Abstract
Background and Objectives:
Ischemic stroke (IS) in young is increasingly recognized as an important health problem in low- and middle-income countries (LMICs). Limited data is available from LMICs about the predictors of outcome and recurrence of IS in young. The study aims to assess the predictors of short-term and long-term functional outcome and the recurrence of the first-ever IS and transient ischemic attack in young.
Methods:
The clinical, radiological data, functional outcome, and recurrence of 569 IS patients aged 18–50 years were recorded. The etiological classification was done. The functional outcome was assessed using the modified Rankin scale (mRS), with a good outcome being mRS 0–2. Logistic regression was used to analyze the predictors of recurrence and outcome.
Results:
The most common risk factors were hypertension (40.3%) and diabetes mellitus (34.3%). Stroke of undetermined etiology (33.6%) was the most common etiological subtype. Among the cardioembolic subtypes, rheumatic heart disease constituted 47.4%. A good functional outcome at 1 year was seen in 76.3%. While baseline stroke severity predicted both the 3-month and 1-year functional outcome, age ≥40 years and male gender predicted poor outcome at 1 year. The risk of recurrent strokes at 1 year was 2.5%. On multiple logistic regression analysis, diabetes mellitus independently predicted recurrent vascular events at 1 year (odds ratio = 2.43, 95% confidence interval 1.07–5.50).
Conclusions:
We found a good functional outcome with a relatively low recurrence at 1 year among young IS patients. Baseline stroke severity, age, and male gender predicted a poor 1-year functional outcome.
Keywords: Young stroke, ischemic, recurrence, outcome
Introduction
In developing countries, the epidemiologic trends of young ischemic stroke (IS) are quite alarming, with an absolute increase in mortality of 36.7% following a stroke.[1] IS in the young presents specific implications that include diverse predisposing factors, social, physical, emotional, vocational, and economic connotations. In India, 10%–15% of the IS is found in the young, and in Kerala, the proportion is 3.8% under the age of 40 years and 9.5% under the age of 50 years.[2] Traditional risk factors like hypertension, dyslipidemia, smoking, and diabetes mellitus are highly prevalent among young IS patients, which is similar to that reported in elderly stroke patients.[3,4] Cumulative data from various Indian studies indicate that 21%–48% of IS in the young is caused by large vessel atherosclerotic disease, 10%–33% is due to nonatherosclerotic large artery occlusive disease, 13%–35% is caused by cardioembolism, 3%–18% by penetrating artery disease, and 8%–15% by prothrombotic states.[5] Approximately 7%–40% of IS remains cryptogenic.[5] Data of young IS from 12 European countries revealed cryptogenic stroke in 39.6%, cardioembolism in 17.3%, small vessel disease in 12.2%, and large artery disease in 9.3%.[6] Young IS patients are at significant risk of recurrent vascular events. A large Dutch study reported a vascular recurrence rate of 20% during a mean follow-up period of 9 years. Similarly, a cumulative 10-year risk of recurrent vascular events of 36% and recurrent stroke of 19% was demonstrated in a Finnish study.[6] Among Chinese, the rate of young IS recurrence was 7.9%.[7] The recurrences affect the functional status of a patient, such that 15%–20% die and 30%–40% suffer severe handicaps with residual dependent status.[8] The Ontario Stroke Registry observed that following young IS, the hazard ratio at 5 years for incurring another stroke, vascular event, death, or admission to a long-term care facility was 5.2 compared to 1.3 in elderly stroke patients.[9] Studies on recurrence and the outcome following an IS in young are limited by the small sample sizes, and the data is limited from the Indian population. Therefore, we aimed to investigate the predictors of short-term and long-term outcome and recurrence in a defined cohort of young patients with first-ever IS and transient ischemic attack (TIA).
Methods
We retrospectively reviewed the data of the patients aged 18–50 years who had a first-ever IS/TIA, within 4 weeks of stroke onset, and were admitted to the comprehensive stroke care center, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India between January 1, 2011 and December 31, 2020. The study was approved by the institutional ethics committee. The demographic data, risk factor profile, disease severity (National Institutes of Health Stroke Scale [NIHSS]), and the type of revascularization done were recorded. Detailed etiological workup of young IS was done, which included complete blood count with erythrocyte sedimentation rate, prothrombin time, activated partial thromboplastin time, liver and renal function tests, blood glucose, glycated hemoglobin, lipid profile, computed tomography (CT)/magnetic resonance imaging of the head, vascular imaging of the brain (CT angiography [CTA]/magnetic resonance angiography [MRA]), transthoracic echo and/or transesophageal echo, Holter monitoring, lower limb Doppler, antinuclear antibody profile, rheumatoid factor, antiphospholipid antibody, antinuclear cytoplasmic antibody, cryoglobulins, human immunodeficiency virus, hepatitis B and C serology, and serum homocysteine levels. The stroke subtypes were categorized according to the Trial of Org 10172 in Acute Stroke Treatment classification. Imaging findings of stenosis or occlusion of the culprit vessel (specific vessel affected) observed using MRA or CTA were recorded. Recurrent stroke was defined as a new persisting (≥24 h) neurological deficit occurring >24 h after the index event and not attributable to other causes of neurological deterioration. The data about the recurrence of IS were collected through chart reviews. The first onset of stroke was taken as the initial event, and recurrent stroke and mortality as the end point event. A favorable outcome was defined as a modified Rankin scale (mRS) score of 0–2.
Statistical analysis was done using Stata package version 15.1. Demographic, risk factors, and clinical variables of the patients were described using univariate analysis like frequencies, mean, and standard deviation (SD). Ordinal data were assessed by a nonparametric test. Dichotomous and categorical variables were compared with the Chi-square test, whereas continuous variables were compared with the unpaired t-test. Univariate analysis was performed between the demographic, risk factors, clinical variables, and outcome measures according to age groups 18–40 years and 40–50 years. Functional outcomes based on the mRS score were divided into good (0–2) and poor (≥3) outcomes. Analysis was performed to determine the predictors associated with outcome variables and recurrent vascular events. The Chi-square test was used to compare categorical variables across groups. A two-tailed probability value (P value) of <0.05 was considered significant. Furthermore, multiple logistic regression was done to identify the independent predictors of outcome parameters.
Results
A total of 569 IS/TIA patients (379 males and 190 females) were included in the study. The mean age was 40.7 (SD = 7.6) years. The mean time from the onset of symptoms to hospital admission was 5.4 days (SD = 7.9). However, 57.1% of patients reached the hospital within 24 h of the onset of symptoms. In our study, 42.2%, 36.9%, and 20.9% of patients had mild, moderate, and severe strokes, respectively. Anterior circulation strokes were more common than posterior circulation strokes (87.5% vs. 12.5%). While 5.3% of patients received intravenous thrombolysis, 6.3% underwent mechanical thrombectomy. Hypertension (40.3%), diabetes mellitus (34.3%), tobacco smoking (28.6%), alcohol abuse (28.8%), and dyslipidemia (24.6%) were the most common risk factors. The etiological classification revealed strokes of undetermined etiology in 33.6%, other determined etiology in 23.2%, cardioembolism in 20.0%, large artery atherosclerosis in 13.2%, and lacunar stroke in 10.0%. Among the cardioembolic strokes, rheumatic heart disease (RHD) constituted 47.4% [Table 1].
Table 1.
Demographic and clinical profile of the study population
| Variables | n=569 |
|---|---|
| Age (years) | |
| <40 | 197 (34.6) |
| ≥40 | 372 (65.4) |
| Gender | |
| Male | 379 (66.6) |
| Female | 190 (33.4) |
| Risk factors | |
| Hypertension | 229 (40.3) |
| Diabetes mellitus | 195 (34.3) |
| Dyslipidemia | 140 (24.6) |
| Current smoking | 163 (28.6) |
| Alcohol use | 164 (28.8) |
| Valvular heart disease | 62 (10.9) |
| Coronary artery disease | 52 (9.1) |
| Prior history of TIA | 32 (5.6) |
| Connective tissue disorders | 26 (4.6) |
| Migraine | 29 (5.1) |
| Prothrombotic state | 12 (2.1) |
| Atrial fibrillation | |
| • Valvular | 25 (4.4) |
| • Nonvalvular | 14 (2.4) |
| Congestive heart failure | 23 (4.0) |
| Congenital heart disease | 14 (2.5) |
| Chronic kidney disease | 11 (19) |
| Vascular involvement (stenosis/occlusion) | |
| MCA | |
| • M1 segment | 116 (20.4) |
| • M2 segment | 35 (6.2) |
| ICA | |
| • Extracranial | 112 (19.7) |
| • Intracranial | 32 (5.6) |
| Vertebrobasilar territory | |
| • VA | 40 (7.0) |
| • BA | 14 (2.5) |
| • PICA | 15 (2.6) |
| • PCA | 15 (2.6) |
| • ACA | 13 (2.3) |
| Stroke subtypes (TOAST) | |
| Large vessel atherosclerotic disease | 75 (13.2) |
| Lacunar | 57 (10.0) |
| Cardioembolic | 114 (20.0) |
| • RHD | 54 (9.5) |
| • PFO | 18 (3.2) |
| • Severe left ventricular dysfunction | 19 (3.3) |
| • Infective endocarditis | 2 (0.4) |
| • Nonvalvular atrial fibrillation | 14 (2.5) |
| • Others (cardiomyopathies, etc.) | 7 (1.3) |
| Specific etiology | 132 (23.2) |
| • Dissection | 87 (15.3) |
| • Vasculitis | 21 (3.6) |
| • Moyamoya disease | 7(1.2) |
| • Prothrombotic states | 9 (1.6) |
| • Others (CADASIL, APLA, Behcet disease) | 8 (1.4) |
| Undetermined etiology | 191 (33.6) |
| NIHSS | |
| • 1–5 | 240 (42.2) |
| • 6–14 | 210 (36.9) |
| • >15 | 119 (20.9) |
| mRS | |
| At 3 months | |
| • 0–2 | 343 (64.8) |
| • ≥3 | 186 (35.2) |
| At 1 year | |
| • 0–2 | 303 (76.3) |
| • ≥3 | 94 (23.7) |
| Revascularization | |
| Intravenous thrombolysis | 30 (5.3) |
| Mechanical thrombectomy | 36 (6.3) |
| Bridging | 9 (1.6) |
All the variables are presented as number (%). TIA: Transient ischemic attack, MCA: Middle cerebral artery, ICA: Internal carotid artery, VA: Vertebral artery, BA: Basilar artery, PICA: Posterior inferior cerebellar artery, PCA: Posterior cerebral artery, ACA: Anterior cerebral artery, TOAST:Trial of ORG 10172 in Acute Stroke Treatment, RHD: Rheumatic heart disease, PFO: Patient foramen ovale, CADASIL: Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy, APLA: Antiphospholipid antibodies, NIHSS: National institute of health stroke scale, mRS: Modified Rankin Scale
Three-month and 1-year follow-up data were obtained in 529 and 397 patients, respectively. Favorable outcome at 3 months and 1 year was observed in 64.3% and 76.3%, respectively. Bivariate analysis of the functional outcome at 3 months [Table 2] revealed high baseline NIHSS, presence of significant stenosis/occlusion of the symptomatic vessel, middle cerebral artery (MCA)-M1 occlusion, and anterior circulation strokes were associated with poor functional outcome. However, on multivariate analysis [Table 3], the baseline stroke severity alone independently predicted poor outcome at 3 months. Bivariate analysis of functional outcome at 1 year [Table 2] showed statistically significant association with age ≥40 years, smoking, baseline NIHSS, presence of symptomatic vessel disease, MCA-M1 segment involvement, and anterior circulation strokes. Multiple logistic regression [Table 3] revealed age ≥40 years, baseline stroke severity, and male gender independently predicted a poor 1-year outcome. Recurrent strokes/TIAs happened in 1.6% and 2.5% at 3 months and 1 year, respectively [Table 4]. On multiple logistic regression analysis, diabetes mellitus independently predicted recurrent vascular events at 1 year (odds ratio [OR] = 2.43, 95% confidence interval [CI] 1.07–5.50). Mortality data revealed 21 deaths (3.7%) in the study population. Current smoking independently predicted the mortality at 1 year on multivariate analysis (OR = 11.53, 95% CI 1.73–76.86).
Table 2.
Predictors of mRS at 3 months and 1 year
| Variables | Three-month outcome |
Odds ratio (95% CI) | P | One-year outcome |
Odds ratio (95% CI) | P | ||
|---|---|---|---|---|---|---|---|---|
| mRS ≤2 | mRS>2 | mRS ≤2 | mRS >2 | |||||
| Age in years | ||||||||
| <40 | 131 (71.6) | 52 (28.4) | Ref | 191 (68.5) | 88 (31.5) | Ref | ||
| ≥40 | 212 (61.3) | 134 (38.7) | 1.6 (1.1–2.3) | 0.019 | 115 (81.6) | 26 (18.4) | 2.0 (1.2–3.3) | 0.005 |
| Gender | ||||||||
| Male | 228 (64.2) | 127 (35.7) | Ref | 204 (71.3) | 82 (28.7) | Ref | ||
| Female | 115 (66.0) | 59 (33.9) | 0.92 (0.6–1.3) | 0.673 | 102 (76.1) | 32 (23.9) | 0.78 (0.5–1.3) | 0.304 |
| Smoking | ||||||||
| Absent | 237 (67.5) | 114 (32.5) | Ref | 218 (77.3) | 64 (22.7) | Ref | ||
| Present | 104 (59.1) | 72 (40.9) | 1.4 (0.9–2.1) | 0.059 | 88 (63.8) | 50 (36.2) | 1.9 (1.2–3.0) | 0.004 |
| Alcohol | ||||||||
| Absent | 252 (66.5) | 127 (33.5) | Ref | 226 (75.3) | 74 (24.7) | Ref | ||
| Present | 91 (60.7) | 59 (39.3) | 1.3 (0.9–1.9) | 0.21 | 80 (66.7) | 40 (33.3) | 1.5 (0.9–2.4) | 0.072 |
| Hypertension | ||||||||
| Absent | 203 (64.4) | 112 (35.6) | Ref | 179 (72.2) | 69 (27.8) | Ref | ||
| Present | 140 (65.4) | 74 (34.6) | 0.9 (0.7–1.3) | 0.82 | 127 (73.8) | 45 (26.2) | 0.9 (0.6–1.4) | 0.707 |
| Diabetes mellitus | ||||||||
| Absent | 237 (67.7) | 113 (32.3) | Ref | 208 (74.0) | 73 (26.0) | Ref | ||
| Present | 106 (59.2) | 73 (40.8) | 1.4 (0.9–2.1) | 0.059 | 98 (70.5) | 41 (29.5) | 1.1 (0.7–1.9) | 0.446 |
| Coronary artery disease | ||||||||
| Absent | 312 (65) | 168 (35.0) | Ref | 279 (73.2) | 102 (26.8) | Ref | ||
| Present | 31 (63.3) | 18 (36.7) | 1.1 (0.6–1.9) | 0.81 | 27 (73.2) | 12 (27.0) | 1.2 (0.6–2.5) | 0.593 |
| Atrial fibrillation | ||||||||
| Absent | 329 (65.5) | 173 (34.5) | Ref | 298 (74.3) | 103 (25.7) | Ref | ||
| Present | 12 (48.0) | 13 (52.0) | 2.1 (0.9–4.1) | 0.079 | 8 (42.1) | 11 (57.9) | 4.0 (1.6–10.2) | 0.004 |
| Valvular heart disease | ||||||||
| Absent | 309 (66.0) | 159 (33.9) | Ref | 276 (74.4) | 95 (25.6) | Ref | ||
| Present | 34 (55.7) | 27 (44.3) | 1.5 (0.9–2.6) | 0.12 | 30 (61.2) | 19 (38.8) | 1.8 (1.0–3.4) | 0.054 |
| Stroke etiology (TOAST) | ||||||||
| Large-artery atherosclerosis | 33 (47.8) | 36 (52.2) | Ref | 32 (57.1) | 24 (42.8) | Ref | ||
| Cardioembolic | 65 (60.2) | 43 (40.2) | 0.6 (0.3–1.1) | 0.12 | 54 (64.3) | 30 (35.7) | 0.7 (0.4–1.5) | 0.396 |
| Lacunar | 45 (80.4) | 10 (18.1) | 0.2 (0.09–0.5) | <0.001 | 36 (87.8) | 5 (12.2) | 0.2 (0.1–0.5) | 0.002 |
| Specific etiology | 77 (63.6) | 44 (36.7) | 0.5 (0.3–1.0) | 0.039 | 73 (75.3) | 24 (24.7) | 0.4 (0.2–0.9) | 0.021 |
| Undetermined | 123 (70.3) | 52 (29.7) | 0.4 (0.2–0.9) | 0.001 | 111 (78.2) | 31 (21.8) | 0.4 (0.2–0.7) | 0.003 |
| NIHSS | ||||||||
| 0–5 | 214 (93.9) | 14 (6.1) | Ref | 180 (95.7) | 8 (4.3) | Ref | ||
| 6–4 | 98 (50.3) | 97 (49.7) | 15.1 (8.2–27.7) | <0.001 | 90 (63.4) | 52 (36.6) | 13 (5.9–28.5) | <0.001 |
| >15 | 30 (28.6) | 75 (71.4) | 38.0 (19.1–75.6) | <0.001 | 36 (40.0) | 54 (60.0) | 33.8 (14.8–76.9) | <0.001 |
| Anterior circulation | ||||||||
| Absent | 210 (77.8) | 60 (22.2) | Ref | 178 (84.8) | 32 (15.2) | Ref | ||
| Present | 131 (50.9) | 126 (49.0) | 3.4 (2.3–4.9) | <0.001 | 128 (60.9) | 82 (39.4) | 3.6 (2.2–5.7) | <0.001 |
| Posterior circulation | ||||||||
| Absent | 287 (63.2) | 167 (36.8) | Ref | 0.08 | 256 (71.0) | 105 (29.1) | Ref | |
| Present | 54 (73.9) | 19 (26.0) | 0.6 (0.3–1.1) | 50 (84.8) | 9 (15.8) | 0.4 (0.2–0.9) | 0.03 | |
| M1 involvement | ||||||||
| Absent | 289 (68.5) | 133 (31.5) | Ref | 253 (76.2) | 79 (23.8) | Ref | ||
| Present | 52 (49.5) | 53 (50.5) | 2.2 (1.4–3.4) | <0.001 | 53 (60.2) | 35 (39.8) | 2.1 (1.3–3.5) | 0.003 |
| Intravenous thrombolysis | ||||||||
| Not done | 319 (64.0) | 179 (35.9) | Ref | 287 (72.7) | 108 (27.3) | Ref | ||
| Done | 22 (75.9) | 7 (24.1) | 0.6 (0.2–1.4) | 0.2 | 19 (76) | 6 (24.0) | 0.8 (0.3–2.2) | 0.003 |
| Mechanical thrombectomy | ||||||||
| Not done | 321 (65.2) | 171 (34.8) | Ref | 285 (73.1) | 105 (26.9) | Ref | ||
| Done | 20 (57.1) | 15 (42.9) | 1.4 (0.7–2.8) | 0.33 | 21 (70.0) | 9 (30.0) | 1.2 (0.5–2.6) | 0.72 |
All the categorical variables are presented as frequency n (%). mRS: Modified Rankin Scale, TOAST: Trial of ORG 10172 in Acute Stroke Treatment, NIHSS: National Institute of health stroke scale, CI: Confidence interval
Table 3.
Variables associated with outcomes – results of multiple logistic regression analysis
| Variables | Three-month outcome (mRS >2) | One-year outcome (mRS >2) | Recurrence | ||||
|---|---|---|---|---|---|---|---|
|
|
|
|
|||||
| Odds ratio (95% CI) | P | Odds ratio (95% CI) | P | Odds ratio (95% CI) | P | ||
| Age in years | |||||||
| <40 | Ref | Ref | - | - | |||
| ≥40 | 1.22 (0.74–2.01) | 0.434 | 1.75 (0.93–3.28) | 0.077 | |||
| Stroke etiology (TOAST) | |||||||
| Large-artery atherosclerosis | Ref | Ref | |||||
| Cardioembolic | 0.38 (0.17–0.84) | 0.017 | 0.61 (0.23–1.59) | 0.314 | - | - | |
| Lacunar | 0.44 (0.16–1.20) | 0.112 | 0.44 (0.11–1.65) | 0.228 | |||
| Specific etiology | 0.74 (0.34–1.61) | 0.451 | 0.77 (0.31–1.90) | 0.575 | |||
| Undetermined | 0.43 (0.20–0.91) | 0.028 | 0.47 (0.20–1.12) | 0.09 | |||
| NIHSS | |||||||
| 0–5 | Ref | Ref | |||||
| 6–14 | 15.27 (8.11–28.73) | <0.001 | 11.2 (4.97–25.39) | <0.001 | - | - | |
| ≥15 | 35.80 (17.11–74.89) | <0.001 | 28.30 (11.71–68.38) | <0.001 | |||
| Ml involvement | |||||||
| Absent | Ref | Ref | - | - | |||
| Present | 0.99 (0.54–1.84) | 0.998 | 0.99 (0.50–1.98) | 0.995 | |||
| Anterior circulation | |||||||
| Absent | Ref | Ref | |||||
| Present | 1.76 (1.01–3.05) | 0.046 | 1.50 (0.70–3.21) | 0.292 | - | - | |
| Posterior circulation | |||||||
| Absent | - | - | Ref | - | - | ||
| Present | 0.86 (0.32–2.30) | 0.767 | |||||
| Smoking | |||||||
| Absent | - | - | Ref | 0.274 | - | - | |
| Present | 1.77 (1.00–3.15) | ||||||
| Atrial fibrillation | |||||||
| Absent | - | Ref | - | - | |||
| Present | - | 1.91 (0.59–6.13) | 0.274 | ||||
| Diabetes mellitus | |||||||
| Absent | - | - | - | - | Ref | ||
| Present | 3.3 (1.4–7.4) | 0.005 | |||||
| Valvular heart disease | |||||||
| Absent | - | - | - | - | Ref | ||
| Present | 6.82 (2.58–18.0) | <0.001 | |||||
| Coronary artery disease | |||||||
| Absent | - | - | - | - | Ref | ||
| Present | 3.18 (1.14–8.86) | 0.027 | |||||
The odds ratios and confidence intervals are provided for the variables included in each model. mRS: Modified Rankin Scale, TOAST: Trial of ORG 10172 in Acute Stroke Treatment, NIHSS: National Institute of health stroke scale, CI: Confidence interval
Table 4.
Predictors of recurrent stroke on bivariate analysis
| Variables | Recurrence |
Odds ratio (95% CI) | P | |
|---|---|---|---|---|
| No | Yes | |||
| Age in years | ||||
| <40 | 190 (96.5) | 7 (3.6) | Ref | |
| ≥40 | 351 (94.4) | 21 (5.7) | 1.6 (0.7–3.9) | 0.277 |
| Gender | ||||
| Male | 362 (95.5) | 17 (4.5) | Ref | |
| Female | 179 (94.2) | 11 (5.8) | 1.3 (0.6-2.85) | 0.499 |
| Hypertension | ||||
| Absent | 324 (95.3) | 16 (4.7) | Ref | |
| Present | 217 (94.8) | 12 (5.2) | 1.1 (0.6–2.4) | 0.773 |
| Diabetes mellitus | ||||
| Absent | 362 (96.8) | 12 (3.2) | Ref | |
| Present | 179 (91.8) | 16 (8.2) | 2.6 (1.2–5.8) | 0.012 |
| Valvular heart disease | ||||
| Absent | 487 (96.1) | 20 (3.9) | Ref | |
| Present | 54 (87.1) | 8 (12.9) | 4.1 (1.7–9.9) | 0.027 |
| Coronary artery disease | ||||
| Absent | 495 (95.7) | 22 (4.3) | Ref | |
| Present | 46 (88.5) | 6 (11.5) | 2.9 (1.1–7.6) | 0.004 |
| Stroke etiology (TOAST) | ||||
| Large-artery atherosclerosis | 70 (93.3) | 5 (6.7) | Ref | |
| Cardioembolic | 104 (92.0) | 9 (8.0) | 1.2 (0.4–3.8) | 0.740 |
| Lacunar | 55 (96.5) | 2 (3.5) | 0.51 (0.1–2.7) | 0.430 |
| Specific etiology | 126 (95.5) | 6 (4.6) | 0.7 (0.2–2.3) | 0.516 |
| Undetermined | 185 (96.9) | 6 (3.1) | 0.5 (0.1–1.5) | 0.204 |
| NIHSS | ||||
| 0-5 | 228 (95.0) | 12 (5.0) | Ref | |
| 6-14 | 200 (95.2) | 10 (4.8) | 0.9 (0.4–2.2) | 0.907 |
| >15 | 113 (94.9) | 6 (5.0) | 1.0 (0.4–2.8) | 0.986 |
All the categorical variables are presented as frequency n (%). TOAST: Trial of ORG 10172 in Acute Stroke Treatment, NIHSS: National Institute of health stroke scale, CI: Confidence interval
Discussion
This study evaluated the predictors of functional outcome and recurrence of IS/TIA in 569 young adults. The functional outcome was favorable in 76.3% of patients at 1 year with 3.7% mortality. Recurrent strokes/TIAs happened in 1.6% and 2.5% at 3 months and 1 year, respectively. Age ≥40 years, high baseline stroke severity, and male gender independently predicted an unfavorable 1-year outcome. Diabetes mellitus independently predicted recurrent vascular events at 1 year.
Hypertension (40.3%), diabetes mellitus (34.3%), tobacco smoking (28.6%), alcohol use (28.8%), and dyslipidemia (24.6%) were the most common risk factors in young IS patients. The data from the stroke in young Fabry patients study showed that the most important individual risk factor for IS was high blood pressure, with a population attributable risk (PAR) of 25.5% and the odds for young IS was 2.3.[10] The Global Burden Study showed that Southeast Asia (54.8%) has the highest PAR for hypertension compared to Eastern and Central Europe and the Middle East (40.7%), suggesting a higher probability of young IS in the Southeast Asian population.[11] Approximately 10% of young IS patients have diabetes mellitus.[12] Diabetes is associated with a higher risk of stroke in young with an odds of 1.9.[10] India, China, and the USA are the top three countries with the highest prevalence of diabetes,[13] and the PAR was highest in Southeast Asia (28.6%) and lowest in Australia, Western Europe, and North America (3.5%).[11] Dyslipidemia is found in about 50%–60% of young stroke patients,[7,12] and it is more often found in patients with large artery atherosclerotic disease or small vessel disease.[14] Smoking is an important risk factor in young adults with an odds of 1.78.[10] A strong dose–response relationship between tobacco smoking and the risk of IS was found in both sexes at a young age compared to older adults,[15] with the highest prevalence reported in Europe (28.7%) and in Southeast Asia (24.8%) and the lowest prevalence in Africa (13.9%).[16] Heavy episodic alcohol consumption is associated with an increased risk of stroke in young adults with an odds of 2.2 in European countries.[10] Even at a young age, the conventional risk factors contribute to IS both in high- and low-income countries, but these risk factors appear to be more prevalent in the developing countries of Southeast Asia, adding on to the burden of cerebrovascular events in these countries.
In our study, 33.6% of the patients had cryptogenic stroke. Various epidemiologic studies have consistently reported that cryptogenic stroke accounts for about 25%–40% of all IS in young. There exists variation in the prevalence of stroke subtypes based on the demographics of the study population, diagnostic definitions, extent of diagnostic evaluation, and methodology. Special emphasis needs to be given to the high prevalence of RHD in the Indian population. Approximately 97% of all RHD occurs in developing countries, with low socioeconomic conditions and poverty.[17] In India, about 44,000 new patients are added every year, and these figures remain underestimated as no data are available from the highly populous and underdeveloped states of India.[18] Around 3%–7.5% of all IS in low- and middle-income countries (LMICs) are related to RHD, with 108,000–269,000 deaths and 1.6 million stroke survivors reported each year.[17] Approximately 29% of cardioembolic stroke in India is related to RHD.[19] The estimated prevalence of RHD in young IS in Northern America and Europe is 1.8%–2.0%, but it is 3.4%–23.2% in Asian countries.[17] These data highlight the importance of RHD as a major cause of IS in developing countries and warrant attention to plan preventive strategies. However, the association between IS and RHD has not been given sufficient importance in the last few decades since most research on stroke takes place in high-income countries where RHD is becoming infrequent.
In our series, a favorable outcome at 3 months and 1 year was observed in 64.3% and 76.3%, respectively, which means that three-fourths of the young IS survivors were able to carry out all their previous activities without assistance at 1 year. Data on the functional outcomes of young IS patients are generally discordant. Leys et al.[20] reported that 87% of young IS patients were independent, which is consistent with our data. Conversely, a worse outcome with only 10.8% having an mRS 0–1 and only 16% becoming independent with an mRS 0–2 was reported in a young Israeli population.[21] Ethnicity might play a role in the functional outcome in different populations. In our study, when a high baseline stroke score predicted a poor outcome at both 3 months and 1 year, age ≥40 years and male gender predicted unfavorable outcomes at 1 year. An Indo–US stroke project across five high-volume tertiary hospitals in India observed that low NIHSS and small artery etiology predicted excellent 3-month outcome.[22] Stroke severity, measured by NIHSS, was not consistently associated with the health-related quality of life (HRQoL), but several prospective studies have confirmed NIHSS score as the independent predictor of HRQoL.[23] Besides, young individuals require and expect to achieve a higher level of functioning because of their parenting and challenging work or family responsibilities. Poststroke fatigue, depression, and anxiety have proved the highest relevance as independent factors contributing to low HRQoL at a young age[24] and correlated with the domains of HRQoL stronger than functional outcomes.[24] In a study conducted by Bonner et al.[25] among Indians, it was found that about half of young patients with mild to moderate poststroke disability do not return to work and this is determined by their functional disability and the type of job. More longitudinal studies are needed to identify the trajectory of potential predictors of unfavorable long-term HRQoL, so that specific young stroke rehabilitation and stroke self-management support programs could be developed.
Several studies from the West have addressed the factors associated with stroke recurrence, but similar data is relatively scarce from Southeast Asian population. In our study, recurrent strokes/TIAs happened in 1.6% and 2.5% at 3 months and 1 year, respectively. In the Western population, the risk of recurrent stroke ranged from 14% to 19%.[26] Among the young Chinese, the recurrence varied from 6.7% to 7.9%.[9] The low recurrence rate in our population may be related to multiple factors, which include increased awareness among young individuals about the need for risk factor control, high literacy rate and good living conditions compared to the rest of India, better support from family and caregivers, and the availability of noncommunicable disease clinics at the primary health center level for the continuum of poststroke care. In our study, diabetes mellitus was the single independent predictor of recurrent vascular events at 1 year. Diabetes mellitus and peripheral artery disease were observed as significant risk factors among the European population as well.[27] Based on the population type and study methodology, the risk factors for recurrence differed, which include cardioembolism, age, diabetes mellitus, anti-phospholipid antibody syndrome, and irregular ingestion of antiplatelet medication.[27] Recurrent strokes in young lead to the accumulation of disabilities, resulting in significant limitations in vital and functional status, such that approximately 15%–20% of patients die, 30%–40% suffer severe handicaps with residual dependent status, and more than 50% remain permanently disabled.[8] These emphasize the importance of proper secondary prevention strategies to avoid stroke recurrence. Overall, the predictive factors for stroke recurrence in most of the studies were age over 35 years (Risk ratio (RR): 1.7), the presence of cardiovascular risk factors, especially diabetes mellitus (RR: 2.5), prior TIA (RR: 1.5), and carotid atherosclerotic disease (RR: 1.7).[8,28]
In the present study, 3.6% of patients died at 1-year follow-up and about 95% of all mortality occurred during the first 92 days following the stroke, highlighting the fact that the highest case fatality occurs during the initial 3 months following a stroke. A mortality rate of 7.3% was reported from one of the tertiary referral centers of Karnataka state, India.[29] Among Taiwanese, the mortality was 4.2%.[30] Their mortality rates increased at an average of 1.9% annually, which is significantly higher than in any Western population.[8,20,26] The first-year IS mortality rates in young adults, in the Western populations, varied from 4.5% to 6.3%, with the average mortality rates varying between 0.6% and 1.8% during subsequent years. These data suggest that the overall mortality of young IS patients is higher among Southeast Asians and did not decrease as much over subsequent years under long-term follow-up compared to the Western population. Although stroke-related mortality has been decreasing in India and East Asian countries, ethnicity might play a pertinent role in determining a patient’s long-term survival after a stroke event.
All the patients were extensively evaluated, and hence, the etiologic subtypes are very reliable. Though retrospective, the 3-month follow-up data of 64% having good functional outcomes is very representative of the stroke outcome in young. The limitations include that the data in our study are mostly derived retrospectively and the study had a relatively small sample size.
Conclusions
Although the risk associated with recurrence and mortality is low in our population, first-ever IS in young has important prognostic implications. Since most strokes occur in young adults in LMICs around the world, it is important to surmount the burden of this disease. Risk factor control and rehabilitation after stroke needs to be targeted in young adults to reduce the burden of the disease.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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