Guido Schnyder

Plasma homocysteine levels and late outcome after coronary angioplasty

OBJECTIVES The aim of this study was to evaluate a possible relationship between homocysteine levels on admission and late outcome after successful percutaneous coronary intervention (PCI). BACKGROUND Increasing evidence suggests that mild to moderate elevation of total plasma homocysteine is a graded and potentially modifiable risk factor for cardiovascular disease and death that appears to be largely independent of other traditional risk factors. METHODS A total of 549 patients were included after successful PCI of at least one coronary stenosis (> or =50%). End points were cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and a composite of major adverse cardiac events (MACE). The relationship between homocysteine levels and study endpoints was assessed. RESULTS After a median (+/- SD) follow-up of 58 +/- 20 weeks, 6 patients died of cardiac death, 14 were diagnosed with a new MI, and 71 underwent repeat TLR. A graded relationship between homocysteine levels (quartiles) and freedom from MACE was found (p = 0.01). Homocysteine levels (+/- SD) were associated with cardiac death (14.9 +/- 1.7 micromol/l vs. 9.6 +/- 4.3 micromol/l, p < 0.005), TLR (10.7 +/- 4.4 micromol/l vs. 9.5 +/- 4.3 micromol/l, p < 0.05), and overall MACE (11.0 +/- 4.4 micromol/l vs. 9.4 +/- 4.3 micromol/l, p < 0.005). These findings remained unchanged after adjustment for potential confounders. CONCLUSIONS Plasma homocysteine is an independent predictor of mortality, nonfatal MI, TLR, and overall adverse late outcome after successful coronary angioplasty.

Association of plasma homocysteine with the number of major coronary arteries severely narrowed

O the past several years, there has been evidence indicating that a moderate elevation of total plasma homocysteine (tHcy) level is a risk factor for coronary artery disease (CAD). The normal range in adults is between 5 and 15 mol/L, depending on the study considered. The atherogenic mechanism of homocysteine-induced vascular damage is still not clearly understood. Elevated levels of tHcy may stimulate proliferation of vascular smooth muscle cells and impair endothelium function. The interaction of homocysteine and endothelial cells may also increase thrombogenicity. A meta-analysis by Boushey and coworkers showed that tHcy in increments of 5 mol/L corresponded to a greater relative risk of CAD of 60% in men and 80% in women. Similar percentages have been reported for cerebrovascular and peripheral arterial disease. However, there is ongoing controversy on the role of tHcy as a risk factor for CAD. The purpose of the present study was to evaluate the relation between tHcy and the severity of CAD in a large cross-sectional study. Six hundred thirty-one consecutive patients referred for diagnostic coronary angiography were included in the present analysis. Informed consent was obtained from all patients according to a protocol approved by the local ethics committee. Patients with recent myocardial infarction ( 2 weeks), renal dysfunction (serum creatinine 1.8 mg/dl), megaloblastic anemia, or who were taking multivitamins were excluded. Coronary artery stenoses were assessed by quantitative coronary angiography and stratified into significant ( 50%) and nonsignificant ( 50%) stenoses. The disease severity was evaluated by counting the number of major epicardial coronary arteries (left anterior descending, circumflex and right) affected with 1 significant stenosis ( 50%). CAD severity was scored as 0 (normal angiographic vessels control group), 1 (1-vessel disease), 2 (2-vessel disease), or 3 (3-vessel disease), respectively. Stenosis of a left main-stem artery without stenosis of the right coronary artery was classified as 2-vessel disease. Patients were divided into 4 groups according to the number of diseased vessels (0, 1, 2, and 3). Fasting tHcy levels were measured using the technique described by Ubbink et al, a sensitive and reproducible method with a variation coefficient of 6.6% and a 2 mol/L lower limit of detection. Coronary angiograms were obtained from 2 orthogonal views after predilation with nitrates. Quantitative coronary angiography was either performed using Philips Integris-BH-3000 (version 2) (Best, The Netherlands) if online or Philips View-Station-CDM3500 (version 2) if offline. The tip of the diagnostic catheter (positioned at the coronary ostium) was used as a scaling device to obtain absolute arterial dimensions. End-diastolic frames in the 2 orthogonal views showing maximal stenosis severity were chosen for luminal diameter measurement. Reference diameter, minimal luminal diameter, and percentage diameter stenosis were calculated as the average value of the 2 views. Angiograms were reviewed by an experienced interventional cardiologist who was unaware of patients’ tHcy levels. Intraobserver variability for minimal luminal diameter and percentage diameter stenosis was 0.15 0.22 mm and 7 12%, respectively. Categorical variables are reported as counts (percentages) and continuous variables as mean SD. A 1-way analysis of variance was used to assess the association between the severity of CAD and continuous variables. For categorical variables, a chi-square test was used to test differences between study groups. A 2-tailed t test was employed to estimate the association between tHcy and categorical variables. The Pearson correlation coefficient was used to estimate the correlation between tHcy and other continuous variables. Multiple logistic regression analysis was used to evaluate whether the relation between the severity of CAD and tHcy was modulated by clinical or laboratory variables. Serum creatinine was used as a covariate because plasma homocysteine is eliminated by the kidneys and indirectly related to creatinine levels. Patients with a history of renal failure were excluded to avoid elevated creatinine values as confounders for increased tHcy levels. A 2-sided 5% level of significance was considered significant for all statistical tests. Data were prospectively collected and analyzed using StatView Version 4.5 (SAS Institute, Cary, North Carolina). A total of 631 consecutive patients (137 women and 494 men) were included in the present analysis. Of the 631 patients, 78 had no angiographic signs of CAD, 205 had 1-vessel disease, 192 had 2-vessel disease, and 156 had 3-vessel disease. There were a total of 1,519 stenoses that were found to be significant ( 50%). About 1/5 of the study population were women, the average age was 61 years, and the cardioFrom the Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland; and Division of Cardiology, University of California–San Diego, San Diego, California. This study was supported in part by a grant from the Swiss National Science Foundation, Bern, Switzerland. Dr. Schnyder’s address is: UCSD Medical Center, Cardiology Division, John Ross Cardiac Catheterization Laboratory, 200 West Arbor Drive, San Diego, California 92103-8784. E-mail: g.schnyder@lycos.com. Manuscript received March 21, 2001; revised manuscript received and accepted June 13, 2001.

Effect of Homocysteine-Lowering Therapy on Restenosis After Percutaneous Coronary Intervention for Narrowings in Small Coronary Arteries

umenting all balloon infl ations on fi lm. To that end, investigators were provided a protocol for acquiring angiograms at the initiation of the trial to ensure optimal angiographic quality. Although compliance with the protocol and fi lm quality were generally excellent, deviations from the protocol were not quantifi ed, and some device use may not have been captured on fi lm. Second, the high frequency of geographic miss in our study, based on our defi nition, may limit our ability to detect differences between the groups because of the small sample of patients without geographic miss. Finally, intravascular ultrasound was not performed systematically at follow-up, but would have provided valuable insight into the mechanism of edge recurrence. In INHIBIT, the presence and length of geographic miss were not associated with increases in overall restenosis for either radiated or placebo patients. The treatment effect of P-32 was maintained despite the presence of geographic miss, and there was no identifiable detrimental interaction between radiation and geographic miss. There is no angiographic evidence that P-32 has a proliferative effect as the dose decreases. 1. Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, Pichard AD, Kent KM, Stone GW, Leon MB. Angiographic patterns of in-stent restenosis: classifi cation and implications for long-term outcome. Circulation 1999;100: 1872–1878.

Concomitant coronary and multiple arch vessel stenoses in patients treated with external beam radiation: Pathophysiological basis and endovascular treatment

External beam radiation‐induced stenoses isolated to the coronary arteries or peripheral vessels have been previously described. We report for the first time the clinical presentation of two patients with concomitant coronary artery and multiple arch vessel disease following external beam radiation of the chest. We review the pathophysiology, discuss the treatment options and describe the percutaneous treatment of coronary, carotid, subclavian, and axillary stenoses related to this rare but likely underdiagnosed disorder. Catheter Cardiovasc Interv 2004;62:385–390.

Complications of vascular closure devices—not yet evidence based

The interesting publication by Dangas et al. [(1)][1]claims to compare arteriotomy closure devices with manual compression after percutaneous coronary intervention. Unfortunately, this is a comparison only in the fashion that can be ascribed to a retrospective trial with mismatched procedural