Abstract
Studies have indicated that increased body fat is associated with cardiovascular risk factors including hypertension. However, there is only limited information about the influence of body fat percentage (BF%) on incident hypertension. In a cohort of Korean genome epidemiology study (KoGES), 4864 non‐hypertensive participants were divided into 5 quintile groups, and followed‐up for 10 years to monitor incident hypertension. Cox proportional hazard model was used to evaluate the hazard ratio (HRs) and 95% confidence interval (CI) for hypertension (adjusted HRs [95% CI]) according to BF% quintile groups. Subgroup analysis was conducted by low or high level of BF% (cutoff: 22.5% in men and 32.5% in women) and low or high level of body mass index (BMI), waist circumference (WC) and waist‐to‐hip ratio (WHR). In adjusted model, compared with BF% quintile 1, the risk of incident hypertension significantly increased over BF% quintile 3 (BF% ≥19.9%) in men (quintile 3:1.42 [1.10‐1.85], quintile 4:1.58 [1.22‐2.05], quintile 5:1.82 [1.40‐2.36]), and quintile 4 (BF% ≥32.5%) in women (quintile 4:1.48 [1.12‐1.94], quintile 5:1.56 [1.20‐2.04]). Subgroup analysis showed that individuals with high BF% were significantly associated with the increased risk of hypertension even in individuals with low BMI, WC, and WHR. The risk of hypertension increased proportionally to BF% over the specific level of BF% in Koreans. Even in non‐obese individuals, increase in BF% was significantly associated with the increased risk of hypertension.
Keywords: body fat, body mass index, hypertension, obesity, waist circumference
1. INTRODUCTION
Hypertension is a major health challenge affecting 24% of men and 20% of women.1 The prevalence of hypertension is expected to increase up to 30% in 2025 as a result of rise in obesity and aging population.2 Several mechanisms explain why obesity is a strong risk factor for hypertension. These mechanisms include adipocyte dysfunction, insulin resistance, dysfunction in sympathetic nervous system, rennin‐angiotensin‐aldosterone system (RAAS), and increased intravascular volume and cardiac output.3, 4, 5 Although obesity is undoubtedly important in the pathogenesis of hypertension, not all individuals with hypertension are obese. In the National Health and Nutrition Examination Survey III, the prevalence of hypertension in individuals with normal body weight was 15.2% in men and 14.9% in women.6
It is known that increased body fat is an important risk factor for cardiovascular diseases (CVD). Anthropometric indices for obesity have been used to assess body fat content. Although BMI is used as a classic index for obesity, BMI is not an ideal indicator of body fat. Waist circumference (WC) or waist‐to‐hip ratio (WHR) are recognized to be more reliable indices for abdominal adiposity and body fat distribution,7 but they are less available in measuring total amount of body fat.
Bioelectrical impedance analysis (BIA) is a commonly used method for estimating body fat percentage (BF%). Accumulating evidence has indicated that increase in BF% was significantly associated with the cardiometabolic risk factors even in individuals with normal body mass index (BMI).8, 9, 10, 11 These results suggest the clinical usefulness of BF% as a potential cardiovascular risk factor.
Nonetheless, evidence is still insufficient in identifying the influence of BF% on the incidental risk of hypertension. Thus, using data from a cohort of Korean Genome and Epidemiology Study (KoGES), we conducted this study to assess the incidental risk for hypertension according to BF% level. Additionally, we examined how the risk of hypertension varies by BF% at the given degree of obesity.
2. RESEARCH DESIGN AND METHODS
2.1. Study subjects
Study participants were participants of the Korean Genome and Epidemiology Study (KoGES) Ansan and Ansung Study, which is a population‐based, epidemiology study of rural and urban community in South Korea. Detailed methods and participants of the present study were described in a previous study.12 The baseline survey of KoGES Ansan and Ansung study was completed in 2001‐2002, and follow‐up surveys were conducted every two years. Initially, a total of 10 038 participants aged 40 to 69 was enrolled in the study. 5018 participants and 5020 participants were recruited from residential district in Ansung and Ansan, respectively. Out of them, 3263 participants with underlying hypertension and missing values of blood pressure (BP) were excluded from study subjects. 1321 were further excluded due to missing value in BF%, waist circumference, and hip circumference. Additionally, during follow‐up, we identified follow‐up loss and incomplete follow‐up data in 590 cases. Finally, total number of study participants was 4864 in the present study (Figure 1). All participants participated in the study voluntarily, and informed consent was obtained in all cases. Ethics approvals for the study protocol and analysis of the data were obtained from the institutional review board of Kangbuk Samsung Hospital.
Figure 1.
Flowchart of enrolled study participants
2.2. Clinical, biochemical, and body composition measurements
Study data included a medical history and sociodemographic information provided by a self‐administered questionnaire, anthropometric measurements, and laboratory measurements. All study participants were asked to respond to a health‐related behavior questionnaire, which included the topics of alcohol consumption, smoking, and exercise. Physical activity divided into two categories: regular exercise (≥90 minutes exercise per week, at least moderate intensity) or inactive group. The questions about alcohol consumption comprised of the frequency of alcohol consumption on a weekly basis and the typical amount consumed on a daily basis (g/day). Smoking status divided into three categories: never, former, and current smoker. Diabetes mellitus (DM) was determined in the presence of one or more conditions as follows: fasting serum glucose level of at least 126 mg/dL, serum HbA1c level of at least 6.5%, 2h‐glucose level at least 200 mg/dL, and present history of diagnosed DM at baseline or follow‐up.13 All participants divided into three group according to baseline and follow‐up DM status (non‐DM on baseline/follow‐up study, baseline DM, follow‐up DM). Hypertension was defined in participants with history of diagnosed hypertension, or measured BP ≥140/90 mm Hg at initial and follow‐up check. At baseline and follow‐up visit, trained health care providers measured BP by auscultatory method in accordance with a standardized protocol.14 BP measurement was done in sitting position after relaxed state for at least 10 minutes. Inflatable cuff placed around the upper arm at the same level as the heart, attached to a mercury manometer, and the first and the fifth phases of Korotkoff sounds were used in detecting systolic blood pressure (SBP) and diastolic blood pressure (DBP). BP measurement was done two times with 5 minutes’ interval, and at each measurement, BP was measured at both arms. In each measurement, SBP and DBP were defined by the average of the both arms’ readings. Using BP checked at two times’ measurement, we determined final SBP and DBP by the arithmetic mean value of BP. All participant's height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Waist circumference (WC) and hip circumference were measured three times at the midpoint between the bottom of the rib cage and top of the iliac crest (WC) and maximum protrusion of the buttocks (hip circumference), respectively. The final waist and hip circumference was calculated by mean value of three readings. Waist‐to‐Hip ratio (WHR) was calculated by WC divided by hip circumference.
After overnight fasting for 12 hours, the plasma concentrations of glucose, total cholesterol (TC), triglyceride (TG), and high‐density lipoprotein‐cholesterol (HDL‐C) were measured enzymatically using a 747 Chemistry Analyzer (Hitachi, Tokyo, Japan). The fasting plasma insulin concentrations were determined by a radioimmunoassay kit (Linco Research,St. Charles, MO). The HbA1C level was measured by high‐performance liquid chromatography (VARIANT II; Bio‐Rad Laboratories, Hercules, CA). Insulin resistance was calculated by homeostasis model assessment‐insulin resistance (HOMA‐IR), using following formula: HOMA‐IR = fasting serum insulin (µU/mL) × fasting serum glucose (mg/dL)/405.15
BF%, muscle mass and lean body mass were measured by tetrapolar bioelectrical impedance analysis (BIA) (Inbody 3.0, Biospace, Korea). Using formulas previously validated on a previous study,16 BIA measures two parameters of fat and lean tissue and calculates BF%. BMI ≥25 kg/m2 was used as a cutoff of obesity based on the Asian‐Pacific specific cutoff point of obesity,17 and WHR ≥0.9 or WC ≥90 cm in men and WHR ≥0.85 or WC ≥85 cm in women were used as a cutoff for abdominal obesity based on the Asian‐Pacific specific cutoff point of obesity and WHO recommendation.18, 19
2.3. Statistical analysis
All study participants were divided into 5 groups according to the quintiles of BF% in each gender. Data are presented as means ± standard deviation for continuous variables and as proportions for categorical variables. To test linear trends of variables across the BF% quintile, linear regression model was used for continuous variables, and Cochran‐Armitage trend test was used for categorical variable.
The unadjusted and multivariate‐adjusted hazard ratios (HR) and their 95% confidence intervals (CI) for hypertension (adjusted HRs [95% CI]) were estimated with the use of the Cox proportional hazards model. Each gender group was categorized into five groups according to their quintile of BF%. The covariates of the adjusted model are age, study area (Ansan or Ansung), DM, regular exercise, smoking, alcohol intake, HOMA‐IR, CRP, HDL‐C, total calorie intake, sodium intake (Model 1). The covariates of model 1 were selected out of the classic cardiovascular risk factors presenting the statistically significant difference in mean levels among groups. Additionally, to identify whether the influence of BF% on the incident hypertension is independent of anthropometric measurements, we analyzed adjusted HRs for incident hypertension after adjusting for model 1 plus each BMI, WC, and WHR, respectively. The incidence cases of hypertension and incidence density (incidence cases per 1000 person‐years) were also calculated in each study groups.
Subgroup analysis was conducted in four subgroups stratified by each cutoff in BF% and anthropometric indices including BMI, WC, and WHR (group 1: low BF% with low BMI/WC/WHR, group 2: high BF% with low BMI/WC/WHR, group 3: low BF% with high BMI/WC/WHR, group 4: high BF% with high BMI/WC/WHR). The cutoff of BF% was determined in quintile 4, which was significantly associated with increased risk for hypertension. Due to the small sample size of quintile three group (n = 15), BF% on quintile three could not be used as a cutoff in men.
Receiver operating characteristic (ROC) and area under curve (AUC) were calculated to compared the discriminative ability of the prediction models (model 1 and model 1 plus BMI/WC/WHR) on the risk of hypertension. Additionally, the event and non‐event Net reclassification index (NRI) were calculated by following formula: event NRI = P (up|event) – P (down|event), non‐event NRI = P (down|non‐event) – P (up|non‐event). Combined NRI obtained by sum of event and non‐event NRI (cutoff point for categorical NRI: 40%).
All statistical analyses were performed using R 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria), and P > .05 was considered to indicate statistical significance.
3. RESULT
Study participants were comprised of 2296 men and 2568 women. The mean age was 50.5 ± 8.3 in men and 50.1 ± 8.4 in women. The final follow‐up was done in 2011‐2012. During 10 years’ follow‐up, 30.2% of men (n = 693) and 25.5% of women (n = 655) had incident hypertension. The overall incidence density is 42.1 cases per 1000 person‐years in men and 34.1 cases per 1000 person‐years in women. The baseline clinical characteristics of study participants are presented in Table 1. The proportion of baseline hypertension and metabolic profiles like fasting glucose, HbA1c, TC, TG, HOMA‐IR, BMI, WC, hip circumference and WHR tended to increase proportionally to the quintile of BF% in both men and women.
Table 1.
Baseline clinical characteristics according to the body fat percentage (BF%) quintile
| Characteristics | Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 | P for trend |
|---|---|---|---|---|---|---|
| Men | ||||||
| Age (year) | 49.9 ± 8.5 | 49.7 ± 8.3 | 50.0 ± 8.2 | 49.4 ± 7.8 | 50.8 ± 8.5 | 0.201 |
| Fasting glucose (mg/dL) | 84.2 ± 15.3 | 87.7 ± 21.8 | 89.1 ± 27.0 | 92.5 ± 23.6 | 92.6 ± 25.3 | <0.001 |
| HOMA‐IR | 1.1 ± 0.6 | 1.4 ± 1.0 | 1.5 ± 0.9 | 1.8 ± 1.6 | 1.9 ± 1.1 | <0.001 |
| TC (mg/dL) | 177.9 ± 33.1 | 189.2 ± 34.7 | 191.8 ± 34.0 | 198.6 ± 34.0 | 201.8 ± 33.9 | <0.001 |
| TG (mg/dL) | 123.1 ± 82.2 | 152.9 ± 91.5 | 169.5 ± 100.2 | 192.6 ± 129.9 | 208.6 ± 119.9 | <0.001 |
| HDL‐C (mg/dL) | 47.8 ± 10.9 | 44.2 ± 9.6 | 42.3 ± 8.9 | 41.2 ± 8.5 | 40.5 ± 8.5 | <0.001 |
| CRP (mg/dL) | 0.2 ± 0.8 | 0.2 ± 0.4 | 0.2 ± 0.4 | 0.2 ± 0.3 | 0.3 ± 0.4 | 0.172 |
| Creatinine (mg/dL) | 1.01 ± 0.08 | 1.02 ± 0.09 | 1.03 ± 0.09 | 1.02 ± 0.09 | 1.03 ± 0.09 | 0.019 |
| BMI (kg/m2) | 21.1 ± 2.0 | 22.8 ± 1.9 | 24.2 ± 1.9 | 25.4 ± 1.9 | 26.8 ± 2.2 | <0.001 |
| Waist circumference (cm) | 75.2 ± 5.6 | 79.4 ± 5.4 | 83.0 ± 5.2 | 86.1 ± 5.1 | 89.6 ± 5.3 | <0.001 |
| Hip circumference (cm) | 89.0 ± 5.0 | 92.1 ± 4.7 | 94.4 ± 4.4 | 96.0 ± 4.3 | 97.6 ± 4.5 | <0.001 |
| Waist‐to‐hip ratio | 0.85 ± 0.06 | 0.86 ± 0.05 | 0.88 ± 0.05 | 0.90 ± 0.05 | 0.92 ± 0.05 | <0.001 |
| BF% | 14.4 ± 2.0 | 18.5 ± 0.8 | 21.2 ± 0.8 | 23.8 ± 0.8 | 28.0 ± 2.1 | <0.001 |
| Diabetes mellitus (%) | ||||||
| Baseline | 10.9% | 12.6% | 14.3% | 18.6% | 20.5% | <0.001 |
| Follow‐up | 7.2% | 8.9% | 11.7% | 15.9% | 19.4% | <0.001 |
| Average alcohol use (g/day) | 16.7 ± 28.0 | 17.3 ± 29.6 | 16.0 ± 23.0 | 16.3 ± 24.3 | 17.7 ± 29.5 | 0.799 |
| Current smoking (%) | 56.0% | 45.7% | 44.8% | 42.5% | 38.3% | <0.001 |
| Regular exercise (%) | 52.3% | 40.5% | 32.8% | 30.1% | 26.3% | <0.001 |
| Total energy intake (kcal/day) | 1964.9 ± 567.1 | 1898.4 ± 485.5 | 1961.9 ± 527.0 | 1948.3 ± 495.1 | 1961.0 ± 525.9 | 0.603 |
| Sodium intake (mg/day) | 3423.7 ± 1622.2 | 3393.5 ± 1467.2 | 3389.9 ± 1451.8 | 3429.8 ± 1458.3 | 3434.4 ± 1453.3 | 0.799 |
| Incidence of hypertension [n, (%)] | 116 (24.7%) | 111 (24.6%) | 138 (29.4%) | 152 (33.6%) | 176 (38.8%) | <0.001 |
| Time to incident hypertension (year) | 6.0 | 4.3 | 4.0 | 4.0 | 4.0 | |
| Women | ||||||
| Age (year) | 49.0 ± 8.5 | 48.8 ± 8.0 | 49.7 ± 8.1 | 50.1 ± 8.1 | 52.8 ± 8.6 | <0.001 |
| Fasting glucose (mg/dL) | 80.9 ± 13.3 | 81.7 ± 15.0 | 83.0 ± 17.1 | 83.7 ± 16.1 | 86.1 ± 19.8 | <0.001 |
| HOMA‐IR | 1.3 ± 1.0 | 1.5 ± 1.0 | 1.6 ± 1.1 | 1.7 ± 1.2 | 1.8 ± 1.4 | <0.001 |
| TC (mg/dL) | 177.7 ± 29.0 | 182.1 ± 30.5 | 188.7 ± 35.9 | 191.2 ± 34.1 | 198.6 ± 37.6 | <0.001 |
| TG (mg/dL) | 109.1 ± 51.4 | 129.9 ± 77.9 | 137.9 ± 69.6 | 137.9 ± 69.6 | 159.2 ± 91.8 | <0.001 |
| HDL‐C (mg/dL) | 49.4 ± 10.2 | 46.8 ± 10.0 | 45.9 ± 9.8 | 45.2 ± 9.5 | 44.5 ± 9.3 | <0.001 |
| CRP (mg/dL) | 0.1 ± 0.3 | 0.1 ± 0.3 | 0.2 ± 0.4 | 0.2 ± 0.5 | 0.2 ± 0.3 | <0.001 |
| Creatinine (mg/dL) | 0.96 ± 0.10 | 0.96 ± 0.10 | 0.97 ± 0.11 | 0.97 ± 0.10 | 0.96 ± 0.11 | 0.516 |
| Waist circumference (cm) | 72.3 ± 6.8 | 76.0 ± 7.1 | 79.4 ± 7.4 | 81.6 ± 7.5 | 87.2 ± 8.4 | <0.001 |
| Hip circumference (cm) | 88.4 ± 4.6 | 92.2 ± 4.2 | 93.5 ± 4.2 | 95.2 ± 4.5 | 99.1 ± 5.5 | <0.001 |
| Waist‐to‐hip ratio | 0.82 ± 0.08 | 0.83 ± 0.08 | 0.85 ± 0.08 | 0.86 ± 0.09 | 0.88 ± 0.08 | <0.001 |
| BF% | 23.5 ± 2.7 | 28.7 ± 1.0 | 31.4 ± 0.6 | 33.6 ± 0.8 | 37.8 ± 2.3 | <0.001 |
| Diabetes mellitus (%) | ||||||
| Baseline | 11.3% | 14.1% | 13.5% | 13.4% | 18.7% | <0.001 |
| Follow‐up | 4.5% | 6.4% | 9.0% | 10.9% | 12.0% | <0.001 |
| Average alcohol use (g/day) | 1.8 ± 9.4 | 1.1 ± 3.8 | 1.5 ± 5.7 | 1.3 ± 4.8 | 1.3 ± 5.2 | 0.329 |
| Current smoking (%) | 2.8% | 3.3% | 2.0% | 2.4% | 1.0% | 0.084 |
| Regular exercise (%) | 36.7% | 30.8% | 34.2% | 28.3% | 27.4% | <0.001 |
| Total energy intake (kcal/day) | 1829.5 ± 597.2 | 1830.6 ± 554.9 | 1827.3 ± 547.7 | 1802.2 ± 508.9 | 1849.5 ± 571.8 | 0.889 |
| Sodium intake (mg/day) | 3134.0 ± 1514.9 | 3074.2 ± 1343.2 | 3152.9 ± 1495.2 | 3305.9 ± 1444.5 | 3203.3 ± 1432.7 | 0.064 |
| Incidence of hypertension [n, (%)] | 113 (21.9%) | 118 (22.2%) | 110 (22.1%) | 139 (26.9%) | 175 (34.5%) | <0.001 |
| Time to incident hypertension (year) | 5.6 | 5.7 | 6.1 | 5.7 | 5.5 | |
Continuous variables are expressed as mean (±SD), and categorical variables are expressed as number (percentage (%)).
BF%, body fat %; BMI, body mass index; CRP, C‐reactive protein; HDL‐C, high‐density lipoprotein cholesterol; HOMA‐IR, homeostasis model assessment of insulin resistance; TC, total cholesterol; TG, triglyceride; time to hypertension, median time to incident hypertension.
Table 2 shows the incidence case, incidence density, unadjusted, and multivariate‐adjusted HRs for hypertension in men and women. When the first quintile 1 of BF% was set as a reference, HRs for hypertension adjusted by model 1 significantly increased above BF% level in quintile 3 (BF% ≥19.9%) in men (quintile 2:1.09 [0.84‐1.43]. quintile 3:1.42 [1.10‐1.85], quintile 4:1.58 [1.22‐2.05], quintile 5:1.82 [1.40‐2.36]), and quintile 4 (BF% ≥32.5%) in women (quintile 2:1.13 [0.86‐1.49], quintile 3:1.12 [0.85‐1.49], quintile 4:1.48 [1.12‐1.94], quintile 5:1.56 [1.20‐2.04]). However, incorporating baseline BMI and WC into adjusting covariates with model 1 negated the statistical significance in all quintile groups in both men and women, and adjustment for model 1 plus WHR also attenuated the association.
Table 2.
Hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension according to body fat percentage (BF%) quintile
| Characteristics | Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 |
|---|---|---|---|---|---|
| Men (BF%) | (7.1‐16.9) | (17.0‐19.8) | (19.9‐22.4) | (22.5‐25.3) | (25.4‐38.3) |
| Unadjusted HR | 1.00 (Reference) | 1.06 (0.81‐1.37) | 1.33 (1.04‐1.71) | 1.52 (1.20‐1.94) | 1.83 (1.45‐2.31) |
| Model 1 | 1.00 (Reference) | 1.09 (0.84‐1.43) | 1.42 (1.10‐1.85) | 1.58 (1.22‐2.05) | 1.82 (1.40‐2.36) |
| Model 1 plus BMI | 1.00 (Reference) | 0.99 (0.75‐1.31) | 1.16 (0.88‐1.55) | 1.20 (0.89‐1.63) | 1.23 (0.87‐1.74) |
| Model 1 plus WC | 1.00 (Reference) | 0.99 (0.76‐1.31) | 1.17 (0.88‐1.55) | 1.21 (0.90‐1.64) | 1.27 (0.91‐1.77) |
| Model 1 plus WHR | 1.00 (Reference) | 1.04 (0.80‐1.37) | 1.30 (0.99‐1.69) | 1.38 (1.05‐1.81) | 1.50 (1.13‐2.00) |
| Incidence cases | 116 | 111 | 138 | 152 | 176 |
| Incidence density | 32.5 | 33.8 | 41.5 | 47.5 | 57.2 |
| Women | (11.6‐26.7) | (26.8‐30.3) | (30.4‐32.4) | (32.5‐35.1) | (35.2‐47.2) |
| Unadjusted HR | 1.00 (Reference) | 1.02 (0.79‐1.32) | 1.01 (0.77‐1.31) | 1.34 (1.05‐1.72) | 1.78 (1.40‐2.25) |
| Model 1 | 1.00 (Reference) | 1.13 (0.86‐1.49) | 1.12 (0.85‐1.49) | 1.48 (1.12‐1.94) | 1.56 (1.20‐2.04) |
| Model 1 plus BMI | 1.00 (Reference) | 1.03 (0.77‐1.37) | 0.96 (0.71‐1.31) | 1.20 (0.87‐1.65) | 1.10 (0.75‐1.62) |
| Model 1 plus WC | 1.00 (Reference) | 1.05 (0.79‐1.39) | 0.98 (0.73‐1.32) | 1.24 (0.92‐1.68) | 1.22 (0.89‐1.68) |
| Model 1 plus WHR | 1.00 (Reference) | 1.10 (0.83‐1.46) | 1.07 (0.80‐1.42) | 1.38 (1.04‐1.83) | 1.45 (1.10‐1.91) |
| Incidence cases | 113 | 118 | 110 | 139 | 175 |
| Incidence density | 28.6 | 28.9 | 28.5 | 37.2 | 48.9 |
Model 1: adjusted for age, study area (Ansan or Ansung), diabetes mellitus (baseline, follow‐up), regular exercise, smoking, alcohol intake, HOMA‐IR, CRP, HDL‐C, total calorie intake, sodium intake. Incidence density: incidence cases per 1000 person‐year.
Data of subgroup analyses stratified by low and high levels in BMI, WC, WHR, and BF% subgroup (group 1: low BMI/WC/WHR and low BF%, group 2: low BMI/WC/WHR and high BF%, group 3: high BMI/WC/WHR and low BF%, group 4: high BMI/WC/WHR and low BF%) are presented in Tables 3, 4, 5. When the group 1 was set as a reference, men with high BF% had the significantly increased adjusted HRs for hypertension in each subgroup of BMI (group 2:1.36 [1.06‐1.74], group 3:1.57 [1.21‐2.05], group 4:1.66 [1.38‐2.01]) (Table 3), WC (group 2:1.31 [1.08‐1.58], group 3:1.56 [0.99‐2.45], group 4:1.80 [1.45‐2.24]) (Table 4), and WHR (group 2:1.34 [1.08‐1.68], group 3:1.15 [0.90‐1.47], group 4:1.62 [1.31‐1.99]) (Table 5). Also in women, this association was similarly observed in each subgroup of BMI (group 2:1.20 [0.90‐1.59], group 3:1.09 [0.81‐1.48], group 4:1.50 [1.24‐1.81]) (Table 3), WC (group 2:1.24 [0.99‐1.55], group 3:0.96 [0.71‐1.29], group 4:1.54 [1.24‐1.90]) (Table 4), and WHR (group 2:1.38 [1.05‐1.80], group 3:1.24 [0.96‐1.62], group 4:1.67 [1.30‐2.15]) (Table 5). However, adjusted HRs in group 3 (high BMI/WC/WHR and low BF%) didn't show the statistically significant results in all cases of men and women.
Table 3.
Hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension according to obesity defined as body fat percentage (BF%) and BMI subgroup
| Characteristics | Group 1 | Group 2 | Group 3 | Group 4 |
|---|---|---|---|---|
| BMI and BF% | ||||
| Men | ||||
| Unadjusted HR | 1.00 (Reference) | 1.38 (1.10‐1.74) | 1.51 (1.17‐1.94) | 1.71 (1.44‐2.02) |
| Model 1 | 1.00 (Reference) | 1.36 (1.06‐1.74) | 1.57 (1.21‐2.05) | 1.66 (1.38‐2.01) |
| Incidence cases | 289 | 93 | 76 | 235 |
| Incidence density | 33.4 | 45.4 | 49.7 | 55.6 |
| Women | ||||
| Unadjusted HR | 1.00 (Reference) | 1.21 (0.96‐1.63) | 1.07 (0.81‐1.43) | 1.67 (1.41‐1.98) |
| Model 1 | 1.00 (Reference) | 1.20 (0.90‐1.59) | 1.09 (0.81‐1.48) | 1.50 (1.24‐1.81) |
| Incidence cases | 285 | 67 | 56 | 247 |
| Incidence density | 28.3 | 34.4 | 30.8 | 46.1 |
Incidence density: incidence cases per 1000 person‐year. Model 1: adjusted for age, study area (Ansan or Ansung), diabetes mellitus (baseline, follow‐up), regular exercise, smoking, alcohol intake, HOMA‐IR, CRP, HDL‐C, total calorie intake, sodium intake. Group 1: low BMI (<25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 2: low BMI (<25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women. Group 3: high BMI (≥25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 4: high BMI (≥25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women).
Table 4.
Hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension according to obesity defined as body fat percentage (BF%) and Waist Circumference subgroup
| Characteristics | Group 1 | Group 2 | Group 3 | Group 4 |
|---|---|---|---|---|
| Waist circumference and BF% | ||||
| Men | ||||
| Unadjusted HR | 1.00 (Reference) | 1.28 (1.07‐1.53) | 1.84 (1.19‐2.86) | 2.08 (1.71‐2.53) |
| Model 1 | 1.00 (Reference) | 1.31 (1.08‐1.58) | 1.56 (0.99‐2.45) | 1.80 (1.45‐2.24) |
| Incidence cases | 344 | 189 | 21 | 139 |
| Incidence density | 34.9 | 44.1 | 64.1 | 70.0 |
| Women | ||||
| Unadjusted HR | 1.00 (Reference) | 1.18 (0.96‐1.46) | 1.50 (1.15‐1.96) | 2.32 (1.92‐2.80) |
| Model 1 | 1.00 (Reference) | 1.24 (0.99‐1.55) | 0.96 (0.71‐1.29) | 1.54 (1.24‐1.90) |
| Incidence cases | 275 | 133 | 66 | 181 |
| Incidence density | 26.7 | 31.1 | 42.2 | 59.6 |
Incidence density: incidence cases per 1000 person‐year. Model 1: adjusted for age, study area (Ansan or Ansung), diabetes mellitus (baseline, follow‐up), regular exercise, smoking, alcohol intake, HOMA‐IR, CRP, HDL‐C, total calorie intake, sodium intake. Group 1: low BMI (<25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 2: low BMI (<25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women. Group 3: high BMI (≥25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 4: high BMI (≥25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women).
Table 5.
Hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension according to obesity defined as body fat percentage (BF%) and Waist‐to‐Hip Ratio (WHR) subgroup
| Characteristics | Group 1 | Group 2 | Group 3 | Group 4 |
|---|---|---|---|---|
| WHR and BF% | ||||
| Men | ||||
| Unadjusted HR | 1.00 (Reference) | 1.32 (1.07‐1.63) | 1.63 (1.31‐2.03) | 2.08 (1.72‐2.50) |
| Model 1 | 1.00 (Reference) | 1.34 (1.08‐1.68) | 1.15 (0.90‐1.47) | 1.62 (1.31‐1.99) |
| Incidence cases | 250 | 129 | 115 | 199 |
| Incidence density | 31.5 | 41.1 | 51.2 | 63.5 |
| Women | ||||
| Unadjusted HR | 1.00 (Reference) | 1.42 (1.10‐1.83) | 2.29 (1.85‐2.84) | 3.07 (2.49‐3.78) |
| Model 1 | 1.00 (Reference) | 1.38 (1.05‐1.80) | 1.24 (0.96‐1.62) | 1.67 (1.30‐2.15) |
| Incidence cases | 149 | 97 | 192 | 217 |
| Incidence density | 19.7 | 27.5 | 44.6 | 57.4 |
Incidence density: incidence cases per 1000 person‐year. Model 1: adjusted for age, study area (Ansan or Ansung), diabetes mellitus (baseline, follow‐up), regular exercise, smoking, alcohol intake, HOMA‐IR, CRP, HDL‐C, total calorie intake, sodium intake. Group 1: low BMI (<25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 2: low BMI (<25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women. Group 3: high BMI (≥25 kg/m2) + low BF % (<22.5% in men, <32.5% in women). Group 4: high BMI (≥25 kg/m2) + high BF % (≥22.5% in men, ≥32.5% in women).
Table S1 presents the analysis of net reclassification index (NRI) and area under curve (AUC) with adjustment for model 1 and model 1 plus each BMI, WC, and WHR. In NRI analysis, compared with NRI with adjustment for model 1, NRI with adjustment for model 1 plus each BMI, WC, and WHR didn't show the distinct difference. AUC analysis also showed similar finding. Compared with AUC adjusted by model 1, AUC adjusted by model 1 plus each BMI, WC and WHR didn't show the statistically significant difference.
4. DISCUSSION
In the present study, we observed that the risk of hypertension significantly increased proportionally to BF% over the specific level. Elevated BF% was associated with increased risk for hypertension, which was identified even in individuals with normal BMI, WC, and WHR. These results suggest that BF% is effective in assessing the risk for hypertension at given BMI, WC, and WHR.
Previous studies have demonstrated findings in line with ours. In an observation for 6171 US adults, individuals with normal BMI and high body fat content were significantly associated with the higher prevalence of metabolic syndrome.8 A cross‐sectional analysis for Koreans also showed that high BF% (≥25% in men and ≥30% in women) was significantly associated with cardiometabolic risk factors including high BP even in individuals with normal BMI.9 Additionally, longitudinal studies have shown the increased risk of hypertension in individuals with elevated BF%. The Aerobics Center Longitudinal Study 20 indicated that men with upper level of BF% had the higher adjusted HRs for hypertension (1.37 [1.11‐1.69]) than men with low level of BF%. In a study for 478 non‐hypertensive South Africans, the risk of hypertension was more significantly associated with baseline body fat mass, trunk, and arm fat mass, rather than changes in these variables.21 Our study may provide additional insight to the association between BF% and hypertension.
First, specific level of BF% was significantly associated with the increased risk of hypertension. Men with BF% more than 19.9% (≥ quintile 3) and women with BF% more than 32.5% (≥ quintile 4) had the significantly increased risk for hypertension, compared with their quintile 1 group. This finding suggests that BF% over specific level is clinically important as a risk factor for hypertension. Additionally, it is inferred that the risk of hypertension in Koreans increases at the level of BF% lower than the classic cutoff of BF% for obesity (25% in men and 35% in women).
Second, elevated BF% was associated with increased risk of hypertension even in individuals with low BMI, WC, and WHR. This result suggests that BF% is a potentially useful in screening high risk group for hypertension among non‐obese population. Nonetheless, these findings should be interpreted with caution. In our analysis, adjustment for model 1 plus each BMI, WC, and WHR markedly attenuated the degree of association between BF% and hypertension, negating the statistical significance in some cases. A recent work presented that WC and WHR were the most useful indices for identifying prevalence of DM and hypertension in South Asian adults.22 The clinical usefulness of BF% may be restricted to a supplementary tool for classic indices like BMI, WC, and WHR in predicting the risk of hypertension.
Third, the risk of hypertension in Koreans increased at the level of BF% lower than the classic cutoff of BF% for obesity (25% in men and 35% in women). These findings are in line with previous reports that Asians have the higher cardiometabolic risk even at given BMI, compared with Caucasians.23, 24 In addition to these reports, our results may be evidence indicating the vulnerability of Asians for cardiovascular risk.
Our results suggest gender difference in the association of BF% with hypertension and CRP. Women had the relatively weaker association between BF% and incident hypertension, where HRs for hypertension were generally lower in women than men. Additionally, women showed the statistically significant difference in baseline CRP levels across BF% quintiles (P < .001), whereas men didn't show the significant difference (P = .516). These findings may be partly explained by menopausal transition and gender difference in the relationship between CRP and BF%. Menopause is a well‐known risk factor for hypertension due to activation of RAAS,25 and drop in estrogen.26, 27 Considering the baseline mean age of women (50.1 ± 8.4), most of them might reach menopausal state over 10 years' follow‐up. Thus, it is speculated that adverse metabolic milieu related to menopause might have a more powerful impact on the development of hypertension rather than BF% itself. Regarding the relationship between CRP and BF%, it was demonstrated that CRP levels increase to a greater degree with increasing adiposity in women than in men.28 Additionally, Khera et al showed that the quantity and distribution of body fat influence CRP to a greater extent in women, compared with men.29 The impact of BF% on CRP may be stronger in women than men, which may account for the more prominent difference in CRP levels across BF% in women than men.
The advantages of our study are substantial number of participantsand identifiable medical data obtained form a cohort of KoGES. These merits allowed us to evaluate the risk for hypertension according to the level of BF% quintile and the subgroups stratified by BF% and each BMI, WC, and WHR.
Nonetheless, several weaknesses should be recognized in the study.
First, the equation of BIA was not sufficiently validated in obese individuals with BMI greater than 34 kg/m2.30 Additionally, BF% derived from BIA was not superior to BMI to predict cardiovascular risk factors in overweight or obese children and adolescents.31 However, considering age and BMI in our subjects, these weakness were not likely to have great impact on our results. Nonetheless, it is acknowledged that BIA has a inherent limitation in assessing cardiovascular risk.
Second, ausculatory BP measurement is not an ideal method in diagnosing hypertension. In particular, there was possibility of masked hypertension and white coat hypertension in our subjects. Previous studies have reported that overall prevalence of masked hypertension and white coat hypertension are 10%‐30% 32 and 10%‐15%,33 respectively. Thus, there might be underestimated or overestimated hypertension in our subjects.
Third, our data didn't include the full information about menopausal state, smoking status, drug use, kidney function, some cardiovascular risk profiles, and history of renal disease that closely link to BP. Changes in these variables over follow‐up may have an impact on incident hypertension. This limitation precludes us from identifying the influence of these variables on our results.
In conclusion, BF% over specific level was significantly associated with the increased risk of hypertension in Koreans. Even in non‐obese population, elevated BF% led the increased risk of hypertension. These results may provide the additional insight to assessing the high risk group of hypertension.
CONFLICT OF INTEREST
Nothing to be declared. The authors report no relationships that could be construed as a conflict of interest.
AUTHOR CONTRIBUTION
All authors had access to the data used in this study and participated in writing the manuscript.
Supporting information
ACKNOWLEDGMENT
Data in this study were from the Korean Genome and Epidemiology Study (KoGES; 4851‐302), National Research Institute of Health, Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea. Therefore, this study could be done by virtue of the labor of all staffs working in KoGES.
Park SK, Ryoo J‐H, Oh C‐M, Choi J‐M, Chung P‐W, Jung JY. Body fat percentage, obesity, and their relation to the incidental risk of hypertension. J Clin Hypertens. 2019;21:1496–1504. 10.1111/jch.13667
Funding information
This research did not receive any specific grant from any funding agency in the public, commercial, or not‐for‐profit sector.
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