Usefulness of mean platelet volume as a biomarker for long-term outcomes after percutaneous coronary intervention

Larger size platelets have enhanced reactivity. The mean platelet volume (MPV) is a marker of platelet activation and is usually measured as part of blood testing. The aim of the present study was to investigate the utility of the MPV as a biomarker in prognosticating the long-term outcomes after percutaneous coronary intervention (PCI). The baseline MPV values from consecutive patients undergoing PCI were screened. Of the 1,432 patients, the composite primary end point of mortality or myocardial infarction at 1 year occurred in 80 (5.6%). The patients in the highest tertile (MPV >9.1 fL) had an increased frequency of the primary end point compared to those in the mid (8.1 to 9.1 fL) and lowest (<8.1 fL) tertiles (9.0%, 4.5%, and 3.5%, respectively; p <0.01). Logistic regression analysis demonstrated diabetes (odds ratio 2.44, 95% confidence interval 1.48 to 4.00) and highest tertile of MPV (odds ratio 2.42, 95% confidence interval 1.47 to 3.99) as the best predictors of adverse outcomes. In patients with acute coronary syndrome, the preprocedural MPV and troponin levels demonstrated a comparable predictive relation to the primary end point (receiver operator characteristics curve analysis, area under the curve 0.64, p = 0.01; and 0.63, p = 0.01, respectively). In conclusion, an elevated MPV was a strong independent predictor of long-term outcomes after PCI. The preprocedural MPV had prognostic value similar to that of troponin in patients with acute coronary syndrome. These findings could be of importance in the clinical evaluation of patients before PCI and the design of future studies assessing antiplatelet therapies.     

Osteoprotegerin is not associated with angiographic coronary calcification

Coronary artery calcification may play a significant role in the pathophysiology of plaque progression and healing. We hypothesized that osteoprotegerin, an inhibitor of osteoclastogenesis, may participate in the calcification of coronary plaques or the response to injury after coronary stenting. A prospective registry was performed in 2004. Blood samples from 100 patients undergoing percutaneous coronary intervention (PCI) were obtained before PCI and 24 h after PCI. The concentrations of osteoprotegerin (OPG), C-reactive protein, interleukin-6, and soluble CD40 ligand (sCD40L) were determined by ELISA. Quantitative coronary angiography was performed to define the presence of culprit lesion calcification (CLC). Comparisons among markers of inflammation and tertiles of OPG were stratified with respect to CLC. Patients with CLC (n = 28) compared with no CLC (n = 71) were older (P < 0.01), had lower creatinine clearance (P < 0.01), lower hemoglobin (P = 0.02), and were less likely to smoke (P = 0.04). Patients without CLC were over twice as likely to present with a marker-positive acute coronary syndrome. CLC was associated with less pre-PCI platelet-mediated inflammation as measured by sCD40L (4.65 vs. 7.15 pg/ml, P = 0.05), but not with lower levels of OPG. Inflammatory cytokines increased significantly after PCI for patients with and without CLC. For patients in the highest tertile of OPG at baseline, there was a reduction in OPG after PCI. Systemic osteoprotegerin levels are not associated with angiographic calcification of culprit plaques. For patients with elevated levels of OPG prior to PCI, there is a significant reduction after PCI consistent with a counterregulatory role for OPG. Condensed Abstract Both calcified and non-calcified culprit plaques exhibited a similar inflammatory response to stent-mediated injury. After PCI, osteoprotegerin decreased while proinflammatory cytokines increased, which may be consistent with a counterregulatory role for osteoprotegerin.This project was supported by an unrestricted research grant from Boston Scientific, Natick, Massachusetts, USA.     

Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation.

OBJECTIVES: This study assessed the predictive value of preprocedural C-reactive protein (CRP) levels on six-month clinical and angiographic outcome in patients undergoing coronary stent implantation. BACKGROUND: Recent data indicate that low-grade inflammation as detected by elevated CRP serum levels predicts the risk of recurrent coronary events. METHODS: We prospectively investigated the predictive value of preprocedural CRP-levels on restenosis and six-month clinical outcome in 276 patients after coronary stent implantation. The primary combined end point was death due to cardiac causes, myocardial infarction related to the target vessel and repeat intervention of the stented vessel. RESULTS: Grouping patients into tertiles according to preprocedural CRP-levels revealed that, despite identical angiographic and clinical characteristics at baseline and after stent implantation, a primary end point event occurred in 24 (26%) patients of the lowest tertile, in 42 (45.6%) of the middle tertile and in 38 (41.3%) of the highest CRP tertile, p = 0.01. On multivariate analysis, tertiles of CRP levels were independently associated with a higher risk of adverse coronary events (relative risk = 2.0 [1.1 to 3.5], tertile I vs. II and III, p = 0.01) in addition to the minimal lumen diameter after stent (p = 0.04). In addition, restenosis rates were significantly higher in the two upper tertiles compared with CRP levels in the lowest tertile (45.5% vs. 38.3% vs. 18.5%, respectively, p = 0.002). CONCLUSIONS: Low-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents.     

Preprocedural white blood cell count and major adverse cardiac events late after percutaneous coronary intervention in saphenous vein grafts

Elevation of white blood cells (WBCs) is associated with worse outcomes in patients with coronary artery disease (CAD), including patients undergoing percutaneous coronary intervention (PCI) of native coronary arteries, but this relation has not been studied in patients with saphenous vein graft disease undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein grafts from May 1997 to July 2002 were followed for >3 years. Major adverse coronary events (MACEs) were assessed as a composite of death, myocardial infarction, or revascularization during follow-up (mean 2.7 years). Patients with MACEs (n = 287) were younger and had more thrombotic and ostial lesions (p < 0.05) than those without MACEs (n = 243). The preprocedural WBC count was also significantly higher in the MACE group than in the non-MACE group (8.1 x 10(3)/mul, range 6.6 to 10.1, vs 7.0 x 10(3)/mul, range 5.6 to 8.2; p < 0.001). After adjusting for covariates, multiple logistic regression analysis revealed the preprocedural WBC count to be an independent predictor for MACEs (odds ratio 1.2; 95% confidence interval 1.1 to 1.3, p < 0.001). Patients in the highest quartile of the preprocedural WBC level had a significantly increased risk of MACEs (lowest vs highest quartile, 41.3% vs 72.4%; odds ratio 3.7; 95% confidence interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated with increased risk of MACEs in patients undergoing PCI for saphenous vein graft lesions.     

Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention

The neutrophil to lymphocyte (N/L) ratio is a recently described independent predictor of death/myocardial infarction in patients who have undergone coronary angiography. We hypothesized that an elevated N/L ratio would be a predictor of long-term mortality in patients undergoing percutaneous coronary intervention (PCI). A total of 1,046 patients who underwent PCI were divided into tertiles based on their preprocedural N/L ratio (mean N/L ratio, tertile 1, 1.7 +/- 0.5; tertile 2: 3.2 +/- 0.6; tertile 3, 11.2 +/- 12.9). Vital status was assessed using the Social Security Death Index. There were a total of 144 deaths over a mean follow-up of 32 months. The best survival was seen in tertile 1, with an increase in long-term mortality seen in tertiles 2 and 3 (p <0.0001). In multivariable modeling, after adjusting for age, chronic obstructive pulmonary disease, left ventricular ejection fraction, serum hemoglobin, serum creatinine, and lesion severity, the log N/L, but not the white blood cell count, was an independent significant predictor of long-term mortality (hazard ratio 1.85, 95% confidence interval 1.3, to 3.04, p = 0.01). The risk persisted when patients with an acute myocardial infarction were excluded from the analysis (hazard ratio 2.46, 95% confidence interval 1.4 to 4.4, p = 0.002). In conclusion, an elevated preprocedural N/L ratio in patients undergoing PCI is associated with an increased risk of long-term mortality.     

Relation of C-reactive protein to coronary collaterals in patients with stable angina pectoris and coronary artery disease

The heterogeneity in the degree of collateralization among patients with coronary artery disease (CAD) is poorly understood. We sought to determine whether chronic subclinical inflammation is related to coronary collateral development in patients with chronic stable angina pectoris and obstructive CAD. High-sensitivity C-reactive protein (CRP) levels were measured in 177 patients with stable angina pectoris before coronary angiography. Multivariable logistic regression revealed an inverse graded association between CRP and the presence of coronary collaterals (Rentrop grade 1 to 3). Compared with patients in the first CRP tertile, the adjusted odds ratio for the presence of coronary collaterals was 0.70 (95% confidence interval, 0.33 to 1.52; p = 0.45) for patients in the second CRP tertile and 0.33 (95% confidence interval, 0.15 to 0.75; p = 0.008) for patients in the third CRP tertile (p for trend = 0.008). In conclusion, an inverse graded association exists between CRP and the presence of coronary collaterals in patients with stable angina pectoris.     

Systemic Inflammation After Drug-Eluting Stent Placement

Background: Systemic inflammation after coronary intervention identifies patients at increased risk of subsequent cardiac events. Cardiac events are less frequent after use of drug eluting stents (DES) compared with bare metal stents (BMS). Thus, we sought to determine whether attenuation of the systemic inflammatory response was contributing to the improved outcomes.Methods: A prospective registry was initiated in late 2003. Peripheral venous blood samples from 75 patients undergoing percutaneous coronary intervention (PCI) were obtained before PCI, and both 1 hour and 24 hours after stenting. The concentrations of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL1-Ra) were determined by ELISA. Eleven patients were excluded from the analysis because they had both DES and BMS.Results: Patients treated with BMS (n = 29) compared with DES (n = 34) had a higher incidence of marker-positive acute coronary syndromes (40% vs. 17%, p = 0.06), vein graft PCI (p = 0.02) and a larger final balloon diameter (p = 0.04). Consistent with the lower baseline clinical risk, pre-PCI concentrations of cytokines were lower in the DES group (p = 0.04 for IL-6 and p = 0.08 for CRP). Comparable and significant increases in CRP, IL-6 and IL1-Ra were evident 24 hours after PCI in patients treated with either DES or BMS. After controlling for baseline levels of CRP, there remained a similar and robust (300%) relative increase in CRP for both DES and BMS patients.Conclusions: The inflammatory response to PCI appears similar in those treated with DES and BMS. Accordingly, the reduction in restenosis after DES is likely not mediated by attenuation of the systemic markers CRP, IL-1Ra, or IL-6.     

Comparison of inflammatory markers in patients with diabetes mellitus versus those without before and after coronary arterial stenting

Patients with diabetes are at increased risk for adverse events after coronary stenting, perhaps reflecting a pro-inflammatory state. To characterize the inflammatory response to coronary stenting in patients with and without diabetes, blood samples were obtained from 75 patients before stenting and 10 minutes, 1 hour, and 24 hours later. C-reactive protein (CRP, microg/ml), interleukin (IL)-6 (pg/ml), IL-1 receptor antagonist (pg/ml), and soluble CD40 ligand (ng/ml) were assayed in each sample by enzyme-linked immunosorbent assay. Concentration changes after stenting were identified by repeated-measures analysis of variance. Multivariate analysis was performed to delineate independent predictors of increased concentrations of inflammation markers. Overall, 88% of patients had acute coronary syndromes; 36% had elevated markers of cardiac injury. The preprocedural concentrations of CRP in those with diabetes were more than twice as high as those in patients without diabetes. Two independent predictors of elevated preprocedural CRP concentrations were diabetes (odds ratio 3.95, 95% confidence interval 1.17 to 13.4) and a cardiac marker-positive acute coronary syndrome (odds ratio 3.70, 95% confidence interval 1.22 to 11.2). Preprocedural concentrations of IL-6, IL-1 receptor antagonist, and soluble CD40 ligand tended to be greater in patients with diabetes. The increase in CRP after stenting was much greater for patients without diabetes compared with that in patients with diabetes such that the apparent intensity of inflammation after 24 hours was similar in those with and without diabetes. Thus, patients with and without diabetes exhibit different inflammatory responses to stenting, reflecting the lower preprocedural inflammation in those without diabetes versus those with diabetes.     

Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention.

AIMS: We investigated the predictive value of plasma concentration of asymmetrical dimethylarginine (ADMA) on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: One-hundred and fifty-three consecutive patients with stable angina and undergoing PCI were prospectively enrolled for clinical follow-up. Plasma ADMA levels were determined before procedure by high performance liquid chromatography. The major adverse cardiovascular events included cardiovascular death, myocardial infarction, and repeat revascularization of target vessels. Patients were grouped into tertiles according to their plasma ADMA levels. Over a follow-up period of 16 months (median), cardiovascular events occurred in 6 patients of tertile I (<0.50microM), in 17 patients of tertile II (0.50-0.62microM), and in 28 patients of tertile III (>0.62microM), P<0.001. By multivariate analysis, tertiles of ADMA levels were independently associated with a higher risk of adverse cardiovascular events after PCI (relative risk: tertile II vs I: 3.0 [1.2-7.7], P=0.022; tertile III vs I: 5.3 [2.2-12.9], P<0.001). Moreover, plasma ADMA level in the highest tertile also appeared as a significant risk factor of subsequent death and non-fatal myocardial infarction after PCI (tertile III vs I, P=0.04). CONCLUSION: Pre-procedural plasma ADMA levels may independently predict subsequent adverse cardiovascular events in patients undergoing PCI. Measurement of plasma ADMA levels could provide a rationale for risk stratification of patients by measuring ADMA levels before intervention.     

Relation of plasma lipoprotein levels with low-grade inflammation in white men without clinical evidence of myocardial ischemia

There is a growing body of evidence indicating that high triglyceride levels are an independent risk factor for cardiovascular disease (CVD) events. In this study we compared the association of fasting levels of non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and triglycerides with white blood cell (WBC) count, an inflammatory marker associated with an adverse CVD prognosis. We studied 458 asymptomatic men (46.0 +/- 7.0 years old) who presented for CVD risk stratification. WBC count (x10(9) cells/L) increased significantly across increasing tertiles of triglyceride level (tertile 1, 6.04 +/- 1.49; tertile 2 6.21 +/- 1.44; tertile 3 6.78 +/- 1.73, p <0.0001), whereas a trend of lower WBC counts was observed across increasing tertiles of HDL cholesterol (tertile 1, 6.52 +/- 1.62; tertile 2, 6.24 +/- 1.50; tertile 3, 6.21 +/- 1.61, p = 0.08). In models adjusted for age, gender, and CVD risk factor, the odds ratio for a high WBC count (quartile > or =4 vs lower 3 quartiles) was significantly higher with increasing levels of triglyceride (2.4, 95% confidence interval 1.3 to 4.8, p = 0.02). When all lipid variables were introduced in the models in addition to traditional CVD risk factors, the association between plasma triglyceride level and WBC count persisted (p = 0.04), which was not found for other lipid parameters. In conclusion, in our study, only plasma triglyceride level was independently associated with a higher WBC count.     

Effect of statins and white blood cell count on mortality in patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention

BACKGROUND: While morbidity and mortality were shown to be increased in the setting of an elevated white blood cell (WBC) count for patients with acute coronary syndrome, the impact of statin therapy on mortality for patients with an elevated WBC count is unknown in high-risk patients with coronary artery disease. HYPOTHESIS: The goal of this study was to determine whether statin therapy improved survival in patients with elevated WBC count undergoing percutaneous coronary intervention (PCI) with preexisting left ventricular (LV) dysfunction, a population at high risk for adverse outcomes. METHODS: We retrospectively evaluated consecutive patient procedures performed at our institution from 1996 through 1999. Patients had a technically adequate angiographic left ventriculogram with a calculated ejection fraction (EF) < or = 50%. Patients with prior coronary artery bypass graft were excluded. Mortality data were retrieved using the U.S. Social Security Death Index. Follow-up ranged from 3.5 to 6.5 years. Means are provided with +/- standard deviation, and p values < 0.05 were considered significant. RESULTS: Of the study population of 238 patients (average EF 39 +/- 9.8%, mean age 57.5 +/- 12 years, 68% men) 61% underwent PCI for a recent myocardial infarction, 68% received stents, and 65% were discharged on statins. Mean WBC count was 9,000 +/- 3,100 cells/mm3, with 28% of patients having a WBC > or = 10,000 cells/mm3. During follow-up, 27% of our population died. Patients with a WBC > or = 10,000 had worse survival than patients with WBC < 10,000 (1-year survival: 86 vs. 96%, p < 0.05; 3-year survival: 79 vs. 89%, p < 0.05). Survival was significantly improved in patients on statin therapy regardless of WBC count, but the greatest benefit tended to be in patients with WBC > or = 10,000 (WBC > or = 10,000; odds ratio [OR] 5.14, 95% confidence interval [CI] 1.44-19.0, WBC < 10,000; OR 2.79,95% CI 1.13-7.1). Proportional hazard regression analysis demonstrated that both statin therapy and WBC count predicted mortality. CONCLUSION: Patients undergoing PCI with LV dysfunction discharged on statins had improved survival regardless of WBC count, with a trend for greater improvement in patients with elevated WBC counts. In addition, WBC count predicts mortality in this high-risk population with LV dysfunction undergoing PCI.     

C-reactive protein plasma levels but not factor VII activity predict clinical outcome in patients undergoing elective coronary intervention

BACKGROUND: Both vascular inflammation as determined by C-reactive protein (CRP) and extrinsic coagulation as measured by factor VII activity (F VII) may predict clinical restenosis rate in patients with stable angina pectoris undergoing elective percutaneous coronary intervention (PCI). HYPOTHESIS: The primary objective of this study was to investigate the associations between baseline CRP levels, F VII activity, and restenosis rate after elective PCI in a 6-month follow-up period. METHODS: This prospective study included 81 patients aged > or = 19 years undergoing PCI for angiographically significant (> or = 70%) stenosis, with or without stenting, and 49 controls. Factor VII activity and CRP were measured in samples collected at angiography and 16-24 h post procedure after overnight fast. Successful PCI was defined as final diameter of < 50% with TIMI 3 flow and no complication within 1 h. After 6 months all patients who had undergone PCI were evaluated via a standardized questionnaire. Clinical restenosis was defined as the occurrence of a major adverse coronary events (MACE), within the follow-up period. RESULTS: Diagnostic angiography led to a significant increase in CRP levels after 16-20 h in patients with discrete CAD (n = 22) but not in patients without any signs of coronary atherosclerosis (n = 27). During a 6-month follow-up after PCI, 17 of 81 (21%) patients developed MACE. Tertiles of CRP levels independently predicted clinical restenosis, as it developed in 33.3% of patients with the highest CRP levels (0.7-4.8 mg/dl), in 16.6% of patients with second tertile CRP levels (0.23-0.69 mg/dl), and in 7.4% of patients with lowest tertile CRP levels (0.0-0.22 mg/dl). There was a significant difference in the restenosis rate between patients from the first and the third tertiles (p = 0.018). Successful PCI was associated with a significant decrease of mean CRP levels after 6 months, whereas PCI in patients suffering from MACE led to no change in CRP levels. There was no association between factor VII activity and clinical outcome after PCI, and F VII activity did not change over a 6-month period. CONCLUSIONS: In patients with stable angina pectoris undergoing elective PCI, increased preprocedural and 6-month follow-up CRP plasma levels are associated with clinical restenosis. Factor VII plasma activity lacks such correlations.     

Response of high-sensitivity C-reactive protein to percutaneous coronary intervention in patients with acute coronary syndrome

Percutaneous coronary intervention (PCI) provokes an inflammatory reaction, as shown by increased concentrations of plasma C-reactive protein (CRP) after PCI. However, the changes of CRP levels after PCI in patients with acute coronary syndrome (ACS) have not been well evaluated. We evaluated the characteristics of the patients with elevated CRP response after PCI and whether an increase in CRP after PCI predicts long-term prognosis in patients with ACS. We studied consecutive 360 patients with ACS who underwent elective coronary stenting. Inflammatory response to PCI was calculated as the difference between the peak postprocedural hsCRP level and the preprocedural hsCRP level (ΔCRP). Twelve months follow-up data were obtained and clinical outcomes were compared with ΔCRP. In receiver operating characteristics analyses, the cutoff point of ΔCRP for major adverse cardiac events (MACE) was 3.0 mg/l, which yielded sensitivity of 61.7% and specificity of 69.7%. The patients with ΔCRP > 3 mg/l revealed higher incidence of myocardial infarction (37.7 vs 14.6%, P < 0.001), and ACC/AHA type B2/C lesion (81.5 vs 68.7%, P = 0.006) than in patients with low ΔCRP. White blood cell count, low-density lipoprotein cholesterol, peak creatinine kinase-MB, and peak troponin T were significantly elevated in patients with ΔCRP > 3 mg/l than in those with ≤3 mg/l. There was significant correlation between ΔCRP and the changes in troponin T after PCI (r = 0.210, P < 0.001). An increase in hsCRP > 3 mg/l after PCI had a higher predictive value for the occurrence of MACE than low hsCRP elevation (hazard ratio 2.1, P = 0.005). In multivariate analysis, ΔCRP and peak troponin T were independent predictors of MACE (P < 0.001 and P = 0.013, respectively). In conclusion, postprocedural hsCRP elevation >3 mg/l was associated with higher incidence of MACE in patients with ACS. ΔCRP determinations may be of value for risk stratification after PCI.     

Oxidative stress and inflammation due to peripheral polymorphonuclear leukocytes after coronary angiography vs percutaneous coronary intervention

AIM: Percutaneous coronary intervention (PCI) as an invasive procedure includes inflation of a balloon and/or implantation of an endovascular prosthesis (stent) in an atherosclerotic coronary vessel at a level where the plaque narrows its cross-sectional area by more than 75%. Various reports have demonstrated that balloon inflation or stent implantation trigger inflammation and subsequent growth of smooth muscle cells. Both oxidative stress (OS) and inflammation parameters worsen, increasing the risk of complications. The polymorphonuclear leukocyte (PMNL) is one of the inflammatory cells releasing reactive oxygen species contributing to OS, inflammation and endothelial injury. The aim of this study was to study the contribution of PMNLs during coronary intervention. METHODS: Patients enrolled in this study were randomized into two groups, namely nine patients undergoing PCI procedure, compared to 11 undergoing diagnostic coronary angiography. PMNLs were separated from patient blood, before and following PCI. PMNL priming was measured by rate of superoxide release from PMNLs and flow cytometry analysis of CD11b levels. PMNL-related inflammation was estimated by white blood cells (WBC) and PMNL count. Systemic inflammation was monitored by C-reactive protein (CRP) and fibrinogen. RESULTS: Tested patients were divided into patients undergoing PCI procedure, compared to those undergoing diagnostic coronary angiography; already at time '0', OS and inflammation parameters were higher in the PCI group of patients. OS parameters decreased significantly following PCI procedure. PCI itself induces increased OS and inflammation. Significant positive correlation was found between serum creatine phosphokinase and rate of superoxide release from PMNLs, indicating correlation between PMNL priming and the severity of cardiac disease. Systemic inflammation parameters, such as fibrinogen and CRP, showed significant decrease in the PCI group after the procedure, while those related to PMNLs did not. CONCLUSION: PMNL contribution to OS and inflammation is lower in patients undergoing diagnostic coronary angiography, compared to the PCI group. This research adds new facet to evaluation of cardiac patients whether they will undergo PCI procedure or diagnostic coronary angiography.     

Comparison of usefulness of C-reactive protein versus white blood cell count to predict outcome after primary percutaneous coronary intervention for ST elevation myocardial infarction

White blood cell (WBC) count and high-sensitive C-reactive protein (hs-CRP) are both used as markers of inflammation and prognosis after an ST elevation myocardial infarction (STEMI), but it is unknown whether they have independent prognostic value. We investigated the association and independent prognostic importance of WBC and hs-CRP after STEMI. In this subanalysis of the On-TIME trial, in 490 of 507 (97%) patients, either WBC count or CRP, and in 362 (71%) patients, both WBC count and CRP, were measured on admission before primary percutaneous coronary intervention. There was no significant correlation between WBC count and CRP (R = 0.080). Higher levels of CRP were associated with a reinfarction or death within 1 year (mean hs-CRP 14.2 +/- 20.4 vs 6.1 +/- 14.2, p = 0.006), but CRP was not associated with enzymatic infarct size (lactate dehydrogenase, LDHQ48) or left ventricular ejection fraction. A higher baseline WBC count was associated with larger LDHQ48 and lower left ventricular ejection fraction but not with 1-year reinfarction or death. In conclusion, although both WBC count and CRP are markers of inflammation and predictors of outcome after STEMI, we did not find a correlation between baseline WBC count and CRP levels in patients treated with primary percutaneous coronary intervention for STEMI. The mechanisms by which WBC counts predict outcome were related to myocardial infarct size whereas CRP were not.     

Preprocedural statin therapy reduces the risk and extent of cardiac biomarker release following percutaneous coronary intervention

This study evaluates the association between statin therapy in patients treated by percutaneous coronary intervention (PCI) for stable angina pectoris and postinterventional myocardial injury with subsequent long-term clinical outcome. Prospectively collected data on 400 consecutive patients with stable angina pectoris or evidence of inducible myocardial ischemia were analyzed. The incidence of myocardial infarction based on postinterventional release of troponin I >1.5 ng/ml was 12% in the statin pretreated patients and 20% in those not pretreated with statin therapy (P = 0.04, odds ratio 1.84, 95% confidence interval 1.06–3.21). Of the patients experiencing a post-PCI troponin elevation >1.5 ng/ml, those pretreated with a statin pre-PCI had a lesser troponin elevation compared with those not receiving a statin pre-PCI (median: 2.9 ng/ml [1.9–11.5] vs 5.0 ng/ml [3.1–8.8]; P < 0.001). In the multivariate model, preprocedural statin therapy was identified as the only independent negative predictor of procedure-related myocardial necrosis based on postprocedural troponin elevation. In the 21-month follow-up period, statin pretreated patients were observed to have fewer deaths, revascularizations, or myocardial infarction; however, this difference was not statistically significant. These results suggest that pretreatment with statins in patients undergoing PCI for stable angina pectoris reduces the risk and extent of procedure-related myocardial injury measured by troponin release.     

Inflammation and frailty in older women

OBJECTIVES: To evaluate relationships between white blood cell (WBC) count and interleukin-6 (IL-6) and prevalent frailty. DESIGN: Cross-sectional study. SETTING: Two population-based studies, the Women's Health and Aging Studies (WHAS) I and II, Baltimore, Maryland. PARTICIPANTS: Five hundred fifty-eight women aged 65 to 101 from WHAS I and 548 women aged 70 to 79 from the merged WHAS I and II cohorts. MEASUREMENTS: Frailty was determined using validated screening criteria. WBC counts and IL-6 levels were measured using standard laboratory methods. Odds ratios (ORs) for frailty were evaluated across tertiles of baseline WBC counts and IL-6 levels, adjusting for age, race, education, body mass index, and smoking status. RESULTS: In WHAS I, those in the top tertile of WBC count and IL-6 had ORs of 4.25 (95% confidence interval (CI)=1.89-9.58) and 3.98 (95% CI=1.76-9.00), respectively, for frailty (both P<.001). In the combined models, participants in the top tertile of WBC count had an OR of 3.15 (95% CI=1.34-7.41), adjusting for IL-6 (P<.01), and those in the top tertile of IL-6 had an OR of 2.81 (95% CI=1.19-6.64), adjusting for WBC count (P<.05). Furthermore, participants in the top tertiles of WBC count and IL-6 had an OR of 9.85 (95% CI=3.04-31.99), and those in the middle/top tertiles had an OR of 5.40 (95% CI=1.83-15.92) (P<.001, trend test) for frailty. These results were validated in the merged WHAS I and II. CONCLUSION: Higher WBC counts and IL-6 levels were independently associated with prevalent frailty in community-dwelling older women.     

Cytokine response after percutaneous coronary intervention in stable angina: effect of selective glycoprotein IIb/IIIa receptor antagonism

Background It is unclear whether modulation of inflammatory markers by glycoprotein IIb/IIIa receptor inhibition after percutaneous coronary intervention (PCI) is caused by an interaction with the α_vβ₃ and α_Mβ₂ receptor or it correlates with ischemic events during PCI. This study investigates the inflammatory profile after elective, nonacute PCI and whether and how administration of the glycoprotein IIb/IIIa receptor antagonist tirofiban modulates the postinterventional inflammatory myocardial response. Methods The time course of inflammatory parameters (C-reactive protein [CRP], interleukin-1 [IL-1], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]) of patients receiving peri- and postinterventional placebo (n = 46) or tirofiban infusion (n = 50) was analyzed by use of enzyme-linked immuno assays. Samples were collected before and 30 minutes, 2.5 hours, 6.5 hours, 12 hours, 24 hours, and 48 hours after elective PCI. Results Among the inflammatory markers analyzed, TNF-α, IL-6, and CRP levels increased significantly. However, the latter markers followed individual time courses in patients given placebo and patients treated with tirofiban after PCI, compared with pre-PCI levels (P < .01), with no significant differences between the placebo and tirofiban-treated groups. However, by subgroup analysis, significant differences were revealed in TNF-α, IL-6, and CRP levels of patients who were troponin T-positive versus patients who were troponin T-negative after PCI. Conclusions The administration of the selective glycoprotein IIb/IIIa receptor antagonist tirofiban has no direct impact on the inflammatory profile after elective PCI. Change of the inflammatory profile was only related to the presence or absence of postinterventional troponin. (Am Heart J 2003;145:693-9.)     

Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five year study

BACKGROUND: Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. OBJECTIVE: To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. METHODS: sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheere's test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. RESULTS: sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects. CONCLUSION: The degree of activation of vascular endothelium is associated with activity and outcome of early RA.