Westergren Helena U, Michaëlsson Erik, Blomster Juuso I, Miliotis Tasso, Svedlund Sara, Gan Li-Ming
Department of Molecular and Clinical Medicine, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
AstraZeneca R&D, Gothenburg, Sweden.
PLoS One. 2017 Apr 27;12(4):e0176511. doi: 10.1371/journal.pone.0176511. eCollection 2017.
Microvascular dysfunction could be responsible for chest pain in patients without myocardial perfusion defects. We evaluated microvascular function using ultrasound-assessed coronary flow reserve (CFR) in patients with chest pain and normal myocardial perfusion scintigram. Secondly, we investigated association between cardiovascular parameters and decreased CFR in a sex specific manner.
A total of 202 (128 women) non-diabetic patients with chest pain and suspected myocardial ischemia, but without myocardial perfusion defects on myocardial perfusion scintigram, were enrolled and underwent CFR examination and blood sampling. All patients were followed-up for cardiovascular events. We used a supervised principal component analysis including 66 variables such as clinical parameters, ongoing medication, coronary artery disease history, lipids, metabolic parameters, inflammatory and other cardiovascular parameters.
During a median follow-up time of 5.4 years, 25 cardiovascular events occurred; (men;18, women;7). Average CFR of the study cohort was 2.7±1.2 and 14% showed impaired CFR<2.0. In an adjusted Cox regression analysis, CFR<2.0 independently predicted event-free survival (HR:2.5, p = 0.033). In the supervised principal component analysis high insulin resistance assessed by Homeostatic model assessment for insulin resistance was the strongest biochemical marker associated with decreased CFR. Interestingly, upon sex specific multivariable linear regression analysis, the association was only significant in men (β = -0.132, p = 0.041) while systolic blood pressure remained an independent predictor in women (β = -0.009, p = 0.011).
In non-diabetic patients with chest pain without myocardial perfusion defects, low CFR has prognostic value for future cardiovascular events. Insulin resistance appears to be a marker for decreased CFR in men. Indeed, in the context of contribution of traditional risk factors in this patient population, the value of systolic blood pressure seems to be important in the women.
微血管功能障碍可能是无心肌灌注缺损患者胸痛的原因。我们使用超声评估的冠状动脉血流储备（CFR）来评估胸痛且心肌灌注显像正常患者的微血管功能。其次，我们以性别特异性方式研究心血管参数与CFR降低之间的关联。
共纳入202例（128例女性）非糖尿病胸痛患者，这些患者疑似心肌缺血，但心肌灌注显像无心肌灌注缺损，他们接受了CFR检查和血液采样。所有患者均接受心血管事件随访。我们使用了一种监督主成分分析，包括66个变量，如临床参数、正在服用的药物、冠心病病史、血脂、代谢参数、炎症及其他心血管参数。
在中位随访时间5.4年期间，发生了25例心血管事件；（男性18例，女性7例）。研究队列的平均CFR为2.7±1.2，14%的患者CFR受损<2.0。在调整后的Cox回归分析中，CFR<2.0独立预测无事件生存（HR：2.5，p = 0.033）。在监督主成分分析中，通过稳态模型评估胰岛素抵抗评估的高胰岛素抵抗是与CFR降低相关的最强生化标志物。有趣的是，在性别特异性多变量线性回归分析中，这种关联仅在男性中显著（β = -0.132，p = 0.041），而收缩压在女性中仍然是独立预测因子（β = -0.009，p = 0.011）。
在无心肌灌注缺损的非糖尿病胸痛患者中，低CFR对未来心血管事件具有预后价值。胰岛素抵抗似乎是男性CFR降低的标志物。实际上，在该患者群体中传统危险因素的作用背景下，收缩压在女性中似乎很重要。
