doi: 10.1161/01.STR.0000023346.80463.A4
(Stroke. 2002;33:1944.)
© 2002 American Heart Association, Inc.
Letters to the Editor |
Cardiac Enzyme Elevations After Stroke: The Importance of Specificity
Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia
To the Editor:
We read with great interest the recent article by Ay et al1 examining cardiac enzyme levels after stroke. The authors are to be commended for drawing attention to the seldom-recognized cardiac complications of stroke. In this study, levels of troponin T, a very specific marker of myocardial damage, were measured in 32 acute hemispheric stroke patients. As there were no significant elevations in troponin T, even in patients with increased serum creatine kinase–MB (CK-MB) levels, it was concluded that the latter was not cardiac in origin.
Cardiac sequelae including myocytolysis, serum enzyme elevations, and arrhythmias are known to develop in a portion of stroke patients. There is a great deal of clinical and experimental evidence that cardiac changes in stroke result from excessive sympathetic nervous activity secondary to insular cortical damage.2–6 It is unclear whether the insula was included, and if so to what extent, in the infarcts of the present cohort. As has been previously reported, the current study demonstrated elevated CK-MB levels in a number of patients.7 Unlike previous investigations, however, this study did not correlate increases in CK-MB with measures of sympathetic nervous activity.8 Although CK-MB rises in the current report appear to have a noncardiac source, this may not be the case in all patients with enzyme elevations. Those patients in whom sympathetic tone is perturbed may in fact develop specific cardiac enzyme changes.
The ultimate clinical goal is the identification of those patients at risk for autonomic and cardiac disturbances after stroke. Future studies may be aided by stratification of patients according to other factors thought to be important in the pathogenesis of poststroke autonomic changes, including age, right hemispheric involvement, and premorbid blood pressure.5,6,9 In addition, correlation of cardiac enzyme increases with other indices of altered autonomic activity including changes in diurnal blood pressure variation, heart rate variability, or QTc interval may also assist in the identification of those patients at risk for neurogenic cardiac damage.10,11
This study assessed the heart with a more specific serological marker than has previously been reported. Importantly, it has revealed that CK-MB elevations are notalways related to the heart. The same degree of specificity may need to be applied to the neurological condition of the patients to definitively conclude that enzyme elevations arenevercardiac in origin. Thus, in the future, troponin T levels should be correlated with both insular cortical lesions and serum catecholamine levels.
References
1. Ay H, Arsava EM, Saribas O. Creatine kinase-MB elevation after stroke is not cardiac in origin: comparison with troponin T levels. Stroke. 2002; 33: 286–289.
2. Butcher KS, Cechetto DF. Insular lesion evokes autonomic effects of stroke in normotensive and hypertensive rats. Stroke. 1995; 26: 459–465.
3. Cheung RT, Hachinski V. The insula and cerebrogenic sudden death. Arch Neurol. 2000; 57: 1685–168.
4. Oppenheimer SM, Hachinski VC. The cardiac consequences of stroke. Neurol Clin. 1992; 10: 167–176.[Medline] [Order article via Infotrieve]
5. Tokgozoglu SL, Batur MK, Topuoglu MA, Saribas O, Kes S, Oto A. Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke. 1999; 30: 1307–1311.
6. Cechetto DF. Cardiovascular consequence of experimental stroke. Baillieres Clin Neurol. 1997; 6: 297–308.[Medline] [Order article via Infotrieve]
7. Norris JW, Hachinski VC, Myers MG, Callow J, Wong T, Moore RW. Serum cardiac enzymes in stroke. Stroke. 1979; 10: 548–553.
8. Myers MG, Norris JW, Hachinski VC, Weingert ME, Sole MJ. Cardiac sequelae of acute stroke. Stroke. 1982; 13: 838–842.
9. Sander D, Klingelhofer J. Extent of autonomic activation following cerebral ischemia is different in hypertensive and normotensive humans. Arch Neurol. 1996; 53: 890–894.
10. Sander D, Klingelhofer J. Changes of circadian blood pressure patterns after hemodynamic and thromboembolic brain infarction. Stroke. 1994; 25: 1730–1737.[Abstract]
11. Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke. Neurology. 2001; 57: 833–838.
Response
, MDDepartment of Neurology, Hacettepe University Hospitals, Ankara, Turkey
We thank Drs Butcher and Parsons for their interest in our article. In the referred study,1 we serially determined cardiac enzyme levels including troponin T and CK-MB from day 1 to day 5 of stroke in 32 consecutive patients, 24 of whom had large middle cerebral artery territory infarctions, also including the insula. The study outlined a specific signature of cardiac enzyme changes, "normal troponin T along with elevated CK-MB." Given that troponin T is a more sensitive and specific marker for minor myocardial injury, our results led us to two clinically important conclusions. First, CK-MB elevations after stroke are not cardiac in origin, and second, CK-MB falsely increases after stroke. The latter might be especially important for the diagnosis of acute coronary syndromes occurring within the acute phase of stroke. This is not a rare event and can occur in up to 9% of all stroke patients.2
Neurogenic influence on the heart is a well-known phenomenon with pathological proof of myocytolysis and electrophysiological proof of cardiac conduction abnormalities. The third proof, however, specific enzyme changes (subtle and gradual CK-MB elevations), is now in question. Indeed, the evidence linking human cerebral lesions to CK-MB elevations from a cardiac source is not concrete. Previous novel studies introducing CK-MB elevations after human cerebral injury fail to provide any direct proof of the heart as the cause of CK-MB elevations3–5; autonomic perturbations and elevated systemic catecholamine levels might have used sources other than the heart to cause the CK-MB elevations observed in these studies. The authors raise the issue that cardiac contribution to the CK-MB elevations observed in our patients (34% of all stroke patients) might still have occurred, especially in those with infarctions in the high-risk brain regions for myocardial injury. This assumption requires that underlying myocardial mechanisms that mediate troponin T release differ from those that mediate CK-MB release. Thus, neurogenic influences could increase CK-MB levels without altering troponin T. To our knowledge, there are no data compatible with this. In contrast, troponin T has been shown to be superior to CK-MB in both ischemic and nonischemic modes of myocardial injury.6,7 It seems more likely that if ever a cardiac contribution to the CK-MB elevations occurs, then troponin-T should also increase.
It is often problematic to identify the cause of cardiac perturbations and sudden deaths observed in patients with stroke. A concomitant coronary artery disease complicated by a coincidental plaque rupture triggered by stroke-related factors might be a cause. An accurate differentiation between the neurogenic and cardiogenic influences through the use of a serologic marker is the ultimate goal. Our study solves a piece of the puzzle by showing that CK-MB is not appropriate for this role. Drs Butcher and Parsons have delicately outlined the direction of future research in this field. While concurring with all, we should like to add that studies examining other cardiac-specific enzymes such as troponin I are also needed. Furthermore, these studies should be tailored with the capability to correlate cardiac enzyme levels with a more properly defined gold standard for neurogenic cardiac injury. Finally, they should not only enroll patients with isolated insular lesions, but also investigate unselected patients with various infarction patterns because the clinical importance of their results should have an impact in more general stroke populations.
References
1. Ay H, Arsava EM, Sariba O. Creatine kinase-MB elevation after stroke is not cardiac in origin: comparison with troponin T levels. Stroke. 2002; 33: 286–289.
2. Rolak LA, Rokey R. The patient with concomitant stroke and myocardial infarction: clinical features. In: Coronary and Cerebral Vascular Disease: A Practical Guide. New York, NY: Futura; 1990: 117–137.
3. Norris JW, Hachinski VC, Myers MG, Callow J, Wong T, Moore RW. Serum cardiac enzymes in stroke. Stroke. 1979; 10: 548–553.
4. Hackenberry LE, Miner ME, Rea GL, Woo J, Graham SH. Biochemical evidence of myocardial injury after severe head trauma. Crit Care Med. 1982; 10: 641–644.[Medline] [Order article via Infotrieve]
5. Kaste M, Somer H, Konttinen A. Heart type creatine kinase (CK MB) in acute cerebral disorders. Br Heart J. 1978; 40: 802–805.
6. Rottbauer W, Greten T, Muller-Bardorff M, Remppis A, Zehelein J, Grunig E, Katus HA. Troponin T: a diagnostic marker for myocardial infarction and minor cardiac cell damage. Eur Heart J. 1996; 17 (suppl F): 3–8.
7. Lang K, Borner A, Figulla HR. Comparison of biochemical markers for the detection of minimal myocardial injury: superior sensitivity of cardiac troponin T ELISA. J Intern Med. 2000; 247: 119–123.[CrossRef][Medline] [Order article via Infotrieve]
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