The Obesity Paradox Explained: Is It Still Valid?

It is generally understood, among medical professionals as well as the public, that obesity is associated with other diseases. That is to say, broadly, obesity equals poorer health. In particular, we know that obesity contributes to heart disease. However, the obesity paradox highlights how complicated this relationship is.

The obesity paradox suggests that individuals with overweight and obesity may have lower mortality rates from certain diseases. Recent research both explains and challenges the paradox.

What is the Obesity Paradox?

The obesity paradox is a concept applied to people with obesity as well as cardiovascular disease. While obesity is a major risk factor for developing these diseases, patients with obesity have better outcomes when they experience myocardial infarction, strokes, or certain types of heart failure. A person without obesity is more likely to die from these experiences.

Carl "Chip" Lavie, MD, let the way in identifying the obesity paradox more than 20 years ago. Dr. Lavie is a Fellow with the American College of Cardiology and Medical Director of the Cardiac Rehabilitation and Prevention Program at the John Oschner Heart and Vascular Institute. He discussed it with Dr. Nicholas Pennings, Executive Director for Clinical Education for the OMA, on an episode of our podcast, Obesity: A Disease.

Dr. Lavie reported that his team discovered the obesity paradox by accident. "We discovered it in our own database. We were doing a study of cardiopulmonary stress testing," he recalls. When reviewing the data from that study, they noticed something so unexpected they wondered at first if it was an error. "The people who died with advanced heart failure had lower BMI and a lower percent body fat than the survivors."

Limitations of Studies Used to Support the Obesity Paradox

Numerous studies have reported on the obesity paradox. The claims sometimes extend to greater survival rates for people with obesity with other diseases, such as cancer, diabetes, and renal disease.

Still, other studies report an inverse relationship between obesity to mortality in lung cancer and hip fracture. However, certain limitations to these conclusions have been proposed.

BMI as an Imperfect Metric of Obesity

The paradox may be due, in part, to the shortcomings of BMI as a metric of obesity. A study published in the European Heart Journal relied, instead, on the waist-to-height ratio of cardiac patients.

The problem, says the study's lead author, is that BMI is a weak indicator of how much fatty tissue a person has. The study analyzed data from 1,832 women and 6,567 men with heart failure and reduced ejection fraction.

They found lower death rates for people with BMIs of 25 or more, but the paradox disappeared when they adjusted the results to account for other factors that can affect outcomes. In the end, the study concluded that greater adiposity was clearly associated with a higher risk of hospitalization.

Reverse Causation

Weight loss/lower weight may be attributed to disease progression, which is why those people have worse health outcomes. It doesn't mean, however, that obesity is somehow protective.

A possible explanation is reverse causation, where an illness actually causes weight loss. This situation can also be described as confounding by pre-existing disease.

Similarly, a person may lose weight due to a secondary, related condition, such as depression. Dr. Lavie reminds us that literature doesn't differentiate between purposeful and unintentional weight loss. He says, "There are very, very few studies of purposeful weight loss and, say, coronary heart disease, heart failure, atrial fibrillation, etc."

He continues, "We do have some recent data that would suggest that patients who had heart failure and then had bariatric surgery and lost a lot of weight, they had less hospitalization and deterioration of the heart disease than the patients who remained at a high weight."

Collider Stratification Bias

Collider stratification bias can create false conclusions about the factors causing and caused by obesity. This bias occurs when an exposure and outcome each influence a third variable.

An example would be when mortality from smoking-related diseases is quantified in people with obesity versus people without obesity. Obesity and smoking are both risk factors, but smoking is a stronger risk factor for mortality. It's not that obesity is protective; it's that smoking is a more dangerous risk factor.

Other Explanations

On the podcast, Dr. Lavie offered another possible explanation for the obesity paradox. For example, he pointed out that while obesity can cause heart disease, lean patients might get heart disease for different reasons, such as genetics.

This would explain why they may have lower triglycerides, lower blood sugar, lower blood pressure, less inflammation, and less metabolic syndrome, yet still experience a higher death rate following a cardiac event.

Findings that Contradict the Obesity Paradox

Some recent research into cardiovascular disease has begun to explain and contradict the primary claims of the obesity paradox.

The European Heart Journal study described above provides one example of research that contradicts, or at least calls into question, the obesity paradox.

A 2006 study in the American Journal of Cardiology stated, "Closer examination of these studies raises important questions on the validity of the paradox."

It points out that some possible flaws in the previous studies, such as inaccurate diagnosis of heart failure in patients with obesity. The authors suggest that perhaps a "U-shaped" outcome curve exists for patients with heart failure.

This would indicate that mortality is lower in patients with healthy weight, overweight, or a lower classification of obesity (according to BMI) but higher again for patients with more severe obesity.

A study published in Nature in 2017 offers explanations for the obesity paradox, such as "misclassification bias caused by using BMI as a measure of obesity, reverse causation, or a form of selection bias called collider stratification bias."

Why Do Some Patients with Obesity Have Paradoxically Better Outcomes for Certain Diseases?

Debunking the obesity paradox requires seeking explanations for why patients with obesity occasionally experience better health outcomes than their lower-weight counterparts.

Protective Versus Pathogenic Fat Depots

Another factor in obesity is the behavior of different types of fat depots, which can be either protective or pathogenic.

For example, peripheral subcutaneous adipose tissue (SAT) stores energy, provides physical padding and insulation, and can limit lipotoxic overflow to other fat depots and organs. On the other hand, it can give rise to fat mass disease.

In addition, during positive caloric balance, adipocyte proliferation and differentiation may be insufficient, leading to excessive adipocyte hypertrophy, endocrinopathies, and immunopathies.

Visceral Adipose Tissue (VAT) can also play both roles.

The Obesity Paradox and Cardiovascular Risk Factors

When it comes to cardiovascular disease in particular, the paradox may depend on risk factors. One key factor is physical fitness. We know that individuals with modest overweight may have improved prognoses if they are physically fit.

Another is cigarette smoking, which can decrease body weight but is associated with increased mortality, especially if it causes cancer or chronic lung disease. It also increases sympathetic nervous system activity, lipolysis, and insulin resistance.

Third, patients with obesity may have greater metabolic reserves. These reserves may provide an advantage during catabolic states like congestive cardiomyopathy or myocardial infarction.

Learn more about the obesity paradox in the Obesity Algorithm®.

Therapeutic Implications of the Obesity Paradox

Greater understanding of the obesity paradox can inform treatment and disease management for people with a wide range of conditions who meet the definition for obesity.

Form the start, it is important to consider factors beyond BMI.

In addition, healthcare providers should consider the factors surrounding an individual's weight gain or loss, including whether it is caused by a secondary disease or condition and whether it is purposeful or not. One should also take care to examine any potential biases that may cloud decision-making.

Certain tenets of good overall health remain true, whomever is being treated.

Dr. Lavie spoke, for example, about how exercise is beneficial for patients with or without obesity in managing cardiovascular health.

He says, "Fitness, or physical activity, markedly alters the relationship between adiposity and subsequent outcomes in patients with cardiovascular disease." Increasing physical activity improves outcomes even if a person does not lose weight.

To learn more, watch our webinar, The Obesity Paradox in Cardiovascular Disease.