論文ID: CJ-18-0346
Background: Stroke is one of the leading causes of disability and mortality in Japan. The aim of the present analysis was to determine the non-acute survival rate after first-ever stroke using data from a large-scale population-based stroke registry in Japan.
Methods and Results: Shiga Stroke Registry is an ongoing population-based registry of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in central Japan. A total of 2,176 first-ever stroke patients, who were registered in 2011, were followed up until December 2013. The 2-year cumulative survival rates were estimated using Kaplan-Meier method according to index stroke subtype. Cox proportional hazards models were used to assess predictors of all-cause death. During a 2-year follow-up period, 663 patients (30.5%) died. The 2-year cumulative survival rate after first-ever stroke was 69.5%. There was heterogeneity in 2-year cumulative survival according to stroke subtype: lacunar infarction, 87.2%; large artery infarction, 76.1%; cardioembolic infarction, 55.4%; intracerebral hemorrhage, 65.9%; and subarachnoid hemorrhage, 56.7%. Older age, male sex, medical history, higher Japan coma scale score on admission, and stroke subtype were associated with risk of all-cause death in ≤2 years.
Conclusions: In the present population-based stroke registry with a real-world setting in Japan, 2-year cumulative mortality after first-ever stroke is still high (>30%), particularly for cardioembolic infarction, subarachnoid hemorrhage and intracerebral hemorrhage.
In Japan, the age-standardized stroke mortality has decreased rapidly during the last 5 decades,1 but stroke is still one of the leading causes of death2 and disability.3 Furthermore, the absolute number of stroke patients is expected to increase because of the rapid aging of Japanese society.4 Effective prevention will require a strategy based on accurate knowledge on current burden and prognosis of stroke in the real world. There is limited evidence, however, of current non-acute mortality after onset of first-ever stroke in general populations, especially in Asian countries. The aim of the present study was therefore to investigate the current cumulative and relative 2-year survival rate using data from a large-scale population-based stroke registry in Shiga Prefecture, Japan.
The design of the Shiga Stroke Registry has been described in detail elsewhere.5 Briefly, the Shiga Stroke Registry is an ongoing multicenter population-based registry study designed to build a complete information system on acute ischemic and non-traumatic hemorrhagic stroke management in Shiga Prefecture, Japan. Shiga Prefecture is located in the central part of Honshu Island, and more than half of the residents in Shiga Prefecture live in the Keihanshin (Kyoto-Osaka-Kobe) Metropolitan Area, according to the Ministry of Internal Affairs and Communications (Figure S1). The population of Shiga Prefecture was 1,400,745 residents (689,859 men and 710,866 women) based on a 2011 census. There is an integrated surveillance system involving the registration of cases in a network of all acute care hospitals with neurology/neurosurgery facilities and smaller hospitals with rehabilitation facilities. Data were extracted from medical records of these hospitals by trained investigators.
A total of 2,176 cases of first-ever stroke, the onset date of which ranged from 1 January to 31 December 2011, were included in the present analysis. The study was approved by the Institutional Review Board of Shiga University of Medical Science.
Definition of Index Stroke and SubtypesDiagnosis of stroke was defined as sudden onset of focal neurological deficits persisting >24 h according to the Monitoring Trends and Determinants in Cardiovascular Disease projects.6 Stroke was then classified as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage or undetermined. Ischemic stroke was further divided into the following clinical categories: lacunar infarction; large artery infarction; cardioembolic infarction; or undetermined type, based on the Trial of Org 10172 in Acute Stroke Treatment criteria.7 All stroke cases were adjudicated by more than 2 independent investigators. In the few cases when there was disagreement, more than 3 investigators discussed the case and consensus was reached in all cases.
Clinical Features and Medical HistoryInformation on clinical features including Japan coma scale (JCS) score8 at baseline was obtained for all stroke patients from the admission record. JCS score is a 10-grade scale and is widely used to assess consciousness in Japan: JCS 0, alert; JCS 1–3, possible eye-opening, not lucid; JCS 10–30, possible eye-opening upon stimulation; JCS 100–300, no eye-opening and coma. Hypertension treatment was defined as use of antihypertensive medication before the incidence of stroke. Diabetes was defined as casual blood glucose ≥200 mg/dL, use of anti-diabetic medication and/or history of diabetes. Dyslipidemia was defined as total cholesterol ≥220 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, medication for dyslipidemia and/or history of dyslipidemia. Atrial fibrillation was defined as medication for atrial fibrillation and/or history of atrial fibrillation. Past history of transient ischemic attack (TIA), and myocardial infarction was extracted from the admission record.
Follow-up Survey and OutcomeAll patients with first-ever stroke were followed up until December 2013 using death certificate information. Death certificate information for all deceased residents was collected with permission of the Japanese Ministry of Health, Labor and Welfare and matched with all stroke cases. The outcome of this study was all-cause death.
Statistical AnalysisCumulative survival rate of first-ever stroke at 28 days, 3 months, 1 year and 2 years was estimated using Kaplan-Meier analysis. Relative survival rate was calculated using the Ederer II method9 with the Japanese cohort survival table.10 The Cox proportional hazards model was used to evaluate the possible predictors for acute death (≤28 days after stroke) as well as for non-acute death (29 days–2 years after stroke). Cases with missing data on TIA history (n=35) were excluded from the analysis. P<0.05 was considered statistically significant.
Baseline characteristics of first-ever stroke patients are listed in Table 1. Mean age was 74.7 years for ischemic stroke, 71.0 years for intracerebral hemorrhage and 64.6 years for subarachnoid hemorrhage. Less than 10% of ischemic stroke patients, 25% of cerebral hemorrhage patients and 45% of subarachnoid hemorrhage patients were in coma (JCS score 100–300).
| Ischemic stroke | Intracerebral hemorrhage |
Subarachnoid hemorrhage |
Total stroke |
|||||
|---|---|---|---|---|---|---|---|---|
| Total | Lacunar infarction |
Large artery infarction |
Cardioembolic infarction |
Other/ Undetermined |
||||
| Total | 1,398 | 352 | 439 | 354 | 253 | 551 | 201 | 2,176 |
| Men | 783 (56.0) | 208 (59.1) | 262 (59.7) | 170 (48.0) | 143 (56.5) | 280 (50.8) | 61 (30.3) | 1,138 (52.3) |
| Age (years) | 74.7±13.2 | 72.5±12.8 | 74.5±13.1 | 80.2±10.4 | 70.5±14.7 | 71.0±14.8 | 64.6±15.8 | 72.9±14.2 |
| Treatment | ||||||||
| Hypertension | 719 (51.4) | 168 (47.7) | 238 (54.2) | 203 (57.3) | 110 (43.5) | 190 (34.5) | 72 (35.8) | 991 (45.5) |
| Diabetes | 241 (17.2) | 63 (17.9) | 87 (19.8) | 49 (13.8) | 42 (16.6) | 49 (8.9) | 13 (6.5) | 305 (14.0) |
| Dyslipidemia | 202 (14.4) | 59 (16.8) | 67 (15.3) | 44 (12.4) | 32 (12.6) | 54 (9.8) | 22 (10.9) | 278 (12.8) |
| Anticoagulation | 102 (7.3) | 11 (3.1) | 14 (3.2) | 70 (19.8) | 7 (2.8) | 37 (6.7) | 5 (2.5) | 145 (6.7) |
| Past history | ||||||||
| TIA | 73 (5.2) | 21 (6.0) | 26 (5.9) | 13 (3.7) | 13 (5.1) | 7 (1.3) | 1 (0.5) | 81 (3.7) |
| MI | 85 (6.1) | 19 (5.4) | 31 (7.1) | 30 (8.5) | 5 (2.0) | 34 (6.2) | 4 (2.0) | 124 (5.7) |
| AF | 328 (23.5) | 11 (3.1) | 21 (4.8) | 283 (79.9) | 13 (5.1) | 46 (8.3) | 10 (5.0) | 385 (17.7) |
| Smoking | ||||||||
| Non-smoker | 803 (62.6) | 196 (61.3) | 244 (60.1) | 233 (72.1) | 130 (55.6) | 331 (67.3) | 105 (61.4) | 1,242 (63.7) |
| Past smoker | 159 (12.4) | 30 (9.4) | 59 (14.5) | 33 (10.2) | 37 (15.8) | 57 (11.6) | 16 (9.4) | 234 (12.0) |
| Current smoker | 321 (25.0) | 94 (29.4) | 103 (25.4) | 57 (17.6) | 67 (28.6) | 104 (21.1) | 50 (29.2) | 475 (24.3) |
| Unknown | 115 | 32 | 33 | 31 | 19 | 59 | 30 | 225 |
| Drinking | ||||||||
| Non-drinker | 708 (58.3) | 174 (57.4) | 229 (59.0) | 190 (62.9) | 115 (51.8) | 277 (58.8) | 102 (61.1) | 1,089 (58.6) |
| Past drinker | 26 (2.1) | 4 (1.3) | 9 (2.3) | 6 (2.0) | 7 (3.2) | 6 (1.3) | 3 (1.8) | 35 (1.9) |
| Current drinker | 481 (39.6) | 125 (41.3) | 150 (38.7) | 106 (35.1) | 100 (45.0) | 188 (39.9) | 62 (37.1) | 734 (39.5) |
| Unknown | 183 | 49 | 51 | 52 | 31 | 80 | 34 | 318 |
| Severity | ||||||||
| JCS 0 | 822 (59.0) | 276 (79.1) | 252 (57.5) | 122 (34.5) | 172 (68.3) | 163 (29.6) | 48 (24.0) | 1,034 (47.8) |
| JCS 1–3 | 335 (24.0) | 61 (17.5) | 113 (25.8) | 111 (31.4) | 50 (19.8) | 141 (25.6) | 28 (14.0) | 504 (23.3) |
| JCS 10–30 | 127 (9.1) | 6 (1.7) | 45 (10.3) | 61 (17.2) | 15 (6.0) | 109 (19.8) | 36 (18.0) | 272 (12.6) |
| JCS 100–300 | 109 (7.8) | 6 (1.7) | 28 (6.4) | 60 (16.9) | 15 (6.0) | 137 (24.9) | 88 (44.0) | 353 (16.3) |
| Unknown | 5 | 3 | 1 | 0 | 1 | 1 | 1 | 13 |
Data given as n, n (%) or mean±SD. AF, atrial fibrillation; JCS, Japan coma scale (JCS 0, alert; JCS 1–3, possible eye-opening, not lucid; JCS 10–30, possible eye-opening upon stimulation; JCS 100–300, no eye-opening and coma); MI, myocardial infarction; TIA, transient ischemic attack.
Cumulative survival rates for stroke and its subtypes are listed in Table 2. Cumulative survival rate after first-ever stroke was 75.4% at 1 year and 69.5% at 2 years. The cumulative survival rate at 2 years was 74.0% for ischemic stroke, 65.9% for intracerebral hemorrhage and 56.7% for subarachnoid hemorrhage. Cumulative survival curve of stroke and ischemic stroke subtypes are shown separately for men and women in Figure.
| Men | Women | Men and Women | ||||||
|---|---|---|---|---|---|---|---|---|
| Death (n) |
Survival rate (%) |
95% CI | Death (n) |
Survival rate (%) |
95% CI | Survival rate (%) |
95% CI | |
| Total stroke | ||||||||
| 28-day | 135 | 88.1 | (86.3–90.0) | 161 | 84.5 | (82.3–86.7) | 86.4 | (85.0–87.8) |
| 3-month | 164 | 85.6 | (83.5–87.6) | 208 | 80.0 | (77.5–82.4) | 82.9 | (81.3–84.5) |
| 1-year | 235 | 79.3 | (77.0–81.7) | 300 | 71.1 | (68.3–73.9) | 75.4 | (73.6–77.2) |
| 2-year | 305 | 73.2 | (70.6–75.8) | 358 | 65.5 | (62.6–68.4) | 69.5 | (67.5–71.5) |
| Total ischemic stroke | ||||||||
| 28-day | 40 | 94.9 | (93.3–96.4) | 62 | 89.9 | (87.5–92.3) | 92.7 | (91.3–94.1) |
| 3-month | 62 | 92.1 | (90.2–94.0) | 97 | 84.2 | (81.3–87.1) | 88.6 | (86.9–90.3) |
| 1-year | 113 | 85.6 | (83.1–88.0) | 154 | 75.0 | (71.5–78.4) | 80.9 | (78.8–83.0) |
| 2-year | 170 | 78.3 | (75.4–81.2) | 193 | 68.6 | (65.0–72.3) | 74.0 | (71.7–76.3) |
| Lacunar infarction | ||||||||
| 28-day | 0 | – | – | 6 | 95.8 | (92.6–99.1) | 98.3 | (96.9–99.6) |
| 3-month | 3 | 98.6 | (96.9–100.0) | 11 | 92.4 | (88.0–96.7) | 96.0 | (94.0–98.1) |
| 1-year | 10 | 95.2 | (92.3–98.1) | 18 | 87.5 | (82.1–92.9) | 92.0 | (89.2–94.9) |
| 2-year | 22 | 89.4 | (85.2–93.6) | 23 | 84.0 | (78.0–90.0) | 87.2 | (83.7–90.7) |
| Large artery infarction | ||||||||
| 28-day | 10 | 96.2 | (93.9–98.5) | 16 | 91.0 | (86.7–95.2) | 94.1 | (91.9–96.3) |
| 3-month | 18 | 93.1 | (90.1–96.2) | 23 | 87.0 | (82.1–92.0) | 90.7 | (87.9–93.4) |
| 1-year | 37 | 85.9 | (81.7–90.1) | 43 | 75.7 | (69.4–82.0) | 81.8 | (78.2–85.4) |
| 2-year | 53 | 79.8 | (74.9–84.6) | 52 | 70.6 | (63.9–77.3) | 76.1 | (72.1–80.1) |
| Cardioembolic infarction | ||||||||
| 28-day | 18 | 89.4 | (84.8–94.0) | 31 | 83.2 | (77.7–88.6) | 86.2 | (82.6–89.8) |
| 3-month | 25 | 85.3 | (80.0–90.6) | 46 | 75.0 | (68.7–81.3) | 79.9 | (75.8–84.1) |
| 1-year | 44 | 74.1 | (67.5–80.7) | 71 | 61.4 | (54.4–68.4) | 67.5 | (62.6–72.4) |
| 2-year | 66 | 61.2 | (53.9–68.5) | 92 | 50.0 | (42.8–57.2) | 55.4 | (50.2–60.5) |
| Other/Undetermined | ||||||||
| 28-day | 12 | 91.6 | (87.1–96.2) | 9 | 91.8 | (86.7–96.9) | 91.7 | (88.3–95.1) |
| 3-month | 16 | 88.8 | (83.6–94.0) | 17 | 84.5 | (77.8–91.3) | 87.0 | (82.8–91.1) |
| 1-year | 22 | 84.6 | (78.7–90.5) | 22 | 80.0 | (72.5–87.5) | 82.6 | (77.9–87.3) |
| 2-year | 29 | 79.7 | (73.1–86.3) | 26 | 76.4 | (68.4–84.3) | 78.3 | (73.2–83.3) |
| Intracerebral hemorrhage | ||||||||
| 28-day | 59 | 78.9 | (74.2–83.7) | 45 | 83.4 | (79.0–87.8) | 81.1 | (77.9–84.4) |
| 3-month | 66 | 76.4 | (71.5–81.4) | 52 | 80.8 | (76.1–85.5) | 78.6 | (75.2–82.0) |
| 1-year | 82 | 70.7 | (65.4–76.0) | 79 | 70.8 | (65.4–76.3) | 70.8 | (67.0–74.6) |
| 2-year | 93 | 66.8 | (61.3–72.3) | 95 | 64.9 | (59.3–70.6) | 65.9 | (61.9–69.8) |
| Subarachnoid hemorrhage | ||||||||
| 28-day | 22 | 63.9 | (51.9–76.0) | 43 | 69.3 | (61.6–76.9) | 67.7 | (61.2–74.1) |
| 3-month | 22 | 63.9 | (51.9–76.0) | 48 | 65.7 | (57.9–73.6) | 65.2 | (58.6–71.8) |
| 1-year | 26 | 57.4 | (45.0–69.8) | 56 | 60.0 | (57.9–68.1) | 59.2 | (52.4–66.0) |
| 2-year | 28 | 54.1 | (41.6–66.6) | 59 | 57.9 | (49.7–66.0) | 56.7 | (49.9–63.6) |
Two-year survival rates after first-ever stroke in (A,B) men and (C,D) women according to (A,C) stroke subtype and (B,D) ischemic stroke subtype.
Age-stratified cumulative survival rates of stroke and its subtypes are listed in Table 3. The cumulative survival rate at 2 years was 84.3% in men aged <65 years, and 82.9% in women. In elderly subjects (age ≥85 years), the cumulative survival rate at 2 years was 37.0% in men and 41.0% in women. Cumulative survival rate curves are shown in Figure S2.
| Age <65 years | Age 65–74 years | Age 75–84 years | Age ≥85 years | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Death (n) |
Survival rate (%) |
95% CI | Death (n) |
Survival rate (%) |
95% CI | Death (n) |
Survival rate (%) |
95% CI | Death (n) |
Survival rate (%) |
95% CI | |
| Men | ||||||||||||
| Total stroke | ||||||||||||
| 28-day | 43 | 89.1 | (86.0– 92.2) |
19 | 93.8 | (91.1– 96.5) |
45 | 85.9 | (82.1– 89.7) |
28 | 76.5 | (68.8– 84.1) |
| 1-year | 54 | 86.3 | (82.9– 89.7) |
34 | 88.9 | (85.4– 92.4) |
87 | 72.7 | (67.8– 77.6) |
60 | 49.6 | (40.6– 58.6) |
| 2-year | 62 | 84.3 | (80.7– 87.9) |
48 | 84.3 | (80.2– 88.4) |
120 | 62.4 | (57.1– 67.7) |
75 | 37.0 | (28.3– 45.6) |
| Ischemic stroke | ||||||||||||
| 28-day | 5 | 97.8 | (95.8– 99.7) |
9 | 96.2 | (93.7– 98.6) |
15 | 93.5 | (90.3– 96.7) |
11 | 88.0 | (81.4– 94.7) |
| 1-year | 11 | 95.1 | (92.3– 97.9) |
19 | 91.9 | (88.5– 95.4) |
43 | 81.4 | (76.4– 86.4) |
40 | 56.5 | (46.4– 66.7) |
| 2-year | 17 | 92.4 | (88.9– 95.9) |
29 | 87.7 | (83.5– 91.9) |
72 | 68.8 | (62.9– 74.8) |
52 | 43.5 | (33.3– 53.6) |
| Intracerebral hemorrhage | ||||||||||||
| 28-day | 18 | 85.4 | (79.1– 91.6) |
7 | 88.3 | (80.2– 96.5) |
19 | 73.6 | (63.4– 83.8) |
15 | 40.0 | (20.8– 59.2) |
| 1-year | 23 | 81.3 | (74.4– 88.2) |
11 | 81.7 | (71.9– 91.5) |
30 | 58.3 | (46.9– 69.7) |
18 | 28.0 | (10.4– 45.6) |
| 2-year | 25 | 79.7 | (72.6– 86.8) |
14 | 76.7 | (66.0– 87.4) |
33 | 54.2 | (42.7– 65.7) |
21 | 16.0 | (1.6– 30.4) |
| Women | ||||||||||||
| Total stroke | ||||||||||||
| 28-day | 21 | 89.8 | (85.6– 93.9) |
21 | 88.6 | (84.1– 93.2) |
41 | 87.4 | (83.8– 91.0) |
78 | 75.8 | (71.1– 80.5) |
| 1-year | 31 | 84.9 | (80.0– 89.8) |
28 | 84.9 | (79.7– 90.0) |
84 | 74.2 | (69.5– 79.0) |
157 | 51.2 | (45.8– 56.7) |
| 2-year | 35 | 82.9 | (77.8– 88.1) |
36 | 80.5 | (74.8– 86.2) |
97 | 70.2 | (65.3– 75.2) |
190 | 41.0 | (35.6– 46.4) |
| Ischemic stroke | ||||||||||||
| 28-day | 2 | 97.4 | (93.9– 100.0) |
7 | 93.5 | (88.9– 98.2) |
14 | 93.1 | (89.6– 96.6) |
39 | 82.8 | (77.9– 87.7) |
| 1-year | 5 | 93.6 | (88.2– 99.0) |
10 | 90.7 | (85.3– 96.2) |
38 | 81.2 | (75.8– 86.6) |
101 | 55.5 | (49.0– 62.0) |
| 2-year | 7 | 91.0 | (84.7– 97.4) |
15 | 86.1 | (79.6– 92.6) |
46 | 77.2 | (71.4– 83.0) |
125 | 44.9 | (38.5– 51.4) |
| Intracerebral hemorrhage | ||||||||||||
| 28-day | 8 | 88.6 | (81.1– 96.0) |
5 | 88.4 | (78.8– 98.0) |
12 | 86.4 | (79.2– 93.5) |
20 | 71.4 | (60.8– 82.0) |
| 1-year | 13 | 81.4 | (72.3– 90.5) |
6 | 86.0 | (75.7– 96.4) |
26 | 70.5 | (60.9– 80.0) |
34 | 51.4 | (39.7– 63.1) |
| 2-year | 15 | 78.6 | (69.0– 88.2) |
8 | 81.4 | (69.8– 93.0) |
29 | 67.0 | (57.2– 76.9) |
43 | 38.6 | (27.2– 50.0) |
Relative survival rates for stroke and its subtypes are listed in Table 4. Relative survival rate at 2 years for total stroke was 79.8% in men and 72.6% in women (ischemic stroke, 86.0% in men and 77.6% in women; intracerebral hemorrhage, 71.9% in men and 70.9% in women; subarachnoid hemorrhage, 55.5% in men and 60.2% in women). Age-stratified relative survival rates are also listed in Table S1.
| Men | Women | |||
|---|---|---|---|---|
| Survival rate (%) | 95% CI | Survival rate (%) | 95% CI | |
| Total stroke | ||||
| 1-year | 83.0 | (80.6–85.5) | 75.1 | (72.2–78.1) |
| 2-year | 79.8 | (77.0–82.6) | 72.6 | (69.4–75.8) |
| Total ischemic stroke | ||||
| 1-year | 89.9 | (87.3–92.5) | 80.1 | (76.4–83.7) |
| 2-year | 86.0 | (82.8–89.2) | 77.6 | (73.4–81.7) |
| Lacunar infarction | ||||
| 1-year | 99.2 | (96.2–100.0) | 92.1 | (86.4–97.7) |
| 2-year | 97.1 | (92.5–100.0) | 92.5 | (85.9–99.1) |
| Large artery infarction | ||||
| 1-year | 90.0 | (85.6–94.4) | 81.1 | (74.3–87.8) |
| 2-year | 87.5 | (82.2–92.9) | 80.6 | (72.9–88.2) |
| Cardioembolic infarction | ||||
| 1-year | 79.6 | (72.5–86.7) | 67.1 | (59.4–74.8) |
| 2-year | 69.6 | (61.3–77.9) | 58.8 | (50.3–67.3) |
| Other/Undetermined | ||||
| 1-year | 87.9 | (81.7–94.0) | 83.7 | (75.9–91.5) |
| 2-year | 85.8 | (78.7–92.9) | 83.1 | (74.4–91.7) |
| Intracerebral hemorrhage | ||||
| 1-year | 73.7 | (68.2–79.3) | 74.2 | (68.6–79.9) |
| 2-year | 71.9 | (66.0–77.9) | 70.9 | (64.7–77.1) |
| Subarachnoid hemorrhage | ||||
| 1-year | 58.2 | (45.6–70.8) | 61.5 | (53.2–69.8) |
| 2-year | 55.5 | (42.7–68.4) | 60.2 | (51.7–68.8) |
†Calculated using the Ederer II method.9
Results of multivariable analysis for predictors of all-cause death after first-ever stroke are listed in Table 5. Stroke subtype, older age, male sex, higher admission JCS score, and past medical history (TIA and diabetes) were associated with risk of acute death (≤28 days). In contrast, older age, male sex and higher admission JCS score were significant predictors of non-acute death (29 days–2 years).
| Variable | ≤2 years | ≤28 days | 29 days–2 years | ||||||
|---|---|---|---|---|---|---|---|---|---|
| HR | 95% CI | P-value | HR | 95% CI | P-value | HR | 95% CI | P-value | |
| Stroke type | |||||||||
| Lacunar infarction |
Ref. | Ref. | Ref. | ||||||
| Large artery infarction |
1.29 | 0.90–1.84 | 0.162 | 2.15 | 0.87–5.30 | 0.096 | 1.19 | 0.8–1.75 | 0.395 |
| Cardioembolic infarction |
1.69 | 1.19–2.40 | 0.003 | 2.68 | 1.12–6.43 | 0.027 | 1.67 | 1.13–2.46 | 0.009 |
| Other/Undetermined | 1.74 | 1.17–2.60 | 0.006 | 4.35 | 1.73–10.94 | 0.002 | 1.33 | 0.83–2.11 | 0.233 |
| Intracerebral hemorrhage |
1.54 | 1.09–2.18 | 0.015 | 3.89 | 1.65–9.15 | 0.002 | 1.07 | 0.71–1.60 | 0.759 |
| Subarachnoid hemorrhage |
2.17 | 1.44–3.26 | <0.001 | 5.23 | 2.15–12.71 | <0.001 | 1.19 | 0.67–2.12 | 0.547 |
| Other or undermined | 6.99 | 3.30–14.82 | <0.001 | 13.13 | 4.44–38.81 | <0.001 | – | – | – |
| Age (years) | |||||||||
| <45 | Ref. | Ref. | Ref. | ||||||
| 45–64 | 3.31 | 1.44–7.62 | 0.005 | 2.44 | 0.87–6.86 | 0.090 | 3.60 | 0.86–15.15 | 0.081 |
| 65–74 | 3.39 | 1.46–7.83 | 0.004 | 2.40 | 0.84–6.85 | 0.101 | 4.83 | 1.16–20.15 | 0.031 |
| 75–84 | 7.20 | 3.15–16.43 | <0.001 | 3.37 | 1.2–9.44 | 0.021 | 12.16 | 2.96–49.97 | 0.001 |
| ≥85 | 13.16 | 5.72–30.28 | <0.001 | 4.81 | 1.7–13.6 | 0.003 | 26.99 | 6.51–111.91 | <0.001 |
| Women | 0.66 | 0.54–0.81 | <0.001 | 0.68 | 0.5–0.92 | 0.012 | 0.71 | 0.54–0.92 | 0.009 |
| Japan coma scale | |||||||||
| 0 | Ref. | Ref. | Ref. | ||||||
| 1 | 2.31 | 1.65–3.23 | <0.001 | 3.48 | 1.68–7.20 | 0.001 | 2.06 | 1.41–3.02 | <0.001 |
| 2 | 2.14 | 1.43–3.22 | <0.001 | 2.93 | 1.20–7.12 | 0.018 | 1.95 | 1.23–3.09 | 0.005 |
| 3 | 2.73 | 2.00–3.73 | <0.001 | 3.35 | 1.63–6.87 | 0.001 | 2.60 | 1.84–3.67 | <0.001 |
| 10 | 2.81 | 2.03–3.91 | <0.001 | 4.02 | 2.03–7.95 | <0.001 | 2.79 | 1.90–4.08 | <0.001 |
| 20 | 4.96 | 3.15–7.81 | <0.001 | 5.22 | 1.89–14.39 | 0.001 | 5.34 | 3.20–8.90 | <0.001 |
| 30 | 5.75 | 3.68–8.98 | <0.001 | 8.81 | 3.80–20.38 | <0.001 | 5.70 | 3.33–9.76 | <0.001 |
| 100 | 5.98 | 4.00–8.94 | <0.001 | 12.45 | 6.15–25.18 | <0.001 | 4.85 | 2.85–8.26 | <0.001 |
| 200 | 10.00 | 7.45–13.42 | <0.001 | 22.30 | 12.62–39.39 | <0.001 | 7.31 | 4.90–10.92 | <0.001 |
| 300 | 23.90 | 17.58–32.49 | <0.001 | 57.98 | 32.89–102.20 | <0.001 | 7.67 | 4.29–13.71 | <0.001 |
| Unknown | 8.97 | 3.85–20.90 | <0.001 | 19.26 | 5.38–68.95 | <0.001 | 8.36 | 2.57–27.19 | <0.001 |
| History of TIA (vs. no) | |||||||||
| Yes | 2.09 | 1.24–3.53 | 0.006 | 5.58 | 1.37–22.71 | 0.016 | 1.30 | 0.74–2.29 | 0.365 |
| Hypertension (vs. no) | |||||||||
| Yes | 0.92 | 0.78–1.09 | 0.353 | 0.91 | 0.70–1.19 | 0.479 | 0.95 | 0.77–1.18 | 0.641 |
| Unknown | 1.84 | 0.91–3.73 | 0.091 | 1.38 | 0.49–3.86 | 0.537 | 1.71 | 0.53–5.56 | 0.370 |
| Diabetes (vs. no) | |||||||||
| Yes | 1.40 | 1.17–1.68 | <0.001 | 1.63 | 1.25–2.14 | <0.001 | 1.22 | 0.95–1.56 | 0.112 |
| Unknown | 0.75 | 0.35–1.60 | 0.456 | 1.24 | 0.45–3.42 | 0.684 | 0.44 | 0.10–1.88 | 0.267 |
| Dyslipidemia (vs. no) | |||||||||
| Yes | 0.91 | 0.75–1.09 | 0.310 | 1.02 | 0.75–1.37 | 0.916 | 0.85 | 0.67–1.09 | 0.203 |
| Unknown | 1.38 | 1.02–1.88 | 0.038 | 1.22 | 0.79–1.88 | 0.376 | 1.28 | 0.82–2.00 | 0.281 |
| Smoking (vs. non-smoker) | |||||||||
| Past smoker | 1.02 | 0.75–1.40 | 0.889 | 1.05 | 0.63–1.73 | 0.864 | 1.08 | 0.73–1.61 | 0.702 |
| Current smoker | 0.99 | 0.76–1.29 | 0.934 | 0.87 | 0.56–1.36 | 0.536 | 1.22 | 0.86–1.71 | 0.264 |
| Unknown | 1.70 | 1.16–2.51 | 0.007 | 2.60 | 1.35–5.01 | 0.004 | 1.03 | 0.62–1.72 | 0.907 |
| Drinker (vs. non-drinker) | |||||||||
| Past drinker | 1.16 | 0.64–2.09 | 0.626 | 0.92 | 0.40–2.14 | 0.847 | 1.23 | 0.55–2.79 | 0.616 |
| Current drinker | 0.71 | 0.56–0.90 | 0.004 | 0.66 | 0.45–0.97 | 0.036 | 0.75 | 0.56–1.01 | 0.054 |
| Unknown | 0.70 | 0.49–0.99 | 0.045 | 0.51 | 0.27–0.95 | 0.035 | 0.96 | 0.64–1.46 | 0.865 |
Abbreviations as in Table 1.
The present large-scale, population-based stroke registry has demonstrated the current status of 2-year prognosis after the onset of first-ever stroke in the real-world setting in Japan. Cumulative survival rate for total stroke was 75.4% at 1 year and 69.5% at 2 years. Lower cumulative 2-year survival rates were observed for cardioembolic infarction (55.4%), intracerebral hemorrhage (65.9%) and subarachnoid hemorrhage (56.7%). Older age, male sex, higher JCS score on admission, history of TIA and diabetes, and drinking status were associated with higher risk of acute death (≤28 days) and/or non-acute death (29 days–2 years).
In the 1980 s and 1990 s, 1-year survival rate in stroke patients ranged from 60% to 80% in Japan.11–14 To the best of our knowledge, however, there are no other recent studies on non-acute prognosis after stroke in the general Japanese population. Although the mean age at stroke onset has increased in the past few decades in Japan, the cumulative survival rates observed in the present study conducted from 2011 to 2013 seem to be similar to those of the 1980 s and 1990 s, illustrating the continuing importance of countermeasures against stroke.
Non-acute survival rates after stroke have been reported in several recent studies from developed and developing countries.15–17 Cumulative 1-year survival rate after first-ever stroke according to population-based stroke registries was 72% in Brazil (mean age at onset, 63 years)17 and 77% in Germany (mean age at onset, 72 years).18 Although mean age at stroke onset was higher in the present analysis of general Japanese population (73 years), cumulative survival rates after stroke in Japan seem to be similar to those in Germany and Brazil.
Cumulative survival rate has been widely used to show the prognosis for stroke.11–17 Cumulative survival rate, however, is calculated using deaths, regardless of cause. Cumulative survival rate reflects the real survival rate after stroke but might be underestimated compared with the long-term survival rate for stroke attributable to stroke, especially in elderly patients. Relative survival rate is an established method for calculating survival rate attributable to a specific disease, especially in cancer epidemiology.19 In this study, we calculated both the 1- and 2-year relative and cumulative survival rate after stroke and its subtypes. From the point of view of public health, monitoring both cumulative and relative survival rates for stroke might be needed to evaluate the social impact of stroke.
More limited evidence is available for long-term survival after different types of stroke. One-year case fatality rate after ischemic stroke in a hospital-based study in the Netherlands was 24% for total ischemic stroke, 14% for lacunar infarction, 24% for atherothrombotic infarction and 40% for cardioembolic infarction.20 Six-month fatality rate after ischemic stroke in a population-based study in Chile was 40% for patients with cardioembolic infarction and 5% for those with small-vessel infarction.21 One-month and 5-year fatality rates after stroke in the late 1990 s in Japan were 85.9% and 57.9% for intracerebral hemorrhage and 70.1% and 54.9% for subarachnoid hemorrhage.14 A higher fatality rate during the early period was observed in hemorrhagic stroke than in cerebral infarction,13 and similar observations were reported from a hospital-based study in China.15 The present analysis from the Shiga Stroke Registry confirms the findings of the previous studies and clearly shows higher mortality rates after cardioembolic infarction, intracerebral hemorrhage and subarachnoid hemorrhage than other subtypes of stroke, particularly ≤28 days after stroke onset.
High JCS score on admission has been reported to predict early death after stroke.22,23 There is limited evidence, however, for the association between on-admission JCS score and non-acute fatality after stroke. In the present population-based study, high JCS score on admission predicted non-acute fatality after stroke as well as short-term death. Older age and male sex were also associated with both acute and non-acute mortality after stroke. Higher mortality rate in women might be due to the different frequencies of stroke subtype and/or older age of onset.
To our knowledge, this is the first study to report the current status of 2-year prognosis of stroke based on a large-scale, comprehensive population-based registry in Asian countries. This study also has several limitations. First, stroke patients who relocated after stroke onset were lost to follow-up because death certificate information was collected only for residents of Shiga Prefecture. Therefore, we might have overestimated the survival rate after stroke. According to reports on internal migration derived from the Basic Resident Registers, however, only 3.6% of residents moved out of Shiga Prefecture in 2 years. Another limitation is that there are a number of stroke patients who were not evaluated using internationally standardized scores of stroke severity, such as the National Institute of Health Stroke Scale. A third limitation is that accuracy of information on pre-stroke morbidity would be somewhat limited because it might be based on self-reported medical history or non-fasting blood test.
In the present population-based stroke registry in a real-world setting in Japan, 2-year cumulative mortality after first-ever stroke is still high (>30%) particularly for cardioembolic infarction, intracerebral hemorrhage and subarachnoid hemorrhage. These findings re-emphasize the importance of public health measures to reduce the risk of stroke in Japan, given the rapid aging of society.
We thank all investigators, participating hospitals, staff at the Shiga Stroke Data Center (Appendix S1), Shiga Medical Association, Shiga Prefecture Hospital Association, Biwako Brain Attack Consortium (BIWA-BAC) (Appendix S2), Department of Public Health Care and Welfare, Shiga Prefecture Government.
Shiga Stroke Registry is supported by Shiga Prefecture, Japan. This study was supported by Japan Agency for Medical Research and development (AMED).
The authors declare no conflicts of interest.
Supplementary File 1
Appendix S1. Members of Shiga Stroke Data Center
Appendix S2. Biwako Brain Attack Consortium (BIWA-BAC)
Figure S1. Location of Shiga Prefecture (black) in Japan.
Figure S2. Two-year survival rates after first-ever stroke in (A) men and (B) women vs. age group.
Table S1. Relative survival rate after first-ever stroke vs. stroke type, gender and age group in the Shiga Stroke Registry
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-18-0346
