Supplementary data from: Fish intake and MRI burden of cerebrovascular disease in older adults

Background and Objective: Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers. Methods: This cross-sectional analysis included participants from the Three-City Dijon population-based cohort study (aged ≥65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with an automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure of CVD burden was defined as the first component of a factorial analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions. Results: In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factorial analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish less than once a week, those consuming fish 2 to 3 times per week and ≥4 times per week had a β = -0.19 units (95% CI, -0.37; -0.01) and β = -0.30 (-0.57; -0.03) lower indicator of global CVD burden, respectively (P for trend <0.001). We found evidence of effect modification by age, so that the association of fish to CVD was stronger in younger participants (65-69 years) and not significant in the older age group (≥75 years). For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in the opposite direction) to the effect of hypertension, and consuming fish ≥4 times had double that effect. Discussion: In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease.

研究背景与目的：鱼类摄入或可预防脑血管疾病（cerebrovascular disease, CVD），但其具体作用机制尚不明确，尤其在其对亚临床损害（subclinical damage）的影响方面。鉴于鱼类可能对脑血管健康具有多效性作用（pleiotropic effect），本研究基于脑磁共振成像（magnetic resonance imaging, MRI）标志物，探讨鱼类摄入与整体脑血管疾病负担的关联。
研究方法：本横断面分析纳入了三城第戎基于人群队列研究（Three-City Dijon population-based cohort study）中年龄≥65岁、无痴呆、卒中或住院心血管疾病病史的参与者，所有参与者均接受脑磁共振成像检查，包括白质高信号（white matter hyperintensities）的自动化评估、隐匿性脑梗死（covert infarcts）的视觉检测以及扩张血管周围间隙（dilated perivascular spaces）的分级评分。鱼类摄入情况通过频率问卷进行评估，脑血管疾病负担的主要结局指标定义为对MRI标志物进行混合数据因子分析（factorial analysis of mixed data）后得到的第一主成分。采用线性回归（linear regressions）分析鱼类摄入与脑血管疾病负担指标的关联。
研究结果：本研究共纳入1623名参与者，平均年龄72.3岁，女性占比63%。混合数据因子分析得到的第一主成分可解释32.4%的变异，其与三项MRI标志物的高水平均呈正相关。鱼类摄入频率越高，脑血管疾病负担越低。在校正总颅内体积的模型中，与每周吃鱼不足1次的参与者相比，每周吃鱼2~3次及≥4次的参与者其整体脑血管疾病负担指标分别低0.19个单位（95%置信区间（confidence interval, CI）：-0.37~-0.01）和0.30个单位（95%置信区间：-0.57~-0.03），趋势检验P<0.001。本研究发现年龄存在效应修饰（effect modification）作用：鱼类摄入与脑血管疾病的关联在较年轻参与者（65~69岁）中更为显著，而在≥75岁的老年组中无统计学意义。进一步对比显示，在较年轻组中，每周吃鱼2~3次的保护效应与高血压的不良效应大致相当（方向相反），每周吃鱼≥4次的保护效应则是前者的两倍。
讨论：本项大规模基于人群的研究显示，鱼类摄入频率越高，脑血管疾病负担越低，尤其在75岁以下的参与者中更为明显，这提示鱼类在显性脑疾病发生前即可对脑血管健康产生有益作用。