Oct. 28, 2002 DALLAS, Oct. 22 – High blood pressure treatment with a calcium channel antagonist slowed progression of atherosclerosis, the disease process responsible for heart attacks and strokes, better than a beta blocker, according to a rapid track report posted online this week in Circulation: Journal of the American Heart Association.
Rapid track articles are released online early because Circulation editors believe the work has major clinical impact or represents important basic science discoveries.
The study tested two high blood pressure medications: lacidipine, a calcium channel blocker, and atenolol, a beta blocker. Beta blockers reduce the heart's tendency to beat faster as it tries to compensate for weakened pumping ability. Allowing the heart to maintain a slower rate lowers blood pressure. Calcium channel blockers interfere with calcium's role in the contraction of these muscles. This causes the muscles to relax, lowering blood pressure and improving blood circulation in the heart.
Ultrasound images taken at the start of the study revealed that patients had measurable atherosclerosis in the carotid arteries. After four years of treatment, the yearly progression rate for this narrowing was 40 percent lower in lacidipine-treated patients than in the patients treated with atenolol.
Researchers tracked plaque progression by measuring intima-media thickness (IMT) in participants' carotid arteries, which carry blood to the brain. IMT is a measurement of the interior lining of blood vessels. During the four-year study, researchers found that people taking atenolol showed an increase in IMT by 0.0145 millimeters per year (mm/yr), while IMT in people taking lacidipine increased by 0.0087 mm/yr.
Alberto Zanchetti, M.D., lead researcher of the European Lacidipine Study on Atherosclerosis (ELSA), says this difference was apparent even though average ambulatory blood pressure reduction among patients taking lacidipine was less than the average reduction achieved by patients taking atenolol.
Zanchetti, who is a professor of medicine at the University of Milan and scientific director of Istituto Auxologico Italiano in Milan, says the finding suggests "it is some specific property of the calcium antagonist we have used in addition to the lowering of blood pressure, that slows down the progression of atherosclerosis."
Calcium channel blockers, also called calcium antagonists, decrease the rate at which calcium flows into the heart and blood vessel walls. This, says Zanchetti, appears to have the beneficial effect of slowing the growth of cells that line the blood vessels and arteries and reducing the size of plaques, the fat deposits that accumulate in arteries.
The report shows that 19.8 percent of the lacidipine-treated patients had a regression of arterial plaque after four years treatment, while 15.7 percent of patients taking atenolol had a similar regression.
The study recruited 2,334 patients with systolic (the top number in a blood pressure reading) pressures ranging from 150-210 millimeters of mercury (mm Hg) and diastolic (the bottom number) pressures ranging from 95 to 115 mm Hg. High blood pressure is defined in an adult as a systolic pressure of 140 mm Hg or higher and/or a diastolic pressure of 90 mm Hg or higher.
The patients' ages ranged from 45 to 75 and they lived in France, Germany, Greece, Italy, Spain, Sweden and the United Kingdom. Patients were randomized to either lacidipine or atenolol once a day. After a month of treatment, if diastolic pressure didn't drop by at least 5 mm Hg to less than 95 mm Hg both drugs were increased and when necessary, a diuretic was added. Patients underwent ultrasound scanning of carotid arteries to measure the thickness of the arterial wall at baseline and every year throughout the study.
When blood pressure was measured in the clinic the drugs achieved virtually the same reductions. When it was monitored using special round-the-clock ambulatory monitoring devices, patients taking atenolol reduced systolic blood pressure an average of 10.3 mm Hg and decreased diastolic pressure by almost 9 mm Hg, while the reduction in the lacidipine group was less: 6.8 mm Hg and 4.9 mm Hg average declines in systolic and diastolic pressures respectively.
Lacidipine is not approved for use in the United States and Zanchetti says it is unknown if other calcium antagonists would be as effective at slowing atherosclerosis. The drug targets dangerous fats that accumulate in the arterial wall and binds with vascular cells.
"So it may be more powerful than other calcium antagonists," he says.
Co-authors are M. Gene Bond, Ph.D.; Michael Hennig, Ph.D., Albrecht Neiss, Ph.D.; Guiseppe Mancia, M.D.; Cesare Dal Palù, M.D.; Lennart Hansson, M.D.; Bruno Magnani, M.D.; Karl-Heinz Rahn, M.D.; John L. Reid, M.D.; Josè Rodcio, M.D.; Michel Safar, M.D.; Lothar Eckes, M.D., Ph.D.; and Paolo Rizzini, M.D.
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