New Research Reveals How Age And Obesity Combine To Cause Heart Failure

AUGUSTA, Ga. - Age and obesity appear to create a perfect storm that can reduce blood flow through the tiny blood vessels that directly feed heart muscle - and increase the risk for heart failure, new research has found.

Scientists call it "aged fat," and now they have evidence of the inflammation created by both age and fat, which increases heart failure risk.

In a news release, Augusta University medical researchers explain that this "aged fat" has an additive effect that can thicken the walls of heart vessels - without any evidence of the classic atherosclerotic plaque that is normally associated with heart disease.

"Older obese patients and sometimes women who suffer heart failure go to the cardiac catheterization lab and the cardiologist finds nothing that would explain their heart failure," said Dr. Zsolt Bagi, vascular biologist in the Vascular Biology Center at the Medical College of Georgia at Augusta University in the news release about the research.

"They have normal large blood vessels in the heart, still the heart failure has developed," Bagi said.

What isn't readily seen with these routine exams is the thickened walls that can hinder dilation of the small capillaries fed by these bigger vessels, a condition called coronary microvascular dysfunction, or cardiac syndrome X, added Bagi, who is a corresponding author of the study in the journal Arteriosclerosis, Thrombosis and Vascular Biology.

In patients and animal models, who are both older and obese, Bagi found a dynamic in the dysfunction of an enzyme called ADAM17, the releases says.

This enzyme, the release explains, is involved in a huge variety of bodily functions, such as releasing growth factors. It is also implicated in diseases such as Alzheimer's and arthritis, the release notes.

ADAM17 levels increase in obesity while levels of its natural inhibitor, the protein caveolin-1, decrease with age, enabling the perfect storm, Bagi explained.

The result is the walls of the hair-sized cardiovascular blood vessels "become thicker, less elastic, less able to dilate and to properly sustain the heart," the release says.

Bagi's research team found ADAM17 highly expressed in fat and even higher in the blood vessels of aged human fat, the release says. The protein level was increased in younger mice on a high-fat diet, but the significant increase in its activity came with age and fat.

In humans, they looked at small pieces of heart tissue as well as fat from around the heart removed during surgery by MCG cardiothoracic surgeons Drs. Vijay Patel and M. Vinayak Kamath. They also studied a combination of mice that included young and obese, old and obese, and just obese or just old. "We tried to examine every possible scenario," Bagi said.

Symptoms of heart failure can include fatigue, shortness of breath that make everyday activities difficult as well as coughing, the release notes.

Rather than having trouble with the heart contracting so it can pump blood out to the body, older, obese individuals in heart failure tend to have issues with the heart muscle being able to relax and fill efficiently, called diastolic heart failure, Bagi said.

Relaxation actually requires more energy than contracting, and the scientist says he hopes his studies will help this patient population, for which currently there are "no good, targeted treatment options."

Baji has also begun looking at antibodies that would directly target and ideally reduce levels of the enzyme in the face of aged fat and at least delay development of small vessel disease.

Bagi saidhe feels a similar process may happen in the brains of older obese individuals, which had led to ongoing studies of how microvascular disease can lead to Alzheimer's in these individuals.

Young, obese individuals could help protect themselves by losing weight while they are young, Bagi said. Activities like walking can also help even the tiniest blood vessels become more accustomed to handling more blood flow, he added.

In the nearly 70-year-old Framingham Heart Study, a higher risk of heart failure was identified among 732 older subjects with inflammatory mediators like TNF and interleukin-6 who never even had a heart attack.

Other studies have shown that elevated levels of TNF in the blood and fat strongly correlate with the severity of coronary artery disease in the elderly.

Bagi's research was supported by the National Institutes of Health and the American Heart Association.