Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy -
Unit of Microbiology and Diagnostic Immunology, Bambino Gesù Children's Hospital, Rome, Italy.
Minerva Med. 2023 Jun;114(3):289-299. doi: 10.23736/S0026-4806.22.07778-3. Epub 2022 Oct 18.
Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. As cytomegalovirus (CMV) may contribute to cardio-vascular (CV) manifestations, we sought to provide a proof-of-concept for the involvement of coronary and/or systemic CMV-reactivation as a possible ACS trigger.
We prospectively enrolled consecutive patients undergoing a coronary angiography for ACS (acute-cases, N.=136), or non-ACS reasons (chronic-cases, N.=57). Matched coronary and peripheral blood-samples were processed for quantification of CMV-DNAemia (RT-PCR), CMV-IgG/IgM, and CMV-IgG avidity (ELISA). Peripheral-blood samples from 17 healthy subjects were included as controls.
Out of the 193 cases included, 18.1% were aged ≤55 years, 92.5% were Central-European, and 100% immunocompetent. CMV-IgG seroprevalence was 91.7% (95%CI: 87.8-95.6), significantly higher than in healthy-controls (52.9% [95%CI: 29.2-76.5]; P<0.001), yet consistent across age-groups (P=0.602), male/females (P=0.765), and acute/chronic-cases (P=0.157). Median (IQR) IgG titers were 110 (84-163) AU/mL, with 0.62 (0.52-0.72) avidity, supporting a long history of infection. No acute CMV infections were found. In 22.6% (n/N.=40/177) of the IgG-positive cases low-level coronary and/or systemic CMV-DNAemia (always <40 copies/mL) was detected. While no differences in peripheral CMV-DNAemia prevalence were observed nor among cases nor controls, coronary CMV-DNAemia was more frequent in acute-cases without modifiable CV risk-factors (n/N.=4/10; 40.0%), than in chronic-cases (n/N.=6/55, 10.9%; P=0.029), or acute-cases with risk-factors (n/N.=16/112, 14.3%; P=0.058).
CMV-IgG seroprevalence was high in patients with heart diseases. CMV-DNAemia can be found, although uncommonly, in coronary circulation during an ACS, with increased prevalence in older subjects and in absence of CV risk-factors, identifying possible areas for novel interventions.
急性冠状动脉综合征(ACS)是发病率和死亡率的主要原因。巨细胞病毒(CMV)可能导致心血管(CV)表现,我们试图为冠状动脉和/或全身 CMV 再激活作为可能的 ACS 触发因素提供一个概念验证。
我们前瞻性地招募了因 ACS(急性病例,N=136)或非 ACS 原因(慢性病例,N=57)而行冠状动脉造影的连续患者。对匹配的冠状动脉和外周血样本进行巨细胞病毒 DNAemia(RT-PCR)、巨细胞病毒 IgG/IgM 和巨细胞病毒 IgG 亲和力(ELISA)的定量。将 17 名健康受试者的外周血样本作为对照纳入。
在纳入的 193 例病例中,18.1%的年龄≤55 岁,92.5%为中欧人,100%免疫功能正常。巨细胞病毒 IgG 血清阳性率为 91.7%(95%CI:87.8-95.6),明显高于健康对照组(52.9% [95%CI:29.2-76.5];P<0.001),但在年龄组(P=0.602)、男性/女性(P=0.765)和急性/慢性病例(P=0.157)中无差异。IgG 滴度中位数(IQR)为 110(84-163)AU/mL,亲和力为 0.62(0.52-0.72),支持长期感染。未发现急性巨细胞病毒感染。在 22.6%(n/N.=40/177)的 IgG 阳性病例中,检测到低水平的冠状动脉和/或全身巨细胞病毒 DNAemia(始终<40 拷贝/mL)。尽管在病例和对照组中均未观察到外周巨细胞病毒 DNAemia 的患病率差异,也未观察到病例组和对照组之间的差异,但在无可改变的心血管危险因素的急性病例(n/N.=4/10;40.0%)中,冠状动脉巨细胞病毒 DNAemia 更为常见,而在慢性病例(n/N.=6/55,10.9%;P=0.029)或有危险因素的急性病例(n/N.=16/112,14.3%;P=0.058)中更为常见。
患有心脏病的患者中 CMV IgG 血清阳性率较高。虽然罕见,但在 ACS 期间可在冠状动脉循环中发现 CMV-DNAemia,其在老年患者和无心血管危险因素的情况下更为常见,这可能为新的干预措施提供了潜在目标。