High blood pressure induces low fat metabolism in heart

The heart, the most energy-hungry organ in the body, is prone to defects under some conditions in its energy metabolism that contribute to heart disease, according to School of Medicine researchers.

Lisa de las Fuentes
Lisa de las Fuentes

The findings were published in a recent issue of the Journal of Nuclear Cardiology by Lisa de las Fuentes, M.D., and colleagues at the School of Medicine.

Earlier research led by de las Fuentes’ colleague Robert J. Gropler, M.D., showed that heart muscle in people with diabetes is overly dependent on fat for energy. Even though fat is an efficient fuel, burning it for energy creates an unusually high demand for oxygen, making the diabetic heart more sensitive to the drops in oxygen levels that occur with coronary artery blockage.

Gropler is director of the Cardiovascular Imaging Laboratory at the Mallinckrodt Institute of Radiology and professor of radiology, medicine and biomedical engineering.

Now, this group of researchers has shown that hearts of non-diabetics with muscle thickening due to high blood pressure have an energy metabolism skewed in the opposite direction — away from the use of fat for energy.

“Whereas Dr. Gropler found that a high level of fatty acid metabolism could be detrimental, we show that a low level may also be harmful,” said de las Fuentes, co-director of the Cardiovascular Imaging and Clinical Research Core Laboratory and assistant professor of medicine. “These findings aren’t contradictory. The heart has to be able to choose the energy source, either fats or glucose, most appropriate for its current energy needs and the availability of fuel.”

De las Fuentes said that hearts with muscle thickening, or hypertrophy, get less energy because of their reduced fat metabolism, which leads them to rely more heavily on carbohydrates. The metabolic abnormality can eventually lead to impaired contraction of the heart and to heart failure.

In this study, the researchers studied patients who had high blood pressure that resulted in hypertrophy of the muscle of the left ventricle, the chamber of the heart that pumps blood to the body. The study showed that the greater the muscle mass of the hypertrophic heart, the lower the ability to burn fat. Magnetic resonance scans suggested that hypertrophic heart muscle had subtle abnormalities in contractile function at rest and was less energy efficient.

Normally, heart muscle will alternate between using fats and carbohydrates as fuel depending on availability. But at times when blood glucose is low, hypertrophic hearts can’t switch to burning fatty acids as normal hearts would, possibly leaving them energy deficient, de las Fuentes explained.

“This is the first time these data have been shown in humans,” said senior author Victor G. Dávila-Román, M.D., director of the Cardiovascular Imaging and Clinical Research Core Laboratory and professor of medicine, of anesthesiology and of radiology. “That is particularly significant because hypertension (high blood pressure) is a huge public-health problem in the United States. Of the 65 million people with hypertension, between 25 and 50 percent of them have some evidence that their heart has been affected by high blood pressure.”

Not everyone who has high blood pressure will develop hypertrophy, and not everyone with hypertrophy has long-term problems, de las Fuentes said. Some people appear to be protected while others appear to be at increased risk, likely due to genetic factors.

Dávila-Román said that by looking at the genetics of hypertension and hypertensive heart disease, they hope to identify genes that predispose people to both good and bad traits associated with these disorders. Such information promises opportunities for both prevention and treatment of cardiac disease.