Two Better Than One
The combination of the selective aldosterone blocker eplerenone with the angiotensin-converting enzyme (ACE) inhibitor enalapril was more effective than the ACE inhibitor alone in effecting regression of left ventricular hypertrophy and controlling blood pressure, said 4E–Left Ventricular Hypertrophy Study investigators in a report in this week’s issue of Circulation (Circulation. 2003;108:1831–1838OpenUrl).
The researchers, led by Bertram Pitt, MD, a professor of internal medicine at the University of Michigan at Ann Arbor, also found that eplerenone alone was as effective as enalapril alone during a 9-month, double-blind, randomized study. They enrolled 202 patients with left ventricular hypertrophy and hypertension. They were randomized to receive 200 mg of eplerenone daily, 40 mg of enalapril daily, or 200 mg of eplerenone and 10 mg of enalapril daily. If the blood pressure was not below 90 mm Hg daily in 8 weeks, hydrochlorothiazide and/or amlodipine was added.
The mass of the left ventricle was assessed by MRI. Measurements indicated that eplerenone significantly reduced left ventricular mass in a manner similar to enalapril. However, the combination of the two drugs was more effective. All treatments reduced blood pressure from the baseline measurement.
The researchers concluded: “Eplerenone, alone or in combination with an ACE inhibitor, seems to be a promising therapy for reducing LVH [left ventricular hypertrophy], and therefore reducing morbidity and mortality, in patients with essential hypertension. The optimal dose-response relationship of eplerenone and/or an ACE inhibitor remains to be determined.”
When You Can’t Use Thrombolytics
Immediate mechanical reperfusion should be considered in patients with acute myocardial infarction with ST-segment elevation who are not candidates for thrombolytics, said researchers in a report in the October 8, 2003, issue of The Journal of the American Medical Association (JAMA. 2003;290:1891–1898OpenUrlCrossRefPubMed).
Between 1994 and 2003, the National Registry of Myocardial Infarction 2, 3, and 4 enrolled 19 917 patients with acute myocardial infarction with ST-segment elevation for whom thrombolytics were contraindicated. Of those, 4705 received immediate mechanical perfusion (either percutaneous intervention or coronary artery bypass graft). Of the entire group, 5173 died in the hospital.
Of those who received reperfusion, 11.1% (521 of 4705) died. However, 30.6% (4652 of 15 212) of those who did not receive reperfusion died. The relative risk reduction was 63.7%, according to the researchers, who were led by Mary Grzybowski, PhD, MPH, of Wayne State University, Detroit, Mich. They noted that 15 212 of the 19 917 patients studied were eligible for reperfusion but did not receive it.
The researchers advocated further studies to confirm their retrospective results and noted that research into ways to make immediate mechanical reperfusion more widely available should be undertaken promptly.
Hypertension and Cognition
A rising blood pressure need not mean a decline in cognition, according to Duke University Medical Center researchers in a report in the September 29, 2003, issue of the journal Aging, Neuropsychology, and Cognition. However, the researchers, led by David Madden, PhD, a cognitive psychologist and researcher of aging, found that middle-aged subjects with high blood pressure were more likely to show a slowing in cognitive performance tests than did their older colleagues.
“While the changes in cognitive performance associated with elevated blood pressure seen in our experiments were statistically significant, they are unlikely to interfere with mental functioning during everyday life,” said Dr Madden. “However, the changes we recorded in the laboratory may represent a situation that could become clinically significant when other diseases, especially those that are cardiovascular in nature, are included. The significance of these cognitive effects will become clearer as additional evidence is obtained regarding the changes in brain structure and function that typically accompany chronically elevated blood pressure.”
The Duke study focused on people who had untreated hypertension and no other signs of cardiovascular disease. A total of 96 adult volunteers were recruited. Half had high blood pressure and half had normal blood pressure. The groups were then divided into three age cohorts: 20 to 39, 40 to 59, and 60 to 79 years. Subjects were tested on a computer to determine how quickly they could respond to visual and memory search tasks. Blood pressure was periodically measured as the subjects performed the tests.
“The results of our experiments show that the interaction between the effects of blood pressure and adult age do not support the predictions of the classical model, which holds that increasing blood pressure accelerates the decline in intelligence tasks,” Dr Madden said. “Our analysis of response times found that a decline in the high blood pressure group was only evident for the middle-aged group, but not for the youngest or oldest participants.”
Inactivating a protein called P13Kγ in mice with chronically high blood pressure appears to have slowed the decline in heart function seen in mice that had the active protein, said researchers at Duke University Medical Center in the October issue of the Journal of Clinical Investigation (J Clin Invest. 2003;112:1067–1079OpenUrlCrossRefPubMed).
P13Kγ is an enzyme required for the internalization and recycling of β-adrenergic receptors on heart cells, the researchers said. β-Adrenergic receptors control the heart’s ability to pump blood when the body is stressed. When stress is chronic, the receptors become overstimulated, leading to loss of the receptors.
In this study, the researchers, led by Howard Rockman, MD, Professor of Medicine at Duke, compared mice bred to lack the gene for P13Kγ with mice that had the gene. All the animals had chronically high blood pressure. The mutant mice experienced a slowed rate of heart failure and actually lived longer than the control mice.
“Our study results show that an intervention that maintains functional β-adrenergic receptors on the heart surface by disrupting PI3Kγ activity leads to improved heart function, a result supporting the idea that the loss of receptors contributes to heart failure,” Dr Rockman said in a released statement. “These findings identify a potential new target for heart drugs and may have important clinical implications.”