Can hyperuricemia predict the progression risk of cerebral small vessel disease?

ABSTRACT

Aims

Uric acid (UA) may play a crucial role in the process of cerebral small vessel disease (SVD), but few follow-up studies have focused on the effect of UA in the progression of SVD. The present study aimed to ascertain whether serum UA levels are associated with the risk of SVD progression.

Methods

We performed an observational clinical study in adults older than 45 years with cranial magnetic resonance imaging (MRI) from 30 October 2015, to 28 January 2021. The patients were divided into two groups according to whether their total burden of SVD scores increased or not during the follow-up: SVD progression (increased by at least one point) and without SVD progression (increased 0 points). Cox regression and Kaplan–Meier survival analyses were used for univariate analysis between groups to identify the risk factors for SVD progression.

Results

Ultimately, 261 eligible patients were included in the final analysis. Of the 261 eligible patients, 73 were included in the SVD progression group, and 188 were included in the group without SVD progression. Correlation analysis found that the levels of UA and the ratio of hyperuricemia (HUA) showed statistically significant correlations with SVD progression risk (r = 0.197 and Crammer’s V = 0.213, respectively, P < 0.01). Cox regression and Kaplan–Meier survival analyses showed that after adjustment for covariates, HUA was an independent risk factor for the incidence of SVD progression. The risk of SVD progression in patients with HUA was higher than that in those without HUA (HR (95% CI), 1.77 (1.03–3.05), P < 0.05).

Conclusions

High serum UA levels are independently related to the risk of SVD progression, thus highlighting not only the influence of traditional risk factors such as hypertension and age on SVD but also the UA levels of patients for individualized treatment.

KEYWORDS:

• Cerebral small vessel disease
• Uric acid levels
• progression risk
• burden
• MRI markers

Abbreviations

BMI, Body mass index; CMBs, Cerebral microbleeds; Cr, Creatinine; SVD, Cerebral small vascular disease; FBG, Glucose fasting blood glucose; FLAIR, Fluid-attenuated inversion recovery; HbA1c: Glycosylated hemoglobin; H-CRP, High-sensitivity C-reactive protein; LDL-C, Low-density lipoprotein cholesterol; Lp (a), Lipoprotein a; Lp-PLA2, Lipoprotein-associated phospholipase A2; MRI, Magnetic resonance imaging; PVS, Perivascular spaces; SWI, Susceptibility weighted imaging; TC, Total cholesterol; TG, Triglycerides; UA, Uric acid; WMH, White matter hyperintensity. HUA, Hyperuricemia; P-WMLs, Periventricular cerebral white matter lesions; CSF, cerebrospinal fluid.

Authors’ contributions

XMC contributed to the study design. Data collection was performed by LW, JYJ and YK. YHY, QD, and XRY were responsible for data analysis. The manuscript was written by CSW. All authors approved the final manuscript for publication.

Availability of data and materials

Study data are available from the corresponding author upon request.

Ethics approval and consent to participate

We obtained ethical approval for this study from the ethics committee of the Affiliated Jiangning Hospital with Nanjing Medical University. Written informed consent was obtained from all study participants.

Contribution to the field statement

SVD causes 25% of strokes and contributes to 45% of dementia cases. The prevalence increases with age, affecting approximately 5% of people aged 50 years and increasing to almost 100% of people older than 90 years. Known risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. However, these risk factors are only able to partially explain the occurrence and development of SVD; therefore, more predictors of SVD progression need to be explored. Our findings reveal that high serum UA levels are independently related to the risk of SVD progression and provide more evidence for the prevention and treatment of SVD.

Disclosure statement

None.

Additional information

Funding

This research was supported by the clinical medical science and technology development fund of Jiangsu University (JLY2021153); and the Nanjing Medical Science and Technique Development Foundation(YKK20203).