Drs. Maurovich-Horvat, Bosserdt, and Kofoed contributed equally to this article. This article was published on March 4, 2022, at NEJM.org.

We sought to analyse plasma levels of peripheral blood microRNAs (miRs) as biomarkers of ST-segmentelevation myocardial infarction (STEMI) due to type-1 myocardial infarction as a model situation of vulnerable plaque (VP) rupture. Samples of 20 patients with STEMI were compared both with a group of patients without angina pectoris in whom coronary angiogram did not reveal coronary atherosclerotic disease (no coronary atherosclerosis-NCA) and a group of patients with stable angina pectoris and at least one significant coronary artery stenosis (stable coronary artery disease-SCAD). This study design allowed us to identify miRs deregulated in the setting of acute coronary artery occlusion due to VP rupture. Based on an initial large scale miR assay screening, we selected a total of 12 miRs (three study miRs and nine controls) that were tested in the study. Two of the study miRs (miR-331 and miR-151-3p) significantly distinguished STEMI patients from the control groups, while ROC analysis confirmed their suitability as biomarkers. Importantly, this was observed in patients presenting early with STEMI, even before the markers of myocardial necrosis (cardiac troponin I, miR-208 and miR-499) were elevated, which suggests that the origin of miR-331 and miR-151-3p might be in the VP. In conclusion, the study provides two novel biomarkers observed in STEMI, which may be associated with plaque rupture. Rupture of a vulnerable atherosclerotic plaque (VP), which leads to acute artery occlusion due to an overlying thrombosis, is a potentially devastating situation resulting in acute coronary syndromes (ACS), ischaemic stroke and other acute complications of atherosclerosis 1-5. Early detection of VP in vivo is essential for effective primary prevention of their rupture, which might aid in the reduction of cardiovascular morbidity and mortality 6. A potent biomarker that would be sensitive enough for the presence of a VP with a reasonable specificity could be a very important piece of this puzzle. MicroRNAs (miRs) are small, non-coding RNA molecules that act as modifiers of gene expression 7-9. Once they bind to their target mRNA, they may cause its degradation or suppression of its translation 7-9. Thus, miRs control many cellular processes and play a role in the pathogenesis of various diseases that include atherosclerosis 7-9. The molecules are very stable, easy to detect with quantitative polymerase chain reaction (qPCR) and are relatively tissue specific 9-12. Due to these properties, miRs appear to be very suitable biomarkers. The aim of this study was to identify plasma miRs from peripheral blood samples of patients with ST-segment-elevation myocardial infarction (STEMI) that might help quicken its diagnostics or may even be used directly as markers of VP. Such biomarkers might be used for the risk stratification of patients and both aid in tailoring the primary preventive measures and help as prognostic markers in patients with clinically manifested atherosclerosis.

Limited insights into the pathophysiology of the atherosclerotic carotid stenosis are available in vivo. We conducted a prospective study to assess safety and feasibility of intravascular ultrasound (IVUS) combined with near-infrared spectroscopy (NIRS) in carotid arteries. In addition, we described the size and the distribution of lipid rich plaques in significant atherosclerotic carotid stenoses. In a prospective single centre study 45 consecutive patients (mean age 66 ± 8 years) with symptomatic (≥50 %) or asymptomatic (≥70 %) stenosis of internal carotid artery (ICA) amendable to carotid stenting were enrolled. A 40 mm long NIRS-IVUS pullback through the stenosis was performed. IVUS and NIRS data were analyzed to assess minimal luminal area (MLA), plaque burden (PB), remodeling index (RI), calcifications, lipid core burden index (LCBI), maximal LCBI in any 4 mm segment of the artery (LCBImx) and LCBI in the 4 mm segment at the site of minimal luminal area (LCBImxMLA). NIRS-IVUS pullbacks were safely performed without overt clinical events. LCBImx was significantly higher than LCBImxMLA (369.1 ± 221.1 vs. 215.7 ± 2589; p = 0.004). Conversely, PB was significantly larger at the site of MLA (87.4 ± 4.8 % vs. 58.3 ± 18.2 %; p < 0001). Distance of the NIRS-IVUS frame with the highest LCBI from the site of MLA was 6.5 ± 7.7 mm. Eighty percent of frames with maximal LCBI were localized within 10 mm from the site of MLA and 67 % proximally to or at the site of MLA. This study suggested safety and feasibility of the NIRS-IVUS imaging of the carotid stenosis and provided insights on the distribution of lipids in the carotid stenosis. Lipid rich plaques were more often located in the sites with a milder stenosis and smaller plaque burden than at the site of MLA.