Reverse causation and illness-related weight loss in observational studies of body weight and mortality.

In studies of weight and mortality, the construct of reverse causation has come to be used to imply that the exposure-outcome relation is biased by weight loss due to preexisting illness. Observed weight-mortality associations are sometimes thought to result from this bias. Evidence for the occurrence of such bias is weak and inconsistent, suggesting that either the analytical methods used have been inadequate or else illness-related weight loss is not an important source of bias. Deleting participants has been the most frequent approach to control possible bias. As implemented, this can lead to deletion of almost 90% of all deaths in a sample and to deletion of more overweight and obese participants than participants with normal or below normal weight. Because it has not been demonstrated that the procedures used to adjust for reverse causation increase validity or have large or systematic effects on relative risks, it is premature to consider reverse causation as an important cause of bias. Further research would be useful to elucidate the potential effects and importance of reverse causation or illness-related weight loss as a source of bias in the observed associations between weight and mortality in cohort studies.

[1]  V. Chang,et al.  Mortality attributable to obesity among middle-aged adults in the united states , 2009, Demography.

[2]  F. Clavel-Chapelon,et al.  Weight change in later life and risk of death amongst the elderly: the European Prospective Investigation into Cancer and Nutrition‐Elderly Network on Ageing and Health study , 2010, Journal of internal medicine.

[3]  Stacey A. Kenfield,et al.  Burden of smoking on cause-specific mortality: application to the Nurses' Health Study , 2010, Tobacco Control.

[4]  Xin Sun,et al.  Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses , 2010, BMJ : British Medical Journal.

[5]  P. Barberger‐Gateau,et al.  Body Mass Index, Disability, and 13-Year Mortality in Older French Adults , 2010, Journal of aging and health.

[6]  S. Anker,et al.  The obesity paradox: weighing the benefit. , 2010, European heart journal.

[7]  O. Franco,et al.  Adiposity and weight change in mid-life in relation to healthy survival after age 70 in women: prospective cohort study , 2009, BMJ : British Medical Journal.

[8]  T. Wyller,et al.  Increased mortality in the slim elderly: a 42 years follow-up study in a general population , 2009, European Journal of Epidemiology.

[9]  N. Timpson,et al.  Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype. , 2009, International journal of epidemiology.

[10]  D. Allison,et al.  Mortality, Health Outcomes, and Body Mass Index in the Overweight Range: A Science Advisory From the American Heart Association , 2009, Circulation.

[11]  W. Willett,et al.  Body Mass Index Before and After Breast Cancer Diagnosis: Associations with All-Cause, Breast Cancer, and Cardiovascular Disease Mortality , 2009, Cancer Epidemiology Biomarkers & Prevention.

[12]  F. Willekens,et al.  Smoking Kills, Obesity Disables: A Multistate Approach of the US Health and Retirement Survey , 2009, Obesity.

[13]  R. Collins,et al.  Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies , 2009, The Lancet.

[14]  P. Pronovost,et al.  The impact of obesity on outcomes after critical illness: a meta-analysis , 2009, Intensive Care Medicine.

[15]  L. Tanoue.  Smoking and Smoking Cessation in Relation to Mortality in Women , 2009 .

[16]  M. Stampfer,et al.  Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis. , 2008, The Lancet. Oncology.

[17]  I. Janssen,et al.  Effect of Current and Midlife Obesity Status on Mortality Risk in the Elderly , 2008, Obesity.

[18]  W. Willett,et al.  Prospective weight change and colon cancer risk in male US health professionals , 2008, International journal of cancer.

[19]  F. Hu,et al.  Cancer and cholesterol: understanding the V-shaped association in patients with diabetes , 2008, Canadian Medical Association Journal.

[20]  R. Cooper.  Which factors confound or modify the relationship between body weight and mortality? , 2008, International Journal of Obesity.

[21]  W. Flanders,et al.  Adjusting for reverse causality in the relationship between obesity and mortality , 2008, International Journal of Obesity.

[22]  D. Melzer,et al.  Obesity, Physical Function, and Mortality in Older Adults , 2008, Journal of the American Geriatrics Society.

[23]  D. Knockaert,et al.  Involuntary weight loss. Does a negative baseline evaluation provide adequate reassurance? , 2008, European journal of internal medicine.

[24]  R. Abbott,et al.  Relationship Between BMI and All‐cause Mortality in Japan: NIPPON DATA80 , 2008, Obesity.

[25]  N. Perrin,et al.  Weight Change and Glycemic Control After Diagnosis of Type 2 Diabetes , 2008, Journal of General Internal Medicine.

[26]  F. Willekens,et al.  The burden of mortality of obesity at middle and old age is small. A life table analysis of the US Health and Retirement Survey , 2008, European Journal of Epidemiology.

[27]  F. Taylor.  Weight change associated with the use of migraine-preventive medications. , 2008, Clinical therapeutics.

[28]  P. Gupta,et al.  Association of body mass index with all-cause and cause-specific mortality: findings from a prospective cohort study in Mumbai (Bombay), India. , 2008, International journal of epidemiology.

[29]  M. Rosén,et al.  Underweight, overweight and obesity as risk factors for mortality and hospitalization , 2008, Scandinavian journal of public health.

[30]  J M Robins,et al.  Causal models for estimating the effects of weight gain on mortality , 2008, International Journal of Obesity.

[31]  J. Brooks.  Why most published research findings are false: Ioannidis JP, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece , 2008 .

[32]  J. Klenk,et al.  Weight change and cancer risk in a cohort of more than 65,000 adults in Austria. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[33]  J. Goodwin,et al.  The Effect of Obesity on Disability vs Mortality in Older American: The Potential Implication of Testosterone—Reply , 2007 .

[34]  S. Anker,et al.  How does cachexia influence survival in cancer, heart failure and other chronic diseases? , 2007, Current opinion in supportive and palliative care.

[35]  Stephen W Lagakos,et al.  Statistics in medicine--reporting of subgroup analyses in clinical trials. , 2007, The New England journal of medicine.

[36]  V. Beral,et al.  Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study , 2007, BMJ : British Medical Journal.

[37]  M. Gail,et al.  Impact of smoking and preexisting illness on estimates of the fractions of deaths associated with underweight, overweight, and obesity in the US population. , 2007, American journal of epidemiology.

[38]  J. Manson,et al.  Body mass index and mortality in men: evaluating the shape of the association , 2007, International Journal of Obesity.

[39]  F. Paccaud,et al.  Associations between obesity and health conditions may be overestimated if self‐reported body mass index is used , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[40]  F. Guillemin.  Primer: the fallacy of subgroup analysis , 2007, Nature Clinical Practice Rheumatology.

[41]  P. Derost,et al.  Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation. , 2007, Brain : a journal of neurology.

[42]  J. Kelsey,et al.  Associations between body composition, anthropometry, and mortality in women aged 65 years and older. , 2007, American journal of public health.

[43]  J. Manson,et al.  Estimating the number of deaths due to obesity: can the divergent findings be reconciled? , 2007, Journal of women's health.

[44]  T. Rice.  Obesity in acute lung injury: The "weight" is over. , 2007, Chest.

[45]  I. Janssen,et al.  Elevated body mass index and mortality risk in the elderly , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[46]  A. Trentham-Dietz,et al.  Breast cancer risk factors and second primary malignancies among women with breast cancer , 2007, Breast Cancer Research and Treatment.

[47]  D. Lawlor,et al.  Reverse Causality and Confounding and the Associations of Overweight and Obesity with Mortality , 2006, Obesity.

[48]  K. Kashihara.  Weight loss in Parkinson’s disease , 2006, Journal of Neurology.

[49]  N. Wolmark,et al.  Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. , 2006, Journal of the National Cancer Institute.

[50]  J. Morris,et al.  Accelerated weight loss may precede diagnosis in Alzheimer disease. , 2006, Archives of neurology.

[51]  W. Chow,et al.  Relation of body mass index to cancer risk in 362,552 Swedish men , 2006, Cancer Causes & Control.

[52]  T. Harris,et al.  Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. , 2006, The New England journal of medicine.

[53]  Sun Ha Jee,et al.  Body-mass index and mortality in Korean men and women. , 2006, The New England journal of medicine.

[54]  J. Robins,et al.  Estimating causal effects from epidemiological data , 2006, Journal of Epidemiology and Community Health.

[55]  S. Lemeshow,et al.  Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury* , 2006, Critical Care Medicine.

[56]  K. Reynolds,et al.  Body weight and mortality among men and women in China. , 2006, JAMA.

[57]  A. Trentham-Dietz,et al.  Weight change and risk of endometrial cancer. , 2006, International journal of epidemiology.

[58]  D. Lawlor,et al.  Association of body mass index with suicide mortality: a prospective cohort study of more than one million men. , 2006, American journal of epidemiology.

[59]  H. Kroger,et al.  Body mass index as a predictor of fracture risk: A meta-analysis , 2005, Osteoporosis International.

[60]  M. Stampfer.  Weight Loss and Mortality: What Does the Evidence Show? , 2005, PLoS medicine.

[61]  C. Lewis,et al.  Voluntary weight reduction in older men increases hip bone loss: the osteoporotic fractures in men study. , 2005, The Journal of clinical endocrinology and metabolism.

[62]  D. McGee,et al.  Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies. , 2005, Annals of epidemiology.

[63]  R. Baumgartner,et al.  Changes in body fat and weight after a breast cancer diagnosis: influence of demographic, prognostic, and lifestyle factors. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  E. Trell,et al.  Premature mortality in middle-aged men: Serum cholesterol as risk factor , 1983, Klinische Wochenschrift.

[65]  Olga Kostopoulou,et al.  Handbook of Health Research Methods: Investigation, Measurement and Analysis , 2005 .

[66]  R. Stewart,et al.  A 32-year prospective study of change in body weight and incident dementia: the Honolulu-Asia Aging Study. , 2005, Archives of neurology.

[67]  J. Manson,et al.  Body mass index and mortality among US male physicians. , 2004, Annals of epidemiology.

[68]  J. Pekkanen.  Commentary: use of antibiotics and risk of asthma. , 2004, International journal of epidemiology.

[69]  Sara T Brookes,et al.  Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. , 2004, Journal of clinical epidemiology.

[70]  S. M. Massompoor.  Unintentional Weight Loss , 2004 .

[71]  P. J. Bowman,et al.  Intentional and Unintentional Weight Loss Increase Bone Loss and Hip Fracture Risk in Older Women , 2003, Journal of the American Geriatrics Society.

[72]  T. Kaptchuk,et al.  Effect of interpretive bias on research evidence. , 2003, BMJ.

[73]  J. Riancho,et al.  Clinical evaluation for cancer in patients with involuntary weight loss without specific symptoms. , 2003, The American journal of medicine.

[74]  T. Key,et al.  Relation between body mass index and mortality in an unusually slim cohort , 2003, Journal of epidemiology and community health.

[75]  J. Manson,et al.  Obesity in the United States: a fresh look at its high toll. , 2003, JAMA.

[76]  D. Allison,et al.  Years of life lost due to obesity. , 2003, JAMA.

[77]  I. Heid,et al.  On the potential of measurement error to induce differential bias on odds ratio estimates: an example from radon epidemiology , 2002, Statistics in medicine.

[78]  E. Barrett-Connor,et al.  The Relationship Between Weight Loss and All‐Cause Mortality in Older Men and Women With and Without Diabetes Mellitus: The Rancho Bernardo Study , 2002, Journal of the American Geriatrics Society.

[79]  R. Holder,et al.  Weight gain following treatment of hyperthyroidism , 2001, Clinical endocrinology.

[80]  J. Cai,et al.  Changes in body mass index prior to baseline among participants who are ill or who die during the early years of follow-up. , 2001, American journal of epidemiology.

[81]  H. Krumholz,et al.  An evidence-based assessment of federal guidelines for overweight and obesity as they apply to elderly persons. , 2001, Archives of internal medicine.

[82]  P. Lankisch,et al.  Unintentional weight loss: diagnosis and prognosis. The first prospective follow‐up study from a secondary referral centre , 2001, Journal of internal medicine.

[83]  T. Peters,et al.  Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. , 2001, Health technology assessment.

[84]  B Järvholm,et al.  Obesity, hypertension, and the risk of kidney cancer in men. , 2000, The New England journal of medicine.

[85]  E. Rimm,et al.  Adiposity and mortality in men. , 2000, American journal of epidemiology.

[86]  J. Cauley,et al.  Risk of Mortality Following Clinical Fractures , 2000, Osteoporosis International.

[87]  T. Byers.  The observational epidemiology of changing weight: an appeal for reasons. , 1999, Epidemiology.

[88]  M. Thun,et al.  Body-mass index and mortality in a prospective cohort of U.S. adults. , 1999, The New England journal of medicine.

[89]  C. Rock,et al.  Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group. , 1999, Journal of the American Dietetic Association.

[90]  G A Colditz,et al.  Guidelines for healthy weight. , 1999, The New England journal of medicine.

[91]  M. Szklo,et al.  Epidemiology: Beyond the Basics , 1999 .

[92]  M. Heo,et al.  Meta-analysis of the effect of excluding early deaths on the estimated relationship between body mass index and mortality. , 1999, Obesity research.

[93]  M. Heo,et al.  Simulation study of the effects of excluding early deaths on risk factor-mortality analyses in the presence of confounding due to occult disease: the example of body mass index. , 1999, Annals of epidemiology.

[94]  G. Viegi,et al.  Independent effects of stable and changing body weight on total mortality. , 1999 .

[95]  Effect of smoking on the body mass index-mortality relation: empirical evidence from 15 studies. BMI in Diverse Populations Collaborative Group. , 1999, American journal of epidemiology.

[96]  N. Keiding,et al.  Independent effects of stable and changing body weight on total mortality. , 1999, Epidemiology.

[97]  J. Manson,et al.  Body weight and mortality: what is the shape of the curve? , 1998, Epidemiology.

[98]  Daniel L. McGee,et al.  Mortality and optimal body mass index in a sample of the US population. , 1998, American journal of epidemiology.

[99]  E. Wouters,et al.  Weight Loss Is a Reversible Factor in the Prognosis of Chronic Obstructive Pulmonary Disease , 1998 .

[100]  Treatment of Obesity in Adults.  Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. , 1998, Obesity research.

[101]  M. Heo,et al.  Examination of "early mortality exclusion" as an approach to control for confounding by occult disease in epidemiologic studies of mortality risk factors. , 1997, American journal of epidemiology.

[102]  S. Cummings,et al.  Body Size and Hip Fracture Risk in Older Women: A Prospective Study , 1997 .

[103]  Pramil N. Singh,et al.  Body mass and 26-year risk of mortality among women who never smoked: findings from the Adventist Mortality Study. , 1997, American journal of epidemiology.

[104]  S. Cummings,et al.  Weight Change and Fractures in Older Women , 1997 .

[105]  S. Cummings,et al.  Weight change and fractures in older women. Study of Osteoporotic Fractures Research Group. , 1997, Archives of internal medicine.

[106]  M. Evans,et al.  Body weight and mortality among women. , 1997, Canadian family physician Medecin de famille canadien.

[107]  S. Cummings,et al.  Body size and hip fracture risk in older women: a prospective study. Study of Osteoporotic Fractures Research Group. , 1997, The American journal of medicine.

[108]  K. Fearon,et al.  Changes in nutritional status associated with unresectable pancreatic cancer. , 1997, British Journal of Cancer.

[109]  C. M. Reife.  Involuntary weight loss. , 1995, The Medical clinics of North America.

[110]  A Kohn,et al.  [Data torturing]. , 1994, Harefuah.

[111]  R. Kushner.  Body weight and mortality. , 2009, Nutrition reviews.

[112]  J. Manson,et al.  Body weight and mortality. A 27-year follow-up of middle-aged men. , 1993, JAMA.

[113]  H. Tyroler,et al.  Changes in plasma lipid and lipoprotein cholesterol and weight prior to the diagnosis of cancer. , 1991, Cancer research.

[114]  B. Duncan,et al.  Obesity and mortality in the Lipid Research Clinics Program Follow-up Study. , 1990, Journal of clinical epidemiology.

[115]  J. Manson,et al.  Body Weight and Longevity-Reply , 1987 .

[116]  J. Manson,et al.  Body weight and longevity. A reassessment. , 1987, JAMA.

[117]  Sander Greenland,et al.  Modern Epidemiology 3rd edition , 1986 .

[118]  S. Pitlik,et al.  Unintentional Weight Loss: A Retrospective Analysis of 154 Cases , 1986 .

[119]  H. Sox,et al.  Involuntary weight loss: diagnostic and prognostic significance. , 1981, Annals of internal medicine.

[120]  M. Shipley,et al.  PLASMA LIPIDS AND MORTALITY: A SOURCE OF ERROR , 1980, The Lancet.

[121]  Plumley Pf.  Letter: the consultants' contract. , 1975, Lancet.