Leisure-Time Exercise Better Than Walking or Biking to Work
Perhaps in part explaining the mystery of the French conundrum, a group of French and Northern Irish researchers have found that leisure-time exercise (a form more common to the French) seems to have a greater positive cardiovascular effect than walking or cycling to work (the exercise more common to those who live in Northern Ireland).
The study, published in this week’s issue of Circulation (Circulation. 2002;105:2247–2252) and led by Aline Wagner, MD, of the Laboratoire d’Epidemiologie et de Sante Publique in Strasbourg, France, and Chantal Simon, MD, PhD, of the Groupe d’Etudes et de Recherche en Nutrition at Strasbourg, examined information from the Prospective Epidemiological Study of Myocardial Infarction (the PRIME Study) to determine the effects of activity levels and patterns on both major coronary events and angina. (The PRIME Study Group included research groups from France and the Queen’s University Belfast, Northern Ireland. The PRIME Study consisted of 9758 men aged 50 to 59 years who were recruited between 1991 and 1993 and who had no signs of coronary heart disease. They were monitored for 5 years.)
During the follow-up period, 321 coronary events were recorded, of which 167 (106 in France, 61 in Northern Ireland) were either fatal or nonfatal myocardial infarctions or coronary deaths. There were 154 instances of angina pectoris (94 in France, 60 in Northern Ireland). The researchers found that the individuals who exercised hardest as a leisure-time activity had the lowest risk of fatal or nonfatal myocardial infarction or coronary deaths. However, walking or bicycling to work did not appear to have a positive effect on such coronary disasters. “Those who walked or cycled to work tended to have a higher incidence of angina,” the researchers wrote.
“In our study, surprisingly, a significant increase in the incidence of angina was observed for the most active subjects,” they wrote. “The mechanism behind such pain is still unclear,” they wrote, “and it hasn’t yet been proven if what is seen is a true increase or an under-diagnosis of angina in more sedentary individuals.”
“In conclusion, these prospective data from a European cohort of middle-aged men show a beneficial effect of leisure-time physical activity (EE) on the incidence of fatal or nonfatal myocardial infarction and coronary deaths. These results could partly explain the unfavorable rate of coronary heart disease in Northern Ireland compared to France.”
Chronic Kidney Disease Adds to Coronary Artery Disease Risk
Chronic kidney disease increases the risk of revascularization procedures, concluded researchers from the Bypass Angioplasty Revascularization Investigation (BARI). Although severe chronic kidney disease was a known independent predictor of cardiovascular mortality, the BARI researchers, led by Lynda Anne Szczech, MD, MSCE, Assistant Professor in the Division of Nephrology at Duke University Medical Center in Durham, NC, wanted to better understand the effects of more mild renal problems.
In a report in this week’s issue of Circulation (Circulation. 2002;105:2253–2258), the researchers identified 76 patients with serum creatinine of >1.5 mg/dL before the procedure, a level that matched their definition of chronic kidney disease. Among the patients undergoing percutaneous transluminal coronary angioplasty, those with chronic kidney disease were more likely to die in the hospital and experience cardiogenic shock. They had more cardiac admissions to the hospital than other patients undergoing either percutaneous transluminal coronary angioplasty or coronary artery bypass grafting, as well as a shorter time to subsequent coronary artery bypass grafting than patients who did not have kidney disease. Patients with chronic kidney disease had heart-related problems and a higher risk of dying from all causes at 7 years.
“These data suggest that, among patients with mild CKD (chronic kidney disease), treatment for atherosclerosis needs to be tailored to address the increased frequency of these events. Greater clinical awareness of the increased mortality and adverse events subsequent to revascularization among patients with mild CKD is needed to stimulate further research in the development of appropriate treatment and surveillance strategies.”
It’s in the Genes
Normalization of myocardial gene expression is behind the positive effects of β-blockers in treating patients with idiopathic dilated cardiomyopathy, according to researchers from the University of Colorado Health Sciences Center in Denver and the University of Utah Health Sciences Center in Salt Lake. The report appears in the May 2, 2002, issue of the New England Journal of Medicine (N Engl J Med. 2002;346:1357–1365).
In their study, the researchers, led by Brian Lowes, MD, of the University of Colorado, randomly assigned 53 patients with idiopathic dilated cardiomyopathy to metoprolol, carvedilol, or a placebo. They then measured the amount of mRNA for contractility-regulating genes and for genes associated with pathological hypertrophy and myocardial levels of adrenergic receptors. Measurement occurred at baseline after 6 months of treatment. Changes in gene expression were compared with changes in the left ventricular ejection fraction.
Of the 32 patients who received β-blockers, 26 experienced a dramatic increase in their left ventricular ejection fraction, as well as positive changes in the genes that regulate the heart’s ability to contract, leading the researchers to conclude that the success of β-blockers in treating such patients is associated with the modulation of genes involved in the proper functioning of the myocardium.
Texas Heart Institute Begins Stem Cell Therapy for Heart Failure in Brazil
Ten Brazilian end-stage heart failure patients have received catheter-delivered bone marrow stem cells in a pioneering attempt to boost the pumping ability of their hearts. The method, which had been tested successfully in animals, was developed at the Texas Heart Institute (THI) by Emerson Perin, MD, Director of New Interventional Cardiovascular Technology at THI in concert with Brazilian cardiologists. The goal of the therapy is to replace damaged heart muscle and encourage growth of new blood vessels to supply oxygen to the organ.
Four patients received the stem cells in late December 2001, nearly 5 months before the trial was announced at the May 7, 2002, press conference. The other 6 received their stems approximately 2 weeks before that date.
“It is too early to determine the effect of the stem cells,” said James T. Willerson, MD, Medical Director and Director of Cardiology Research at THI, as well as president of The University of Texas Health Science Center at Houston. “We have seen some encouraging results, but the numbers are not great enough and the patients have not been followed long enough.”
Dr Willerson and Yong J. Geng, MD, PhD, Director of the THI Heart Failure Laboratory, have been evaluating the treatment in animals with the use of embryonic animal stem cells that develop into cardiovascular stem cells. The treatment results in a 30% reduction in scar tissue within the first 2 weeks.
“THI is very interested in this kind of work,” said Dr Willerson. “This is one of the largest series of patients treated worldwide, and we will continue this work.” He anticipates similar transplantations being performed under THI auspices in other parts of the world, as well as in Houston, where the institute is located.
“This is the first step. I ultimately want these cells to carry genes that the failing heart is missing,” said Dr Willerson. Using the stem cells as a vector to take new genes into heart muscle eliminates the concerns about using viruses that can cause inflammation and other negative effects. The stem cells, when introduced into a specific organ system, differentiate along the lines of that particular kind of tissue, according to Dr Willerson. “The mechanism isn’t entirely clear, and we are interested in that as well.”
Because the stem cells are taken from the patient’s own marrow, the threat of rejection is eliminated, he said. In the current treatments, bone marrow taken from the patients on the day of the transplantation is processed to select out certain mononuclear cells, said Dr Willerson. Ideally, he said, work in the laboratory will identify markers for cells that are most likely to become the kinds of cells the heart needs.
“Younger stem cells might have greater potential,” said Dr Willerson, “but adult stem cells might be all we need to accomplish our goals.” Use of pluripotent embryonic stem cells in human experiments has been a controversial issue, and last summer, President George Bush limited such work to cells taken from certain established cell lines. However, the work presented by Dr Willerson and his colleagues was performed with adult stem cells, which have been shown to have unexpected potential in the area of differentiation and have not been the subject of controversy.
One advantage of the technique used in Brazil is that no surgery is involved, said Dr Emerson Perin. “This is a catheter-based technique,” he said.
During the procedure, a 2.6-mm catheter is introduced into the left ventricle of the heart, which has already been mapped with the use of a 3-dimensional technique. During that mapping, physicians identified the areas most in need of new heart muscle cells and blood vessels.
A needle is positioned carefully over one of 12 or more spots in the heart muscle and then plunged into the tissue, delivering millions of stem cells into the appropriate area.
The patients in whom the technique has been attempted so far were extremely ill. There were no other conventional treatments that could be offered to them and their life expectancies were short, said Dr Perin.