In the present study, we identified baPWV > 1,400 cm/s, WC > 85 cm, FBG > 100 mg/dL, male sex, and fatty liver as significant independent predictors for VFA ≥ 100 cm2 in 148 individuals from the general Chinese population, using multiple logistic regression analysis. High baPWV was the strongest predictor for VFA ≥ 100 cm2, and VFA was significantly positively correlated with baPWV (γ = 0.365, P < 0.001).
Arterial stiffness is recognized as an important predictor of cardiovascular events and all-cause mortality, expressed by carotid-femoral PWV in a meta-analysis of prospective cohort studies [23] and by baPWV in prospective cohort studies [24, 25]. Many studies examining the association between obesity and arterial stiffness used anthropometric parameters such as BMI [26, 27], WC [28], waist-height ratio [29, 30], or body-shape index [31], but these results failed to conclusively establish an association between arterial stiffness and body fat parameters. However, arterial stiffness was recently identified as the strongest predictor for VFA and visceral fat mass, with positive correlations with baPWV and carotid-femoral PWV [32, 33], as used in the present study.
Ethnic-specific WC cut-off values have been proposed in relation to the worldwide definition of metabolic syndrome [17]. WC > 85 cm was a predictor for VFA ≥ 100 cm2, irrespective of SFA or BMI, in the present study. This was in accord with the optimal WC cut-off of values for identifying metabolic risk factors of 85 cm in men and 80–85 cm in women in a recent study in the general Chinese population from the Kadoorie Biobank [1]. A large international CT imaging study also revealed that a high WC was predictive of high visceral adiposity [34]. WC measurement is thus a simple and convenient tool for determining visceral obesity.
Male sex was also a predictor for VFA ≥ 100 cm2. Men display android-type obesity, including a predominantly visceral and upper thoracic distribution of adipose tissues, whereas woman show gynecoid-type obesity, predominantly in the lower part of the body.
Arterial stiffness was the strongest predictor for visceral obesity. Regarding the pathophysiology of visceral obesity, intra-abdominal visceral fat accumulation provides high levels of free fatty acids and triglycerides to the liver via the portal vein, leading to ectopic fat deposition in the liver, induced insulin resistance, and increased production of hepatic glucose to induce glucose intolerance [12], Hypertrophied adipocytes and macrophages associated with visceral obesity increase proinflammatory cytokine levels (tumor necrosis factor-α, interleukin-6, plasminogen activator inhibitor-1) and decrease anti-atherogenic adiponectin [12, 13]. Visceral obesity thus eventually increases the risk factors for metabolic syndrome [18], finally causing type 2 diabetes, atherosclerosis, and cardiovascular disease [19].
The current single regression analysis revealed that serum FBG ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, ALT ≥ 29 U/L, uric acid ≥ 5.7 mg/dL, and baPWV ≥ 1400 cm/s were significant predictors for VFA ≥ 100 cm2. Notably, serum FBG ≥ 100 mg/dL and triglycerides ≥ 150 mg/dL are also included in the worldwide criteria of metabolic syndrome [17]. These findings show that VFA ≥ 100 cm2 is an appropriate criterion for assessing the risk factors for metabolic syndrome.
RBC ≥ 470×104/µL and Hb ≥ 14.2 mg/dL were also identified as predictors for VFA ≥ 100 cm2 in single regression analysis in the present study. High Hb levels have been significantly associated with the presence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, especially in men [35]. Hb was also significantly associated with insulin resistance [36] and free fatty acid deposition in the liver increased insulin resistance in NAFLD [12]. These findings imply that the availability of serum Hb is a predictor of NAFLD. The overall prevalence of NAFLD in China in an analysis according to regional domestic products was about 30% [37], while the estimated prevalence of fatty liver in the present study was 41.2%. Fatty liver and FBG were independent predictors for VFA ≥ 100 cm2 in the present study. Individuals in the VFA ≥ 100 cm2 group had significantly higher risk factors for NAFLD, including fatty liver, higher AST, ALT, and γ-GTP, and higher risk factors for metabolic syndrome, namely higher SBP, DBP, FBG, triglycerides, and hsCRP, compared with the VFA < 100 cm2 group.
The new concept of MAFLD was defined as evidence of fatty liver plus one of overweight/obesity, type 2 diabetes, or evidence of metabolic dysfunction, while alcohol intake is not essential for a diagnosis [20]. Indeed, fatty liver plus at least two risk factors for metabolic syndrome, insulin resistance and high hsCRP, played a crucial role in subjects with normal weight.
MAFLD is a new definition of fatty liver disease, with particular importance in Asia, Latin America, and Africa, due to their characteristics of non-obesity but high amounts of visceral fat [38]. Visceral fat is a key mediator of MAFLD. VFA > 100 cm2 was an independent risk factor for fatty liver [39] and visceral fat accumulation was significantly associated with insulin resistance [40, 41], hepatic inflammation, and fibrosis [42]. MAFLD identified patients with significantly higher levels of fibrosis compared with NAFLD [43, 44]. Metabolically abnormal non-obese Chinese patients with MAFLD had a greater risk of liver damage [45].
As discussed above, visceral obesity is a central target for interventions to prevent and treat metabolic syndrome and MAFLD through lifestyle modifications, including diet and exercise, and via medical methods.
Health promotion and education programs designed to reduce visceral fat could be useful in middle-aged Japanese individuals with visceral fat accumulation, decreasing the numbers of metabolic risk factors [46] and preventing cardiovascular events [47]. In addition, a systematic review and meta-analysis revealed that both calorie reduction by diet, and especially exercise training, successfully reduced visceral fat [48], suggesting that exercise was more important than diet in terms of reducing visceral fat. A recent meta-analysis also showed the potential beneficial effects of thiazolidinedione [49] and sodium-glucose co-transporter 2 inhibitors [50, 51] for improving MAFLD among patients with type 2 diabetes.
The present study had some limitations. The cross-sectional nature of the study meant that the causal relationships between visceral obesity and arterial stiffness and MAFLD could not be clarified.