中年系统性炎症、晚年白质完整性与脑小血管疾病：社区动脉粥样硬化风险研究
Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study.
作者信息
Walker Keenan A, Power Melinda C, Hoogeveen Ron C, Folsom Aaron R, Ballantyne Christie M, Knopman David S, Windham B Gwen, Selvin Elizabeth, Jack Clifford R, Gottesman Rebecca F
机构信息
From the Department of Neurology (K.A.W., R.F.G.) and Department of Internal Medicine (E.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health (M.C.P.); Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.); Center for Cardiovascular Disease Prevention, Houston Methodist DeBakey Heart and Vascular Center, TX (R.C.H., C.M.B.); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.); Department of Neurology (D.S.K.) and Department of Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Department of Medicine, University of Mississippi Medical Center, Jackson (B.G.W.); and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (R.F.G., E.S.).
出版信息
Stroke. 2017 Dec;48(12):3196-3202. doi: 10.1161/STROKEAHA.117.018675. Epub 2017 Nov 3.
BACKGROUND AND PURPOSE
It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.
METHODS
Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspecific marker of inflammation-and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.
RESULTS
We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (-0.09 SD; 95% confidence interval, -0.15 to -0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03-0.15) in deep WM and lower fractional anisotropy (-0.07 SD; 95% confidence interval, -0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants ( interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.
CONCLUSIONS
Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.
背景与目的
目前尚不清楚中年时期的全身炎症是否会促进老年人白质（WM）异常和小血管疾病的发展。在一项双种族前瞻性队列研究中，我们研究了中年时期全身炎症与晚年WM高信号体积、深部和脑室周围WM微观结构完整性（分数各向异性和平均扩散率[MD]）、脑梗死及微出血之间的关联。
方法
在社区动脉粥样硬化风险研究中，采用线性和逻辑回归分析中年时期高敏C反应蛋白（CRP）——一种非特异性炎症标志物——与21年后评估的脑磁共振成像标志物之间的关系。
结果
我们纳入了1485名参与者（基线年龄56[5]岁；28%为黑人）。在调整人口统计学因素和心血管疾病后，中年CRP每增加1个标准差，深部WM的分数各向异性降低（-0.09标准差；95%置信区间，-0.15至-0.02），MD增加（0.08标准差；95%置信区间，0.03 - 0.15），脑室周围WM的分数各向异性降低（-0.07标准差；95%置信区间，-0.13至0.00）。我们发现黑人参与者中CRP与脑室周围WM微观结构完整性之间的关联更强（交互作用=0.011）。虽然在我们的初步分析中，仅在ε4阳性参与者中发现较高的CRP水平与更大的WM高信号体积之间存在关联（0.14标准差；95%置信区间，0.01 - 0.26；交互作用=0.028），但在考虑差异失访后，这种关系扩展至整个样本。中年CRP与晚年脑梗死或微出血的存在无关。
结论
我们的研究结果支持以下假设，即中年时期的全身炎症可能促进老年人慢性微血管结构性WM异常的发展。
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