Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study

Kinlay, Scott; Schwartz, Gregory G.; Olsson, Anders; Rifai, Nader; Szarek, Michael; Waters, David D.; Libby, Peter; Ganz, Patricia A.

doi:10.1161/atvbaha.107.151787

Cited by 60 publications

(34 citation statements)

References 41 publications

(45 reference statements)

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“…Researchers in other studies (26)(27)(28)(29) were made in this investigation, including assumption of a linear relationship between concentration and signal intensity and the absence of agent effl ux in the Patlak model. From a physiologic perspective, we did not control for factors, such as hematocrit level, that can affect plasma concentration, nor did we assess the natural variability of perfusion characteristics over short time periods.…”

Section: Discussionmentioning

confidence: 99%

Carotid Artery Atherosclerosis: Effect of Intensive Lipid Therapy on the Vasa Vasorum—Evaluation by Using Dynamic Contrast-enhanced MR Imaging

Dong

Kerwin²,

Chen³

et al. 2011

Radiology

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Purpose:To investigate whether short-term, intensive lipid therapy leads to changes in microvascular characteristics, as measured by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods:Institutional review board approval and informed consent were obtained for this HIPAA-compatible study. Subjects with established coronary artery disease or carotid artery stenosis of 15% or greater determined by using ultrasonography and with levels of apolipoprotein B of 120 mg/dL (1.2 g/L) or greater were enrolled in an ongoing study (clinical trial NCT00715273). All received intensive lipid therapy to achieve targeted high-and low-density lipoprotein cholesterol levels and underwent serial serum monitoring including high-sensitivity C-reactive protein (HsCRP) level measurements. Carotid artery MR imaging examinations including morphologic and DCE MR images were obtained at baseline and 1 year after treatment. In subjects with advanced lesions ( . 2 mm thick), MR image analysis was performed, including measurement of lipid-rich necrotic core size and kinetic modeling of DCE MR images to assess changes in the transfer constant ( K trans ). The differences in K trans between baseline and 1-year follow-up were compared by using the Wilcoxon signed rank test, and associations were assessed by using the Spearman rank correlation coeffi cient. Results:Twenty-eight subjects with interpretable DCE MR imaging results at both baseline and 1-year follow-up were included. After 1 year of treatment, a signifi cant reduction was found in mean K trans (0.085 min 2 1 6 0.037 [standard deviation] to 0.067 min 2 1 6 0.028, P = .02). Reduction in K trans was not signifi cantly correlated with observed reductions in lipid-rich necrotic core size or reductions in HsCRP level. Conclusion:These fi ndings suggest that DCE MR imaging may be a useful imaging method for the assessment of the therapeutic response of the vasa vasorum in patients with atherosclerotic plaque.Clinical trial registration no. NCT00715273.q RSNA, 2011

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Section: Discussionmentioning

confidence: 99%

Carotid Artery Atherosclerosis: Effect of Intensive Lipid Therapy on the Vasa Vasorum—Evaluation by Using Dynamic Contrast-enhanced MR Imaging

Dong

Kerwin²,

Chen³

et al. 2011

Radiology

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“…In the GRACE registry, prior statin use was associated with reduced stroke risk in ACS patients [35]. More recently, Kinlay et al [39] using the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) data reported elevated inflammatory markers in those who developed stroke after ACS when compared to nonstroke patients. These inflammatory markers included C-reactive protein, serum amyloid A and interleukin-6.…”

Section: Discussionmentioning

confidence: 99%

“…The INTERSTROKE study [7] that enrolled 3,000 patients with first stroke in 22 countries has recently reported risk factors for stroke which include hypertension, smoking, abdominal obesity, diabetes, stress and depression; however, there is little agreement in the literature about predictors of stroke after AMI with the exception of older age and prior stroke [4,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. For example, hypertension [14,15,22,33,34] and diabetes [22,27,32,33,36,37] were shown in some, but not all, studies to be predictors of stroke.…”

Section: Introductionmentioning

confidence: 99%

Early Stroke following Acute Myocardial Infarction: Incidence, Predictors and Outcome in Six Middle-Eastern Countries

Albaker

Zubaid²,

Alsheikh‐Ali³

et al. 2011

Cerebrovasc Dis

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Background and Objectives: Stroke is a potential complication of acute myocardial infarction (AMI). The aim of this study was to identify the incidence, risk factors predisposing to stroke and in-hospital outcome during the index admission with AMI among patients in the Middle East. Methods: For a period of 6 months in 2006 and 2007, 5,833 consecutive AMI patients were enrolled from 64 hospitals in 6 Middle East countries. Results: The incidence of in-hospital stroke following AMI was 0.85%. Most cases were ST segment elevation AMI-related and ischemic in nature. Patients with in-hospital stroke were older than patients without stroke and were more likely to be female (36 vs. 18.6%, p = 0.0033). They were also more likely to have diabetes mellitus, dyslipidemia, prior AMI, or percutaneous/surgical coronary revascularization. Patients with stroke were more likely to present with advanced Killip class II–IV, higher mean heart rate and higher serum creatinine. Independent predictors of stroke were age, prior stroke, prior coronary artery bypass surgery, anterior AMI and systolic blood pressure >190 mm Hg on presentation. Early administration of statins was independently associated with reduced stroke risk (odds ratio, OR, 0.4, 95% confidence interval, CI, 0.19–0.90, p = 0.025). Stroke was fatal in 44% of the cases and was independently associated with in-hospital mortality (adjusted OR 12.5, 95% CI 5.7–27.4, p < 0.01). Conclusion: There is a low incidence of in-hospital stroke in Middle-Eastern patients presenting with AMI but with very high fatality rates. Early statin therapy was associated with a significant reduction in stroke risk. Future work should be focused on reducing the risk and improving the outcome of this devastating complication.

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“…The protective role of statins in AF prevention in patients with coronary artery disease remains a matter of heated debate (2,81,125,174). Indeed, in the Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial, the protection afforded by statin treatment in patients with acute coronary disease did not reach statistical significance (OR = 0.97, 95% CI: 0.72-1.31) (78). More recently, a meta-analysis suggested that statins could reduce the AF risk in patients with acute coronary syndrome.…”

Section: Primary Prevention Of Afmentioning

confidence: 99%

Targeting Inflammation and Oxidative Stress in Atrial Fibrillation: Role of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibition with Statins

Pinho-Gomes

Reilly

Brandes

et al. 2014

Antioxidants & Redox Signaling

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Significance: Atrial fibrillation (AF) is a burgeoning health-care problem, and the currently available therapeutic armamentarium is barely efficient. Experimental and clinical evidence implicates inflammation and myocardial oxidative stress in the pathogenesis of AF. Recent Advances: Local and systemic inflammation has been found to both precede and follow the new onset of AF, and NOX2-dependent generation of reactive oxygen species in human right atrial samples has been independently associated with the occurrence of AF in the postoperative period in patients undergoing cardiac surgery. Anti-inflammatory and antioxidant agents can prevent atrial electrical remodeling in animal models of atrial tachypacing and the new onset of AF after cardiac surgery, suggesting a causal relationship between inflammation/oxidative stress and the atrial substrate that supports AF. Critical Issues: Statin therapy, by redressing the myocardial nitroso-redox balance and reducing inflammation, has emerged as a potentially effective strategy for the prevention of AF. Evidence indicates that statins prevent AF-induced electrical remodeling in animal models of atrial tachypacing and may reduce the new onset of AF after cardiac surgery. However, whether statins have antiarrhythmic properties in humans has yet to be conclusively demonstrated, as data from randomized controlled trials specifically addressing the relevance of statin therapy for the primary and secondary prevention of AF remain scanty. Future Directions: A better understanding of the mechanisms underpinning the putative antiarrhythmic effects of statins may afford tailoring AF treatment to specific clinical settings and patient's subgroups. Large-scale randomized clinical trials are needed to support the indication of statin therapy solely on the basis of AF prevention. Antioxid. Redox Signal. 20, 1268Signal. 20, -1285

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Inflammation, Statin Therapy, and Risk of Stroke After an Acute Coronary Syndrome in the MIRACL Study

Cited by 60 publications

References 41 publications

Carotid Artery Atherosclerosis: Effect of Intensive Lipid Therapy on the Vasa Vasorum—Evaluation by Using Dynamic Contrast-enhanced MR Imaging

Carotid Artery Atherosclerosis: Effect of Intensive Lipid Therapy on the Vasa Vasorum—Evaluation by Using Dynamic Contrast-enhanced MR Imaging

Early Stroke following Acute Myocardial Infarction: Incidence, Predictors and Outcome in Six Middle-Eastern Countries

Targeting Inflammation and Oxidative Stress in Atrial Fibrillation: Role of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibition with Statins

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