Journal of Clinical and Scientific Research

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 9  |  Issue : 1  |  Page : 11--15

A study of prognostic significance of serum troponin I in patients with acute ischaemic stroke


Pranuthi Pynam, B Vengamma, SV Naveen Prasad, Sai Neelima Challa, R Rakesh 
 Department of Neurology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Correspondence Address:
B Vengamma
Director Cum Vice-Chancellor, Senior Professor and Head, Department of Neurology, Sri Venkateswara Institute of Medical Sciences, Alipiri Road, Tirupati 517 507, Andhra Pradesh
India

Abstract

Background: Serum troponins have also been reported to be elevated in patients with acute cerebrovascular disease and poor clinical outcome. Methods: We prospectively evaluated 360 patients with acute ischaemic stroke (AIS) to study the relationship between serum troponin I (TnI) levels and severity of AIS and to compare serum TnI levels in patients with favourable and unfavourable functional outcomes. Results: Their mean age was 58.8 ± 13.3 years; there were 230 (63.9%) males. Majority (n = 288; 80%) had presented with anterior circulation stroke and 58 (16.1%) had posterior circulation stroke. Majority (52.5%) had large artery atherosclerosis. The median (interquartile range) National Institutes of Health Stroke Scale (NIHSS) score was 18 (16–20). Serum TnI was positive in 87 (24.2%) and negative in 273 (75.8%). The NIHSS score at admission was higher in the positive serum TnI group. Moderate-to-severe stroke, severe stroke and cardioembolic stroke were more frequently seen in the serum TnI-positive group. Outcome was favourable in 157 (47.7%) and unfavourable outcome was seen in 172 (52.3%) patients. Conclusions: Elevated serum TnI levels were associated with increased severity of AIS and poor functional outcome.



How to cite this article:
Pynam P, Vengamma B, Naveen Prasad S V, Challa SN, Rakesh R. A study of prognostic significance of serum troponin I in patients with acute ischaemic stroke.J Clin Sci Res 2020;9:11-15


How to cite this URL:
Pynam P, Vengamma B, Naveen Prasad S V, Challa SN, Rakesh R. A study of prognostic significance of serum troponin I in patients with acute ischaemic stroke. J Clin Sci Res [serial online] 2020 [cited 2020 Aug 8 ];9:11-15
Available from: http://www.jcsr.co.in/text.asp?2020/9/1/11/285717


Full Text



 Introduction



Cerebrovascular and coronary artery diseases share many of the same risk factors. Cardiac troponins are important biomarkers of acute myocardial infarction, and serum troponins have also been reported to be associated with poor clinical outcome in patients with acute cerebrovascular diseases. Abnormal levels of cardiac troponins have also been reported to be associated with poor clinical outcome in patients with acute cerebrovascular diseases, including acute ischaemic stroke (AIS),[1] intracerebral haemorrhage,[2] and spontaneous subarachnoid haemorrhage.[3] In a systematic review[4] of studies, measuring serum troponin within 7 days of symptom onset in acute stroke patients found that >18% of patients had a high serum troponin level. Elevated serum troponin levels are reported in patients with cardioembolic stroke who also had evidence of atrial fibrillation, ischaemic heart disease or heart failure.[5]

The mechanism of serum troponin elevation in AIS is uncertain, as does the mechanistic link between elevated serum troponin levels and adverse outcomes in AIS.[6] The present study was done to study the prognostic significance of serum troponin I (TnI) in patients with AIS.

 Material and Methods



The present prospective observational study was conducted at our tertiary care teaching institute in Tirupati, South India, during the period May 2017 to December 2018. Patients aged more than 18 years admitted with AIS, within 7 days of symptom onset and confirmed by neuroimaging were included in the study. Patients with venous stroke, chronic kidney disease, sepsis, critical illness, pulmonary embolism, chronic obstructive pulmonary disease and advanced heart failure were excluded from the study. The study was initiated after obtaining clearance from the institutional ethics committee

A detailed history was recorded. All the participants are subjected to a detailed physical and neurological examination. Details of comorbid conditions were noted. All patients are subjected to plain computed tomography of the brain and magnetic resonance angiogram of the brain to confirm the diagnosis. Stroke severity is assessed by the National Institutes of Health Stroke Scale (NIHSS) at admission.[7] Ischemic stroke subtype will be classified as per the Trial of ORG 10172 in Acute Stroke Treatment classification.[8] Functional outcome was evaluated using the modified Rankin scale (mRS).[9]

In all patients, electrocardiogram, two-dimensional echocardiography and carotid and vertebral artery Doppler studies were carried out. Peripheral venous blood sample was obtained at the time of initial presentation, and serum homocysteine levels and serum TnI were estimated. Serum TnI was estimated using conventional VIDAS Troponin I Ultra assay (bioMerieux, Marcy L'Etoile, France). The analytical limit of detection and the 99th percentile upper reference limit was 0.01 μg/L. An abnormal elevation of serum TnI was defined as a serum TnI serum level >0.01 μg/L.

Statistical analysis

The data were recorded on a pre-designed pro forma and managed using Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA). All the entries were double-checked for any possible error.

Descriptive statistics for the categorical variables were performed by computing the frequencies (percentages) in each category. For the continuous variables, the approximate normality of the distribution was assessed. Variables following normal distribution were summarised by mean and standard deviation. Variables that are not normally distributed were summarised as median (interquartile range [IQR]). Univariate analysis was carried out to compare the demographic, clinical and laboratory variables between patients with favourable and unfavourable outcomes using unpaired t-test, Mann–Whitney U-test for continuous variables and Chi-square test for categorical variables. The association between serum TnI and functional outcome was assessed by multiple logistic regression analysis. A two-tailed P < 0.05 was considered statistically significant. The statistical software IBM SPSS Statistics Version 20 (IBM Corp., Somers, NY, USA) was used for statistical analysis.

 Results



During the study period, 360 patients with AIS were included in this study. Their mean age was 58.8 ± 13.3 years; there were 230 (63.9%) males. Majority (27.8%) of the patients were in the sixth decade of life; 99/360 (27.5%) were aged under 50 years.

Out of 360 patients studied, 286 (79.4%) patients had anterior circulation stroke, 57 (15.8%) patients had posterior circulation stroke and 17 (4.7%) patients had infarcts in both anterior and posterior circulation. The distribution of infarcts in vascular territories was 166 (46.1%) in middle cerebral artery, 76 (21.1%) in anterior cerebral artery, 57 (15.8%) in posterior circulation, 17 (4.7%) in multiple territories and 44 (12.2%) border zone infarcts. The large artery atherosclerosis (thrombosis/embolus) was seen in 189 (52.5%) patients, cardioembolic stroke in 88 (24.4%) patients, small vessel occlusion in 49 (13.6%) patients, stroke of other determined aetiologies in 9 (2.5%) patients and stroke of undetermined aetiology in 25 (6.9%) patients.

The median (IQR) NIHSS score was 10 (6–15). Of the 360 patients studied, 33 (9.2%) had minor stroke, 160 (44.4%) had moderate stroke, 124 (34.4%) had moderate-to-severe stroke and 43 (11.9%) patients had severe stroke. Various risk factors found in this study were hypertension in 242 (67.2%), old age (>70 years) in 67 (18.6%), diabetes mellitus in 138 (38.3%), tobacco smoking in 176 (48.9%), alcohol use in 136 (37.8%), coronary artery disease in 57 (15.8%), previous stroke in 80 (22.2%), rheumatic heart disease in 37 (10.3%), hyperhomocystinemia in 70 (19.4%), vasculitis in 14 (3.9%), peripheral artery disease in 34 (9.4%), thyroid disease in 11 (3.1%) and chronic liver disease in 2 patients.

Taking serum TnI level > 0.01 μg/mL as cutoff, patients were classified into TnI-positive and TnI-negative groups. Eighty-seven (24.2%) patients tested serum TnI positive and 273 (75.8%) tested serum TnI negative.

Comparison of demographic parameters, risk factors between the serum TnI positive and negativepositive and negative groups showed that these two groups were comparable. There was a statistically significant association of positive serum TnI with long hospital stay (>15 days) (56/87 vs. 16/273, P < 0.01). Among patients older than 70 years, with positive serum TnI levels, females outnumbered males (31/87 vs. 99/273; P < 0.01).

There was a statistically significant association between coronary artery disease (23/87 vs. 34/273, P < 0.01), rheumatic heart disease (14/87 vs. 23/273, P < 0.05), past history of stroke (28/87 vs. 52/273, P < 0.01) and positive serum TnI levels. There was no statistically significant difference in the distribution of cardioembolic stroke, small vessel occlusion and stroke of other determined aetiologies between patients with positive and negative serum TnI. A significant association was noted between positive serum TnI and stroke due to large artery atherosclerosis (41/87 vs. 148/273, χ2 = 26.44, P < 0.01).

The median (IQR) NIHSS score in the positive serum TnI group was significantly higher (18 [16–20] vs. 10 [5–15]). A higher proportion of patients with moderate-to-severe (40/124) and severe (23/43) stroke had a positive serum TnI compared with minor (2/33) and moderately severe (22/160) stroke than the negative group (P < 0.01). There was no statistically significant association between infarct site and positive serum TnI levels.

The mRS scores at discharge (n = 360) and at 3-month follow-up (n = 329) are shown in [Figure 1]. Thirty-one patients expired during hospital stay and were excluded during 3-month follow-up. The mRS score <3 or equal to 3 at 3-month follow-up was considered as favourable outcome, whereas unfavourable outcome was defined as a mRS score of >3 at 3-month follow-up.{Figure 1}

The relationship of serum TnI levels with functional outcome is shown in [Table 1]. In the favourable outcome group, positive and negative serum troponin levels were seen in 3.8% and 96.1% of patients, respectively, whereas in the unfavourable outcome group, these were seen in 40.1% and 59.9% of patients, respectively (P < 0.01), indicating that positive serum TnI status was associated with unfavourable functional outcome.{Table 1}

The results of multivariable analysis are shown in [Table 2]. Older age (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.97–1.01, P = 0.002), high NIHSS score (OR: 3.60, 95% CI: 1.26–10.30, P = 0.02) and positive TnI levels (OR: 9.69, 95% CI: 3.69–25.42, P = 0.003) were associated poor functional outcome.{Table 2}

 Discussion



Like many other serious medical illnesses, stroke has heterogeneous aetiology, caused by modifiable and unmodifiable risk factors. Stroke is becoming an important cause of pre-mature death and disability in low- and middle-income countries such as India. This can be largely attributed to demographic changes and increasing prevalence of the key modifiable risk factors.

Stroke poses an increased risk for electrocardiographic changes, cardiac arrhythmias and myocardial cell damage. It has been shown that highly specific myocardial necrosis markers such as troponin can be increased in stroke victims, a phenomenon that has been explained by several pathophysiologic mechanisms: primary cardiac damage with secondary cardioembolic cerebral ischemia or primary cerebral ischemia with secondary cardiac damage caused by increased levels of catecholamines (caused by sympathetic system activation).[10] Some studies associate increased troponin levels with a certain localisation of stroke: insular or right hemisphere.[10],[11],[12],[13]

The demographic characteristics of our patients were comparable with observations documented in previous studies, except mean age that was lower when compared to Western studies.[8],[9],[10],[11],[12],[13] This is probably due to the distribution of risk factors for stroke in our patients. In our study, hypertension (66.7%) was the most common risk factor, followed by tobacco smoking (55.2%), diabetes mellitus (40.2%), alcoholism (40.2%) and dyslipidaemia (27.6%). Similar observations were reported in other studies.[10],[12],[13]

Out of 360 patients with AIS, positive serum TnI status was seen in 87 (24.2%) patients. There was no significant difference in the distribution of demographic characteristics between the two groups. There was a significant difference in the distribution of risk factors between the two groups; a significant association was found between positive serum TnI and risk factors such as coronary artery disease, rheumatic heart disease and past history of stroke. In a study[10] from Pittsburgh, positive TnI was reported in 18% of patients. In a study[11] from Taiwan, positive TnI was noted in 16.8% of patients. However, in these studies,[10],[11] serum troponin levels of >0.1 μg/L were considered positive. In the present study, serum TnI level of >0.01 μg/L was considered positive which might be responsible for slightly higher positive serum TnI status in the present study. Further, differences in the troponin assessment methods could also have contributed to the differences observed.

In our study, among patients with positive serum TnI (n = 87), large artery atherosclerosis was the most common subtype (n = 41, 47.1%), followed by cardioembolic stroke (n = 37, 42.5%) and small-vessel occlusion stroke (n = 2). Stroke of undetermined aetiology accounted for seven cases. Similar results were reported in other studies.[8],[10]

The present study included patients who presented within 7 days from symptom onset. This time window could be so broad in view of the fact that troponin I levels continuously changed in acute stage of ischemic stroke. Second, TnI was checked only once in each patient in the emergency room without defining an exact time period from onset of symptoms to TnI measurement. The serial measurement of TnI was not done. The present study limited to a single academic institution; multicentre studies are needed to validate our findings.

The present study showed that elevated serum TnI levels were associated with increased severity of acute ischemic stroke and poor functional outcome. Acute stroke-related increased sympathetic activity with excessive catecholamine release results in coagulative myocytolysis or cardiomyopathy may be the cause for this effect. Further studies are needed to confirm this association and to determine whether positive TnI levels can be used to predict functional outcome in ischaemic stroke patients. Larger prospective studies are needed to confirm these findings.



Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Di Angelantonio E, Fiorelli M, Toni D, Sacchetti ML, Lorenzano S, Falcou A, et al. Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2005;76:76-81.
2Hays A, Diringer MN. Elevated troponin levels are associated with higher mortality following intracerebral hemorrhage. Neurology 2006;66:1330-4.
3Deibert E, Barzilai B, Braverman AC, Edwards DF, Aiyagari V, Dacey R, et al. Clinical significance of elevated troponin I levels in patients with nontraumatic subarachnoid hemorrhage. J Neurosurg 2003;98:741-6.
4Etgen T, Baum H, Sander K, Sander D. Cardiac troponins and N-terminal pro-brain natriuretic peptide in acute ischemic stroke do not relate to clinical prognosis. Stroke 2005;36:270-5.
5Newby LK, Jesse RL, Babb JD, Christenson RH, De Fer TM, Diamond GA, et al. ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: A report of the American College of Cardiology Foundation task force on clinical expert consensus documents. J Am Coll Cardiol 2012;60:2427-63.
6Barber M, Morton JJ, Macfarlane PW, Barlow N, Roditi G, Stott DJ. Elevated troponin levels are associated with sympathoadrenal activation in acute ischaemic stroke. Cerebrovasc Dis 2007;23:260-6.
7Kerr G, Ray G, Wu O, Stott DJ, Langhorne P. Elevated troponin after stroke: A systematic review. Cerebrovasc Dis 2009;28:220-6.
8Budincevic H, Sremec J, Crnac P, Ostojic V, Galic E, Bielen I. Impact of troponin I on outcome of ischemic stroke patients. Rom J Intern Med 2017;55:19-22.
9Bustamante A, Díaz-Fernández B, Pagola J, Blanco-Grau A, Rubiera M, Penalba A, et al. Admission troponin-I predicts subsequent cardiac complications and mortality in acute stroke patients. Eur Stroke J 2016;1:205-12.
10Batal O, Jentzer J, Balaney B, Kolia N, Hickey G, Dardari Z, et al. The prognostic significance of troponin I elevation in acute ischemic stroke. J Crit Care 2016;31:41-7.
11Su YC, Huang KF, Yang FY, Lin SK. Elevation of troponin I in acute ischemic stroke. PeerJ 2016;4:e1866.
12Purandare V, Paramshetti S, Palange P. Significance of cardiac troponin estimation in acute ischemic stroke. Med Pulse Int Med J 2016;3:1089-92.
13Raza F, Alkhouli M, Sandhu P, Bhatt R, Bove AA. Elevated cardiac troponin in acute stroke without acute coronary syndrome predicts long-term adverse cardiovascular outcomes. Stroke Res Treat 2014;2014:621650.