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Morphology and histology of silent and symptom-causing atherosclerotic carotid plaques – Rationale and design of the Helsinki Carotid Endarterectomy Study 2 (the HeCES2)

Krista NuotioMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland; Correspondence[email protected]

http://orcid.org/0000-0003-4588-050X View further author information

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Petra IjäsMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland;

http://orcid.org/0000-0002-7292-1971 View further author information

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Hanna M. HeikkiläMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland;

http://orcid.org/0000-0002-5718-7289 View further author information

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Suvi M. KoskinenClinicum, Department of Neurosciences, University of Helsinki, Helsinki, Finland; ;Department of Radiology, Hospital District of Helsinki and Uusimaa Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;

http://orcid.org/0000-0002-0000-8163 View further author information

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Jani SaksiMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland;

http://orcid.org/0000-0003-2833-9498 View further author information

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Pirkka VikatmaaAbdominal Center, Vascular Surgery, Helsinki University Hospital, Helsinki, Finland;

http://orcid.org/0000-0001-6426-8653 View further author information

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Pia SortoMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; View further author information

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Laura MäkitieMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland; View further author information

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Henrietta ErikssonMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland; View further author information

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Sonja KasariMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; View further author information

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Heli SilvennoinenDepartment of Radiology, Hospital District of Helsinki and Uusimaa Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;

http://orcid.org/0000-0003-3179-2859 View further author information

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Leena ValanneDepartment of Radiology, Hospital District of Helsinki and Uusimaa Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; View further author information

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Mikko I. MäyränpääDepartment of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland;

http://orcid.org/0000-0002-0877-9640 View further author information

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Petri T. KovanenWihuri Research Institute, Helsinki, FinlandView further author information

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Lauri SoinneMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland;

http://orcid.org/0000-0002-6831-5688 View further author information

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Perttu J. LindsbergMolecular Neurology, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; ;Department of Neurology, Helsinki University Hospital and Clinical Neurosciences, University of Helsinki, Helsinki, Finland;

http://orcid.org/0000-0001-7690-811X View further author information

Abstract

Introduction: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.

Materials and Methods: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses.

Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing “hot spot” area 53%.

Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis.

Key Messages

This article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.
The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment.
In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.

KEYWORDS:

Acknowledgments

Reeta Levo, Anita Mäkelä and Taru Puhakka are thanked for skilful technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by the grants from Academy of Finland, Paavo Nurmi Foundation, the Paulo Foundation, Päivikki and Sakari Sohlberg Foundation, Jane and Aatos Erkko foundation, Helsinki University Hospital District governmental research funds and the Finnish Medical Foundation. Wihuri Research Institute is maintained by the Jenny and Antti Wihuri Foundation.