Scientists have unraveled one of the mysteries of precisely how a popular type of blood pressure pill protects against heart attacks, showing it not only lowers blood pressure but also directly improves the health of the artery walls.
Doctors had suspected that blood pressure reduction alone could not explain the whole benefit of the pills, called angiotensin converting enzyme, or ACE, inhibitors, because studies have shown they prevented heart attacks and deaths even in patients with normal blood pressure or those whose high blood pressure did not budge.
ACE inhibitors ease blood pressure by reducing production of a chemical that squeezes arteries. But a new study, presented Tuesday at Europe's largest medical conference, found that the drug also preserves the delicate lining of the wall of the blood vessel, which repels plaque.
All cells are programmed to die off after some time, in a process known as apoptosis. New cells then replace them. In heart disease, that programmed suicide is accelerated in endothelial cells, which make up the fragile lining of the blood vessel wall. The acceleration strips the lining of the artery away faster than it can be replenished. This means the vessel lining has holes in it that allow the process of plaque buildup to begin.
The drug in the study, perindopril, appeared to slow the cell suicide rate.
"We have seen over the years a number of huge clinical trials that are actually rather blunt. They just tell you if you survive better or get less (heart attacks)," said Dr. Lars Ryden, a prominent cardiologist and professor at the Karolinska Institute in Stockholm, Sweden. "Here, the investigators took upon them a rather demanding task and did an extremely elegant experimental study, not with rat tissue or anything else _ as it often is _ but in humans."
"I am excited," said Ryden, who was not connected with the research. "We have seen a number of things that start to explain, which means that the next drug that will come will be much better."
The research, led by Italian heart specialist Roberto Ferrari, was a spin-off of a large study testing perindopril's benefits in preventing heart attacks and deaths.
Perindopril is known as Coversyl in Europe and elsewhere outside the United States. Other ACE inhibitors include Zestril, Accupril and Enaprin. The pills have few serious side effects. The most common and annoying is a persistent cough, which occurred in about 4 percent of patients in the study.
In the study, Ferrari, a professor of cardiology at the University of Ferrara in Italy, isolated human endothelial cells and cultivated them in blood from healthy volunteers or from 150 heart disease patients enrolled in the larger study, in which patients got either the drug or a fake pill.
The blood was tested on the cells both at the beginning of the trial and after one year of treatment with either the drug or the fake pill.
"This technique allowed us to mimic the effects of the blood of a patient with coronary artery disease on its own endothelium and to see whether treatment with perindopril is able to modify the effect," Ferrari said.
Unsurprisingly, the experiment showed that the drug widened the blood vessels by increasing amounts of an enzyme that controls blood vessel flexibility.
However, when it came to programmed cell death, the drug seemed to calm the suicide rate. In healthy people, 1.3 percent of the endothelial cells die every 30 minutes. In the heart disease patients given the fake pill the rate was 7.8 percent per 30 minutes both at the beginning and the end of the study.
However, in the patients given the drug, the death rate fell from 7.8 percent in the beginning to 4.7 percent by the end of the study.
Other ACE inhibitors have been shown to improve endothelial problems, but previous studies have only measured the improvement indirectly by testing how easily blood flows through the arm. The latest study is the first to test the effect directly.
(er/twx)
