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Obesity drives risk for heart disease, requires collaboration
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NASHVILLE, Tenn. — Obesity “unquestionably” increases rates of coronary disease, heart failure, stroke, atrial fibrillation and mortality, and obesity medicine specialists and cardiologists must work together to address a growing health epidemic that requires collaboration, according to a speaker here.
Even among physically fit and so-called metabolically healthy people with obesity, cardiovascular risk is greater when compared with those without excess weight, Steven E. Nissen, MD, MACC, chairman of the department of cardiovascular medicine at the Cleveland Clinic and professor of medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, said during a keynote presentation at ObesityWeek 2018.
Obesity drives several “mechanisms of harm,” Nissen said, including glucose intolerance, hypertension, inflammation, increased triglycerides and low HDL cholesterol. Additionally, abdominal adiposity, measured via waist circumference, is more closely linked to adverse outcomes vs. BMI.
“Heart disease is how obesity kills most of our patients,” Nissen said during his presentation. “It is still the leading cause of death, and we’re going to have to tackle this. We are taking care of the same patients. We need to work together and collaborate if we’re going to make progress.”
Weight loss, he said, can reduce risk factors, but only very substantial weight reduction has been associated with reduced CV risk.
“We see the consequences of obesity on a daily basis in cardiology, and this epidemic is only getting worse,” Nissen told Endocrine Today before his presentation.
How obesity drives risk
CV risk rises in part through what Nissen called CV “dysmetabolic syndrome,” a constellation of risk factors that include obesity, hypertension, dyslipidemia and insulin resistance.
Additionally, increasing BMI is associated with an increasing risk for type 2 diabetes, which further increases the risk for CVD.
“It is important that we all understand that it is abdominal obesity that seems to be the disproportionate factor here,” Nissen said. “It’s not just body weight. It’s the distribution of fat in the abdomen.”
Nissen cited a recent U.K. database analysis, published online in October in The Lancet Diabetes & Endocrinology, that highlighted a J-shaped association between BMI and overall mortality in more than 3.6 million adults. The findings, reported by Endocrine Today, suggest that for each 5-kg/m² increase in BMI, estimated HR for all-cause death was 0.81 (95% CI, 0.8-0.82) for those with BMI less than 25 kg/m², whereas the HR increased to 1.21 (95% CI, 1.2-1.22) for those with BMI of at least 25 kg/m².
The researchers observed the same J-shaped association between BMI and most specific causes of death, including cancer and CV and respiratory diseases, with lowest risk for death in the BMI range of 21 kg/m² to 25 kg/m².
Challenging the ‘o besity paradox ’
In recent years, several studies have suggested that obesity could be protective in some adults, whereas low BMI is sometimes associated with increased mortality risk.
“The idea that somehow being overweight or obese is somehow protective, the evidence for that is not very good,” Nissen told Endocrine Today. “It’s an artifact of how the studies were done.”
There are three key issues to remember when reviewing study findings that promote the idea of an obesity paradox, Nissen said. Any findings are confounded by smoking, which is associated with low body weight but high CV risk. Additionally, the time horizon needs to be long enough to see the effects of obesity, whereas some individuals with low BMI are very thin because they have other chronic diseases that result in relative cachexia.
Cardiometabolic risk is increased even in physically fit people with obesity, Nissen said, but to a lesser extent when compared with those with obesity who are sedentary.
“Encouraging physical activity, even if people don’t lose weight, may help them avoid the disease that I treat,” Nissen said during his presentation.
Weight - loss strategies
Weight loss, Nissen said, tends to reduce cardiometabolic risk factors in people with obesity, but only very substantial weight reduction has been linked to reduced CV risk.
“There are very good studies that obesity is closely linked to hypertension, but if you lose even a modest amount of weight, blood pressure goes down,” Nissen said in an interview, adding that modest weight loss is also associated with a reduction in triglyceride levels and C-reactive protein, which promotes inflammation.
Diet therapy, he said, continues to be the “holy grail” for researchers and clinicians, yet large studies demonstrate that it remains difficult for people to lose and maintain body weight over time with lifestyle management.
In the landmark Look AHEAD study, a long-term, intensive lifestyle intervention targeting weight loss in overweight and obese patients with type 2 diabetes, weight loss was modest, whereas participants did not experience a reduction in CV events, including nonfatal myocardial infarction and nonfatal stroke, Nissen said.
“All this energy, all this effort, and they only got 4 kg of weight loss over 10 years.” he said. “The trial failed not because weight loss isn’t good. It’s because they didn’t get much weight loss. This was a strategy that just didn’t work out.”
Medical therapy for weight loss, Nissen said, is not a solution for reducing CV risk. Popular weight-loss medications, such as phentermine, have not been assessed for CV safety.
Researchers conducted a CV outcome trial for the serotonin receptor agonist lorcaserin (Belviq, Eisai), mandated by the FDA, Nissen said. In that study, participants with obesity lost small amounts of weight over 40 months — about 4.2 kg over 4 years vs. placebo —with no effect on morbidity or mortality.
“It’s very hard for me to argue in favor of giving any of these drugs,” Nissen said. “We have to demand that obesity drugs have [CV] outcome trials.”
Recent studies suggest that bariatric surgery can lead to the substantial weight loss needed to reduce CV risk.
In a retrospective analysis of more than 20,000 patients published in October in JAMA Cardiology and reported by Endocrine Today, researchers found that adults with obesity and type 2 diabetes who underwent bariatric surgery were half as likely to experience macrovascular complications over 4 years, including acute MI or stroke, compared with similar patients receiving usual care.
Working together
With any weight-loss intervention, Nissen said, there will always be outliers — the person with obesity who can lose significant weight participating in an intervention and gain a substantial CV benefit, but outliers are not representative of the millions of people who struggle with excess weight.
“We have to figure out how to do lifestyle [intervention] better, we need to understand the drugs better,” Nissen said. “We have a problem that affects tens of millions of people, and we have to find a societal approach to this.”
“We share these patients,” he said. “Let’s work together on trying to make them better.” – by Regina Schaffer
Reference:
Nissen SE. Opening session keynote. Presented at: ObesityWeek 2018; Nov. 11-15, 2018; Nashville, Tenn.
For more information:
Steven E. Nissen, MD, MACC, can be reached at the Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195; email: nissens@ccf.org.
Disclosure: Nissen reports he has conducted clinical trials supported by AbbVie, Amgen, AstraZeneca, Eli Lilly, Esperion, Ethicon Endosurgery, Novartis, Orexigen, Pfizer, Resverlogix, Takeda and The Medicines Company.