcutaneous fat accumulation by more accurate radiographic measures owing to limitations of epidemiological screening conditions. Therefore, the amount and size of thigh subcutaneous adipocyte and intermuscular adipocyte and thigh muscle mass are not clear. Second, since the current study is a cross-sectional analysis, we cannot draw conclusions on causality from our findings. Third, it is unclear whether our findings in overweight and obese middle‐aged and older Chinese subjects can be generalized to normal-weight or younger people of other ethnicities.
Conclusions In summary, large thigh circumference is independently associated with lower prevalence of hypertension, while small thigh circumference is linked to higher prevalence of hypertension in overweight and obese Chinese individuals. Based on the observations, it is necessary to include thigh circumference in routine anthropometric measurements, when evaluating populations at high risk of hypertension, cardiovascular diseases, or diabetes.
Declaration of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding This work was supported by the National Natural Science Foundation of China (81670743, 81370953); Shanghai Health System Outstanding Young Talents Training Program (XYQ2013098); and Shanghai Health and Family Planning Commission (21740173).
Availability of data This study is a part of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) study. All data analyzed in this study are based on REACTION study. The data are held in a secure and confidential database that can only be assessed by members of the REACTION group. The REACTION study website is http://www.rjh.com.cn/pages/neifenmike/REACTION/index.shtml.
Ethics approval and consent to participants This study protocol was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Written informed consent was obtained from all participants.
Author contribution statement Z Y, L Q, and Q S designed the study. Y N, W Z, X L, H Z, N L, H G, J W, and G N recruited the subjects, processed samples, and contributed to acquisition of data. Z Y and J S analyzed the data. J S wrote the manuscript. Z Y revised the manuscript.