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Leading Avoidable Cause of Premature Deaths Worldwide: Case for Obesity

      In the United States, 2 of 3 adults currently are overweight or obese.
      • Ogden C.L.
      • Carroll M.D.
      • Kit B.K.
      • Flegal K.M.
      Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010.
      The prevalence of obesity has not changed in recent years, but it is still 3 times greater than in 1980. During the last several decades, there has been a systematic underestimation of the hazards of obesity.
      • Kassirer J.P.
      • Angell M.
      Losing weight—an ill-fated New Year's resolution.
      The dangers of obesity have been grossly underestimated due to several biases.
      • Manson J.E.
      • Stampfer M.J.
      • Hennekens C.H.
      • Willett W.C.
      Body weight and longevity: a reassessment.
      The first is the failure to control for cigarette smoking. Cigarette smokers are thinner because of appetite suppression and increased metabolic rates and also die at higher rates. Thus, the failure to control for this confounder leads to the erroneous conclusion that obesity is less harmful. The second is inappropriate control for direct biologic effects of obesity such as hypertension, dyslipidemia and diabetes. Inappropriate control for direct effects of obesity, which are not confounders, leads to gross underestimates of harm. The third is failure to exclude subjects at baseline with severe weight loss due to subclinical disease. In large prospective cohort studies, lower weight at baseline due to subclinical disease leads to premature mortality, so failure to exclude such subjects underestimates the hazards of obesity.
      The dangers of obesity have been grossly underestimated in clinical outcome studies because of the failure to control for cigarette smoking, inappropriate control for the biologic effects of obesity (eg, hypertension and diabetes), and failure to exclude subjects at baseline with severe weight loss due to subclinical disease.
      • Manson J.E.
      • Stampfer M.J.
      • Hennekens C.H.
      • Willett W.C.
      Body weight and longevity: a reassessment.
      Cigarette smokers are thinner because of appetite suppression and increased metabolic rates. Failure to control for this confounder leads to the erroneous conclusion that obesity is less harmful. In addition, excessive and unjustified control for direct effects of obesity, such as hypertension and diabetes, leads to gross underestimates of harm. Finally, in large prospective cohort studies, lower weight at baseline due to subclinical disease leads to premature mortality, so failure to exclude such subjects underestimates the hazard of obesity. In the United States today, there is an approximate 10-pound weight gain per decade in middle-aged persons, so an unexplained weight loss of 10 or more pounds may be a harbinger of doom. All of these considerations are less than comforting news to a society that has been the fattest in the world and, perhaps, in the history of the world.
      Body mass index (BMI), the ratio of weight in kilograms to height in meters squared, is a risk factor for many major causes of death, including coronary heart disease, stroke, and cancers of the large intestine, kidney, uterus, and breast in postmenopausal women.
      Prospective Studies Collaboration
      Body-mass and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.
      Even more alarming, in many populations, including developing countries throughout the world, the average BMI is increasing by several percentage points per decade.
      In the Prospective Studies Collaboration,
      Prospective Studies Collaboration
      Body-mass and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.
      a collaborative analysis of data from 57 studies of approximately 900,000 adults, overall mortality was lowest at a BMI of 22 to 25 kg/m2 in men and women of all ages. In those with a BMI greater than 25 kg/m2, each 5 kg/m2 increase in BMI increased total mortality by 30%. These relative risks for BMI, combined with recent population BMI values, suggest that during the next decade in the United States, approximately 29% of deaths due to cardiovascular disease and 8% of deaths due to cancer will be attributable to a BMI greater than 25 kg/m2 in middle-aged people.
      In adulthood, avoidance of weight gain may be easier to achieve than weight loss. In that regard, avoidance of increases in BMI from 28 to 32 kg/m2 in early middle age would allow an individual to gain approximately 2 years of life expectancy. By avoiding an increase in BMI from 24 to 32 kg/m2, a young adult would gain approximately 3 extra years of life. Further, for men and women, the median survival is reduced by 0 to 1 year for people aged 60 years with a BMI of 25 to 27.5 kg/m2, by 1 to 2 years in those with a BMI of 27.5 to 30 kg/m2, by 2 to 4 years in those with a BMI of 30 to 35 kg/m2, and by 8 to 10 years for those with a BMI greater than 40 kg/m2. This extreme reduction in survival with morbid obesity is approximately as much as the 10-year reduction in survival caused by persistent cigarette smoking.
      Prospective Studies Collaboration
      Body-mass and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.
      The pandemic of obesity results from genetic and environmental factors, chiefly increased caloric intake and physical inactivity beginning in childhood.
      • Hennekens C.H.
      • Schneider W.R.
      • Barice E.J.
      Obesity in childhood: introduction and general considerations.
      More alarming, these trends also have been well documented in many developing countries. In the most populous country in the world, China, the remarkable increase in the prevalence of obesity in urban areas is already accompanied by remarkable increases in the prevalence of diabetes.
      • Yang W.
      • Lu J.
      • Weng J.
      China National Diabetes and Metabolic Disorders Study Group
      Prevalence of diabetes among men and women in China.
      In data from a random sample of the US population aged 20 years or older, 20% have metabolic syndrome, a constellation of obesity, hypertension, dyslipidemia, and insulin resistance, a precursor of diabetes.
      • Ford E.S.
      • Giles W.H.
      • Dietz W.H.
      Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.
      In those aged 50 years or more, 30% have metabolic syndrome, and their 10-year risk of a first coronary event is 16% to 18%, which is approximately as high as that of a patient receiving secondary prevention. The therapeutic lifestyle changes of weight loss and increased physical activity would preclude the need for pharmacologic therapies for the majority. Unfortunately, in the United States, many prefer the prescription of pills to the proscription of harmful lifestyles. Thus, although lifestyle changes should be strongly recommended, clinicians should not let the perfect be the enemy of the possible. Evidence-based doses of statins, aspirin, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers should be prescribed as adjuncts, not alternatives, to therapeutic lifestyle changes.
      • Hennekens C.H.
      • Schneider W.R.
      The need for wider and appropriate utilization of statins and aspirin in treatment and prevention of cardiovascular disease.
      At present, most of the remarkable decline in mortality from cardiovascular disease in the United States during the past several decades is due to treatment, not prevention, and the rate of decline is decreasing. As this current generation of US children and adolescents reach middle age, morbidity and mortality from cardiovascular disease will increase.
      • Hennekens C.H.
      Increasing global burden of cardiovascular disease; current knowledge and future directions for research on risk factors Special report: Conner Lecture at AHA.
      It is likely that the current generation of children and adolescents in the United States will be the first since 1960 to have higher mortality rates due to cardiovascular disease, including coronary heart disease and stroke, than their parents. The alarming increases in obesity and tobacco consumption in developing countries have led to reliable estimates that cardiovascular disease has already increased from the number 5 killing disease to the leading killing disease in the world. Approximately 17.3 million people died of cardiovascular disease in 2008, a figure that will increase to approximately 23.6 million by 2030. More than 80% of premature deaths from cardiovascular disease already occur in low- and middle-income countries.
      • Lozano R.
      • Naghavi M.
      • Foreman K.
      • et al.
      Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
      The need for primary prevention of obesity beginning in childhood is clear, but there is no consensus regarding the best approach that should include therapeutic lifestyle changes and pharmacologic therapies. Further research is certainly warranted but so are clinical and health policy measures.

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