Download Acute Myocardial Infarction, Ischemic, Inflammation

Acute Myocardial Infarction, Ischemic
Stroke, Sympathetic Stress, and
Inflammation
Birds of a Feather
1. Jose I. Suarez, MD
+ Author Affiliations
1. From the Department of Neurology, University Hospitals of Cleveland, Case Western
Reserve University, Cleveland, Ohio.
1. Correspondence to Jose I. Suarez, MD, Department of Neurology, Case Western Reserve
University, 11100 Euclid Avenue, Cleveland, OH. E-mail [email protected]
Key Words:
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acute myocardial infarction
acute stroke
inflammation
sympathethic stress
thrombolysis
See related article, pages 2546–2551
Stroke, the leading cause of neurological death, is the leading cause of disability in the US.1
Ischemic stroke represents about 85% of all strokes and is a heterogeneous condition. Generally
speaking, ischemic strokes can be classified into different categories according to their presumed
mechanism as follows: infarct with large artery thrombosis; embolism attributed to cardiac
sources or cardioembolic; lacunar infarction; or cryptogenic infarction or infarct of undetermined
cause.2 Cardioembolic strokes are a major mechanism of ischemic strokes with nonvalvular atrial
fibrillation alone accounting for about 25% of all ischemic events.3 Other cardiac conditions that
have been associated with cardioembolic strokes include acute myocardial infarction (AMI),
ventricular aneurysm, rheumatic valvular disease, mechanical prosthetic valve, and left atrial or
ventricular thrombi to name the most common.
The association between ischemic stroke and AMI has been recognized for several decades. The
risk of ischemic stroke in patients presenting with AMI has declined from 2.4% to 3.5% in
earlier reports to about 0.6% to 1.8% in more recent studies incorporating thrombolytic or
anticoagulant therapy in the acute phase.4–6 Despite such infrequent occurrence of ischemic
strokes after AMI, the outcome of patients is poor with high mortality (17%) and disability
(80%).5
It is commonly accepted that the relationship between ischemic strokes in the setting of AMI is
most likely multifactorial. Factors frequently cited in the literature include older age, history of
prior stroke, diabetes, or hypertension, and the presence of large akinetic segments of
myocardium with or without left ventricular thrombus.5,7,8 These studies have evaluated the risk
of ischemic strokes between 30 days to 5 years after AMI. In this issue of Stroke, van de Graff et
al present an interesting study investigating the relationship between time to revascularization for
AMI and risk of in-hospital ischemic stroke.9 The authors analyzed data from the National
Registry of Myocardial Infarction 3 and 4 databases that included 45 997 patients who received
thrombolytic therapy and 47 876 patients who were treated with primary percutaneous
transluminal coronary angioplasty for AMI. The authors found that the risk of in-hospital
ischemic stroke after AMI was independently associated with timing to revascularization and
that this association was not related to improved cardiac function. This is a significant finding for
various reasons. First, it underscores the importance of early revascularization for patients
presenting with AMI, not only to improve cardiac outcome but also to reduce neurological
complications. Second, similar to what has been reported for acute ischemic stroke,10 earlier
treatment for AMI improves outcome. Third, cardiac dysfunction may not be as important a
factor as previously reported in the short-term risk of ischemic stroke in patients with AMI.
If cardiac dysfunction is not an important factor, then what are the possible explanations for this
apparent time-dependent decreased risk of ischemic stroke reported by van de Graff et al? 9 As
the authors stated in their article, it has been elucidated that inflammatory response plays an
important role in the genesis and progression of atherosclerotic lesions.11–13 Inflammation of
vulnerable atherosclerotic plaques may contribute to the development of acute coronary
syndromes and such plaque instability may extend to other vascular beds such as the carotid
arteries. High levels of serum C-reactive protein are frequently observed in unstable angina and
AMI. Such elevation of C-reactive protein is mostly regulated by proinflammatory cytokines and
is largely unaltered by the administration of anti-inflammatory medications.11 van de Graff et al
postulate that such inflammatory response induces a thrombogenic state that may be responsible
for the increased risk of early ischemic strokes in patients with AMI.9 Thus, the earlier coronary
revascularization may result in a lesser inflammatory response and an associated lower risk of
ischemic stroke. One factor that is not addressed in this article is the role of sympathetic stress in
AMI. Sympathetic activity may promote coagulation (via upregulation of platelet activation and
factor VIII and downregulation of the fibrinolytic system) and inflammation (via upregulation of
T helper cytokines).14 This evidence suggests that sympathetic activity along with inflammation
can induce, and be further stimulated by, thrombotic events such as AMI and ischemic strokes.
We find further support in the fact that higher heart rate, presumably a surrogate marker for
sympathetic activity, is an independent predictor of ischemic stroke in patients with AMI.5 van
de Graff et al reported that there was no difference in the use of β-blocking medications among
the various groups stratified by time from presentation to initiation of therapy.9 However, the
authors did not comment on the dosages given and the minimum heart rate and blood pressure
achieved, which may reflect limitations in the data collection process for the databases used. One
can only speculate that those patients treated earlier may have received β-blocking drugs sooner
accompanied by lower sympathetic activity leading to a lower risk of in-hospital ischemic stroke
compared with those patients treated at later time epochs. Further prospective studies are needed
to elucidate this very important question. Regardless of the mechanisms involved, this study
suggests one thing: that the earlier the treatment of AMI the lower the risk of cerebrovascular
complications.
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Acknowledgments
Disclosures
None.
Previous SectionNext Section
Footnotes
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The opinions in this editorial are not necessarily those of the editors or of the American
Heart Association.
Previous Section
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Stroke. 2006;37:2546-2551, published online before print September 7 2006,
doi:10.1161/01.STR.0000240495.99425.0f