We're fat and getting fatter.

Unless you have secluded yourself on an island with super models, you've probably noticed obesity has ballooned to epidemic proportions in the United States, as well as much of the industrialized world.

Normal BMI tips the scales at 18.5–24.9 kg/m2 and during the past 20 years, the number of individuals with a BMI >30 kg/m2 has doubled. But wait, we're just getting started! Those weighing in with a BMI >40 kg/m2 has quadrupled and the number of Americans measuring >50 kg/m2 has quintupled. Today, 65% of Americans are classified as overweight or obese.

Considering the increasing prevalence and well-established detrimental effects of obesity, the clinical arsenal for treating it is tragically thin. Recently, Anthony N. DeMaria, MD, editor in chief of JACC, noted, "It is stunning that few medical interventions [for obesity] are available."¹ Although two new weight-loss drugs have expanded the alternatives, we don't know what role they play in patients with heart disease. Which leaves us where? Dr. DeMaria again: "It is perhaps a strong statement concerning the current state of overweight that a surgical procedure is increasingly being performed as the best therapy for morbid obesity."

Weight loss serves up a number of important CV benefits (Table). Still, even with the advent of less invasive laparoscopic techniques, cardiologists appear averse to recommending a surgical procedure for a supposedly simple issue of energy imbalance: too many calories in; too few calories expended. Vera Bittner, MD, MSPH, professor of medicine, University of Alabama Birmingham, said it's not just cardiologists who are hesitant: "I have tried to refer some patients for obesity surgery, but patients are very reluctant and so are the surgeons when somebody has a history of myocardial infarction and other CV health problems."

Indeed, some of the studies evaluating these procedures only enrolled patients without CHD and—in some cases—without other identifiable cardiac risk factors.

Nibbling Away at Weight Loss

One such paper was published in JACC by Oliver Rider, MD, and colleagues.² When the study was undertaken, obese patients were known to have higher rates of left ventricular hypertrophy (LVH), but it was not clear whether the LVH resulted solely from obesity or from related conditions, such as hypertension, diabetes, or hypercholesterolemia. That's why Dr. Rider studied the effects of substantial weight loss over 1 year in obese subjects without other risk factors for LVH.

Thirty-seven obese (BMI >30 kg/m2) and 20 normal-weight subjects underwent cardiac MRI. Thirty of the obese subjects underwent repeat imaging after 1 year of significant weight loss, achieved by diet or bariatric surgery (a median loss of 21 kg, or ~46 pounds). Obesity significantly increased LV and RV mass; LV diastolic function and aortic distensibility also were impaired. At 1 year, either diet or bariatric surgery led to comparable partial regression of cardiac hypertrophy and reversal of both diastolic dysfunction and aortic distensibility impairment. Thus, LVH can be caused solely by obesity and can regress with substantial weight loss.

What's the role of bariatric surgery at this point? Dr. Rider, University of Oxford, told CardioSource WorldNews, "I don't think the answer is clear, and there are no systematic trials looking at bariatric surgery in terms of hard outcomes in patients with heart failure or angina. Certainly the benefits are perceptible and 'metabolic surgery' to unload the failing heart is an attractive option, and patients are likely to gain benefit from a technique with proven long-term weight loss."

Dr. Rider added that this has to be weighed against the increased risk in operating on these patients plus the potential that weight loss might remove HF's "obesity paradox" survival advantage.

Current Data: Sticking a Fork in It?

At ACC.13, Amita Singh, MD, and colleagues at NYU's Langone Medical Center, presented 5-year follow-up of a single-center prospective steady, albeit in just 47 patients. They reported:

• Sustained reductions in weight, measures of abdominal adiposity, and improvement in HDL and triglycerides (TG) appeared early and persisted up to 5 years following gastric banding surgery, even in patients with relatively mild baseline lipid abnormalities.
• Despite significant weight loss, there were no demonstrable effects on LDL cholesterol, particle number, or particle size.
• The rise in HDL particle number and particle size together suggest a beneficial HDL "remodeling" process.
• There was no correlation between TG reductions and measures of weight loss, but reductions in TG levels did correlate with observed changes in lipoproteins.

Singh et al. also reported that the weight loss following laparoscopic gastric banding produces resolution of metabolic syndrome by improving multiple diagnostic criteria, and reduces use of hyperglycemic and anti-hypertensive agents. These changes persisted during 5 years following surgery. In a study of 15 systolic HF patients, Vest et al. reported a significant improvement in mean LV ejection fraction that was unrelated to BP change or time from surgery.

John Morton, MD, MPH, chief of bariatric and minimally invasive surgery at Stanford School of Medicine, reported pre-op and 12-month data prospectively collected for 1,398 consecutive surgeries, including 1,152 Roux-en-y gastric bypass (RNYGB), 132 gastric banding, and 114 sleeve gastrectomy. All bariatric procedures demonstrated considerable post-op reductions in weight and overall CV risk.

Nevertheless, RNYGB showed significantly more improvement in every studied CV risk factor. Gastric bypass also achieved the lowest average BMI at 12 months, despite patients being of higher average BMI pre-operatively.

 

Benefits of Weight Reduction on the Cardiovascular System ↓ blood volume ↓ stroke volume ↓ cardiac output ↓ pulmonary capillary wedge pressure ↓ left ventricular mass improvement of LV diastolic dysfunction improvement of LV systolic dysfunction ↓ resting heart rate ↓ QTc interval ↑ heart-rate variability Source: Paul Poirier, MD, Québec Heart and Lung Institute, Canada7, 8

This all seems right in line with a recent systematic review of 73 studies involving 19,543 subjects undergoing bariatric surgery for weight loss.³ Besides reducing a broad swath of CV risk factors, bariatric surgery also cooked up evidence of LVH regression and improved diastolic function.

Weight loss is but one course that drives the CV benefits seen. In May 2013, investigators reported that gastric bypass appears to change the hormones and amino acids produced during digestion, which could explain how the surgery eliminates symptoms of type 2 diabetes.⁴ In gastric bypass surgery, the stomach is divided into two sections, with food directed to the smaller section so people feel full after eating less food. In this study, four women undergoing gastric bypass surgery had a catheter inserted into the larger, bypassed section of her stomach. This allowed investigators to evaluate hormone activity during digestion in the smaller section.

Patients' levels of insulin and other hormones were much higher when a meal was digested in the smaller compartment compared to the larger bypassed section. Amino acid levels also were higher in the smaller part of the stomach, while levels of free fatty acids were lower. The increased levels of hormones—particularly insulin—during digestion in the smaller part of the stomach enabled patients to maintain better control of their blood glucose.

One month earlier, a Swedish team published a paper detailing how weight-loss surgery changes the levels of genes involved in burning and storing fat.⁵ "We provide evidence that in severely obese people, the levels of specific genes that control how fat is burned and stored in the body are changed to reflect poor metabolic health," said senior author Juleen Zierath, MD, a professor with the Karolinska Institute in Sweden. "After [weight-loss] surgery, the levels of these genes are restored to a healthy state, which mirrors weight loss and coincides with overall improvement in metabolism." The findings may help lead to the development of new drugs that mimic this weight-loss-associated control of gene regulation.

While cardiologists may hesitate to refer patients, new guidelines are expanding the population considered candidates for weight-loss surgery.⁶ The American Society for Metabolic and Bariatric Surgery, the American Association of Clinical Endocrinologists, and The Obesity Society now recommend mildly-to-moderately obese people with diabetes or metabolic syndrome be considered for weight-loss surgery. Under the new rules, eligible patients would have a BMI of 30 to 34.9. The guidelines do note that we lack enough current evidence to recommend weight-loss surgery for blood sugar control alone, fat lowering alone, or heart disease risk reduction alone, independent of BMI criteria.

Bypassing the Stomach, Not the Heart

What about a patient with established CVD; maybe a patient with a previous MI who is stable now but has a high Framingham risk score? Dr. Morton told CSWN, "A lot of those risk factors in the Framingham risk score are going to be amenable to change with bariatric surgery and there are data that help support the assumption that bariatric surgery can decrease cardiac risk. There was a study by Ted Adams, PhD, MPH, a few years ago in the New England Journal of Medicine comparing those who had surgery versus those who didn't. There was a pretty profound (40%) reduction in cardiac death at 7 years. If we believe that cardiac risk factors predict future events, then we can extrapolate and feel fairly certain that a decrease in cardiac risk factors ought to decrease cardiac events."

Is it safe to bypass the stomach with the hope of eventually bypassing or delaying the need for CABG? Dr. Morton's team at Stanford presented a study in May at Digestive Disease Week 2013 showing that it's possible to risk stratify candidates for bariatric surgery and predict who will have a perioperative cardiac event.

Dr. Morton said current data already support offering more CHD patients the option of weight-loss surgery. For patients who are obese, refractory to lipid therapy, or who have diabetes—the big risk factors for heart disease mortality—he called bariatric surgery "an excellent option and certainly we are doing our part in making sure the surgery is safe." National 30-day mortality rates are about 0.1%, equivalent to hip replacement surgery or gall bladder removal.

Bariatric surgeons want to partner with cardiologists to deal with two of the biggest cardiac risk factors: obesity and diabetes, as well as for cardiac risk assessment, which is important now that it looks like it's feasible to predict who is most likely to be at risk from bariatric surgery.

"We are all in this together," said Dr. Morton, "in the sense that we are working towards the same goals to improve the health of patients at cardiac risk. Virtually all of our patients have cardiac risk factors and we can see improvements with bariatric surgery."

References

1. DeMaria AN. J Am Coll Cardiol. 2013;61:784-6. http://content.onlinejacc.org/article.aspx?articleid=1569998
2. Rider OJ, Francis JM, Ali MK, et al. J Am Coll Cardiol. 2009;54:718-26. http://content.onlinejacc.org/article.aspx?articleid=1139968
3. Vest AR, Heneghan HM, Agarwal S, et al. Heart. 2012;98:1763-77.
4. Lindqvist A, Spégel P, Ekelund M, et al. J Clin Endocrinol Metab. 2013;98:E856-61.
5. Barres R, Kirchner H, Rasmussen M, et al. Cell Rep. 2013;3:1020-7.
6. Mechanick JI, Youdim A, Jones DB, et al. Obesity (Silver Spring). 2013;21 Suppl 1:S1-S27.
7. Poirier P, Alpert M, Fleisher LA, et al. Circulation. 2009;120:86-95.
8. Poirier P, Cornier MA, Mazzone T, et al. Circulation. 2011;123:1683-701.

Keywords: Heart Diseases, Prevalence, Bariatric Surgery, Stomach, Weight Loss, Obesity, Morbid, Risk Factors, Diabetes Mellitus, United States, Minimally Invasive Surgical Procedures, Goals

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