Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Jiaxin Guan; Lu Gan; Chaoqi Yan; Boyu Hou; Ying Fan

doi:10.1515/fzm-2024-0011

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

doi: 10.1515/fzm-2024-0011

Jiaxin Guan^{1, #},
Lu Gan^{1, #},
Chaoqi Yan²,
Boyu Hou¹,
Ying Fan^{1
, ,}

1.
Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
2.
The Physical examination center of the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China

Funds:

the National Natural Science Foundation of Heilongjiang Province of China LH2020H051

Key R&D projects of Natural Science Foundation of Heilongjiang Province 2023ZX06C03

Foundation of Harbin Science Technology Bureau of China 2014RFQGJ042

More Information

Corresponding author: Ying Fan, fanyingyan@163.com

摘要

Abstract: Background and objective Commonly plaguing in the frigid zone of the world, vitamin D deficiency, as indicated by low levels of 25-hydroxyvitamin D, exacerbated inflammatory responses and impaired endothelial function. Leukoaraiosis (LA) is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses. This study aimed to investigate the impact of vitamin D on the severity of LA. Methods Patients with LA were categorized based on 3.0 T brain MRI findings into mild (N = 43), moderate (N = 40), or severe groups (N = 29) using the Fazekas scale (scoring 1-6). A control group consisting of 41 healthy individuals was included. Serum fibrinogen C, homocysteine, plasma 25-hydroxyvitamin D, and intercellular cell adhesion molecule-1 (ICAM-1) levels were measured using ELISA. Results All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group, with a more pronounced decrease observed as LA severity increased. Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA (P < 0.05) according to Multiple logistic regression analysis. Additionally, a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1. Conclusions Disease severity positively correlated with levels of the inflammatory marker ICAM-1, worsening as plasma 25-hydroxyvitamin D concentration decreased. Low 25-hydroxyvitamin D emerged as an independent risk factor for LA, potentially exacerbating the inflammatory response. These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.
- cerebral small vascular disease /
- degenerative disease /
- leukoaraiosis /
- white matter hyperintensities /
- lacunar infarction /
- 25-hydroxyvitamin D /
- ICAM-1 /
- fibrinogen-C /
- inflammatory factor /
- fazekas scale

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Figure 1. Selection of participants for the control and Leukoaraiosis groups

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Figure 2. Correlation between 25-hydroxyvitamin D and ICAM-1 levels

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Table 1. Statistical methods for different data

Data	Statistical methods
Normal distribution data	Analysis of variance (ANOVA)
Non normal distribution data	Kruskal-Wallis H test
Enumeration data	Chi-squared test (χ²)
	Fisher's exact test
Multivariate analysis	Multiple logistic regression analysis
Correlation analysis	Spearman's rho analysis

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Table 2. Basic medical history of the Leukoaraiosis (LA) and control groupsa

	Control (N = 41)	LA-mild (N = 43)	LA-moderate (N =40)	LA-severe (N =29)	χ²/H	P
Gender M/F, N/N	18/23	22/21	14/26	14/15	2.408	0.492
Age, y	63.00 (59.50, 70.00)	65.00 (60.00, 68.00)	66.00 (62.00, 70.75)	71.00 (63.00, 79.00)^a	10.50	0.015
LI	28 (68)	36 (83)	39 (98)	29 (100)^a	20.302	< 0.001
Smoking	6 (15)	15 (35)	78 (20)	6 (21)	5.269	0.153
Drinking	1 (2)	12 (28)^a	2 (5)^b	3 (10)	16.048	0.001
Diabetes	4 (10)	8 (19)	10 (25)	10 (34)	6.856	0.077
Hypertension	15 (37)	20 (47)	23 (58)	20 (69)^a	8.177	0.042
CHD	6 (15)	10 (23)	8 (20)	4 (14)	1.546	0.672
Data were presented as N (%), unless indicated otherwise. Age was not normally distributed among the 4 groups and was summarized using the median (interquartile 25, interquartile 75) and subjected to the Kruskal-Wallis H test.^aCompared with control group, P < 0.05. ^bCompared with LA-mild, P < 0.05. CHD, coronary heart disease; LI, lacunar infarction.

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Table 3. Blood indicators of the Leukoaraiosis (LA) and control groups

	Control (N = 41)	LA-mild (N = 43)	LA-moderate (N =40)	LA-severe (N =29)	F	P
Apo B, g/L	1.03 ± 0.29	0.92 ± 0.23	0.96 ± 0.25	1.02 ± 0.31	1.503	0.216
LDL, mmol/L	3.00 ± 0.85	2.65 ± 0.70	2.73 ± 0.84	2.95 ± 0.96	1.631	0.185
ALB, g/L	43.35 ± 3.83	43.72 ± 3.38	43.69 ± 3.97	41.73 ± 3.88	1.992	0.118
25(OH)D, ng/mL	33.59 ± 19.21	25.03 ± 13.63^a	21.69 ± 9.86^a	17.98 ± 8.70^{a, b}	8.409	< 0.001
Data were presented as mean±SD. ^aP < 0.05 compared with control group; ^bP < 0.05 compared with LA-mild group. Apo B, apolipoprotein B; ALB, albumin; LDL, low-density lipoprotein; 25(OH)D, 25-hydroxyvitamin D.

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Table 4. Blood indicators of the Leukoaraiosis (LA) and control groups

	Control (N = 41)	LA-mild (N = 43)	LA-moderate (N =40)	LA-severe (N =29)	H	P
HcyH, µmol/L	10.48 (8.56, 12.86)	11.59 (9.52, 13.25)	10.50 (9.02, 13.11)	10.17 (8.38, 13.60)	2.480	0.479
ApoA1, g/L	1.25 (1.11, 1.37)	1.25 (1.11, 1.36)	1.28 (1.08, 1.45)	1.27 (1.10, 1.45)	0.040	0.998
TC, mmol/L	4.78 (4.21, 5.71)	4.45 (3.86, 5.16)	4.73 (3.74, 5.63)	5.11 (3.92, 5.79)	4.292	0.232
TG, mmol/L	1.35 (1.02, 1.74)	1.12 (0.86, 1.90)	1.46 (1.08, 2.24)	1.46 (1.08, 2.24)	4.820	0.185
HDL, mmol/L	1.28 (1.05, 1.63)	1.29 (1.08, 1.51)	1.34 (1.07, 1.57)	1.24 (1.08, 1.53)	0.303	0.960
FBG, mmol/L	5.37 (4.98, 5.77)	5.48 (4.89, 6.09)	5.35 (4.94, 6.67)	5.52 (4.88, 7.37)	1.701	0.637
Cr, µmol/L	72.00 (64.50, 92.00)	71.00 (65.00, 80.00)	71.50 (61.25, 85.75)	72.00 (62.00, 89.00)	0.311	0.958
UA, µmol/L	325.00 (277.80, 386.95)	307.00 (261.40, 404.90)	300.05 (236.00, 364.01)	308.80 (250.05, 385.95)	1.546	0.672
FBG-C, g/L	2.93 (2.66, 3.36)	2.86 (2.65, 3.58)	3.18 (2.98, 3.63)	3.56 (3.14, 3.91)^{a, b}	17.196	0.001
ICAM-1, ng/mL	439.86 (346.10, 628.29)	584.38 (432.30, 632.81)	581.26 (514.33, 669.53)	620.31 (596.04, 757.30)^{a, b}	21.247	< 0.001
Data were presented as median (interquartile 25, interquartile 75). ^aP < 0.05 compared with control group; ^bP < 0.05 compared with LA-mild group. Abbreviations: ApoA1, apolipoprotein A; Cr, creatinine; FBG, fasting blood glucose; HcyH, homocysteine; HDL, high-density lipoprotein; TC, total cholesterol; TG, triglycerides; UA, uric acid.

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Table 5. Variable assignment table for multiple logistic regression

	Variable Name	Variable assignment
Dependent variable	Leukoaraiosis severity	Severe = 1, Moderate =2,
		Mild = 3, Not ill = 4
Independent variable	Gender	Male = 1, Female = 0
	Lacunar infarction	Yes = 1, No = 0
	Alcohol consumption	Yes = 1, No = 0
	Hypertension	Yes = 1, No = 0
	Age, y	Continuous
	25-hydroxyvitamin D	Continuous
	ICAM-1	Continuous
	FBG-C fibrinogen	Continuous

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Table 6. Multiple logistic regression analysis of Leukoaraiosis

	b	SE	Wald χ²	P	OR (95% CI)
Gender	0.696	0.478	2.120	0.145	2.007 (0.786, 5.124)
Lacunar infarction	1.432	0.675	4.499	0.034	4.187 (1.115 15.728)
Alcohol consumption	3.266	1.234	7.008	0.008	26.219 (2.335, 294.387)
Hypertension	0.308	0.476	0.419	0.517	1.361 (0.535, 3.459)
Age, y	0.017	0.032	0.304	0.581	1.017 (0.924, 1.045)
25-hydroxyvitamin D	–0.055	0.016	12.345	< 0.001	0.946 (1.025, 1.090)
ICAM-1	0.005	0.001	9.616	0.002	1.005 (0.992, 0.998)
FBG-C fibrinogen	0.031	0.350	0.008	0.929	1.031 (0.488, 1.925)
b, regression coefficient; CI, confidence interval; OR, odds ratio; SE, standard error.

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