Invest Clin 67(2): 205 - 217, 2026 https://doi.org/10.54817/IC.v67n2a04

Corresponding author: Mingming Fang. Affiliated Hospital of Integrated Traditional Chinese and Western Medi-

cine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, China. Email: fangmmnucm@

elnu-edu.cn

Predictive value of carotid atherosclerotic

plaques assesment, in combination

with glycosylated hemoglobin A1c and

C-reactive protein levels, for disease

progression in young patients with acute

ischemic stroke.

Shuting Jiang1,2†, Hongquan Liu1,2†, Chen Zhong3,4, Jie Yang1,2, Yue Qin1,2,

Yechen Lu1,2 and Mingming Fang1,2*

1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing

University of Chinese Medicine, Nanjing, Jiangsu Province, China.

2Department of Neurology, Jiangsu Province Academy of Traditional Chinese Medicine,

Nanjing, Jiangsu Province, China.

3Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key

Laboratory of Liver Transplantation, Nanjing, Jiangsu Province, China.

4Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary Cancers,

Nanjing Jiangsu Province, China.

†The two authors contributed equally to this study.

Keywords: Ischemic Stroke; Plaque, Atherosclerotic; Carotid Arteries; C-Reactive

Protein; Hemoglobin HA1c.

Abstract. This study evaluated the predictive significance of combining

carotid atherosclerotic plaques assesment with glycosylated hemoglobin A1c

(HbA1c) and C-reactive protein (CRP) levels for disease progression in young

acute ischemic stroke (AIS) patients. A total of 130 subjects were evenly re-

cruited, comprising young patients with AIS admitted between January 2015

and March 2025 (case group) and healthy individuals undergoing physical ex-

aminations during the same period (control group). Comparisons were con-

ducted on the incidence rate of carotid atherosclerotic plaques and serum

HbA1c and CRP levels. The case group was categorized into mild-moderate and

severe groups according to the National Institute of Health Stroke Scale (NI-

HSS) score. Significant differences were observed between the severe and mild-

moderate groups in NIHSS scores, carotid atherosclerotic plaque incidence,

and serum levels of HbA1c and CRP (p<0.05). Increased serum HbA1c levels,

elevated CRP levels, and presence of carotid atherosclerotic plaques functioned

as risk factors for AIS progression in young patients (odds ratio>1, p<0.05).

206 Jiang et al.

Investigación Clínica 67(2): 2026

Valor predictivo de la detección de placas ateroscleróticas

carotídeas, en combinación con los niveles de hemoglobina

glicosilada A1c y proteína C reactiva, para la progresión de la

enfermedad en pacientes jóvenes con accidente cerebrovascular

isquémico agudo.

Invest Clin 2026; 67 (2): 205 – 217

Palabras clave: Accidente Cerebrovascular Isquémico; Placa Aterosclerótica; Arterias

Carótidas; Proteína C-Reactiva; Hemoglobina HA1c.

Resumen. Este estudio evaluó la significancia predictiva de combinar

placas ateroscleróticas carotídeas con niveles de hemoglobina glicosilada A1c

(HbA1c) y proteína C reactiva (PCR) para la progresión de la enfermedad en

pacientes jóvenes con accidente cerebrovascular isquémico agudo (AIS). Se re-

clutó de manera uniforme un total de 130 sujetos, que comprendían pacientes

jóvenes con AIS ingresados entre enero de 2015 y marzo de 2025 (grupo de

casos) e individuos sanos sometidos a exámenes físicos durante el mismo pe-

ríodo (grupo de control). Se realizaron comparaciones en la tasa de incidencia

de placas ateroscleróticas carotídeas y los niveles séricos de HbA1c y PCR. El

grupo de casos se categorizó en grupos leve-moderado y grave según la pun-

tuación de la Escala de Accidente Cerebrovascular del Instituto Nacional de

Salud (NIHSS). Se observaron diferencias significativas entre los grupos grave

y leve-moderado en las puntuaciones NIHSS, la incidencia de placa ateroscle-

rótica carotídea y los niveles séricos de HbA1c y PCR (p<0,05). El aumento

de los niveles séricos de HbA1c, los niveles elevados de PCR y la presencia de

placas ateroscleróticas carotídeas funcionaron como factores de riesgo para

la progresión del AIS en pacientes jóvenes (odds ratio > 1, p<0,05). Los nive-

les séricos de HbA1c y PCR, junto con la presencia de placas ateroscleróticas

carotídeas, mostraron una correlación positiva con las puntuaciones NIHSS (r

>0, p<0,05). Las áreas bajo las curvas ROC de los niveles séricos de HbA1c y

PCR, las placas ateroscleróticas carotídeas y su combinación para evaluar la

progresión del AIS en pacientes jóvenes fueron 0,810, 0,823, 0,781 y 0,905,

respectivamente. Los niveles elevados de HbA1c, PCR y presencia de placas ca-

rotídeas se asocian con la gravedad del AIS en pacientes jóvenes. La detección

combinada mejora la precisión predictiva, lo que sugiere utilidad clínica para la

estratificación del riesgo.

Received: 07-10-2025 Accepted: 02-03-2026

Serum HbA1c and CRP levels, along with the presence of carotid atheroscle-

rotic plaques, showed a positive correlation with NIHSS scores (r>0, p<0.05).

The areas under the ROC curves of serum HbA1c and CRP levels, carotid athero-

sclerotic plaques and their combination for assessing AIS progression in young

patients were 0.810, 0.823, 0.781, and 0.905, respectively. Elevated HbA1c,

CRP, and the presence of carotid plaques are associated with AIS severity in

young patients. Combined detection improves predictive accuracy, suggesting

clinical utility for risk stratification.

Prediction of acute ischemic stroke in young patients 207

Vol. 67(2): 205 - 217, 2026

INTRODUCTION

Acute ischemic stroke (AIS) is defined

as a cerebrovascular disease attributed to

blood supply disorders to brain tissues,

which displays high mortality and disability

rates. Besides, AIS exhibits a significantly

increasing incidence rate in young people

in recent years along with improved living

standards and changed dietary patterns of

people, which has become a major disease

jeopardizing the health of young adults.

Through extensive and in-depth research on

the pathogenesis of AIS in young patients,

it is discovered that atherosclerosis acts as

the underlying cause. Hence, clarifying the

predictors of atherosclerosis and imple-

menting early interventions after accurately

predicting the development and progression

risk of AIS are of great clinical significance

for reducing the incidence, mortality and

disability rates of AIS in young adults. Ath-

erosclerotic plaques are a product of athero-

sclerosis, and the presence of carotid ath-

erosclerotic plaques gives rise to narrowed

inner diameter of the carotid artery, leading

to artery stenosis, which, when reaching a

certain degree, can cause blood shortage to

the brain. Once unstable plaques rupture,

the dislodged plaques can result in thrombo-

sis in distal intracranial vessels and eventu-

ally AIS 1,2. Abnormal glucose metabolism is

able to not only induce damage to vascular

endothelial cells, but also facilitate smooth

muscle hyperplasia and inflammatory re-

sponses, thereby triggering atherosclerosis,

which serves as a crucial cause of the devel-

opment and progression of cerebrovascular

diseases 3. Glycosylated hemoglobin A1c

(HbA1c), formed by the binding of hemoglo-

bin to blood glucose in red blood cells, is a

frequently measured biomarker in patients

with abnormal glucose metabolism. There-

fore, the glucose metabolism status in the

body can be effectively mastered by measur-

ing serum HbA1c level. C-reactive protein

(CRP)-mediated inflammatory responses

participate in the whole process of athero-

sclerosis development and progression, serv-

ing as a risk factor inducing cerebrovascular

diseases 4. Research has shown that athero-

sclerotic plaques and levels of serum HbA1c

and CRP are correlated with the onset and

advancement of AIS, potentially serving as

reliable indicators of the condition.

Given this, in the present study, analy-

ses were carried out on the distribution of

carotid atherosclerotic plaques and expres-

sions of HbA1c and CRP in young patients

with AIS, as well as their correlations with

and predictive value for the progression of

AIS.

MATERIALS AND METHODS

Subjects

A total of 65 young AIS patients admit-

ted to our hospital between January 2015

and March 2025 were consecutively enrolled

as the case group, including 59 males and

6 females, aged 23-45 years (mean age,

39.11±5.61 years). The body mass index

(BMI) of the case group ranged from 21 to

26 kg/m2, with a mean value of 23.46 ± 0.45

kg/m2. During the same period, 65 age- and

sex-matched healthy individuals undergoing

routine physical examinations at our hospi-

tal were recruited as the control group, com-

prising 57 males and 8 females, aged 23-46

years (mean age, 38.86±5.46 years), with

a BMI ranging from 21 to 26 kg/m2 (mean,

23.42±0.48 kg/m2).

Inclusion and exclusion criteria

Inclusion criteria for the case group

were: 1) patients diagnosed with AIS via cra-

nial Computed Tomography (CT) images 5,

2) ischemia duration of less than 72 hours,

3) informed consent obtained from family

members, and 4) first episode of the disease.

The exclusion criteria were listed be-

low: 1) patients with such diseases as brain

tumors and brain traumas, 2) those with se-

vere insufficiency of the heart, liver, kidneys

or other organs, 3) those with a history of

cardiogenic AIS or AIS induced by rheumatic

208 Jiang et al.

Investigación Clínica 67(2): 2026

heart disease, atrial fibrillation, or other fac-

tors, 4) those with a history of administra-

tion of such drugs as propranolol, morphine

and hydrochlorothiazide, or 5) those with a

history of surgery or traumas or a history of

nosocomial infection with obvious signs and

clinical evidence in the past 1 week.

Blood sample collection

A 5 mL fasting venous blood sample

was collected from the median cubital vein

of participants in the health group during

their physical examination and from the

case group on the morning before treat-

ment, then allowed to stand at room tem-

perature for 30 minutes. After that, centrifu-

gation was conducted (centrifugal radius: 10

cm, centrifugation speed: 2500 r/min, and

centrifugation time: 10 min). The upper se-

rum was transferred to a centrifuge tube and

stored at -80°C for future analysis.

Measurement of serum HbA1c and CRP

levels

The serum was removed from refrigera-

tion, thawed at room temperature, and ana-

lyzed for HbA1c using a latex agglutination

test (RB, USA) with a reference range of 3.8-

5.8%, and for CRP levels using a double-anti-

body sandwich ELISA [Pointe Biotechnology

(Nanjing) Co., Ltd.] with a reference range

of 0-5 mg/L.

Detection of carotid atherosclerotic

plaques

Color Doppler ultrasonic diagnostic ap-

paratus (produced by Aloka, Japan) was em-

ployed to detect the distribution of carotid

atherosclerotic plaques in both groups. Dur-

ing examination, the subjects were instructed

should be instructed to lie in a relaxed po-

sition, with the shoulders elevated with the

help of soft pads and the head turning to the

opposite side to fully extend the neck. Next, a

linear array probe was selected, with the fre-

quency set at 3-11 MHz, and evenly applied

with the couplant on the surface. Ultrasonic

scans were performed on the common carot-

id artery, its bifurcation, and the carotid bulb

(typically 4.0-6.0 cm above the bifurcation).

The carotid intima-media thickness (IMT) was

measured three times, and the results were

averaged. Presence of carotid atherosclerotic

plaques was considered in case of IMT ≥1.5

mm or localized thickening exceeding 50% of

the surrounding intimal thickness.

Evaluation of AIS progression

The severity of AIS in the case group

was evaluated using the NIHSS score (Natio-

nal Institutes of Health Stroke Scale) 6. Pa-

tients with a score of ≤15 were categorized

as mild-moderate, while those scoring >15

were classified as severe.

Collection of general data

The collected data included gender, age,

BMI, allergic constitution (yes/no), smok-

ing history (≥5 years, >10 cigarettes/day),

drinking history (≥5 years, >1 liang/day),

hypertension (yes/no), NIHSS score, and

laboratory indicators such as white blood cell

count (WBC), triglycerides (TG), total cho-

lesterol (TC), high-density lipoprotein (HDL),

and low-density lipoprotein (LDL).

Statistical analysis

Statistical analysis was completed with

SPSS 23.0 software. Measurement data un-

derwent normality testing. Normally distrib-

uted data were expressed as mean ± stan-

dard deviation (X±SD) and analyzed using

independent-samples t-tests for intergroup

comparisons and paired-samples t-tests for

intragroup comparisons. A logistic regression

analysis was conducted to determine risk fac-

tors influencing AIS progression in young

patients. Kendall’s Tau-b and Pearson correla-

tion analyses were used to examine the rela-

tionships between NIHSS scores and carotid

atherosclerotic plaques, as well as serum

HbA1c and CRP levels. ROC curves were uti-

lized to evaluate the predictive values of ca-

rotid atherosclerotic plaques, serum HbA1c

levels, serum CRP levels, and their combina-

tion for AIS progression, and the optimal cut-

Prediction of acute ischemic stroke in young patients 209

Vol. 67(2): 205 - 217, 2026

off values were determined using the Youden

index. AUCs >0.90 indicate high predictive

value, 0.71-0.90 suggest fair value, 0.50-0.70

denote low value, and <0.50 reflect no pre-

dictive value. A p-value less than 0.05 was

considered statistically significant.

RESULTS

Baseline and key characteristics

Baseline demographic, clinical, and

laboratory characteristics of the case and

control groups are presented in Table 1. No

significant differences were observed be-

tween the two groups in age, sex, BMI, aller-

gic constitution, smoking or drinking histo-

ry, hypertension status, WBC count, or lipid

profiles (TG, TC, HDL-C, and LDL-C) (all

p>0.05). In contrast, serum HbA1c and CRP

levels were significantly higher in the case

group, and carotid atherosclerotic plaques

were more frequently detected in the case

group, whereas no plaques were observed in

the control group (all p<0.001).

Relevant data in case and health groups

The case group exhibited significantly

higher serum HbA1c levels (6.05±1.84%

vs. 4.26±0.50%) and serum CRP levels

(3.08±2.98 mg/L vs. 0.55±0.30 mg/L)

compared with the healthy group (both p

< 0.001). In addition, carotid atheroscle-

rotic plaques were detected in 19 patients

(29.23%) in the case group, whereas no

plaques were observed in the control group

(p<0.001) (Table 2).

Disease progression in case group

Among the 65 patients in the case

group, 50 patients (76.92%) were classi-

fied as having mild–moderate AIS, and 15

patients (23.08%) were classified as having

severe AIS based on NIHSS scores.

Relevant data of patients in mild-

moderate and severe groups

No significant differences were found

between the mild-moderate and severe

groups in terms of sex distribution, age,

BMI, allergic constitution, smoking history,

drinking history, hypertension, WBC or se-

rum lipid profiles, including TG, TC, HDL-

C, and LDL-C (all p>0.05). In contrast, the

severe group exhibited significantly higher

NIHSS scores, as well as a higher prevalence

of carotid atherosclerotic plaques and signif-

icantly elevated serum HbA1c and CRP lev-

els, compared with the mild-moderate group

(p<0.001) (Table 3).

Results of logistic regression analysis

on AIS progression in young patients

Logistic regression analysis was carried

out with AIS progression in young patients as

the dependent variable (1=severe, 0=mild-

moderate) and variables showing statistical-

ly significant differences in univariate analy-

ses (except NIHSS score) as the independent

variables. Serum HbA1c level (OR=17.583,

95% CI: 2.545-121.500, p=0.004), serum

CRP level (OR=14.391, 95% CI: 2.852-

72.625, p=0.001), and the presence of ca-

rotid atherosclerotic plaques (OR=12.667,

95% CI: 2.361-67.958, p=0.003) were inde-

pendently associated with an increased risk

of AIS progression in young patients (Table

4 and Fig. 1).

Results of correlation analyses

Correlation analyses demonstrated that

NIHSS scores were positively correlated with

serum HbA1c levels (r=0.401, p=0.001), se-

rum CRP levels (r=0.430, p<0.001), and the

presence of carotid atherosclerotic plaques

(r=0.522, p=0.004) in young patients with

AIS (Table 5).

Value of serum HbA1c levels, serum CRP

levels, carotid atherosclerotic plaques

and their combination for assessing AIS

progression in young patients

ROC curves analyses were performed to

evaluate the ability of serum HbA1c levels,

serum CRP levels, presence of carotid ath-

erosclerotic plaques, and their combination

to discriminate severe AIS from mild–mod-

210 Jiang et al.

Investigación Clínica 67(2): 2026

erate AIS (Fig. 2). As shown in Table 6, the

AUCs were 0.810 for serum HbA1c levels,

0.823 for serum CRP levels, and 0.781 for

carotid atherosclerotic plaques. The com-

bined model demonstrated the highest dis-

criminative performance, with an AUC of

0.905 (p<0.001).

DISCUSSION

In the pathogenetic process of AIS, a

range of extremely complex pathophysiolog-

ical variations are triggered owing to isch-

emia and hypoxia at lesion sites, involving

multiple factors.

Table 1. Baseline characteristics and key study parameters of the case and control groups.

Variable Case group (n=65) Control group (n=65) Statistical test p value

Age (years) 39.11±5.61 38.86±5.46 t=0.258 0.797

Gender, n (%) χ2=0.080 0.777

Male 59 (90.77) 57 (87.69)

Female 6 (9.23) 8 (12.31)

Body mass index (kg/m²) 23.46±0.45 23.42±0.48 t=0.490 0.625

Allergic constitution, n (%) χ2=0.301 0.583

Ye s 9 (13.85) 6 (9.23)

No 56 (86.15) 59 (90.77)

Smoking history, n (%) χ2=0.040 0.841

Ye s 18 (27.69) 16 (24.62)

No 47 (72.31) 49 (75.38)

Drinking history, n (%) χ2=0.037 0.847

Ye s 20 (30.77) 18 (27.69)

No 45 (69.23) 47 (72.31)

Hypertension, n (%) χ2=0.035 0.851

Ye s 22 (33.85) 20 (30.77)

No 43 (66.15) 45 (69.23)

WBC (×109/L) 6.78±1.52 6.62±1.47 t=0.610 0.543

Serum TG (mmol/L) 1.54±0.46 1.48±0.42 t=0.777 0.439

Serum TC (mmol/L) 4.62±0.71 4.58±0.69 t=0.326 0.745

Serum HDL-C (mmol/L) 1.12±0.24 1.15±0.22 t=-0.743 0.459

Serum LDL-C (mmol/L) 2.76±0.58 2.69±0.55 t=0.706 0.481

Serum HbA1c (%) 6.05±1.84 4.26±0.50 t=7.569 <0.001

Serum CRP (mg/L) 3.08±2.98 0.55±0.30 t=6.810 <0.001

Carotid atherosclerotic plaque,

n (%)

Fisher’s

exact test <0.001

Present 19 (29.23) 0 (0.00)

Absent 46 (70.77) 65 (100.00)

Data are presented as mean ± standard deviation for continuous variables and number (percentage) for categorical

variables. WBC: white blood cell count; TG: triglycerides; TC: total cholesterol; HDL-C: high-density lipoprotein

cholesterol; LDL-C: low-density lipoprotein cholesterol; HbA1c: glycated hemoglobin A1c; CRP: C-reactive protein.

Comparisons between the case and control groups were performed using the independent-samples t test for conti-

nuous variables and the chi-square test or Fisher’s exact test for categorical variables, as appropriate.

Prediction of acute ischemic stroke in young patients 211

Vol. 67(2): 205 - 217, 2026

Table 2. Relevant data in case and health groups.

Group n Serum HbA1c

level (%)

Serum CRP

level (mg/L)

Carotid atherosclerotic plaque, n (%)

Ye s No

Control 65 4.26±0.50 0.55±0.30 0 (0.00) 65 (100.00)

Case 65 6.05±1.84 3.08±2.98 19 (29.23) 46 (70.77)

t7.569 6.810 22.252

p <0.001 <0.001 <0.001

Data are presented as mean ± standard deviation or number (percentage). HbA1c: glycated hemoglobin A1c; CRP:

C-reactive protein. Comparisons between the case and control groups were performed using the independent-

samples t test for continuous variables and the chi-square test for categorical variables.

Table 3. Relevant indicators of patients in mild-moderate and severe groups

Indicator Mild-moderate group

(n=50)

Severe group

(n=15)

Statistical

value p

Gender, n (%) Male 28 (56.00) 6 (40.00) 1.184 0.277

Female 22 (44.00) 9 (60.00)

Allergic constitution, n (%) Ye s 3 (6.00) 0 (0.00) 0.073 0.787

No 47 (94.00) 15 (100.00)

Smoking history, n (%) Ye s 6 (12.00) 3 (20.00) 0.130 0.718

No 44 (88.00) 12 (80.00)

Drinking history, n (%) Ye s 8 (16.00) 2 (13.33) 0.025 0.875

No 42 (84.00) 13 (86.67)

Carotid atherosclerotic

plaque, n (%)

Ye s 6 (12.00) 13 (86.67) 27.592 <0.001

No 44 (88.00) 2 (13.33)

Hypertension, n (%) Ye s 22 (44.00) 4 (26.67) 1.444 0.229

No 28 (56.00) 11 (73.33)

Age (year) 39.11±5.61 40.13±5.23 0.627 0.533

BMI (kg/m2) 23.46±0.44 23.43±0.43 0.233 0.817

WBC (×109/L) 3.95±0.28 3.89±0.27 0.734 0.466

Serum TG (nmol/L) 2.03±0.25 2.05±0.26 0.269 0.789

Serum TC (nmol/L) 6.85±0.16 6.88±0.18 0.619 0.538

Serum HDL-C (nmol/L) 0.84±0.17 0.82±0.16 0.405 0.687

Serum LDL-C (nmol/L) 4.87±0.13 4.85±0.15 0.504 0.616

Serum HbA1c (%) 5.50±0.55 7.88±0.62 14.276 <0.001

Serum CRP (mg/L) 2.84±0.25 3.88±0.36 12.697 <0.001

NIHSS score (points) 22.15±4.24 38.24±5.12 12.282 <0.001

Data are presented as mean ± standard deviation for continuous variables and number (percentage) for categorical

variables. BMI: body mass index; WBC: white blood cell count; TG: triglycerides; TC: total cholesterol; HDL-C: high-

density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; HbA1c: glycated hemoglobin A1c; CRP:

C-reactive protein; NIHSS: National Institutes of Health Stroke Scale; AIS: acute ischemic stroke. Comparisons

between mild-moderate and severe AIS groups were conducted using the independent-samples t test for continuous

variables and the chi-square test or Fisher’s exact test for categorical variables, as appropriate.

212 Jiang et al.

Investigación Clínica 67(2): 2026

Table 4. Results of logistic regression analysis on acute ischemic stroke

progression in young patients.

Variable B Standard

error Wals p Odds ratio 95% confidence

interval

Serum HbA1c level 2.776 0.975 7.340 0.004 17.583 2.545-121.500

Serum CRP level 2.556 0.715 9.444 0.001 14.391 2.852-72.625

Presence of carotid

atherosclerotic plaques

2.428

0.656

7.764

0.003

12.667

2.361-67.958

B represents the regression coefficient. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated

using multivariable logistic regression. Serum HbA1c and serum CRP levels were entered into the model as con-

tinuous variables (per 1% increase in HbA1c and per 1 mg/L increase in CRP). Presence of carotid atherosclero-

tic plaques was entered as a binary variable (present vs. absent). HbA1c: glycated hemoglobin; CRP: C- reactive

protein.

Table 5. Correlations of serum HbA1c and CRP levels and carotid atherosclerotic plaques

with acute ischemic stroke progression in young patients.

Coefficient Serum HbA1c level Serum CRP level Carotid atherosclerotic plaque

r 0.401 0.430 0.522

p 0.001 <0.001 0.004

Correlation coefficients (r) were calculated using Pearson or Kendall’s Tau-b correlation analysis, as appropriate.

Serum HBA1c (%) and serum CRP (mg/L) were analyzed as continuous variables. Presence of carotid atheroscle-

rotic plaques was treated as a binary variable. p values <0.05 were considered statistically significant. HbA1c:

glycated hemoglobin; CRP: C- reactive protein.

Fig. 1. Forest plot of clinical characteristics based on multivariate logistic regression analysis. Odds ratios

(ORs) and 95% confidence intervals (CIs) are presented for each variable. Serum HbA1c was analyzed

as a continuous variable per 1% increase, and serum CRP was analyzed per 1 mg/L increase. Presence

of carotid atherosclerotic plaque was treated as a binary variable (present vs. absent). The horizontal

lines represent 95% CIs, and the solid circles indicate the corresponding ORs. The x-axis is displayed

on a logarithmic scale.

Prediction of acute ischemic stroke in young patients 213

Vol. 67(2): 205 - 217, 2026

Table 6. Value of serum HbA1c levels, serum CRP levels, carotid atherosclerotic plaques

and their combination for assessing acute ischemic stroke progression in young patients.

Item Optimal cut-

off value

Area under

the curve

Standard

error p

95%

confidence

interval

Sensitivity Specificity Youden

index

Serum HbA1c level 7.565 % 0.810 0.063 0.002 0.688-0.934 0.640 0.900 0.540

Serum CRP level 3.015 mg/L 0.823 0.091 0.001 0.644-0.998 0.840 0.800 0.640

Carotid atherosclerotic

plaque

0.781

0.082

0.005

0.620-0.940

0.760

0.800

0.560

Combination - 0.905 0.067 <0.001 0.772-0.999 0.900 0.900 0.800

Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of each para-

meter for AIS progression. Serum HbA1c (%) and serum CRP (mg/L) were analyzed as continuous variables, and

the optimal cut-off values were determined using the Youden index. Presence of carotid atherosclerotic plaques was

treated as a binary variable. The combined model was derived from multivariable logistic regression and repre-

sents the predicted probability of AIS progression. AIS: acute ischemic stroke; HbA1c: glycated hemoglobin; CRP:

C- reactive protein.

Fig. 2. ROC curves showing the predictive performance of serum HbA1c, serum CRP, carotid atheroscle-

rotic plaque, and their combination for AIS progression in young patients. Serum HbA1c (%) and

serum CRP (mg/L) were analyzed as continuous variables, and optimal cut-off values were deter-

mined using the Youden index. Presence of carotid atherosclerotic plaque was treated as a binary

variable. The combined model demonstrated the highest discriminative performance, with an AUC

of 0.905 (p<0.001).

214 Jiang et al.

Investigación Clínica 67(2): 2026

A recent study reported that athero-

sclerotic changes in the brain and neck

serve as the initiating factors for the devel-

opment and progression of AIS 7. Therefore,

risk stratification of patients by identifying

predictors directly associated with athero-

genesis or susceptibility to atherosclerosis

is conducive to more accurate implementa-

tion of interventions, and is of great clinical

significance for hindering the progression of

atherosclerosis to AIS.

In the present study, carotid atheroscle-

rotic plaques were more frequently detected

in the case group than in the control group,

and their prevalence was significantly high-

er in patients with severe AIS than in those

with mild–moderate AIS. Moreover, carotid

atherosclerotic plaques were positively cor-

related with NIHSS scores and were inde-

pendently associated with AIS progression

in logistic regression analysis. These find-

ings indicate that the presence of carotid

atherosclerotic plaques is closely associat-

ed with disease severity and progression in

young patients with AIS. Rather than estab-

lishing causality, these associations suggest

that carotid atherosclerotic plaques may

reflect a higher vascular risk burden in this

population. It is speculated to be attribut-

able to the following fact: Healthy arteries

are elastic, but local lipid accumulation, fi-

brous tissue proliferation, and calcinosis of

the arterial wall occur over time, starting

from the intima of arteries, which gives rise

to gradual hardening of arterial vessels and

thus results in atherosclerosis 8,9. As athero-

sclerosis progresses, atherosclerotic plaques

will form in blood vessels and then gradually

enlarge over time. When the plaques erode

and migrate to the small blood vessels in the

brain, narrowing and blockage of the arterial

lumen will be induced, affecting blood flow

and normal nutrient delivery and thereby

arousing various symptoms and diseases as-

sociated with AIS 10,11.

Serum HbA1c and CRP levels were sig-

nificantly higher in the case group than in

the control group and were elevated in pa-

tients with severe AIS compared with those

with mild–moderate AIS. Both biomarkers

showed positive correlations with NIHSS

scores and were independently associated

with AIS progression in multivariable logis-

tic regression analysis.

These results suggest that higher se-

rum HbA1c and CRP levels are associated

with greater neurological impairment and

increased risk of disease progression in

young AIS patients. This is ascribed to the

under-mentioned facts. Elevated HbA1c lev-

els cause a leftward shift in the oxygen dis-

sociation curve, reducing the dissociation

rate of oxyhemoglobin and increasing the

affinity of red blood cells for oxygen. This

results in a significant decrease in 2,3-di-

phosphoglycerate levels within red blood

cells. If uncorrected over time, these chang-

es can disrupt blood and oxygen supply to

the brain, potentially inducing AIS 12,13. Sec-

ondly, hypoxia-ischemia brain damage exac-

erbates progressively as HbA1c levels con-

tinuously increase, together with constant

AIS progression in young patients. Thirdly,

an elevation in HbA1c levels enhances en-

dothelial activity, activates smooth muscle

endothelin-A receptors, and stimulates the

renin-angiotensin system, leading to vaso-

constriction. Additionally, it enhances pro-

tein glycosylation and oxidation, with the

resulting glycosylation end products stimu-

lating LDL-C cytophagy and oxidation by

lymphocytes and monocytes on the arterial

wall. This process leads to foam cell forma-

tion, advancing atherosclerosis and contrib-

uting to the development and progression

of AIS 14-16. CRP is a highly sensitive inflam-

matory marker, typically present at very

low levels in the blood, but it significant-

ly increases during acute inflammation,

trauma, or necrosis. If CRP levels increase,

nuclear factor-kB is continuously activated,

resulting in abnormalities in hemorheology

and making the blood in the arterial blood

vessels hyperviscous and hypercoagulable

and flow slowly. Consequently, thrombosis

is readily triggered, leading to the onset

Prediction of acute ischemic stroke in young patients 215

Vol. 67(2): 205 - 217, 2026

and advancement of AIS 17-19. Fifthly, CRP

may stimulate nerve cells and glial cells to

release various inflammatory factors like

tumor necrosis factor-α and interleukin by

activating autoreceptors and the comple-

ment system. These inflammatory factors

further induce peripheral immune cells to

enter the brain, exacerbating inflammatory

responses, which not only aggravate brain

tissue damage, but also affect the recovery

of neurological function, and thus boosting

the progression of AIS 20,21.

ROC curve analyses further demon-

strated that serum HbA1c levels, serum

CRP levels, and carotid atherosclerotic

plaques each exhibited moderate discrimi-

native ability for AIS progression, whereas

their combined assessment achieved the

highest predictive performance. This find-

ing suggests that integrating metabolic,

inflammatory, and vascular indicators may

improve risk stratification for AIS progres-

sion in young patients. Physicians can also

better understand AIS progression in young

patients based on the above indicators,

and thus develop more effective treatment

plans. The present study clarified the cor-

relations of carotid atherosclerotic plaques

and varying serum HbA1c and CRP levels

with AIS in young adults, which, however,

had some shortcomings. For instance, the

sample size was small, and subjects were all

from the same hospital, which may result

in some degree of selection bias. Besides,

only univariate logistic regression analysis

was conducted in data statistics, and no in-

vestigation was carried out on independent

risk factors for the development and pro-

gression of AIS in young adults, which may

have a certain impact on research results.

Future research should increase sample siz-

es for multicenter prospective studies and

utilize univariate and multivariate logistic

regression analyses to examine the impact

of independent risk factors on AIS develop-

ment and progression.

In conclusion, elevated serum HbA1c

and CRP levels and the presence of carotid

atherosclerotic plaques were associated with

increased disease severity and progression

in young patients with AIS. The combined

evaluation of these indicators demonstrated

improved predictive performance and may

provide additional value for clinical risk as-

sessment.

Acknowledgements

None.

Funding

This study was financially supported by

The Second-Level Key Project of the Sixth

Phase of Jiangsu Province “333” Talent

Project (No. BRA2-2201), Jiangsu Province

Traditional Chinese Medicine Science and

Technology Development Plan General Proj-

ect (No. MS2023035), and Jiangsu Province

Traditional Chinese Medicine Science and

Technology Development Plan Key Project

(No. ZD202415).

ORCID ID of the authors

• Shuting Jiang (SJ):

0009-0004-7236-8127

• Hongquan Liu (HL):

0009-0003-5246-3939

• Chen Zhong (CZ):

0009-0009-6729-6823

• Jie Yang (JY):

0009-0004-8218-9376

• Yue Qin (YQ):

0009-0006-7083-8679

• Yechen Lu (YL):

0009-0005-6100-435X

• Mingming Fang MF):

0009-0007-8211-0789

Conflict of interest

The authors report no conflicts of in-

terest.

216 Jiang et al.

Investigación Clínica 67(2): 2026

Author's contributions

SJ and MF designed the study, HL and

CZ conceived and supervised the study, JY,

YQ and YL performed and analyzed the ex-

periments, SJ and MF drafted the paper. All

authors read and approved the final manu-

script.

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