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Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study

BMC Geriatrics volume 24, Article number: 884 (2024) Cite this article

Abstract

Background

The exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi’an Stroke Registry Study in China.

Methods

The age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55–64 years, age 65–74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE.

Results

This study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age.

Conclusions

Age significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

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Background

The latest Chinese Stroke Burden study revealed that ischemic stroke comprised 86.8% of all stroke types in patients aged > 40 years [1], marking a pivotal focus in stroke public health. Ischemic cerebrovascular disease encompasses various types, including disabling (disability) and non-disabling (non-disability) forms, which are determined by the severity and clinical consequences of stroke onset [2]. Previous studies predominantly concentrated on disabling ischemic cerebrovascular events, which often occur in the acute phase and require immediate and intensive medical interventions to prevent further neurological damage [3, 4]. Although these treatments have notably decreased disability and mortality rates among stroke patients, a substantial portion continues to experience disability due to non-regenerative neurons and limited recovery.

In recent years, Chinese scholars introduced a novel concept non-disabling ischemic cerebrovascular event (NICE) based on the definition of transient ischemic attack (TIA) released by the American Stroke Association (ASA) in 2009 and the previous definition of minor stroke [5, 6]. NICE refers to ischemic cerebrovascular diseases without neurological disability and includes three primary categories: (1) TIA, (2) minor ischemic stroke, and (3) rapid resolution of symptoms without disability [2, 7]. This concept differs from previous definitions of minor ischemic stroke, which are typically characterized by any of the following: ① a National Institutes of Health Stroke Scale (NIHSS) score ≤ 3; ② NIHSS score ≤ 5; or ③ a modified Rankin Scale (mRS) score ≤ 3. With rapid economic development and lifestyle changes, China has witnessed significant shifts in the age structure, life expectancy, mortality rates, disease prevalence, and prognostic outcomes of stroke populations in China have undergone and continue to undergo fundamental changes. This makes it necessary to reevaluate the management approaches for different types of stroke [8].

Previous studies have shown that stroke treatment and prevention strategies have historically focused on disabling ischemic stroke, with a primary goal of minimizing disability and mortality. These strategies often involve acute interventions like thrombolysis and mechanical thrombectomy, which may not be applicable or necessary in NICE cases due to the absence of significant disability. On the other hand, prevention strategies for disabling stroke tend to emphasize aggressive risk factor management, including intensive blood pressure control, lipid management, and anticoagulation in atrial fibrillation [9]. However, in NICE, particularly among different age groups, these approaches may require modification to balance the risk of adverse effects with the potential benefits [10].

Age significantly impacts stroke treatment and prevention strategies. In younger patients (≤ 54 years), aggressive management of modifiable risk factors, such as hypertension and dyslipidemia, is emphasized alongside lifestyle modifications like smoking cessation and increased physical activity [11]. Intensive statin therapy is common to prevent atherosclerosis [12]. For older patients (≥ 75 years), treatment focuses on balancing stroke prevention with the risk of adverse drug reactions, especially in those with comorbidities [13]. Anticoagulants are used cautiously to avoid hemorrhagic complications, and medication doses may be adjusted to account for declining renal function [14]. Prevention in older adults also involves managing multiple risk factors and preventing falls, which could lead to secondary complications [3]. Ever, given the distinct age composition and clinical features of NICE compared to other stroke types, direct adoption of previous stroke prevention and treatment protocols is impractical. Hence, there is a critical need to explore tailored prevention and treatment strategies based on the diverse age groups affected by NICE. According to a literature review, to date, no studies have investigated the differences in clinical characteristics and prognostic outcome events of NICE among patients of varying ages. In this study, we used data from the Xi ‘an Stroke Registry Study to explore the differences in clinical characteristics and 1-year outcomes among different age groups, aiming to provide theoretical guidance for tailored health management and prevention strategies for NICE across different age groups.

Materials and methods

Study population

A total of 3117 patients with stroke admitted to four third-grade A hospitals ( Xi’an No.1 Hospital, Xi’an Central Hospital, Ninth Hospital of Xi’an, and Xi’an Traditional Chinese Medicine Hospital) in the Xi’an area from January to December 2015 were continuously collected through the Xi’an Stroke Registry Study Platform designed as a prospective cohort study. This study aims to investigate the differences in clinical characteristics and 1-year prognostic outcomes of NICE across different age brackets. All NICE patients in this study were diagnosed within 24 h of hospital admission and underwent a one-year follow-up. Patients with non-disabling ischemic cerebrovascular disease were selected based on the following criteria: Inclusion criteria: (1) Patients clinically diagnosed with acute ischemic stroke (AIS) meeting the World Health Organization’s diagnostic criteria and confirmed by head computed tomography (CT) or magnetic resonance imaging (MRI) [11]; (2) Age ≥ 18 years; (3) Patients with a NIHSS score ≤ 3 or experiencing TIA; (4) Time from onset to inclusion ≤ 7 days; (5) Patients who consented to participate in this study and provided signed informed consent. The exclusion criteria were as follows: (1) Non-AIS cases (including cerebral hemorrhage and subarachnoid hemorrhage) and non-cerebrovascular diseases such as brain tumor, subdural hemorrhage, or brain trauma. (2) Patients who declined participation in the study or were lost to follow-up. Ultimately, 1121 patients with NICE were analyzed after excluding 1776 patients with NIHSS score on admission > 3 score, 89 patients with non-AIS, and 131 patients lost to follow-up within 1 year. The detailed screening process for the study population is illustrated in Fig. 1. All participating hospitals adhered to the same diagnostic criteria. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Academic Committee and Ethics Committee of Xi’an No.1 Hospital (Approval No. 2014 [5]). Written informed consent was obtained from all participating patients.

Fig. 1
figure 1

Flow chart depicting the screening and enrollment of study participants. NIHSS, national institutes of health stroke scale; G1-4, Four age groups, group 1–4

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Data collection

Baseline clinical data of patients were meticulously collected through the Xi’an Stroke Registry Study. The data included demographic characteristics (age, gender and education level); medical insurance type (Including Urban employees’ medical insurance: covers urban employees, representing a middle or higher socioeconomic level, with better medical coverage. New type rural cooperative medical system: covers rural residents, representing a lower socioeconomic level, with lower reimbursement rates and greater financial burden. Commercial insurance: a high-end medical insurance held by a small group, representing a higher socioeconomic level. Out-of-pocket medical: for those without insurance, requiring personal payment, typically representing individuals with poorer socioeconomic conditions.), vascular risk factors (smoking, alcohol consumption, peripheral vascular disease, previous stroke, dyslipidemia, hypertension, diabetes mellitus, atrial fibrillation, pneumonia during hospitalization, heart rate, body mass index (BMI), NIHSS score on admission); blood pressure on admission including systolic blood pressure (SBP), diastolic blood pressure (DBP); laboratory test indicators within 24 h of admission including total cholesterol (TC), triglycerides(TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase(ALP), homocysteine, serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA), white blood cell(WBC) counts, and platelet (PLT) counts. Dyslipidemia was diagnosed if any of the following indicators were abnormal: TC ≥ 5.18 mmol/L, TG ≥ 1.70 mmol/L, LDL-C ≥ 3.37 mmol/L, HDL-C < 1.04 mmol/L [15]. Hypertension and diabetes mellitus were defined according to relevant definitions and guidelines [16, 17]. The eGFR was estimated using the collaborative equation of chronic kidney disease epidemiology [18]. Smoking was defined as smoking at least 1 cigarette per day before stroke onset, continuously or cumulatively, for more than 6 months; smoking cessation was defined as meeting the smoking definition but abstaining from smoking for 6 months. Alcohol consumption was defined as approximately 50 mL per week before stroke onset. Patients who met one of the following criteria were diagnosed with atrial fibrillation: (1) previously diagnosed with atrial fibrillation with at least one electrocardiogram (ECG) confirming atrial fibrillation rhythm or initiated relevant medication; or (2) follow-up ECG during the first ECG or hospitalization showing atrial fibrillation and confirming the diagnosis. Definitions and criteria for other associated risk factors were consistent with those of the Chinese National Stroke Registry (CNSR) Study [19].

Four age groups

The age range of patients with NICE was 23–96 years. Based on the age distribution of patients included in the study, they were divided into four groups with a 10-year age interval, centered at 55, 65, and 75 years. The age ranges for each group were as follows: Group1 (G1) < 55 years, n = 250; Group2 (G2) 55–64 years, n = 336; Group3 (G3) 65–74 years, n = 288; Group4 (G4), ≥ 75 years, n = 247.

Outcome assessment and follow-up information

The outcome events in this study included all-cause mortality, recurrent stroke, and poor prognosis at 1-year follow-up. All-cause mortality referred to the total number of deaths from all causes after hospitalization until the end of the follow-up period. Recurrent stroke was defined as rehospitalization due to a new stroke event during the 1-year follow-up period, including ischemic stroke, subarachnoid hemorrhage, or intracranial hemorrhage. A poor prognosis was indicated by a modified Rankin Scale (mRS) score of 3–6 (including death). Patients underwent follow-ups at 1, 3, 6 months, and 1 year from the time of stroke diagnosis, with a margin of error of no more than seven days. Death, stroke recurrence, and poor prognosis of the patients were monitored within 1 year. Patients able to visit the hospital were interviewed face-to-face at one month and three months, while those unable to visit were followed up by telephone at six months and one year. Patients who refused to continue participating in the study during follow-up or those unreachable by phone after five attempts per day for five working days were deemed lost to follow-up.

Statistical analysis

Continuous variables with a normal distribution are presented as mean ± Standard deviation, while those without normal distribution are expressed as median (P25-P75). Categorical variables are shown as frequencies (N%). The t-test was used for comparisons between two groups with normal distribution and homogeneity of variances, and one-way analysis of variance (ANOVA) for comparisons between multiple groups. The Kruskal-Wallis rank-sum test was utilized for groups lacking normal distribution and homogeneity of variance simultaneously. The χ2 test was used to compare the rates of each group of categorical variables, with the Fisher exact probability method employed when the theoretical frequency was less than 10. The Kaplan-Meier (K-M) method and log-rank test were used to analyze the 1-year cumulative recurrent stroke and survival. A transverse bar chart depicted the percentage distribution of mRS scores in the 1-year poor prognosis group. A time-dependent Cox proportional hazards regression model was used to analyze the association between age, 1-year recurrent stroke, and all-cause mortality in patients with NICE. Multivariate logistic regression was used to analyze the relationship between age and poor prognosis. Adjusted variables were screened based on clinical significance and whether the variable had a greater than 10% effect value hazard ratio (HR)/odds ratio (OR) on age and 1-year outcome events. All data analyses were performed using Free Statistical Analysis software (version 1.7) (Beijing FreeClinical Medical Technology, Inc., Beijing, China) and R software (version 4.2.1) (R Foundation, http://www.R-project.org). Statistical significance was set at a two-sided P-value < 0.05.

Results

Comparison of clinical characteristics across four age groups

A total of 1121 eligible subjects (697 men and 424 women) were enrolled in the study after screening for the inclusion and exclusion criteria. The mean age of all subjects was 63.7 ± 12.2 years, and the mean age of the four groups (G1-G4) was 46.7 ± 6.3 years for G1, 59.8 ± 2.9 years for G2, 69.6 ± 3.0 years for G3, and 79.4 ± 3.9 years for G4, respectively. Demographic characteristics, vascular risk factors, blood pressure at admission, and laboratory test indicators were compared among the four age groups of patients with NICE (Table 1). The findings revealed that, compared with G1, patients in G3 or G4 had a higher proportion of women, urban employees’ medical insurance, elementary or lower education levels, history of never smoking and smoking cessation, peripheral vascular disease, previous stroke, hypertension, atrial fibrillation, pneumonia during hospitalization, and a higher NIHSS score on admission. Additionally, patients in G3 and G4 had a lower proportion of out-of-pocket medical payments and alcohol consumption, lower BMI, lower DBP, and a higher proportion of SBP. Furthermore, patients in G3 or G4 had higher levels of HDL-C and serum creatinine, along with TC, TG, LDL-C, ALT, eGFR, BUN, WBC count, and PLT count. No statistically significant differences were observed in dyslipidemia, diabetes mellitus, heart rate, FBG, AST, ALP, homocysteine, or UA levels among the four age groups.

Table 1 Baseline and biochemical characteristics by four age groups in patients with NICE
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Rates of 3-month and 1-year follow-up outcome events across four age groups

The rate of outcome events in patients with NICE across the four age groups was compared at 3 months and 1 year of follow-up, respectively. Results indicated that at the 3-month follow-up, the rates of recurrent stroke, all-cause mortality, and poor prognosis were 1.1% (12/1121), 1.2% (14/1121), and 6.9% (77/1121), respectively. The proportion of all-cause mortality in groups G1 and G4 was significantly higher than that in groups G2 and G3 (G2:0.3% and G3:0.7% vs. G1:1.6% and G4:2.8%), with statistical significance (P = 0.041). Furthermore, compared with G1-G3, the rate of poor prognosis was significantly higher in G4 at the 3-month follow-up (G4, 17.8% vs. G1, 2.8%; G2, 3%; G3, 5.6%), with a statistically significant difference (P < 0.001). There was no significant difference in recurrent stroke among G1-G4 at the 3-month follow-up (P = 0.840). At the 1-year follow-up, the rate of recurrent stroke, all-cause mortality, and poor prognosis were 3.4% (38/1121), 3.3% (37/1121), and 9.3% (104/1121), respectively. Compared with other age groups, the rates of recurrent stroke (6.1%), all-cause mortality (7.7%), and poor prognosis (23.5%) in G4 were significantly increased at the 1-year follow-up, with statistical significance (P < 0.001) (Table 2).

Table 2 The rates of 3-month and 1-year follow-up outcome events in four age groups
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Multivariable regression analysis of 3-month and 1-year follow-up outcome events in patients with NICE

Age was examined both as a continuous and categorical variable (G1-G4) to assess the risk of outcome events in patients with NICE at the 3-month and 1-year follow-ups.

3-month follow-up: Regardless of adjustment for potential confounding factors, Cox regression analysis revealed a significant increase in the risk of poor prognosis with advancing age (Crude: HR = 1.08, 95%CI: 1.06 ~ 1.11, P < 0.001; adjusted: HR = 1.08, 95%CI: 1.05 ~ 1.11, P < 0.001). However, there was no statistically significant increase in the risk of recurrent stroke (adjusted HR = 1.04, 95%CI: 0.98 ~ 1.11, P = 0.163) or all-cause mortality (adjusted HR = 1.03, 95%CI: 0.97 ~ 1.08, P = 0.331). When age was treated as a categorical variable (G1-G4), there was no significant increase in the risk of recurrent stroke and all-cause mortality in G2, G3, and G4 compared with G1. Only G4 showed a significantly increased risk of poor prognosis at 3 months (OR = 6.43, 95%CI: 2.57 ~ 16.04, P < 0.001).

1-year follow-up: Following adjustment for potential confounders, Cox regression analysis demonstrated significant increases in the 1-year risk of recurrent stroke (adjusted HR = 1.05, 95%CI: 1.01 ~ 1.09, P = 0.006), all-cause mortality (adjusted HR = 1.07, 95%CI: 1.03 ~ 1.11, P = 0.001), and poor prognosis (adjusted OR = 1.09, 95%CI: 1.06 ~ 1.11, P < 0.001). Notably, in the four age groups, there was a significant increase in all-cause mortality (adjusted HR = 4.05, 95%CI: 1.24 ~ 13.23, P = 0.021) and poor prognosis (adjusted OR = 8.08, 95%CI: 3.51 ~ 18.61, P < 0.001) in G4 compared with G1, while no statistically significant increase in the risk of recurrent stroke was observed in the G4 (Table 3).

Table 3 Multivariable regression analysis of 3-month and 1-year follow-up outcomes in patients with NICE
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Trend tests revealed a significant difference only in the increased risk of poor prognosis from G1 to G4 at the 3-month follow-up. At the 1-year follow-up, the increased risks of recurrent stroke, all-cause mortality, and poor prognosis were statistically significant. Kaplan-Meier curve analysis indicated no significant differences in the cumulative rates of recurrent stroke and all-cause mortality among the groups at the 3-month follow-up (Fig. 2A and C), but significant differences were observed at the 1-year follow-up (Fig. 2B and D). Additionally, according to the distribution of mRS scores during follow-up, the rates of poor prognosis in group G4 at 3 months (Fig. 2E) and 1 year (Fig. 2F) were significantly higher than those in the other groups. Stratification by gender revealed that after adjustment for potential confounders, male patients aged ≥75 years old had a significantly increased 1-year risk of recurrent stroke (HR = 6.01, 95%CI: 1.20-30.19, P = 0.029) and all-cause mortality (HR = 6.36,95%CI: 1.27–30.82, P = 0.024) compared with those aged < 55. However, no statistically significant difference in recurrent stroke or all-cause mortality was observed among women of different ages (Supplementary Table 1).

Fig. 2
figure 2

Kaplan-Meier (K-M) analysis illustrating recurrent stroke and all-cause mortality, along with the distribution of modified Rankin Scale (mRS) scores indicating poor prognosis in patients with NICE across four age groups at 3-months and 1-year follow-up, respectively. (A) K-M curve of recurrent stroke at 3 months; (B) K-M curve of recurrent stroke at 1 year; (C) K-M survival curve of all-cause mortality at 3 months; (D) K-M survival curve of all-cause mortality at 1 year; (E) Distribution of mRS scores for poor prognosis at 3 months; (F) Distribution of mRS scores for poor prognosis at 1 year. The four age groups: G1 ≤ 54 years; G2 55–64 years; G3 65–74 years; G4 ≥ 75 years

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Subgroup analysis

To evaluate whether alcohol consumption and comorbidities had an age-related effect on 1-year outcome events in patients with NICE, subgroup analyses were conducted (Table 4). Results indicated that irrespective of alcohol consumption, the risk of 1-year all-cause mortality, recurrent stroke, and poor prognosis in patients with NICE significantly increased with age. Interaction analysis revealed that patients who consumed alcohol had a significantly higher 1-year risk of all-cause mortality (P = 0.015) and a poorer prognosis (P = 0.014) than those who did not. Regardless of hypertension status, the risk of recurrent stroke and poor prognosis at 1 year significantly increased with age. However, the risk of all-cause mortality significantly increased only in patients with NICE and hypertension. The 1-year risk of poor prognosis significantly increased with age, regardless of diabetes mellitus status. However, increases in the risks of recurrent stroke and all-cause mortality were significant only in patients without diabetes mellitus. In NICE patients without atrial fibrillation, the risk of adverse outcomes at 1 year significantly increased with age. However, owing to the small number of patients with atrial fibrillation, statistical analysis failed to yield normal results.

Table 4 Subgroup analysis of age and 1-year outcome events in patients with NICE
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Discussion

This study aimed to compare the clinical characteristics of NICE patients across different age groups and to investigate the impact of age on the 1-year adverse outcomes in these patients. Our findings revealed significant variations in gender, vascular risk factors, and other clinical characteristics among patients with NICE across different age groups. While there were no significant differences in recurrent stroke risks among age groups at 3 months, the risks increased significantly at 1 year, particularly in older patients (G4 group). Both all-cause mortality and poor prognosis risks also showed significant increases over time, especially in the oldest age group. Subgroup analysis highlighted that alcohol consumption significantly increased the risk of 1-year all-cause mortality and poor prognosis in older patients with NICE. These results offer a theoretical framework for considering the influence of age in the formulation of primary prevention and treatment strategies for NICE.

Previous studies have shown that approximately 75% of strokes occur in individuals over 50 years old, with stroke prevalence increasing with age [20,21,22]. In this study, patients were categorized into four age groups at the nodes of 55, 65, and 75 years, aligning with previous studies and the age distribution of the included NICE cases. We believe this grouping holds practical clinical significance when discussing the differences in NICE among different age groups. Analysis revealed significant differences only in medical insurance type and dyslipidemia between patients lost to follow-up at the end of 1 year and those who were not lost (see Supplementary Table 2). Nonetheless, other clinical variables remained comparable between the groups. Overall, the data from patients lost to follow-up appeared random, suggesting minimal impact on study results. Following assurance of the representativeness of the included clinical samples, we investigated age-related clinical characteristics and 1-year outcomes of patients with NICE.

Our study show that the rate of NICE in patients under 55 years old is 22.3%, with a higher proportion of alcohol consumption (37.6%) and smoking (37.6%), and lower urban employees’ medical insurance coverage (39.6%). Patients aged 55–64 have the highest rate of NICE, accounting for 30% of all cases, with similar characteristics to those under 55, including high rates of smoking, drinking, and elevated TC levels (4.6 ± 1.1 mmol/L). For these age groups, preventive and intervention strategies should focus on smoking cessation, reducing alcohol consumption, increasing insurance coverage for those under 55, and enhancing lipid control in those aged 55–64. In patients aged 65–74, the rate of NICE is 25.7%, with lower smoking rates (20.8%) but a higher prevalence of peripheral vascular disease (4.5%) compared to other groups. Early detection and intervention for peripheral vascular disease should be prioritized for this age group. For patients over 75 years old, the rate is 22%, with low smoking (12.1%) and drinking (1.7%) rates, but higher systolic blood pressure (147.9 ± 22.2 mmHg) and lower BMI (22.6 ± 3.1 kg/m²). In this elderly population, blood pressure monitoring and enhanced nutritional support are essential to reduce adverse outcomes. The combined proportion of NICE patients under 65 is 52.3%, exceeding the rate of ischemic stroke patients under 65 in the CNSR study (46.6%) and the rate of minor stroke and TIA patients under 65 in the CHANCE study. Additionally, a population-based stroke surveillance study conducted in the United States found that the rate of ischemic stroke in patients aged 75 or older was approximately 58% [23], significantly higher than the 22% of NICE patients in this age group in our study. These findings highlight the distribution of clinical characteristics of NICE across different age groups, underscoring the importance of considering age in healthcare planning for prevention and treatment strategies. Our study demonstrates that developing targeted prevention strategies based on specific age distribution is crucial for effectively improving the prognosis of NICE patients.

Our study also noted that while the overall proportion of men in the NICE group exceeded that of women, the proportion of women increased notably in the over-65 age bracket, possibly attributable to longer life expectancy [24,25,26]. Rates of current smoking and alcohol consumption were higher in patients aged under 55 years old, consistent with previous findings in patients with ischemic stroke [27]. Although the symptoms of NICE are relatively mild, they should not be treated lightly. If smoking and alcohol consumption are not addressed in a timely manner, they may exacerbate the severity of strokes, leading to functional impairment or life-threatening events. Therefore, smoking cessation and alcohol moderation are crucial for reducing adverse outcomes in NICE patients. Our findings suggest that, compared to other age groups, patients with NICE under the age of 55 may not place enough importance on smoking cessation and alcohol moderation. We recommend that relevant authorities prioritize health education for patients with NICE under 55, encouraging smoking cessation and alcohol moderation, which could effectively reduce the risk of adverse outcomes in this age group. Additionally, regular health check-ups and assessments can help identify and manage risk factors early. Our study showed that compared with other age groups, the proportion of patients with previous stroke, hypertension, and dyslipidemia was higher in patients aged 65–74 years, and the proportion of patients aged > 75 years with atrial fibrillation and pneumonia was significantly higher than in other age groups. These findings align with previous studies in patients with other symptoms of ischemic stroke [26,27,28,29]. However, no significant age-related differences were found in the rate of diabetes mellitus among patients with NICE, contrary to reports of high diabetesrate in elderly stroke patients [29]. This suggests a potential lack of association between diabetes and aging in patients with NICE, warranting further investigation.

Our study found that patients aged 75 years or older had a significantly lower BMI compared to those in the other age groups. This decline may be due to decreased metabolic function and lower nutritional reserves in the elderly population. To address this, clinicians should conduct nutritional assessments and provide personalized nutritional plans for patients aged 75 years or older. Additionally, the proportion of patients with NICE aged 65–75 years with peripheral vascular diseases was notably higher than in other age groups, which may be related to the higher incidence of atherosclerosis within this demographic.Therefore, regular vascular examinations are recommended for patients aged 65–75 years to detect and manage atherosclerosis early. Furthermore, comprehensive vascular evaluations and standardized secondary prevention measures should be implemented to improve patient outcomes. Our study also revealed that patients with NICE aged 75 years or older had significantly lower levels of TC, TG, LDL-C, ALT, WBC, and PLT counts compared to other age groups. While this suggests relatively good blood lipid control in elderly patients with NICE, advancing age can lead to weakness and immune dysfunction, rendering them more susceptible to viral infections or hematological diseases. This increased vulnerability significantly increases the risk of all-cause mortality in elderly patients with NICE [30]. Thus, it is essential to enhance immune support through vaccinations and regular health monitoring for infection prevention in patients aged 75 and above. Moreover, compared to other age groups, patients aged 75 years or older had higher levels of serum creatinine and blood urea nitrogen and lower levels of eGFR. Although most patients’ test values fell within the normal range, these findings indicate a potential heightened risk of kidney damage among elderly patients with NICE. These observations align with previous studies, highlighting the frequent occurrence of concurrent kidney dysfunction in stroke patients [31, 32]. Hence, regularly testing kidney function in elderly patients is vital to detect and address abnormalities early. In addition to implementing active interventions during the early stages of NICE, clinicians should also prioritize strengthening the promotion of medical knowledge and primary prevention among middle-aged and young populations.

A literature review identified limited research on stroke outcomes across different age groups, particularly in patients with NICE. In this study, we explored the probability of adverse outcomes and the associated risk with increasing age among patients with NICE in various age brackets. Our findings revealed that at 3 months, patients with NICE under 55 years old and those over 75 years old had a higher risk of mortality and poor prognosis compared to the other two groups (Table 2). Based on our analysis, we analyzed the potential factors contributing to the all-cause mortality of NICE under 55 years old, which may include the following aspects: a larger proportion of patients under 55 years old are current alcohol drinkers (37.6%) compared to other groups, and alcohol consumption is a known risk factor for stroke and poor prognosis [33, 34]. Additionally, the male-dominant group may underestimate the severity of mild symptoms and continue drinking, increasing stroke-related mortality. NICE under 55 years old also has a lower proportion of urban employees’ medical insurance coverage, with many patients relying on new type rural cooperative medical system or self-payment, which may lead to delayed treatment. This lower socioeconomic status (new type rural cooperative medical system or out-of-pocket payment) leads to poor adherence to medication and follow-up due to financial pressure, making timely management of stroke risk factors difficult and increasing recurrence risk. Additionally, these patients may lack access to health education, have insufficient health management, and face inadequate preventive care due to limited healthcare resources. Smoking rates are also higher in NICE under 55 years old (37.6%), further contributing to elevated mortality risk. These observations are based on univariate analysis and require further investigation.

In patients aged 75 years or older, the proportion of NICE patients with a history of previous stroke, hypertension, and atrial fibrillation is higher. Additionally, elevated serum creatinine levels and decreased eGFR in elderly patients suggest renal dysfunction, which may be related to mortality. Previous studies have indicated that a history of stroke is associated with a higher risk of post-stroke death [35]. Furthermore, existing research has clearly identified hypertension [36], atrial fibrillation [37], and renal dysfunction [38] as significant factors related to stroke mortality. These findings suggest that mortality in NICE patients may be linked to these factors. In addition, since the mortality in our study is defined as all-cause mortality, deaths among NICE patients may also be attributed to other unrecorded factors in our data (e.g., cancer-related deaths).

The regression results for adverse outcomes at 3 months and 1 year across different age groups indicate that, at 3 months, the risk of poor prognosis significantly increases with age, while the risks of stroke recurrence and all-cause mortality do not show a significant increase. Notably, at 1 year, patients aged 75 years or older displayed significantly higher risks of experiencing adverse outcomes (Table 3). These results echo those of a UK study on nonfatal stroke, which reported a higher rate of first strokes and subsequent major adverse outcomes in older adults compared to younger counterparts [39]. Our findings can help clinicians assess risks more effectively and develop personalized treatment plans for NICE patients in different age groups. This study highlights the risks faced by younger patients under 55 and elderly patients over 75, emphasizing the importance of early intervention. Additionally, it provides valuable information for improving healthcare policies for NICE patients across different age groups and promotes patient self-management and health education.Previous studies have reported significant differences in the incidence, severity, and prognosis of stroke between different sexes [40, 41]. For instance, a long-term follow-up study by Chen et al. revealed a higher risk of recurrent stroke in male patients with AIS compared to females [42]. Similarly, the Chinese National Stroke Registry Study found that female patients with AIS aged 65 years or older were more likely to have a poor prognosis at 3 months [40]. However, limited research exists on sex differences and outcomes in patients of different ages with NICE. In our study, we observed a significant increase in the 1-year risk of recurrent stroke, all-cause mortality, and poor prognosis among men aged 75 years or older with NICE, while women exhibited a significantly higher 1-year risk of poor prognosis only (Supplementary Table 1). These findings, alongside previous studies, suggest that male patients with NICE, particularly elderly males, face a higher risk of stroke recurrence and death, whereas female patients are more prone to poor prognoses. Clinicians should take into account these sex differences as they relate to the prognosis of elderly patients with NICE, and targeted education and interventions may help mitigate the rate of stroke recurrence and death in this population of patients.

Subgroup analysis revealed that alcohol consumption significantly increased the risk of 1-year all-cause mortality and poor prognosis in patients with NICE (Table 4). Moreover, our study aligns with previous findings that demonstrated an increased risk of adverse outcomes (such as recurrent stroke, all-cause mortality, and poor prognosis) in patients with NICE with hypertension and advancing age [12]. The analysis revealed that patients with NICE without diabetes mellitus had a significantly higher risk of recurrent stroke and all-cause mortality at 1 year, whereas those with diabetes mellitus showed a significantly increased risk of poor prognosis at 1 year, deviating from previous studies [14]. This discrepancy in results may be attributed to the lower proportion of diabetic patients in the NICE group or to stress glycemic responses in non-diabetic patients with NICE. However, due to the small number of patients with atrial fibrillation included in our study, statistically significant results could not be obtained after adjusting for related confounders. Therefore, conclusions regarding the impact of atrial fibrillation on stroke outcomes at one year associated with age could not be drawn. Further analyses with larger sample sizes are warranted to obtain more accurate and reliable results.

Despite its contributions, our study had some limitations. Firstly, the four hospitals included were not randomly selected, and all participants were from tertiary grade A hospitals in Xi’an City, China, limiting the generalizability of the results to patients from other regions and hospital grades. Secondly, our study focused solely on analyzing age-related clinical characteristics at baseline and outcome events at one year in patients with NICE without collecting data on the dynamic trajectory of clinical indicators in these patients. Additionally, we did not conduct a comparative analysis between NICE patients and the general population regarding risk factors and outcomes. Moreover, only 1-year follow-up was conducted, necessitating longer follow-up studies for extended outcome events. Thirdly, the Trial of ORG 10,172 in acute stroke treatment classification and imaging data of patients were not collected in our study design; therefore, no comparative analysis of ischemic stroke types and imaging-related indicators was performed. In addition, our study did not collect ritm holter monitoring data, which may only represent a subset of patients with atrial fibrillation in relation to this condition. We will continue to improve on these findings in future studies. Lastly, many indicators related to inflammation were missing in the data, potentially leading to inadequate consideration of the patient’s inflammatory responses in the analysis.

Conclusions

Our study revealed significant disparities in gender, vascular risk factors, and clinical characteristics among NICE patients across different age groups. Notably, patients aged 75 and above showed higher risks of recurrent stroke, all-cause mortality, and poor prognosis after one year. Clinicians should consider these age-specific characteristics and adopt personalized prevention and treatment strategies to improve patient outcomes. Tailored approaches can help address the increased risks associated with older age, alcohol consumption, and comorbidities. Additionally, future research can investigate the differences in risk factors for adverse outcomes among NICE patients of different age groups, providing theoretical support for effective prevention and intervention strategies tailored to different age groups.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

AIS:

Acute ischemic stroke

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

ANOVA:

analysis of variance

ASA:

American Stroke Association

AST:

Aspartate aminotransferase

BMI:

Body mass index

BUN:

Blood Urea Nitrogen

CNSR:

Chinese National Stroke Registry

CT:

Computed tomography

DBP:

Diastolic blood pressure

eGFR:

Estimated Glomerular Filtration Rate

FBG:

Fasting blood glucose

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

mRS:

Modified Rankin Scale

MRI:

Magnetic resonance imaging

NIHSS:

National Institute of Health Stroke Scale

NICE:

Non-disabling ischemic cerebrovascular event

OR:

Odds ratio

SBP:

Systolic blood pressure

TIA:

Transient ischemic attack

TG:

Triglycerides

TC:

Total cholesterol

UA:

Uric acid

WBC:

White blood cell

ANOVA:

Analysis of variance

HR:

Hazard ratio

ECG:

Electrocardiogram

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Acknowledgements

We are grateful to all the laboratory technicians, medical staffs and nurses from the participating hospitals.

Funding

This study was supported by Shaanxi Provincial Innovation Capability Support Plan (Grant No.2023-CX-PT-47); the project of Shaanxi Administration of Traditional Chinese Medicine (Grant no. 2022-SLRH-LJ-013); the Science and Technology Program of Shaanxi Province (Grant no.2023-YBSF-041); Xi’an City Major Project-Discipline Capacity Building (Grant no. 23YXYJ0005); the Science and Technology Plan Project of Xi’an City [Grant no.22YXYJ0061 and 22YXYJ0074 ]; Scientific research project of Shaanxi Provincial Health Commission [Grant no. 2022C005]; and the Scientific Research Projects of the Xi’an Health Commission (Grant nos. 2020ms03 and 2022qn11). The funders had no role in design and analysis of this trial.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, China

    Zhongzhong Liu & Lingxia Zeng

  2. Department of Neurology, The First Affiliated Hospital of Northwest University, Xi’an No.1 Hospital, Xi’an, China

    Zhongzhong Liu, Songdi Wu, Xuemei Lin, Qingli Lu, Weiyan Guo, Na Zhang, Tong Liu & Linna Peng

  3. Center for Chronic Disease Control and Prevention, Global Health Institution, Xi’an Jiaotong University, Xi’an, China

    Zhongzhong Liu & Lingxia Zeng

  4. Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi’an, China

    Zhongzhong Liu & Lingxia Zeng

  5. Xi’an Key Laboratory for Innovation and Translation of Neuroimmunological Diseases, Xi’an, China

    Zhongzhong Liu, Songdi Wu, Xuemei Lin, Qingli Lu, Weiyan Guo, Na Zhang, Tong Liu & Linna Peng

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Contributions

LXZ, SDW and ZZL and had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LXZ, SDW and ZZL planned and designed the study. SDW, XML, QLL, WYG, NZ, TL and LNP contributed to data acquisition and interpretation. ZZL analyzed the data and was primarily responsible for writing the manuscript. LXZ and SDW revised the manuscript for important intellectual content. All authors read and approved the final version of the manuscript.

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Correspondence to Lingxia Zeng.

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The study was approved by the academic committee and the ethics committee of Xi’an No. 1 hospital, and was conducted in accordance with the ethical principles for medical research involving human participants as described in the declaration of Helsinki. All patients/participants provided their written and oral informed consents for participating in this study.

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Liu, Z., Wu, S., Lin, X. et al. Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study. BMC Geriatr 24, 884 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12877-024-05491-3

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BMC Geriatrics

ISSN: 1471-2318

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