Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction

Ishida, Kentaro; Geshi, Toru; Nakano, Ayako; Uzui, Hiroyasu; Mitsuke, Yasuhiko; Okazawa, Hidehiko; Ueda, Takanori; Lee, Jong–Dae

doi:10.1016/j.ijcard.2011.11.015

Cited by 18 publications

(14 citation statements)

References 34 publications

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“…Prospective identification of patients with significant inflammatory milieu or microvascular dysfunction may allow clinicians to tailor the intensity of risk modification strategies. Patients with elevated hsCRP level may be offered intensive statin therapy as statins have been shown to exert pleiotropic effects on improving endothelial and microvascular function ( 40 , 41 ). Inhibition of renin–angiotensin system should also be considered in high-risk population as it was shown to improve microvascular function ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease

Tong

Whitbourn

MacIsaac

et al. 2018

Front. Cardiovasc. Med.

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BackgroundInflammation and microvascular dysfunction (MVD) are independently associated with adverse cardiovascular outcomes in patients with ischemic heart disease. This study aimed to assess the relationship between inflammation, MVD, and myocardial injury.MethodsCoronary microvascular function was assessed in 74 patients undergoing percutaneous coronary intervention (PCI) using the index of microvascular resistance (IMR) by a pressure–temperature sensor-tipped wire. Serum high-sensitivity C-reactive protein (hsCRP) level was quantified by rate turbidimetry. Severe MVD was defined as IMR ≥ 30. Pearson correlation was computed to assess the relationships between hsCRP, troponin, and IMR of culprit vessel. Predictors of severe MVD were assessed by regression analysis.ResultsAcute coronary syndromes (ACSs) represented 49% of the total cohort. Study cohort was divided into low C-reactive protein (CRP) (hsCRP < 3 mg/L) and high CRP (hsCRP ≥ 3 mg/L) groups. There was higher representation of smokers (78 vs. 52%), diabetics (39 vs. 18%), and ACS (61 vs. 33%), as well as higher body mass index (29.4 ± 4.6 vs. 27.2 ± 4.1) in the high CRP group. Pre-PCI and post-PCI IMR were significantly elevated in the high CRP group compared to the low CRP group (pre-PCI IMR: 29.0 ± 13.9 vs. 17.4 ± 11.1, p < 0.0001; post-PCI IMR: 23.0 ± 16.8 vs. 15.5 ± 8.4, p = 0.02). Peak troponin levels were significantly raised in the high CRP group (9.96 ± 17.19 vs. 1.17 ± 3.00 μg/L, p = 0.002). There was a strong positive correlation between hsCRP and pre-PCI IMR (r = 0.85, p < 0.0001). Pre- and post-PCI IMR levels were correlated with peak troponin level (r = 0.45, p < 0.0001; r = 0.33, p = 0.005, respectively). Predictors of severe MVD include male gender (OR 3.0), diabetes (OR 3.7), smoking history (OR 4.0), ACS presentation (OR 8.5), and hsCRP ≥ 3 mg/L (OR 5.6).ConclusionhsCRP is a significant predictor of MVD while MVD is associated with myocardial injury, supporting the central role of inflammation and MVD in the pathophysiology and complications of coronary artery disease.Clinical Trial RegistrationAustralian New Zealand Clinical Trials Registry (ACTRN): 12617000648325. Universal Trial Number (UTN): U1111-1196-2246.

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Section: Discussionmentioning

confidence: 99%

High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease

Tong

Whitbourn

MacIsaac

et al. 2018

Front. Cardiovasc. Med.

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“…ACCEPTED MANUSCRIPT 22 Statins have also been shown to exert pleiotropic effects on endothelial and microvascular function in post-AMI patients (121)(122)(123). In fact, pre-treatment with statins has been shown to preserve microvascular integrity lower and reduce the extent of periprocedural myocardial injury in AMI patients undergoing PCI, resulting in better left ventricular functional recovery as demonstrated on echocardiography (124).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Novel risk factors for acute coronary syndromes and emerging therapies

Tong

Wilson

Layland

2016

International Journal of Cardiology

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“…These pleiotropic effects reflect amelioration of endothelial dysfunction by several mechanisms, reviewed in references [14–21]. Briefly, these include, enhanced NO bioavailability and upregulation of endothelial nitric oxide synthase (eNOS), mainly via inhibition of Rho protein prenylation in the mevalonate pathway [22, 23]. Statins decrease production of superoxide anion via downregulation of angiotensin (AT)-II induced free radical production by Rac-I mediated NAD(P)H oxidase activity [24].…”

Section: Introductionmentioning

confidence: 99%

Short-term High-Dose Effect of Lovastatin on Thrombolysis by rt-PA in a Human Whole-Blood in vitro Clot Model

Kandadai¹,

Meunier²,

Lindsell³

et al. 2012

CNR

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High-dose hydroxymethylglutaryl coenzyme. A reductase inhibitor (statin) administration reduces neuronal injury and improves outcomes in experimental models of acute ischemic stroke, and has been shown to be safe in a phase 1 dose-escalation study using lovastatin at doses higher than currently approved for daily use. Statins also affect the hemostatic system by upregulating t-PA expression and decreasing plasminogen activator inhibitor (PAI-1) expression, platelet adhesion and thrombus formation in animal models. Since a thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), is currently the only FDA-approved therapy for use in ischemic stroke patients, it is important to ascertain whether high statin doses impact the efficacy of rt-PA. The main goal of this study was to evaluate the effect of a high dose of lovastatin and its active form, lovastatin hydroxy acid, on rt-PA thrombolysis in an in vitro model. Percentage clot lysis was measured in the presence and absence of rt-PA in three different treatment groups: lovastatin, lovastatin hydroxy acid, and ethanol. The effect of ethanol on clot lysis was studied since ethanol was used to disperse the highly hydrophobic lovastatin. The decrease in clot width over time was measured using microscopic imaging of an in vitro human whole blood clot model; an approximately 400 μm diameter clot was formed on suture silk, suspended in human fresh frozen plasma (hFFP) and exposed to treatment. In the absence of rt-PA. clot lysis did not show statistically significant differences in the percentage clot lysis between different treatment groups (p=0.103). In the presence of rt-PA, clot lysis was greater than in the absence of rt-PA for all groups, but there were no statistically significant differences between treatment groups (p=0.385). In this in vitro study, high doses of lovastatin neither impaired nor enhanced the lytic efficacy of rt-PA.

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Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction

Cited by 18 publications

References 34 publications

High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease

High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease

Novel risk factors for acute coronary syndromes and emerging therapies

Short-term High-Dose Effect of Lovastatin on Thrombolysis by rt-PA in a Human Whole-Blood in vitro Clot Model

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