Obesity-related hypertension is considered as a distinct phenotype [9, 12], but the underlying mechanisms remain elusive. The pathophysiology of obesity-induced hypertension involves various potential pathways [4, 5, 8–12]. Excess visceral adiposity is associated with altered secretion of bioactive peptides like adiponectin, leptin, interleukin-6, and tumor necrosis factor-α, predisposing to inappropriate inflammatory responses, insulin resistance, increased sympathetic activity and RAAS activation. These changes impair endothelial function and increase tubular reabsorption of sodium and water, leading to elevated BP [4, 9]. In the present study, aortic systolic BP, systemic vascular resistance, and large arterial stiffness were elevated with higher intra-abdominal fat content in the absence of changes in volume balance, cardiac sympathovagal balance, or circulating RAAS. The regression analyses confirmed that WHtR was independently associated with aortic BP, SVRI, and large arterial stiffness.
WHtR better correlates with intra-abdominal fat content than waist circumference, BMI, or waist to hip ratio [2]. WHtR also presents with stronger inverse correlation with cardiovascular health than waist circumference [29]. A cutoff value of 0.5 for WHtR has been suggested for the risk assessment of cardiovascular disease [30], and this value was exceeded in three of the present quartiles that exhibited mean BMI values ranging from 25.1 to 31.9 kg/m2. According to a recent survey, mean BMI in Finland is 27.7 kg/m2 in men and 27.5 kg/m2 in women, while 27% of men and 26% of women aged 30–64 years are obese [31].
Previously, a direct correlation between BMI and plasma aldosterone concentration was reported in overweight patients independent of age, sex and sodium intake [32]. In addition, weight loss was found to reduce plasma renin activity and aldosterone concentration in overweight subjects [33]. In the present study, no differences were detected in plasma renin activity or aldosterone concentration between the quartiles, and measurements of extracellular volume balance did not indicate volume retention with higher WHtR. Thus, there were no findings indicating changes in circulating RAAS activity between the WHtR quartiles. However, increased WHtR was associated with an unfavorable lipid profile, and in linear regression analyses LDL cholesterol was associated with systolic and diastolic BP and SVRI, as previously reported [34].
As expected, systolic and diastolic BP were increased with higher WHtR. Heart rate was also increased, but stroke volume and cardiac output adjusted to body surface area were decreased with higher WHtR, suggesting that hyperdynamic circulation was not the cause for elevated BP. In contrast, SVRI was increased with higher WHtR. The hemodynamic pattern of reduced CI and increased SVRI has been shown in subjects with essential hypertension [35]. Also, Krzesiński et al. reported that hypertensive patients with or without abdominal obesity presented with similar SVRI, whereas left ventricular contractility and thoracic fluid content were lower in hypertensive subjects with abdominal obesity [36].
PWV is an acknowledged measure of large arterial stiffness [37]. We found that PWV, and also forward wave amplitude that has been associated with aortic stiffness [19], were increased with higher fat content in the central body. However, the indices of wave reflection AIx and AIx@75 [24, 37], did not differ between the quartiles. AIx is influenced by arterial stiffness, but also by height, sex, ventricular ejection duration, heart rate, and systemic vascular resistance [24, 37]. We also evaluated arterial compliance by calculating the ratio of stroke volume to aortic pulse pressure [20], and found that this variable was lower with higher WHtR. Our findings are in line with the view that obesity is associated with increased arterial stiffness [38].
Obesity related increase in plasma leptin concentration is assumed to induce unfavorable cardiovascular changes via the activation of the sympathetic nervous system [39] and RAAS [40], leading to hypertension and increased large arterial stiffness. Studies investigating the association of leptin and arterial stiffness have provided variable results [6, 7]. In the present study, subjects with high WHtR presented with elevated plasma leptin levels, and leptin was moderately related with PWV in the regression analysis, but RAAS activity or sympathetic modulation of HRV were not increased. Thus, the association of WHtR with BP and arterial stiffness may be more related to abdominal obesity itself than high level of circulating leptin.
Excess body fat has been associated with increased sympathetic activity, but the matter remains controversial [41–43]. We evaluated cardiac autonomic tone using HRV analyses, and found no differences in LF power or HF power, reflecting predominantly sympathetic and parasympathetic activity, respectively [25], or LF/HF ratio between the quartiles of WHtR. Previously, Skrapari et al. reported lower LF and HF power in obese (BMI ~ 40 kg/m2) versus lean (BMI ~ 22 kg/m2) subjects [42], while Hillebrand et al. found that BMI was associated with LF power but not with HF power [43]. Emdin et al. reported decreased LF power throughout the 24-hour recording period in obese (BMI ~ 35 kg/m2) versus lean (BMI ~ 24 kg/m2) subjects, while HF power was lower, and the LF/HF ratio was higher, during the postprandial phases [41]. Higher daytime LF/HF ratios have been related with higher plasma insulin concentrations independent of BMI, sex, age, and heart rate [41]. In the present study, subjects in the upper quartiles of WHtR were more insulin resistant based on their QUICKI values, but no parallel changes in cardiac sympathovagal modulation were observed.