Obesity Paradox in Heart Disease Challenged by New Analysis

March 07, 2018

A new analysis of data of long-term follow-up from 10 population-based cohorts challenges the so-called obesity paradox  — previous counterintuitive findings suggesting that patients with heart disease may live longer if they are overweight or obese.

"Our research differs from previous studies in that we have included a lifespan perspective — we started to follow people before they developed heart disease," lead author, Sadiya Khan, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois, told Medscape Medical News.

"We found that obese people live shorter lives, and while overweight people had similar length of life to those of a normal weight, they developed cardiovascular disease earlier than people with normal BMI."

She explained that previous studies have suggested that obesity may in some way be associated with lower mortality in cardiovascular disease (CVD), known as the obesity paradox. But these studies included patients who already had CVD at the time of the study, and this can introduce many biases, particularly the issue that obese patients may be diagnosed with heart disease earlier and so may appear to live with heart disease for a longer time.   

"Our results provide a different context by following people before the onset of cardiovascular disease, which should therefore eliminate this 'lead time bias'," Khan said. "We found that obese people develop cardiovascular disease at a younger age and so they have more years with heart disease but in the context of a shorter lifespan."

The paper was published online in JAMA Cardiology on February 28.

In the paper, the researchers state: "Taking a life course perspective, we observe that the obesity paradox…appears largely to be caused by earlier diagnosis of CVD. Study of inception cohorts of people at the time of cardiovascular diagnosis would not detect this finding, leading to unclear messaging about the true risks of being overweight."

They say this "false reassurance" is akin to the phenomenon of lead-time bias observed in other situations, such as with cancer screening.

Commenting on the paper for Medscape Medical News, Naveed Satter, MD, professor of cardiovascular and medical sciences at the University of Glasgow, United Kingdom, said that the problem with previous studies is that "not all heart disease is equal."

"You can be a thin smoker or an obese nonsmoker," Satter said. "There are many different confounders. When you take a population with any chronic condition you see a different picture which may not tell the truth. We also have to consider when the patient developed heart disease. By starting to follow people before they developed heart disease, these researchers have removed one of the biggest confounders."

Other strengths of these data are a large population, a wide age range, a long follow-up, and robust statistical methods to overcome other confounders, he added. "And when looking at this cleaner picture, we see clearly than lower BMI is better."

"Better-quality studies such as this, which have longer-term follow-up and do not include people with disease at baseline, tend to find that lowest risks for bad outcomes are in the leaner people," Satter said. "We are understanding the complexities of these studies better now and there is more evidence that lowest risks for heart disease or death are in normal weight folk, not those who are overweight or obese."

The study analyzed individual-level data from 190,672 in-person examinations across 10 large prospective cohorts with an aggregate of 3.2 million years of follow-up. All of the participants were free of CVD at baseline and had objectively measured height and weight to assess BMI.

Results showed that compared with individuals with a normal BMI (defined as a BMI of 18.5 to 24.9), lifetime risks for incident CVD were higher in people in the overweight (BMI, 25.0 to 29.9) and obese (BMI, 30.0 to 39.9) groups.

Compared with normal weight, overweight middle-aged men had a hazard ratio for incident CVD of 1.21; for overweight women, the hazard ratio was 1.32.

Obese men had a hazard ratio for CVD of 1.67, and the corresponding figure for obese women was 1.85.

The hazard ratios for the morbidly obese (BMI, 40.0) were 3.14 for men and 2.53 for women. All these results were statistically significant.   

The researchers found the strongest association between BMI categories and heart failure (HF) compared with other subtypes of CVD, with a fivefold increase in incident HF in middle-aged men with morbid obesity, which they say "has particularly important implications for focusing on weight management strategies for HF prevention."

In terms of lifespan, normal weight middle-aged men lived 1.9 years longer than obese men and 6 years longer than those who were morbidly obese. Normal-weight men had longevity similar to that of overweight men.

Normal-weight middle-aged women lived 1.4 years longer than overweight women, 3.4 years longer than obese women, and 6 years longer than morbidly obese women.

The researchers point out that "our findings suggest that earlier occurrence of CVD in those with obesity is most strongly associated with a greater proportion of life lived with CVD and shorter overall survival in adults aged 20 to 59 years at baseline."

However, they note that the association of obesity with mortality may change at older ages, which may explain why some earlier studies in older individuals showed no difference in total life expectancy in older men and women with obesity.

"Our results provide critical perspective on the cardiovascular disease burden associated with overweight, highlight unhealthy years lived with increased cardiovascular morbidity, and challenge the prevalent view that overweight is associated with greater longevity compared with normal BMI," they conclude.

The study was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute.

JAMA Cardiol. Published online February 28, 2018. Full text 

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