In the present study, we performed a large cross-sectional study using data from the China H-type Hypertension Registry. The results demonstrated that VAI was positively associated with PAD in normal-weight patients with hypertension. In addition, a positive association between higher VAI levels and PAD prevalence was found among men than women.
Most previous studies assessing the effects of VAI on cardiometabolic risks[26, 27]established a statistical correlation between higher VAI levels and a higher prevalence of arterial stiffness, coronary heart disease, hypertension,and cardiovascular mortality[31, 32]. However, there have been few studies on VAI and PAD. Only Wung et al. explored the relationship between obesity-related indicators and PAD in 1,872 patients with type 2 diabetes. The results showed that an increase in VAI levels was related to PAD prevalence. However, no sex difference was found in Wung et al.’s research due to differences in the research population, design, and sample size.
The mechanism between VAI and PAD in normal-weight patients with hypertension may be explained by insulin resistance (IR) and inflammation. Previous studies have shown that even people with normal-weight may be metabolically obese. A more sensitive VAI can then replace the metabolic obesity produced at this time, and we know that VAI shows the strongest correlation between IR and lipid metabolism. A more sensitive VAI can then replace the metabolic obesity produced at this time, and we know that VAI shows the strongest correlation between IR and lipid metabolism[34, 35]; thus, causing the production of reactive oxygen species in arterioles. Nitric oxide production and consumption decrease and increase under the combined action of inflammatory factors and reactive oxygen species, respectively. Therefore, pro-inflammatory cytokines and reactive oxygen species from obesity can produce peripheral IR and directly affect the endothelium, leading to endothelial dysfunction and atherosclerosis cascade reaction. The prevalence of diabetes and early abnormal glucose metabolism in men is higher than that in women because insulin sensitivity differs between men and women[38, 39].Therefore, men are more likely to have an increased risk of IR than women. Therefore, the positive correlation between VAI and PAD was more obvious in men.
The present study provides an opportunity to explore the dose-response relationship between VAI and PAD in normal-weight patients with hypertension. The data used were obtained from a large-scale observational study of the China H-type Hypertension Registry Study. Our results provide new insights into this field. To our knowledge, this is the first study to explore the relationship between VAI and PAD in normal-weight patients with hypertension and to find a positive correlation between them. The results showed that an increase in VAI levels was related to PAD prevalence. Second, according to related research, even in the general population, obesity is strongly correlated with cardiovascular disease and death. BMI is usually used to evaluate obesity.Nevertheless, BMI is limited in that it cannot distinguish between muscle and fat content and cannot provide body fat distribution[42, 43]. Obesity is a metabolic disease. However, some normal-weight people may have metabolic disorders similar to those with obesity. These individuals are metabolically obese with normal-weight. At the same time, related studies show that the population, as mentioned earlier, accounts for 20% of the normal-weight population[13, 14].Compared with BMI, visceral fat can better reflect metabolic changes. The VAI, a simple index calculated using blood lipid, WC, and BMI, can be used as a simple biomarker of body fat distribution and metabolic disorders and is closely related to visceral fat measured using MRI. Finally, our results showed significant sex differences, with a positive association between higher VAI levels and PAD prevalence among males than females. The fat distribution differs between men and women owing to differences in sex hormone levels.. The decrease in estrogen levels in postmenopausal women leads to the accumulation of adipose tissue in the center/viscera[45–47], where VAI stands for visceral fat. All the women in this study were postmenopausal; therefore, women had higher VAI levels than men. However, there was no significant correlation between VAI and PAD in women. A possible reason for this result may be that, compared with women, men have more risk factors for PAD, such as smoking. Further research is needed to confirm the relationship between VAI and PAD prevalence, and our study results are only in the generated hypothesis stage.
The limitations of the present study should be noted. First, although we adjusted for most of the covariates as much as possible, there may still be unmeasured and residual confounding factors. Second, all the participants in this study were patients with hypertension in Southern China; thus, our conclusions may not be generalizable to different populations. In addition, because this was a limitation of a cross-sectional study, we could not determine the causality and long-term clinical results between them.
In clinical practice, clinicians can closely monitor the VAI level of normal-weight patients with hypertension and observe PAD-related signs in patients with high VAI. At the same time, this study also emphasizes the important role of visceral obesity in the occurrence and development of PAD. Therefore, further large-scale prospective cohort studies are needed to explore the occurrence and development of VAI and PAD in normal-weight patients with hypertension and encourage researchers to dissect the molecular mechanisms involved.