Coronary Arteriosclerosis in Patients With Acute Ischemic Stroke Prevalence and Characteristics as Measured by CT Angiography, Echocardiography and Biomarkers

Background:

Stroke and myocardial infarction are leading causes of death and disability in the industrialized countries. Multiple interactions exist between the various forms of cardiovascular and cerebrovascular diseases and several risk factors for the development of stroke and major cardiovascular diseases are similar, as emphasized by the recent publication of a common set of guidelines for the primary prevention of both. Following myocardial infarction the stroke incidence is markedly increased, particular early after myocardial infarction. Additionally, non-stroke cardiovascular disease, especially coronary artery disease, is the main cause of long-term mortality in patients surviving cerebrovascular diseases. The history of ischemic heart disease in stroke patients is often unreliable because of cognitive and language impairments or simply because ischemic heart disease is asymptomatic. For at least 25 years myocardial damage has repeatedly been proposed as a consequence of an acute stroke, i.e. being neuromediated. Most prior studies were performed in patients with subarachnoid hemorrhage, and consequently only limited data regarding ischemic stroke, the most common cerebrovascular ailment, are available. Recently it has been demonstrated that highly sensitive and specific markers for the detection of myocardial necrosis, i.e., cardiac troponins, may be elevated in 0 % - 34 % of patients with ischemic stroke. However, the majority of the studies conducted have not sufficiently evaluated coexisting coronary artery disease. The neuromediated theory has been supported in patients with subarachnoid hemorrhage and elevated troponin levels due to lack of significant obstructive coronary artery disease evaluated by coronary angiograms. Little is known about a conceivable cause-effect relationship between acute ischemic stroke and myocardial necrosis, i.e., neuromediation, or if the elevated levels of troponin are caused by direct cardiac damage, i.e., AMI.

Recently, several reports have demonstrated that levels of natriuretic peptides are increased in patients with acute ischemic stroke. The hormone Brain Natriuretic Peptide (BNP) and its split product (NT-proBNP) derives predominantly from the myocardium and is processed as a response to stretch of cardiomyocytes and hemodynamic stress. The mechanism of elevated levels of NT-proBNP in the setting of acute ischemic stroke is unknown. Myocardial ischemia is known to cause release of NT-proBNP. Accordingly, levels of NT-proBNP are higher in acute ischemic stroke patients with ST-segment depression on 12-lead ECG than in those without. However, it is unknown whether levels of NT-proBNP are correlated to coronary arteriosclerosis and left ventricle function in patients with acute ischemic stroke.

The current gold standard for the detection of atherosclerotic coronary artery disease (CAD), invasive coronary angiography (CAG), allows direct visualization of the coronary artery lumen. Inconvenience to patients and a small but not negligible risk of complications related to CAG have prompted an intensive search for alternative, reliable non-invasive means of coronary artery visualisation. Standard non-invasive methods such as stress testing lack sufficient sensitivity in detecting significant CAD. Over the last decade multislice computed tomography (MSCT) has emerged as a promising non-invasive method in the assessment of CAD. Previous studies have convincingly demonstrated a very high negative predictive value of MSCT coronary angiography (CTA) with CAG as the reference. Thus, a normal CTA seems to allow the clinician to rule out the presence of hemodynamic relevant coronary artery stenoses with a high degree of reliability. In addition to detecting significant coronary artery stenosis, recent focus has been on visualising and characterising coronary artery plaques. Both necropsy and coronary intravascular ultrasound (IVUS) studies have shown that "normal" vessels at CAG may in fact contain a significant amount of atherosclerotic plaques. Independent of the degree of coronary artery stenosis, some plaques may be at increased risk of erosion or rupture. The latter, unstable plaques are thought to trigger acute coronary ischemic events. Accordingly, the release of troponins, NT-proBNP and ECG changes observed in these patients could be due to CAD. So far serial investigation of CAD has never been performed in patients with acute ischemic stroke.

Objective: