Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study

Purpose

The study purpose was to evaluate the ability of 6 biomarkers to improve the prediction of cardiovascular events among persons with established coronary artery disease.

Background

Cardiovascular risk algorithms are designed to predict the initial onset of coronary artery disease but are less effective in persons with preexisting coronary artery disease.

Methods

We examined the association of N-terminal prohormone brain natriuretic peptide (Nt-proBNP), cystatin C, albuminuria, C-reactive protein (CRP), interleukin-6, and fibrinogen with cardiovascular events in 979 Heart and Soul Study participants with coronary artery disease after adjusting for demographic, lifestyle, and behavior variables; cardiovascular risk factors; cardiovascular disease severity; medication use; and left ventricular ejection fraction. The outcome was a composite of stroke, myocardial infarction, and coronary heart disease death during an average of 3.5 years of follow-up.

Results

During follow-up, 142 participants (15%) developed cardiovascular events. The highest quartiles (vs lower 3 quartiles) of 5 biomarkers were individually associated with cardiovascular risk after multivariate analysis: Nt-proBNP hazard ratio (HR) = 2.13 (95% confidence interval [CI], 1.43-3.18); cystatin C HR = 1.72 (95% CI, 1.10-2.70); albuminuria HR = 1.71 (95% CI, 1.15-2.54); CRP HR = 2.00 (95% CI, 1.40-2.85); and interleukin-6 HR = 1.76 (95% CI, 1.22-2.53). When all biomarkers were included in the multivariable analysis, only Nt-proBNP, albuminuria, and CRP remained significant predictors of events: HR = 1.88 (95% CI, 1.23-2.85), HR = 1.63 (95% CI, 1.09-2.43), and HR = 1.82 (95% CI, 1.24-2.67), respectively. The area under the receiver operator curve for clinical predictors alone was 0.73 (95% CI, 0.68-0.78); adding Nt-proBNP, albuminuria, and CRP significantly increased the area under the receiver operator curve to 0.77 (95% CI, 0.73-0.82, P <.005).

Conclusion

Among persons with prevalent coronary artery disease, biomarkers reflecting hemodynamic stress, kidney damage, and inflammation added significant risk discrimination for cardiovascular events.     

Serum B-type natriuretic peptide levels on admission predict not only short-term death but also angiographic success of procedure in patients with acute ST-elevation myocardial infarction treated with primary angioplasty

Background

B-type natriuretic peptide (BNP) levels are predictive of short-term death in patients with acute coronary syndromes. Few data are available for BNP levels obtained on admission in patients with acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods

Blood samples for BNP estimation, obtained on admission in 126 consecutive patients (mean age, 58.8 ± 10.7 years) with STEMI, were measured at the bedside by using a simple point-of-care test in a 15-minute period before PCI. Follow-up up to 42 days was performed.

Results

A baseline BNP value of 331 pg/mL had a sensitivity of 87.9% and a specificity of 90% for predicting death in a follow-up study. There was no difference in subgroups by median BNP (100 pg/mL) in Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 before PCI, although higher BNP levels were observed among patients with TIMI <3 after PCI than among those with TIMI 3 (356.7 ± 350.8 vs 144.9 ± 191.2 pg/mL; P < .0001). In multivariate logistic regression analysis, admission BNP was the independent predictor for the following: death (odds ratio [OR], 16.3; 95% confidence interval [CI], 1.4 to 186.7; P = .03), TIMI grade <3 after PCI (OR, 3.4; 95% CI, 1.2 to 9.6; P = .02), and the no-reflow phenomenon (OR, 6.2; 95% CI, 1.7 to 23; P = .007) after adjusting for other variables.

Conclusions

BNP levels obtained on admission are a powerful, independent predictor of short-term death and angiographic success after PCI in patients with STEMI. The no-reflow phenomenon may be predicted in STEMI on the basis of high serum BNP values on admission.     

Serologic markers of persistent Chlamydia pneumonia infection and long-term prognosis after successful coronary stenting

Background

Previous studies have shown an incremental role of inflammation in late prognosis following coronary stenting (CS). In particular, high preprocedural levels of plasma C-reactive protein (CRP) have been related to increased hazard of late ischemic complications. Persistent Chlamydia pneumoniae (Cp) infection, detected by positive IgA anti-Cp titers, may be associated with this inflammatory process and portend a high risk of late adverse prognosis after CS.

Methods

A total of 483 consecutive patients with either stable or unstable coronary syndromes were followed-up for 1 year after successful CS. The composite of cardiac death, myocardial infarction, rehospitalization for rest-unstable angina, and exertional angina, whichever occurred first, was the clinical end point. Additionally, the rate of in-stent restenosis and progression of coronary artery disease during this period were evaluated. Anti-Cp titers and plasma CRP levels were measured before the procedure.

Results

Positive immunoglobulin A (IgA), but not positive immunoglobulin G (IgG), titers were significantly associated with high plasma CRP levels in patients with unstable coronary syndromes (P = .005), but not in those with stable angina (P = .7). Moreover, positive IgA titers were significantly related to increased risk of both the composite clinical end point (P = .04) and progression of coronary artery disease (P < .001) in patients with unstable coronary syndromes but not in those with stable angina. Neither positive IgA nor positive IgG titers were associated with the rate of in-stent restenosis.

Conclusions

Persistent Cp infection may drive an inflammatory response in the coronary vasculature and portends an adverse late outcome after CS in patients with unstable coronary syndromes.     

Prognostic stratification of patients with left-sided endocarditis determined at admission

Background

The prognosis of patients with left-sided endocarditis remains poor despite the progress of surgical techniques. Identification of high-risk patients within the first days after admission to the hospital would permit a more aggressive therapeutic approach.

Methods

We designed a prospective multicenter study to find out the clinical, microbiologic, and echocardiographic characteristics available within 72 hours of admission that might define the profile of high-risk patients. Of 444 episodes, 317 left-sided endocarditis cases were included and 76 variables were assessed. Events were surgery in the active phase of the disease and in-hospital death. A stepwise logistic regression analysis was undertaken to determine variables predictive of events.

Results

Multivariate analysis of the clinical variables found to have statistical significance in the univariate analysis identified the following as predictive: patient referred from another hospital (odds ratio [OR]: 1.8; confidence interval [CI], 1.1-2.9), atrioventricular block (OR: 2.5; CI, 1.1-5.9), acute onset (OR: 1.7; CI, 1.1-2.9), and heart failure at admission (OR: 2.3; CI, 1.4-3.8). When the echocardiographic and microbiological variables statistically significant in the univariate analysis were introduced, the presence of heart failure at admission (OR: 2.9; CI, 1.8-4.8), periannular complications (OR: 1.8; CI, 1.1-3.1), and Staphylococcus aureus infection (OR: 2.0; CI, 1.1-3.8) retained prognostic power. Risk could be accurately stratified when combining the 3 variables with predictive power: 0 variables present: 25% of risk; 1 variable present: 38% to 49% of risk; 2 variables present: 56% to 66% of risk; and 3 variables present: 79% of risk.

Conclusions

The risk of patients with left-sided endocarditis can be accurately stratified with the assessment of variables easily available within 72 hours of admission to the hospital.     

Activated factor 12 (FXIIa) predicts recurrent coronary events after an acute myocardial infarction

Background

Activated factor XII (FXIIa) is involved in vascular injury and repair, participating in inflammation, thrombosis, and fibrinolysis. We wanted to test the hypothesis that FXIIa may predict an acute coronary syndrome (ACS) after a myocardial infarction (MI) and to evaluate whether FXIIa is related to global markers of end-stage coagulation and inflammation, including fibrin monomer (FM) and ultrasensitive C-reactive protein (μCRP).

Methods

In a prospective study of 300 patients with acute MI, we evaluated the predictive value of FXIIa in blood samples drawn 4 to 6 days after admission. Cardiac death, re-MI, and troponin-T-positive unstable angina pectoris were registered during a median follow-up period of 1.5 years.

Results

In the upper quartile of FXIIa (Q4) (≥2.23 ng/mL) 32.0% of patients had an ACS as compared with 16.9% of patients with FXIIa in the three lower quartiles (Q1-3, P = .008). Relative risk of recurrent ACS for patients with FXIIa in the Q4 as compared with Q1-3 was 1.89 (95% CI, 1.22 to 2.93). A secondary ACS occurred earlier in patients with FXIIa in the Q4 as compared with those with FXIIa in the Q1-3 (P = .0039). Conventional risk factors as potential confounders were not associated with time to event. FXIIa did not correlate with FM or μCRP, and the FM and μCRP levels were of a similar magnitude in the Q4 as compared with the Q1 and the Q1-3 of FXIIa.

Conclusions

FXIIa predicts recurrent coronary events after MI. The prognostic ability of FXIIa was not reflected by markers of hypercoagulability or inflammation.     

Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes

Background

Coronary artery disease (CAD) and, increasingly, diabetes are recognized as having an inflammatory basis. Membrane toll-like receptors (TLRs) activate signaling pathways that up-regulate inflammation. We evaluated whether the Asp299Gly polymorphism in the TLR4 gene, which impairs inflammatory responses, is associated with reduced vascular inflammation (assessed by C-reactive protein [CRP]) and a decreased risk for CAD and diabetes.

Methods

1894 patients without acute myocardial infarction undergoing coronary angiography were studied. Genotyping was performed by real-time polymerase chain reaction. CAD was defined as ≥70% stenosis. Diabetes was diagnosed by patients' referring physicians. CRP was measured by fluorescence polarization immunoassay. Regression analyses adjusted for traditional cardiac risk factors.

Results

Patients averaged 64 ± 11 years of age, and 69% were male. Asp299Gly genotype frequencies were: AA = 0.911 (n = 1725), AG = 0.086 (n = 164), and GG = 0.003 (n = 5), in keeping with Hardy-Weinberg equilibrium. CRP was lower among G-allele carriers (median = 1.11 mg/dL) than wild-type (AA) subjects (1.23 mg/dL, adjusted P = .044). G-allele carriers also had a lower prevalence of CAD (65% vs. 73%, OR = 0.67, CI = 0.46-0.99, adjusted P = .048) and diabetes (11% vs. 18%, OR = 0.63, CI = 0.42-0.95, adjusted P = .029), which persisted in multivariate logistic regression analyses. 299Gly carriage did not affect clinical outcomes nor interact with statin therapy.

Conclusions

The TLR4 299Gly allele was associated with reduced CRP levels and, in parallel, a decreased risk of angiographic CAD and clinical diabetes. These findings suggest that down-regulation of innate immune responsiveness could beneficially modify CAD and diabetes risk and might provide a novel basis for genetic risk stratification and therapeutic targeting.     

Benefits of direct angioplasty for women and men with acute myocardial infarction: results of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B) Angioplasty Substudy

Background

Direct angioplasty (PTCA) and thrombolytic therapy are the chief therapies for treating an ST-segment elevation myocardial infarction (MI).

Objective

This study was designed to evaluate sex differences in the relative benefit of direct PTCA versus thrombolytic therapy among patients enrolled in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes Angioplasty (GUSTO II-B PTCA) Substudy.

Methods

Women and men presenting with an acute ST-segment elevation MI were randomized to receive either direct PTCA or accelerated tissue plasminogen activator (t-PA). Patients were then randomized to treatment with either heparin or bivalirudin. A gender analysis of outcome was performed.

Results

Women were older than men (68.6 ± 11.5 vs 59.5 ± 12.0 years, P < .001) and were more likely to have diabetes (22.5% vs 13.5%, P <.0001) and hypertension (53.3% vs 34.8%, P = .001). After adjusting for differences in baseline variables, the odds ratio (OR) for reaching a 30-day clinical end point (death, nonfatal infarction, or nonfatal disabling stroke) was similar for women and men (1.35, 95% CI 0.88-2.08). The OR for reaching a clinical end point at 30 days for the PTCA-treated women compared with the t-PA-treated women was 0.685 (95% CI 0.36-1.32) and similar to the OR in men, 0.565 (95% CI 0.35-0.91), P for interaction = .535. Because women had a higher event rate than men, the absolute number of major events prevented when treating women with direct PTCA was higher than men (56 events/1000 women treated with PTCA vs 42 events per 1000 men treated with PTCA).

Conclusions

Although the relative benefit of direct PTCA to t-PA for the treatment of an acute MI appears to be similar in women and men, women may derive a larger absolute benefit from direct PTCA.     

Prognostic value of admission glucose in non-diabetic patients with myocardial infarction

Background

Patients with acute myocardial infarction (AMI) who have diabetes have an increased risk of death. In nondiabetic patients, admission glucose levels may be a predictor of survival. However, data regarding admission glucose and long-term outcome in nondiabetic patients treated with reperfusion therapy for AMI are limited.

Methods

We investigated long-term clinical outcome in 356 consecutive nondiabetic patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention or thrombolysis as reperfusion therapy. Mean follow-up time was 8 ± 2 years. The patients were divided on the basis of admission glucose level: group 1, <7.8 mmol/L; group 2, 7.8 to 11.0 mmol/L; and group 3, ≥11.1 mmol/L.

Results

Mortality rate in group 1 (n = 163) was 19.0%; in group 2 (n = 151), 26.5%; and in group 3 (n = 42), 35.7% (P < .05). Higher glucose levels were associated with larger enzymatic infarct sizes (P < .01) and more reduced residual left ventricular function (P < .05). Multivariate analysis showed that Killip class >1 at admission (OR, 2.9; 95% CI, 1.7 to 5.0; P < .001), age ≥60 years (OR, 2.4; 95% CI, 1.5 to 4.0, P = .001), thrombolysis as compared with percutaneous coronary intervention (OR, 1.7; 95% CI, 1.1 to 2.7, P = .02), admission glucose category (OR, 1.4; 95% CI, 1.0 to 1.9, P = .04), and anterior location (OR, 1.6; 95% CI, 1.0 to 2.6, 0.03) were independent predictors of long-term clinical outcome.

Conclusions

Elevated admission glucose levels in nondiabetic patients treated with reperfusion therapy for ST-segment elevation myocardial infarction are independently associated with larger infarct size and higher long-term mortality rates.     

N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease

Purpose

C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) provide prognostic information in patients with stable coronary heart disease. The aim of the study was to investigate whether combined use of NT-proBNP and CRP improves risk stratification in these patients.

Methods

This cohort study included 989 patients with stable coronary heart disease who underwent coronary stenting. CRP and NT-proBNP were measured before angiography. The primary end point of the study was all-cause mortality. Using median values of NT-proBNP (279.9 ng/L) and CRP (1.2 mg/L), patients were divided into 4 groups: low NT-proBNP-low CRP group (305 patients with NT-proBNP<median and CRP<median); low NT-proBNP-high CRP group (190 patients with NT-proBNP<median and CRP≥median; high NT-proBNP-low CRP group (237 patients with NT-proBNP≥median and CRP<median); and high NT-proBNP-high CRP group (257 patients with NT-proBNP≥median and CRP≥median).

Results

During a median follow-up of 3.6 years (interquartile range 3.3 to 4.5 years), there were 85 deaths: 6 deaths in the low NT-proBNP-low CRP group, 11 deaths in the low NT-proBNP-high CRP group, 20 deaths in the high NT-proBNP-low CRP group, and 48 deaths in the high NT-proBNP-high CRP group with Kaplan-Meier mortality estimates of 2.7%, 8.9%, 12.1% and 35.6%, respectively (P <.001). Cox proportional hazards model showed that combination NT-proBNP-CRP was the strongest independent correlate of mortality (hazard ratio [HR] 4.3, 95% confidence interval [CI], 2.0-9.3; P <.001 for high NT-proBNP-high CRP vs low NT-proBNP-low CRP).

Conclusion

Combined use of NT-proBNP and CRP improves long-term risk prediction of mortality in patients with stable coronary heart disease.     

GuardWire emboli protection device is associated with improved myocardial perfusion grade in saphenous vein graft intervention

Background

Use of emboli protection devices (EPD) during saphenous vein graft percutaneous coronary intervention (SVG-PCI) has been proven to reduce major adverse cardiac events (MACE). However, the impact of EPD on the microcirculation using Thrombolysis in Myocardial Infarction myocardial perfusion grade (TMP) has not been fully characterized. We sought to analyze TMP after SVG-PCI with and without EPD and determine its impact on inhospital MACE.

Methods

From August 2001 to December 2002, 305 patients had SVG-PCI suitable for EPD; 210 (69%) had an angiogram appropriate for TMP evaluation. Of those, 46 (22%) had an EPD (GuardWire, Medtronic, Minneapolis, Minn) deployed during the coronary intervention. Both groups were similar with regard to most demographic and clinical features.

Results

A TMP score of 2.5 or 3 was obtained in 98% of the EPD group versus 85% of the unprotected SVG-PCI (P = .01). There was a trend towards reduction in MACE when using EPD (15% vs 27%, respectively, P = .07). Peak postprocedural creatine kinase-MB was somewhat lower in the EPD group (6.03 ± 7.8 ng/mL vs 14.87 ± 42 ng/mL, P = .17) Patients with a TMP grade of 2.5 or 3 had a statistically significant reduction in MACE (OR 0.36, 95% CI 0.14-0.87, P = .02).

Conclusions

Compared with SVG-PCI without emboli protection, EPD significantly improved TMP and trended towards a reduction in MACE.     

The Association between Smoking and Low Back Pain: A Meta-analysis

Objective

To assess the association between smoking and low back pain with meta-analysis.

Methods

We conducted a systematic search of the MEDLINE and EMBASE databases until February 2009. Eighty-one studies were reviewed and 40 (27 cross-sectional and 13 cohort) studies were included in the meta-analyses.

Results

In cross-sectional studies, current smoking was associated with increased prevalence of low back pain in the past month (pooled odds ratio [OR] 1.30, 95% confidence interval [CI], 1.16-1.45), low back pain in the past 12 months (OR 1.33, 95% CI, 1.26-1.41), seeking care for low back pain (OR 1.49, 95% CI, 1.38-1.60), chronic low back pain (OR 1.79, 95% CI, 1.27-2.50) and disabling low back pain (OR 2.14, 95% CI, 1.11-4.13). Former smokers had a higher prevalence of low back pain compared with never smokers, but a lower prevalence of low back pain than current smokers. In cohort studies, both former (OR 1.32, 95% CI, 0.99-1.77) and current (OR 1.31, 95% CI, 1.11-1.55) smokers had an increased incidence of low back pain compared with never smokers. The association between current smoking and the incidence of low back pain was stronger in adolescents (OR 1.82, 95% CI, 1.42-2.33) than in adults (OR 1.16, 95% CI, 1.02-1.32).

Conclusions

Our findings indicate that both current and former smokers have a higher prevalence and incidence of low back pain than never smokers, but the association is fairly modest. The association between current smoking and the incidence of low back pain is stronger in adolescents than in adults.     

Factors associated with failure to identify the culprit artery by the electrocardiogram in inferior ST-elevation myocardial infarction

Background

Right and left circumflex coronary artery occlusions cause inferior myocardial infarction. To improve the targeting of diagnostic and therapeutic measures individually, factors interfering with identification of the culprit artery by the electrocardiogram (ECG) were explored.

Methods

Patients with inferior preinfarction syndrome (n = 266) were included to the Danish Trial in Acute Myocardial Infarction-2 substudy. The culprit vessel was predicted by the ECG, and findings were correlated with angiography. Factors associated with false identification of the culprit artery by the ECG were examined.

Results

Electrocardiogram criteria for right coronary artery occlusion to predict coronary angiography findings had sensitivity, specificity, and positive and negative predictive values of 95%, 52%, 84%, and 81%. For left circumflex coronary artery occlusion, the corresponding values were 51%, 93%, 70%, and 85%, respectively. False ECG identification of the culprit artery was independently associated with left coronary dominance (P < .001; odds ratio [OR], 22.0; 95% confidence interval [CI], 7.2-67.0), multivessel disease (P = .035; OR, 2.2; 95% CI, 1.1-4.7), and absence of proximal occlusion pattern in the ECG (P = .003; OR, 4.0; 95% CI, 1.6-9.8).

Conclusions

Left coronary artery dominance, multivessel disease, and absence of ECG signs of proximal culprit lesion are associated with failure to predict the culprit artery of inferior myocardial infarction by the 12-lead ECG.     

Myonecrosis and inflammatory response following percutaneous coronary angioplasty. A protective role for betablockers?

Introduction

Percutaneous coronary intervention (PCI) is widely used actually for the treatment of coronary disease. Stent implantation in the vessel wall is associated with local healing processes and some myonecrosis. However, little is known about the relationships between systemic inflammatory response, myonecrosis and the patient's and procedural characteristics.

Objectives

(i) To evaluate the level of C-Reactive Protein (hsCRP) and cardiac troponin I (cTnI) elevation after PCI; (ii) to determine the patient's and procedural factors associated with those elevations.

Method

This is a prospective monocentric study carried out in patients hospitalised for elective PCI or for ACS without cTnI elevation. CRP and cTnI were assessed before, after and 24 hours after the procedure.

Results

Thirty-four patients (mean age 64 ± 10.9 years; sex ratio 28 males/six females) were included. hsCRP increased in 26 patients (76.4%) and cTnI in 16 patients (47%) after PCI. cTnI elevation did not correlate with inflammatory response. Whereas none of the studied parameters were statistically linked with hsCRP increase, cTnI elevation was significantly associated with AHA-ACC B₂/C type lesion, the number and the total length of stents implanted, the duration of procedure and treatment by betablockers. Multivariate analysis showed that the independent predictors of cTnI elevation were procedure duration (p = 0.032 OR = 14.2 CI 95% 7.69-100) and the absence of pretreatment with betablockers (p = 0.036, OR = 2,6 CI 95% 1.35-35).

Conclusion

cTnI elevation following PCI is very frequent and related with the duration of the procedure. Our data suggest a protective role of betablockers in the occurrence of cTnI elevation after PCI. Confirmation of the protective role of betablockers in larger cohort is mandatory.     

Limitations of biomarkers serum levels during pulmonary vein isolation

Introduction and objectives

Several biomarkers have been used for evaluation and quantification of myocardial injury after effective ablation. We studied possible different thermal stability and usability of the proteins released by cardiac cells injured by different energy sources.

Methods

Firstly, we tested in vitro thermal stability of creatinine kinase (CK), myocardial bound creatinine kinase (CKMB), cardiac troponins I (cTnI) and cardiac troponins T (cTnT) in collected blood samples from 15 patients (pts) with confirmed ST-segment elevated myocardial infarction (STEMI). Secondly, the biomarkers were collected and analyzed in 82 pts treated with radiofrequency ablation (RFA) and in 79 pts treated with cryo-balloon ablation (CBA).

Results

In vitro experiment showed that all biomarkers were stable in low temperature of -30^oC. Troponins were stable in the high temperatures analyzed. A substantial drop in CK and CKMB levels were measured at 50 °C and 40° C, respectively. In vivo study showed that the increase in CKMB levels was highly significant in CBA pts only. Pathological CKMB values were observed in 24% of RFA pts and 98% of CBA pts. Pathological cTnI values were observed in all pts and the rise in cTnI levels was highly significant in both groups after ablation.

Conclusions

Both in vitro and in vivo results show that CKMB cannot be used for quantitative determination of myocardial injury produced by radiofrequency energy. Only cardiac troponins reflect myocardial injury, regardless of energy source, and may be considered in future studies for comparison of biomarkers effects of cryo versus radiofrequency ablation.Full English text available from: www.revespcardiol.org     

Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial

Background

The efficacy of statin drugs after an acute coronary event is now well established, but the evidence for statin use in the early treatment of acute coronary events remains unclear.

Methods

We tested the effects of administering pravastatin within 24 hours of the onset of symptoms in patients with unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. Patient recruitment of 10,000 with 1200 end points was planned, but the trial was stopped early. A total of 3408 patients were randomly assigned to treatment with pravastatin (1710 patients) or matching placebo (1698 patients). Treatment was continued for 4 weeks. The primary end point of the study was a composite of death, recurrence of myocardial infarction, or readmission to hospital for unstable angina within 30 days of random assignment.

Results

The primary end point occurred in 199 of patients allocated to pravastatin (11.6%) and in 211 patients allocated to placebo (12.4%). A relative risk reduction of 6.4% favored allocation to pravastatin but was not statistically significant (95% CI, −13.2% to 27.6%). No adverse effects were seen.

Conclusions

We conclude that 20 to 40 mg of pravastatin can be safely administered within 24 hours of the onset of symptoms of an acute coronary event, with a favorable but not significant trend in outcome at 30 days compared with placebo.     

The relationship of serum erythropoietin level with coronary collateral grade

Background

Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade.

Methods

Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II.

Results

The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals.

Conclusions

Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.     

Efficacy and safety of abciximab on acute myocardial infarction treated with percutaneous coronary interventions: a meta-analysis of randomized, controlled trials

Objective

To evaluate the efficacy and safety of abciximab following acute myocardial infarction (AMI) treated with percutaneous coronary interventions.

Methods

A meta-analysis of randomized controlled trials of platelet glycoprotein IIb/IIIa inhibitor abciximab as adjunctive therapy to percutaneous coronary interventions for AMI was performed. Main outcomes measured were: (1) mortality, (2) reinfarction, (3) target vessel revascularization (TVR), (4) major cardiac events (MACE) that were a composite endpoint of death, reinfarction, and TVR, and (5) major bleeding.

Results

Six trials randomized 3755 patients who were followed for a mean of 5.5 months. Compared with the control, abciximab significantly reduced mortality (OR 0.70, 95% CI 0.50-0.97), TVR (0.79, 95% CI 0.65-0.96) and MACE (0.76, 95% CI 0.65-0.90). Reduction on TVR and MACE was confirmed in stent patients, but not in balloon angioplasty patients. Abciximab was associated with an increased risk of major bleeding (OR 1.39, 95% CI 1.03-1.87), but bleeding was observed only with a 100U/kg heparin bolus followed by a maintenance infusion (OR 1.89, 95% CI 1.10-3.28) and not with a bolus of 70U/kg (OR 1.22, 95% CI 0.85-1.73).

Conclusions

Abciximab, as adjunctive therapy to percutaneous coronary interventions, reduces mortality, TVR and MACE following AMI. The reduction of clinical outcomes occurs with stent implantation but not with balloon angioplasty. A 70U/kg heparin bolus must be used to avoid major bleeding.     

C-reactive protein is an independent predictor of severity in community-acquired pneumonia

Background

C-reactive protein (CRP) is an acute phase protein synthesized by the liver primarily in response to interleukin-6. Initial studies have suggested that inflammatory markers may have a role in predicting severity. We investigated whether admission and day 4 CRP could predict severity in community-acquired pneumonia.

Methods

A prospective study was carried out over a 2-year period in a large teaching hospital. CRP was measured on admission and on day 4. The outcomes of interest were: 30-day mortality; need for mechanical ventilation and/or inotropic support; development of complicated pneumonia (lung abscess, empyema, or complicated parapneumonic effusion); the value of predictive tests were assessed using multivariate logistic regression.

Results

There were 570 patients included in the study; 30-day mortality was 9.6%. Low CRP levels showed a high negative predictive value for excluding 30-day mortality (CRP <10 mg/L = 100%, CRP <50 = 99.1%, CRP <100 = 98.9%, CRP <200 = 94.9%). Low admission CRP levels <100 mg/L were independently associated with reduced 30-day mortality (odds ratio [OR] 0.18; 0.04-0.85), P = .03; need for mechanical ventilation and/or inotropic support (OR 0.21; 0.14-0.4), P = .002; and complicated pneumonia (OR 0.05; 0.01-0.35), P = .003. A CRP that fails to fall by 50% or more within 4 days of admission is independently associated with increased 30 day mortality (OR 24.5; 6.4-93.4), P <.0001; need for mechanical ventilation and/or inotropic support (OR 7.1; 2.8-17.8), P <.0001 and complicated pneumonia (OR 15.4; 6.32-37.6), P <.0001.

Conclusions

Admission CRP <100 mg/L has reduced risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. Failure of CRP to fall by 50% or more at day 4 leads to an increased risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. C-reactive protein is an independent marker of severity in community-acquired pneumonia.     

Selective serotonin reuptake inhibitor use by patients with acute coronary syndromes

Background

Selective serotonin reuptake inhibitors are commonly used to treat anxiety, depression, and other conditions that commonly affect patients with coronary artery disease. Selective serotonin reuptake inhibitors inhibit platelet activation and may, therefore, affect outcomes in patients with acute coronary syndromes.

Methods

A retrospective study was performed of 1254 patients with acute coronary syndromes comparing in-hospital bleeding and cardiac event rates in 158 patients who received a selective serotonin reuptake inhibitor and a propensity score-matched group of patients who did not. All patients were treated with a glycoprotein IIb/IIIa inhibitor and almost all also received aspirin, clopidogrel, and heparin.

Results

Patients who received a selective serotonin reuptake inhibitor were significantly more likely to experience any bleeding (37.3% vs 26.6%, OR 1.65, 95% confidence interval (CI), 1.02-2.66, P =.04) and significantly less likely to experience recurrent myocardial ischemia, heart failure, or asymptomatic cardiac enzyme elevation while in the hospital (7.0% vs 13.9%, OR 0.46, 95% CI, 0.22-0.99, P =.04). No differences were observed in death, myocardial infarction during the hospitalization, urgent revascularization, or major bleeding. Bleeding and cardiac events were not affected by antidepressants other than selective serotonin reuptake inhibitors.

Conclusions

Selective serotonin reuptake inhibitor use during a hospitalization for an acute coronary syndrome is associated with reduced rates of recurrent ischemia, heart failure, or cardiac enzyme elevation at the expense of increased bleeding in patients receiving maximal conventional antiplatelet medications and heparin. Clinicians should be aware of this association when treating patients with an acute coronary syndrome.     

Hormone therapy, C-reactive protein, and progression of atherosclerosis: data from the Estrogen Replacement on Progression of Coronary Artery Atherosclerosis (ERA) trial

Objective

To compare the effects of estrogen and estrogen plus progestin on levels of C-reactive protein (CRP) and interleukin-6 (IL-6), and to examine the relationship between these changes and progression of angiographically defined coronary disease.

Methods

Baseline and follow-up (year 1 and year 3) plasma levels of IL-6 and CRP were measured in a subset of 232 patients from the Estrogen Replacement in Atherosclerosis (ERA) trial.

Results

Serial angiograms were also available at baseline and closeout. Estrogen alone increased CRP by 40% (P = .01) at 1 year and 38% P = .002) at closeout. Estrogen plus medroxyprogesterone acetate increased CRP by 44.7% P = .001) at 1 year and 54.7% P = .0001) at closeout as compared with baseline levels. There were no significant changes in IL-6 with either treatment. In women in the active treatment arm, change in CRP during the first year was not associated with progression of coronary disease P = .2).

Conclusions

Estrogen and estrogen plus medroxyprogesterone significantly raise CRP levels in women with established coronary disease. In contrast, IL-6 levels are not affected by estrogen or estrogen plus progestin. Estrogen-induced changes in CRP are not associated with progression of atherosclerosis.