Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China.
Sun yat sen university, Zhongshan school of medicine, Guangzhou, People's Republic of China.
Cardiovasc Diabetol. 2024 Nov 4;23(1):395. doi: 10.1186/s12933-024-02495-6.
Plasma ceramide plays a potentially significant role in the pathogenesis of coronary microvascular dysfunction. However, the relationship between plasma ceramide and coronary microvascular resistance in patients remains unclear. This study aimed to evaluate the association between plasma ceramide levels, as well as their distinct ratios, and coronary microvascular resistance.
This single-center observational study retrospectively enrolled patients who underwent both ceramide measurement and coronary angiography during hospitalization. The microvascular resistance of the coronary arteries was assessed in all patients using the angiography-derived index of microcirculatory resistance (Angio-IMR). The cumulative coronary microvascular resistance was calculated by summing the microvascular resistance of the three main coronary arteries. Multiple linear and logistic regression analyses were employed to evaluate the relationship between plasma ceramide and cumulative coronary microvascular resistance. Restricted cubic spline (RCS) analysis was conducted to investigate the association between plasma ceramide levels and cumulative coronary microvascular resistance. Receiver operating characteristic (ROC) curves were employed to evaluate the predictive value of plasma ceramide for coronary microvascular resistance. Additionally, subgroup analyses and interaction tests were performed.
A total of 225 patients were included in this study, with a median cumulative coronary microvascular resistance of 48.04 (40.32-56.73). After adjusting for potential confounding factors, both plasma 16:0 ceramide and the 16:0/24:0 ceramide ratio were positively associated with cumulative coronary microvascular resistance [standardized β ± standard error: 75.05 ± 8.46 (P < 0.001) and 91.72 ± 20.41 (P < 0.001), respectively]. Similar independent associations were observed in predicting high cumulative microvascular resistance [β = 8.03 ± 1.91 (P < 0.001) and 9.98 ± 3.88 (P = 0.010), respectively]. Additionally, a significant nonlinear relationship was observed between plasma 16:0 ceramide, the 16:0/24:0 ceramide ratio, and cumulative coronary microvascular resistance (P for nonlinear < 0.05). The ROC analysis revealed that the optimal cut-off for plasma 16:0 ceramide is 0.178 µmol/L, with a specificity of 57.1% and a sensitivity of 91.2%. For the 16:0/24:0 ceramide ratio, the optimal cut-off is 0.072, yielding a specificity of 73.2% and a sensitivity of 54.9%. Subgroup analysis indicated that the association between plasma ceramide and coronary microvascular resistance was trending toward non-significance in patients with acute coronary syndrome (ACS).
A significant nonlinear relationship exists between plasma ceramide and coronary microvascular resistance, which holds important clinical implications for the risk stratification of coronary microvascular disease. New insights into the potential effects of ceramides enhance our understanding of the complex mechanisms underlying coronary microvascular disease and warrant further investigation in a broader population.
血浆神经酰胺在冠状动脉微血管功能障碍的发病机制中可能具有重要作用。然而，血浆神经酰胺与冠状动脉微血管阻力之间的关系在患者中仍不清楚。本研究旨在评估血浆神经酰胺水平及其不同比值与冠状动脉微血管阻力之间的关系。
这是一项单中心观察性研究，回顾性纳入了在住院期间同时进行神经酰胺测量和冠状动脉造影的患者。所有患者均采用血管造影衍生的微血管阻力指数（Angio-IMR）评估冠状动脉的微血管阻力。通过将三支主要冠状动脉的微血管阻力相加来计算累积冠状动脉微血管阻力。采用多元线性和逻辑回归分析评估血浆神经酰胺与累积冠状动脉微血管阻力之间的关系。采用受限立方样条（RCS）分析评估血浆神经酰胺水平与累积冠状动脉微血管阻力之间的关系。采用受试者工作特征（ROC）曲线评估血浆神经酰胺对冠状动脉微血管阻力的预测价值。此外，还进行了亚组分析和交互检验。
本研究共纳入 225 例患者，累积冠状动脉微血管阻力中位数为 48.04（40.32-56.73）。在调整了潜在混杂因素后，血浆 16:0 神经酰胺和 16:0/24:0 神经酰胺比值均与累积冠状动脉微血管阻力呈正相关[标准化β±标准误：75.05±8.46（P<0.001）和 91.72±20.41（P<0.001）]。在预测高累积微血管阻力方面也观察到类似的独立相关性[β=8.03±1.91（P<0.001）和 9.98±3.88（P=0.010）]。此外，还观察到血浆 16:0 神经酰胺、16:0/24:0 神经酰胺比值与累积冠状动脉微血管阻力之间存在显著的非线性关系（P 非线性<0.05）。ROC 分析显示，血浆 16:0 神经酰胺的最佳截断值为 0.178 μmol/L，特异性为 57.1%，灵敏度为 91.2%。对于 16:0/24:0 神经酰胺比值，最佳截断值为 0.072，特异性为 73.2%，灵敏度为 54.9%。亚组分析表明，在急性冠状动脉综合征（ACS）患者中，血浆神经酰胺与冠状动脉微血管阻力之间的关系呈非显著趋势。
血浆神经酰胺与冠状动脉微血管阻力之间存在显著的非线性关系，这对冠状动脉微血管疾病的风险分层具有重要的临床意义。对神经酰胺潜在作用的新认识增强了我们对冠状动脉微血管疾病复杂机制的理解，并需要在更广泛的人群中进一步研究。
