Obesity paradox

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The obesity paradox is the finding in some studies of a lower mortality rate for overweight or obese people within certain subpopulations. [1] [2] [3] The paradox has been observed in people with cardiovascular disease and cancer. Explanations for the paradox range from excess weight being protective to the statistical association being caused by methodological flaws such as confounding, detection bias, reverse causality, or selection bias. [1]

Contents

Description

The terminology "reverse epidemiology" was first proposed by Kamyar Kalantar-Zadeh in the journal Kidney International in 2003 [4] and in the Journal of the American College of Cardiology in 2004. [5] It is[ clarification needed ] a contradiction to prevailing medical concepts of prevention of atherosclerosis and cardiovascular disease; however, active prophylactic treatment of heart disease in otherwise healthy, asymptomatic people has been and is controversial in the medical community for several years. [6] [7] [ clarification needed ]

The mechanism responsible for this reversed association is unknown, but it has been theorized that, in chronic kidney disease patients, "The common occurrence of persistent inflammation and protein energy wasting in advanced CKD [chronic kidney disease] seems to a large extent to account for this paradoxical association between traditional risk factors and CV [cardiovascular] outcomes in this patient population." [8] Other research has proposed that the paradox also may be explained by adipose tissue storing lipophilic chemicals that would otherwise be toxic to the body. [9]

The obesity paradox (excluding the cholesterol paradox) was first described in 1999 in overweight and obese people undergoing hemodialysis, [10] and has subsequently been found in those with heart failure, [5] [11] [12] myocardial infarction, [13] acute coronary syndrome, [14] chronic obstructive pulmonary disease (COPD), [15] pulmonary embolisms, [16] and in older nursing home residents. [17]

While obese people have twice the risk of developing heart failure compared to individuals with a normal BMI, [18] once a person experiences heart failure, those with a BMI between 30.0 and 34.9 had lower mortality than those with a normal BMI. This has been attributed to the fact that people often lose weight when they have severe and chronic illness (a syndrome called cachexia). [19] Similar findings have been made in other types of heart disease. Among people with heart disease, those with class I obesity do not have greater rates of further heart problems than people of normal weight. In people with greater degrees of obesity, however, risk of further events is increased. [20] [21] Even after cardiac bypass surgery, no increase in mortality is seen in the overweight and obese. [22] [23] One study found that the improved survival could be explained by the more aggressive treatment obese people receive after a cardiac event. [24] Another found that if one takes into account COPD in those with peripheral artery disease, the benefit of obesity no longer exists. [25] The obesity paradox is also relevant in discussion of weight loss as a preventative health measure – weight-cycling (a repeated pattern of losing and then regaining weight) is more common in obese people, and has health effects commonly assumed to be caused by obesity, such as hypertension, insulin resistance, and cardiovascular diseases. [26]

Criticisms

Methodology

The obesity paradox has been criticized on the grounds of being an artifact arising from biases in observational studies. Strong confounding by smoking has been noted by several researchers, [27] [28] although others have suggested that smoking does not account for the observed patterns. [29] [30] Since smokers, who are subject to higher mortality rates, also tend to be leaner, inadequate adjustment for smoking would lead to underestimations of the risk ratios associated with the overweight and obese categories of BMI among non-smokers. In an analysis of 1.46 million individuals, restriction to never-smoking participants greatly reduced the mortality estimates in the underweight group, as well as strengthening the estimates in the overweight and obese groups. [31] This study concluded that, for non-Hispanic white adults who have never smoked, the BMI range of 20.0 to 24.9 was associated with the lowest mortality rates. [31] A similar 2016 study found that, of the BMI ranges studied (which ranged from 18.5 to >30), the "normal" 18.5–22.4 BMI range combined with healthy eating, high levels of physical activity, not smoking, and no more than moderate alcohol consumption was associated with the lowest risk of premature death. [32]

Another concern is reverse causation due to illness-induced weight loss. That is, it may not be low BMI that is causing death (and thereby making obesity seem protective) but rather imminent death causing low BMI. Indeed, unintentional weight loss is an extremely significant predictor of mortality. [33] Terminally ill individuals often undergo weight loss before death, and classifying those individuals as lean greatly inflates the mortality rate in the normal and underweight categories of BMI, while lowering the risk in the higher BMI categories. Studies that employ strategies to reduce reverse causation such as excluding sick individuals at baseline and introducing time lag to exclude deaths at the beginning of follow-up have yielded estimates of increased risk for body mass indices above 25 kg/m2. [34]

The obesity paradox may therefore result from people becoming lean due to smoking, sedentary lifestyles, and unhealthy diets – all factors which also negatively impact health. [32]

Critics of the paradox have also argued that studies supporting its existence almost always use BMI as the only measure of obesity.[ citation needed ] However, because BMI is an imperfect method of measuring obesity, critics argue that studies using other measures of obesity in addition to BMI, such as waist circumference and waist to hip ratio, render the existence of the paradox questionable. [35]

One probable methodological explanation for the obesity paradox in regards to cardiovascular disease is collider stratification bias, which commonly emerges when one restricts or stratifies on a factor (the "collider") that is caused by both the exposure (or its descendants) of an unmeasured variable and the outcome (or its ancestors / risk factors). In the example of the obesity-cardiovascular disease relationship, the obesity is the collider, the outcome is cardiovascular disease, and the unmeasured variables are environmental and genetic factors – given that obesity and cardiovascular disorders are often associated with each other, medical professionals may be reluctant to consider both other causes of cardiovascular disease or other causes of protection against said diseases. [36] [37]

A study from 2018 found that the reason why overweight or obese patients supposedly live longer with cardiovascular disease than people of normal weight is simply because overweight / obese patients get cardiovascular disease at an earlier age, meaning while they survive more years with it, non-obese patients don't get cardiovascular disease at all up until later in life. In fact, the obese have shorter lifespans because they get cardiovascular disease at an early age and have to live a longer proportion of their life with it. This also shows a misunderstanding regarding the paradox: While survival rate once sick is indeed higher for those with obesity than for those few non-obese that have cardiovascular disease, people without obesity usually do not get cardiovascular disease in the first place. [38] [39]

Ties to Coca-Cola

It has also been noted that Coca-Cola has promoted the hypothesis and funded researchers who agree with the hypothesis, which has raised questions about what research the company supports and why. [40]

Weight relativism

Dixon et al. have proposed that a paradox does not actually exist, as people can be healthy at a range of sizes. As one study puts it, "There is no 'obesity paradox' to explain, if we accept the premise that varying ideal weight ranges apply to individuals over different stages of the life span, accordingly allowing us to abandon the rigid biologically implausible concept of a single 'ideal weight' (for height) or weight range." [41]

See also

Related Research Articles

<span class="mw-page-title-main">Body mass index</span> Relative weight based on mass and height

Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms (kg) and height in metres (m).

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart muscle due to plaque buildup in the hearts arteries

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.

<span class="mw-page-title-main">Obesity</span> Medical condition in which excess body fat harms health

Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it negatively affects health. People are classified as obese when their body mass index (BMI)—a person's weight divided by the square of the person's height—is over 30 kg/m2; the range 25–30 kg/m2 is defined as overweight. Some East Asian countries use lower values to calculate obesity. Obesity is a major cause of disability and is correlated with various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis.

<span class="mw-page-title-main">Mediterranean diet</span> Diet inspired by the Mediterranean region

The Mediterranean diet is a diet inspired by the eating habits and traditional food typical of southern Spain, southern Italy, and Crete, and formulated in the early 1960s. It is distinct from Mediterranean cuisine, which covers the actual cuisines of the Mediterranean countries. While inspired by a specific time and place, the "Mediterranean diet" was later refined based on the results of multiple scientific studies.

<span class="mw-page-title-main">Cardiovascular disease</span> Class of diseases that involve the heart or blood vessels

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases, stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

<span class="mw-page-title-main">Chronic kidney disease</span> Medical condition

Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure, bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization.

Bariatrics is the branch of medicine that deals with the causes, prevention, and treatment of obesity.

Malnutrition–inflammation complex (syndrome) (MICS), also known as malnutrition–inflammation–cachexia syndrome, is a common condition in chronic disease states such as chronic kidney disease and chronic heart failure.

<span class="mw-page-title-main">Overweight</span> Above a weight considered healthy

Being overweight or fat is having more body fat than is optimally healthy. Being overweight is especially common where food supplies are plentiful and lifestyles are sedentary.

<span class="mw-page-title-main">Preventable causes of death</span> Causes of death that could have been avoided

Preventable causes of death are causes of death related to risk factors which could have been avoided. The World Health Organization has traditionally classified death according to the primary type of disease or injury. However, causes of death may also be classified in terms of preventable risk factors—such as smoking, unhealthy diet, sexual behavior, and reckless driving—which contribute to a number of different diseases. Such risk factors are usually not recorded directly on death certificates, although they are acknowledged in medical reports.

<span class="mw-page-title-main">Obesity-associated morbidity</span> Medical condition

Obesity is a risk factor for many chronic physical and mental illnesses.

<span class="mw-page-title-main">Classification of obesity</span> Overview of the classification of the condition of obesity

Obesity classification is a ranking of obesity, the medical condition in which excess body fat has accumulated to the extent that it has an adverse effect on health. The World Health Organization (WHO) classifies obesity by body mass index (BMI). BMI is further evaluated in terms of fat distribution via the waist–hip ratio and total cardiovascular risk factors. In children, a healthy weight varies with age and sex, and obesity determination is in relation to a historical normal group.

Management of obesity can include lifestyle changes, medications, or surgery. Although many studies have sought effective interventions, there is currently no evidence-based, well-defined, and efficient intervention to prevent obesity.

A person's waist-to-height ratio (WHtR), occasionally written WtHR or called waist-to-stature ratio (WSR), is defined as their waist circumference divided by their height, both measured in the same units. It is used as a predictor of obesity-related cardiovascular disease. The WHtR is a measure of the distribution of body fat. Higher values of WHtR indicate higher risk of obesity-related cardiovascular diseases; it is correlated with abdominal obesity.

Kamyar Kalantar-Zadeh is an Iranian-American physician doing research in nephrology, kidney dialysis, nutrition, and epidemiology. He is best known as a specialist in kidney disease nutrition and chronic kidney disease and for his hypothesis about the longevity of individuals with chronic disease states, also known as reverse epidemiology including obesity paradox. According to this hypothesis, obesity or hypercholesterolemia may counterintuitively be protective and associated with greater survival in certain groups of people, such as elderly individuals, dialysis patients, or those with chronic disease states and wasting syndrome (cachexia), whereas normal to low body mass index or normal values of serum cholesterol may be detrimental and associated with worse mortality. Kalantar-Zadeh is also known for his expertise in kidney dialysis therapy, including incremental dialysis, as well as renal nutrition. He is the brother of Kourosh Kalantar-zadeh, who is an Australian scientist involved in research in the fields of materials sciences, nanotechnology, and transducers.

<span class="mw-page-title-main">Frank Hu</span> Nutrition researcher

Frank B. Hu is a Chinese American nutrition and diabetes researcher. He is Chair of the Department of Nutrition and the Fredrick J. Stare Professor of Nutrition and Epidemiology at the Harvard T.H. Chan School of Public Health, and Professor of Medicine at the Harvard Medical School.

Metabolically healthy obesity or metabolically-healthy obesity (MHO) is a disputed medical condition characterized by obesity which does not produce metabolic complications.

Carl J. "Chip" Lavie is an American cardiologist. He is the medical director of cardiac rehabilitation and preventive cardiology at the John Ochsner Heart and Vascular Institute in New Orleans, Louisiana. He is also a professor at the Ochsner Clinical School of the University of Queensland in Brisbane, Australia, and the editor-in-chief of the medical journal Progress in Cardiovascular Diseases.

The association between obesity, as defined by a body mass index of 30 or higher, and risk of a variety of types of cancer has received a considerable amount of attention in recent years. Obesity has been associated with an increased risk of esophageal cancer, pancreatic cancer, colorectal cancer, breast cancer, endometrial cancer, kidney cancer, thyroid cancer, liver cancer and gallbladder cancer. Obesity may also lead to increased cancer-related mortality. Obesity has also been described as the fat tissue disease version of cancer, where common features between the two diseases were suggested for the first time.

Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol, which are triglyceride-poor lipoproteins. However, remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL.

References

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  36. ↑ J., Rothman, Kenneth (2008). Modern epidemiology. Greenland, Sander, 1951–, Lash, Timothy L. (3rd edition, thoroughly revised and updated ed.). Philadelphia. ISBN   9780781755641. OCLC   169455558.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: multiple names: authors list (link)
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  40. ↑ Julia Belluz (October 20, 2015). "The obesity paradox: Why Coke is promoting a theory that being fat won't hurt your health". Vox . Retrieved December 21, 2021.
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