A prospective cohort study on the association of lean body mass estimated by mid‐upper arm muscle circumference with hypertension risk in Chinese residents

1 INTRODUCTION

Lean body mass (LBM) or skeletal muscle mass plays a key role in energy metabolism, and the promotion of LBM and muscular strength is always advocated in preventing obesity-related metabolic abnormalities, as well as geriatric sarcopenia and frailty.1-3 Elevated blood pressure (BP) and hypertension are major risk factors of several cardiovascular diseases (CVDs), and generate huge health and economic burdens.4-6 The unfavorable relationship between LBM and hypertension has been found in cross-sectional studies, while opposite findings were also reported.7-10 Such inconsistency was probably resulted from the variances of populations, as well as the utilities of different measurements of LBM. On the other hand, the deficiency of longitudinal design in published studies made it failed to verify the causality between increased LBM and hypertension.

Currently, accurate measurements of LBM are majorly based on image methods, such as dual-energy x-ray absorptiometry (DXA) and computed tomography (CT). However, high costs and complicated operations limit their wide utilities among general populations.11 Mid-upper arm muscle circumference (MAMC) is a novel anthropometric index of LBM (skeletal muscle majorly) calculated using mid-upper arm circumference (MUAC) and triceps skinfold thickness (TST), both of which respectively reflected the overall amount of muscle and fat, and the subcutaneous fat of mid-upper arm.12-14 As an easier obtained measurement, MAMC has been proven to be closely correlated to some other more accurate measurements based on DXA and CT in various populations.15-17 However, studies about the relationship between MAMC and cardiovascular abnormalities are limited.18, 19

In addition, despite that positive associations of both MUAC and TST with hypertension have been reported, no study has disclosed which one was stronger associated with hypertension.20, 21 If the positive relationship between LBM and hypertension existed, MUAC, as a measurement of both fat and lean mass perhaps should be stronger associated with hypertension than TST. Such comparative analysis we thought would be necessary to indirectly verify the relationship between LBM and hypertension.

Therefore, in this study, we aimed to find out if MAMC, as an easier obtained anthropometric surrogate of LBM was positively associated with hypertension risk based on a large-scale longitudinal study among Chinese population; and also compare strengths of associations with hypertension between MUAC and TST to further elucidate the relationship between LBM and hypertension.

2 METHODS 2.1 Study design and populations

The China Health and Nutrition Survey (CHNS) is an ongoing open cohort project aiming to examine the effects of social and economic transformation of Chinese society on nutrition and health behaviors and outcomes among general Chinese residents.22 CHNS started from 1989 including 15 907 participants, and 10 rounds of follow-up surveys in 15 provinces and municipal cities have been completed by 2015.23 Considering that the biospecimens were collected from 2009, three waves of surveys (ie, 2009, 2011, 2015) were only included in our analysis. As shown in Figure 1, there were 9516 participants undergoing the baseline investigation in 2009, among whom 8054 were investigated in the follow-up surveys of 2011 or 2015 (39 736 person-years in total). We firstly excluded participants who were not eligible for the following analyses, including 836 younger than 18 years old; 84 with a history of myocardial infarction; 121 with a history of stroke; 62 in pregnancy; 46 missing either information of BP measurements or situation of hypertension treatments; 192 missing either information of weight or height; and 175 missing either information of MUAC or TST. As a result, 8185 participants were finally remained for the baseline analysis, among whom 5600 were without hypertension. By further excluding those without relevant follow-up information, 3442 participants were eligible for the cohort analysis. The data of CHNS are publicly available, and the researchers from the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention and the Carolina Population Center, University of North Carolina at Chapel Hill had received ethic approval in the Institute Review Board.

Details are in the caption following the image

Flow chart of this study

2.2 Measurements of MUAC and TST

The mid-point of the mid-upper arm was defined as the midway between the olecranon process of the ulna and the acromion process of the scapula, which was located after bending the right arm to a 90° angle at the elbow. MUAC was measured at the mid-point of mid-upper arm with the elbow fully extended using a metric scale, and recorded results to the nearest 0.1 cm. TST was measured at the halfway between the acromion process and the olecranon process, while the arm was hanging relaxed at the participant's side. The fold of skin and underlying subcutaneous fat 2.0 cm above the place where the measurement was to be taken were firstly grasped using the thumb and index finger, and then measured using a skinfold caliper with a constant pressure of 10 g/mm.2 The jaws of calipers were placed at the marked level, perpendicular to the skinfold, and the measurement was read within 3 s and to the nearest 0.5 mm. All measurements were performed by trained health care workers following the World Health Organization-recommended protocols.20, 24 For both MUAC and TST, 3-time measurements were respectively obtained per participant on the right arm as the first choice, and the average were used for the following analyses.

MAMC was calculated using the standard formula: MAMC (cm) = MUAC (cm) – π * TST (mm) /10.24, 25

2.3 BP measurements and the definition of hypertension

BP was measured using a standard mercury-column sphygmomanometer with an appropriate adult upper arm cuff size after 5 min of rest in the sitting position based on the standardized procedural guideline. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were determined by the first and the fifth Korotkoff sounds. BP on both right and left arm was firstly measured, and the arm with higher blood pressure would be selected to obtain three consecutive measurements with a time interval of at least 1 min. Then, the average on the selected arm would be recorded as the final BP. Before measuring, participants were also need to be asked for not doing following behaviors: drinking alcohol, tea or coffee; smoking; or taking any exercise for at least 30 min before measuring BP.26, 27 In this study, we defined hypertension as SBP/DBP ≥ 140/90 mmHg or antihypertensive medication use.

2.4 Measurements of confounders

All participants were asked to undergo body weight and height measurements while wearing light clothes without shoes. Body weight and height were measured using a vertical weight scale and the metric scale with a standardized protocol, respectively. Both body weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively. BMI was then calculated as weight (kg) divided by the square of the height (m).

Blood samples (12 mL) were collected after at least 8 h of overnight fasting, and then transferred to the local hospital for further treatment within 2 h of collection. The blood samples in red-stoppered tube (4 mL) were centrifuged at 3000 × g for 15 min at room temperature; serum samples were frozen and stored at −86 °C for the subsequent laboratory analysis. According to strict quality control standards, all samples were verified and analyzed in a national central laboratory in Beijing (Medical laboratory accreditation certificate: ISO 15189:2007). Triglycerides (TG) was measured using glycerol-phosphate oxidase (GPO-PAP) method (Kyowa, Tokyo, Japan). High density lipid-cholesterol (HDL-C) was measured using enzymatic methods (Kyowa), and total cholesterol (TC) was measured by the cholesterol oxidase-phenol and aminophenazone (CHOD-PAP) method. Fasting glucose (FG) was measured by glucose oxidase-phenol and aminophenazone (GOD-PAP) method (Randox, Crumlin, UK). All biochemical assessment aforementioned were performed using Hitachi 7600 automated analyzer (Hitachi Inc., Tokyo, Japan).28, 29

In addition, self-administered questionnaires were also used to obtain information on demographic characteristics, medical history, medication use, smoking habits, and other pertinent factors. Trained staff members confirmed the reported information with each participant. In this study, smoking status was categorized as current smokers, past smokers, and never. Drinking status were categorized as current drinkers and never.

2.5 Statistical analysis

All continuous variables were presented as mean and standard deviation (SD). Categorical variables were presented as percentages. Student t test and chi-square test were respectively used to estimate the difference of continuous and categorical variables between men and women.

In the baseline analysis, multivariable linear regression analyses were used to estimate the association of BP (SBP and DBP) with per SD increase of MAMC, MUAC and TST in participants without any antihypertensive medication use. The associations of hypertension with MAMC, MUAC and TST were estimated using multivariable logistic regression models, and results were shown using odds ratio (OR) and 95% confidence interval (95% CI).

In the cohort analysis, associations of changes of BP values during the follow-up with MAMC, MUAC, and TST were firstly estimated using linear regression models. We then used COX regression models to estimate the hypertension risk attributed to MAMC, MUAC and TST, and results were shown as hazard ratio (HR) and 95% CI. Restricted cubic splines (RCS) analyses with three knots at the 10th, 50th, and 90th centiles of MAMC, MUAC and TST were also used to estimate their associations with hypertension with flexibility by running rms package in R (v.4.0.3) software, and the values of their medians were set as the reference. On the other hand, associations of changes of MAMC, MUAC and TST during the follow-up with both changes of BP values and hypertension risk were estimated. We performed all above analyses in 3 models: Model 1 (adjusted for age), Model 2 (adjusted for smoking and alcohol drinking in addition to Model 1), and Model 3 (adjusted for TG, TC, HDL-C, and FG in addition to Model 1). All analyses were respectively completed in both men and women, and P-values of interaction by gender were given.

All above statistical analyses were completed using SAS 9.4 (SAS Institute, Inc., Cary, NC, USA) expect those with special notes. p-Value < .05 was considered as statistical significance.

3 RESULTS 3.1 General characteristics

Characteristics of the 8,185 participants (3,819 men) are shown in Table 1 as mean ± SD and percentages. No difference of age or BMI was found between men and women. Compared to women, larger MAMC and MUAC, as well as smaller TST were found in men with statistical significance. Both BP values and prevalence of hypertension were higher in men. Among biochemical biomarkers, higher FG and TG, but lower TC and HDL-C were found in men. In addition, men also showed dramatically higher percentages of cigarette smoking and alcohol drinking than women.

TABLE 1. Baseline characteristics of participants (no. = 8185) Men (n=3,819) Women (n=4,366) P-value Age (years old) 50.2 ± 15.1 50.5 ± 14.8 0.275 Weight (kg) 65.3 ± 11.4 56.9 ± 9.7 <0.001 Height (cm) 167.0 ± 6.7 160.0 ± 6.5 <0.001 BMI (kg/m2) 23.3 ± 3.4 23.4 ± 3.5 0.616 MAMC (cm) 23.1 ± 3.4 21.0 ± 3.2 <0.001 MUAC (cm) 27.7 ± 3.6 26.6 ± 3.6 <0.001 TST (mm) 14.6 ± 7.7 18.1 ± 7.2 <0.001 SBP (mmHg) 125.8 ± 17.3 123.4 ± 19.9 <0.001 DBP (mmHg) 82.1 ± 11.1 79.1 ± 11.3 <0.001 FG (mmol/L) 5.5 ± 1.6 5.3 ± 1.3 <0.001 TG (mmol/L) 1.8 ± 1.7 1.5 ± 1.2 <0.001 TC (mmol/L) 4.8 ± 1.0 4.9 ± 1.0 <0.001 HDL-C (mmol/L) 1.4 ± 0.5 1.5 ± 0.5 <0.001 Hypertension (%) 32.1 27.9 <0.001 Antihypertensive medication (%) 8.6 10.3 0.012 Smoking (%) <0.001 Current 55.6 3.7 Past 6 0.4 Never 38.4 96 Alcohol drinking (%) 60.7 8.9 <0.001 Values are presented as mean ± SD, or %. Abbreviations: BMI, body mass index; MAMC, mid-upper arm muscle circumference; MUAC, mid-upper arm circumference; TST, triceps skinfold thickness; SBP, systolic blood pressure; DBP, diastolic blood pressure; FG, fasting glucose; TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipid cholesterol. 3.2 Associations of MAMC, MUAC and TST with BP and hypertension prevalence at baseline

Among 7,406 participants without any antihypertensive treatment at baseline, SBP was independently associated with MAMC in both men and women, and the increase of SBP per SD of MAMC were 1.97  and 1.63 mmHg respectively in men and women after adjusted for age and biochemical markers in Model 3 (Table 2). The independently positive association of SBP with MUAC was found in both men and women, while for TST, the statistically significant association was only found in women. Statistically significant p-value for interaction by gender was found for TST (p-value = .014). Consistent results were found for DBP. As shown in Table 2, the increases per SD of MAMC were 1.58  and 1.08 mmHg respectively in men and women in Model 3. The positive association of DBP with MUAC was found in both men and women, while the association of DBP with TST was only found in women in Model 3, and p-value for interaction by gender was .012. Compared with TST, MUAC showed stronger association with BP due to a larger value of BP increase per SD of MUAC in both men and women.

TABLE 2. Adjusted associations of blood pressure with per SD increase of MAMC, MUAC, and TST (no. = 7406) Men (n=3,489) Women (n=3,917) BP (mmHg) 95% CI P-value BP (mmHg) 95% CI P-value P-value for interaction SBP Model 1 MAMC 2.15 1.65, 2.66 <0.001 1.93 1.40, 2.46 <0.001 0.440 MUAC 2.65 2.14, 3.17 <0.001 2.66 2.17, 3.15 <0.001 0.536 TST 0.76 0.26, 1.26 0.003 1.79 1.27, 2.31 <0.001 0.044 Model 2 MAMC 2.12 1.61, 2.63 <0.001 1.93 1.40, 2.46 <0.001 0.458 MUAC 2.61 2.09, 3.12 <0.001 2.66 2.17, 3.15 <0.001 0.537 TST 0.7 0.20, 1.21 0.006 1.8 1.28, 2.32 <0.001 0.040 Model 3 MAMC 1.97 1.46, 2.48 <0.001 1.63 1.10, 2.16 <0.001 0.622 MUAC 2.37 1.84, 2.89 <0.001 2.28 1.78, 2.78 <0.001 0.978 TST 0.46 -0.04, 0.97 0.072 1.45 0.93, 1.98 <0.001 0.014 DBP Model 1 MAMC 1.74 1.39, 2.08 <0.001 1.33 0.99, 1.67 <0.001 0.074 MUAC 2.52 2.17, 2.87 <0.001 2.15 1.84, 2.46 <0.001 0.047 TST 1.15 0.80, 1.49 <0.001 1.78 1.45, 2.11 <0.001 0.047 Model 2 MAMC 1.68 1.33, 2.03 <0.001 1.33 0.99, 1.67 <0.001 0.098 MUAC 2.44 2.09, 2.79 <0.001 2.15 1.84, 2.47 <0.001 0.067 TST 1.08 0.73, 1.42 <0.001 1.78 1.45, 2.11 <0.001 0.034 Model 3 MAMC 1.58 1.23, 1.92 <0.001 1.08 0.74, 1.42 <0.001 0.124 MUAC 2.28 1.93, 2.64 <0.001 1.84 1.53, 2.16 <0.001 0.190 TST 0.90 0.55, 1.24 <0.001 1.51 1.18, 1.85 <0.001 0.012 MAMC, MUAC, and TST were analyzed in separate regression models. Model 1: adjusted for age; Model 2: adjusted for smoking and alcohol drinking in addition to Model 1; Model 3: adjusted for TG, TC, HDL-C, and FG in addition to Model 1. Abbreviations: BP, blood pressure; 95% CI, 95% confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAMC, mid-upper arm muscle circumference; MUAC, mid-upper arm circumference; TST, triceps skinfold thickness.

As shown in Table 3, the association of MAMC with the prevalence of hypertension were found in both men and women in Model 3 (OR = 1.36, 95%CI: 1.26, 1.47 in men; OR = 1.33, 95%CI: 1.22, 1.44 in women), and no interaction by gender was found (Table 3). Also, positive associations of MUAC and TST with hypertension were found, respectively. Compared with TST, MUAC showed stronger association with the prevalence of hypertension with a larger OR per SD of MUAC in both men and women.

TABLE 3. Adjusted associations of hypertension prevalence with per SD increase of MAMC, MUAC, and TST (no. = 8185) Men (n=3,819) Women (n=4,366) OR 95% CI P-value OR 95% CI P-value P-value for interaction Model 1 MAMC 1.41 1.30, 1.52 <0.001 1.39 1.28, 1.50 <0.001 0.193 MUAC 1.59 1.47, 1.72 <0.001 1.62 1.49, 1.75 <0.001 0.555 TST 1.19 1.11, 1.28 <0.001 1.39 1.28, 1.50 <0.001 0.111 Model 2 MAMC 1.40 1.29, 1.51 <0.001 1.39 1.28, 1.51 <0.001 0.210 MUAC 1.58 1.46, 1.71 <0.001 1.62 1.50, 1.75 <0.001 0.538 TST 1.18 1.10, 1.27 <0.001 1.39 1.28, 1.50 <0.001 0.098 Model 3 MAMC 1.36 1.26, 1.47 <0.001 1.33 1.22, 1.44 <0.001 0.381 MUAC 1.52 1.41, 1.65 <0.001 1.53 1.41, 1.66 <0.001 0.305 TST 1.15 1.07, 1.24 <0.001 1.33 1.23, 1.44 <0.001 0.048 MAMC, MUAC, and TST were analyzed in separate regression models. Model 1: adjusted for age; Model 2: adjusted for smoking and alcohol drinking in addition to Model 1; Model 3: adjusted for TG, TC, HDL-C, and FG in addition to Model 1. Abbreviations: OR, odds ratio; 95% CI, 95% confidence interval; MAMC, mid-upper arm muscle circumference; MUAC, mid-upper arm circumference; TST, triceps skinfold thickness. 3.3 Associations of MAMC, MUAC, and TST with changes of BP value during the follow-up and hypertension risk in cohort analysis

Results of cohort analysis showed that the change of SBP during the follow-up were only associated with MUAC and TST in men in Model 2 (p-values were .049 and .029 for MUAC and TST, respectively), while such associations were abolished in Model 3 (Table S1). For DBP, both MAMC and MUAC were positively associated with the changes of BP values in men in Model 3. No interaction by gender was found for either SBP or DBP regardless of adjusted models. As shown in Table 4, the association of MAMC with the incidence of hypertension was statistical significant in both men and women in Model 3 (HR = 1.10, 95%CI: 1.01, 1.19 for men; HR = 1.15, 95%CI: 1.06, 1.26 for women). Stronger association with hypertension risk was found for MUAC in both men and women compared with TST. No interaction by gender was found for MAMC, MUAC or TST. In RCS analysis, although no P-value for nonlinearity was statistically significant, J-shaped relationships between hypertension risk and MAMC, as well as MUAC were found (Figure 2). As shown in figures, the hypertension risk did not dramatically increase until the values of MAMC and MUAC became larger than their medians. On the contrary, statistically significant increase of hypertension risk was only found in the situation of TST less than the median in men.

TABLE 4. Adjusted associations of hypertension incidence with per SD increase of MAMC, MUAC, and TST (no. = 3442) Men (n=1,504) Women (n=1,938) HR 95% CI P-value HR 95% CI P-value P-value for interaction Model 1 MAMC 1.11 1.02, 1.21 0.017 1.17 1.07, 1.28 <0.001 0.681 MUAC 1.21 1.11, 1.32 <0.001 1.21 1.11, 1.31 <0.001 0.414 TST 1.11 1.03, 1.20 0.006 1.05 1.01, 1.19 0.023 0.402 Model 2 MAMC 1.10 1.01, 1.20 0.031 1.18 1.08, 1.29 <0.001 0.663 MUAC 1.20 1.10, 1.31 <0.001 1.22 1.12, 1.32 <0.001 0.387 TST 1.11 1.03, 1.19 0.008 1.10 1.01, 1.19 0.021 0.403 Model 3

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