Correlation Between Blood Pressure Variability And Serum Vascular Endothelial Growth Factor Concentration In Patients With Cerebral Small Vessel Disease

Objective To investigate the correlation between blood pressure variability(BPV)and serum vascular endothelial growth factor(VEGF)levels in patients with cerebral small vessel disease(CSVD).Methods 144 patients with cerebral small vessel disease admitted to the Department of Neurology of the PLA General Hospital between December 2021 and December 2022 were included,and all enrolled patients underwent full sequence scan of 3.0T brain MRI.The international total CSVD burden score was used,and a score of 1 was scored for any of the following: ≥1 lacunar lesion,presumed vascular origin of deep white matter hyperintensity(WMH)≥2 points and/or paraventricular WMH score of 3 points in the Fazekas score,deep or infratentorial cerebral microbleeds≥1,and enlarged perivascular space(EPVS)in the basal ganglia.According to this,all subjects were sequentially divided into subgroups 0(total burden 0 points),1(total burden 1 points),2(total burden 2 points),3(total burden 3 points),and 4(total burden 4 points).Patients with a total load score of 0-2 were defined as mild patients,3 as moderate patients,and 4 as severe patients.All subjects underwent 24-hour ambulatory blood pressure monitoring within 7 days after admission,and venous blood was drawn early in the morning on the day of monitoring to measure the serum concentration of vascular endothelial growth factor(VEGF).The differences in general information of the five groups were compared,including gender,age,history of smoking,history of alcohol consumption,BMI,history of hypertension,history of diabetes mellitus,history of hyperlipidemia,and laboratory data including triglycerides,HDL,LDL and homocysteine,the differences in blood pressure variability and serum VEGF levels.Spearman correlation analysis was used to analyze the correlation between total CSVD burden and blood pressure variability as well as total CSVD burden and serum VEGF concentrations.Finally,the correlation between serum VEGF levels and blood pressure variability was analyzed.Results A total of 144 patients with cerebral small vessel disease,72 males and 72 females,with a mean age of 66.4±9.8 years,21 in subgroup 0,35 in subgroup 1,30 in subgroup 2,36 in subgroup 3,and 28 in subgroup 4 were included in this study.There were significant differences in age and history of hypertension among the 5 groups(p=0.003,p=0.004).There were no significant differences in gender,diabetes mellitus,hyperlipidemia,history of smoking,history of alcohol consumption,BMI,total cholesterol,triglycerides,HDL and LDL cholesterol levels among the different groups.The differences of serum VEGF levels among the five groups were statistically significant(p<0.05),with the lowest mean concentration in subgroup 4 and the highest mean concentration in subgroup 3.24 h SBP(p<0.001),24 h SBP-SD(p=0.001),24 h SBPCV(p=0.009),24 h SBP-ARV(p=0.009),DSBP(p<0.001),DSBP-SD(p=0.033),DSBP-ARV(p=0.016),NSBP(p=0.001),NSBP-SD(p=0.026),SBP-w SD(p=0.013),24 h DBP(p=0.002),24 h DBP-SD(p=0.030),DDBP(p=0.001)and NDBP(p=0.03)were statistically different between the 5 groups of subjects.Total CSVD burden was significantly and positively correlated with 24 h SBP(r=0.331,p<0.001),24 h SBP-SD(r=0.337,p<0.001),24 h SBP-CV(r=0.214,p=0.01),24 h SBP-ARV(r=0.330,p<0.001),DSBP(r=0.346,p<0.001),DSBP-SD(r=0.241,p=0.004),DSBP-ARV(r=0.279,p=0.001),NSBP(r=0.241,p=0.001),NSBP-SD(r=0.200,p=0.016),SBP-w SD(r=0.312,p<0.001),24 h DBP(r=0.309,p<0.001),24 h DBPSD(r=0.241,p=0.004),DDBP(r=0.313,p<0.001)、and NDBP(r=0.235,p=0.005).In the group of patients with mild to moderate CSVD(total CSVD burden score 0-3),serum VEGF levels were significantly and positively correlated with total CSVD burden(r=0.386,p<0.001).There was no significant linear correlation between serum VEGF concentration and BPV in all groups of CSVD patients.In patients with mild CSVD,serum VEGF concentrations were mildly elevated,and BPV was mildly elevated.In patients with moderate CSVD,serum VEGF concentrations were significantly elevated,and 24 h SBP-SD,DSBP-SD,24 h DBP-SD,DDBP-SD,24 h SBP-CV,24 h DBP-CV,DSBP-ARV,DDBP-ARV,and DBP-w SD showed a more pronounced decrease.In patients with severe CSVD,serum VEGF concentration decreased significantly,and all BPV indicators increased significantly except NSBP-SD and NSBP-CV,which decreased.CSVD patients with a total load score of 0-2 had relatively mild disease,low degree of cerebral ischemia and hypoxia,and relatively weak promoting effect on the generation of VEGF.The ability of low concentration of VEGF to regulate BPV was weak,and BPV showed a slight upward trend.Due to the severe degree of intracranial ischemia and hypoxia,patients in group 3 had a strong promoting effect on the generation of VEGF,and the concentration of VEGF in serum was significantly increased.The higher concentration of VEGF had a greater ability to regulate BPV,leading to a relatively obvious decline in multiple BPV indexes of patients in Group 3.However,in CSVD patients in group 4,the degree of cerebral ischemia and hypoxia increased significantly,and larger BPV caused greater damage to endothelial cells in small cerebral vessels.Under the combined action of the two factors,vascular endothelial cells were destroyed in large quantities,and endothelial progenitor cells in circulating blood were consumed in large quantities in the early stage of the disease,and in the late stage of the disease,endothelial progenitor cells in circulating blood were relatively insufficient.Ultimately,the production of VEGF decreases sharply,resulting in significantly lower serum VEGF concentration in patients with severe CSVD than in patients with mild to moderate CSVD.Conclusion VEGF may delay the progression of CSVD by stabilizing blood supply to the brain,promoting the production of small blood vessels in the brain,and maintaining vascular endothelial cell function in the brain,thereby reducing the effects of blood pressure variability on CSVD patients.