Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis
BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j4849 (Published 14 November 2017) Cite this as: BMJ 2017;359:j4849
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Obesity accounts for 60% cases of Diabetes, 40% cases of hypertension and 20% cases of Cardiovascular diseases. The World Health Organization says that around 39% of those aged above 18 years were obese or overweight in 2014; the main cause of Obesity is a change in lifestyle. There are various treatment modalities available to treat Obesity. A multidisciplinary approach to Obesity is one in which many disciplines work with a common goal.
Dietary advice, Physical activity, Pharmacological innervations, Bariatric surgery etc. are various options available to manage Overweight and Obesity. A multidisciplinary approach like Dietary advice such as intake of low energy-dense foods and avoiding consumption of ‘fast foods’ and hot beverages like alcohol. Encouragement to do physical exercises like Yoga, breathing exercise, Psychological concealing to reduce sedentary behavior.
It is better to manage the prevalence of obesity as a traditional disease (1). These approaches are beneficial in preventive, curative and promotive aspects of the management of obesity (2). Finally, Richard Attias rightly said, ‘Obesity is a problem that nearly every nation in the world is facing, but there is much that we can do to fix it'.
References:
1. Frank A. A multidisciplinary approach to obesity management: the physician's role and team care alternatives. Journal of the American Dietetic Association. 1998 Oct 31;98(10):S44-8.
2. McMahon MM, Sarr MG, Clark MM, Gall MM, Knoetgen J, Service FJ, Laskowski ER, Hurley DL. Clinical management after bariatric surgery: value of a multidisciplinary approach. InMayo Clinic Proceedings 2006 Oct 31 (Vol. 81, No. 10, pp. S34-S45). Elsevier.
Competing interests: No competing interests
The metanalysis by Ma et al depends heavily on the LOOK AHEAD trial, which has a 55% weighting. Of the remaining 53 trials, 19 had the odd characteristic of having zero or one death in the intervention group. These 19 trials had 18 deaths in the controls and 9 with the intervention. A small change in the inclusion criteria for very-low-mortality studies could have easily led to a very different overall result. Except for the two largest studies, the dropout rate in all the studies exceeds the mortality by at least a factor 10. Many more patient outcomes are simply unknown relative to the number of documented deaths.
A crucial point found in the supplemental data tables is that a reduction in mortality only reached statistical significance when a "physical activity facility was provided". This metanalysis supports the conclusion that exercise is of critical importance for the longevity of the obese.
Competing interests: No competing interests
Ma et al1 assessed whether weight loss interventions for adults with obesity affect all cause, cardiovascular, and cancer mortality, cardiovascular disease, cancer, and body weight with Design Systematic review and meta-analysis of randomised controlled trials (RCTs) using random effects, estimating risk ratios, and mean differences. They observed that weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity.
Cardiometabolic syndrome consisting of obesity, dyslipidemia of high triglycerides or low high-density lipoprotein cholesterol, pre-hypertension, and pre-diabetes showing fasting glucose >100 mg/dl are major risk factors for cardiovascular diseases (CVD) such as hypertension, diabetes mellitus, coronary heart disease, and heart failure as well as cancer, congenital malformations, and dementia. Obesity is the most important factor among others and also can be controlled by diet and exercise.2-4 Indeed, exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.5 This study points to the importance of therapeutic life style changes compared with drugs intervention. All physicians should think about this message in this time of many drugs being prescribed while elderly population is increasing fast and life expectancy is longer.2,3
Obesity is currently one of the greatest public health issues worldwide. However, despite its known deleterious effects on health, recent findings led to the development of concepts such as the obesity paradox, and protective subcutaneous fat depots have raised a lively debate on the disparate effects of obesity on health outcomes.4,6-8
At the population level, it is clear that obesity is an established risk factor for the development of CVD, cancer, and even dementia and all cause mortality. In addition, multiple biological mechanisms linking obesity and CVD events have been identified. However, the possible existence of a metabolically healthy obese phenotype (which could be more appropriately be referred to as a lower risk form of obesity), the important role of regional body fat distribution and ectopic fat accumulation, and the presence of an obesity (body mass index, BMI) paradox in patients with coronary heart disease are all observations which emphasize the remarkable heterogeneity of obesity. At the population level, these complex obesity-related issues have remained the biggest challenge for clinicians dealing with numerous obese phenotypes. There is, however, robust evidence indicating that a subset of overweight and moderately obese individuals with a high level of fitness may be protected from obesity-related health outcomes.4 Thus, although it is clear that there is a strong link between the BMI and the incidence of various clinical outcomes, whether reducing the BMI should be the primary target at the clinical level remains debated. It has rather been suggested that targeting key behaviors such as improving nutritional quality, usually low in fat and saturated fat, and improving cardiorespiratory fitness through regular physical activity would be legitimate approaches contributing to generate “healthy weight loss modalities”.2-4,9 Further investigations should consider both metabolic risk and cardiorespiratory fitness in addition to the selection of appropriate obesity index to better identify and manage patients who are “at risk” for the development of CVD, cancer, and dementia.
Funding: None, Disclosures: None
REFERENCES
1. Ma C, Avenell A, Bolland M, Hudson J, Stewart F, Robertson C, Sharma P, Fraser C, MacLennan G. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849.
2. Koh KK. To take or not to take drugs? That is the question. BMJ 2013, Published 30 December 2013, http://www.bmj.com/content/347/bmj.f5577/rr/679697
3. Koh KK. Reconfirm to follow guidelines to prevent cardiovascular diseases.
BMJ 2016, Published on 5 March 2016, http://www.bmj.com/content/352/bmj.i721/rr-0.
4. Kim SH, Després JP, Koh KK. Obesity and cardiovascular disease: friend or foe?
Eur Heart J. 2016;37:3560-3568.
5. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug
interventions on mortality outcomes: metaepidemiological study. BMJ 2013;347:f5577
6. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13-22.
7. Mariscalco G, Wozniak MJ, Dawson AG, Serraino GF, Porter R, Nath M, Klersy C, Kumar T, Murphy GJ. Body mass index and mortality among adults undergoing cardiac surgery: A nationwide study with a systematic review and meta-analysis. Circulation. 2017;135:850-863.
8. Sundström J, Bruze G, Ottosson J, Marcus C, Näslund I, Neovius M. Weight loss and heart failure: A Nationwide study of gastric bypass surgery versus intensive lifestyle treatment.
Circulation. 2017;135:1577-1585.
9. Koh KK. Letter by Koh Regarding Article, “Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China)” and “Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population”
(What is the best risk prediction tool in the primary and secondary prevention?) Circulation. 2017;135:e818-e819.
Competing interests: No competing interests
We thank you for your interesting question.
In the context of weight loss randomized trials and the clinical outcomes in our review, there are two considerations for describing control group interventions.
Firstly, in the context of interventions causing weight loss in control groups, in a systematic review and meta-regression, Waters and colleagues (1) found that control groups only receiving follow-up measurements lost 1kg less than control groups getting ‘usual care’ over a median period of 6 months. But Waters and colleagues were unable to determine which factors for control groups predicted greater weight loss.
In a second systematic review with meta-regression, Johns and colleagues (2) found that minimal control group interventions were associated with 1kg weight loss at 12 months. Intensity of control group interventions and additional weigh-ins independently predicted control group weight loss, but when both were modelled together neither was associated with weight change.
Details of the content of control group interventions (and weight loss interventions too) are often poorly provided. In our current NIHR funded REBALANCE project (3) we are attempting to predict weight loss in control groups and intervention groups by including coding of the 93 behaviour change techniques from the taxonomy (4). To do this properly requires additional information to that which authors put into the public domain. Trial materials that contain this information are difficult to obtain. For example, only one third of the authors we contacted in REBALANCE provided us with information to allow us to accurately code control group intereventions.
Secondly, because behavioural weight loss trials are unblinded, care given outside the trial may differ between intervention and control arms. These differences are even less likely to be described than trial procedures. This may have particular bearing on the cardiovascular mortality and events in our review. In the largest trial in our review, the Look AHEAD trial, (5) the investigators commented that the increased use of statins in the control group compared with the intervention group may have lessened differences between the groups for cardiovascular events.
Thus detailing and classifying control group interventions for the purposes of our review carries unique challenges, which we are trying to address in our REBALANCE project.
References
(1) Waters L, St George A, Chey T, Bauman A. Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study. BMC Med Res Methodol 2012;12:120
(2) Johns DJ, Hartmann-Boyce J, Jebb SA, Aveyard P, on behalf of the Behavioural Weight Management Review Group. Weight change among people randomized to minimal intervention control groups in weight loss trials. Obesity 2016;24:772-780.
(3) (REBALANCE) REview of Behaviour And Lifestyle interventions for severe obesity: AN evidenCE synthesis. https://www.journalslibrary.nihr.ac.uk/programmes/hta/150904/#/ (accessed 17/11/2017).
(4) Michie S, Richardson M, Johnston M, Abraham, Francis J, Hardeman W, et al. The behavior change techniques taxonomy (v1) of 93 hierarchically clustered techniques: building an international consensus for the reporting of behaviour change interventions. Ann Behav Med 2013;46:81-95.
(5) Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-54 [Erratum in: N Engl J Med 2014;370:1866.].
Competing interests: No competing interests
This systematic review and meta-analysis, level I evidence, clearly concludes that weight reducing diets, usually low in fat and saturated fat, and exercise programmes, do not reduce cardiovascular events/cardiovascular specific mortality/cancer specific mortality.
From now on, various Company claims for cancer prevention/cardiovascular benefits of their products/diets/yoga classes/gym programmes/fitness machines/etc might be considered misleading.
In fact, intake of total fat is associated with lower risk of total mortality and lower risk of stroke.
Reference
http://thelancet.com/journals/lancet/article/PIIS0140-6736(17)32252-3/fulltext
Competing interests: No competing interests
Could the mortality reducing effect of weight loss interventions be partly, or in total, explained by increased exercise?
In the Supplemental Appendix Table 6 (p. 34 point 1.8) it is shown that weight loss interventions not including an exercise program did not convincingly reduce mortality 0.78 [0.44, 1.37], I² = 0%, p=0.38. Whereas, weight loss interventions including an exercise program did significantly reduce mortality 0.84 [0.72, 0.97], I² = 0%, p=0.02.
The authors conclude that "Weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity".
However, the data only support that weight loss interventions, not solely weight reducing diets, reduce mortality, and the subgroup analysis does not robustly support that interventions without exercise programs reduced mortality even though this is concluded in the article.
The authors could have discussed the apparent importance of including proper exercise programs, and not only advice to exercise, in weight loss interventions.
Competing interests: No competing interests
"Many of the trials had quite intensive control group interventions, and the unblinded nature of the interventions could have led to more medical treatment in control groups, tending to reduce differences between groups."
What is meant by "quite intensive control group interventions"? Since the risk ratio is determined by the relative efficacy of each comparator intervention, it would have been helpful for the authors to provide a brief description of each comparator in Table 1. Did the authors also consider conducting a sensitivity analysis to exclude comparators that were more "intensive"?
Competing interests: No competing interests
Authors' reply to Ernsberger, Koh and Saripanidis
We thank you for your interest in our research.
Ernsberger and Køster-Rasmussen highlight the subgroup analysis for mortality for the importance of a physical activity facility as part of the intervention (RR 0.84, 95% CI 0.72 to 0.97). Firstly, statistical testing for this group against the groups that only got physical activity advice, or the groups that were not reported as receiving physical activity advice, was unable to demonstrate statistical heterogeneity (Chi² = 1.22, df = 2, P = 0.54, I² = 0%). Secondly, even if that was the case, subgroup testing in meta-analysis should be regarded with great caution (1), particularly as there are many other differences between the groups of trials in subgroup testing. Individual patient data meta-analyses would be required for further exploration of these subgroup findings for physical activity.
Ernsberger highlights the influence of the Look AHEAD trial (2), which carried 55% of the weighting in the meta-analysis of mortality. That is the reason that we undertook a post hoc analysis without this trial, which showed that weight loss interventions were still associated with decreased all-cause mortality (n=33 trials, 309 events; RR 0.78, 95% CI: 0.63 to 0.96; I2=0%). Sensitivity analysis to take account of rare events, using a random effects Bayesian logistic regression model, found a similar result.
As we acknowledge, we may have failed to identify all trials with outcome data, which may have biased results if trialists did not present these outcomes, particularly for those who dropped out, although we could not see obvious funnel plot asymmetry for all-cause mortality for our included studies. We also examined the drop out rate closely, it averaged 16% across all intervention groups and 16% across all control groups. We agree that trials described patient outcomes poorly, but think it unlikely that the many smaller trials with few events would have consistently failed to describe deaths in control groups when they described them in the intervention groups.
Saripanidis states that we conclude that ‘weight reducing diets do not reduce cardiovascular events/cardiovascular specific mortality/cancer specific mortality’. This is not our conclusion. Our conclusion is that we have been unable to demonstrate an effect on these outcomes. As is clear from our report and appendices, many studies did not provide details on the causes of death (see particularly Appendix Table 1), or did not collect or were unable to provide data on cardiovascular events. Thus our statistical power for these outcomes was limited.
Koh states that there is robust evidence that a ‘subset of overweight and moderately obese individuals with a high level of fitness may be protected from obesity-related health outcomes’, quoting the review from their group, which focused on cardiovascular disease (3). We did not examine the effect of interventions on those who are overweight as defined by BMI in our review. We think caution is required in suggesting that people with obesity or subgroups of obese patients are protected from obesity-related health outcomes. Firstly, a narrow focus on cardiovascular disease is likely to obscure harms that are relevant to patients such as diabetes, several common cancers, osteoarthritis, non-alcoholic fatty liver disease and cirrhosis, infertility, stress incontinence, erectile dysfunction, and most importantly overall quality of life. Secondly, there is no consensus for Koh’s suggestion that there is a group of people who can be easily and prospectively identified and are not at long-term risk of meaningful obesity-related complications.
References
(1) Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G. How to use a subgroup analysis. Users’ guides to the medical literature. JAMA 2014;311:405-11.
(2) Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-54 [Erratum in: N Engl J Med 2014;370:1866.].
(3) Kim SH, Després JP, Koh KK. Obesity and cardiovascular disease: friend or foe? Eur Heart J 2016;37:3560-8.
Competing interests: No competing interests