Predictor Of Recurrent Ischemic Events Research Articles

Perfusion deficit and vessel wall characteristics to predict recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion.

To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

Relationship between recurrent ischemic events in cerebrovascular disease and cytochrome P450 2C19 gene polymorphism on the basis of thrombelastography.

Recurrent ischemic events in cerebrovascular disease present a difficult problem in clinical practice. The predictive value of cytochrome P450 2C19 (CYP2C19) gene polymorphism and high platelet reactivity for recurrent ischemic events in cerebrovascular disease is not clear. A total of 295 patients with acute ischemic cerebrovascular disease admitted to the cerebrovascular disease center of Northern Theater General Hospital between January 1, 2020 and February 2, 2021 were enrolled in this study. Thrombelastography (TEG) was used to detect platelet reactivity and CYP2C19 gene polymorphism. Among the 118 noncarriers, 97 had normal platelet reactivity and 21 had high platelet reactivity. Of the 177 carriers, 120 showed normal platelet reactivity and 57 showed high platelet reactivity. The area under the curve (AUC) of CYP2C19 gene polymorphism in predicting recurrent ischemic events was 0.66. The regression coefficients of hypertension, stroke history, carriers, and high platelet reactivity with recurrent ischemic events were 0.341, 0.402, 0.358, and 0.281, respectively, with significant positive correlation (P<0.05). Hypertension, stroke history, carriers, and high platelet reactivity are all independent risk factors for recurrent ischemic events. CYP2C19 gene polymorphism and high platelet reactivity can be used as effective predictors of recurrent ischemic events in clinical cerebrovascular disease.

New Antithrombotic Strategies and Coronary Stent Technologies for Patients at High Bleeding Risk Undergoing Percutaneous Coronary Intervention.

Patients at High Bleeding Risk (HBR) are a sizable part of the population undergoing Percutaneous Coronary Intervention (PCI) and stent implantation. This population historically lacks standardized definition, thus limiting trial design, data generalizability, and clinical decision-- making. To overcome this limitation, the Academic Research Consortium (ARC) has recently released comprehensive guidelines defining HBR criteria for study design purposes and daily clinical practices. Furthermore, several risk scores have been developed aiming to discriminate against HBR patients and support physicians for clinical decision-making when faced with this complex subset of patients. Accordingly, the first part of this review article will explore guideline-recommended risk scoring as well as ARC-HBR criteria and their relative application for daily clinical practice. The second part of this review article will explore the complex interplay between the risk of bleeding and coronary thrombotic events in patients deemed at HBR. Indeed, several features that identify these patients are also independent predictors of recurrent ischemic events, thus challenging revascularization strategies and optimal antithrombotic therapy. Accordingly, several clinical trials have been conducted to evaluate the safety and efficacy of the new generation of coronary platforms and different antithrombotic strategies for HBR patients to minimize both ischemic and bleeding events. Accordingly, in this part, we discuss current guidelines, trials, and observational data evaluating antithrombotic strategies and stent technologies for patients at HBR.

Recovery of self-rated health as a predictor of recurrent ischemic events after first myocardial infarction: A 13-year follow-up.

Following the trajectory hypothesis for the validity of self-rated health (SRH), we tested whether subjective recovery of health, that is, return to the same or higher level of SRH after a major health event, independently predicts better long-term prognosis. Participants were 640 patients (≤ 65 years) admitted to the eight medical centers in central Israel with incident MI in a 1-year period (mean age 54, 17% female). Baseline data were collected within days of the index MI. SRH in the preceding year was assessed at baseline, and current SRH was assessed 3-6 months later. Recurrent ischemic events (recurrent MI, hospitalization with unstable angina pectoris, or cardiac death) were recorded during a mean follow-up of 13 years. A reduced risk of recurrent events was associated with an upward change of one level (e.g., from 3 at T1 to 4 at T2) in SRH (HR = 0.76, 95%CI: 0.69-0.85), controlling for baseline retrospective SRH. Risk was still significantly lower for each unit of improvement after adjusting for sociodemographics, preevent comorbidity, cardiac risk factors, MI severity, and early post-MI events (HR = 0.85, 95% CI 0.75-0.95). Individuals who perceived themselves 3-6 months after a first MI to be healthier than they had been in the year preceding the MI were more likely to survive event-free throughout the next 13 years, controlling for baseline retrospective SRH and multiple cardiac risk factors. Failure to experience such subjective recovery of one's health is a serious risk factor, which indicates that SRH should be monitored regularly after a MI.

Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke

ObjectiveThere is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis.MethodsOne hundred seventy-nine symptomatic patients with ≥50% stenosis were prospectively recruited, underwent carotid MRI, and were clinically followed up until CEA, death, or ischemic event. MRIPH was diagnosed if the plaque signal intensity was >150% that of the adjacent muscle. Event-free survival analysis was done using Kaplan–Meier plots and Cox regression models controlling for known vascular risk factors. We also undertook a meta-analysis of reported data on MRIPH and recurrent events.ResultsOne hundred fourteen patients (63.7%) showed MRIPH, suffering 92% (57 of 62) of all recurrent ipsilateral events and all but 1 (25 of 26) future strokes. Patients without MRIPH had an estimated annual absolute stroke risk of only 0.6%. Cox multivariate regression analysis proved MRIPH as a strong predictor of recurrent ischemic events (hazard ratio [HR] = 12.0, 95% confidence interval [CI] = 4.8–30.1, p < 0.001) and stroke alone (HR = 35.0, 95% CI = 4.7–261.6, p = 0.001). Meta-analysis of published data confirmed this association between MRIPH and recurrent cerebral ischemic events in symptomatic carotid artery stenosis (odds ratio = 12.2, 95% CI = 5.5–27.1, p < 0.00001).InterpretationMRIPH independently and strongly predicts recurrent ipsilateral ischemic events, and stroke alone, in symptomatic ≥50% carotid artery stenosis. The very low stroke risk in patients without MRIPH puts into question current risk–benefit assessment for CEA in this subgroup. ANN NEUROL 2013;73:774–784

Chronic kidney disease — Is it a true risk factor of reduced clopidogrel efficacy in elderly patients with stable coronary artery disease?

BackgroundChronic kidney disease (CKD) is an established predictor of recurrent ischemic events in patients with coronary artery disease (CAD). This association has been partially ascribed to high post-treatment platelet reactivity (HPPR) according to platelet function testing. However, the influencing factors of HPPR are assay-dependent, and the relevant data of elderly patients with stable CAD are absent. Patients and Methods310 elderly patients (>80years of age) with stable CAD taking prolonged maintenance clopidogrel (75mg/day) were studied. Maximal platelet aggregation rate (MPA%) with light transmittance aggregometry and Platelet Reactive Units (PRU) with VerifyNow (VN) P2Y12 system were obtained. Markers of platelet activation, including PAC-1 and CD62P, were also determined. ResultsPatients on different stages of CKD presented similar MPA% and expression of PAC-1 and CD62P. Although severe CKD patients were more likely to present HPPR identified by VNP2Y12 (odds ratio: 1.85, p=0.038), multiple logistic regression diminished this effect (adjusted odds ratio: 1.19, p=0.642), and revealed anemia as a possible predictor of HPPR (adjusted odds ratio: 5.92, p=0.001). However, in a parallel way, hemoglobin correlated with baseline PRU values as well as with post-treatment values (r=−0.624 and r=−0.463, respectively, p<0.001). Association between hemoglobin and PRU inhibition rate was not found. Moreover, hemoglobin exerted no influence on MPA% at all. ConclusionCKD is not necessarily associated with reduced antiplatelet effects of clopidogrel in elderly patients with stable CAD taking prolonged maintenance clopidogrel, and the seemingly influence of CKD on HPPR assessed by VNP2Y12 assay may be due to the artifactual effect of hemoglobin on VNP2Y12.

Impact of Anemia on Platelet Response to Clopidogrel in Patients Undergoing Percutaneous Coronary Stenting

High residual platelet reactivity (HRPR) on clopidogrel is a predictor of recurrent ischemic events in patients undergoing percutaneous coronary interventions (PCI). Significant intraindividual variability in platelet aggregation on repeat testing has been reported. To understand factors contributing to the variability in platelet aggregation testing, we examined clinical and laboratory elements linked to HRPR in 255 consecutive patients tested ≥12 hours after PCI using light transmission aggregometry (LTA) in response to adenosine diphosphate 5 μmol/L and VerifyNow P2Y12 assay (VNP2Y12; Accumetrics). HRPR was defined as >46% residual aggregation for LTA and >236 P2Y12 response units (PRUs) for VNP2Y12. On multivariate analysis the only variable independently associated with HRPR with both LTA and VNP2Y12 was laboratory-defined anemia. Prevalences of HRPR by LTA were 34.3% in anemic patients, 15.6% in patients with normal hemoglobin levels, and 59.8% versus 25.9% by VNP2Y12 (p <0.005 for the 2 comparisons). In a subgroup of 50 patients, testing was done before and after the clopidogrel loading dose. At baseline there were no differences in platelet aggregation with either assay; however, absolute decrease in reactivity after the clopidogrel load was significantly less in anemic patients compared to patients with normal hemoglobin (change in residual aggregation by LTA 15.8 ± 5.8% vs 28.8 ± 3.2%, p <0.05; change in PRU by VNP2Y12 56.5 ± 35.5 vs 145.0 ± 14.2 PRUs, p <0.05, respectively). In conclusion, anemia is an important contributor to apparent HRPR on clopidogrel and may explain some of the intraindividual variability of platelet aggregation testing.

Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment

The pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications via plaque rupture. Circulating leukocytes and particularly neutrophils have been shown to be an independent predictor of recurrent ischemic events. However, neutrophils are poorly documented within atherosclerotic plaques. We hypothesized that intraplaque hemorrhage could convey neutrophils into the lesion, spreading into the necrotic core, thus participating in its protease enrichment. One hundred human carotid endarterectomy specimens were dissected into culprit-stenosing plaques (CPs) and adjacent noncomplicated plaques. Half of CPs exhibited hemorrhage, which was confirmed by the release of hemoglobin. Pro- and active forms of matrix metalloproteinase-9 (MMP-9) were increased in media conditioned by hemorrhagic plaques. Higher levels of lipocalin [neutrophil gelatinase-associated lipocalin (NGAL)]/MMP-9 complexes, specifically released by neutrophils, were also found in conditioned media from plaques with hemorrhage. Immunohistochemical analysis of the corresponding carotid samples showed that neutrophil markers such as elastase, NGAL/MMP-9, CD66b, and proteinase 3 colocalized with blood constituents (i.e., hemoglobin, plasminogen). All markers of neutrophil degranulation were positively correlated in CP-conditioned media (alpha1-antitrypsin/elastase complexes, myeloperoxidase, and alpha-defensins), and higher levels came from CPs containing intraplaque hemorrhages. Addition of an elastase inhibitor at the time of incubation led to a decrease in the proMMP-9 activation in CPs, suggesting cross-talk between proteases released by neutrophils. Finally, we found that neovessels observed at the interface between cap and core exhibit an activated endothelium, which may favor leukocyte diapedesis. Our study thus provides evidence for the involvement of neutrophils in plaque vulnerability.

Predictors of recurrent ischemic events and death in unstable coronary artery disease after treatment with combination antithrombotic therapy

Background Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS. Methods We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days. We created multivariable regression models to predict these end points from baseline factors. Results Overall, 682 patients (21%) reached the triple end point and 220 (6.8%) reached the double end point. Independent predictors of the triple end point were admission with myocardial necrosis, ST-segment depression, prior angina severity, symptom duration, and allocation to enoxaparin treatment in patients with ST-segment depression (significant interaction). Independent predictors of the double end point were admission with myocardial necrosis, ST-segment depression, enrollment region, age >75 years, prior angina severity, and rales. By deciles, the average predicted risk for the double end point ranged from 2% to 20%: a patient aged <75 years with no risk factors had a 3.5% risk, whereas a patient aged >75 years with 2 additional high-risk features (myonecrosis and ST depression) had a risk of death or reinfarction of 26%. Conclusions Patients with non-ST-segment elevation ACS exhibit a broad range of risk of adverse recurrent ischemic events. The predictive power of the model for the triple end point, using baseline variables, was modest. However, a subgroup at very low risk of the double end point (average 2%) can be identified with baseline variables. (Am Heart J 2000;139:962-70.)

Incidence and predictors of early recurrent ischemia after successful percutaneous transluminal coronary angioplasty for acute myocardial infarction

Two hundred forty consecutive patients with acute myocardial infarction treated within 48 hours by successful percutaneous transluminal coronary angioplasty (PTCA) were analyzed to determine the incidence and predictors of recurrent ischemic events during hospitalization. Thirty-nine patients had recurrent ischemia: 20 patients had chest pain or electrocardiographic changes requiring repeat PTCA or bypass surgery, or resulting in a second creatine kinase elevation suggestive of myocardial infarction; 12 had total occlusion of the dilated artery on follow-up angiography; and 7 had exercise-induced ischemia and ≥ 70% diameter stenosis that required PTCA or bypass surgery before hospital discharge. In-hospital mortality was 15% in the recurrent ischemia group, compared to 1% in the group without recurrent myocardial ischemia (p < 0.001). Angiographic follow-up before hospital discharge was obtained in 198 patients, including 38 of the 39 patients with ischemic events. Thus, the true incidence of recurrent ischemic events was between 39 of 199 and 39 of 240, or 16 and 20%. In multivariate analyses, recurrent ischemia was predicted by translesional gradient >25 mm Hg (p = 0.001), dissection (p = 0.01) and post-PTCA Thrombolysis in Myocardial Infarction 2 flow pattern (p = 0.016). However, even in the absence of these risk factors recurrent ischemic events occurred in 13% of patients. Post-PTCA percent diameter stenosis (whether assessed by objective or visual assessment), degree of the early systemic fibrinolytic state, post-PTCA residual minimal diameter and concomitant use of thrombolytic agents were not predictive. Thus, recurrent ischemia after successful PTCA for acute myocardial infarction occurs in 16 to 20% of patients, is significantly more common with post-PTCA translesional gradient ≥ 25 mm Hg, dissection or Thrombolysis in Myocardial Infarction 2 flow, but may also occur unpredictably.