The 'obesity paradox': Cardiovascular mortality lowest among overweight patients

Credit: Peter Häger/Public Domain

20 july 2014--High body mass index (BMI) is associated with multiple cardiovascular diseases. However, emerging data suggest that there is an "obesity paradox," that being overweight may actually protect patients from cardiovascular mortality. Investigators have now confirmed that the risk of total mortality, cardiovascular mortality, and myocardial infarction is highest among underweight patients, while cardiovascular mortality is lowest among overweight patients, according to two reports published today in Mayo Clinic Proceedings.

Currently more than two-thirds of adult Americans are classified as overweight or obese. Because of the high prevalence of coronary heart disease (CAD), overweight and obese patients more frequently undergo revascularization procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). Obesity has been considered a risk factor for worst clinical outcomes following cardiovascular procedures like these, however, emerging data suggest that higher BMI protects against adverse outcomes in many acute and chronic disease states. This prompted experts to reexamine assumptions about body fat and explore the counterintuitive phenomenon known as the "obesity paradox."

In a landmark meta-analysis of 36 studies, Abhishek Sharma, MD, Cardiology Fellow at the State University of New York Downstate Medical Center in Brooklyn, New York, and colleagues determined that low BMI (less than 20 kg/m2) in tens of thousands of patients with coronary artery disease who underwent coronary revascularization procedures was associated with a 1.8- to 2.7-fold higher risk of myocardial infarction and all-cause and cardiovascular mortality over a mean follow up period of 1.7 years. Conversely overweight and obese patients had more favorable outcomes. Cardiovascular mortality risk was lowest among overweight patients with a high BMI (25-30 kg/m2) compared to people with a normal BMI (20-25 kg/m2). Indeed, in obese and severely obese patients with a BMI in the 30-35 and over 35 kg/m2 range, all-cause mortality was 27% and 22% lower than people with normal BMI.

Dr. Sharma observes, "At this stage we can only speculate on the reasons for this paradox. One explanation may be that overweight patients are more likely to be prescribed cardioprotective medications such as beta blockers and statins and in higher doses than the normal weight population. Further, obese and overweight patients have been found to have large coronary vessel damage, which might contribute to more favorable outcomes. This population may have a higher metabolic reserve, which might act protectively in chronic conditions like CAD. Also, there could be a difference in the pathophysiology of cardiovascular disease in over- and underweight patients. A non-modifiable genetic predisposition may also play a role in underweight patients."

He concludes, "However, this is still speculation. Further prospective studies are needed to investigate this association and explore potential underlying mechanisms."

In a second study published in the same issue, investigators examined the "obesity paradox" from another perspective by evaluating the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing BMI and decreasing mortality. They estimated BF and LMI in nearly 48,000 people with a preserved left ventricular ejection fraction of more than 50% and examined the survival advantages of obesity across strata of these body compositions.

This large observational study showed that higher lean body mass was associated with 29% lower mortality, and while higher fat mass also exhibited survival benefits, this advantage disappeared after adjustment for lean body mass, suggesting that non-fat tissue bears the primary role in conferring greater survival.

"Body composition plays a critical role in the obesity paradox," says senior investigator Carl Lavie, MD, FACC, FACP, FCCP, Medical Director of Cardiac Rehabilitation and Preventative Cardiology at the John Ochsner Heart & Vascular Institute, Ochsner Clinical School, the University of Queensland School of Medicine, New Orleans. "Whenever examining a potential protective effect of body fat, lean mass index – which likely represents larger skeletal muscle mass – should be considered. At higher BMI, body fat is associated with an increase in mortality."

Noted expert Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Department of Medicine, University of California Irvine Medical Center, Orange, CA, observes that "although the underlying mechanisms of the obesity paradox and reverse epidemiology remain unclear, the consistency of the data is remarkable, leaving little doubt that these observational data are beyond statistical constellations and bear biologic plausibility.

"The findings in these studies should not be considered as an attempt to undermine the legitimacy of the anti-obesity campaign in the best interest of public health. Nonetheless, given the preponderance and consistency of epidemiologic data, there should be little doubt that in certain populations higher BMI, which is associated with higher risk of metabolic syndrome and poor cardiovascular outcomes in the long-term, confers short-term survival and cardiovascular advantages. Metaphorically we can liken cardiovascular risk factors to a friend who is a negative influence, causing you to misbehave and be sentenced to jail, but once imprisoned the friend remains loyal and protects you against poor prison conditions and other inmates."

More information: "Relationship of Body Mass Index With Total Mortality, Cardiovascular Mortality, and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis," by Abhishek Sharma, MD; Ajay Vallakati, MD; Andrew J. Einstein, MD, PhD, FACC; Carl J. Lavie, MD, FACC, FACP, FCCP; Armin Arbab-Zadeh, MD, PhD, FACC; Francisco Lopez-Jimenez, MD, MSc, FAHA, FACC; Debabrata Mukherjee, MD, MS, FACC; and Edgar Lichstein, MD, FACC:dx.doi.org/10.1016/j.mayocp.2014.04.020

"Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox," by Alban De Schutter, MD; Carl J. Lavie, MD, FACC, FACP, FCCP; Sergey Kachur, MD; Dharmendrakumar A. Patel, MD; and Richard V. Milani, MD: dx.doi.org/10.1016/j.mayocp.2014.04.025

Provided by Elsevier

COULD BEING FAT BE GOOD FOR YOU

24 may 2009--Overweight heart attack victims should stay fat as they are more likely to live longer”, the Daily Mail reported. It said that the controversial claim that being fat can be useful for heart attack patients has come from a review published in a journal.

This news report is based on a review that looked at selected studies describing the ‘obesity paradox’. The paradox is that, in some studies, overweight people have a better survival rate after heart disease than those who are a normal weight. The review itself does not claim that staying fat is good for health, but describes a few studies that have shown trends in people who already have heart disease.

The ‘obesity paradox’ will need more systematic research. People who have had a heart attack are advised to enrol in cardiac rehabilitation programmes where they will receive a physical activity programme and advice on the ideal diet for preventing future heart problems.

Where did the story come from?

The research was carried out by Dr Carl J Lavie, Richard V Milani and Hector O Ventura from the Ochsner Medical Center in New Orleans, Louisiana. Funding for the study is not reported. The study was published in the peer-reviewed Journal of the American College of Cardiology.

What kind of scientific study was this?

In this review, doctors from a cardiac rehabilitation and exercise laboratory discuss the impact of obesity on the risk of heart disease, including heart failure (HF), coronary heart disease (CHD), sudden cardiac death and atrial fibrillation, and how it is associated with reduced overall survival. They also investigate a phenomenon they refer to as the “obesity paradox”, in which overweight and obese people have a better survival rate after heart disease than those who are normal weight or underweight.

The authors do not report the methods they used in this review, but do refer to 87 other papers on obesity, its harmful effects and the various biological mechanisms and hormones involved.

What were the results of the study?

The authors begin by discussing how obesity might have an effect on cardiovascular health. They suggest that the hormone leptin, which is produced by fat cells and controls food intake and energy metabolism, may be particularly related to heart disease. They also refer to studies that suggest that C-reactive protein, a marker of inflammation that is associated with an increased risk of major cardiovascular events, such as heart attacks, may also play a role.

The authors list the adverse effects that obesity has on blood pressure, the lipids (fats) in the blood, the metabolism of glucose, the heart muscle and the lining of the blood vessels, and how it has an association with sleep disorders, arthritis and cancer. They say that obesity has reached global epidemic proportions in both adults and children. They say that, due to the harmful effect it has on various heart disease risk factors, obesity is also strongly associated with diseases such as heart failure, coronary heart disease, sudden cardiac death and atrial fibrillation. In addition, obesity is associated with increased overall mortality.

The authors say that numerous studies have documented an “obesity paradox” in which overweight and obese people who already have heart diseases, such as high blood pressure, heart failure or heart attacks, have a better prognosis compared with non-overweight or non-obese patients. They say that high blood pressure usually leads to a thickening of the muscular walls of the heart without increases in the volume of the pumping chamber (ventricle). However, obesity is conversely associated with an increase in chamber dilation without marked increases in wall thickness.

They refer to several studies that illustrate the “obesity paradox”. One example they mention is a recent study of 22,576 patients with known heart disease and high blood pressure. The study found that, after two years, overweight and obese patients had 30% lower deaths from all causes. This was despite their blood pressure being less well controlled than the normal weight group. They also refer to similar findings from selected studies in people with heart failure and peripheral arterial disease (narrowing of the arteries in the legs). However, the authors say that the pattern was not seen in studies of people with stroke, irregular heart beats or sleep disorders, which are all conditions that increase the risk of death for the obese.

What interpretations did the researchers draw from these results?

The researchers say that “overwhelming evidence supports the importance of obesity” as a cause of and contributor to the progression of heart disease. They say that, although a paradox exists, the data still support “purposeful weight reduction in the prevention and treatment of CV diseases”.

What does the NHS Knowledge Service make of this study?

This narrative review gives the authors’ views and also gives a presentation of both sides of the debate from selected papers on the topic. The suggestion that obesity may be protective in some cases is not new, and has been highlighted previously. There are several points to note about this research:

• As a narrative review it is not clear how the referenced papers were selected and if all the research, positive and negative, has been systematically identified and evaluated. This would require a systematic review.
• Although some suggestions are made about how obesity might protect the heart, these biological mechanisms are not yet certain and more research will be needed.
• The review is mostly based on observational studies. These types of study are subject to confounding, which means that there may be other explanations for the improved survival of obese people with heart disease. For example, obese people may be preferentially referred for cardiac rehabilitation or treated more intensively because of associated risk factors such as diabetes.

As the authors confirm, more research is needed in all of these areas. They warn that, if the current obesity epidemic continues, “we may soon witness an unfortunate end to the steady increase in life expectancy”.

Links to the headlines

For heart survivors, a big waistline could be a lifeline. Daily Mail, May 19 2009

Links to the science

Lavie CJ, Milani RV, and Ventura HO. Obesity and Cardiovascular Disease. Risk Factor, Paradox, and Impact of Weight Loss. J Am Coll Cardiol, 2009; 53: 1925-1932

Further reading

Shaw KA, Gennat HC, O'Rourke P, Del Mar C. Exercise for overweight or obesity. Cochrane Database of Systematic Reviews 2006, Issue 4.

Summerbell CD, Waters E, Edmunds L, et al. Interventions for preventing obesity in children. Cochrane Database of Systematic Reviews 2005, Issue 3

Obesity may offer some protection after stenting

03 july 2008--Paradoxically, obesity may offer some protection against heart-related "events," like heart attack, in people who have a stent placed to prop open a clogged coronary artery, research shows.
In a study, researchers found that obese patients who had stents placed in diseased arteries had a lower incidence of adverse cardiac events than their normal-weight counterparts.
Larger randomized trials are needed to confirm or refute the obesity paradox seen in this and other relatively small studies of drug-eluting stents, Dr. Ahmed A. Khattab of the Segeberger Kliniken in Bad Segeberg, Germany, and colleagues note in a report in the American Journal of Cardiology.
A stent is a tiny hollow tube that is placed in the coronary arteries to maintain blood flow after the blood vessel has been dilated with angioplasty. In the past, stents were simply made out of metal and did not release any drugs. In recent years, several "drug-eluting"
stents have become available.
Khattab's team analyzed the outcomes at one year for 607 patients with coronary artery disease who were treated with stents that release the immune-suppressing drug sirolimus.
The group included 176 normal weight patients, 289 overweight patients, and 142 obese patients
At 30 days, the incidence of adverse cardiac events was 3.4 percent in the normal weight group and 3.1 percent in overweight patients, compared with just 2.8 percent in obese patients.
At one year, the combined cumulative incidence of death, heart attack, stroke, and repeat angioplasty or other "revascularization" procedure was higher in the normal weight patients (10.8 percent) and the overweight patients (11.8 percent) than in the obese patients (7.0 percent).
There was also "a clear trend" for a greater benefit from sirolimus-eluting stents compared with bare-metal stents with increasing body weight, the investigators report.
SOURCE: American Journal of Cardiology, June 2008.

Obesity paradox seen in people with heart disease

Thu Nov 15, 5:20 PM ET
The "obesity paradox" -- an unexpected decrease in illness and death with increasing body weight or BMI, which has been described in people with heart failure and in patients having angioplasty -- exists in people with high blood pressure and diseased heart arteries as well, new study findings show.
In the study, researchers found that overweight and obese adults with high blood pressure and coronary artery disease had a lower risk of heart attack, stroke or death, compared with their normal-weight counterparts.
The reasons for the apparent protective effect of increased BMI in these populations "are unclear," note Dr. Seth Uretsky from St. Luke's-Roosevelt Hospital in New York City and colleagues in the American Journal of Medicine.
They investigated the effect of overweight and obesity on heart-related outcomes in 22,576 people with treated high blood pressure and coronary artery disease who participated in a large study.
Compared to normal-weight subjects with a BMI between 20 and 25, the risk of death, heart attack, or stroke was lower in subjects who were overweight (BMI 25 to 30), and in those with class I obesity (BMI 30 to 35) and class II-III obesity (BMI 35 or greater).
"This 'obesity paradox' occurred in men and women across all age groups, even though blood pressure was better controlled in normal-weight patients," the investigators note.
In a commentary, Dr. Carl J. Lavie and colleagues of the Ochsner Medical Center, New Orleans caution that while improved outcomes appear to be consistently associated with increased BMI, "one should not conclude that weight reduction is detrimental in overweight populations."
Results of numerous studies, they point out, clearly support the benefits of "purposeful weight reduction" in obese patients with heart disease, despite the obesity paradox.
"As we continue to investigate the obesity paradox in cardiovascular disease ... we should remember the old proverb, "Only one thing is certain - that is nothing is certain," Lavie and colleagues advise.
SOURCE: American Journal of Medicine, October 2007.