Association Between Renal Function And Risk Of Intracranial Atherosclerotic Stenosis

Background: At present,arising mortality and disability rates was attributed to ischemic stroke with the increasing aging population.Intracranial atherosclerotic stenosis(ICAS)as the most common cause of ischemic stroke,has become the interest target for early management in public prevention.It is necessary to identify and reduce risk factors associated with ICAS in stroke prevention.ICAS is considered a marker of extensive cerebrovascular and systemic atherosclerosis.Advanced age,metabolic syndrome,diabetes,hypertension,and dyslipidemia are deemed to be linked with a high incidence of ICAS.These factors mostly affect the vascular structure and function through oxidative stress,hemodynamic instability,decreasing antioxidant enzymes and fibrinolytic activity,degrading the buffering capacity of arterial walls,aggregating platelets,and elevating activity of sympathetic and renin-angiotensin-aldosterone systems.Mounting evidence supports that chronic renal disease induces various pathogenic patterns,such as oxidative stress,inflammation,vascular calcification,and formation of uremic toxins,thus damaging blood vessels.Few studies have looked at the relationship between renal function and ICAS.The purpose of this study was to investigate the correlation between renal function indicators,including estimated glomerular filtration rate(eGFR),serum creatinine(Scr),blood urea nitrogen(BUN),and ICAS,and whether renal function indicators can be used as potential biomarkers of ICAS.Methods: The study prospectively recruited 1244 participants according to strict inclusion and exclusion criteria.All parameters The participants were all Han Chinese over 40 years old.According to Warfarin Aspirin Symptomatic Intracranial Disease(WASID)test criteria,the presence of ICAS was defined as intracranial artery(including internal carotid artery)stenosis or occlusion ≥50% and vascular lesions consistent with atherosclerotic changes.Multivariate Logistic regression was used to analyze the correlation between renal function indicators and ICAS,and all models were corrected for associated risk factors(univariate Logistic regression P<0.05).Furthermore,the relationship between renal function and the number of intracranial stenosis groups was further analyzed.All statistical analyses were performed using R software(version 4.0.4)and Graph Pad Prism(version 8.02)for statistical analysis and data visualization.The significance level for each analysis was set at P<0.05.Results: A total of 1244 participants(median(IQR)age,68.0 years and 44.8% females)were included in this study,including 272 ICAS patients and 972 non-ICAS subjects(NICAS).Participant characteristics are shown in Table 1.Compared with the NICAS group,individuals with ICAS were older and prone to develop alcohol habits and higher levels of FBG(P<0.05).No significant differences in the prevalence of hypertension and the proportion of smokers were observed between the two groups.Poorer renal function as reflected by higher levels of Scr(P=0.008)and BUN(P=0.003)and lower levels of eGFR(P=0.001)was observed in patients with ICAS than those in the NICAS group(Figure 1).Of the 272 ICAS participants,only 260 had statistically relevant stenosis,181(69.6 %)had 1 stenosis,79(30.4 %)had ≥ 2 stenoses.The multivariableadjusted model indicated that individuals with the highest quintile levels of Scr and BUN had 1.946 folds(OR,1.946;95% CI,1.173-3.230;P=0.010)and 1.710 folds(OR,1.710 95% CI,1.101-2.656;P=0.017)risks of ICAS respectively when compared to those with the highest quintile levels.In accord,the poorest renal function measured as the lowest quartile level of e GRF was substantially associated with the highest risk of ICAS(OR,1.565;95% CI,1.025-2.389;P=0.038).Multinomial logistic regression was performed to examine the association between renal function and the presence of stenoses.Compared with participants with Scr ≤56.15umol/L,those with Scr ≥83.33umol/L has 1.818 times elevated odds(95% CI 1.002-3.300)of having 1 vs 0stenosis in fully adjusted model and 2.894 times elevated odds(95% CI 1.184-7.077)for having ≥2 vs 0 stenosis.BUN(assessed as continuous variables)was associated with presence of ≥2 stenoses(OR 1.162,95% CI 1.058-1.276)but not with 1 stenosis.In addition,decreased eGFR(assessed as continuous variables)was associated with presence of ≥2 stenoses(OR 1.011,95% CI 1.001-1.022).Conclusions: In summary,our study found that elevated Scr,BUN levels and decreased eGFR level were associated with high risk of ICAS.These results could offer evidence that renal function might play a important role in the etiology of atherosclerosis.It further confirmed the importance of renal function management in early prevention of ICAS.Further prospective clinical studies are needed to clarify the physiological and pathological role of renal function in ICAS.