Table_1_Threshold effect of plasma total homocysteine levels on cognitive function among hypertensive patients in China: A cross-sectional study.DOCX

BackgroundIncreased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China.
MethodsA total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function.
ResultsThis analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (β) per standard deviation (SD) increase: −0.26, 95% confidence interval (CI) −0.35, −0.16, P < 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 μmol/L. The effect size [β (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was −0.93 (−1.24, −0.6) on the left side and −0.07 (−0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was <0.001). Moreover, subgroup analyses revealed that sex could influence the negative association between plasma tHcy levels and MMSE scores up to a specific threshold (P-value for interaction <0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels and MMSE scores in female patients with tHcy concentrations less than 26.9 μmol/L compared to male patients with tHcy concentrations less than 32.0 μmol/L.
ConclusionsPlasma tHcy levels had a threshold effect on MMSE scores among hypertensive patients in China. Increased plasma tHcy levels were independently inversely associated with cognitive decline among hypertensive patients with tHcy concentrations <27.1 μmol/L.

【背景】血浆总同型半胱氨酸（plasma total homocysteine, tHcy）水平升高是普通人群认知障碍的影响因素。然而，针对高血压患者认知障碍风险与血浆tHcy水平之间关联的研究仍较为有限。本研究旨在探讨中国高血压患者血浆tHcy水平与通过简易精神状态检查表（Mini-Mental State Examination, MMSE）评分评估的认知功能之间的关联。
【方法】本研究共纳入来自中国高血压登记研究（Chinese Hypertension Registry Study）的9527名受试者。采用高效液相色谱法（high-performance liquid chromatography）结合荧光检测器（fluorescence detector）定量检测血浆tHcy水平。认知功能评估采用简易精神状态检查表（MMSE）完成。本研究通过线性回归模型、两种分段线性回归模型及平滑曲线拟合，分析血浆tHcy水平与认知功能之间的关联。
【结果】本次分析共纳入9527名中国成年高血压患者。线性回归模型结果显示，血浆tHcy水平与MMSE评分呈负相关[每标准差（standard deviation, SD）升高对应的β系数（beta coefficient, β）为-0.26，95%置信区间（confidence interval, CI）为-0.35~-0.16，P<0.001]。经完全校正的平滑曲线拟合结果显示，血浆tHcy水平与MMSE评分之间存在非线性关联。阈值效应分析显示，tHcy的拐点约为27.1 μmol/L。在拐点左侧，血浆tHcy浓度每升高1个SD，其对MMSE评分的效应量[β（95% CI）]为-0.93（-1.24~-0.6）；拐点右侧则为-0.07（-0.24~0.10）（对数似然比检验（log-likelihood ratio test, LLR）的P值<0.001）。此外，亚组分析显示，性别可影响血浆tHcy水平与MMSE评分之间的负相关关系至特定阈值（交互作用P值<0.001）。线性回归模型结果表明，当血浆tHcy浓度低于26.9 μmol/L时，女性患者中tHcy水平与MMSE评分的负相关强度高于tHcy浓度低于32.0 μmol/L的男性患者。
【结论】中国高血压患者的血浆tHcy水平对MMSE评分存在阈值效应。当血浆tHcy浓度<27.1 μmol/L时，血浆tHcy水平升高与高血压患者的认知衰退呈独立负相关。