General obesity, abdominal adiposity, and the risk of incident hypertension—From anthropometry to modern imaging techniques

Obesity is a well‐established, modifiable, risk factor with global burden and rising trends over the past 3 decades in children, adolescents, and adults.1 The worldwide prevalence of overweight and obesity among adults, defined as a body mass index (BMI) ≥25 kg/m², increased during 1980‐2013 from 28.8% to 36.9% in men and from 29.8% to 38.0% in women.2 In parallel, the number of adults with elevated blood pressure (BP) increased from 594 million in 1975 to 1.13 billion in 2015,3 with the obesity epidemic being considered as a major contributing factor to the worldwide rise in the burden of hypertension. Obesity is also implicated in pathogenesis of a cascade of cardio‐metabolic disorders and is closely associated with increased rates of cardiovascular morbidity and mortality.4, 5

The association of obesity with the risk of developing hypertension has been explored in numerous longitudinal studies. Risk estimates from the Framingham Offspring Study, for example, support the notion that 78% of incident cases of hypertension in men and 60% of incident cases of hypertension in women are attributable to excess weight gain.6 In a 2018 meta‐analysis of 59 longitudinal studies (incorporating data from 830,685 participants), the risk of incident hypertension was shown to be magnified by 50% for each 5‐unit increment in BMI [relative risk (RR): 1.50; 95% confidence interval (CI): 1.40‐1.59] and by 25% for each 10‐cm increment in waist circumference (RR: 1.25; 95% CI: 1.19‐1.32).7 The relative importance of different anthropometric indices reflecting general and/or abdominal obesity in prognosticating the risk of incident hypertension was explored in a subsequent meta‐analysis of 57 prospective cohort studies (incorporating data from ~2.3 million participants).8 The pooled RR of incident hypertension was 1.49 for a 5‐unit increment in BMI (95% CI: 1.41‐1.58), 1.27 for a 10‐cm increment in waist circumference (95% CI: 1.15‐1.39) as well as 1.37 (95% CI: 1.24‐1.51) and 1.71 (95% CI: 1.35‐2.13) for each 0.1‐unit increment in waist‐to‐hip ratio and waist‐to‐height ratio, respectively.8 The association of BMI with the circadian BP phenotype was also evaluated in large‐scale cross‐sectional studies using the “gold‐standard” method of 24‐hour ambulatory BP monitoring, in which overweight and obesity were associated with higher odds for a non‐dipping nocturnal BP pattern.9, 10, 11

In this issue of The Journal of Clinical Hypertension, Rhee et al12 explored the association of abdominal obesity with the risk of developing hypertension in a national‐wide, population‐based cohort study of 16 312 476 normotensive Koreans, who received a health screening evaluation covered by the National Health Insurance Service (NHIS) of Korea during 2009‐2012. Screening examinations included routine anthropometric measurements (ie, body weight, height, waist circumference) and standardized office BP monitoring. Adjudication of hypertension status, which was the prespecified outcome of this analysis, was performed in 2015 on the basis of claim records of the NHIS with ICD‐10 codes I10‐I15 and claims for antihypertensive drug use throughout the observational period. Over a median follow‐up of 5.48 years, the overall incidence of hypertension was as high as 7.8%.12 When participants were stratified into 6 sub‐groups according to the baseline level of waist circumference, the incidence of hypertension increased linearly from 4.2% in category 1 (waist circumference <80 cm for men and <75 cm for women) to 17.5% in category 6 (waist circumference >100 cm for men and >95 cm for women). Using the waist circumference category 3 as reference standard, those participants stratified in category 6 had 73.6% higher risk of incident hypertension [hazard ratio (HR): 1.736; 95% CI: 1.720‐1.753].12 This association remained significant even after adjustment for age, gender, smoking status, alcohol consumption, income level, and history of diabetes and dyslipidemia. In sub‐group analysis, participants with abdominal obesity at baseline had significantly higher risk for developing hypertension than those without abdominal obesity regardless of self‐reported intensity of physical activity (HR: 1.741; 95% CI: 1.718‐1.764).12

The above observations should be interpreted within the spectrum of the strengths and limitations of the study design. Important strength of this study is the huge and national‐wide sample size that provided adequate statistical power to the Cox‐regression hazard analysis. This is by far the largest study conducted so far in the area, and as such, the analysis can clarify the linear pattern in the association between abdominal obesity and hypertension risk. However, the study suffers also from some methodological limitations that should be taken into consideration. First, identification of hypertension status at the end of the observational period was based on claim records derived from the NIHS of Korea in the absence of standardized BP recordings in a prespecified follow‐up visit. Accordingly, outcome adjudication may be, at least in part, influenced by recording bias, and the possibility of misclassification of participants with respect to their hypertension status cannot be fully excluded. Second, the fact that inclusion of physical activity in analysis did not modify the risk relationship between waist circumference and hypertension incidence may be attributable to the absence of direct estimates of intensity of physical exercise with objective tools during follow‐up; several studies and meta‐analyses are supportive of a protective effect of physical activity on hypertension risk.13 Third, statistical analysis was not adjusted for several other factors that may influence the risk of developing of hypertension. Whether residual confounding from unrecorded parameters, such as familiar burden of hypertension, daily sodium intake, dietary habits, modifies the association of abdominal obesity with incident hypertension remains unclear.

Another issue surrounded by substantial controversy is whether simple and widely applied anthropometric measures of obesity (such as BMI, waist circumference, waist‐to‐hip ratio) are reflective of alterations in body fat distribution. Accordingly, the question that emerges is whether these simple anthropometric indices can accurately prognosticate the risk of obesity‐inducible hypertension. Earlier meta‐analyses of observational studies showed that anthropometric measures reflecting more closely abdominal obesity, especially waist‐to‐hip ratio, are superior to BMI in discriminating several cardiovascular risk factors, including hypertension, diabetes, and dyslipidemia in both men and women.14, 15 Waist circumference and waist‐to‐hip ratio, however, are limited by their inability to distinguish subcutaneous adiposity from visceral abdominal adipose tissue deposition. From a pathophysiological standpoint, subcutaneous adipose tissue is relatively metabolically inert,16 whereas accumulation of adipose tissue in other body compartments (ie, visceral adipose tissue) is associated with increased cytokine production and insulin resistance.1 The availability of novel imaging techniques that enable the precise quantification of body fat distribution may advance our understanding on the complex interplay between general obesity, abdominal adiposity, and risk of new‐onset hypertension.17

In a cohort study of 300 normotensive Japanese Americans, body fat distribution was assessed by performing abdominal, thoracic, and thigh computed tomography (CT) scan.18 Over a follow‐up of 10‐11 years, 92 incident cases of hypertension were recorded. After adjustment for age, gender, BMI, baseline BP levels, and several other confounding factors, participants in the highest quartile of intra‐abdominal fat area at baseline had 5.07‐fold higher odds for developing hypertension during follow‐up [odds ratio (OR): 5.07; 95% CI: 1.75‐14.73].18 Intra‐abdominal fat area remained a significant predictor of incident hypertension even after adjustment for total subcutaneous area, abdominal subcutaneous area, and waist circumference.18 The relative importance of BMI and body fat distribution as predictors of incident hypertension was explored in a secondary analysis of 903 normotensive patients participating in the Dallas Heart Study.19 In univariate analysis, BMI was associated with the risk of developing hypertension over a median follow‐up of 7 years (RR: 1.24; 95% CI: 1.12‐1.36, per 1‐SD higher BMI). When magnetic resonance imaging (MRI) parameters of body fat distribution were inserted in a multivariate model, the association of BMI with incident hypertension was disappeared and the only parameter independently associated with incident hypertension was the MRI‐derived quantity of visceral adipose tissue (RR: 1.22; 95% CI: 1.06‐1.39).19 In a subsequent longitudinal study enrolling 2,119 randomly selected normotensive Danish adults, abdominal visceral and subcutaneous adipose tissue was quantified via ultrasound imaging at baseline.20 Over a 5‐year‐long observational period, abdominal visceral adipose tissue was shown to be associated with increased risk of incident hypertension (OR: 1.22; 95% CI: 1.01‐1.48); this association remained significant even after adjustment for BMI and abdominal subcutaneous adipose tissue quantity.20 It has to be noted, however, that these modern imaging techniques are costly and require in‐hospital assessment of abdominal adiposity, and their prognostic association with incident hypertension and other cardiovascular outcomes warrants further investigation in future longitudinal studies.

In conclusion, the study of Rhee et al12 is the largest prospective observational study conducted so far to demonstrate a strong linear relationship between abdominal obesity and risk of new‐onset hypertension in a national‐wide population of >16 million Korean adults. This observation confirms and expands the results of recent dose‐response meta‐analyses, calling for properly designed randomized trials aiming to ascertain the role of several weight loss interventions in the prevention and overall management of hypertension.

CONFLICT OF INTEREST

Both authors have no conflict of interests to disclose.