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European Journal of Heart Failure 2000 2(2):145-150; doi:10.1016/S1388-9842(00)00067-2
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© 2000 European Society of Cardiology

Cardiovascular disease and outcome of acute stroke: influence of pre-existing cardiac failure

Jagdish C. Sharmaa,*, Sally Fletchera, Michael Vassalloa and Ian Rossb

a King's Mill Centre for Healthcare Services Mansfield Road, Sutton in Ashfield, Nottinghamshire NG18, UK
b Newark Hospital Newark NG24 4DE, UK

* Corresponding author. Mansfield Community Hospital, Stockwell Gate, Mansfield NG18 5QJ, UK. Tel.: +44-1623-785-045; fax: +44-1623-785-180. E-mail address: jsharma{at}lineone.net (J.C. Sharma).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background and aims: Whilst a number of variables, mostly a consequence of a stroke, are known to predict mortality of acute stroke there is limited information on the significance of pre-existing cardiovascular variables on stroke mortality. We have investigated the influence of pre-existing cardiovascular factors in one cohort of stroke patients.

Methods: We studied 295 patients, mean age 74 ± 10 (range 34–96) years; 133 males, presenting with acute stroke for pre-existing cardiovascular disease (CVD) defined as hypertension, atrial fibrillation (AF), ischaemic heart disease (IHD) and cardiac failure (CF). In addition, data were collected on epidemiological and neurological variables known to influence stroke mortality. The most significant of the cardiovascular factors was further investigated against all the other cardiovascular groups together and against those without any CVD. Outcome was measured as their influence on acute phase and 3-month mortality.

Results: There was no significant difference in 3-month mortality with hypertension (P = 0.62) and IHD (P = 0.33) but there was a significant higher mortality in patients with AF (P = 0.05) and CF (P < 0.001). CF was more significant than all other CVD (hypertension+AF+IHD) together without the failure (P < 0.001); odds ratio of 4.5 (95% CI 2.28–9.07). Partial correlation coefficient revealed CF to be an independent significant variable to influence stroke mortality when controlled with AF, stroke syndromes, age, incontinence, pyrexia, dysphagia and Glasgow coma score.

Conclusions: Pre-existing CF has an adverse influence on stroke mortality independent of other known factors. Cardiovascular factors without failure do not have such an effect except the marginal effect of AF.

Key Words: Stroke mortality • Cardiac failure • Cardiovascular factors

Received February 18, 2000; Accepted February 22, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
A number of factors are known to predict outcome of stroke for mortality and disability. Most of these are either direct consequences of a stroke, i.e. level of consciousness [1] incontinence and infarct size [2], a measure of stroke severity, i.e. total anterior circulation syndromes in the Oxford Community Stroke Project (OCSP) classification [3] or a complication, i.e. pyrexia [4] and dysphagia [5] and the non-modifiable factor of age [1].

Cardiovascular factors of atrial fibrillation (AF), hypertension, ischaemic heart disease (IHD) and cardiac failure (CF) are known predisposing risk factors for stroke [6] but there are limited reports about the influence of these factors on mortality after an acute stroke. Whilst there is a reference to the relationship between AF and stroke, there is either no mention of the significance of CF in acute stroke or only a brief reference in text books on the subject of stroke [7,8].

CF has not been investigated in some of the studies for cardiovascular factors influencing mortality following acute stroke [1,9] although in one [9] cardiac arrhythmia was found to have an adverse effect on 6-month mortality. AF patients have a higher risk of acute and delayed death [10,11]; coronary heart disease is a cause of stroke and has a higher stroke mortality in the presence of CF as revealed in a follow-up of cardiology patients [12].

These cardiovascular variables have been studied in different groups of stroke patients and the relationship of various variables to each other and their relative significance for stroke mortality in one cohort of stroke patients have not been reported so far. We report here an investigation into the influence of pre-existing cardiovascular factors studied in one cohort of acute stroke patients on acute phase and 3-month mortality following an acute stroke, concentrating the discussion on 3-month mortality.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
We studied 295 consecutive patients who were admitted with an acute stroke to a district general hospital, the patients and methods have been described in detail elsewhere [13]; this paper focuses mainly on cardiovascular factors. Briefly, the patients were studied for pre-existing hypertension, IHD, CF and the presence of AF at the time of admission. This information was obtained from the referring general practitioners’ letter, review of past medical notes and patient or relative interview for the presence of hypertension, angina or myocardial infarct and CF, a method reported earlier [1]. Drug history at the time of admission was an additional source of this information. Patients were categorized to have pre-existing CF if they had been diagnosed as CF in the past and were on appropriate treatment, the degree of failure was not assessed. Stroke was defined as a focal neurological deficit or global loss of consciousness for which no other cause than a vascular lesion is found. Since not all patients had a computerized scan of brain no categorization is done for haemorrhagic and ischaemic strokes.

In addition, patients were assessed for details of neurological deficit, OCSP classification [3], level of functional impairment on the 20-Barthel index [14], level of consciousness on the Glasgow coma scale [15], infarct size on computerized tomography scan (in 202 patients; large infarct being the lesion across two lobes, i.e. temporo-parietal), presence of incontinence (involuntary emptying of bladder), dysphagia (unsafe swallowing due to oro-pharyngeal dysfunction or impaired consciousness) and pyrexia (elevation of temperature above 37°C). These measurements were completed within 72 h of admission. Patients were initially admitted to acute wards (referred to as acute phase) and were either discharged home or to rehabilitation wards if they did not die in the acute wards. Outcome was measured as mortality in acute phase and at 3 months, more detailed analysis relating to 3-month mortality.

Statistical analysis was performed using SPSS [16] to analyse the significance of AF, hypertension, IHD and CF on mortality on bivariate methods for the {chi}2-test. Since there was a coexistence of CF with other factors, a correlation analysis was performed between CF and these variables. Means were tested on an independent sample t-test. The most significant variable was further studied for clinical and neurological characteristics and analysed for significance on 3-month mortality against other factors using categorical {chi}2 analysis with Yates’ correction where appropriate. Odds ratio for mortality was assessed for different groups with the group without any cardiovascular disease (CVD) taken as the reference. A partial correlation test was performed to assess the significance of the most significant factor while controlling for a number of other factors.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
Two hundred ninety five patients admitted with the diagnosis of stroke were studied; demographic and basic characteristics are as in Table 1. Sixty-four patients died in acute phase and 109 patients had died at 3 months.


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  		Table 1 Demographic and other characteristics

 
As expected there was an overlap in patients within CVD; AF, hypertension and IHD were more frequent in patients with CF but in none of these was a significant correlation with CF (Table 2).


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  		Table 2 Correlation (coexistence) of CF with other cardiovascular factors

 
Of the four cardiovascular variables studied, CF was found to be the most significant association with higher mortality (Table 3) both in the acute phase (P<0.001) and at 3 months (P<0.001); pre-existing AF was of no significance in the acute phase, P=0.24, but there was a significant influence at 3 months, P=0.05; there was no association of hypertension and IHD with mortality.


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  		Table 3 Acute phase and 3-month mortality in relation to cardiovascular variables

 
Since CF was the most significant cardiovascular factor influencing mortality this variable was further studied in detail for association with other clinical and neurological variables studied (Table 4). Patients with CF were older (77±7.8 years vs. 73±10.6 years, P=0.02), had a lower Barthel index (i.e. more disability) on admission (3±5 vs. 6±6, P=0.01) but there was no difference in Glasgow coma score (11±4 vs. 12±4, P=0.10) than the patients without CF. There was no significant difference between the two groups for severe OCSP stroke syndromes, CF patients had similar frequency of total anterior circulation infarcts as the non-CF patients (37% vs. 47%, P=0.22). CF patients did not have a higher frequency of total anterior circulation syndrome (P=0.62) or large cerebral infarcts (P=0.21) on CT scan. They had a significantly higher frequency of pyrexia (P=0.001) and incontinence (P=0.01) but not of dysphagia (P=0.22).


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  		Table 4 Other characteristics of patients with CFa

 
In addition we categorized all patients into three groups according to their cardiac status: (1) no cardiovascular disease; (2) cardiovascular factors of hypertension, AF and IHD without CF considered together as one group; and (3) CF patients. Analysis to determine the most significant factor associated with the 3-month mortality revealed that the presence of CF was the most significant cardiovascular variable associated with the highest mortality (P<0.001, Table 5) and such patients were 4.5 times more likely to die at 90 days as compared with those without any CVD and had a higher mortality than the patients with other CVD but without the CF. The latter group patients reached a marginal significance for higher mortality, the 95% CI approaching unity, odds ratio 1.69 as compared with the odds ratio of 1.5 for patients without any form of CVD (see Fig. 1 showing the survival curve for the three groups).


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  		Table 5 Mortality according to cardiovascular status

 


Figure 1
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  		Fig. 1 CVD and outcome of acute stroke: influence of pre-existing CF.

 
Since CF patients had significant association with other factors known to adversely influence stroke mortality, further analysis using a partial correlation coefficient was performed to assess the significance of CF when controlled for these factors. This revealed that CF remained a significant independent variable for acute phase (P<0.001) and 3-month (P<0.001) mortality when controlled for age, OCSP stroke syndromes, Glasgow coma score, incontinence, pyrexia, dysphagia and AF.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
This study is perhaps the first report of a prospective study of the influence of pre-existing cardiovascular factors on mortality in one cohort of acute stroke patients and also describes clinical and neurological details of patients with the most significant of these factors, i.e. pre-existing CF. Previous reports have been on different groups of patients for different variables and have not studied clinical and neurological features and complications related to the cardiovascular factors. Moreover, the report of relationship of CF and stroke was primarily a study of follow-up of cardiac patients who later developed stroke rather than a prospective study of stroke patients [12].

Hypertension and AF are known modifiable risk factors for stroke. CF is a known factor for all cause and stroke deaths [12], coronary heart disease is a risk factor for stroke [6] and a number of neurological sequelae of stroke predict poor outcome of disability and death [1–5]. While AF has been reported to have higher stroke mortality it is not clear whether these patients also suffered co-existent CF [10]. There is a lack of information whether pre-existent CF of any aetiology has an influence on stroke mortality and how do different cardiovascular factors influence stroke mortality in one cohort.

Our results are in concordance with the previous report [9] that pre-existing hypertension (not the blood pressure at admission) does not influence survival but unlike their results our study did not find IHD (myocardial infarct) as significant association of stroke mortality. This study did not investigate the influence of CF.

We find that the patients with pre-existing CF have a higher mortality than other cardiovascular factors from a very early stage following admission with a stroke and CF is the only such variable to be associated with significant mortality in acute phase. These patients stay longer in acute wards probably due to more severe illness and complications as is indicated by the higher frequency of pyrexia in early stage.

Our study demonstrates that the presence of prior CF of any aetiology is a significant risk factor for stroke mortality in acute phase and at 3 months, independent of the influence of other known factors known to have adverse effects on survival from acute stroke. In our study presence of AF, hypertension and a history of IHD without CF had only a marginal adverse influence on 3-month stroke mortality, the most significance of these being AF, but there was no influence on acute phase mortality. The adverse effect of AF may be due to thrombo-embolic phenomenon or poor cerebral perfusion.

We have not studied the underlying cause or degree of prior CF. This is a limitation of this study since we have categorized a patient in the CF group based on the information obtained from various sources, i.e. patients, surrogates, general practitioners and previous medical notes. Whilst this is not be a very reliable method of a definitive diagnosis of CF, it is expected that the patients had been diagnosed as CF by the primary and secondary care practitioners following a reliable evidence prior to the event of stroke leading to the admission. We recognize that we have only 51 patients with CF but the results are statistically significant. It is, however, proposed that a larger study should be conducted to investigate relationship between CF of different aetiology and severity in a larger cohort and whether an intensive management in acute phase improves their outcome.

Reasons for poor outcome of pre-existing CF patients is not investigated but is probably to be deterioration of cardiac status following a stroke due to the effect of stroke as suggested by the electrocardiographic and cardiac enzyme changes in acute stroke patients [7], or inability to continue with the prescribed anti-failure medication. Presence of CF probably signifies generalized vascular disease and thus a poor adaptability following a stroke leading to higher mortality. Higher age of patients with prior CF may be a contributory factor [13] although in our study CF is an independent factor when adjusted for a number of other variables including age. Other plausible explanations might be the post-stroke thrombo-embolic phenomenon, hypoxic damage to cerebral tissue due to reduced cerebral perfusion in the presence of CF and higher frequency of complications such as pyrexia and its detrimental effect [4]. Since CF patients did not have more severe stroke syndromes or large infarcts and did not suffer more impairment of consciousness on the Glasgow coma scale, it is unlikely that underlying stroke severity is the explanation for the poor outcome of these patients.

This observation has a number of implications. Since pre-existent CF is a non-modifiable factor, such patients should be excluded from interventional studies in acute stroke since such patients may not respond to intervention due to prior illness. Another implication is that to make an impact on the influence of cardiac disease on stroke mortality the overall prevalence of CF needs to be reduced in the population by appropriate mass measures. Reducing cardiovascular morbidity may reduce stroke mortality.

Acute stroke care is gaining momentum and interest. The relationship of pre-existing CF and the mechanism of higher stroke mortality requires further confirmation and investigation since it may be possible to identify treatable factors in this context so as to reduce stroke mortality in CF patients.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Henon H., Godefroy O., Mounier-Vehier F., et al. Early predictors of death and disability after acute cerebral ischaemic event. Stroke (1995) 26:392–398.[Abstract/Free Full Text]
  2. Hankey G.J., Davis S.J., Stewart-Wynne E.G., Chakera T.M. Cranial CT scan appearances that correlate with patient outcome in acute stroke. Clin Exp Neurol (1987) 23:71–74.[Medline]
  3. Bamford J., Sandercock P., Dennis M., Burn J., Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet (1991) 337:1521–1526.[CrossRef][Web of Science][Medline]
  4. Castillo J., Martinez F., Leira R., Prieto J.M., Lema M., Noya M. Mortality and morbidity of acute cerebral infarction related to temperature and body analytic parameters. Cerebrovasc Dis (1994) 4:66–71.[CrossRef][Web of Science]
  5. Gordon C., Langton Hewer R., Wade D.T. Dysphagia in acute stroke. Br Med J (1987) 295:411–414.[Abstract/Free Full Text]
  6. Kannel W.B., Wolf P.A., Verter J. Manifestations of coronary disease predisposing to stroke. The Framingham study. J Am Med Assoc (1983) 250:2942–2946.[Abstract/Free Full Text]
  7. Devuyst G., Bogousslavsky J. Which cardiac diagnostic tests apply in the acute phase of stroke and when are they useful? In: Acute stroke treatment—Bogousslavsky J., ed. (1997) London:: Martin Dunitz Ltd. 65–78.
  8. Warlow C.P., Dennis M.S., van Gijn J., et al. Stroke: a practical guide to management (1996) Edinburgh: Blackwell. 369.
  9. Lai S.M., Alter M., Friday G., Sobel E. Prognosis for survival after an initial stroke. Stroke (1995) 26:2011–2015.[Abstract/Free Full Text]
  10. Kaarisalo M.M., Immonen-Raiha P., Marttila R.J., et al. Atrial fibrillation and stroke. Mortality and causes of death after the first acute ischaemic stroke. Stroke (1997) 28(2):311–315.[Abstract/Free Full Text]
  11. Candelise L., Pinardi G., Morabito A. Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group. Stroke (1991) 22:169–174.[Abstract/Free Full Text]
  12. Jelinek M.V., Ansari M.Z. Congestive cardiac failure (CCF) as a cause of fatal stroke and all cause death. Aust N Z Med (1998) 28:799–804.
  13. Sharma J.C., Fletcher S., Vassallo M. Strokes in the elderly-higher acute and three month mortality — an explanation. Cerebrovasc Dis (1999) 9:2–9.[Web of Science][Medline]
  14. Wade D.T., Collin C. The Barthel ADL index: a standard measure of physical disability. Int Disabil Stud (1988) 10:64–67.[Medline]
  15. Teasdale G., Jennet B. Assessment of coma and impaired consciousness. A practical scale. Lancet (1974) ii:81–84.
  16. SPSS 7.5 for Windows. SPSS Inc. Chicago.

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