Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.

The Lancet (Impact Factor: 45.22). 04/2009; 373(9669):1083-96. DOI: 10.1016/S0140-6736(09)60318-4
Source: PubMed

ABSTRACT The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies.
Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975-85], mean BMI 25 [SD 4] kg/m(2)). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other.
In both sexes, mortality was lowest at about 22.5-25 kg/m(2). Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m(2) higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m(2) [HR] 1.29 [95% CI 1.27-1.32]): 40% for vascular mortality (HR 1.41 [1.37-1.45]); 60-120% for diabetic, renal, and hepatic mortality (HRs 2.16 [1.89-2.46], 1.59 [1.27-1.99], and 1.82 [1.59-2.09], respectively); 10% for neoplastic mortality (HR 1.10 [1.06-1.15]); and 20% for respiratory and for all other mortality (HRs 1.20 [1.07-1.34] and 1.20 [1.16-1.25], respectively). Below the range 22.5-25 kg/m(2), BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI.
Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5-25 kg/m(2). The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30-35 kg/m(2), median survival is reduced by 2-4 years; at 40-45 kg/m(2), it is reduced by 8-10 years (which is comparable with the effects of smoking). The definite excess mortality below 22.5 kg/m(2) is due mainly to smoking-related diseases, and is not fully explained.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. To reconcile "the obesity paradox," we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients. Methods. We analyzed data of diabetic patients attending a community-based prospective, "Tehran lipid and glucose study." In the mortality analysis, anthropometric measures-body mass index (BMI), waist, and hip circumference-were assessed using Cox models incorporating cubic spline functions. Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m(-2) were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m(-2) increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained. Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical.
    International Journal of Endocrinology 08/2014; 2014:282089. DOI:10.1155/2014/282089 · 1.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Public health initiatives focused on obesity prevention and lifestyle intervention programmes for patients with obesity have struggled to contain the obesity epidemic to date. In recent years, antiobesity drug therapies have had a limited role in clinical treatment algorithms for patients with obesity. Indeed, a number of high-profile antiobesity drug suspensions have markedly impacted upon the landscape of obesity pharmacotherapy. In this review, we discuss the advent of an increasing array of pharmacotherapeutic agents, which are effective both in inducing weight loss and in maintaining weight loss achieved by lifestyle measures. The development of these drugs as antiobesity agents has followed varying paths, ranging from lorcaserin, a selective serotonin agent, exploiting the beneficial central actions of fenfluramine but without the associated systemic side effects, to liraglutide, a gut hormone already used as a glucose-lowering drug but with appetite-suppressant properties, or the novel drug combination of phentermine/topiramate, two 'old' drugs used in lower doses than with previous therapeutic uses, resulting in an additive effect on weight loss and fewer side effects. We summarize the key findings from recent randomized controlled trials of these three drugs. Although these agents lead to clinically important weight loss when used as monotherapy, the use of antiobesity drugs as adjunctive therapy post intensive lifestyle intervention could prove to be the most successful strategy. Moreover, a progressive approach to obesity pharmacotherapy perhaps offers the best opportunity to finally address the obesity crisis on a mass scale.
    05/2014; 5(3):135-148. DOI:10.1177/2040622314522848
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective A key public health priority is to minimise obesity-related health consequences. We aim to establish whether physical activity (PA) or less sedentary behaviour ameliorate associations of obesity with biomarkers for cardiovascular disease (CVD) and type 2 diabetes. Methods Data on obesity (33 y), PA (42 y), TV-viewing and health biomarkers (45 y) are from the 1958 British birth cohort (N = 9377). Results Obesity was associated with an adverse biomarker profile for CVD and type 2 diabetes. For PA, men active ≥1/week had 1.09% (0.28, 1.90) lower diastolic blood pressure (DBP) than less active men; triglycerides were 2.08% (0.52, 3.64) lower per unit higher PA (on 4-point scale). TV-viewing was independently associated with several biomarkers, e.g. per unit higher TV-viewing (on 4-point scale) DBP was raised by 0.50% (0.09, 0.90) and triglycerides by 3.61% (1.58, 5.64). For both TV-viewing and PA, associations with HbA1c were greatest for the obese (pinteraction ≤ 0.04): compared to a reference value of 5.20 HbA1c% in non-obese men viewing 0–1 h/day, HbA1c% differed little for those viewing >3 h/day; among obese men HbA1c% was 5.36 (5.22, 5.51) and 5.65 (5.53, 5.76), for 0–1 and >3 h/day respectively. For PA in non-obese men, the reduction associated with activity ≥1/week was negligible compared to a reference value of 5.20 HbA1c% for those less active; but there was a reduction among obese men, HbA1c% was 5.50 (5.40, 5.59) vs 5.66 (5.55, 5.77) respectively. Conclusion Reduced TV-viewing and prevention of infrequent activity have greatest beneficial associations for glucose metabolism among the obese, with benefits for other biomarkers across obese and non-obese groups.
    Atherosclerosis 04/2014; 233(2):363–369. DOI:10.1016/j.atherosclerosis.2014.01.032 · 3.97 Impact Factor