Surgery May Be Better Than PCI in Patients With Multivessel Disease at High Risk
Coronary artery bypass graft surgery was associated with lower risk of mortality in patients with multivessel coronary artery disease and high-risk characteristics than was percutaneous intervention, said researchers from the Cleveland Clinic Foundation in a report in this week’s issue of the journal Circulation (Circulation. 2004;109:2290–2295OpenUrl).
In the study, researchers led by Sorin J. Brener, MD, studied 6033 consecutive subjects who underwent revascularization during the last decade. Percutaneous interventions were carried out in 872 of them and surgery was performed on 5161. A total of 931 deaths were recorded during 5 years’ follow-up. The 1-year mortality rates were 5% for PCI and 4% for coronary artery bypass graft surgery. The 5-year mortality rates were 16% for PCI and 14% for CABG. Percutaneous intervention was associated with an increased risk of death with an adjusted hazard ratio of 2.3. The researchers noted that the comparison is affected by procedure selection bias, duration of follow-up, and type of event.
The researchers wrote: “Despite these limitations, we conclude that at a large tertiary institution with particularly low surgical mortality, patients with multivessel CAD [coronary artery disease] and many high-risk features appear to have a better 5-year survival when treated with CABG than with PCI. Further research is needed to determine whether drug-eluting stents and improved medical management will close the mortality gap in these patients.”
COX-2 Gene Variation Associated With Low Heart Attack, Stroke Risk
A variation in the COX-2 gene appears associated with a decreased risk of heart attack or stroke, said Italian researchers in the May 12, 2004, issue of the Journal of the American Medical Association (JAMA. 2004;291:2221–2228OpenUrlCrossRefPubMed).
In this study, led by Francesco Cipollone, MD, of the G. d’Annunzio University of Chieti and G. d’Annunzio University Foundation, Chieti, Italy, researchers evaluated 864 patients with first myocardial infarction or ischemic stroke and compared them with 864 hospitalized, matched controls. They found that the prevalence of the −765C polymorphism in the COX-2 gene was 2.41 times higher in the controls who had not had a heart attack or stroke than in the subjects who had suffered such events. The prevalence of a second variant called −765CC was 5.81 times higher than in the subjects. The relative risk of myocardial infarction and ischemic stroke was 52% and 67% lower, respectively, in those with the −765C and −765CC polymorphism after adjustment for age, sex, smoking status, body mass index, hypercholesterolemia, hypertension, and diabetes.
The authors wrote: “Our study also raises a number of provocative questions regarding the potential clinical importance of this genotype in asymptomatic patients taking selective coxibs. The individual pharmacodynamic response to COX-2 inhibitors may vary, as responders and nonresponders to coxibs have been described. Thus, patients with the −765GC and −765CC genotypes may represent subgroups of patients with different drug responses. Further research will be needed to determine whether genotyping patients for the COX-2 polymorphism leads to better treatment outcomes. We found that the −765GC polymorphism of the COX-2 gene is associated with a reduction in the risk of MI [myocardial infarction] and stroke, suggesting that this [variation] may offer protection against clinical events related to atherosclerotic plaque rupture.”
Homocysteine and Osteoporosis
High levels of homocysteine were associated with fractures related to osteoporosis in two reports in the May 13, 2004, issue of the New England Journal of Medicine (N Engl J Med. 2004;350:2042–2049; N Engl J Med. 2004;350:2033–2041OpenUrlCrossRefPubMed).
In one study, led by Joyce B.J. van Maeurs, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, researchers studied the relationship between levels of homocysteine in the blood and risk of osteoporotic fracture in 2406 subjects who were 55 years of age or older. The subjects were participants in the Rotterdam Study and the Longitudinal Aging Study Amsterdam. A total of 191 subjects suffered fracture during the varying follow-up periods. Risk was similar in men and women and between the cohorts. In the highest age-specific quartile of homocysteine level, risk of fracture was 1.9 times higher. The risk, said the researchers, appeared independent of bone mineral density and other risk factors for fractures.
The findings could be expected, the researchers wrote. They said, “According to a long-standing hypothesis, the mechanism underlying the association between the homocysteine level and the risk of fracture may involve interference by homocysteine in collagen cross-linking. Homocysteine has been shown to interfere specifically with the formation of collagen cross-links and fibrils in solution. In addition, lower amounts of collagen cross-links have been found in serum from patients who have homocystinuria—that is, persons with very high levels of circulating homocysteine—than in normal controls.”
They also noted: “The association between elevated homocysteine levels and the risk of fracture should be confirmed in other large population studies. Proof of a causal relationship between increased homocysteine levels and bone disease could be established by intervention studies aimed at lowering the serum homocysteine level.”
In the second study, researchers from the Hebrew Rehabilitation Center for Aged Research and Training Institute, Tufts University, the Harvard Medical School Division on Aging, Boston University School of Public Health, and the Framingham Study in Massachusetts, led by Robert R. McLean, MPH, studied 825 men and 1174 women aged 59 to 91 years from whom blood samples had been obtained at baseline (1979–1982) to measure plasma total homocysteine. Men suffered 41 hip fractures during 12.3 years’ (average) follow-up, and women suffered 146 in 15 years of follow-up. Men and women in the highest quartile of homocysteine levels had a greater risk of hip fracture than did those in the lowest levels. The risk was 4 times higher for men and 1.9 times higher for women.
The researchers wrote: “We were not able to establish causality definitively, because plasma homocysteine concentrations may only be a marker for nutritional or metabolic differences that are the real causal factors in hip fracture. Furthermore, we cannot determine whether the association observed in our study population is a result of the same mechanisms that lead to an increased prevalence of osteoporosis among patients with homocystinuria. This study suggests that the total homocysteine concentration is strongly associated with the risk of hip fracture. If the relationship proves to be one of cause and effect, this finding may have important implications for the development of interventions to prevent hip fractures, because total homocysteine concentrations can be effectively and easily modified by dietary intake of folic acid and vitamins B6 and B12.”