High Blood Pressure Treatment May Help Prevent Diabetes

December 3, 2003

GAINESVILLE, Fla. — Aggressively lowering high blood pressure with a treatment strategy that includes a calcium antagonist not only decreases the risk of heart attack, stroke or death – in a surprising twist, it also appears to slash the chance high-risk patients will develop diabetes, University of Florida researchers reported Tuesday in the Journal of the American Medical Association.

Scientists involved in the landmark International Verapamil SR-Trandolapril study, known as INVEST, were intrigued by the finding in part because patients with high blood pressure and cardiovascular disease are much more likely to develop diabetes, and those who do are much more likely to suffer a heart attack or stroke or die. Study participants randomly assigned to receive a sustained-release form of the calcium antagonist verapamil followed by the angiotensin-converting enzyme inhibitor trandolapril were 15 percent less likely to develop diabetes than those who received the beta-blocker atenolol and the diuretic hydrochlorothiazide, said the study’s principal investigator Dr. Carl J. Pepine, a professor and chief of cardiovascular medicine at UF’s College of Medicine.

“All hypertensive patients are at risk for diabetes, but patients who had diabetes when they entered the trial had almost a twofold risk in the primary outcome, which was death, heart attack or stroke,” said Pepine, also the current president of the American College of Cardiology. “What that means is once a patient with hypertension and coronary disease has those problems, and then they develop diabetes, it imparts double the risk of having those events. Patients who develop diabetes are very important because it immediately takes them into a very high-risk group.”

UF researchers said if the findings, still considered preliminary, can be confirmed by another study, one or two out of every 100 hypertensive heart disease patients treated with a verapamil SR-trandolapril strategy for at least three years could avoid diabetes – an advance that would affect thousands. It’s not yet clear whether the approach protected against the emergence of diabetes in high-risk patients, or whether the other strategy actually provoked the disease, Pepine said.

UF researchers tracked more than 22,500 patients from 14 countries for two to five years and found that both approaches controlled high blood pressure exceptionally well, safely lowering it below 140/90 in 72 percent of participants, who were mostly elderly.

INVEST was primarily designed to test treatment strategies for lowering blood pressure. But shortly after starting the study, sponsored by Abbott Laboratories, new information became available on the potential for different blood pressure-lowering medications to prevent or delay the onset of diabetes, Pepine said. Accordingly, researchers started tracking the development of diabetes in participants soon after the study began.

Calcium antagonists decrease the work of the heart’s blood pumping, reduce the pressure of blood flow through the body and improve blood circulation through heart muscle. Since the 1960s, beta-blockers have ranked among the most widely used drugs for the treatment of high blood pressure, but a small percentage of patients can’t tolerate them because they develop fatigue or other side effects. The drugs fight the condition by reducing the heart’s workload, slowing heart rate and decreasing the force with which the heart muscle contracts. Diuretics lower blood pressure.

Study participants assigned to the verapamil strategy also could receive the drug trandolapril and/or a diuretic to achieve the target blood pressure or minimize side effects. Those in the atenolol group also could use trandolapril, an angiotensin-converting enzyme, or ACE, inhibitor, if needed. ACE inhibitors block an enzyme in the body that causes blood vessels to narrow. If the blood vessels are relaxed, blood pressure decreases and the heart uses less oxygen to pump blood.

More than 50 million Americans have high blood pressure, according to the American Heart Association. Elevated blood pressure is associated with up to half of all cases of coronary artery disease, the No. 1 killer of men and women in the United States. Yet surveys have shown that 30 percent or less of the patients in the United States who are known to be hypertensive comply with treatment and even a smaller percentage achieve the targeted blood pressure goal.

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of diabetes-related deaths. About two thirds of deaths that occur among people with diabetes are due to heart disease and stroke. Most have blood pressure greater than or equal to 130/80 mmHg. An estimated 18.2 million Americans, meanwhile, have diabetes.

“Diabetes has reached epidemic proportions in our society,” Pepine said. “We’re searching for ways to reduce it and for causes of it. It seems to be one of the potential causes might be some of the treatments we’re using.”

Having diabetes is as much a risk factor for subsequent heart disease as having had a prior heart attack, said Rhonda Cooper-DeHoff, a research assistant professor at UF’s College of Medicine. The findings are particularly relevant to blacks and Hispanics, who are at greatly increased risk of diabetes: In 2002, more than 11 percent of blacks and 8 percent of Hispanic-Americans over the age of 20 had the disease, she said.

“In INVEST, being Hispanic was the No. 1 predictor of increased risk of developing diabetes,” Cooper-Dehoff said. “We currently have under way in-depth analyses of both the Hispanics and the blacks enrolled in INVEST to evaluate control of blood pressure and heart disease outcomes in those populations specifically, as well as the onset of diabetes.”

Scientists aren’t yet sure why the verapamil strategy lowered the risk of diabetes, but it may have had something to do with how the medications affect the body’s ability to use sugar for fuel, Cooper-Dehoff said. Preventing diabetes would have tremendous public health implications and could greatly cut related health-care costs, she added.

It is well known, thanks to other studies, that ACE inhibitors may prevent diabetes, said Dr. Valentin Fuster, director of the Cardiovascular Institute at Mount Sinai School of Medicine in New York.

“The use in this study of the combination of verapamil SR and trandolapril, and particularly of trandolapril based on previous studies, supports original data in which an aggressive strategy in treating high blood pressure when diabetes and hypertension are combined is key, because it can significantly decrease the impact of the diabetes on cardiovascular disease,” said Fuster, also past president of the American Heart Association.