探討類風溼性關節炎病患之傳統與非傳統心血管疾病危險因子

The Traditional and Non-traditional Risk Factors of Cardiovascular Disease in Patients with Rheumatoid Arthritis

黃詩茜(Shih-Chien Huang)

指導教授 ： 黃怡嘉

中山醫學大學/健康管理學院/營養學研究所/博士(2011年)

https://doi.org/10.6834/CSMU.2011.00117

摘要

本研究探討傳統與非傳統之心血管疾病危險因子對於類風濕性關節炎病患其內皮細胞功能受損與否之關係，以及給予類風濕性關節炎病患高劑量維生素B-6補充劑後，對於改善發炎反應與免疫功能之效應。本研究共募集43位類風濕性關節炎病患，測量其內皮細胞功能、血壓、血脂質、白蛋白、發炎指標、免疫功能指標、血漿同半胱胺酸、維生素B-6、維生素B-12及葉酸濃度。35位受試者接受隨機分派後，分別給予維生素B-6補充劑合併葉酸 (維生素B-6 100 mg/天合併葉酸 5 mg/天，n = 20) 或葉酸(5 mg/天，n = 15)，持續3個月。結果顯示內皮細胞功能異常之病患其收縮壓有顯著較高的情形。調整相關因子後，收縮壓為造成病患內皮細胞功能受損之最重要危險因子 (B= 20.7, P < 0.01)，同時也是預測病患內皮細胞功能受損之最佳指標 (AUC = 0.80; 95% CI, 0.65 – 0.94)。當病患收縮壓高於112 mmHg時，其內皮細胞功能受損之風險將會提高。當病患維生素B-6濃度缺乏時 (< 20 nmol/L)，其發炎反應與免疫功能指標顯著高於維生素B-6正常組，但並未發現病患血漿磷酸比哆醛濃度與發炎反應指標有相關性。若進一步調整血漿白蛋白濃度，血漿磷酸比哆醛濃度與免疫功能指標之相關性亦會隨之消失。若在不考慮病患血漿白蛋白濃度之下，給予病患高劑量維生素B-6介入12週後，結果顯示補充維生素B-6組，其血漿細胞介素-6與腫瘤壞死因子-a 濃度顯著低於第0週，並發現血漿細胞介素-6濃度與血漿磷酸比哆醛濃度成顯著負相關 (B = -0.01, P = 0.01)。為降低類風濕性關節炎病患罹患心血管疾病，應建議病患監控血壓變化。雖然本研究在調整血漿白蛋白濃度後，並未發現到血漿磷酸比哆醛濃度與發炎反應及免疫功能有關，但若給予病患高劑量維生素B-6介入後，可降低病患的前發炎反應。

關鍵字

類風濕性關節炎 ； 心血管疾病 ； 內皮細胞功能 ； 維生素B-6 ； 發炎反應 ； 收縮壓

並列摘要

The purposes of this study were to investigate traditional and non-traditional risk factors for cardiovascular disease (CVD) in relation to the endothelial function in patients with rheumatoid arthritis (RA); to determine which measure is a better predictive indicator for the risk of endothelial dysfunction in RA patients, and to study the effect of a high dose of vitamin B-6 on improving inflammatory and immune responses in RA patients. Forty-three RA patients (5 men, 38 women) participated in this study. Thirty-five patients were randomly allocated into either the control (5 mg/day folic acid only; n = 15) group or the vitamin B-6 (5 mg/day folic acid plus 100 mg/day vitamin B-6; n = 20) supplementation group for 12 weeks. Traditional (i.e., smoking, drinking, systolic and diastolic blood pressures and lipid profiles) and non-traditional risk factors [i.e., indicators of inflammatory and immune responses, plasma homocysteine and deficiency of B-vitamins (i.e., folate, vitamin B-6 and B-12)] for CVD were recorded or measured. The results showed systolic blood pressure (SBP) was significantly higher in RA patients with abnormal endothelial function. Among the risk factors being investigated, SBP was significantly associated with the degree of abnormal endothelial function (β = 20.7, P < 0.01) than RA patients with normal endothelial function after adjusting for potential confounders. SBP had the highest area under the receiver operating characteristic curve (AUC) (AUC = 0.80; 95% CI, 0.65-0.94) to predict the risk of endothelial dysfunction. Patients with vitamin B-6 deficiency [plasma pyridoxal 5’-phosphate (PLP) < 20 nmol/L] had significantly higher hs-CRP levels and immune parameters than did patients with adequate plasma PLP concentration. There was no significant association between plasma PLP levels and inflammatory parameters. The significant inverse correlation of plasma PLP with the numbers of white blood cell, neutrophils, total lymphocytes, T lymphocytes and T helper cells disappeared after serum albumin concentration was considered. Plasma IL-6 and TNF-α levels significantly decreased in patients receiving vitamin B-6 supplementation at week 12. In addition, the inverse association between plasma PLP and plasma IL-6 remained significant after adjusting for potential confounders (β = −0.01, P = 0.01). SBP could be a practical measure to screen the risk of endothelial dysfunction for patients with RA. Patients with RA should monitor their blood pressure in order to reduce the risk of CVD. RA patients with deficient plasma PLP concentration had more severe inflammatory and immune responses than did patients with adequate plasma PLP concentration. There is a lack of association of low plasma PLP concentration with inflammatory and immune parameters after serum albumin concentration was considered in patients with RA. Howener, a high dose vitamin B-6 supplementation may have suppressed pro-inflammatory cytokines in patients with RA.

並列關鍵字

Rheumatoid arthritis ； Cardiovascular disease ； Endothelial function ； Vitamin B-6 ； Inflammatory response ； Systolic blood pressure

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