Gave Her the Long Stroke Again

Noesis of the epidemiology of stroke has increased over the last decades, although it is well established that stroke is associated with a high gamble for death, especially in the offset few weeks afterward the set on. Studies of incidence and mortality have shown that case fatality rates vary considerably among populations.^1,2 Few studies have been published on the long-term prognosis later on stroke, and they are somewhat heterogeneous equally regards written report objectives, design, and the subjects investigated.

Studies of the determinants and probabilities of survival and at diverse times after the index stroke have included all strokes,³ get-go stroke,^4–6 or ischemic stroke,^7–10 with accent on stroke subtype,¹¹ age,¹² or place of management.¹³ The absolute risk for death after a stroke is an appropriate variable in analyses of prognostic factors, only the inferences to be drawn from the absolute survival probability may exist limited considering well-nigh stroke patients were in their 70s or 80s. Few community-based studies have included comparisons of mortality rates after stroke with the mortality rates and causes of death in the general population of the aforementioned age and sexual practice.^{4–half-dozen,14}

In this article we describe the long-term accented and relative risks for death and the causes of death of a large, unselected, customs-based cohort of stroke patients registered in the Danish portion of the World Health System (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Projection and compare them with the groundwork population from which the accomplice was drawn.

Subjects and Methods

A stroke register was established within the Glostrup Population Studies in 1982, with the objective of monitoring stroke events in the customs over a x-year catamenia^xv and contributing data to the WHO MONICA Project.^1,2

The Danish MONICA population was defined equally all residents (approximately 330 000) of eleven municipalities in Copenhagen County. Stroke events were registered among the subpopulation anile 25 years or older (approximately 210 000), and validated, irrespective of survival status and identify of occurrence and management. Multiple and overlapping sources were used to identify strokes among both hospitalized and nonhospitalized patients. The details of case ascertainment were described recently.¹⁵

Stroke was defined every bit apace developing signs of focal (or global) disturbance of cognitive role lasting >24 hours (unless interrupted by surgery or expiry), with no apparent nonvascular cause; the study population included patients presenting with clinical signs and symptoms suggestive of subarachnoid hemorrhage, intracerebral hemorrhage, or cognitive infarct.

At the end of 1991, when the stroke register was completed, 5262 stroke events had been registered prospectively for the ten years. The events were subdivided into first or recurrent and into fatal or nonfatal, a fatal stroke being defined as one in which decease occurred within 28 days. All patients were followed up for vital condition for at least five.five years (range, five.five to 15.5 years) and for causes of death for at least 4 years (range, 4 to xiv years). Data were obtained by tape linkage to the Danish Civil Registration System and the Cause of Decease Registry on the basis of the unique individual person number (a 10-digit code including the date of birth). Data on deaths and causes of decease in the general population covered by the stroke register (the Danish MONICA population), distributed by sex, age, and calendar twelvemonth, were derived from the aforementioned official registries. The expected number of deaths in the general population was estimated for each sex by computing the age- and time-specific person-years of observation multiplied by the similar age- and time-specific population death rate. Standardized bloodshed ratios (SMRs) and excess decease rates (EDRs) were estimated and 95% conviction limits were established subsequently it was assumed that the numbers of deaths followed a Poisson distribution. The SMR is the quotient of the observed to the expected numbers of deaths, and the EDR is the observed minus the expected number of deaths per one thousand person-years. The SMR is suitable for comparing mortality rates amidst stroke patients with those of the general population, whereas EDR is a mensurate of the excess number of deaths due to the illness over that expected. SMRs and EDRs were calculated for all causes of death, and SMRs were calculated for specific causes of decease: cardiovascular diseases, cancer, other diseases, accidents, and suicide. Information on the crusade of death subsequently a nonfatal stroke (ie, among 28-day survivors) was available for 1828 patients who died before January 1, 1996; no information was bachelor in 11 such cases.

For patients who survived for at least 28 days but for whom the exact date of onset of stroke was non specified, it was assumed to take occurred on the 15th twenty-four hours of the month. 1 hundred 70-three patients with fatal stroke were randomly assigned a survival time between 0 and 27 days when only month of onset was known and death occurred before the 28th day in the following calendar month.

Stroke was clinically defined in the protocol of the MONICA Projection. The stroke subtype was recorded for patients with fatal stroke who were examined postmortem and for patients examined by neuroimaging techniques within 28 days of onset. Cases with insufficient information on stroke subtype were labeled "astute only sick-divers stroke." Since stroke was defined as an outcome lasting 28 days, we chose to regard stroke as the cause of death in fatal events. Hence, nosotros analyzed short-term survival in relation to the subtype of stroke only did not farther explore the direct cause of death in these cases. Because the protocol of the MONICA Project did non include clinical information on the severity of stroke or on comorbidity in private patients, our information do non let analyses of determinants of survival.

Time trends in survival probability up to v years after a stroke were analyzed in a Cox regression model that included the covariates sexual activity, historic period at stroke onset, and fourth dimension. Changes in mortality rates in the general population were taken into account by including the expected number of deaths in the model with the "offset variable" facility in the "proc phreg" procedure in the SAS software package.^sixteen

Results

A total of 4162 patients with a offset stroke were eligible for the analyses. Table i shows the proportions of fatal and nonfatal stroke past sex and age group.

Fatal and Nonfatal Offset Strokes in the Danish MONICA Population 1982–1991, past Sex activity and Age

Stroke	Men						Women
	25–69 y		≥70 y		≥25 y		25–69 y		≥70 y		≥25 y
	No.	%	No.	%	No.	%	No.	%	No.	%	No.	%
Fatal	237	18.ane	296	33.eight	533	24.four	169	22.6	470	38.iii	639	32.4
Nonfatal	1073	81.9	581	66.2	1654	75.6	580	77.4	756	61.7	1336	67.6
All	1310	100.0	877	100.0	2187	100.0	749	100.0	1226	100.0	1975	100.0

Short-Term Survival past Stroke Subtype

Valid information on stroke subtype was available for 1887 (45.3%) of the patients. The subtypes were cerebral infarct in 1318, principal intracerebral hemorrhage in 331, and subarachnoid hemorrhage in 238. The remaining 2275 were classified as ill-divers stroke. The patients with subarachnoid hemorrhage were younger than the other patients (hateful age, 53.1 years), whereas patients with documented cerebral infarct or main intracerebral hemorrhage were of similar ages, the hateful ages being 61.four years and 62.8 years, respectively. Sufficient information on stroke subtype was more frequently bachelor for younger than for older patients: the mean age of patients with ill-defined stroke was 74.0 years. Effigy 1 shows the Kaplan-Meier estimates of the survival probability for each stroke subtype and sick-divers stroke. The short-term survival probability was conspicuously best for cerebral infarct and poorest for primary intracerebral hemorrhage. The patients with sick-defined stroke had survival probabilities like to those with known cognitive infarct, despite their markedly greater age.

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Figure ane. Brusque-term survival probability (Kaplan-Meier estimates) subsequently a first stroke past subtype. SAH indicates subarachnoid hemorrhage; PICH, primary intracerebral hemorrhage; CI, cerebral infarct; and IDS, sick-defined stroke.

Long-Term Survival

A total of 2990 patients (72%) survived their first stroke by >27 days, and 2448 (59%) were still alive one year after the stroke; thus, 41% died later one year. The risk for death between 4 weeks and 12 months later on the first stroke was 18.1% (95% CI, xvi.seven% to xix.5%). After the first year, the annual risk for death was approximately 10% and remained almost constant.

The estimated cumulative run a risk for decease was 60%, 76%, and 86% at v, 10, and 15 years later alphabetize stroke, respectively.

Effigy 2 shows the long-term survival probability for a person aged 65 at the time of a offset nonfatal stroke. The prognosis was better for subarachnoid hemorrhage than for the other 3 categories (P<0.001, adjusted for the effect of sex and age). There were no differences in long-term survival for the other 3 categories (P=0.sixteen).

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Figure 2. Long-term survival probability for patients aged 65 years at first nonfatal stroke past subtype (Cox regression). Abbreviations are equally defined in Figure one.

Table 2 shows the SMRs and EDRs for men and women by age group for various periods after a nonfatal stroke. Those who had survived their initial stroke by four weeks had an almost five-fold greater risk for dying inside ane year after the stroke than persons of the same historic period and sex in the general population in the same geographic expanse. The excess risk for death was significantly higher for women than for men during the kickoff yr after a stroke but did not differ significantly between sexes afterward the first year.

SMRs^* and EDRs^† by Sex and Age for Patients After a First Nonfatal Stroke

Age Group, y	Years After Stroke	SMR (95% CI)			EDR (95% CI)
		Men	Women	All	Men	Women	All
*Quotient of observed to expected numbers of deaths.
†Observed minus expected number of deaths per 1000 person-years.
25–69	0–1	4.64 (three.71–5.72)	9.27 (vi.94–12.1)	v.72 (4.81–6.75)	66.7 (49.eight–86.6)	86.eight (62.iv–117)	73.seven (59.v–89.8)
	1–5	3.01 (2.63–iii.43)	3.52 (2.80–4.35)	3.14 (two.eighty–3.fifty)	43.three (35.1–52.3)	31.1 (22.3–41.4)	38.ix (32.vii–45.7)
	5–10	2.75 (2.39–3.xv)	3.32 (two.66–4.09)	2.90 (2.58–3.25)	49.9 (39.5–61.3)	38.six (27.6–51.4)	45.6 (37.nine–54.0)
	x–fifteen	2.50 (1.94–3.eighteen)	2.45 (i.threescore–3.59)	2.49 (2.01–3.05)	55.5 (34.7–80.4)	31.two (xiii.0–55.viii)	45.7 (thirty.9–62.eight)
≥70	0–1	3.70 (3.xv–four.32)	5.18 (iv.54–5.87)	4.46 (4.04–4.92)	245 (195–301)	328 (278–383)	291 (255–329)
	1–5	i.92 (1.68–2.18)	2.05 (ane.81–2.thirty)	i.99 (one.82–2.17)	93.iii (69.two–120)	92.ix (71.8–116)	93.1 (77.0–110)
	five–x	1.89 (1.56–ii.27)	1.99 (ane.67–2.36)	one.94 (one.71–two.20)	117 (73.8–166)	104 (69.6–142)	109 (82.ane–139)
	10–15	2.49 (1.48–3.93)	1.67 (1.08–2.47)	i.94 (1.40–2.61)	253 (80.7–498)	98.0 (12.i–214)	143 (61.6–246)
≥25	0–one	3.98 (three.50–4.51)	5.62 (five.00–6.30)	four.73 (iv.34–five.15)	124 (104–145)	213 (184–244)	162 (145–180)
	ane–5	ii.34 (2.13–two.56)	two.27 (2.04–two.52)	two.31 (2.fifteen–ii.47)	56.ane (47.4–65.five)	57.9 (47.four–69.two)	56.9 (50.1–64.0)
	5–10	2.37 (two.11–2.64)	2.37 (two.07–2.70)	2.37 (2.17–2.58)	threescore.0 (49.0–72.0)	57.1 (44.5–71.0)	58.8 (l.4–67.7)
	10–15	2.50 (ii.00–iii.09)	two.00 (1.49–2.63)	ii.28 (ane.92–2.70)	66.4 (44.ii–92.vi)	42.7 (xx.9–69.7)	56.ane (40.0–74.iii)

The mean age at stroke was 67.two years during 1982–1986 and 68.7 years during 1987–1991. The survival probability improved significantly during the observation period for patients with infarcts or ill-defined stroke. Figure three shows, every bit an case, the survival probability for a person aged 65 years with onset of cerebral infarct or ill-defined stroke during 1982–1986 compared with 1987–1991. The difference is statistically significant (P<0.01). The survival curves prove that the risks for acute and early decease did not differ, merely the probability of long-term survival increased afterwards the showtime yr beyond the alphabetize stroke.

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Figure 3. Long-term survival probability for patients aged 65 years at first cerebral infarct or sick-defined stroke by menstruation of attack (Cox regression).

Causes of Decease

Two thirds of the patients with nonfatal stroke subsequently died from vascular diseases (Table 3). The mortality charge per unit due to all cardiovascular diseases was almost four times higher than that in the background population (Tabular array 4). More than patients died from cerebrovascular illness than from middle illness, particularly women. The risk for cerebrovascular death was 8 to nine times that of the general population, merely the excess mortality was non confined to vascular diseases since the rates for cancer, other diseases, accidents, and suicide were as well significantly higher than expected. Ischemic heart disease and other vascular diseases were more than than twice equally often the cause of death than expected, but vascular diseases other than stroke contributed only slightly more other diseases to the overall excess mortality. The frequency of other diseases, accidents, and suicide as the cause of expiry was approximately double that for the general population, and stroke survivors also had a statistically meaning 26% increment in the risk for dying from cancer.

Causes of Death of Patients With Nonfatal Stroke Who Died Before January one, 1996

Cause of Expiry*	Men		Women		All
	No.	%	No.	%	No.	%
International Classification of Diseases (ICD) codes: 8th edition for deaths before January 1, 1994; 10th edition for deaths subsequently January 1, 1994.
*Unknown in 11 cases.
Cardiovascular diseases ICD-eight: 390–458; ICD-10: I00–I99	626	63.iv	608	72.3	1234	67.5
Ischemic heart affliction ICD-8: 410–414; ICD-x: I20–I25	242	24.5	173	20.6	415	22.7
Cerebrovascular affliction ICD-8: 430–438; ICD-ten: I60–I69	268	27.2	318	37.8	586	32.ane
Cancer ICD-8: 140–209; ICD-10: C00–D09	133	xiii.5	83	9.9	216	eleven.8
Other diseases ICD-eight: 0–136, 210–389, 460–796; ICD-10: A00–B99, D10–H95, J00–R99	205	20.viii	130	15.4	335	xviii.3
Accidents and suicide ICD-8: E800–E999; ICD-10: V00–Y99	23	two.3	20	ii.4	43	two.4
Total	987	100	841	100	1828	100

SMRs^* by Sex and Causes of Death of Patients After a Outset Nonfatal Stroke

Cause of Death	SMR (95% CI)
	Men			Women
	Cerebral Infarct	Sick-Defined Stroke	All Strokes†	Cerebral Infarct	Ill-Defined Stroke	All Strokes†
*Quotient of observed to expected numbers of deaths.
†Subarachnoid hemorrhage, primary intracerebral hemorrhage, cerebral infarct, and ill-defined stroke.
Cardiovascular diseases	4.01 (3.43–4.66)	3.62 (3.29–3.98)	3.75 (3.46–4.06)	5.77 (4.67–7.06)	iii.77 (iii.44–iv.12)	4.03 (3.71–four.36)
Ischemic heart disease	2.85 (2.22–3.60)	two.62 (ii.24–3.06)	2.64 (2.32–2.99)	3.64 (2.42–5.26)	two.41 (2.03–2.84)	2.fifty (2.14–2.xc)
Cerebrovascular illness	9.07 (vii.07–xi.5)	vii.lxx (half dozen.62–viii.91)	8.32 (7.35–ix.37)	12.1 (eight.89–16.0)	8.xix (seven.20–9.27)	eight.89 (7.94–9.92)
Other cardiovascular diseases	two.99 (2.03–iv.25)	2.58 (two.04–3.21)	2.lxx (2.23–3.24)	iii.98 (2.40–6.21)	2.41 (1.95–2.94)	two.54 (2.10–iii.05)
Cancer	1.40 (1.03–1.86)	1.fifteen (0.92–i.43)	i.22 (1.02–1.44)	one.87 (one.21–2.76)	1.17 (0.87–1.53)	1.33 (1.06–i.65
Other diseases	2.17 (1.64–2.82)	2.24 (i.89–ii.64)	2.20 (1.91–2.52)	2.48 (1.63–3.threescore)	ane.74 (1.41–2.eleven)	one.83 (1.53–2.18)
Accidents and suicide	2.lx (1.25–4.78)	1.44 (0.72–ii.58)	one.88 (1.19–ii.83)	2.86 (0.93–six.68)	1.72 (0.97–2.84)	1.82 (1.11–2.81)
Total	2.68 (2.38–3.01)	2.55 (2.36–2.75)	ii.58 (2.43–ii.75)	3.58 (3.03–4.xix)	2.73 (two.53–2.95)	2.85 (2.66–3.05)

Discussion

In this community-based report, in which nosotros followed upwardly unselected patients with a outset stroke for a sufficient length of time and in sufficiently large numbers for accurate statistics on the absolute and relative long-term risks for death, our results are in agreement with those of previous investigations, showing that the highest risk for decease is in the acute phase of a stroke and then gradually declines. More than one twelvemonth after a first stroke, the excess mortality appears to level off, the risk for death being approximately twice that of the full general population. In the Oxfordshire Community Stroke Project,⁵ 675 patients with a first stroke were followed upwardly for up to six.five years, and the relative risk of death was plant to vary between ane.1 and 2.9 at ii to 6 years after the stroke. In the Perth Community Stroke Study,⁴ in which 362 patients with a first stroke were followed up for 5 years, the relative run a risk for death across 1 year after the stroke was between 2.0 and 2.three. Loor et al⁶ followed upwardly 221 patients upwardly to three years and reported the relative risk for expiry to be two.0 in the interval ii to 3 years after the stroke. We found a SMR ≥2.0 for as long every bit 10 to 15 years after the initial stroke. Hence, we conclude that persons who survive a stroke have a continuing excess adventure of decease, which remains at least double that of the groundwork population.

Case fatality rates vary considerably among populations,¹ and information technology has been found oftentimes that the age-standardized case fatality rates are college for women than for men. We found that, after 4 weeks, women continued to take a higher run a risk for death than men for every bit long as i year after the stroke. The female person stroke victims were older than the men, but the effect of age was controlled for in the analyses, and our information do non offer any explanation for the departure. A similar difference was found in a written report in kingdom of the netherlands^half-dozen; in other community-based studies, risk estimates were not reported by sex.

The most frequent cause of death in patients with nonfatal strokes was cardiovascular disease (either cerebrovascular disease or middle affliction). The distribution of causes of death is similar to that establish amongst xxx-mean solar day survivors in other studies: cerebrovascular diseases accounted for 43% and other vascular causes for 26% of deaths in the netherlands,⁶ and the corresponding figures were 36% and 34% in Oxfordshire⁵ and 27% and 31% in Perth, Australia.^iv We establish that 32.1% of deaths after nonfatal stroke were due to cerebrovascular illness and 22.7% to ischemic heart affliction. In comparison with the background population, the risk for death from cardiovascular diseases other than stroke was more than double that expected (Table iv), and the estimated gamble for expiry from cerebrovascular disease was more than 8-fold that expected. Ischemic heart disease and vascular diseases other than stroke contributed little more than did the category "other diseases" to the overall excess mortality. The relative distribution of causes of decease may, notwithstanding, exist biased. Since our analyses were based on official death statistics, it is likely that the SMRs for cerebrovascular disease are overestimated, because certifying doctors may more readily have recorded "cerebrovascular disease" equally the crusade of death when there was a history of stroke and no more obvious specific crusade. The ratios for center disease and other diseases may be underestimated for the same reason, whereas the registration of cancer deaths, accidents, and suicide is less likely to be influenced.

The finding that death from cancer was more frequent may reflect an association with stroke every bit a issue of shared risk factors such as smoking. There was a trend to excess mortality from lung cancer among male but not amongst female stroke patients (data not shown), whereas deaths from chronic bronchitis and emphysema were more than frequent among female person patients simply not among male patients (information not shown).

A caste of disability after a stroke that made the patient ineligible for antineoplastic therapy may also have played a role in the excess mortality from cancer, and this factor may similarly have limited the possibilities for constructive handling of any other status, thereby accounting in part for the excess death rates. In the report in Perth, physical inability before a stroke increased the risk for expiry of stroke patients; nosotros presume that poststroke disability may accept a similar issue.

Disabled persons may also have a college take a chance for accidents, in particular falls. In the study of Loor et al,^vi it was found that 5 of 62 deceased patients (8%) died of complications after a fracture of the femur. It can merely be speculated that poststroke depression might lead to suicide.

In view of the definition in the protocol of the WHO MONICA Project of a stroke event, we analyzed survival probability after a fatal stroke by stroke subtype and not past direct or indirect causes of death. In studies in which the straight cause of death inside thirty days after a outset stroke was examined,^4–six death was due to cerebrovascular affliction in 91% of patients in the Oxfordshire Community Stroke Projection and in 85% in the Perth Community Stroke Study. Loor et al⁶ constitute that merely 1 of 58 patients did non die of the index stroke. A study in Rochester, Minn, ¹⁰ included stroke of uncertain type in the analyses of cerebral infarct because information technology was assumed that the overwhelming majority of patients had had a cognitive infarct. We were tempted to reach a similar conclusion for our category of ill-divers stroke because the survival curves for verified cerebral infarct and ill-defined stroke were almost identical. Still, the accomplice was established during a period when neuroimaging was less frequently used than today. An verbal diagnosis was established more oft in younger than in older patients, and a consummate workup was causeless to have been done more often for patients presenting with severe symptoms and suspected to take intracranial bleeding.

Because some diagnoses were established postmortem, the short-term survival rates for patients with item stroke subtypes are biased. The short-term prognosis was assumed to be improve for all patients with cerebral infarct than for those in whom this subtype was diagnosed. Simply the survival rates for patients with subarachnoid hemorrhage can be considered to exist unbiased. These patients constituted 6% of the total, and we consider it unlikely that there were many cases of this subtype among the ill-defined strokes.

Our findings clearly testify that stroke is a medical emergency with a high risk for decease before long afterwards onset. The selection bias in the take chances estimates for subtypes of stroke exercise non alter the fact that hemorrhagic stroke is more than often fatal than cerebral infarct, illustrating why relatively few cases of bleeding complications tin balance the therapeutic proceeds of rapid treatment of cerebral infarct.

Our findings propose that the probability of long-term survival was significantly ameliorate for patients with ischemic or sick-defined stroke during 1987–1991 than for patients with stroke onset at the beginning of the written report period. A like improvement in survival over time was found in northern Sweden.¹⁷ In previous analyses of all strokes,^fifteen nosotros plant no positive time tendency in short-term survival: the age-adjusted 28-day case fatality rates did not change significantly during 1982–1991, and the comeback was restricted to those who survived longer. Our data practise not offer any specific explanation because we had no data on stroke severity or comorbidity. We know, however, that the incidence rates of stroke declined.¹⁵ We consider this to be in part the result of improved chief prevention, in item control of hypertension. Sensation of means for preventing cardiovascular diseases in general increased during the 1980s, and it was at the stop of this decade that warfarin was shown to be constructive in preventing stroke in patients with arterial fibrillation; this was also the time when the concept of dedicated stroke units was introduced. No such unit of measurement was available to the patients included in the present written report, just nosotros strongly believe that the focus on appropriate stroke management has had a positive influence on patient care.

We have pointed to stroke-related disability as a possible explanation for the excess mortality from other diseases, cancer, accidents, and suicide. If this assumption is truthful, information technology emphasizes the demand for improved rehabilitation to minimize poststroke disability. The about important risk of stroke survivors is recurrent cerebrovascular disease, which was >8 times college than that of the background population and much more pronounced than the backlog take chances for death from other causes, including ischemic heart disease. In our stance, this is a potent argument in favor of standing and increasing efforts in the field of secondary stroke prevention.

The incidence of stroke declined,^xv and the present results suggest that long-term survival improved in Denmark during a fourth dimension when information technology became articulate that stroke is a public health effect. This improvement may be the result of improve prevention, better direction or, more than likely, a combination of the two.

The DAN-MONICA Stroke Project was supported in part by grants from the Danish Heart Foundation. The authors wish to acknowledge the work of all members of the Danish MONICA team and the back up received from collaborating institutions and organizations.

Footnotes

Correspondence to Henrik Brønnum-Hansen, National Institute of Public Health, 25 Svanemøllevej, DK 2100 Copenhagen Ø, Denmark. E-postal service [e-mail protected]

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Source: https://www.ahajournals.org/doi/10.1161/hs0901.094253

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