Marker Of Restenosis Research Articles

Markers of Restenosis after Percutaneous Transluminal Balloon Angioplasty in Patients with Critical Limb Ischemia.

Among cardiovascular diseases, chronic obliterating lesions of the arteries of lower extremities, which are one of the important problems of modern healthcare, are distinguished. In most cases, the cause of damage to the arteries of lower extremities is atherosclerosis. The most severe form is chronic ischemia, characterized by pain at rest and ischemic ulcers, ultimately increasing the risk of limb loss and cardiovascular mortality. Therefore, patients with critical limb ischemia need limb revascularization. Percutaneous transluminal balloon angioplasty is one of the least invasive and safe approaches, with advantages for patients with comorbidities. However, after this procedure, restenosis is still possible. Early detection of changes in the composition of some molecules as markers of restenosis will help screen patients at the risk of restenosis, as well as find ways to apply efforts for further directions of inhibition of this process. The purpose of this review is to provide the most important and up-to-date information on the mechanisms of restenosis development, as well as possible predictors of their occurrence. The information collected in this publication may be useful in predicting outcomes after surgical treatment and will also find new ways for the target implication to the mechanisms of development of restenosis and atherosclerosis.

Lipoprotein(a) in Cardiovascular Diseases

Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

Mean Platelet Volume and Long-Term Mortality in Patients Undergoing Percutaneous Coronary Intervention

Increased platelet activity is associated with adverse cardiovascular events. The mean platelet volume (MPV) correlates with platelet activity; however, the relation between the MPV and long-term mortality in patients undergoing percutaneous coronary intervention (PCI) is not well established. Furthermore, the role of change in the MPV over time has not been previously evaluated. We evaluated the MPV at baseline, 30 days, 60 days, 90 days, 1 year, 2 years, and 3 years after the procedure in 1,512 patients who underwent PCI. The speed of change in the MPV was estimated using the slope of linear regression. Mortality was determined by query of the Social Security Death Index. During a median of 8.7 years, mortality was 49.3% after PCI. No significant difference was seen in mortality when stratified by MPV quartile (first quartile, 50.1%; second quartile, 47.7%; third quartile, 51.3%; fourth quartile, 48.3%; p= 0.74). For the 839 patients with available data to determine a change in the MPV over time after PCI, mortality was 49.1% and was significantly greater in patients with an increase (52.9%) than in those with a decrease (44.2%) or no change (49.1%) in the MPV over time (p <0.0001). In conclusion, no association was found between the baseline MPV and long-term mortality in patients undergoing PCI. However, increased mortality was found when the MPV increased over time after PCI. Monitoring the MPV after coronary revascularization might play a role in risk stratification.

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.

Vitamin D receptor: a new risk marker for clinical restenosis after percutaneous coronary intervention

Objective: Restenosis is the main drawback of percutaneous coronary intervention (PCI). Inherited factors may explain part of the risk of restenosis. Recently, the vitamin D receptor (VDR) has been shown to be involved not only in bone metabolism but also in modulating immune responses and cell proliferation. Since the inflammatory response is implicated in restenosis, VDR-gene variants could therefore contribute to the risk of restenosis. Methods/results: Systematic genotyping for 15 haplotype tagging single-nucleotide polymorphisms (SNPs) of the VDR gene was performed with the high throughput TaqMan allelic discrimination assays in the Genetic Determinants of Restenosis (GENDER) population. A haplotype-based survival analysis revealed an association of haplotypes in blocks 2, 3 and 4 of the VDR-gene with the risk of clinical restenosis (p-values 0.01, 0.04 and 0.02 respectively). After adjustment for clinical risk factors for restenosis, the individual effect of the block 2 AA haplotype (p = 0.011) persisted. Conclusions: The present study indicates that VDR plays a role in restenosis after PCI. Therefore, VDR genotype may be used as risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice.

Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease

RationaleThere is growing evidence that obstructive sleep apnea is associated with coronary artery disease. However, there are no data on the course of coronary stenosis after percutaneous coronary intervention in patients with obstructive sleep apnea.ObjectivesTo determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.Methods78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea – Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 ± 3.1 months.Main resultsAngiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 ± 0.69 mm vs. 0.38 ± 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 ± 0.47 mm vs. 0.99 ± 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206).ConclusionIn summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.

Atherosclerotic Plaque Composition and Occurrence of Restenosis After Carotid Endarterectomy

Previous studies have assessed the predictive value of clinical and angiographic parameters for development of restenosis after vascular interventions. The composition of the atherosclerotic plaque at the intervention site has had limited evaluated as a marker for restenosis [corrected]. To investigate the relationship between atherosclerotic plaque histology and the occurrence of restenosis after carotid endarterectomy. The Athero-Express study is a longitudinal vascular biobank study that includes the collection of atherosclerotic plaques of patients undergoing primary carotid endarterectomy. Five hundred patients were prospectively followed up between April 1, 2002, and March 14, 2006, to assess carotid artery restenosis measured by duplex ultrasound 1 year after the intervention. Risk of carotid restenosis in relation to predefined histological characteristics (macrophage and smooth muscle cell infiltration, collagen, calcifications, intraplaque bleeding, luminal thrombus, and lipid core size), adjusted for clinical characteristics (multivariate logistic regression analysis). At 1 year, 85 patients (17%) developed 50% or greater restenosis, including 40 patients (8%) who developed 70% or greater restenosis of the target vessel. Patients whose histological examination of the plaque revealed marked macrophage infiltration (n = 286) had a lower risk than those with none or minor macrophage infiltration (n = 214) of developing 50% or greater restenosis (risk difference, 11.5% vs 24.3%; adjusted odds ratio [OR], 0.43; 95% confidence interval [CI], 0.26-0.72) and a lower risk of developing 70% or greater restenosis (risk difference, 4.5% vs 12.6%; adjusted OR, 0.36; 95% CI, 0.17-0.74). Patients (n = 177) with a plaque having a large lipid core size (>40%) had a lower risk than those (n = 94) with a plaque having a lipid core size of less than 10% of developing 50% or greater restenosis (risk difference, 11.3% vs 25.5%; adjusted OR, 0.40; 95% CI, 0.19-0.81) and a lower risk of developing 70% or greater restenosis (risk difference, 5.6% vs 14.9%; adjusted OR, 0.42; 95% CI, 0.17-1.04), independent of clinical characteristics. Plaque composition is an independent predictor of restenosis after carotid endarterectomy. The dissection of a lipid-rich, inflammatory plaque is associated with reduced risk of restenosis.

Are common leptin promoter polymorphisms associated with restenosis after coronary stenting?

The hypertrophy of vascular smooth muscle cells as well as neointimal proliferation is critical in vascular remodeling, whereas leptin has proved to play an important role recently. The aim of the study was to investigate possible associations of two common leptin gene polymorphisms with restenosis after percutaneous coronary intervention (PCI). To study the association of two promoter polymorphisms, LEP -2548 G/A and LEP -188 C/A (dbSNP ID rs7799039 and rs791620) with neointimal proliferation in humans, 98 consecutive patients undergoing stenting into small coronary arteries (<3 mm) were genotyped. After a 6-month follow-up, the restenosis rate was estimated. Restenosis >50% occurred in 33.3% of patients carrying both A alleles, 33.3% of carriers of A and C alleles, and 31.4% of carriers of two CC alleles of LEP -188 C/A polymorphism; and in 25.0% of patients with AA, 32.7% with AG, and 30.4% with GG genotype of LEP -2548 G/A polymorphism. Interestingly, the heterozygote AG genotype of LEP -2548 polymorphism represented a highly significant risk for multiple-vessel disease when compared to both homozygote genotypes AA/GG (odds ratio = 4.038, 95% confidence interval: 1.732-9.465, P(corr) = 0.001). Based on our findings, the AG genotype of LEP -2548 G/A polymorphism might be considered a genetic marker for multiple-vessel disease but not for restenosis after PCI. The role of the leptin gene polymorphisms as genetic markers of restenosis will require further investigation to elucidate the underlying pathophysiological consequences.

Clinical Restenosis after Coronary Stent Implantation Is Associated with the Heme Oxygenase-1 Gene Promoter Polymorphism and the Heme Oxygenase-1 +99G/C Variant

Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR)=1.9; 95% confidence interval (95% CI), 1.0-3.4; P=0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR=3.4; 95% CI, 1.2-9.1; P=0.017) in nonsmokers than in smokers (OR=2.0; 95% CI, 0.7-5.2; P=0.18). The long allele of the HO-1 gene promoter (>29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the >29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.

Mean platelet volume as marker of restenosis after percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris

Introduction Several experimental and clinical studies have demonstrated that platelet size and function correlate since large platelets are hemostatically more reactive than platelets of normal size. Since platelets play a crucial role in vascular remodeling after percutaneous transluminal coronary angioplasty (PTCA), we investigated the influence of the mean platelet volume (MPV), a parameter of platelet size, on restenosis after PTCA. Methods The retrospective study comprised 174 patients who underwent elective PTCA and follow-up angiography within 6 months thereafter. According to the follow-up angiograms, the patients were assigned to group A (“restenosis”, n = 74) or group B (“no restenosis”, n = 100). Both groups were compared in regard to pre-procedural hematological routine parameters including MPV, platelet count, hematocrit, white blood cell count and fibrinogen. Results MPV was significantly increased in group A, compared with that in group B (8.75 ± 0.99 fl vs. 8.04 ± 0.74 fl, p < 0.001). This difference in MPV was evident in patients with stable and unstable angina pectoris. In addition, MPV had an impact on the time-related incidence of angiographic restenosis, as early restenosis was associated with higher pre-procedural MPV values. Platelet count correlated inversely with MPV ( r = −0.36, p < 0.01) and was significantly lower in group A than in group B. The remaining hematological parameters were not different in both groups. Conclusions The MPV seems to be a marker of coronary restenosis in patients undergoing PTCA. Patients with high pre-procedural MPV values might benefit from an intensified antiplatelet therapy after coronary interventions.

Elevated whole-blood tissue factor procoagulant activity as a marker of restenosis after percutaneous transluminal coronary angioplasty and stent implantation.

Experimental data suggest that tissue factor (TF) may induce neointimal hyperplasia after arterial injury. In this study, we investigated the hypothesis that elevated levels of TF in the circulation contribute to the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Whole-blood TF procoagulant activity (TF-PCA) was measured using a previously described assay before, at 3 hours after, and at 24 hours after the intervention in 61 patients with stable angina undergoing PTCA (n=20) or stent implantation (n=41). Coronary angiography was performed 4 to 6 months after the intervention, and luminal narrowing > or =50% was defined as restenosis. Whole-blood TF-PCA levels did not correlate with intracellular monocyte tumor necrosis factor-alpha expression, a marker of activation of these cells. Baseline levels and time course of whole-blood TF-PCA after the intervention were compared in patients who did or did not subsequently develop restenosis. Whole-blood TF-PCA levels did not change significantly in the 24 hours after either intervention. However, in both the PTCA and stent groups, initial TF-PCA was significantly higher in patients who subsequently developed restenosis (P=0.018 and 0.039 compared with those who did not develop restenosis for PTCA and stent groups, respectively). Higher baseline values of whole-blood TF-PCA may be a predictor of restenosis after PTCA and stent implantation.

3523 QT interval dispersion as a new marker of restenosis after percutaneous transluminal coronary angioplasty

3523 QT interval dispersion as a new marker of restenosis after percutaneous transluminal coronary angioplasty

Serum amyloid type A may be a predictor of restenosis.

Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PTCA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. Serum amyloid type A levels > 100 micrograms/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied, 75% increased their SAA level 24 h after angioplasty. An increase of SAA by > 100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.

Analysis of atherosclerotic plaques obtained by coronary atherectomy: Foam cells correlated positively with subsequent restenosis

Restenosis following coronary intervention is a complex process the mechanisms of which remains mostly unknown. Tissue obtained by atherectomy is an important means to study restenosis. Previous studies on atherectomy-retrieved tissue have not identified histologic features that correlate with restenosis. We performed an histopathologic evaluation on atherosclerotic plaque tissue obtained by atherectomy from 58 patients, all of whom had a 6-month angiographic follow-up. We identified macrophages and lymphocytes and localized tumor necrosis factor-α expression in the tissue by immunohistochemistry. Histopathology was correlated with late angiographic outcomes. Of 10 histologic features evaluated in the plaque tissue, only the presence of foam cells, identified in paraffin sections, correlated positively with restenosis ( p = 0.04). Immunohistochemistry showed that macrophages ( p = .07), tumor necrosis factor-α ( p = .07), and lymphocytes ( p = .14) were more prominent, but not significantly so, in lesions from patients with foam cells and restenosis than in lesions from patients without foam cells or restenosis. Thus the presence of foam cells in primary lesions obtained by atherectomy as identified in paraffin-embedded tissue appears to be a marker for restenosis.

Evaluation of neopterin as a marker for restenosis following percutaneous transluminal coronary angioplasty

Evaluation of neopterin as a marker for restenosis following percutaneous transluminal coronary angioplasty

Detection of restenosis following percutaneous coronary angioplasty in single-vessel coronary artery disease: the value of clinical assessment and exercise tolerance testing.

Chest pain and submaximal exercise testing were prospectively assessed over a 6-month period, for detecting the evolution of restenosis in patients undergoing percutaneous coronary angioplasty, following either acute myocardial infarction or treatment of an anginal syndrome. Seventy-eight patients with one-vessel coronary artery disease underwent a modified treadmill exercise test at the 1-week, 3-month and 6-month follow-up after angioplasty, when a final angiogram was also performed. Forty-four patients (group A) were examined after myocardial infarction; in 34 patients (group B) angioplasty was done for incapacitating angina. Both groups showed similar results with low sensitivity and relatively moderate specificity of both chest pain and exercise tests; this was also the case for the time of restenosis to occur. It is thus concluded that the parameters examined are somewhat limited markers of restenosis following coronary angioplasty.