Comparison of effects of drug-eluting stents versus bare metal stents on plasma C-reactive protein levels

After coronary stenting, inflammatory mechanisms play a crucial role in the pathogenesis of neointimal proliferation and in-stent restenosis. Drug-eluting stents (DESs) have been shown to decrease in-stent restenosis in different studies. We compared plasma C-reactive protein (CRP) levels after DES implantation with levels after bare metal stent (BMS) implantation. We performed percutaneous coronary intervention with a single stent in 67 patients (54 men; 59 +/- 9 years of age; n = 21 in the BMS group, n = 46 in the DES group) who had stable angina. Plasma CRP levels were determined before intervention and at 48 hours, 72 hours, and 2 weeks after coronary stenting. There was no difference in clinical and angiographic baseline characteristics except that the DES group had more patients with diabetes (34.8% vs 9.5%, p = 0.04), smaller reference vessels (2.95 +/- 0.53 vs 3.29 +/- 0.53 mm, p = 0.02), and smaller stent diameters (3.0 +/- 0.4 mm vs 3.4 +/- 0.5 mm, p <0.01). Plasma CRP levels at 48 hours (13.4 +/- 14.7 vs 5.9 +/- 4.9 mg/L, p <0.01) and 72 hours (16.7 +/- 19.8 vs 5.4 +/- 3.9 mg/L, p <0.01) after stent implantation were significantly higher in the BMS than in the DES group. In conclusion, DESs showed significantly lower plasma CRP levels after coronary stenting compared with BMSs. This may reflect the potent effects of DESs on acute inflammatory reactions induced by coronary intervention.     

Elevated preprocedural high-sensitivity C-reactive protein levels are associated with neointimal hyperplasia and restenosis development after successful coronary artery stenting.

BACKGROUND: Recent data indicate that an elevated serum level of high-sensitivity C-reactive protein (hs-CRP) predicts the risk of recurrent coronary events, and that statin therapy decreases the risk of coronary events. This study assessed the relationship between the pre-procedural hs-CRP level and in-stent neointimal hyperplasia (NIH) after stenting and the effects of statins on the relationship between restenosis after stenting and the serum hs-CRP levels of patients with coronary artery disease. METHODS AND RESULTS: This study included 100 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a normal C-reactive protein (CRP) group (<0.5 mg/dl, n=59) and elevated CRP group (>or=0.5 mg/dl, n=41). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline CRP level was 0.29+/-0.08 mg/dl in the normal CRP group and 2.90+/-2.31 mg/dl in the elevated CRP group. The NIH cross-sectional area (CSA) in the minimal lumen CSA at follow-up was significantly larger in the elevated CRP group compared with the normal CRP group (1.9+/-1.3 mm2 vs 3.0+/-1.5 mm2, p=0.001). A significant positive correlation was found between pre-interventional CRP level and NIH area (r=0.52, p<0.001). In patients with normal CRP, an association between statin therapy and restenosis was not observed. However, when the analysis was confined to patients with elevated CRP, statin therapy significantly reduced the restenosis rate (20% vs 37.5%, p=0.031). In the normal CRP group, the intra-stent neointimal area at 6 months was not different between the non-statin and statin groups (2.2+/-1.4 mm2 vs 1.8+/-1.1 mm2). However, in the elevated CRP group, statin therapy significantly decreased the neointimal area at 6-month follow-up (3.6+/-1.7 mm2 vs 2.4+/-1.3 mm2, p<0.001). CONCLUSION: Measuring the pre-interventional hs-CRP level may help predict the development of restenosis after stenting and statin therapy will significantly reduce the restenosis rate in patients with an elevated hs-CRP.     

Association between C-reactive protein and angiographic restenosis after bare metal stents: an updated and comprehensive meta-analysis of 2747 patients

BACKGROUND: Previous studies have shown conflicting results about the relationship between baseline C-reactive protein (CRP) and restenosis after stenting with bare metal stent (BMS). METHODS: We assessed the association between serum CRP and angiographic restenosis after BMS by meta-analysis. Studies that reported basal serum CRP levels, above a prespecified cutoff value, before BMS deployment were included. An inverse random weighted meta-analysis was performed by entering the logarithm of the odds ratio (OR) of angiographic restenosis with its standard error for each study. RESULTS: Nine studies enrolling 2747 patients were selected. CRP threshold value was around 3 mg/l in three studies, 5 mg/l in four studies, and 6.98 and 10 mg/l in one study. Follow-up duration was 6.2+/-3.0 (mean+/-S.D.) months. Higher preprocedural CRP levels were a significant predictor of angiographic restenosis: OR 1.59, 95% confidence interval 1.21-2.07, P=.001. Heterogeneity was found: chi2 14.47, P=.07; I2=44.7%. Publication bias was also detected (P=.01, Egger's test). A sensitivity analysis, after excluding each study in turn, confirmed the predictive value of higher CRP levels, in agreement with the results of the main analysis. CONCLUSIONS: Among patients with coronary artery disease, undergoing percutaneous coronary intervention with BMS, higher baseline CRP levels are associated with higher risk of angiographic restenosis. A targeted therapeutic approach to patients with high baseline CRP, based on statins, oral corticosteroids, or PPAR gamma agonists, or selective use of drug-eluting stents, aiming at abating the higher risk of in-stent restenosis should be considered.     

Predictive value of the adipocyte-derived plasma protein adiponectin for restenosis after elective coronary stenting

The purpose of this study was to test the hypothesis that plasma levels of adiponectin can predict angiographic in-stent restenosis after coronary stenting. We prospectively examined adiponectin levels in 127 consecutive patients undergoing elective coronary stenting. Restenosis was defined as more than 50% stenosis at follow-up study by quantitative coronary angiography. There were no significant differences in the clinical characteristics or angiographical findings between the groups with restenosis and no restenosis. The levels of adiponectin did not differ between the restenosis group and the no restenosis group (5.7 +/- 2.8 vs 5.9 +/- 3.6 microg/mL, p = 0.72). The plasma levels of adiponectin were not related with the late loss index after coronary stenting (r = 0.01, p = 0.89). The levels of adiponectin were significantly lower in men than in women (5.5 +/- 3.2 vs 8.8 +/- 3.7 microg/ mL, p < 0.001), and negatively correlated with body mass index (r = -0.21, p = 0.01). We analyzed adiponectin levels in male, female, obese, non-obese, diabetes, and non-diabetes patients, however, there were no significant differences between the restenosis group and no restenosis group. This study has demonstrated that the measurement of adiponectin could not predict angiographic restenosis after elective coronary stenting, whereas the plasma levels of adiponectin were associated with some coronary risk factors in patients with coronary artery disease.     

C-reactive protein and immunoglobulin-E response to coronary artery stenting in patients with stable angina

Recent reports indicate that inflammatory mechanisms play a crucial role in the pathogenesis of atherosclerosis and neointimal proliferation as well as coronary restenosis. To provide baseline data for further studies regarding stenting, restenosis and inflammatory response. we prospectively conducted a clinical study to investigate the time related response of plasma levels of immunoglobulin-E (IgE) and C-reactive protein (CRP) which are two different inflammatory markers mediated by different cytokines in stable patients who underwent elective coronary artery stenting. Thirteen consecutive stable patients who underwent coronary artery stenting were included in the study. Levels of IgE and CRP were determined pre- and poststent implantation on four consecutive days and at the end of the first as well as third month. Levels of these two markers were gradually elevated on postprocedure days while reaching peak values on the second and third days for IgE (initial 278 +/- 335 IU/mL vs peak 350 +/- 489 IU/mL, P = 0.01) and CRP (initial 0.5 +/- 0 mg/dL vs peak 2.7 +/- 3 mg/dL, P = 0.002), respectively. High levels gradually returned to baseline values determined at the end of the first and even third months after stent implantation implying an acute inflammatory reaction. Stent implantation seems not to cause any persistent and ongoing inflammatory response in the long-term.     

C-Reactive protein, clinical outcome, and restenosis rates after implantation of different drug-eluting stents

Sirolimus-eluting stents (SESs), paclitaxel-eluting stents (PESs), and dexamethasone-eluting stents (DEXs) have anti-inflammatory properties; thus, the decreased in-segment restenosis rate observed with the use of these stents might be related to a weaker postprocedural inflammatory response. One hundred sixty consecutive patients with stable coronary artery disease who underwent successful single-vessel/lesion coronary artery stenting were prospectively studied. Thin-strut bare metal stents were deployed in 39 patients, SESs in 30, PESs in 61, and DEXs in 30. The 4 groups were similar with respect to demographic and angiographic variables and prevalence of risk factors. C-reactive protein (CRP) was measured at baseline and 24 and 48 hours after the procedure. Maximal increase in CRP was calculated as the increase in CRP at 48 hours/CRP compared with baseline. Angiographic follow-up was performed after 12.9 +/- 1.3 months or sooner, if needed, on the basis of clinical evidence. All patients presented a postprocedural increase in CRP that peaked at 48 hours (median 10.0 mg/L). Maximal CRP increase was similar across the 4 groups (medians 3.5 mg/L in the bare metal stent group, 3.6 mg/L in the SES group, 4.0 mg/L in the PES group, 3.5 mg/L in the DEX group, p = 0.45). Incidences of angiographic binary restenosis (>50% lumen diameter decrease) were 20.5% in the bare metal stent group, 3.3% in the SES group, 4.9% in the PES group, and 36.6% in the DEX group (p = 0.0004 for SES and PES groups vs bare metal stent and DEX groups). Postprocedural increase in CRP was significantly correlated with clinical and angiographic outcomes. In conclusion, the acute postprocedural systemic inflammatory response induced by drug-eluting stent implantation appears to be similar to that induced by bare metal stents. However, the restenosis rate is lower for SESs and PESs than for DEXs and bare metal stents. Thus, the decreased incidence of stent restenosis that was observed after SES and PES deployment is unlikely to be related to a decreased acute systemic inflammatory response, but rather to an increased local resistance to inflammatory mediators.     

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.     

Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study)

OBJECTIVES: This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND: Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS: Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS: Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS: In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.     

Preprocedural inflammatory markers do not predict restenosis after successful coronary stenting

Background

Levels of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) can predict coronary restenosis following angioplasty and stent deployment in patients with unstable angina. We investigated whether measurement of periprocedural inflammatory markers predicted the angiographic outcome at 6 months in stable angina patients undergoing coronary stenting.

Methods

We prospectively studied 182 patients; 152 patients underwent elective and successful stenting procedure for de novo lesions in native and nongrafted coronary arteries and 30 individuals in the control group underwent diagnostic angiography alone. CRP, SAA, and IL-6 were determined by high-sensitivity immunoassays.

Results

At 6 months, quantitative computer-assisted angiographic analysis in 133 patients with stents showed a binary restenosis rate of 33.8%. Statins were being taken by 80% of the patients. There were no significant differences between the pre- or postprocedure values of CRP, SAA, or IL-6 in patients with or without in-stent restenosis.

Conclusions

Preprocedural inflammatory markers in stable angina subjects undergoing coronary artery stent deployment did not correlate with the development of in-stent restenosis. Differences in pathobiology between stable and unstable coronary syndromes, the widespread use of statins with anti-inflammatory activity in our cohort of patients, along with different mechanisms underlying the early angiographic appearances of restenosis as compared to clinical end points, most likely explain our findings.     

Direct coronary stent implantation does not reduce the incidence of in-stent restenosis or major adverse cardiac events: six month results of a randomized trial.

STUDY OBJECTIVE: To compare the long-term angiographic, clinical and economic outcome of direct stenting vs stenting after balloon predilatation. PATIENT POPULATION AND METHODS: Four hundred patients with coronary stenoses in a single native vessel were randomized to direct stenting vs stenting after predilatation. A major adverse cardiac and cerebral event (MACCE) was defined as death, myocardial infarction, stent thrombosis, target restenosis, repeat target- and non-target vessel-related percutaneous coronary intervention, target lesion revascularization, coronary artery bypass surgery and stroke. RESULTS: Stents were successfully implanted in 98.3% of patients randomized to direct stenting vs 97.8% randomized to stenting preceded by predilatation. The primary success rate of direct stenting was 88.3%, vs 97.8% for stenting preceded by balloon dilatation (P=0.01). The angiographic follow-up at 6 months included 333 of the 400 patients (83%). The binary in-stent restenosis rate was 23.1% of 163 patients randomized to direct stenting vs 18.8% of 166 patients randomized to balloon predilatation (P=0.32). By 185+/-25 days, MACCE had occurred in 31 of 200 (15.5%) patients randomized to direct stenting, vs 33 of 200 (16.5%) randomized to predilatation (P=0.89). At 6 months, costs associated with the direct stenting strategy (Euros 3222/patient) were similar to those associated with predilatation (Euros 3428/patient, P=0.43). However, procedural costs were significantly lower. It is noteworthy that, on multivariate analysis, a baseline C-reactive protein level >10 mg l(-1)was a predictor of restenosis (odds ratio: 2.10, P=0.025) as well as of MACCE (odds ratio: 1.94, P=0.045). CONCLUSIONS: Compared to stenting preceded by balloon predilatation, direct stenting was associated with similar 6-month restenosis and MACCE rates. Procedural, but not overall 6-month costs, were reduced by direct stenting. An increased baseline CRP level was an independent predictor of adverse long-term outcome after coronary stent implantation.     

Changes in C-reactive protein levels following coronary stent implantation depend on the extent of periprocedural arterial injury

BACKGROUND: Coronary stenting is associated with acute inflammation within the arterial wall followed by neointimal growth. Acute inflammatory response is expressed by a marked systemic elevation of the inflammatory biomarker C-reactive protein (CRP). It has been shown that the degree and extent of CRP increase may be related to clinical presentation or periprocedural treatment. AIM: To investigate whether an increase in CRP level is associated with the extent of arterial injury during stent deployment. METHODS: CRP levels were measured with a high-sensitivity CRP (hsCRP) assay. Seventy-three patients (51 males) with normal baseline plasma CRP (<3 mg/L) underwent percutaneous coronary intervention (PCI) with stent implantation for stable coronary disease. Blood samples for hsCRP were drawn before the intervention, and 6, 12 and 24 hours after the procedure. Both quantitative (single vs multivessel coronary intervention) and qualitative analyses (including lesion classification according to the ACC/AHA grading system) were performed in all patients. The examined angiographic parameters and procedural data obtained included reference diameter, lesion location, lesion length, total stented segment length, diameter of stent after deployment, maximal deployment pressure, total inflation number and duration. RESULTS: The mean hsCRP level increased in all patients between baseline and 24 hours (1.36+/-0.93 mg/L and 4.34+/-3.3 mg/L, p <0.0001). Single vessel procedure was performed in 51 patients and multivessel coronary intervention in 22 patients. Mean hsCRP was similar at baseline and after 6 hours in both groups and the increase after 12 and 24 hours was higher among patients with multivessel coronary intervention compared to patients with single vessel procedure (2.69+/-2.48 vs 4.15+/-3.17; p=0.039 and 3.76+/-3.13 vs 5.69+/-3.38; p=0.021, respectively). There was no correlation between hsCRP and the degree of lesion complexity. Multiple regression analysis showed that the total stented segment length (p=0.01) contributed to the hsCRP increase after 24 hours. CONCLUSIONS: The inflammatory response expressed by hsCRP levels is higher in patients with multivessel coronary intervention with longer total segment stented.     

Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening

Inflammation in the injured vessel wall plays an essential role in the mechanism of restenosis. Pentraxin3 (PTX3) is synthesized at the inflammatory site in response to primary inflammatory stimuli. To establish the clinical significance of plasma PTX3 levels in the pathophysiology of inflammation in the injured vessels, we serially measured the levels in 20 patients undergoing elective coronary stenting. Plasma PTX3 levels increased 15 min after coronary stenting, and reached a maximum at 24h in the coronary sinus (P<0.001 versus baseline) and peripheral blood (P<0.001 versus baseline). The transcardiac gradient of PTX3 at 15 min after PCI was higher in patients with than those without restenosis (0.40+/-0.64 versus -0.19+/-0.33 ng/ml, P=0.02). Furthermore, the increase in PTX3 at 24h was positively correlated with the increase in activated Mac-1 on the surface of neutrophils at 48 h (r=0.48, p<0.05) in the coronary sinus. Stepwise multiple regression analysis demonstrated that the relative increase in PTX3 at 24h was the most powerful predictor of late lumen loss (r=0.547, P=0.007). Coronary stenting enhanced circulating PTX3 levels in association with an inflammatory response. PTX3 may be a useful marker for evaluation of inflammatory reaction and neointimal thickening after vascular injury.     

Intravascular Red Light Therapy after Coronary Stenting Ñ Angiographic and Clinical Follow-up Study in Humans

In animal models of coronary restenosis, intravascular red light therapy (IRLT) using a diode laser source has been shown to reduce neointimal hyperplasia following balloon-induced injury and coronary stenting. We studied the safety and efficacy of catheter-based IRLT for preventing restenosis after coronary stenting in 22 patients with angina pectoris. IRLT was performed using a diode laser (650 nm) at an energy level of 10 megawatts delivered through a rapid exchange balloon system containing the fiberoptics. The procedure was successful in all patients, with no procedural or in-hospital complications. Two patients with recurrence of symptoms had angiography at 3 and 4.1 months respectively. Angiographic follow-up was also done after 6 months in the 20 remaining asymptomatic patients. The mean minimal lumen diameter (MLD) for the whole group at 6 months follow-up was 2.57 +/- 0.62 mm. The calculated late lumen loss was 0.49 +/- 1.12 mm with a late loss index of 0.21 +/- 0.54. Four patients (2 symptomatic and 2 asymptomatic) in the series developed angiographic restenosis. Clinical events at follow-up of 10.9 +/- 3.5 months were repeat angioplasty in 2 patients for symptomatic restenosis with a 91% event free survival. These preliminary results demonstrate that IRLT after coronary artery stenting is safe and feasible; it is associated with low rates of angiographic indices of restenosis.     

Effect of a short antibiotic treatment with roxithromycin on circulating adhesion molecules after coronary stenting: a single-center pilot trial.

BACKGROUND: The aim of this study was to assess the effect of periprocedural antibiotic treatment with roxithromycin on circulating cell adhesion molecules and restenosis after coronary stent implantation. METHODS: Case-control study enrolling 25 consecutive patients submitted to coronary stenting for stable, single-vessel coronary artery disease, treated with 300 mg roxithromycin once daily for 5 days, starting 2 days before the procedure (group R). Twenty-five patients, matched for lesion site, length and diameter, as control group (group C). The serological status for Chlamydia pneumoniae (CP) infection (IgG, ELISA) was assessed in all patients. The plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and C-reactive protein at 1 month after coronary stenting were compared with baseline values. Binary restenosis (> or = 50%) was also evaluated at 6 months. RESULTS: sICAM-1 significantly decreased at 1 month in group R vs group C (371 +/- 181 vs 573 +/- 273 ng/ml, p = 0.005). This decrease was more evident in patients with a positive serology for CP (CP+) (group R 373 +/- 131 vs group C 597 +/- 255 ng/ml, p = 0.014). Antibiotic treatment had no effects on circulating E-selectin levels at 1 month (56.7 +/- 97 vs 49.8 +/- 62 ng/ml, p = 0.54). The restenosis rate (9/50, 18%) was similar in the two groups (group R 5/25 [20%], group C 4/25 [16%]). The restenosis rate was similar in the CP+ vs CP- group (6/35 [17%] vs 3/15 [20%]). CONCLUSIONS: A short course of treatment with roxithromycin at the time of coronary stenting induces a significant reduction in the sICAM-1 levels at 1 month but apparently does not influence the restenosis rate.     

Significance of changes in plasma adiponectin concentration after the implantation of stents in patients with stable angina

OBJECTIVE: Although plasma adiponectin levels may be a marker for the severity of coronary artery disease (CAD) and can help to predict future cardiovascular events in patients with CAD, the significance of changes in plasma adiponectin levels after the implantation of stents in patients with stable angina is unclear. METHODS: The subjects included 32 consecutive patients with stable angina who had undergone successful coronary stenting [bare metal stent (BMS, n=16) or sirolimus-eluting stent (SES, n=16)]. Blood sampling was performed at baseline, and at 24h, 48h, 14 days and 6 months after stenting. RESULTS: Plasma high-sensitivity C-reactive protein (hs-CRP) levels at baseline (0.16+/-0.15mg/dl) were significantly increased at 24h (0.36+/-0.45mg/dl, p=0.011) and 48h (1.01+/-1.01mg/dl, p<0.001), and plasma adiponectin levels at baseline (6.7+/-4.2mug/ml) were significantly decreased at 24h (6.1+/-4.2mug/ml, p=0.019) and 48h (6.2+/-4.9mug/ml, p=0.010) in all subjects. Although there were no significant differences in changes in plasma hs-CRP and adiponectin levels between BMS and SES groups during the study period, BMS group (6.5+/-0.9mug/ml at baseline) showed a significant reduction of plasma adiponectin at 48h (5.8+/-1.1mug/ml, p=0.022) and 6 months after stenting (4.7+/-2.3mug/ml, p=0.011). Percent diameter stenosis (%DS) at 6 months after stenting was negatively correlated with changes in the plasma adiponectin levels within 6 months [Deltaadiponectin (6 months-baseline)]. In addition, multiple logistic regression analysis revealed that the %DS at 6 months after stenting was most closely correlated with Deltaadiponectin (6 months-baseline) after adjusting for age, sex and body mass index. CONCLUSIONS: Coronary stenting may decrease circulating adiponectin in association with an inflammatory response. The changes in plasma levels of adiponectin after stenting may also be a predictor of coronary restenosis in patients with CAD.     

C-reactive protein as possible early prognostic marker of restenosis development in coronary artery stents

AIM: To study possible link between inflammatory response of the body to stent implantation and development of instent restenosis. METHODS: C-reactive protein (CRP) was determined in 24 patients subjected to coronary stenting. Coronary angiography was repeated in 7.1-/+0.68 months after initial procedure. RESULTS: At repeat angiography positive results of stenting persisted in 18 while restenosis developed in 6 patients. All patients had increased CRP levels on days 2-3 after stenting. Day 2 CRP levels were higher in patients with than without restenosis (28-/+4.22 mg/l and 14.17-/+2.14 mg/l, respectively, p<0.05). CRP levels tended to normalize by day 5. CONCLUSION: Coronary artery stenting in patients with angina pectoris is associated with transitory elevation of CRP level. Day 2 CRP >or=24 mg/l with high degree of probability predicts restenosis in remote period.     

Peripheral CD34+ cells and the risk of in-stent restenosis in patients with coronary heart disease

In-stent restenosis represents the major limitation of percutaneous coronary revascularization. The underlying neointimal hyperplasia mainly consists of smooth muscle cells (SMCs), which can be derived from bone marrow cells. We hypothesized that changes in the peripheral progenitor cell counts after coronary stenting may predict the development of restenosis. We prospectively studied men with atherosclerotic coronary artery disease who had undergone successful elective stenting of solitary target lesions (n = 17). Peripheral blood samples were drawn at baseline (before stenting) and 1 day after stenting. The CD34+ cell count was determined by flow cytometry. Follow-up quantitative coronary angiography was performed after 8.1 +/- 2.6 months. Except for longer primary lesions in patients with angiographic restenosis, no significant differences in patient and lesion characteristics were seen. The rate of restenosis (75% vs 11%, p = 0.015) and the extent of diameter stenosis at follow-up (56.9 +/- 26.9% vs 26.5 +/- 16.5%, p = 0.012) were higher in patients with a postprocedural increase in CD34+ cells than in those with a decrease in CD34+ cells. Postprocedural CD34+ cell counts were increased in patients with restenosis but decreased in those without restenosis (p = 0.002). A robust correlation was seen between the change in CD34+ cells and late lumen loss (r = 0.65, p <0.005). In a multivariate regression model, the change in CD34+ cells, lesion length, and preprocedural minimal lumen diameter independently predicted for late lumen loss. In conclusion, an increase in circulating CD34+ cells after coronary stenting constitutes an independent risk factor predicting in-stent restenosis and may be suggestive of their involvement in neointimal hyperplasia.     

Association between plasma pregnancy-associated plasma protein a and restenosis after percutaneous coronary angioplasty

BACKGROUND: Restenosis after percutaneous coronary angioplasty remains an important limitation of this procedure. This study evaluates the association between plasma pregnancy-associated plasma protein A (PAPP-A) levels and restenosis after coronary angioplasty. METHODS AND RESULTS: Blood samples were collected from all patients at baseline, and their levels of PAPP-A, inflammation (high-sensitivity C-reactive protein (hsCRP)) and platelet activation (soluble CD40 ligand (sCD40L)) were determined. Those patients whose PCI was successful underwent a repeat angiography at a median of 6.4 months (interquartile range 6-9.8 months). Their baseline and follow-up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. Endpoints were restenosis (> or =50%) and a composite of major adverse cardiac events. Of the 184 patients, 162 patients underwent an angiographic follow up at 6 months. Patients with restenosis had significantly higher PAPP-A levels than those without (19.24+/-2.56 vs 11.95+/-2.32 mIu/L; p<0.001). The PAPP-A levels were significantly correlated to follow up diameter stenosis (r=0.54, p=0.01). Late lumen loss at follow-up was significantly smaller when PAPP-A levels were <12.51 mIu/L (0.55+/-0.61 vs 0.90+/-0.57 mm; p<0.001). The rates for restenosis (28.4 vs 50.6%; p<0.001) and major advent cardiac events (15.6 vs 51.1%, p<0.001) were significantly lower in patients with PAPP-A levels <12.51 mIu/L. Univariate analysis revealed that PAPP-A (p<0.001), hsCRP (p=0.009) and sCD40L (p=0.03) were significantly related to restenosis. However, only PAPP-A could predict restenosis (odds ratio 0.95; 95% confidence interval 0.84-1.13; p=0.02) in multivariate analysis. CONCLUSIONS: The PAPP-A level is a strong independent predictor of restenosis in patients who have undergone coronary angioplasty.     

血红素氧化酶基因启动子GT序列变化与冠状动脉支架术后再狭窄

目的:观察I型血红素氧化酶(HO-1)基因启动子GT重复长短对冠状动脉支架置入术后再狭窄的影响。方法:187例行冠状动脉支架置入术者,6个月时随访再狭窄情况。PCR和DNA测序仪确定HO-1启动子GT重复次数。高敏法测术前及术后24h、48h血浆白介素-6(IL-6)和C反应蛋白(CRP)值。结果:各基因型间术后IL-6和CRP水平及再狭窄发生率无差异,携较短GT者术前血浆IL-6水平比非短GT序列携带者低约33．3％(P=0．0008)。结论:HO-1基因多态性不影响支架置入术后炎症介质水平及再狭窄,但可能影响动脉粥样硬化形成的炎症过程。     

Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease

Many clinical studies have evaluated the inflammatory response (mainly interleukin [IL]-6 and C-reactive protein [CRP]) after percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). The aim of this study was to verify the source of possible elevation of IL-6 and CRP after PCI using coronary sinus sampling. We studied 87 subjects who underwent coronary angiography for diagnostic, therapeutic, or follow-up purposes. Blood samples were taken by the PCI team during the catheterization study from the coronary sinus. We measured coronary IL-6 levels by sandwich enzyme-linked immunosorbent assay, and high-sensitivity CRP levels were measured by latex immunonephelometry. The subjects were then classified according to their coronary angiographic findings into non-CAD (no evidence of significant organic CAD), mild CAD (1 vessel narrowed), and severe CAD (>or=2 vessels narrowed) groups. PCI (including stent deployment) was performed in 16 patients with CAD. The mean coronary IL-6 value was higher in the severe than in the mild CAD group (3.67 +/- 2.48 vs 2.3 +/- 1.15 pg/ml, p = 0.027). The mean coronary IL-6 value was higher in the subjects who underwent PCI than in those who did not (2.9 +/- 1.23 vs 1.87 +/- 0.9 pg/ml, p = 0.037), and the same was found regarding CRP (1.244 +/- 0.72 vs 0.498 +/- 0.51 mg/L, p = 0.032). The coronary IL-6 values correlated positively with the coronary CRP values (r = 0.374, p = 0.017). In conclusion, the increase in coronary IL-6 and CRP levels after PCI in patients with CAD might be attributed to their release from the coronary atheroma secondary to the direct mechanical effect applied on the atheroma itself by balloon inflation and stent deployment.