Abnormal cells may predict impending heart attack

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MedWire News: Patients with acute ST-segment elevation myocardial infarction (STEMI) have an excess of large, misshapen circulating endothelial cells (CECs), which may be used as a biomarker for arterial injury, US researchers report.

Study leader Eric Topol (The Scripps Research Institute, La Jolla, California) and colleagues explain that “acute myocardial infarction, which involves the rupture of existing atheromatous plaque, remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease.”

They say a clinical measurement that can identify individuals at greatest risk for MI is therefore desperately needed.

Elevated levels of CECs have previously been associated with acute coronary syndromes, but so far they have not routinely been measured in clinical practice because of the lack of a practical, widely-accepted technique.

In the present study, Topol and team characterized CECs from 50 consecutive patients with STEMI and 44 consecutive healthy controls using a commercially available cell isolation platform combined with three-channel fluorescence microscopy assay.

They report in Science Translational Medicine that CEC counts were significantly elevated in STEMI cases compared with controls, with median numbers of 19 versus 4 cells/mL, respectively.

Of note, no correlation was observed between CECs and typical markers of myocardial necrosis, namely creatine kinasemyocardial band and troponin.

A receiver-operating characteristic (ROC) curve analysis showed that CEC count was highly accurate at distinguishing STEMI from control patients, with an area under the ROC curve of 0.95.

At a cutoff of 9 CECs/mL, CEC count predicted STEMI with a sensitivity of 90% and a specificity of 93%. Increasing the cutoff to 16.5 CECs/mL increased the specificity to 98%, but at the expense of a reduced sensitivity (60%).

To further characterize the morphologic features of CECs from STEMI patients and controls, the team performed a detailed computational analysis of the fluorescent images.

They observed that the mean cellular area of CECs from STEMI patients was a significant 2.7-fold higher than that in CECs from younger healthy controls, age-matched individuals, as well as CECs obtained from patients with preexisting peripheral vascular disease. Similarly, there was significant twofold increase in nuclear area of MI CECs versus control CECs.

Furthermore, STEMI patients were the only group with CEC images that contained more than three nuclei per image, indicating that multicellular and multinuclear clusters are specific for acute STEMI, say Topol et al.

They comment that their method – which is equivalent to a fluid-phase biopsy of the coronary artery – “provides a unique window into the disease from the precise cells that are being shed as a result of injury to inflamed arterial segments.”

The team concludes that their findings “may ultimately support the development of an assay to help predict imminent risk of a heart attack.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

Sci Transl Med 2012; 4: 126ra33

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