Comparative prognostic value of C-reactive protein & fibrinogen in patients with coronary artery disease.

BACKGROUND & OBJECTIVES: The comparative prognostic value of C-reactive protein (CRP) and fibrinogen for cardiovascular events has been inconclusively investigated. t0 his study was carried out to compare the prognostic value of CRP versus fibrinogen in patients with coronary artery disease (CAD). METHODS: The study included 13,100 patients with coronary angiography-confirmed CAD. Plasma CRP and fibrinogen levels were measured before angiography in all patients. The levels of CRP>3 mg/l and fibrinogen>350 mg/dl were considered as elevated. The primary outcome was 1-year all-cause mortality. RESULTS: Patients were divided into four groups: patients with CRP≤3 mg/l and fibrinogen ≤350 mg/dl (n=4206); patients with CRP≤3 mg/l and fibrinogen >350 mg/dl (n=3132); patients with CRP>3 mg/l and fibrinogen ≤ 350 mg/dl (n=1273) and CRP >3 mg/l and patients with fibrinogen >350 mg/dl (n=4489). There were 634 deaths: 75 deaths in patients with CRP ≤3 mg/l and fibrinogen ≤350 mg/dl, 91 deaths in patients with CRP ≤3 mg/l and fibrinogen >350 mg/dl, 87 deaths in patients with CRP >3 mg/l and fibrinogen ≤350 mg/dl and 381 deaths in patients with CRP >3 mg/l and fibrinogen >350 mg/dl (Kaplan-Meier estimates of all-cause mortality, 1.8, 3.0, 7.0 and 8.7 %, log-rank test P<0.001). The multivariate analysis showed that CRP [adjusted hazard ratio (HR)=1.31, 95% confidence interval (CI) 1.18-1.45, for each standard deviation increase in the logarithmic scale] but not fibrinogen [adjusted HR=0.99 (0.90-1.09), for each standard deviation increase in the logarithmic scale] was an independent correlate of mortality. INTERPRETATION & CONCLUSIONS: The findings indicated that in patients with CAD, CRP was a better predictor of mortality than fibrinogen and offered prognostic information beyond that provided by the conventional cardiovascular risk factors.

Relation of fibrinogen level with cardiovascular events in patients with coronary artery disease.

Evidence on the usefulness of fibrinogen for the risk stratification of patients with coronary artery disease remains inconclusive. The aims of this study were to investigate the association of fibrinogen with cardiovascular events and to assess whether this biomarker provides additional prognostic information on top of that provided by traditional cardiovascular risk factors. This study included 13,195 patients with angiography-proved coronary artery disease and fibrinogen measurements available. Receiver-operating characteristic curve analysis showed that the best fibrinogen cutoff for mortality prediction was 402.0 mg/dl. On the basis of this cutoff, patients were divided into 2 groups: the group with fibrinogen >402.0 mg/dl (n = 5,198) and the group with fibrinogen ≤402.0 mg/dl (n = 7,997). The primary outcome was 1-year mortality. All-cause deaths occurred in 393 patients with fibrinogen >402.0 mg/dl and in 246 patients with fibrinogen ≤402.0 mg/dl (Kaplan-Meier estimates of mortality 7.7% and 3.1%, log-rank test p <0.001). The relation between fibrinogen and mortality followed a J-shaped pattern, with lowest mortality in patients with fibrinogen concentrations of 295 to 369 mg/dl. After adjustment for cardiovascular risk factors and relevant clinical variables, fibrinogen remained an independent correlate of all-cause mortality (adjusted hazard ratio 1.07, 95% confidence interval 1.04 to 1.10, p <0.001, for each 50 mg/dl increase in fibrinogen level), but it did not improve the discriminatory power of the model for mortality prediction (integrated discrimination improvement 0.002, p = 0.32). In conclusion, in patients with coronary artery disease, fibrinogen is an independent correlate of mortality, but it does not provide additional prognostic information on top of that provided by traditional cardiovascular risk factors.

Impact of perfusion restoration at epicardial and tissue levels on markers of myocardial necrosis and clinical outcome of patients with acute myocardial infarction.

AIMS: To assess the impact of reperfusion after primary percutaneous coronary intervention (PCI) on myocardial salvage and outcome of patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This study included 1,406 patients with STEMI undergoing primary PCI. Blood flow restoration at epicardial and tissue levels was assessed by Thrombolysis in Myocardial Infarction (TIMI) and myocardial perfusion grade (MPG). Patients had paired scintigraphic examinations before, and 7-14 days after intervention. Based on TIMI and MPG grades, patients were divided into three groups: patients with optimal epicardial/optimal tissue perfusion (TIMI=3/MPG=3; n=801), patients with optimal epicardial/suboptimal tissue reperfusion (TIMI=3/MPG ≤ 2; n=412) and patients with suboptimal epicardial/suboptimal tissue reperfusion (TIMI ≤ 2/MPG ≤ 2; n=193). In these groups, the median infarct size (25th-75th quartiles) in the 7-14 days scintigraphy was: 7.0% (1.0%-19.0%), 12.6% (5.0%-27.6%) and 18.7% (10.4%-33.7%) of the left ventricle (p<0.001); frequency of aborted myocardial infarction was: 15.5%, 10.0% and 4.7%, (p<0.001); estimates of 5-year mortality were: 7.8%, 16.0% and 20.1% (adjusted hazard ratio=0.43, 95% confidence interval 0.21-0.89; p=0.02 for optimal epicardial/optimal tissue vs suboptimal epicardial/suboptimal tissue reperfusion). CONCLUSIONS: In patients with STEMI undergoing primary PCI, restoration of blood flow at epicardial and tissue levels was associated with increased myocardial salvage and improved long-term survival.

Sensitive troponin and N-terminal probrain natriuretic peptide in stable angina.

BACKGROUND: High-sensitivity cardiac troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) are powerful predictors of mortality in patients with stable coronary artery disease. Whether their combined use may further improve mortality prediction in these patients is unknown. MATERIALS AND METHODS: The study included 869 patients with stable coronary artery disease who underwent percutaneous coronary intervention. Hs-TnT and NT-proBNP were measured before angiography. Using median values of hs-TnT (0·008 µg L(-1)) and NT-proBNP (250·0 ng L(-1)) as cut-off points, patients were divided into four groups: low hs-TnT/low NT-proBNP group (293 patients with hs-TnT and NT-proBNP < median); low hs-TnT/high NT-proBNP group (142 patients with hs-TnT < median and NT-proBNP ≥ median); high hs-TnT/low NT-proBNP group (142 patients with hs-TnT ≥ median and NT-proBNP < median) and high hs-TnT/high NT-proBNP group (292 patients with hs-TnT and NT-proBNP ≥ median). The primary end point was all-cause mortality. RESULTS: The 4-year follow-up was complete in 90·7% of the patients. There were 76 deaths during the follow-up: seven in low hs-TnT/low NT-proBNP, 8 in low hs-TnT/high NT-proBNP, 10 in high hs-TnT/low NT-proBNP and 51 in high hs-TnT/high NT-proBNP groups (mortality estimates, 2·5%, 5·9%, 7·4% and 18·1%, respectively; odds ratio = 8·64, 95% confidence interval 3·85-19·4, P < 0·001 for high hs-TnT/high NT-proBNP vs. low hs-TnT/low NT-proBNP). Inclusion of hs-TnT and NT-proBNP in the multivariable model increased the discriminatory power of the model regarding mortality prediction compared with the model without biomarkers (absolute and relative integrated discrimination improvement 0·039 and 26·0%, P = 0·0015). CONCLUSIONS: Combined use of hs-TnT and NT-proBNP improves long-term risk prediction of mortality in patients with stable coronary heart disease.

Retrograde salvage approach to treat tibial artery perforation during attempted revascularization of a chronically occluded artery.

Arterial perforation is a well-recognized complication of attempted percutaneous revascularization of a chronic totally occluded tibial artery and typically necessitates termination of the procedure. This report describes a step-by-step approach on how to perform a direct posterior tibial artery puncture and a sheathless wire introduction, to salvage a case of tibial artery perforation induced during attempted anterograde recanalization of an occluded tibial artery. After control of blood loss, retrograde wire passage and balloon inflation can facilitate relocation of the anterograde wire in the true lumen allowing uneventful completion of the procedure. © 2010 Wiley-Liss, Inc.

Characterization of patients with bleeding complications who are at increased risk of death after percutaneous coronary intervention.

Bleeding complications in patients undergoing percutaneous coronary interventions (PCIs) are associated with increased risk of subsequent mortality. We undertook this study to characterize the subset of patients with bleeding complications who are at an increased risk of death within the first year after a PCI procedure. The study included 331 patients with bleeding complications among 9 954 patients who underwent PCI. The primary outcome analysis was 1-year mortality. Within the first year following PCI there were 39 deaths among 331 patients (11.8%), with bleeding complications and 240 deaths among 9 623 patients without bleeding complications (Kaplan-Meier estimates of 1-year mortality; 11.8% vs 2.5%, odds ratio 5.09, 95% confidence interval 3.76-6.90, P < 0.001). Time to death (median [25th-75th percentiles]) was 38.5 [7.2-125.9] days in patients with bleeding complications vs 137.1 [68.3-234.0] days in patients without bleeding complications (P < 0.001). Compared with survivors (n = 292), nonsurvivors (n = 39) had a significantly more adverse risk profile. The Cox proportional hazards model identified the elevated troponin level as the only independent correlate of 1-year mortality (hazard ratio = 2.35, 95% confidence interval 1.04-5.31, P = 0.039). In conclusion, patients with peri-PCI bleeding complications who die have a more adverse cardiovascular risk profile than patients with bleeding complications who survive the first year after PCI. Patients with bleeding complications and an elevated troponin level are at high risk of death within the first year following PCI. The majority of deaths in patients with peri-PCI bleeding occur within the first 3 months after PCI procedure.

5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction.

OBJECTIVES: The objective of this study was to investigate the impact of no-reflow phenomenon on 5-year mortality among patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). This impact was also assessed in relation to infarct size. BACKGROUND: The impact of no-reflow on long-term mortality in patients with STEMI has been insufficiently studied. METHODS: This study included 1,406 patients with STEMI treated by primary PCI. No-reflow was diagnosed using angiographic criteria. Infarct size was measured with single-photon emission computed tomography imaging 7 to 14 days after the acute event. The primary outcome was 5-year mortality. RESULTS: The no-reflow phenomenon was diagnosed in 410 patients (29%). Infarct size was 15.0% (6.0% to 29.0%) of the left ventricle in the no-reflow group versus 8.0% (2.0% to 21.0%) of the left ventricle in the reflow group (p < 0.001). There were 132 deaths during follow-up. Of them, 59 deaths occurred among patients with no-reflow and 73 deaths occurred among patients with reflow (Kaplan-Meier estimates of 5-year mortality 18.2% and 9.5%, respectively; odds ratio: 2.02; 95% confidence interval: 1.44 to 2.82; p < 0.001). The Cox proportional hazards model adjusting for infarct size among other variables identified the no-reflow phenomenon as an independent correlate of 5-year mortality (hazard ratio: 1.66; 95% confidence interval: 1.17 to 2.36; p = 0.004). CONCLUSIONS: In patients with STEMI treated by primary PCI, no-reflow phenomenon is a strong predictor of 5-year mortality. No-reflow phenomenon after PCI provides prognostic information that is independent of and beyond that provided by infarct size.

Predictive factors and impact of no reflow after primary percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The investigation of no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with acute ST-segment-elevation myocardial infarction has therapeutic implications. We investigated the predictive factors, persistence in time, and impact of no reflow on myocardial salvage, ventricular function, and mortality. METHODS AND RESULTS: The study included 1140 patients with ST-segment-elevation myocardial infarction undergoing primary PCI and paired scintigraphic examinations (before intervention and 7 to 14 days thereafter). After primary PCI, 108 patients had no reflow and 1032 patients had normal coronary flow. The median salvage index was 0.34 (interquartile range, 0.15, 0.49) in patients with no reflow versus 0.55 (interquartile range, 0.29, 0.81) in patients with normal flow (P<0.001). Left ventricular ejection fraction at 6 months after PCI was 47.7+/-13.1% in the no-reflow group versus 54.2+/-13.9% in the group with normal flow after PCI (P<0.001). In 80.3% of patients with no reflow, normalization of blood flow >6 months after PCI occurred and correlated with improvement in the left ventricular ejection fraction. Independent predictors of no reflow were residual flow in the infarct-related artery (P<0.001), initial perfusion defect (P=0.03), C-reactive protein (P<0.001), and previous myocardial infarction (P=0.013). Kaplan-Meier estimates of 1-year mortality were 16.7% (n=18) in patients with no reflow versus 5.5% (n=56) in patients with normal flow (hazard ratio, 3.35; 95% CI, 1.97 to 5.69; P<0.001). CONCLUSIONS: No reflow after primary PCI was associated with reduced myocardial salvage, larger infarct size, worse left ventricular ejection fraction at 6 months, and increased risk of 1-year mortality. In 4 of 5 patients with no reflow after PCI, restoration of normal flow occurred 6 months after reperfusion.

Impact of body mass index on clinical outcome in patients with acute coronary syndromes treated with percutaneous coronary intervention.

Studies that have tested the relationship between body weight as assessed by body mass index (BMI) and clinical outcome after percutaneous coronary intervention (PCI) have given contradictory results. The aim of the study was to investigate the impact of BMI on clinical outcome and assess the impact of adjustment for other cardiovascular risk factors on the relationship between obesity and clinical outcome in patients with acute coronary syndromes (ACS) following PCI. This study included 9146 patients with ACS who underwent coronary angiography and PCI: 2610 patients with ST-segment elevation acute myocardial infarction, 2792 patients with non-ST-segment elevation acute myocardial infarction, and 3744 patients with unstable angina. The primary outcome of this analysis was 1-year mortality. Quartiles of BMI were: 12.8 to <24.3 (1st quartile), 24.3 to <26.4 (2nd quartile), 26.4 to <29.1 (3rd quartile), and >29.1 to 50.7 (4th quartile). Within the first year following PCI, there were 756 deaths: 228 deaths in the 1st BMI quartile, 209 deaths in the 2nd BMI quartile, 161 deaths in the 3rd BMI quartile and 158 deaths in the 4th BMI quartile (Kaplan-Meier estimates of mortality 10.3%, 9.1%, 7.2%, and 7.0%, respectively; odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.22-1.86, P < 0.001 for 1st vs 4th BMI quartile). After adjustment in the Cox proportional hazards model, the association between BMI and 1-year mortality was attenuated to the level of statistical insignificance (hazards ratio [HR] = 1.25, 95% CI 0.94-1.64; P = 0.127 for 1st vs 4th BMI quartile). In conclusion, in patients with ACS undergoing PCI, obesity as assessed with BMI was not an independent correlate of 1-year mortality.

Bleeding after percutaneous coronary intervention with Bivalirudin or unfractionated Heparin and one-year mortality.

Compared to unfractionated heparin (UFH), bivalirudin decreases bleeding during percutaneous coronary interventions (PCIs). We sought to investigate the association between periprocedural bleeding and 1-year mortality as a function of antithrombotic therapy with bivalirudin or UFH. This analysis of the association between bleeding with bivalirudin or UFH and 1-year mortality included the 4,570 patients with negative biomarkers enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3) trial. Major or minor bleeding occurred in 555 patients (12.1%): 225 patients treated with bivalirudin (9.8%) and 330 patients treated with UFH (14.5%, p <0.001). There were 82 deaths (1.8%) within the first year after PCI: 29 deaths occurred in patients who had bled, and 53 deaths occurred in patients who had not bled (Kaplan-Meier estimates of 1-year mortality 5.2% and 1.3%, odds ratio 4.12, 95% confidence interval 2.59 to 6.54, p <0.001). One year after PCI, there were 15 deaths in patients who bled with bivalirudin versus 14 deaths in patients who bled with UFH (Kaplan-Meier estimates of 1-year mortality 6.7% vs 4.2%, odds ratio 1.61, 95% confidence interval 0.76 to 3.40, p = 0.20). Major bleeding occurred in 70 patients (3.0%) treated with bivalirudin and 104 patients treated with UFH (4.5%, p = 0.008). One-year mortality was 11.4% (n = 8) in patients with major bleeding with bivalirudin versus 4.8% (n = 5) in patients with major bleeding with UFH (p = 0.10). In conclusion, these data suggest that in patients with negative biomarkers undergoing PCI, bivalirudin decreases bleeding after PCI compared to UFH, without affecting 1-year mortality in those who had bled.

Prognostic value of minimal blood flow restoration in patients with acute myocardial infarction after reperfusion therapy.

PURPOSE: The prognostic impact of low-flow reperfusion after percutaneous coronary intervention (PCI) in patients with ST-segment elevation acute myocardial infarction (STEMI) is unknown. The aim of the study was to investigate the impact of low-flow reperfusion after PCI in patients with STEMI. METHODS: This study included 1,761 patients with STEMI with a baseline thrombolysis in myocardial infarction (TIMI) flow grade 0 and no collateral circulation to the infarcted region before primary PCI. The primary outcome was 1-year mortality. RESULTS: At the end of PCI procedure there were 115 patients with post-PCI TIMI flow grade 0; 57 patients with TIMI flow grade 1; 218 patients with TIMI flow grade 2; and 1,371 patients with TIMI flow grade 3. At 1 year there were 36 deaths in patients with TIMI grade 0; 28 deaths in patients with TIMI grade 1; 42 deaths in patients with TIMI grade 2; and 162 deaths in patients with TIMI grade 3 [estimates of mortality 32.6, 49.1, 19.6 and 12.1%, respectively; odds ratio (OR) = 1.76, 95% CI 1.08-2.86, P = 0.02, for TIMI flow grade 1 vs. TIMI flow grade 0]. The Cox proportional hazards model identified post-PCI TIMI flow grade as an independent predictor of 1-year mortality [hazard ratio (HR) = 1.99, 95% CI 1.17-3.28; P = 0.01 for TIMI flow grade 1 vs. TIMI flow grade 0]. CONCLUSIONS: Patients with STEMI with totally occluded infarct-related arteries and no collateral blood flow to the infarcted region show a greater mortality with post-PCI TIMI flow grade 1 than TIMI flow grade 0.

Serum potassium levels on admission and infarct size in patients with acute myocardial infarction.

BACKGROUND: Little data exist on the relationship between potassium level and infarct size after ST-segment elevation acute myocardial infarction (STEMI). We investigated the influence of potassium levels on infarct size measured with single photon emission computed tomography (SPECT) in patients with STEMI after mechanical reperfusion. METHODS: The study included 598 patients. Potassium measurements at baseline and 2 SPECT examinations, at baseline and 7-14 days after intervention, were performed. Infarct size in the 7-14 days SPECT and salvage index were the primary outcome analyses. RESULTS: Tertiles of baseline potassium were: <4.05 mEq/L (1st tertile), 4.05-4.37 mEq/L (2nd tertile) and >4.37 mEq/L (3rd tertile). In potassium 1st, 2nd and 3rd tertiles, the infarct size in the 7-14 days SPECT (median [25th-75th percentiles]) was 9.0% [2.0%-21.8%], 10.0% [3.5%-22.0%] and 12.0% [5.0%-25.5%] of left ventricle (p=0.026); salvage index was 0.50 [0.26-0.84], 0.56 [0.26-0.81] and 0.40 [0.23-0.75] (p=0.09). Patients with anterior infarction in upper potassium tertile had greater infarct size compared with patients in lower potassium tertile (p=0.049). After adjustment in multivariable analysis, potassium was an independent correlate of infarct size in the 7-14 days SPECT (p=0.05). CONCLUSIONS: In patients with STEMI, higher baseline potassium levels are associated with a larger scintigraphic infarct size.

Patterns of presentation and outcomes of patients with acute coronary syndromes.

OBJECTIVES: We undertook this study to assess the relationship between presentation pattern and mortality in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention. METHODS: This registry included 10,455 patients with ACS, of whom 2,853 patients had ST-segment elevation myocardial infarction(STEMI), 3,060 patients had non-ST-segment elevation myocardial infarction (NSTEMI) and 4,542 patients had unstable angina. The primary outcome was 1-year mortality. RESULTS: At 1 year there were 976 deaths, 390 (13.7%) among STEMI patients, 366 (12.0%) among NSTEMI patients and 220 (4.8%) among patients with unstable angina (OR = 1.17, 95% CI 1.01-1.35 for STEMI vs. NSTEMI; OR = 3.00, 95% CI 2.56-3.51 for STEMI vs. unstable angina, and OR = 2.58, 95% CI 2.20-3.04 for NSTEMI vs. unstable angina). In the Cox proportional hazards model ACS form was an independent correlate of 1-year mortality (HR = 0.90, 95% CI 0.73-1.13 for STEMI vs. NSTEMI; HR = 1.56, 95% CI 1.13-2.14 for STEMI vs. unstable angina; HR = 1.72, 95% CI 1.30-2.29 for NSTEMI vs. unstable angina). CONCLUSIONS: The presentation pattern affects 1-year mortality in patients with ACS, with unadjusted mortality being highest in patients with STEMI and lowest in patients with unstable angina.

Total leucocyte count, but not C-reactive protein, predicts 1-year mortality in patients with acute coronary syndromes treated with percutaneous coronary intervention.

Although an association between elevated leucocyte count and mortality in patients with ACS (acute coronary syndromes) has been established, the independence of this association from coronary risk factors and C-reactive protein has been inadequately studied. In the present study, this prospective registry included 4329 patients with ACS treated with PCI (percutaneous coronary intervention): 1059 patients with STEMI [ST-segment elevation MI (myocardial infarction)], 1753 patients with NSTEMI (non-STEMI) and 1517 patients with unstable angina. Blood samples were obtained before angiography for leucocyte count and C-reactive protein measurements. The primary outcome of this analysis was 1-year mortality. At 1 year, 345 patients (8%) had died: 45 patients in the 1st tertile, 93 patients in the 2nd tertile and 207 patients in the 3rd tertile of leucocyte count [Kaplan-Meier estimates of mortality, 3.2%, 6.4% and 14.1% with an OR (odds ratio)=2.42, 95% CI (confidence interval)1.78-3.12; P<0.001 for tertile 3 compared with tertile 2 and an OR=1.99, 95% CI 1.77-2.25; P<0.001 for tertile 2 compared with tertile 1]. The Cox proportional hazards model adjusting for coronary risk factors, ACS presentation, extent of coronary artery disease, C-reactive protein and other covariates identified leucocyte count with a HR (hazard ratio)=1.05 (95% CI 1.02-1.07; P<0.001 for 1000 cells/mm(3) increase in the leucocyte count), but not C-reactive protein (HR=1.13, 95% CI 0.95-1.34; P=0.15 for a 1 tertile increase in the C-reactive protein concentration) as an independent correlate of 1-year mortality. We conclude that elevated leucocyte count, but not C-reactive protein, predicts 1-year mortality independent of cardiovascular risk factors across the entire spectrum of patients with ACS treated with PCI.

Prognostic significance of epicardial blood flow before and after percutaneous coronary intervention in patients with acute coronary syndromes.

OBJECTIVES: The aim of the study was to assess the relationship between baseline and post-procedural Thrombolysis In Myocardial Infarction (TIMI) epicardial blood flow grade and mortality in patients with acute coronary syndromes (ACS) who were treated with early percutaneous coronary intervention (PCI). BACKGROUND: The impact of baseline and post-procedural TIMI flow grade on mortality in patients with ACS has been insufficiently studied. METHODS: This prospective registry included 10,455 patients with ACS who underwent coronary angiography and PCI: 2,853 patients with ST-segment elevation acute myocardial infarction, 3,060 patients with non-ST-segment elevation acute myocardial infarction, and 4,542 patients with unstable angina. The primary outcome was 1-year mortality. RESULTS: At 1 year, there were 976 deaths: 117 deaths among patients with TIMI flow grade 0 to 1, 105 deaths among patients with TIMI flow grade 2, and 754 deaths among patients with TIMI flow grade 3 (Kaplan-Meier estimates of mortality 28.3%, 18.4%, and 8.0%, respectively; odds ratio: 1.66, 95% confidence interval [CI]: 1.57 to 1.76, p < 0.001, for TIMI flow grade 0 to 1 vs. TIMI flow grade 2 and odds ratio: 2.51, 95% CI: 2.06 to 3.06, p < 0.001, for TIMI flow grade 2 vs. TIMI flow grade 3). By using the Cox proportional hazards survival model, we identified post-PCI TIMI flow grade (hazard ratio: 0.60, 95% CI: 0.52 to 0.70; p < 0.001, for 1 grade increase in TIMI flow grade) but not baseline TIMI grade (hazard ratio: 1.08, 95% CI: 0.96 to 1.22; p = 0.20, for 1 grade increase in TIMI flow grade) as an independent correlate of 1-year mortality. CONCLUSIONS: In patients with ACS treated with early PCI, post-procedural TIMI flow grade but not baseline TIMI flow grade is an independent correlate of 1-year mortality.

Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques.

OBJECTIVES: To measure circulating levels of oxidized-low-density lipoproteins (ox-LDL) in patients with stable and unstable angina and controls, and to investigate their correlation with the extent of coronary artery disease (CAD) and the presence of complex plaques at coronary angiography. METHODS AND RESULTS: Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina (UA, n=26), stable angina (SA, n=29) and in controls (C, n=27). All patients underwent coronary angiography. The extent of CAD was evaluated using a quantitative score, while the presence of complex, vulnerable plaques was angiographically assessed. Ox-LDL were higher in UA patients than in SA patients and in C subjects, and in SA patients than in C subjects (C, 45.6+/-12.8 U/L; SA, 58.8+/-11.0 U/L; UA, 73.7+/-13.6 U/L; p<0.001). No correlation was found with the extent of atherosclerotic disease in the coronary tree. Patients with angiographic complex lesions showed significantly higher levels of ox-LDL (68.4+/-13.9 U/L versus 55.2+/-16.4 U/L, p<0.001). Multiple regression analysis showed that ox-LDL were independent predictors of the presence of complex plaques (p<0.023). CONCLUSIONS: Ox-LDL levels are higher in unstable patients and correlate with the presence of angiographically documented complex plaques. Ox-LDL might be markers of destabilization of CAD.

Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina.

OBJECTIVES: The purpose of this study was to investigate the effect of circulating levels of oxidized low-density lipoprotein (ox-LDL) on nuclear factor-kappa B (NF-kB) activation in peripheral blood mononuclear cells (PBMC) of patients with unstable angina (UA) or stable angina (SA) and control subjects. BACKGROUND: Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions. METHODS: Levels of plasma ox-LDL and circulating NF-kB in PBMC (and in separated lymphocytes and monocytes) were measured in 27 control subjects and 29 SA and 27 UA patients. In in vitro studies, the effect of ox-LDL and of the sera derived from a subgroup of UA patients and control subjects on monocytic NF-kB activation was also evaluated. RESULTS: The UA and SA patients had higher levels of circulating ox-LDL and NF-kB in PBMC than control subjects (p < 0.001). The increase in circulating NF-kB was mainly due to the activation of monocytes. In the in vitro studies, ox-LDL dose-dependently increased the activation of NF-kB in monocytes, but not in lymphocytes derived from healthy volunteers. This increase was related to the expression of lectin-like ox-LDL receptor-1 on monocytes. The incubation of monocytes with the sera derived from the UA patients induced a significant increase in NF-kB activation compared with the sera derived from the control subjects. CONCLUSIONS: The data suggest that the activation of NF-kB in monocytes of UA patients is, at least in part, induced by circulating molecules such as ox-LDL, which has been found to be particularly elevated in UA patients.