Angiotensin-converting enzyme (ACE) inhibitors, which dilate blood vessels and improve blood flow, appear to prevent and even reverse unhealthy buildup of stiff muscle in the heart's main pumping chamber, a condition called left ventricular hypertrophy (LVH).
LVH occurs when the heart muscle becomes over-bulky and rigid from the extra burden of high blood pressure or valve problems. The condition, which occurs more often in people with hypertension, and particularly blacks, stymies proper circulation. That, in turn, causes potentially deadly heart attacks, strokes, and heart failure.The latest findings, reported in the Oct. 2 issue of Circulation: Journal of the American Heart Association, are based on analysis of a larger study that looked at the effects of the ACE inhibitor ramipril on a variety of cardiovascular conditions. Data from that trial, released in 1999, showed that ramipril, sold as Altace by Monarch Pharmaceuticals, cut the risk of cardiovascular deaths by one quarter, heart attacks by one-fifth and strokes by nearly a third.
In the analysis, a team led by Dr. James Mathew of the University of Iowa College of Medicine compared the effects of ramipril and a dummy pill on heart size in nearly 8,300 people over an average of about 4.5 years. In particular, Mathew's group sought to learn if the drug could prevent or reverse LVH, as measured by electrocardiogram (ECG) scans.
Some subjects had high blood pressure that was being controlled by medication; others had coronary artery disease. All were considered to be at high risk for a heart attack, heart failure or a stroke.
Patients who took ramipril were modestly less likely to develop LVH than those who received a placebo. The drug was somewhat more impressive at shrinking LVH in patients who had the condition at the start of the trial.
But the bigger impact was on patients whose LVH improved or who didn't develop the ailment, Mathew says. Their risk of heart attack, stroke and cardiovascular-related death was 12.3 percent, vs. 15.8 percent in the group with worse LVH, a difference of more than 28 percent. And their risk of congestive heart failure was 65 percent lower: 9.3 percent vs. 15.4 percent.
"What this study shows is if you have LVH by ECG, regardless of your blood pressure or the presence of coronary disease, you seem to benefit from the use of ACE inhibitors," says Mathew.
The effects of ramipril seemed to be much greater than expected from its blood-pressure lowering effects alone, which were only about 1 to 2 millimeters of mercury, Mathew says. Indeed, he says, "We see similar effects in patients with normal blood pressure and no history of hypertension."
The molecules that ACE inhibitors inhibit are present in both heart muscle and circulating blood. Mathew says ramipril's ability to improve LVH suggests that it is quite active on muscle molecules.
However, he says, it's unclear if related drugs would be equally potent, especially if they target blood molecules more than the muscular versions.
Dr. Gregory Lip, in an editorial accompanying the journal article, says the study is "one of the first that convincingly demonstrates that reversal of LVH results in a clinical benefit in a population at high risk of heart problems." But Lip, a cardiologist at City Hospital in Birmingham, England, says "unanswered questions remain."
Blacks, for example, are significantly more likely than whites to develop LVH, and reducing it may or may not lead to improved prognosis, Lip says. Only 11 percent of the patients in the latest study weren't white.
In addition, nine of 10 people in the group that took dummy pills didn't get LVH or saw it improve. Since they were motivated to participate in a long-term clinical trial, and since they received comprehensive follow-up care, including education and advice on lifestyle changes to better their health, the "placebo-control group may not truly be 'untreated,'" Lip says.
What To Do
For a description of LVH, check the Medical University of South Carolina.