In our analysis of this community-based hypertension registry study in China, we noted a "U-shaped" relationship between BMI and risk of PAD. The BMI value with lowest risk of PAD was estimated to be 25.7 kg/m2.
A number of studies have reported the relationship between BMI and the risk of PAD. However, the association between BMI and PAD risk was not consistent. Epidemiological studies more than two decades ago reported a positive association between BMI and intermittent claudication in middle-aged males in Israel[14]. However, many population studies after adjusting for the relevant covariates fail to support the significant association between BMI and the prevalence of PAD[4, 15]. In addition, the San Diego study reported an independent and significantly inverse association between BMI and prevalence of PAD (OR: .88) in multi-ethnic population[16]. Studies on the diabetic population in Taiwan showed that compared with diabetic patients without PAD, the BMI of patients with PAD was lower (23.5 ± 3.2 vs.24.8 ± 3.5 kg/m2, P < .005). Heffron et al. who gathered data from more than 20 000 sites (n = 3 250 350) in the United States from 2003 to 2008, recently reported BMI and the prevalence of PAD in females showed a "J-shaped" nonlinear relationship; a significant positive correlation between obesity and PAD in females, while only a slight positive correlation between obesity (BMI ≥ 40 kg/m2) and PAD in males (OR = 2.98 vs. 1.37)[9]. Stepwise logistic regression analysis showed that the association between BMI and PAD was inverse[17].
To our knowledge, the "U-shaped" relationship between BMI and the risk of PAD shown in our study was the first reported in Chinese population. Different from the very large sample population studies[9] in the United States, where participants were nearly 30% obese and 3.4% underweight, as well as study of the prevalence of PAD in African[10], where obesity was only 4.5%, 34.1% underweight, we were 6.3%(691) underweight and only 4.2%(454) obesity, nearly 90% of the population was normal BMI and overweight. Over a third of the study population was underweight. A “U-shaped” relationship between BMI and the risk of PAD was observed. Compare to the subjects with normal BMI, underweight and obesity were statistically significant association with the risk of PAD (OR, 2.09; 95%CI 1.35, 3.22; p = .0009; OR,1.90; 95% CI 1.04, 3.23; p = .0336), but not overweight (OR, 1.56; 95% CI 0.70, 2.51; p = .7342)[10]. However, Heffron et al. found a “J-shaped” relationship between BMI and PAD only in females, not in males, which may be due to the height and weight data used in this study for self-reporting of participants. Self-reported data may lead to personal BMI classification appear serious mistakes[18], difficult to correct the mistakes[19], especially in the stratified analysis according to gender[20]. Thus, self-report bias may have contributed to the fact that this study found a "J-shaped" relationship between BMI and PAD risk only in females, and not in males.
At present, few studies have elaborated on the possible mechanism of the correlation between BMI and PAD. A cross-sectional study of hemodialysis patients reported a lower prevalence of atherosclerosis and lower levels of inflammation (CRP) in patients with normal BMI and overweight compared with those with underweight and obesity[21]. Lower levels of inflammation and atherosclerosis may be associated with the lowest risk of PAD in this population (normal BMI and overweight).
Not only that, there have been also many reports on the “U-shaped” relationship between BMI and cardiovascular disease and death. A meta-analysis of 97 studies showed that obesity (all grades) and grades 2 and 3 obesity were significantly associated with all-cause mortality relative to normal BMI. However, overweight was associated with a significant reduction in all-cause mortality[20]. Among more than 1 million East Asian populations in the Asia Cohort Consortium BMI Project, including Chinese, Japanese, and Korean, the Cox proportional hazard regression model was used to analyze the relationship between BMI and mortality risk, which showed that the population with BMI between 22.6 and 27.5 had the lowest mortality risk[22]. Based on this, we speculate that the "U-shaped" relationship between BMI and peripheral atherosclerosis may, on one hand, explain the causes of the lowest cardiovascular disease risk and all-cause mortality in normal BMI/overweight.
Limitations And Future Directions
Nonetheless, these results must be interpreted with caution, and a number of limitations should be borne in mind. First, subjects in our analysis were middle-aged and elderly patients with hypertension. The “U-shaped” relationship between BMI and the risk of PAD was not necessarily applicable to the general population, but as an independent risk factor for PAD, exploring the relationship between BMI and the risk of PAD in the hypertensive population can serve the high-risk population more precisely. In addition, the association between BMI and the risk of PAD was still controversial. By design, our study was a cross-sectional study and cannot study the chronology of BMI and PAD. There might be a reverse causal relationship. The weight change caused by the disease may distort the relationship between BMI and PAD. In the future, large prospective cohort studies on PAD were urgently needed. Final, the obesity rate in our study was low. It has no enough power to assess the relationship between different degrees of obesity or morbid obesity and the risk of PAD. However, our study reflects the real situation of hypertension population in Chinese hypertention, and the results obtained were more suitable for the application of hypertension in middle-aged and elderly people in China.