In this analysis involving a nonobese Chinese population, the risk of ACM was not significantly different among individuals who were classified as MH and MUH by this new definition. The results indicated that this new MH definition might not be suitable for mortality risk stratification for nonobese Chinese people. Further studies are needed to explore the role of this new MH definition in larger populations.
Despite the general association between obesity and its co-morbidities, there are individuals who are normal-to over-weight but having abnormal metabolic profiles, namely the metabolically unhealthy non-obese (MUNO) or metabolically obese normal-weight (MONW) phenotype [20–23]. It was demonstrated that individuals with MONW/MUNO were at higher risk of increased arterial stiffness and carotid atherosclerosis[21], stroke[22, 23], as well as higher risk of ACM and cardiovascular mortality[24, 25], when compared to MHO. Those findings highlight that it maybe the abnormal metabolic profile, rather than obesity defined by BMI, placing individuals at increased risk for cardiovascular diseases and mortality. Therefore, screening for metabolic risk factors in non-obese but unhealthy individuals should be emphasized.
A meta-analysis showed that the prevalence of MONW around the world varies largely, ranging from 6.6–45.9%[26]. This heterogeneity was affected by several factors, including participants’ age, gender, ethnicities, region, sample size, MONW criteria (criteria for obesity and metabolically healthy) and so on. A recent study demonstrated that the overall prevalence of MONW was 16.1% in a general Chinese population [27]. In this study, individuals were considered as MONW if they had at least two metabolically abnormal trait based on the metabolic syndrome criteria from the International Diabetes Federation in 2015 and BMI of 18.5-23.9 kg/m2. While a more previous study showed that the prevalence of MONW was as low as 4.3% in a Chinese Bejing urban cohort[28]. In this study, MONW was defined as BMI of 18.5-25 kg/m2 and metabolic abnormality referenced at least 3 abnormal traits among the factors of BP, WC, TG, FPG, and HDL-C. In our present study, according to the new MH definition, the prevalence of MUNO was 20.5%. As we can see, there are various criteria to evaluate MUNO/MONW currently, no consensus has been reached to a final definition, and thus interpretation of those results or comparisons of prevalence across different studies should be cautious.
In the univariable analysis for the crude sample, the new defined MH was a significantly protective factor for ACM in our nonobese participants. However, after adjustment for potential confounders and PSM, the association changed materially. The mixed results between the original study and the present study might be explained by several reasons. First of all, different BMI categories and cutoffs. In the original study, there were three BMI categories, namely normal weight (BMI, 18.5-24.9 kg/m2), overweight (BMI, 25.0-29.9 kg/m2) and obesity (BMI, ≥ 30 kg/m2). In our study, the participants were all non-obese with BMI less than 28 kg/m2. In addition, the cutoff value of WHR may also not be optimal for Chinese people due to the different ethnicities and baseline characteristics. Secondly, the new MH definition only took SBP into consideration but not DBP since it failed to achieve statistical significance to predict outcomes in the original study. In our study, DBP is also a significant risk factor for ACM. Historical studies have revealed a J-curve relation between DBP and cardiovascular outcomes[29]. as well as cardiovascular and all-cause death[30]. In this case, higher DBP could also potentially lead to adverse prognosis. Thirdly, comparing to traditional metabolic criteria, the biggest distinctions for the new MH definition is the lack of dyslipidemia, which is also a well-established risk factor for CVD and mortality [31, 32].
To our knowledge, this is the first study to assess the role of the new MH definition for ACM in a non-obese Asian population. The negative results based on multiple statistical analyses in the present study indicated that the generalization of the new definition in other populations needs to be validated. This study has several limitations. First, the mortality was relatively low in our study. For the relatively small number of ACM, multivariable models only adjusted for some basic variables to ensure the convergence of the model. On the other hand, for including those covariates, the convergence of the model may be poor, and the results were exploratory. Second, most of the specific cause for death could not be determined. We can only make a conclusion about the relationship between the new MH definition and ACM. Third, the relatively small sample from a single center might also affect the statistical power of the results. Multicenter-based larger studies are needed to confirm and extend the present finding.