From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences University of Oxford, United Kingdom (B.L., K.K.L., L.L., C.L., W.K., P.M.R.); and Department of Neurology, Cerebrovascular Centre, West China Hospital, Sichuan University (B.L., M.L.).
Stroke. 2018 Apr;49(4):899-904. doi: 10.1161/STROKEAHA.117.019650. Epub 2018 Mar 9.
It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age.
In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent).
Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69-2.75; <0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69-9.32; =0.002; 60-79 years: OR, 1.01; 95% CI, 0.72-1.41; =0.963; ≥80 years: OR, 0.95; 95% CI, 0.59-1.54; =0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56-1.02; =0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21-7.98; =0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but were strongest for cerebral microbleeds (OR, 5.84; 95% CI, 1.45-23.53; =0.013) and moderate-severe periventricular white matter hyperintensities (OR, 6.28; 95% CI, 1.54-25.63; =0.010).
The association of renal impairment and cerebral SVD was attenuated with adjustment for shared risk factors at older ages, but remained at younger ages, consistent with a shared susceptibility to premature disease.
据推测，脑小血管疾病（SVD）和慢性肾功能不全可能是多种小血管疾病的一部分，但它们的关联可能只是由于共同的风险因素（如高血压），而不是对过早 SVD 的系统性易感性。然而，大多数先前的研究都是基于医院的，大多数研究对高血压的调整不足，许多研究仅限于腔隙性卒中患者，且均未按年龄分层。
在一项短暂性脑缺血发作和缺血性卒中（OXVASC [牛津血管研究]）的基于人群的研究中，我们评估了 SVD 的磁共振成像标志物，包括腔隙、白质高信号、脑微出血和扩大的血管周围间隙。我们研究了肾功能不全（估计肾小球滤过率<60 mL/min/1.73 m）和总 SVD 负担（总 SVD 评分）在调整年龄、性别、血管危险因素和发病前血压（事件前 15 年期间的平均血压）后的年龄特异性相关性。
在 1080 例连续患者中，1028 例（95.2%）具有完整的磁共振成像方案和基线时的肌酐测量值。肾功能不全与总 SVD 评分相关（比值比[OR]，2.16；95%置信区间[CI]，1.69-2.75；<0.001），但仅在年龄<60 岁时（<60 岁：OR，3.97；95%CI，1.69-9.32；=0.002；60-79 岁：OR，1.01；95%CI，0.72-1.41；=0.963；≥80 岁：OR，0.95；95%CI，0.59-1.54；=0.832）。调整年龄、性别、高血压史、糖尿病和发病前平均收缩压后，肾功能不全与总 SVD 评分的总体相关性减弱（调整 OR，0.76；95%CI，0.56-1.02；=0.067），但<60 岁时肾功能不全和总 SVD 评分的独立相关性仍然存在（调整 OR，3.11；95%CI，1.21-7.98；=0.018）。<60 岁时，肾功能不全与 SVD 的相关性在每个 SVD 标志物上均一致，但与脑微出血（OR，5.84；95%CI，1.45-23.53；=0.013）和中度至重度脑室周围白质高信号（OR，6.28；95%CI，1.54-25.63；=0.010）的相关性最强。
在调整年龄较大时的共同风险因素后，肾功能不全与脑 SVD 的相关性减弱，但在年龄较小的情况下仍然存在，这与对早期疾病的共同易感性一致。
