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Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

BMJ 2016; 355 doi: (Published 24 November 2016) Cite this as: BMJ 2016;355:i5855

What Should We Do To Reduce the Risk of all Cause and Cause-specific Mortality?

What Should We Do To Reduce the Risk of all Cause and Cause-specific Mortality?
Veronese N, et al evaluated the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality from Nurses' Health Study and Health Professionals Follow-up Study with 32 years of follow-up. In each of the four categories of body mass index (BMI) studied, people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors. This study suggests to consider diet and lifestyle factors in the evaluation of the association between BMI and mortality.1

To use BMI is simple and easy to estimate the degree of obesity, however, there is the flaw of the BMI because of its limitations including its inability to discriminate between fat mass and muscle mass.2 Furthermore, the U shaped relation between BMI and mortality observed in many epidemiological studies is driven by an over-representation of individuals who are lean because of chronic metabolic and pathological conditions caused by exposure to smoking, a sedentary lifestyle, and/or unhealthy diets, making them more susceptible to death. Accordingly, we should think about the effects of lifestyle factors becasue these have reduced mortality and morbidity.3-6 A study investigated to quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events. They observed that although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%.3 Another study investigated dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease. They observed that total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day) and coronary heart disease (0.91). Further, insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease.5

On the other hand, we may think about new adiposity-related biomarkers to improve the inherent shortcomings of BMI assessment. Nonetheless, a recent mata-analysis reported the associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents, supporting strategies to combat the entire spectrum of excess adiposity in many populations.7 In this regard, Lee JJ, et al8 explored the degree to which changes in abdominal fat quantity and quality are associated with changes in cardiovascular disease (CVD) risk factors and reported that increasing accumulation of fat quantity and decreasing fat attenuation (fat quality) are associated with worsening of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose tissue volumes. This study showed an additional 500 cm3 increase in fat volume was associated with incident hypertension (odds ratio [OR]: 1.21 for subcutaneous adipose tissue; OR: 1.30 for and visceral adipose tissue), However, Sullivan CA, et al9 determined whether a change in specific fat depots predicts the development of hypertension. Mid-thigh subcutaneous fat area, abdominal subcutaneous fat area, and intra-abdominal fat area were directly measured by computed tomography at baseline and 5 years. The relative odds of developing hypertension for a 5-year increase in intra-abdominal fat was 1.74, after adjusting for age, sex, BMI, and others. In contrast, there were no significant associations between baseline and change in thigh or abdominal subcutaneous fat areas and incident hypertension. In this cohort of Japanese Americans, the risk of developing hypertension is related to the accumulation of intra-abdominal fat rather than the accrual of subcutaneous fat in either the thigh or the abdominal areas.

Also, ectopic fat accumulation around the heart and vessels (PAT) has been also reported to be related to cardiovascular risk, despite the fact that these fat cells represent a very small proportion of total body adipose tissue. Although PAT quantity is reported to be correlated with cardiometabolic complications, PAT quantity is correlated with the amount of visceral adipose tissue. However, due to its proximity to the vascular structure and the heart, inflammatory processes in PAT might directly contribute to cardiovascular complications. However, how these impair endothelial-dependent vasodilation and potentiate coronary contraction will require further investigation.10

Effective therapies to prevent cardiovascular disease and coronary heart disease are very important in the public health. To aligned with its paramount importance, general recommendations of diet and exercise with a confirmed evidence have been released. Nonetheless, pretty many dietary supplements are widespread and many people are taking them. Money spent for them is uncountable. It should be noted that recent three studies reported no effectiveness of supplementation with a multivitamin.11-13 These would suggest that supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful and therefore, these vitamins should not be used for chronic disease prevention.14

On the other hand, Naci H, et al investigated to determine the comparative effectiveness of exercise, another component of therapeutic life style changes versus drug interventions on mortality outcomes. They observed that no statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. They concluded that although limited in quantity, existing randomised trial evidence on exercise interventions suggests that 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.15

All these studies points the importance of therapeutic life style changes mostly consisting of healthy diet and regular exercise compared with drugs intervention. All physicians should think about this message in time of many drugs and mineral or multivitamin supplementation being prescribed while elderly population is increasing fast and life expectancy is longer.

Funding: None, Disclosures: None

1. Veronese N, Li Y, Manson JE, Willett WC, Fontana L, Hu FB. Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study. BMJ 2016;355:i5855.

2. Kim SH, Després JP, Koh KK. Obesity and cardiovascular disease: friend or foe? Eur Heart J 2015 Dec 18. pii: ehv509. Review.

3. Kyu H, Bachman V, Alexander L, et al. Physical activity and risks of breast cancer, colon
cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review
and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ

4. Koh KK. Which one matters? Lower or higher levels of activity? Or diet?. BMJ 2016, Published 12 August 2016,

5. Threapleton DE, Greenwood DC, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 2013;347:f6879.

6. Koh KK. Reconfirm the importance of therapeutic life style changes. BMJ 2014, Published 1 January 2014,

7. Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents.
Lancet 2016;388:776-86.

8. Lee JJ, Pedley A, Hoffmann U, et al. Association of changes in abdominal fat quantity and
quality with incident cardiovascular disease risk factors. J Am Coll Cardiol 2016;68:1509–21.

9. Sullivan CA, Kahn SE, Fujimoto WY, Hayashi T, Leonetti DL, Boyko EJ. Change in intra-abdominal fat predicts the risk of hypertension in Japanese Americans. Hypertension 2015;66:134-40.

10. Lee HY, Després JP, Koh KK. Perivascular adipose tissue in the pathogenesis of cardiovascular disease. Atherosclerosis 2013;230:177-84.

11. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013; 159:824-834.

12. Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al, for the TACT (Trial to Assess Chelation Therapy) Investigators. Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial. Ann Intern Med 2013;159:797-805.

13. Grodstein F, O’Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial Ann Intern Med 2013;159:806-814.

14. Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER, III. Enough is enough: stop wasting money on vitamin and mineral supplements. Ann Intern Med 2013;159:850-851.

15. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug
interventions on mortality outcomes: metaepidemiological study. BMJ 2013;347:f5577.

Competing interests: No competing interests

27 November 2016
Kwang Kon KOH
Professor of Medicine
Department of Cardiovascular Medicine, Gachon University, Gil Medical Center
774 Beongil 21, Namdongdaero, Namdong-Gu, Incheon, Korea 21565