The current issue of Circulation marks the second appearance of the journal’s new section, Mini-Review: Expert Opinions. The section is designed to provide assistance to physicians and care givers of patients with cardiovascular disease and to stimulate future research on pertinent topics. The topic featured in this week’s issue is Stem Cell Therapy and includes a review article by Bodo Strauer, MD, and Ran Kornowski, MD, a review article by Emerson Perin, MD, PhD, Yong-Jian Geng, MD, PhD, and James T. Willerson, MD, and an Editorial comment by Dean Kereiakes, MD, FACC.
CURE: Early and Late
Clopidogrel reduced the risk of ischemic vascular events as early as 24 hours after the beginning of treatment and continued for a year, according to the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) investigators, led by Salim Yusuf, MBBS, of McMaster University in Hamilton, Canada. Their report appears in this week’s issue of Circulation (Circulation. 2003;107:966–972).
In the study, 12 562 patients with acute coronary syndromes were randomized to receive either clopidogrel or placebo for 3 to 12 months. Dosage of clopidogrel began with 300 mg at the beginning and was followed by 75 mg/day for the duration of the study.
At 30 days, 5.4% of patients in the placebo group and 4.3% in the clopidogrel group had experienced either death from heart disease, heart attack, or stroke. Beyond 30 days, the rates were 6.3% in the placebo group and 5.2% in the clopidogrel group. The difference in life-threatening bleeding incidents was not statistically significant between the two groups.
Studies of the early data showed that benefits began to accrue within 24 hours of the initiation of treatment, according to the researchers. They concluded that treatment with clopidogrel in this group of patients shows consistent benefit.
Vitamins E and C: ASAP?
Supplementation with vitamin E and slow-release vitamin C slows the progress of atherosclerosis in patients with high cholesterol, according to Finnish and Danish researchers in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study published in this week’s issue of Circulation (Circulation. 2003;107:947–953).
The researchers led by Riitta M. Salonen, MD, PhD, of The Research Institute of Public Health, University of Kuopio, Kuopio, Finland, noted that in the first three years of the trial, supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice a day slowed the progression of carotid atherosclerosis in men but not in women. They have continued their study for an additional 6 years, studying 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years. All had cholesterol of 193 mg/dl. A total of 440 patients completed the study.
They assessed the effect of the supplementation on the common carotid artery intima-media thickness. In men, the reduction was significantly higher than that of women. Taking the two sexes together, the average annual increase in the mean carotid artery intima thickness increase was .014 mm in those who did not receive supplements, and 0.10 mm in those who did. In men, they noted, the treatment effect was 30%. Vitamin E, however, had no effect on HDL cholesterol.
The researchers concluded: “Our study suggests that the benefit is greatest in men and may even be limited to men only.”
They also noted: “The size of the treatment effect is not trivial. We observed in all men a 30% treatment effect and in both genders combined, a 25% treatment effect. The treatment effect among participants who had carotid plaques at baseline was >50%. These effects are comparable to those of the most effective cholesterol-lowering medications, but with fewer adverse effects and lower cost.”
Circulating Endothelial Cells Predict Heart Disease
The number of circulating endothelial progenitor cells that give rise to the cells that line blood vessels may give important clues to the status of a person’s cardiovascular health, according to researchers from the National Heart, Lung, and Blood Institute (NHLBI) and the Emory University School of Medicine in the February 13, 2003, issue of the New England Journal of Medicine (N Engl J Med. 348;7:594–599).
In a study led by Jonathan M. Hill, MRCP, of the NHLBI, the researchers noted that they had hypothesized that impaired mobilization or depletion of endothelial progenitor cells derived from bone marrow might indicate endothelial dysfunction. The endothelial progenitors are involved in ongoing endothelial repair.
To determine if this was so, they measured colony-forming units of endothelial progenitor cells in the peripheral blood samples of 45 men who had various degrees of cardiovascular risk but lacked a history of heart disease. They assessed endothelium-dependent and endothelium-independent function by high-resolution ultrasonography of the brachial artery.
They reported a high level of correlation between the number of circulating endothelial progenitor cells and the risk status of the individuals being studied. The flow-mediated brachial-artery reactivity showed a significant relation between endothelial function and the number of progenitor cells. In fact, the researchers noted: “The levels of circulating endothelial progenitor cells were a better predictor of vascular reactivity than was the presence or absence of conventional risk factors. In addition, endothelial progenitor cells from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk.”
They concluded that, “In healthy men, levels of endothelial progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease.”
In an accompanying perspective (N Engl J Med. 2003;348:581–582), Anthony Rosenzweig, MD, of the Program in Cardiovascular Gene Therapy at the Massachusetts General Hospital in Charlestown, Mass, called the notion that these cells are involved in the repair of normal adult blood vessels “intriguing.” “Further studies are needed to test this hypothesis vigorously,” he wrote. “Nevertheless, at the very least, endothelial progenitor cells appear to provide a useful index of cumulative cardiovascular risk and vascular function. These studies reflect the growing realization that adult cells and tissues have far more plasticity and potential for regeneration that previous thought.”
Resynchronization Prevents Heart Failure Mortality
A meta-analysis of 11 reports of 4 clinical trials of cardiac resynchronization via pacemakers in 1634 patients with heart failure showed that mortality from the disease was 1.7% in those who received the pacemakers and 3.5% in controls, according to a report in the Journal of the American Medical Association by researchers from Johns Hopkins School of Medicine and School of Public Health in Baltimore, Md, and the Mayo Clinic and Mayo Foundation in Rochester, Minn (JAMA. 2003;289:730–740).
They also found that cardiac resynchronization reduced hospitalization for heart failure by 29% in those patients who received the therapy compared with control. It was not associated with reduction of all-cause mortality, however. The researchers also determined that among those patients who had implantable cardioverter defibrillators, resynchronization had no clear effect on ventricular fibrillation or tachycardia.
In conclusion, the researchers noted that, “cardiac resynchronization reduced mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction. The finding suggests that cardiac resynchronization may have a substantial impact on the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization also reduced heart failure hospitalization.”
Bush Budget and the Progress of Research
The Association of American Medical Colleges (AAMC) has raised concerns that President Bush’s FY 2004 budget may impede the ability to continue the nation’s progress in the area of biomedical research because only a 2% increase has been recommended for the National Institutes of Health (NIH). This comes after the success of a push to double federal support that began during the previous Administration.
The AAMC also said that the administration proposal threatens health care access for the nation’s poor and disadvantaged by continuing to cut programs that train health workers in rural and underserved areas.
Under the current budget proposal, the NIH would receive a 2% increase to its $549 million budget in 2004. The AAMC called for a 10% increase in order to maintain the biomedical progress.
“Unless there is sustained federal support, the recent momentum we have gained in research could be lost completely in just a few years,” said AAMC President Jordan J. Cohen, MD. “With only minimal budget increases, current research grants will be hard to maintain and innovative proposals will be put on hold at a time when the nation is confronted with health challenges ranging from new and re-emerging infectious diseases to an aging population prone to chronic diseases.”