Stroke subtypes
After excluding patients with duplicate registration, there were 8155 consecutive patients; 1310 patients (17.6%) were ≤ 55 years old and 6845 patients were > 55 years old. The mean age for the early-onset group was 45.9 ± 8.3 years, and there were significantly more males than females (male/female ratio 1.9:1). The early-onset patients had a higher percentage of hemorrhagic stroke (50.8%) than ischemic stroke (49.2%, Figure 2A). Of hemorrhagic stroke, hypertensive ICH, SAH and undetermined ICH represented 85.0% of the patients (36.2%, 30.2% and 18.8%, respectively) (Figure 2B). Regarding ICH, the top causes were hypertensive ICH (51.8%), undetermined (26.9%), and structural angiopathy (15.9%). Specifically, most of the structural angiopathy was arteriovenous malformation (59.5%), followed by cavernoma (23.0%) and aneurysm (8.1%). Regarding infarction, large artery atherosclerosis as well as other determined and undetermined etiologies were the top 3 subtypes, accounting for 32.6%, 21.7% and 20.2% of all ischemic infarctions, respectively (Figure 2C). Among the other determined etiologies, arterial dissection (n = 73, 52.1%, table 1), Moyamoya disease (7.1%), cerebral venous thrombosis (7.1%) and anti-phospholipid syndrome (5.7%) were the most common causes (Table 1). Importantly, 9 patients (6.4%) had a monogenic cause (Table 1).
Risk factors
Figure 3A lists the differences in risk factor frequencies between the early-onset and late-onset stroke patients. For infarction, hypertension was the leading risk factor in both early-onset and late-onset patients (52.5% and 77.2%, respectively) and was more frequent in the late-onset patients (χ² = 181.6, p < 0.001). Diabetes, ischemic heart diseases and atrial fibrillation were also more common in the late-onset patients (diabetes, late-onset 36.8% vs early-onset 27.8%, χ² = 20.2, p < 0.001; ischemic heart diseases, late-onset 16.8% vs early-onset 6.7%, χ² = 44.4, p < 0.001; atrial fibrillation, late-onset 20.4% vs early-onset 3.4%, χ² = 109.5, p < 0.001). In contrast, 41.8% of the early-onset patients with infarction were smokers, 27.6% were alcoholics, 11.3% were obese, and 9.6% had a positive family history of stroke, which were significantly higher than the ratios in the late-onset patients (22.0%, χ² = 120.6, p < 0.001; 14.9%, χ² = 68.5, p < 0.001; 5.0%, χ² = 20.8, p < 0.001; 3.7%, χ² = 46.3, p < 0.001; respectively).
Regarding ICH, hypertension was also the most common risk factor in both the early- and late-onset patients, with a higher frequency in the late-onset patients (72.7% vs 55.3%, χ² = 46.4, p < 0.001). Similarly, a higher proportion of the late-onset patients had diabetes (23.2% vs 11.6%, χ² = 29.7, p < 0.001), ischemic heart diseases (11.9% vs 3.4%, χ² = 27.2, p < 0.001) and atrial fibrillation (8.7% vs 1.1%, χ² = 31.7, p < 0.001). Nevertheless, more early-onset patients were smokers (39.4% vs 24.8%, χ² = 35.5, p < 0.001), alcoholics (35.3% vs 21.5%, χ² = 31.9, p < 0.001), obese (14.2% vs 4.7%, χ² = 41.7, p < 0.001), and had a family history of stroke (4.5% vs 2.5%, χ² = 5.3, p < 0.05).
Family history of stroke
Comparing early-onset patients with and without a family history of stroke (n=87 versus 1223, Table 2), we noted that familial stroke patients were more commonly male. Infarction was significantly more common in patients with familial stroke, whereas SAH was significantly more common in patients without familial stroke. The subtypes of infarction and ICH, however, did not differ between groups. However, monogenic causes of infarction were significantly more prevalent in familial stroke. The stroke risk factors, including hypertension, diabetes, obesity, alcohol overconsumption and smoking, also made up similar proportions between groups. Among familial stroke patients, a greater percentage had hypercholesterolemia and ischemic heart disease. The 1-year stroke recurrence rate was significantly higher in familial stroke than in non-familial stroke patients, whereas the 1-year outcomes in mRS were lower in familial stroke.
Outcomes
A total of 7590 (93.1%) patients completed the 1-year follow-up. In the young patients (n = 1280), 76.8% of patients with infarction had favorable outcomes (mRS = 0 – 2) at 1 year after stroke, whereas only 52.7% of patients with ICH had favorable outcomes (p < 0.001). In the old patients (n = 5988), the proportions of patients with favorable outcomes at 1 year were lower for both infarction and ICH, but patients with infarction remained more likely to have favorable outcomes (48.5% vs 29.7%, p < 0.001). Two-way ANOVA revealed a significant main effect of age (F = 113.6, p < 0.001) on the 1-year changes of mRS, and there was no interaction between stroke type and age (F = 1.7, p = 0.20). Regardless of hemorrhagic versus ischemic stroke type, young patients still showed greater improvement in mRS score (-1.0 ± 0.05 vs -0.5 ± 0.03, Figure 3C). The one-year mortality rate was higher after ICH than after infarction for both the young and the old patients (young: ICH 18.0% vs infarction 7.1%, χ² = 29.0, p < 0.001; old: ICH 31.5% vs infarction 16.7%, χ² = 113.2, p < 0.001). The predictors for favorable outcomes in the young patients were the absence of diabetes (p = 0.003), absence of a previous history of stroke or TIA (p = 0.007), and lower mRS scores at 3 months after stroke (p < 0.001).
In early-onset stroke patients, logistic regression found that after adjustments for covariates (age, NIHSS score at admission and counts of documented vascular risk factors), infarction type (p = 0.005) but not hemorrhagic type predicted stroke recurrence. Among the young patients, the stroke recurrence rate at 1 year was higher after infarction (3.6%) than after ICH (0.5%, χ² = 11.0, p = 0.001). Of the 24 young patients with recurrent stroke within 1 year, 21 had infarction, 2 had ICH and 1 had SAH as the first stroke. Of the 21 patients with an initial infarction, 18 (85.7%) had recurrent ischemic infarction, and 3 (14.3%) had unknown subtypes of stroke. Of the 2 patients with an initial ICH, 1 had recurrent ICH, and the other had recurrent infarction. The patient with SAH had recurrent SAH as well.