Cheng Xuehua, Peng Ting, Han Li
Department of Traditional Chinese Medicine (TCM) Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China.
Department of Neonatology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, PR China.
J Stroke Cerebrovasc Dis. 2025 Aug;34(8):108373. doi: 10.1016/j.jstrokecerebrovasdis.2025.108373. Epub 2025 Jun 7.
BACKGROUND: Stroke is a common fatal and disabling disease in the elderly. We investigated the correlation and potential benefits of dietary intake of flavonoid compounds and their subclasses in elderly stroke patients. METHODS: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) for the cycles 2007-2010 and 2017-2018. Dietary flavonoids intake was calculated based on food frequency questionnaires (FFQ) through a 24-hour dietary recall. To explore the relationship between flavonoids intake and their subclasses with stroke prevalence, we employed multivariable logistic regression models, adjusting for relevant covariates. Restricted cubic splines (RCS) and generalized additive models (GAMs) were applied to explore potential nonlinear relationships between flavonols subclasses and stroke prevalence. Multivariable logistic regression models were conducted both for the overall population and stratified by flavonols subclasses intake. Additionally, we utilized Bayesian kernel machine regression (BKMR) to evaluate the overall effect of flavonols intake levels on stroke status, accounting for potential interaction and correlation between subclasses. Given the high correlation among flavonols subclasses, we incorporated a hierarchical variable selection approach using a Markov Chain Monte Carlo (MCMC) algorithm. Finally, we analyzed the XGBoost model by applying SHAP (SHapley Additive exPlanations) values to assess the specific contribution of different flavonoids intake to stroke. RESULTS: Including 3,806 elderly stroke patients, the study revealed an inverse relationship between dietary flavonoids and their subclasses and stroke prevalence. After adjusting for potential confounders, it was found that higher quartiles of flavonols intake were associated with lower stroke prevalence. Specifically, with each unit increase in flavonols (Q4) intake, the odds of stroke in the elderly decreased by 61 % (OR=0.390, 95 % CI [0.209-0.728]; P = 0.005). Similar results were observed for the subclasses of flavonols. Subgroup analyses indicated that age and poverty index ratio (PIR) were effect modifiers in the relationship between flavonols intake and stroke. We further examined the intake levels of dietary flavonols subclasses such as isorhamnetin, kaempferol, myricetin, and quercetin and their association with stroke status stratified by population characteristics. In addition to age and PIR, hyperlipidemia and body mass index (BMI) were found to be the most common significant influencing factors in the relationship between flavonols subclasses and stroke prevalence. Furthermore, RCS revealed a "U"-shaped nonlinear relationship between flavonols, including their quercetin and kaempferol subclasses, and stroke, whereas the relationship between stroke and myricetin was linear. Our study also assessed the overall impact of dietary flavonols subclasses on stroke in the elderly and the interrelationships among these subclasses. The results consistently indicated a negative joint effect of flavonols subclass mixtures on the stroke status in the elderly. When evaluating the impact of individual flavonols subclasses on stroke status, a potential dose-response relationship was observed, with increasing intake of myricetin being associated with a decreased risk of stroke. Furthermore, SHAP plots show that flavonols intake is predominantly associated with negative SHAP values, indicating that higher dietary flavonols intake corresponds to a lower predicted stroke risk. CONCLUSION: These results emphasize that adhering to an increased dietary intake of flavonoid compounds, particularly flavonols and their subclasses such as myricetin, is inversely associated with the prevalence of stroke among the U.S. elderly population. This offers potential benefits for stroke patients, especially among elderly individuals aged 60-70 and those with higher incomes.
背景:中风是老年人常见的致命性和致残性疾病。我们研究了老年中风患者膳食中类黄酮化合物及其亚类的摄入量与中风之间的相关性和潜在益处。 方法:本研究分析了2007 - 2010年和2017 - 2018年国家健康与营养检查调查(NHANES)的数据。通过24小时膳食回顾,基于食物频率问卷(FFQ)计算膳食类黄酮摄入量。为了探究类黄酮摄入量及其亚类与中风患病率之间的关系,我们采用多变量逻辑回归模型,并对相关协变量进行了调整。应用受限立方样条(RCS)和广义相加模型(GAMs)来探究黄酮醇亚类与中风患病率之间潜在的非线性关系。针对总体人群以及按黄酮醇亚类摄入量分层的人群分别进行多变量逻辑回归模型分析。此外,我们利用贝叶斯核机器回归(BKMR)来评估黄酮醇摄入量水平对中风状态的总体影响,同时考虑亚类之间潜在的相互作用和相关性。鉴于黄酮醇亚类之间的高度相关性,我们采用马尔可夫链蒙特卡罗(MCMC)算法纳入分层变量选择方法。最后,我们通过应用SHAP(SHapley Additive exPlanations)值分析XGBoost模型,以评估不同类黄酮摄入量对中风的具体贡献。 结果:该研究纳入了3806名老年中风患者,结果显示膳食类黄酮及其亚类与中风患病率呈负相关。在调整潜在混杂因素后,发现黄酮醇摄入量处于较高四分位数与较低的中风患病率相关。具体而言,黄酮醇(Q4)摄入量每增加一个单位,老年人中风的几率降低61%(OR = 0.390,95% CI [0.209 - 0.728];P = 0.005)。黄酮醇的亚类也观察到类似结果。亚组分析表明,年龄和贫困指数比(PIR)是黄酮醇摄入量与中风关系中的效应修饰因素。我们进一步研究了异鼠李素、山奈酚、杨梅素和槲皮素等膳食黄酮醇亚类的摄入量及其与按人群特征分层的中风状态之间的关联。除年龄和PIR外,高脂血症和体重指数(BMI)被发现是黄酮醇亚类与中风患病率关系中最常见的显著影响因素。此外,RCS显示黄酮醇(包括其槲皮素和山奈酚亚类)与中风之间呈“U”形非线性关系,而中风与杨梅素之间的关系是线性的。我们的研究还评估了膳食黄酮醇亚类对老年人中风的总体影响以及这些亚类之间的相互关系。结果一致表明黄酮醇亚类混合物对老年人中风状态具有负向联合效应。在评估单个黄酮醇亚类对中风状态的影响时,观察到潜在的剂量反应关系,杨梅素摄入量增加与中风风险降低相关。此外,SHAP图显示黄酮醇摄入量主要与负的SHAP值相关,表明较高的膳食黄酮醇摄入量对应较低的中风预测风险。 结论:这些结果强调,坚持增加膳食中类黄酮化合物的摄入量,特别是黄酮醇及其亚类如杨梅素,与美国老年人群中风患病率呈负相关。这为中风患者带来潜在益处,尤其是在60 - 70岁的老年人和收入较高的人群中。
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