(Stroke. 1995;26:2011-2015.)
© 1995 American Heart Association, Inc.
Articles |
From the University of Kansas (Kansas City) (S.M.L.), the Medical College of Pennsylvania, Philadelphia, Pa (M.A., G.F.), and the University of Southern California, Los Angeles, Calif (E.S.).
| Abstract |
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Methods All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed regularly at about 6-month intervals until death or the end of the study (mean of 24 months).
Results At 6 months, 90.8% of the 30-day stroke survivors were still alive. At 1, 2, 3, and 4 years, the cumulative survival rates were 86.9%, 78.7%, 73.2%, and 72.0%, respectively. Older age and the number of neurological deficits at onset of initial stroke increased risk of death. Compared with patients of the same age, sex, number of neurological deficits, and comorbidities, increased risk of death is present among those with myocardial infarction, cardiac arrhythmia, and diabetes mellitus. Hazard ratios were 1.7 (P=.006), 1.5 (P=.023), and 1.4 (P=.059), respectively. Hypertension and transient ischemic attacks were not significantly associated with increased mortality.
Conclusions This study clarifies prognosis for survival after an initial stroke by taking into account other confounding variables that could also contribute to risk of death.
Key Words: prognosis risk factors survival
| Introduction |
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| Subjects and Methods |
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To ascertain death of study patients, obituaries were reviewed daily; if a death was missed in these notices, it was identified when an attempt was made to schedule the follow-up visit. The cause of death was determined from hospital records, telephone contacts with family members, and death certificates retrieved from the Bureau of Vital Statistics in Pennsylvania and New Jersey. When discrepancies in cause of death existed among these sources, the most plausible cause of death based on all of the available evidence was deemed correct, with priority given to hospital records.
A t test or
2 was used when
appropriate to determine significance of differences among
variables compared. The effect on mortality of the five baseline
medical conditions was similarly analyzed, listing each as
normal or abnormal. For comorbidities, a survival-analysis
technique was used, with survival time defined as the time from the
date of stroke onset to date of death. For those who survived until the
end of study, survival time was from date of stroke onset until the end
of the study. Because occurrence of a second stroke was a study end
point, patients who developed a second stroke were censored, as were
those who moved away, were lost to follow-up, or refused further
follow-up. The log rank statistic was used to test the statistical
significance of differences in survival curves. Only a factor with a
value of P<.1 from the univariate
analysis was included in the multivariate
analysis. The Cox proportional hazards model was used to
identify the baseline risk factors associated with the mortality from
any cause while taking into account demographic characteristics (age
and sex) as covariates, number of neurological deficits from the
initial stroke, stroke type, and the varying lengths of follow-up.
The stroke types were categorized into the following three groups:
thrombosis/embolus/nonspecific infarct, lacunar stroke, and
intracerebral hemorrhage. The number of
neurological deficits ranged from zero (ie, no deficit) to eight
deficits. The eight deficits were for abnormalities of consciousness,
orientation, language, memory, cranial nerve status, motor status,
sensory status of lower or upper extremities, coordination of lower and
upper extremities, and gait. The interactions between the risk factors
were also examined.
| Results |
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Demographic features and distribution of comorbidities among this
cohort for each stroke type are shown in Table 1
. All
stroke types had a similar average age at enrollment. There were more
men with lacunar stroke (58.6%) but more women with
intracerebral hemorrhage (56.1%). Hypertension
was most common in those with a lacunar stroke, DM was most common in
those with lacune or cerebral thrombosis/embolus/nonspecific infarct,
and TIA was most common in those with cerebral
thrombosis/embolus/nonspecific infarct (but history of TIA was used as
a criterion for diagnosing cerebral thrombosis). The distribution of
number of deficits is also shown in Fig 1
. Only 15
patients (0.02%) had no deficit. One hundred seventy-six patients
(26.6%) had any of three deficits.
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The causes of death based on all available data sources were cardiac (n=53, 38.4%), the initial stroke (after 30 days, n=19, 13.8%), infection (n=19, 13.0%), metabolic (n=8, 5.8%), pulmonary (n=5, 3.6%), gastrointestinal hemorrhage (n=3, 2.2%), cancer (n=16, 11.6%), trauma (n=1, 0.7%), and unknown cause (n=14, 10.9%). Since only 9 patients with lacunes and 6 with intracerebral hemorrhage died during follow-up, the list of causes reflects essentially the causes of death among the 123 patients with a thrombosis, embolus, or nonspecific cerebral infarct.
The cumulative survival rates among patients who survived at least 30
days after an initial stroke was 90.8% at 6 months, 86.9% at 1 year,
78.7% at 2 years, 73.2% at 3 years, and 72.0% at the end of the
fourth year. The three stroke types had a similar survival curve over
time. Comparison of survival among patients who had a given medical
condition at enrollment with those who did not showed significantly
increased mortality for those with cardiac arrhythmia
(P=.0001; Fig 2
), MI (P=.0003; Fig 3
), and DM (P=.02; Fig 4
).
However, patients with a history of hypertension at enrollment had no
significantly increased mortality compared with those without
hypertension (P=.99), and those with a history of TIA
actually had a lower mortality than patients without a history of TIA,
although the difference was not statistically significant
(P=.4).
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A proportional hazards model analysis was also carried out to
determine the effect of five selected medical conditions while taking
into account age, sex, initial stroke type, the number of neurological
deficits at baseline, and varying length of follow-up (Table 2
). Older age, as expected, increased
risk of death (P=.0001), whereas sex was not associated with
higher risk of death. However, the patient's age and sex were both
included in the model as covariates. A higher number of neurological
deficits from the initial stroke also increased risk of death
(P=.007). Patients diagnosed with MI on the baseline ECG had
1.7 times higher risk of death compared with patients of the same age
and sex, number of neurological deficits, and comorbidities who did not
have MI on the baseline ECG. The same type of analysis
showed that patients with cardiac arrhythmia on the baseline
ECG had a 1.5 times higher risk of death compared with patients of the
same age, sex, number of neurological deficits, and comorbidities who
did not have a cardiac arrhythmia on the baseline ECG. Patients
with DM had 1.4 times higher risk of death compared with patients of
the same sex, age, number of neurological deficits, and comorbidities
who did not have DM. No significant risk-factor interactions on
risk of death were observed among the factors studied. No significant
increased mortality was found for those with hypertension or in those
with history of TIA compared with those without these comorbidities,
again controlling for the other potential confounders and covariates
with the proportional hazards model.
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| Discussion |
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In the Framingham study in the United States,8 stroke patients with coronary heart disease or congestive heart failure had a poorer prognosis for survival than patients with neither of these conditions. As in our study, the status of the heart in stroke patients was an important marker for survival prognosis after stroke. In the Rochester Epidemiology Project, Broderick et al14 identified the independent predictors of death to be prior MI (hazard ratio=2), atrial fibrillation present at onset of stroke (hazard ratio=1.7), congestive heart failure before the stroke, and an agexcongestive heart failure interaction. Anderson et al,9 working in Australia, also noted a poorer survival prognosis in patients with heart disease. There was a 6.5-fold increased mortality in his series for those with cardiac failure and a twofold increased mortality in those with atrial fibrillation at 1 year compared with those without these medical conditions. Olsson et al10 in Sweden investigated risk factors associated with mortality for stroke patients with diabetes. They reported that cardiac failure was a significant predictor of mortality after stroke. The authors did not find a poorer survival among those with atrial fibrillation or previous MI. In a Canadian study,6 7 after adjusting for heart failure, DM emerged as a significant predictor for mortality, but lack of association with increased mortality after stroke was reported for atrial fibrillation, MI, and hypertensive heart disease.
The differences in results among these various studies could well be due to methodological differences. For example, some studies of stroke mortality were retrospective or included patients with an initial as well as with a recurrent stroke.6 7 10 17 20 Risk factors may not have been assessed systematically, as it was in our study. Analyses may not have taken into account possible interactions among medical conditions, nor were stroke type and the number of neurological deficits taken into account.6 7 10 Our study addressed these possible sources of influence on mortality and attempted to adjust for them in the study design and data analysis.
The lack of association between hypertension and risk of death in the present study may seem counterintuitive. However, we know from other analyses21 that most patients in this stroke cohort had good or at least fair control of hypertension during follow-up. Therefore, presence of hypertension at enrollment by history does not necessarily imply a poor outcome measured as risk of death. Perhaps because hypertension was well controlled, risk of death in hypertensive patients was not appreciatively greater than in those who were nonhypertensive.
Diabetic control in these patients was good, as reflected by the HbA1c assay. Yet, DM was still associated with increased mortality. This implies that diabetic vasculopathy may be less reversible than hypertensive vascular changes.
The seemingly better prognosis for survival of patients with a history of TIA in this cohort as shown in the univariate analysis, if true, was unexpected. We considered two possible explanations: patients with TIA may have been more likely to be taking an antiplatelet-aggregating drug, such as aspirin, or an anticoagulant. Indeed, more than half of this cohort was taking one or the other of these drugs (or both at some time) after the stroke.22 This may have prevented not only stroke recurrence but also may have decreased risk of death, since risk of cardiac death is higher after stroke and aspirin has been shown to reduce death from cardiac causes. Alternatively, the vessel responsible for the TIA may have occluded with the initial stroke, and thereafter these patients may have had a risk of death no greater than those with no history of TIA. Indirectly supporting this notion is our observation that patients who developed TIA after the initial stroke were at higher risk of death than those who had no TIA after the initial stroke (Reference 22 and G.F. et al, unpublished data).
The data we have reported in this analysis assess the role of at least some common medical conditions in relation to risk of death after stroke and generally support work by others.8 9 10 11 14 15 17 Besides the five comorbidities that we studied, future studies could analyze other risk factors for stroke such as smoking, lipid level, exercise, body mass, and race in relation to prognosis for survival with use of a similar design. Such analyses could clarify even further the complex interplay of conditions that need to be considered in estimating prognosis for survival after stroke.
| Selected Abbreviations and Acronyms |
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| Footnotes |
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Received May 1, 1995; revision received June 22, 1995; accepted August 4, 1995.
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