Background
Overall mortality has been reported to be lower among individuals classified as overweight/obese based on body mass index (BMI, kg/m
2) when compared with their normal weight counterparts (“obesity paradox”) both in the general population and in population subgroups [
1‐
5]. In a systematic review of prospective studies of obesity and mortality among general populations of adults using normal weight (BMI 18.5 to < 25) as a reference group, overweight (BMI 25 to < 30) was associated with a significantly lower overall mortality, grade 1 obesity (BMI 30 to < 35) was not associated with a higher overall mortality, and grades 2 and 3 obesity (BMI ≥ 35) were associated with a significantly higher overall mortality [
1]. Similar findings have been reported in the elderly population and among patients with chronic kidney disease, coronary heart disease, heart failure and chronic obstructive pulmonary disease [
2‐
5].
The J-shaped relationship between BMI and overall mortality is perplexing and cannot be completely explained by potential selection biases, such as survival bias and healthy participant effect [
6]. One plausible reason is that BMI does not differentiate the weight of fat mass from the weight of lean body mass or fat mass distribution phenotypes across the BMI continuum and as such is not a reliable measure of the risk of obesity-related disease. In a prospective cohort study of US male health professionals, a strong positive monotonic association was observed between predicted fat mass and overall mortality and a U-shaped association between predicted lean body mass and overall mortality, suggesting the “obesity paradox” may be largely attributable to low lean body mass, rather than low fat mass, in the lower BMI range [
7]. Similarly, in a population-based cohort study of older men in UK [
8], both sarcopenia and central adiposity were found to be associated with greater overall mortality, with the highest risk found in sarcopenic obese men.
Waist circumference (WC) is the most common and simplest way to measure central adiposity, which is a major contributor to disease and death. Among African Americans who are known to have relatively less of their body mass in their trunks and relatively more in their extremities compared to non-Hispanic white, WC measures of obesity may offer a more reliable assessment of obesity and mortality relationships [
9]. In this study, we compared the associations of overall mortality with BMI and with other obesity measures, including WC, waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) in the Jackson Heart Study (JHS), a population-based African American cohort in the US. We hypothesized that obesity measures that incorporate waist circumference, a better measure of central adiposity and risk of obesity-related disease than BMI, will show a more consistent pattern of increasing risk of overall mortality with increasing level of obesity. In addition, we also evaluated the associations of these obesity measures with two leading causes of mortality, CVD and cancer, given the strong correlations between measures of obesity and cardiometabolic risk factors as well as risks of some cancers [
10‐
12].
Discussion
Our results show that obesity classified per WC and WHR, but not per BMI or WHtR, was associated with a significantly higher overall mortality after adjusting for age, sex and smoking status. We found a J-shaped relationship between BMI, WC, WHtR and overall mortality and a linear relationship between WHR and overall mortality. We found similar results for obesity classified per BMI, WC, WHR, and WHtR and CVD mortality. However, we found no associations between any of the obesity classifications and cancer mortality.
Our findings on BMI and overall mortality were consistent with findings reported in the literature. Overweight and mild obesity were associated with a lower overall mortality compared with normal BMI (BMI < 25). This “J-shaped” association persisted even after excluding “early deaths,” defined as participants who died within one year of enrollment and thus may have low BMI due to wasting.
We found that both WHR and WC adjusted for HC, but not WC alone, were linearly associated with overall mortality. This finding suggests that not only body fat but also the distribution of body fat is important in discriminating overall mortality risk. In a recent study, using computed tomography (CT)-measured body fat, including both visceral and subcutaneous fat area, Lee et al. [
23] showed that only the visceral-to-subcutaneous fat area ratio (VSR) was independently associated with overall mortality in the fully adjusted model with age, sex, comorbidities and total fat mass. In another study using data from NHANES, Dong et al. [
24] demonstrated that both amount of body fat and body fat distribution (measured via WHR) were independently associated with overall mortality and the effect was sex-dependent.
Some investigators have advocated that waist and hip circumferences be considered as separate variables and not as a ratio, considering two persons with the same WHR may have markedly different levels of waist circumferences [
25]. We evaluated this approach in our study and found that the model with waist and hip circumferences as separate variables outperformed the model with WHR in predicting overall mortality. These results provide further support on the interplay of the visceral and gluteofemoral fat depots and body shape on overall mortality. Possible mechanisms of the protective effect of gluteofemoral fat include long-term fatty acid storage in this location thus reducing adverse effects associated with ectopic fat deposition [
26]. Gluteofemoral fat has also been found to be associated with a beneficial adipokine profile, positively associated with leptin and adiponectin levels and negatively associated with inflammatory cytokines [
26].
Our analyses exploring the effect of having multiple determinants of obesity on overall mortality showed that adding BMI or WC to WHR as determinants of obesity did not substantially improve the prediction of mortality risks. Participants deemed obese by WHR were 45% more likely to die compared to those deemed not obese. Whereas participants deemed obese by both BMI and WHR were 50% more likely to die compared to those deemed obese by neither; participants deemed obese by both WC and WHR were 54% more likely to die compared to those deemed obese by neither.
Our findings of the effects of obesity on CVD mortality were similar to those on overall mortality and, as would be expected, obesity had a greater effect on CVD mortality than on overall mortality. Of note, although BMI ≥ 30 kg/m2 (obese) was not associated with overall mortality after adjusting for age, sex and smoking compared to BMI < 30 kg/m2, BMI-defined obesity was associated with a higher CVD mortality. This reaffirms the usefulness of this commonly used obesity indicator for monitoring trends of obesity and cardiovascular health.
We did not find an association between obesity and cancer mortality. It is possible that obesity-related metabolic dysregulations rather than merely obesity are required to show an association with cancer mortality [
27,
28]. For example, in an analysis using data collected in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, obesity was shown to be associated with a reduced risk for cancer mortality whereas glucose dysregulation and metabolic syndrome were associated with an increased risk for cancer mortality [
28].
A limitation of the study is that because JHS is a sample of African Americans, we are unable to address directly whether or not race matters in body composition or outcome in this study. It has been observed that body compositions differ across race/ethnic groups. For a given BMI, non-Hispanic (NH) blacks typically have the lowest percent fat mass (%fat) followed by NH whites and Mexican Americans have the greatest %fat [
9]. NH blacks also have smaller waist circumferences than NH whites and Mexican Americans with similar BMI. Therefore, the findings of this study may not be generalizable to other race or ethnic groups.
Conclusions
In conclusion, we found that obesity classified by WC and WHR was significantly associated with an increased risk of overall and CVD mortality in this large cohort of African Americans. Additionally, obesity classified by BMI was significantly associated with an increased risk of CVD mortality. WHR was the only obesity measure that showed a monotonic increasing relationship with overall and CVD mortality. Further studies are warranted to determine the extent to which: (1) WC and/or WHR strata can be used as mortality risk indicators in research and population health policy for African Americans as is currently being done for BMI; and (2) individuals with normal BMI but in high risk WC and/or WHR strata might represent an appreciable target population subgroup for potential lifestyle modification. Our findings suggest that WHR, a measure that captures both central adiposity and body composition, may be an important anthropometric measure to collect to monitor obesity and obesity-related risks among African Americans. These findings should be verified in other ethnically diverse populations.
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