Change In Minimal Lumen Diameter Research Articles

Impact of myocardial bridge on non-culprit vessel lumen changes in patients with acute coronary syndrome.

This study aims to clarify the impact of myocardial bridge (MB) on the presence and progression of atherosclerosis in left descending coronary artery (LAD) in patients with acute coronary syndrome (ACS). Ninety-eight patients who underwent percutaneous coronary intervention with the diagnosis of ACS and follow-up coronary angiography but had no significant stenosis in the LAD were included. MB was defined based on coronary angiography. Quantitative coronary angiography was performed to determine the segments where MB was present and proximal to the MB (proximal segment) in patients with MB. In patients without MB, a corresponding region was quantitatively analyzed. The primary endpoint was changes in minimum lumen diameter (MLD) and percentage of diameter stenosis (%DS) in the proximal segment from baseline to follow-up angiography, namely ΔMLD and Δ%DS. MB was identified in 29 (29.6%) patients. Patients with MB had larger MLD and smaller %DS in the proximal segment than their counterpart. During the mean follow-up period of 12.9 ± 5.7months, MLD and %DS in the proximal segment did not change significantly from baseline to follow-up in patients with and without MB. No significant between-group differences were observed in ΔMLD and Δ%DS. Baseline MLD was identified as the only factor associated with ΔMLD in the proximal segment. ACS patients who had MB but no significant stenosis in the LAD had larger MLD and smaller %DS at the segment proximal to MB compared to those without. In this selected population, serial lumen changes assessed by ΔMLD were not associated with the presence of MB in the LAD.

Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease.

Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility. We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 μg. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach. The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 µg of Ach at doses above 50 μg and 100 µg, while this decrease in MLD was not observed in women (P<0.001). The %MLD constriction at 20 μg versus 50 μg and 50 μg versus 100 μg were not equivalent while the %MLD constriction at 100 μg versus 200 μg were equivalent. Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 μg, while women have minimal change in MLD with doses above 50 µg. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.

Progression of cardiac allograft vasculopathy assessed by serial three-vessel quantitative coronary angiography.

BackgroundThe purpose of the present study was to assess the short- and long-term progression of cardiac allograft vasculopathy (CAV) using serial 3-vessel quantitative coronary angiography (QCA).MethodsCAV progression was assessed using serial 3-vessel QCA analysis at baseline, 1-year and long-term angiographic follow-up (8.5±3.7 years) after heart transplantation. The change in minimal lumen diameter (MLD) and percent diameter stenosis (%DS) was serially assessed within matched segments. Patients were graded according to the ISHLT-CAV classification and grouped as ISHLT-CAV0 and ISHLT-CAV1-3. The primary endpoint was mean change in MLD and %DS.ResultsA total of 41 patients and 520 matched segments were available for serial 3-vessel QCA. Overall, MLD decreased non-significantly from baseline to 1-year follow-up and significantly from 1-year to the long-term angiographic follow-up (Δ-0.08mm/year [95%CI -0.11 to -0.05], P<0.001). %DS increased significantly from baseline to 1-year (Δ+0.96%/year [95%CI 0.04 to 1.88], P = 0.041) and from 1-year to long-term angiographic follow-up (Δ+0.61%/year [95%CI 0.33 to 0.88], P<0.001). ISHLT-CAV1-3 at 1 year and at long-term angiographic follow-up was observed in 22% and 61%, respectively. Between baseline and long-term angiographic follow-up, a significant reduction in MLD was observed within both groups without a significant difference in the reduction between the two groups (ISHLT-CAV0: median -0.49mm [IQR -0.54 to -0.43] vs. ISHLT-CAV1-3: median -0.40mm [IQR -0.44 to -0.35], P = 0.4).ConclusionThe current data suggest that QCA can’t predict CAV beyond 1 year, but, QCA affirmed that CAV progresses to a similar extent in patients who do not develop visual CAV during long-term follow-up.

The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study

The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (-0.25 mm, 95% CI -0.36 to -0.17 mm) when compared with patients without NA (-0.13 mm, 95% CI -0.17 to -0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms.SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT00617084.

Prediction of Chronic Vessel Enlargement by a Novel Intravascular Ultrasound Finding

Coronary arterial segments distal to the severely stenotic lesion sometimes shrink as a result of decreased coronary flow. Pathological studies have shown that vessel shrinkage is accompanied by folding of the internal elastic membrane (IEM). A peri-medial high-echoic band (PHB) by intravascular ultrasound (IVUS) may represent folding of the IEM and therefore detect chronically shrunken coronary segments that have potential to enlarge subsequently. METHODS AND RESULTS: IVUS imaging of the distal reference segments was performed in 27 patients after stenting. PHB was defined as a high-echoic band observed at the luminal side of the media. Serial (baseline and 9 months) changes in minimal lumen diameter (LD) were compared between those with (PHB group) and without PHB (non-PHB group). During follow-up, LD increased significantly in PHB group (1.2±0.3 vs. 1.7±0.5 mm, P=0.001) but not in the non-PHB group (2.0±0.7 vs. 2.1±0.7 mm, P=NS). Late lumen gain (LLG) was observed in 16 of the 27 (59%) lesions. Lesions with LLG showed a trend toward smaller baseline lumen cross-sectional area and significantly higher prevalence of PHB (88% vs. 18%, P=0.007). By multivariable logistic regression analysis, PHB was the only IVUS predictor of LLG. Presence of PHB on IVUS predicts chronic enlargement of the coronary segments distal to the stented lesion.

Biodegradable stents: the golden future of angioplasty?

Key steps in the biodegradable stent revolution, including the first-in-man results of magnesium1,2 and poly-L-lactide (PLLA) stents,3,4 have been reported in The Lancet. With more than 60 000 Absorb bioresorbable vascular scaffolds implanted in the past 3 years, a randomised comparison of metallic and fully bioabsorbable stents, both eluting the antiproliferative drug everolimus, is now presented by Patrick Serruys and colleagues.5 The ABSORB II trial had a 2:1 single-masked design and a small sample population of 501 patients, with sophisticated coprimary endpoints of nitrate-induced vasomotion and changes in minimum lumen diameter (in-stent late loss) at 3 years.

The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and meta-analysis.

BackgroundStudies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease.MethodsMultiple electronic databases were searched from inception through August 2012. Studies examining 9p21-3 genotype in patients with known coronary artery disease were included. We extracted the association of the 9p21-3 locus with measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen diameter (∆MLD) and number of new lesions at follow-up], and key clinical outcomes (all-cause mortality, recurrent myocardial infarction and the need for coronary revascularization). Relative risks (RR) and weighted mean difference (WMD) were pooled using the random effects models.Results23 cohorts enrolling 16,860 participants were analyzed. There was no significant difference between HR and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction or the frequency of coronary revascularization. HR genotype was associated with increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01) and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03). However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P = 0.26). HR genotype did not predict ∆MLD or number of new lesions at follow-up.ConclusionsPatients of coronary atherosclerosis who carry the high risk genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD. However the effect of this allele on CAD progression and disease specific clinical outcomes are not observed possibly due to diminishing genetic risk following dietary modification and therapy.

Abstract 373: The Association of 9p21.3 Locus with Coronary Atherosclerosis: A Systematic Review and Meta-Analysis

Background The association between the 9p21-3 locus and coronary heart disease (CHD) is well known. We performed a systematic review of the literature to assess whether this locus was associated with severity of coronary atherosclerosis. Data Sources Multiple relevant electronic databases were searched through September 2012 for English language studies with comparative design. Data extraction We tested the association of the 9p21-3 locus: 1) measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CHD Prognostic Index (Dc.PI)]. 2) angiographic outcomes [change in minimum lumen diameter ([[Unable to Display Character: &amp;#8710;]]MLD) and number of new lesions at follow-up] and 3) key clinical outcomes (all-cause mortality, recurrent myocardial infarction and need for coronary revascularization). Genotypes were classified either as homozygous low risk (Lo) or homozygous high risk (Hi). Data Synthesis Relative risks (RR) were pooled using the random effects model. Seventeen distinct data sets that included 15,826 participants were analyzed. Ten studies (n=9807) reported number of diseased vessels at baseline. Hi genotype was associated with a 33.7% increased risk of triple vessel disease (95% CI 1.08-1.65; p=0.01). The Hi genotype was associated 0.27 higher baseline Gensini Score (95% CI 0.04-0.48; p=0.01) in 3787 individuals. The locus was not associated with Dc.PI [RR=0.21 (95% CI -0.14-0.55; p=0.25)]. The high risk genotype did not predict [[Unable to Display Character: &amp;#8710;]]MLD or number of new lesions at follow-up. There was no difference between Hi and Lo genotypes in terms of all-cause mortality [RR=1.13 (95%CI 0.90-1.41;p=0.28)], recurrent myocardial infarction (95%CI 0.92-1.40; p=0.24) or frequency of coronary revascularization [RR=1.101 95% CI (0.78-1.57); p=0.56]. Conclusion An association between 9p21-3 and greater baseline severity of coronary atherosclerosis was seen in this meta-analysis. However no association was seen between 9p21-3 and adverse angiographic and clinical outcomes which may be due to diminishing genetic risk following dietary modification and statin therapy.

Randomized Trial of Cutting Balloon Compared With High-Pressure Angioplasty for the Treatment of Resistant Pulmonary Artery Stenosis

We sought to determine the safety and efficacy of Cutting Balloon therapy (CB) compared with conventional high-pressure balloon therapy (HPB) for the treatment of pulmonary artery stenosis. This prospective, randomized, multicenter, investigational device exemption trial compared CB with HPB. Patient eligibility was determined at the precatheterization assessment; vessel eligibility was determined at catheterization. In all vessels, low-pressure balloon dilation to 8 atm was performed, and if it was not successful, the vessel was randomized to CB or HPB. The primary efficacy outcome was percent change in minimum lumen diameter. A core laboratory performed all vessel measurements and angiographic assessment of vessel damage. The primary safety outcome was any serious adverse event attributable to vessel dilation as assessed by the Data and Safety Monitoring Board. Seventy-three patients from 8 institutions were enrolled between 2004 and 2008. In these patients, 72 vessels responded to low-pressure balloon dilation. Of the 173 vessels that met eligibility criteria, 107 were randomized to CB and 66 to HPB. In randomized vessels, CB therapy was associated with greater percent increase in lumen diameter (85% versus 52%; P=0.004). After crossover was introduced, 26 of 47 vessels treated with HPB underwent CB therapy and experienced an additional 48% increase in lumen diameter; the final diameter after CB was 99% greater than the initial diameter. There were no serious adverse events related to treatment in a study vessel. CB therapy for pulmonary artery stenosis not responsive to low-pressure balloon is more effective than HPB therapy and has an equivalent safety profile.

Angiographic evidence of progressive lumen narrowing over 2 years following drug-eluting stent implantation

BackgroundQuestions persist regarding the ability of drug-eluting stents (DES) to inhibit intimal growth in the long-term. MethodsWe prospectively enrolled 766 lesions treated with DES that underwent angiographic examination at 6months and 2years after stenting. Lesions with 6-month restenosis (>50% of visual stenosis) were excluded. The primary end point was quantitative change in minimal lumen diameter (MLD) according to serial angiography of the segment (in-segment), the stented region (in-stent) and both edges. Late loss, defined as MLD change, was categorized as early (between post-procedure and 6months), delayed (between 6months and 2years), or overall (between post-procedure and 2-years). ResultsMLD progressively decreased in both the in-stent and edge regions at both 6months and 2years (p<0.001 in all paired analyses). In-segment MLD decreased from a median 2.27mm (interquartile range; 1.98, 2.62) at post-procedure to 2.18mm (1.86, 2.47; p<0.001 with post-procedure) at 6months, and to 2.02mm (1.66, 2.37; p<0.001 with 6months) at 2years. Late loss was 0.06mm (−0.05, 0.26) in the early phase, 0.09mm (−0.01, 0.28) in the delayed phase, and 0.20mm (0.03, 0.50) overall. Two-year angiographic restenosis occurred in 54 (7.0%) lesions, and 65 (8.5%) underwent target lesion revascularization over a median follow-up of 52.5months. ConclusionSerial angiographic analysis showed that DES lumen diameter progressively narrowed over 2years post-procedure. However, the incidence of target lesion revascularization was relatively low due to the small amount of late loss in the delayed phase.

Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction—Angiographic and intravascular ultrasound—Results from the TErapia Celular Aplicada al Miocardio Pilot study

We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy.

Effect of Homocysteine-Lowering B Vitamin Treatment on Angiographic Progression of Coronary Artery Disease: A Western Norway B Vitamin Intervention Trial (WENBIT) Substudy

Total plasma homocysteine (tHcy) is an independent risk factor for coronary artery disease, and tHcy is lowered by B vitamins. To assess the effect of homocysteine-lowering B-vitamin treatment on angiographic progression of coronary artery disease, this substudy of the Western Norway B Vitamin Intervention Trial (WENBIT) included patients who had undergone percutaneous coronary intervention. The patients were randomized to daily oral treatment with folic acid, vitamin B(12), and vitamin B(6) or placebo in a 2 x 2 factorial design. The coronary angiograms obtained at baseline and follow-up were evaluated. The primary angiographic end points were the changes in minimum lumen diameter and diameter stenosis. A total of 348 subjects (288 men) with a mean +/- SD age of 60 +/- 10.2 years were followed up for a median of 10.5 months (twenty-fifth, seventy-fifth percentile 9.2, 11.8). The baseline median plasma tHcy level was 10.0 mumol/L (twenty-fifth, seventy-fifth percentile 8.1, 11.0), and treatment with folic acid/vitamin B(12) lowered the tHcy levels by 22%. At follow-up, we found 309 lesions with a significant decrease from baseline in the minimum lumen diameter of a mean of -0.16 +/- 0.4 mm and an increase in the diameter stenosis of 4.4 +/- 0.7%. Treatment with folic acid/vitamin B(12) or vitamin B(6) was not associated with a change in diameter stenosis or minimum lumen diameter. In a post hoc analysis, folic acid/vitamin B(12) treatment was significantly associated with rapid progression (odds ratio 1.84, 95% confidence interval 1.07 to 3.18). In conclusion, vitamin B treatment showed no beneficial effect on the angiographic progression of coronary artery disease, and the post hoc analyses suggested that folic acid/vitamin B(12) treatment might promote more rapid progression.

Antihypertensive therapy and regression of coronary artery disease: Insights from the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) and Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) trials

In patients with coronary artery disease (CAD), therapies designed to prevent clinical events are not always associated with significant reduction in coronary obstruction, as measured by quantitative coronary angiography. We set out to explore the relationship between quantitative coronary angiography parameters, baseline characteristics, and clinical events in a large trial of CAD regression with antihypertensive agents. Patients randomized to amlodipine, enalapril, or placebo in the CAMELOT trial were followed for 24 months for major ischemic events. Among 431 patients participating in the angiographic and intravascular ultrasound substudy NORMALISE, 298 (99 amlodipine, 96 enalapril, and 103 placebo) had complete angiographic and intravascular ultrasound data. The patients did not differ significantly with respect to baseline characteristics (except for diabetes) or extent of CAD. After 24 months, the change in minimal lumen diameter (MLD) was -0.02 +/- 0.13 for amlodipine, -0.03 +/- 0.12 for enalapril, and -0.03 +/- 0.17 mm for placebo (P = .40). Major ischemic events occurred in 20.2%, 24%, and 25.2%, respectively (P = .68). There was no significant correlation between change in MLD and age, sex, statin therapy, or systolic blood pressure at baseline. The change in MLD did not differ in patients with and without cardiovascular events, regardless of treatment assignment (P = .54). Only the extent of CAD was independently predictive of ischemic events. As compared to placebo, amlodipine treatment resulted in fewer ischemic events after 24 months of therapy, but the clinical benefit was not associated with a commensurate improvement in arterial lumen dimensions.

Renal dysfunction increases the risk of saphenous vein graft occlusion: Results from the Post-CABG trial

Objectives Saphenous vein grafts are common among patients with a history of coronary artery bypass graft (CABG) surgery. Chronic kidney disease (CKD) is an established cardiovascular risk factor, but its role in graft disease has not been evaluated. Methods and results The Post-CABG Trial randomized 1351 patients who had undergone CABG surgery 1–11 years earlier to high- or low-dose lovastatin and to low-dose warfarin or placebo. Coronary angiography was conducted at baseline and after a median follow-up time of 4.2 years. Subjects were grouped according to their baseline estimated glomerular filtration rate (eGFR). The primary trial endpoint was significant graft disease progression assessed angiographically. Additional pre-defined endpoints included occlusion of grafts patent at baseline, change in minimum lumen diameter, and a composite endpoint of recurrent clinical events. Decreasing eGFR was associated with an increased risk of graft occlusion ( P trend = 0.040), but not substantial atherosclerotic progression ( P trend = 0.30), per-graft change in minimum lumen diameter ( P trend = 0.067), or recurrent clinical events ( P trend = 0.86). We did not observe significant effect modification of treatment effects by the presence of CKD. Conclusions CKD may be associated with increased risk of atherosclerotic plaque disruption rather than atherosclerotic progression in saphenous vein grafts.

Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65 ± 8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and nonelevated uric acid levels (233 ± 10 μM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10 −7 to 10 −5 μM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051 ± 0.001 vs 0.019 ± 0.005 μU/mg protein; p < 0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh ( n = 13), oxypurinol markedly attenuated ACh-induced vasoconstriction (−23 ± 4 vs −15 ± 4% at ACh 10 −5 μM, p < 0.05) and significantly increased CBF (16 ± 17 vs 62 ± 18% at ACh 10 −5 μM, p < 0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8 ± 4.2 vs 5.2 ± 0.7%, p > 0.05) or CBF (135 ± 75 vs 154 ± 61%, p > 0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1 ± 1.5 before to 7.6 ± 1.5% after oxypurinol administration ( p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.

Plasma C-Reactive Protein and Lipoprotein Levels, and Progression of Coronary Artery Disease after Myocardial Infarction Treated with Thrombolysis

Background: There is a paucity of studies using quantitative coronary angiography (QCA) to determine progression of coronary artery disease (CAD) after an acute coronary event. Furthermore, despite a great interest in effects of inflammation and ‘early’ lipid lowering therapy, no data have been published on the role of plasma C-reactive protein (CRP) and lipoprotein levels in CAD progression after myocardial infarction. Methods: Seventy-two patients with myocardial infarction treated with thrombolysis, but not with statins, were investigated with QCA during admission and after 6 months. Plasma CRP concentrations were measured by a high sensitive method 2 days after the acute event, and plasma high-sensitive CRP and lipoprotein levels were determined 3 months after myocardial infarction. Results: Overall, there was no significant progression of CAD, but when stenoses were grouped into those reducing the lumen diameter greater or less than 50%, progression was seen in stenoses originally <50%, whereas regression was seen in stenoses >50%. No consistent associations were seen between plasma CRP, lipoprotein lipid or lipoprotein(a) levels and CAD. Conclusions: Progression of stenoses <50% might be of clinical importance since these stenoses are more prone to rupture. Furthermore, the lack of associations between change in minimum lumen diameter and plasma CRP and lipoprotein concentrations suggests that positive effects on CAD progression of early treatment with anti-inflammatory or lipid-lowering drug therapy may not be expected in this subset of patients.

Usefulness of Serum Endothelin Levels in Predicting Death and Myocardial Infarction But Not Coronary Progression in Postmenopausal Women With Coronary Disease (from the Women’s Angiographic Vitamin and Estrogen [WAVE] Study)

We performed a cohort study of 392 postmenopausal women who had coronary disease to assess whether baseline serum endothelin-1 level predicts angiographic disease progression, nonfatal myocardial infarction, or death. Angiographic progression was defined as the annualized change in minimal lumen diameter of all qualifying lesions for each patient. Twenty-nine patients died or had a myocardial infarction during follow-up. Each picogram per milliliter increase in endothelin-1 was associated with a 1.8-fold increased risk of death or myocardial infarction. After adjustment for potential confounders, endothelin-1 remained a predictor of clinical events but was not correlated with angiographic progression.

Clinical and Angiographic Predictors of Luminal Changes Beyond 6 Months After Implantation of Thicker Strut Coronary Stents

Late luminal changes beyond 6 months after thicker strut stent implantation have not been fully elucidated. The purpose of this study was to clarify the clinical and angiographic predictors of late changes in minimal lumen diameter (MLD) after 6-month follow-up of stenting. Fifty-one lesions from 44 patients who underwent successfully S670/660 stent (Medtronic Vascular, Santa Rosa, CA, USA) implantations without target lesion revascularization were studied at 6-month follow-up and coronary angiography was repeated after the follow-up. Late luminal loss beyond 6 months after stenting significantly correlated with late loss (r=-0.42, p=0.0025) and MLD (r=0.28, p=0.047) at 6-month follow-up. On multivariate analysis, age (p=0.005), diabetes mellitus (p=0.002), hyperlipidemia (p=0.023), smoking (p=0.015), bifurcation lesion (p=0.018), small stent diameter (p=0.001) and MLD at 6-month follow-up (p<0.001) were identified as independent predictors of late luminal loss. This study demonstrated that older age, diabetes mellitus, hyperlipidemia, smoking and small stent diameter (<3.0 mm) were associated with late luminal loss beyond 6 months after stenting, and that a bifurcation lesion and small lumen diameter at 6 months were associated with late luminal recovery.

Effects of PPARalpha, gamma and delta haplotypes on plasma levels of lipids, severity and progression of coronary atherosclerosis and response to statin therapy in the lipoprotein coronary atherosclerosis study.

Peroxisome proliferator-activated receptors (PPARs) alpha, delta and gamma are nuclear transcription factors that regulate fatty acid biosynthesis. Our objectives were to determine the effects of PPAR haplotypes on biochemical, angiographic, clinical phenotypes and their responses to treatment with fluvastatin. We genotyped 372 Lipoprotein and Coronary Atherosclerosis Study subjects for seven single nucleotide polymorphisms (SNPs) in PPARalpha (-35 089A>C, 484C>G), delta (-4401C>T, 294T>C) and gamma (34C>G, 25 506C>T, 161C>T) by restriction mapping or 5' exonuclease assay. We reconstructed and estimated haplotypes frequencies using four algorithms. Linkage disequilibrium (LD) was calculated by D' and haplotype effects by permutation and regression analyses. The PPARD and PPARG SNPs were in LD. The baseline plasma triglyceride levels and their responses to treatment with fluvastatin were associated with PPARD haplotypes (P = 0.01). Triglyceride levels were lowest and highest in homozygotes with diplotypes 3 and 4 (130.1 +/- 40.8 and 194.2 +/- 44.6 mg/dl, P < 0.001), respectively. PPARD haplotype 3 was also an independent determinant of plasma apolipoprotein (apo)B (P = 0.021) and apoC-III (P = 0.001) levels, mean number of coronary lesions (P = 0.046) and changes in triglyceride (P = 0.01) and apoC-III (P = 0.047) levels in response to fluvastatin. Plasma triglyceride levels (P = 0.044), the mean number of coronary lesions (P = 0.026) and changes in minimum lumen diameter in response to fluvastatin (P = 0.022) were also associated with PPARG haplotypes. No significant associations between PPARA haplotypes and the phenotypes or significant interactions between PPAR haplotypes and the occurrence of new clinical events were detected. PPARD and PPARG haplotypes are independent determinants of plasma levels of lipids, severity of coronary atherosclerosis and its response to therapy.

Metabolic syndrome and coronary angiographic disease progression: the Women’s Angiographic Vitamin & Estrogen trial

Background The metabolic syndrome is a cluster of clinical characteristics thought to be associated with increased coronary risk. This analysis evaluates angiographic progression of coronary disease in women who are postmenopausal with and without the metabolic syndrome enrolled in the Women’s Angiographic Vitamin & Estrogen (WAVE) trial, a randomized, controlled trial of hormone therapy and antioxidant vitamins. Methods A total of 425 women who are postmenopausal and have angiographic coronary disease were enrolled at 7 clinics between July 1997 and August 1999. Women were categorized as having the metabolic syndrome when they met the National Cholesterol Education Program Adult Treatment Panel III definition. Coronary angiograms were performed at baseline and after 2.8 ± 0.9 years (mean ± SD). Quantitative coronary angiographic analysis was performed at a core laboratory. Results Women with the metabolic syndrome (177/294, 60%) were more likely to be taking cholesterol-lowering medication (65% vs 51%, P = .01) and had higher body mass index (33 ± 6 vs 28 ± 6 kg/m 2, P <.001). The mean reduction in minimum lumen diameter was greater (−0.041 ± 0.151 vs −0.023 ± 0.148 mm/year, P = .33) and new lesions were more frequent (34% vs 23%, P = .054) in women with the metabolic syndrome. In multivariate analysis, the metabolic syndrome was not an independent predictor of angiographic disease progression. However, clinical events (myocardial infarction, stroke, or coronary death) were more frequent among women with the metabolic syndrome ( P = .02). Conclusion The metabolic syndrome was prevalent among postmenopausal women with coronary disease enrolled in the WAVE trial. Having the metabolic syndrome was not independently associated with changes in minimum lumen diameter or the development of new or progressing coronary lesions, but did confer an increased risk of clinical cardiovascular events.