冠心病患者血清维生素水平与同型半胱氨酸水平的相关性及后者与PON1活性、冠状动脉粥样硬化严重程度的关联

Correlation between serum vitamin levels and homocysteine level in patients with coronary heart disease, and association of homocysteine level with PON1 activity and severity of coronary atherosclerosis

摘要:

目的]采用横断面研究设计,分析冠心病患者血清B族维生素(B₁、B₂、B₆、B₉、B₁₂)水平与同型半胱氨酸(HCY)水平的相关性,并进一步探究HCY水平与对氧磷酶1(PON1)活性、高密度脂蛋白胆固醇(HDLC)水平及冠状动脉病变严重程度(Gensini评分)的关联。 [方法]选取2022年3月—2024年1月昆明医科大学第六附属医院(玉溪市人民医院)心内科收治的390例冠心病患者为研究对象。采用高效液相色谱-串联质谱法检测血清B族维生素水平,循环酶法检测血清HCY水平,对氧磷底物法测定PON1活性,酶法检测HDLC水平,免疫比浊法检测载脂蛋白A1(ApoA1)水平。按血清HCY水平分为3组:参照组(LHCY组,HCY＜15.00 μmol/L,n＝45)、中度升高组(MHCY组,15.00 μmol/L≤HCY＜30.00 μmol/L,n＝271)、重度升高组(HHCY组,HCY≥30.00 μmol/L,n＝74)。所有患者行冠状动脉造影后计算Gensini评分。采用非参数检验、Spearman相关分析及多元线性回归分析各指标间的关联。 [结果]HHCY组血清维生素B₁水平较LHCY组降低23.1%、较MHCY组降低14.6%,维生素B₁₂水平较LHCY组降低27.9%、较MHCY组降低22.7%(均P＜0.05)；而维生素B₂、B₆、B₉水平在三组间差异均无统计学意义(均P＞0.05)。HHCY组PON1活性较LHCY组降低12.7%,HDLC水平较LHCY组降低15.3%(均P＜0.01)；HHCY组Gensini评分较LHCY组升高103.6%(P＜0.001)。Spearman相关分析显示,血清HCY水平与维生素B₁(r＝－0.108,P＝0.033)、维生素B₁₂(r＝－0.193,P＜0.001)、PON1活性(r＝－0.243,P＜0.001)、HDLC(r＝－0.490,P＜0.001)均呈显著负相关,与Gensini评分呈显著正相关(r＝0.382,P＜0.001)。校正年龄、性别、体重指数、血脂等混杂因素后,HCY每升高10 μmol/L,PON1活性降低4.8%(95%CI:－6.4%～－3.2%,P＜0.001),HDLC降低0.07 mmol/L(95%CI:－0.10～－0.04,P＜0.001)。 [结论]冠心病患者中,仅血清维生素B₁、B₁₂水平与HCY呈显著负相关(维生素B₂、B₆、B₉未见显著关联)；高HCY水平与PON1活性降低、HDLC水平下降及Gensini评分升高显著相关,提示高HCY血症可能通过影响PON1-HDL抗氧化通路参与冠状动脉粥样硬化进展。

Abstract:

Aim A cross-sectional study was used to analyze the correlations between serum levels of B vitamins (B₁, B₂, B₆, B₉, B₁₂) and homocysteine (HCY) level in patients with coronary heart disease (CHD). Furthermore, the associations were explored between HCY level and paraoxonase 1 (PON1) activity, high density lipoprotein cholesterol (HDLC) level, as well as the severity of coronary artery lesions (Gensini score). Methods A total of 390 patients with CHD admitted to the Department of Cardiology at the Sixth Affiliated Hospital of Kunming Medical University (Yuxi People's Hospital) from March 2022 to January 2024 were selected as study subjects. Serum levels of B vitamins were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), serum HCY level was determined by a circulating enzyme assay, PON1 activity was assessed via the paraoxon substrate method, HDLC level was measured enzymatically, and apolipoprotein A1 (ApoA1) level was detected by immunoturbidimetric assay. Patients were divided into three groups based on serum HCY levels:reference group (LHCY group, HCY＜15.00 μmol/L, n＝45), moderately elevated group (MHCY group, 15.00 μmol/L≤HCY＜30.00 μmol/L, n＝271), and severely elevated group (HHCY group, HCY≥30.00 μmol/L, n＝74). All patients underwent coronary angiography followed by calculation of the Gensini score. Nonparametric tests, Spearman correlation analysis, and multiple linear regression analysis were employed to examine the associations between various parameters. Results Serum vitamin B₁ levels of the HHCY group decreased by 23.1% compared with the LHCY group and by 14.6% compared with the MHCY group, while vitamin B₁₂ levels decreased by 27.9% compared with the LHCY group and by 22.7% compared with the MHCY group (all P＜0.05). No statistically significant differences were observed in vitamin B₂, B₆, or B₉ levels among the three groups (all P＞0.05). PON1 activity of the HHCY group was reduced by 12.7% compared with the LHCY group, and HDLC level decreased by 15.3% (both P＜0.01); however, the Gensini scores of the HHCY group were elevated by 103.6% compared with the LHCY group (P＜0.001). Spearman correlation analysis revealed that serum HCY level was significantly negatively correlated with vitamin B₁ (r＝－0.108, P＝0.033), vitamin B₁₂ (r＝－0.193, P＜0.001), PON1 activity (r＝－0.243, P＜0.001), and HDLC (r＝－0.490, P＜0.001), while it was significantly positively correlated with the Gensini score (r＝0.382, P＜0.001). After adjusting for confounding factors such as age, gender, body mass index, and blood lipid levels,each 10 μmol/L increase in HCY was associated with a 4.8% reduction in PON1 activity (95%CI:－6.4%～－3.2%, P＜0.001) and a 0.07 mmol/L decrease in HDLC (95%CI:－0.10～－0.04, P＜0.001). Conclusion Among CHD patients, only serum levels of vitamin B₁ and B₁₂ were significantly negatively correlated with HCY, whereas no significant associations were observed for vitamin B₂, B₆ and B₉. Elevated HCY level was significantly associated with reduced PON1 activity, decreased HDLC level, and increased Gensini score, suggesting that hyperhomocysteinemia may contribute to the progression of coronary atherosclerosis by affecting the PON1-HDL antioxidant pathway.