14 December, 2015: 

Obesity is a well-known major risk factor for many disease situations as well as for mortality. This risk is easily identified by a simple measurement of weight or of body mass index (BMI). However, there are several additional related parameters, namely lean body mass, total body fat, visceral fat, body composition and distribution of body fat, which have been investigated in light of their potential prognostic values. A recent study presented data from the Women's Health Initiative on associations between BMI, body composition, and incident mortality [1]. About 10,500 postmenopausal women, who underwent dual-energy X-ray absorptiometry scans (DXA) for estimation of total body fat and lean body mass, were followed for 13.6 (± 4.6) years. Their baseline characteristics were: age 63 (± 7) years; age at menopause 47 (± 7) years; weight 74 kg (± 16) kg; BMI 28 (± 6) kg/m2; total lean body mass 53% (± 7%); total fat body mass 44% (± 7%). Overall, BMI 35 kg/m2 was associated with increased mortality (adjusted HR 1.45, 95% CI 1.16–1.82), while total body fat and lean body fat were not. Among women aged 50–59 years, higher % total body fat increased risk of death (HR 2.44, 95% CI 1.38–4.34) and higher % lean body mass decreased risk of death (HR 0.41, 95% CI 0.23–0.74), despite broad-ranging BMIs. However, the relationships were reversed among women aged 70–79 years (p < 0.05). When the results were stratified by waist circumference, the protective association of higher lean body mass in younger women (age < 60 years) was seen only among those with low waist circumference (< 88 cm) and not those with larger waists (≥ 88 cm). Furthermore, the increased mortality risk among older women (ages 60–69 and ≥ 70 years) with higher lean body mass was seen only among those with a high waist circumference.

Comment

Body weight and BMI give pretty good correlations with many metabolic, cardiovascular and neoplastic diseases.

But is it the best risk predictor? Would the addition of another parameter improve such forecast? Indeed, in Bea's study, BMI was significantly associated with all-cause mortality incidence in the full cohort [1]. However, what is typically considered adverse body composition (high % total body fat and/or low % lean body mass) was associated with higher mortality only among younger postmenopausal women. In fact, there was an opposing association in older women. So perhaps it is not only weight that matters, but also how much fat tissue is there and where this fat tissue is located. Bea's results suggest that body composition is an important factor for evaluating mortality risk in postmenopausal women, especially women aged 50–59 years. Higher mortality risk may not be captured by BMI measurements alone as many postmenopausal women with normal BMI but excess total body fat upon DXA assessment of body composition may be at increased risk of mortality. Such women may not receive appropriate lifestyle and therapeutic recommendations to address their adiposity-associated mortality risk. Furthermore, since weight loss alone induces loss of both lean body mass and total fat, lifestyle recommendations should include the use of lean body mass-preserving strategies, such as physical activity, while losing weight.

This discussion raises some associated thoughts about postmenopausal hormone replacement therapy (HRT) due to potential changes in body composition as a result of estrogen deficiency, on the one hand, and exogenous estrogen replacement on the other hand. The typical premenopausal 'pear shape' altering to postmenopausal 'apple shape', and the menopause-related increase in waist circumference and abdominal fat are good examples for these processes. A recent study from Denmark and Sweden included about 2900 women (mean age 49 ± 9 years at baseline) [2]. During a 6-year follow-up, both large baseline waist circumference and 6-year increase in waist circumference were associated with increased total mortality and cardiovascular disease incidence and mortality. A baseline waist circumference above 82 cm or an increase in waist circumference by more than 8 cm doubled the risk. Associations were particularly strong for women with normal weight. Some basic science explanations for the role of estrogen in regulation of body composition are brought in a comprehensive review by Van Pelt and colleagues in the September issue of Endocrinology and Metabolism Clinics of North America [3]. The authors point at a well-established finding that the disruption of estradiol signaling accelerates abdominal fat accumulation, which leads to insulin resistance and dyslipidemia. They also claim that the presence of mitochondrial estrogen receptors suggests a role of estradiol in the regulation of cellular bioenergetics. In animals, a decrease in energy expenditure through reduction in the level of spontaneous physical activity is seen in response to estrogen deficiency, and the end result is fat accumulation. A large part of Van Pelt's review deals with clinical data. Cross-sectional comparisons of premenopausal and postmenopausal women and prospective cohort studies of women through the menopause transition have yielded evidence both for and against menopause as the mediator of changes in body composition. The reason for this inconsistency is probably the complexity of physiological alterations during perimenopause and the role of aging per se in this respect. Still, solid evidence favors healthy diet and regular physical activity as the most effective measures for cardiovascular risk reduction.

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

References

1. Bea JW, Thomson CA, Wertheim BC, et al. Risk of mortality according to body mass index and body composition among postmenopausal women. Am J Epidemiol 2015;182:585-96 http://www.ncbi.nlm.nih.gov/pubmed/26350478

2. Klingberg S, Mehlig K, Lanfer A, et al. Increase in waist circumference over 6 years predicts subsequent cardiovascular disease and total mortality in Nordic women. Obesity (Silver Spring) 2015;23:2123-30 http://www.ncbi.nlm.nih.gov/pubmed/26337249

3. Van Pelt RE, Gavin KM, Kohrt WM. Regulation of body composition and bioenergetics by estrogens. Endocrinol Metab Clin North Am 2015;44:663-76 http://www.ncbi.nlm.nih.gov/pubmed/26316249