Lidia Pavlovna Choroshinina, Doctor of Medical Sciences, Professor.
Place of work: Department of Faculty Therapy named after Prof. V.A.Waldman, St. Petersburg State Pediatric Medical University, Position: Professor of the Department
Lawson Arman. H, Doctor of Medical Sciences, Professor
It is a well-established idea that the leading factor in the development of a significant number of somatic diseases and related problems occurs precisely in obese patients. It is logical to expect a severe course of diseases and an unfavorable general medical prognosis in obese people. However, in recent years sensational scientific publications have appeared that refute the well-established opinion of clinicians and pathophysiologists about the unequivocally adverse effects of obesity on human health. This strange fact is called the “obesity paradox” and is considered an epidemiological discovery.
In 2013, analysis of the results of 97 studies was carried out with a total sample size of more than 2.88 million people[ Katherine M Flegal , Brian K Kit , Heather Orpana et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis // JAMA. 2013 Jan 2;309(1):71-82. ]. The relationship between all-cause mortality in overweight people and obesity was studied. The total mortality rates from all causes were estimated in people with normal body weight, when the body mass index (BMI) was 18.5- 24.9 kg/m², overweight (BMI 25-<30 kg/m²), and class I obesity (BMI from 30 to <35 kg/m²), class II obesity and class III obesity (BMI ≥35 kg/m²). It was shown that overweight and class I obesity were associated with significantly lower mortality from all causes. The existence of the obesity paradox did not depend on demographic characteristics or the presence of concomitant diseases in the examined people [Rubie Sue Jackson ,James H Black 3rd,Ying Wei Lum, et al. Class I obesity is paradoxically associated with decreased risk of postoperative stroke after carotid endarterectomy \\ J Vasc Surg. 2012 May;55(5):1306-12. ]. In 2014, a meta-analysis of 10 scientific articles was conducted [Vaughn W Barry , Meghan Baruth , Michael W Beets et. al. Fitness vs. fatness on all-cause mortality: a meta-analysis //Prog Cardiovasc Dis Jan-Feb 2014;56(4):382-90], according to which overweight and obese people had the same risk of death as those with normal body weight. A meta-analysis of publications on mortality among 19,538 elderly people living in nursing homes [N.Veronese , E Cereda , ,M Solmi et al. Inverse relationship between body mass index and mortality in older nursing home residents: a meta-analysis of 19,538 elderly subjects // Obes Rev. 2015 Nov;16(11):1001-15.] , revealed an inverse relationship between the body mass index of these people and mortality rates. Underweight was a risk factor for higher mortality due to infections. Overweight and obese nursing home residents had lower infection-related mortality rates than those in the normal body weight group.
Patients with detected cardiovascular diseases being overweight or obese with body mass index (BMI) between 25 and 29.9 kg/m² and ≥30 kg/m², respectively, had a better medical prognosis than patients with similar diseases but reduced body weight [Carl J Lavie, Alban De Schutter, Edward Archer et.al. Obesity and prognosis in chronic diseases–impact of cardiorespiratory fitness in the obesity paradox //Curr Sports Med Rep Jul-Aug. Jul-Aug 2014;13(4):240-5.]. Patients with cardiovascular disease, moderate obesity and overweight had a better prognosis compared to people who were thin, but provided that people with obesity did feasible physical exercise [Vaughn W Barry , Meghan Baruth , Michael W Beets et. al. Fitness vs. fatness on all-cause mortality: a meta-analysis //Prog Cardiovasc Dis Jan-Feb 2014;56(4):382-90.]. Surveyed 9563 men with an average age of 47.4 years, with documented or suspected ischemic heart disease (ICD) [ Paul A McAuley, Enrique G Artero, Xuemei Sui et al. The obesity paradox, cardiorespiratory fitness, and coronary heart disease The obesity paradox, cardiorespiratory fitness, and coronary heart disease/ Mayo Clin Proc 2012 May;87(5):443-51]. [Carl J Lavie, Alban De Schutter, Parham Parto et. al. Obesity and Prevalence of Cardiovascular Diseases and Prognosis-The Obesity Paradox Updated // Prog Cardiovasc Dis Mar-Apr 2016;58(5):537-47.], taking into account the age, year of survey (1977-2002) and multiple baseline risk factors in men with different physical training. The study revealed a higher risk of death from all causes in a group of men with poor physical fitness, and this risk was not related to the degree of obesity or normal body weight. There were no reliable differences in the risk factors for cardiovascular disease and mortality among men with high physical fitness, taking into account BMI, waist circumference and body fat percentage, that is, to assess obesity, as a risk factor for mortality in men with СHD, should be taken into account the physical shape of patients, since even people with obesity have a lower risk of death from all causes when they perform physical activity [Vaughn W Barry , Meghan Baruth , Michael W Beets et. al. Fitness vs. fatness on all-cause mortality: a meta-analysis //Prog Cardiovasc Dis Jan-Feb 2014;56(4):382-90.].
The relationship between obesity and heart failure is currently being studied [ Carbone S, Lavie CJ, Arena R Obesity and Heart Failure: Focus on the Obesity Paradox . //Mayo Clin Proc. 2017 Feb;92(2):266-279]. The obesity paradox was found in a significant number of patients with verified heart failure, when patients have excess body mass and obesity, but a better short-term prognosis is determined than in people with reduced body weight [ Carl J Lavie , Abhishek Sharma, Martin A Alpert, et al. Ventura Update on Obesity and Obesity Paradox in Heart Failure //ProgCardiovasc].
An extensive examination of 6,142 patients with acute decompensated heart failure was conducted, who were included in 12 prospective observational cohorts and lived on four continents [Ravi Shah , Etienne Gayat , James L Januzzi ,et al. GREAT (Global Research on Acute Conditions Team) Network Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox . J Am Coll Cardiol. 2014 Mar 4;63(8):778-85;
Paul J Chase , Paul G Davis , Daniel R Bensimhon The obesity paradox in chronic heart failure: what does it mean? Curr Heart Fail Rep. 2014 Mar;11(1):111-7. ;
Carl J Lavie , Martin A Alpert , Ross Arena et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure //JACC Heart Fail. 2013 Apr;1(2):93-102. ].It was noted that people over the age of 75 who were obese had an inverse correlation between BMI and mortality, but it was typical for people who did not suffer from diabetes and had an ejection fraction <50%. People with a low BMI had a high risk of death and this was related to age and severity of the clinical condition. The effect of BMI on the survival of men and women with progressive systolic heart failure has been studied [Amanda R Vest , Yuping Wu , Rory Hachamovitch et al. The Heart Failure Overweight/Obesity Survival Paradox: The Missing Sex Link // JACC Heart Fail. 2015 Nov;3(11):917-26]: in 1995 – 2011, 3811 patients with a left ventricular ejection fraction <40% were examined. Overweight women (25.0-29.9 kg/m²) had the lowest mortality rate in the cohort. Overweight and obese men had a higher mortality rate than men of normal weight. The largest multicenter study on atrial fibrillation [Follow-up Investigation of Rhythm Management(AFFIRM)] involved 4060 patients [Apurva O, Badheka, Ankit Rathod, Mohammad A. et al. Influence of obesity on outcomes in atrial fibrillation: yet another obesity paradox // Am J Med, 2010 Jul;123(7):646-51.] For three years, the effect of obesity on the outcomes of atrial fibrillation was studied. The patients were structured according to their rhythm and heart rate. 3 groups of patients were studied: those with normal body weight (BMI=18.5-25 kg/m²), overweight (BMI=25-30 kg/m²) and obesity (BMI >>30 kg/m²). More than 3/4 of all patients were overweight or obese. It was noted that overweight and obese people had lower cardiovascular mortality compared with patients from the normal body weight group. Thus, patients with obesity and atrial fibrillation had better long-term outcomes than patients without obesity. The effect of obesity, overweight, and blood adipokine values on the severity of postinfarction remodeling with myocardial infarction and Q wave was determined in 49 men (average age = 57.06+1.21 years) who were urgently admitted with acute myocardial infarction (AMI) and ST segment elevation [Lebedev P.A., Verbova A.F., Mateesku C.A. and Soavt. Obesity paradox and post-infarction remodeling in patients with Q myocardial infarction // CARDIOLOGY: NEWS, OPINIONS, LEARNING, 2018 : 3 (18): 74-82]. It was noted that with men having AMI and tooth Q, overweight and obesity had protective properties. Depending on the BMI, the risk of death was studied in patients in intensive care units. 3902 patients admitted to intensive care units (Piedmont region, Italy) from 3 April to 29 September 2006 [Yasser Sakr ,Cristina Elia,Luciana Mascia et al. Being overweight or obese is associated with decreased mortality in critically ill patients: a retrospective analysis of a large regional Italian multicenter cohort \\ J Crit Care, 2012 Dec;27(6):714-21.] Patients in intensive care units who were overweight and obese had a reduced risk of death, in contrast to the group of people with underweight or morbidly obese, who had an increased risk of death.
Obesity was compared in patients of older age groups with overweight, obesity and stroke. Higher survival rates were observed in patients after stroke compared to patients with normal body weight [Ralf Baumgartner et.al. Obesity Paradox and Stroke .Praxis (Bern 1994). 2016 Jul 6;105(14):835-41.]. A Dutch study (366 patients) examined the relationship between BMI and disease outcome in patients with acute ischemic stroke who received endovascular treatment [ France Anne Victoire Pirson H Hinsenveld ,Julie Staals . et al. Effect of Body Mass Index on Outcome after Endovascular Treatment in Acute Ischemic Stroke Patients: A Post Hoc Analysis of the MR CLEAN Trial //Cerebrovasc Dis. 2019;48(3-6):200-206.]. A shift towards a better outcome of this clinical condition was found in the group of patients with a higher BMI, while mortality rates were inversely related to BMI, and a higher BMI was associated with a lower risk of stroke progression.
Additional analysis did not reveal a relationship between BMI and the effect of endovascular treatment on functional outcome, mortality, and other indicators. 23,652 patients (American College of Surgeons 2005 – 2009) were examined to determine the relationship between BMI and 30-day outcomes in patients after isolated carotid endarterectomy [ Rubie Sue Jackson ,James H Black 3rd,Ying Wei Lum, et al. Class I obesity is paradoxically associated with decreased risk of postoperative stroke after carotid endarterectomy \\ J Vasc Surg. 2012 May;55(5):1306-12. ]. The result of this study was the statement that isolated carotid endarterectomy in patients with: obesity of the first degree reduced the risk of stroke, determined the tendency to reduce the risk of mortality; obesity of the second degree was associated with the risk of cardiovascular complications compared to the group of people with normal body weight.
The peculiarities of surgical intervention in obese patients were studied. A prospective multicenter cohort study was conducted in 118 707 patients who underwent general surgery [ John T Mullen , Donald W Moorman,Daniel L Davenport The obesity paradox: body mass index and outcomes in patients undergoing nonbariatric general surgery // Ann Surg. 2009 Jul;250(1):166-72]. The relationship between BMI and 30-day mortality was studied after adjusting for all significant perioperative risk factors of death. The risk of death in such patients, taking into account BMI, had a U-shaped relationship: the highest mortality rates were in people with underweight and morbidly obese; the lowest mortality rates were in people with overweight and moderate obesity. The progressive number of complications increased with increasing BMI and was due to an increase in the frequency of wound infection.
Samples of medical histories (2016) of 248,288 patients with peripheral artery diseases were analyzed [DipeshLudhwani ,Joyce Wu Obesity Paradox in Peripheral Arterial Disease: Results of a Propensity Match Analysis from the National Inpatient Sample // Cureus. . 2019 May 21;11(5):e4704.]. It was found that people with peripheral artery disease and associated obesity had a lower chance of being amputated, less need for surgery, less hospital mortality, better short-term prognosis, but there was a high probability of acute kidney damage. 1,180 residents of Olmstead County (Minnesota) have identified a link between the BMI and post-operative intra-hospital non-cardiac complications following an urgent hip fracture reposition. People who underwent hip fracture surgery (1988-2002) were examined [ John A Batsis Jeanne M Huddleston, L Joseph Melton et al. Body mass index (BMI) and risk of noncardiacpostoperative medical complications in elderly hip fracture patients: a population-based study // J Hosp Med. 2009 Oct;4(8):E1-9. ].BMI was classified as underweight with a BMI <18.5 kg/m2, normal- with a BMI of 18.5-24.9 kg/m2, overweight – with a BMI of 25.0-29.9 kg/m2, obese – a BMI greater than or equal to 30 kg/m2. People with insufficient body weight had higher rates of hospital mortality than patients with a normal BMI (9.3 vs. 4.4%). BMI does not have a significant effect on post-operative non-cardiac complications in patients with hip fracture, therefore there is no concern that patients with this pathology and obesity, and with insufficient weight may be exposed to a higher risk of post-operative complications in the hospital. In 2011-2014, they examined adults (American College of Surgeons), who had received planned hip treatment (n =63 148 ) and urgent hip surgery (n = 29 047) [ Joyce C Zhang , John Matelski,Rajiv Gandhi, et al. Patient Selection Explain the Obesity Paradox in Orthopaedic Hip Surgery? An Analysis of the ACS-NSQIP Registry //Clin Orthop Relat Res. 2018 May;476(5):964-973.]. The groups were structured by BMI according to the usual classification. It was noted that in the obese group who underwent routine surgery, 30-day mortality was lower than in patients with normal BMI. In the morbidly obese group who underwent emergency surgery, there were no differences in the rates of 30-day mortality compared with patients with a normal BMI. The morbidly obese group had a high risk of developing wound complications with planned and urgent treatment. In the two follow-up groups (planned and emergency interventions), underweight patients died most often within 30 days. The relationship of BMI with the frequency of early postoperative complications in patients (802 medical records) who underwent total endoprosthesis of the hip joint with inpatient stay 5 days or more was studied [ Naum Shaparin ,James Widyn ,Singh Nair et al. Does the obesity paradox apply to early postoperative complications after hip surgery? A retrospective chart review J Clin Anesth. 2016 Aug;32:84-9.]. It was revealed that the overall complication rate corresponded to a U-shaped distribution : the highest incidence (23.5%) was in the underweight group; the second most common incidence is in the group with normal body weight (17.3%). The incidence decreased to a minimum in the group with overweight (8.0%) and type I obesity (10.0%), but the incidence increased again in the groups of patients with type II (14.3%) and type III (16.7%) obesity. The diagnosis of a hip fracture, normal body weight, and grade III obesity were the factors associated with the highest incidence of early complications following total hip replacement surgery. The effect of obesity in patients with severe sepsis has been studied [ Timothy Glen Gaulton , C Marshall MacNabb, et al. A retrospective cohort study examining the association between body mass index and mortality in severe sepsis // Intern Emerg Med. 2015 Jun;10(4):471-9.]: A retrospective analysis of 1,190 records of patients with severe sepsis was carried out (2005 – 2007), the average age of patients was 57 years: obese and morbidly obese patients were younger, less seriously ill and more likely to have soft tissue infections; patients with morbid obesity had a lower 28-day mortality; obese and morbidly obese patients had a lower risk of death compared to patients who had a normal body weight. There were no statistically significant differences in the adjusted 28-day mortality for underweight patients compared to people with normal body weight.
The problem of cancer development in obese patients is of scientific interest Surveyed 133,273 people, including 106,630 (80.01%) men and 26,643 (19.99%) women (North China) [Lanwei Guo ,Ni Li , Gang Wang et al. Body mass index and cancer incidence:a prospective cohort study in northern China Zhonghua Liu Xing Bing Xue ZaZhi. 2014 Mar;35(3):231-6.]. In almost 5 years there have been 1,647 cases of cancer, including 1,348 – men and 299 – women. Men with insufficient body mass had an increased risk of developing stomach cancer, liver cancer. Men with overweight or obesity had an increased risk of developing colon cancer, but the incidence of lung cancer decreased : excess body mass compared to normal body mass and obesity compared to normal body mass. Only men with excess body weight had reduced the incidence of bladder cancer. Further analysis of lung cancer cases stratified by smoking showed that overweight was associated with a reduced risk of lung cancer in both non-smokers and smokers. In women, obesity increased the risk of ovarian cancer and increased the risk of breast cancer in postmenopause, but not in premenopause.14 studies were conducted in the USA [ Arjun Gupta ,Kaustav Majumder ,Nivedita Arora et al. Premorbid body mass index and mortality in patients with lung cancer: A systematic review and meta-analysis //Lung Cancer. 2016 Dec;102:49-59.], which included 3,008,137 people who did not have malignant diseases at the time of follow-up. Subsequently, lung cancer was reported in 592 deaths. The relationship between premorbid obesity (BMI≥30 kg/m2) and mortality due to lung cancer was studied: relatively low mortality from lung cancer was reported in overweight and obese patients compared with patients with normal body weight in BMI. This association was determined by gender differences, smoking habits, and geographic region of residence. In China, 48,799 non-smoking men were observed for 4.5 years, while 198 cases of lung cancer were reported
[ S H Xie , Г Ванг , Л Ш Го , et al. Association between body mass index and risk of lung cancer in non-smoking males: a prospective cohort study // Article in Chinese. 2016 Sep 10;37 (9):1213-1219.]. In non-smoking men, lung cancer baseline BMI was negatively associated with lung cancer risk and this risk decreased by 22% for every extra +5 kg/m2 BMI. The inverse relationship between BMI and lung cancer risk was significant among non–smoking men aged ≥50 years and among those who exercised less than 4 times a week, who never abused alcohol, and for every extra + 5 kg/m2 BMI, the risk of lung cancer decreased by 26%. A similar result was obtained after excluding cancer patients who were diagnosed with lung cancer within 1 year of the start of follow-up.
The problem of significant weight loss in a sick person is of scientific interest. 1,000 patients were followed for 3 years, taking into account the decrease in body weight in patients with a BMI >30 and heart failure
[ Elisabet Zamora , Carles Díez-López , Josep Lupón et al. Weight Loss in Obese Patients With Heart Failure //J Am Heart Assoc. 2016 Mar 24;5(3):e002468.]. In a multifactorial analysis adjusted for age, gender, body mass index, functional class, left ventricular ejection fraction, duration of heart failure, ischemic etiology, diabetes mellitus and treatment, it was noted that a significant decrease in body weight was associated with higher mortality in such patients; mortality was significantly higher in patients with significant weight loss (27.6% versus 15.3%). Overall conclusion: a decrease in body weight ≥5% was associated with high long-term mortality, especially in patients with obesity and heart failure. 777 outpatient patients (average age 53.2 ± 9.2 years) with heart failure (NYNA class III or IV) and significant weight loss were observed [ Jacek T Niedziela , Bartosz Hudzik , Krzysztof Strojek et al. Weight loss in heart failure is associated with increased mortality only in non-obese patients without diabetes //J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1307-1315.], which was defined as a decrease of 7.5% over a period of 6 months. Significant weight loss was an independent predictor of mortality in patients without obesity and without diabetes mellitus, however, the presence of diabetes mellitus or obesity in other patients without diabetes mellitus negated the adverse effect of significant weight loss on long-term outcomes.
There is information in the scientific literature about the existence of many phenotypes of obesity, which have different risks of developing a number of somatic diseases, according to the physical characteristics of a person and his lifestyle. The need for a new approach to the concept of “obesity” is emphasized, which should take into account the heterogeneity of obesity [Alessandra Vecchié , Franco Dallegri , Federico Carbone et.аl.Obesity phenotypes and their paradoxical association with cardiovascular diseases // Eur J Intern Med. 2018 Feb; 48: 6-17.] . The published data on the “obesity paradox” is so unusual that even researchers on this topic, when publishing their data, speak very cautiously in their final assessment; other scientists, trying to criticize the scientific results obtained by their colleagues, talk about the imperfection of BMI as a classifier of obesity, randomization bias …, but more and more new research conducted on thousands and even millions of patients, they only clarify the data obtained earlier. Apparently, the time has come when, instead of the “obesity paradox”, it is necessary to introduce the term “leanness paradox”, in which overweight adults (according to BMI) have a more unfavorable prognosis for the development of a number of diseases and clinical conditions than obese people [ Andrew Elagizi, Sergey Kachur, Carl J Lavie et al. An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases //Prog Cardiovasc Dis Jul-Aug 2018;61(2):142-150.].
