An association between subcutaneous fat mass accumulation and hypertension

Abstract Evidence to assess relationships between subcutaneous fat area (SFA) and lifestyle‐related diseases, including hypertension, remains limited. The aim of this study was to investigate the relationship between SFA and hypertension. This study was a single‐institution, cross‐sectional study of 1,899 eligible Japanese participants who underwent health checkups between December 2016 and December 2018. All patients were measured for SFA and visceral fat area (VFA) by abdominal computed tomography (CT). SFA was divided into quartiles by gender, and multivariate logistic regression analysis was performed to estimate associations between SFA quartiles (Q) and hypertension. Mean age and SFA were 60.9 9 (standard devastation [SD]:12.0) years and 123.0 (56.9) cm2 in men, and 60.6 (12.8) years and 146.6 (79.0) cm2 in women, respectively. Risk of hypertension from multivariate regression modeling compared with the lowest quartile (Q) in both sexes was as follows: for men Q2 [odds ratio (OR), 1; 95% confidence interval (CI), 0.55‐1.51 ], Q3 (OR, 1.73; 95%CI, 1.17‐2.56), and Q4 (OR, 1.96; 95%CI, 1.31‐2.94); for women Q2 (OR, 0.87; 95%CI, 0.48‐1.58), Q3 (OR, 1.73; 95%CI, 1.02‐2.95), and Q4 (OR, 2.54; 95%CI, 1.51‐4.28). The optimal SFA cutoff value at risk of hypertension was 114.7 cm2 in men and 169.3 cm2 in women. The prevalence of hypertension was positively associated with SFA quartiles in both genders. The present results may indicate the necessity of considering not only VFA, but also SFA for the primary and secondary prevention of hypertension.

considerable attention 5 . Similarly, between 1975 and 2014, obesity became a public health problem worldwide 6 . In Japan, as in other high-income countries, the number of presumed hypertension patients has been decreasing 7 . Nevertheless, an estimated 43 million Japanese have hypertension, and the treatment achievement rate is only 30.2%. Hypertension remains an important risk factor for cardiovascular diseases and poses a major public health challenge in Japan, as in other countries around the world 8 .
Obesity has been on the rise in Japan according to both 1956-2005 and 1995-2011 national surveys 9,10 . Hypertension without obesity accounts for more than half of cases in Japan, but the increasing proportion of hypertension with obesity is also an issue, particularly among young-to middle-aged men. Patients with this type of hypertension are considered prone to transition to metabolic syndrome (MetS). In recent years, MetS also has attracted attention as a risk factor for arteriosclerosis-related cardiovascular disease, as well as hypertension 11,12 . MetS is attributed to a combination of visceral fat-type obesity, hypertension, hyperglycemia, and abnormal lipid metabolism. Different diagnostic criteria have been proposed, and ideas have varied from country to country. The pathogenic mechanisms are thought to be based on overlapping risk factors 13,14 , leading from insulin resistance caused by visceral fat accumulation 11,15 .
In Japan, excess visceral fat accumulation is an essential item in the diagnostic criteria for Mets, and the standard criterion is a visceral fat area (VFA) ≥100 cm 2 . However, imaging tests such as CT and MRI are difficult to use for VFA measurement at all facilities because of problems of radiation exposure and examination costs, and waist circumference (WC) measurements (men ≥85 cm, women ≥90 cm) are therefore accepted for the diagnosis of central obesity 16 .
Subcutaneous fat area (SFA) accounts for the majority of body fat, but is not considered an independent risk factor for MetS.
Various studies have examined the relationships between obesity and arteriosclerosis-related cardiovascular factors among obese Caucasians [17][18][19] . However, studies involving suitably large cohorts of Asian individuals have been limited. Although several reports have suggested that SFA was independently associated with blood pressure, studies of wider age groups are needed 20,21 . Although there have already been several reports on subcutaneous fat and dyslipidemia and glucose intolerance, 22 the association between SFA and hypertension thus remains controversial.
This study aimed to investigate the association between SFA and hypertension, one of the components of MetS, by direct measurement from computed tomography (CT) to estimate abdominal adiposity.

| MATERIAL S AND ME THODS
This cross-sectional study surveyed 2,885 Japanese individuals who participated in a health checkup single institution in Tokyo, Japan, between December 2016 and December 2018. Participants with all of the physical measurements, blood tests, and abdominal CT were included in this study. Among these, 985 participants were excluded due to some missing data and one was excluded as a duplicate case.
A final total of 1,899 participants were thus analyzed in the study as eligible cases.
Participants' clinical data were retrospectively retrieved from single institutional database. All examinations included in this study were performed as part of the voluntary health checkup. The participants' data were anonymized prior to the analysis. The Ethics Committee of the Juntendo University Hospital approved the study protocol (No. , and written comprehensive informed consent was obtained consent from all participants when they were received health checkup. As part of the voluntary routine health checkup, participants were asked to complete self-administered questionnaires regarding medical history (hypertension, dyslipidemia, diabetes), past other medical history, and health behaviors as listed in Breslow's seven health habits 24 . Breslow's seven health habits were non-daily alcohol consumption, non-smoker status, exercise at least ≥2 times/week for at least 30 minutes, BMI 18.5-24.9 kg/m 2 , adequate sleep duration, daily breakfast consumption, and no snacking between meals 25 .

| Definition of lifestyle-related disorders
Lifestyle-related disorders were defined as follows in this study.

| Statistical analysis
Results were analyzed by gender. SFA was stratified into quartiles

| RE SULTS
The baseline characteristics of eligible participants in this study are shown in Table 1 hypertension was 29.6% in men and 19.5% in women. Frequencies of dyslipidemia and diabetes mellitus were 43.8% and 17.2% in men, and 35.4% and 6.4% in women, respectively. Table 2 shows the SFA quartile-stratified characteristic SFA quartile in men, and Table 3 shows those in women. BMI, WC, VFA, blood pressure-related variables, and lipid-related variables all correlated positively with SFA in both sexes. A positive correlation was seen between SFA and total BMI and total score of healthy lifestyle characteristics in men, and between hypertension and diabetesrelated variables and alcohol intake in women. Table 4 shows the results of logistic regression analysis.
Associations between hypertension and SFA quartiles were observed in both sexes after adjusting for related factors. The appropriate cutoff value, sensitivity, specificity, and AUC for SFA in men were 114.7 cm 2 , 0.66, 0.63, and 0.69, respectively. The appropriate cutoff value, sensitivity, specificity, and AUC for SFA in women were 169.3 cm 2 , 0.58, 0.74, and 0.71, respectively (Figure 1).  in Japanese Americans, finding no significant association between subcutaneous fat and blood pressure 29 . Another study of Caucasian

| Limitations
This study has some limitations that should be considered. First, as a cross-sectional observational study, causal relationships between SFA levels and hypertension could not be evaluated. Therefore, we will consider prospective cohort studies in the future. Second, the study was affected by selection bias. All participants were Japanese subjects who had undergone voluntary health checkups at a single institution in metropolitan area, and may have been inherently more aware of their health behaviors relative to residents in rural areas.
Further multicenter analyses that include data from other populations are required. Third, some key data on items such as detailed information on medications, medication dosages, medication adherence, and status of menopause were not collected. Such data should be collected in future analyses. Finally, a self-administered questionnaire was used to evaluate lifestyle habits, and some respondents may have under or overestimated their actual habits.

| CON CLUS ION
Our cross-sectional study revealed significant associations between prevalence of hypertension and SFA quartiles after adjusting for confounders among participants undergoing voluntary health F I G U R E 1 ROC curve analysis of subcutaneous fat area for hypertension Man W oman checkups. Better management of subcutaneous fat accumulation as well as visceral fat accumulation may be necessary for primary and secondary prevention of hypertension.

ACK N OWLED G EM ENT
The authors thank all participants who underwent the voluntary medical checkups, as well as the data collection staff at Juntendo University.

CO N FLI C T O F I NTE R E S T
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

E TH I C A L S TATEM ENT
The Ethics Committee of Juntendo University reviewed and approved the research protocol using the retrospective data (No 18-296), and written comprehensive informed consent was obtained from all participants when they were received health checkup.