Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study.

INTRODUCTION

Coronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show a quarter of patients have disease in the absence of any known risk factor, and half have only one risk factor. Improvements in quantification and characterisation of coronary atherosclerosis by CT coronary angiography (CTCA) can provide quantitative measures of subclinical atherosclerosis-enhancing the power of unbiased 'omics' studies to unravel the missing biology of personal susceptibility, identify new biomarkers for early diagnosis and to suggest new targeted therapeutics.

METHODS AND ANALYSIS

BioHEART-CT is a longitudinal, prospective cohort study, aiming to recruit 5000 adult patients undergoing clinically indicated CTCA. After informed consent, patient data, blood samples and CTCA imaging data are recorded. Follow-up for all patients is conducted 1 month after recruitment, and then annually for the life of the study. CTCA data provide volumetric quantification of total calcified and non-calcified plaque, which will be assessed using established and novel scoring systems. Comprehensive molecular phenotyping will be performed using state-of-the-art genomics, metabolomics, proteomics and immunophenotyping. Complex network and machine learning approaches will be applied to biological and clinical datasets to identify novel pathophysiological pathways and to prioritise new biomarkers. Discovery analysis will be performed in the first 1000 patients of BioHEART-CT, with validation analysis in the following 4000 patients. Outcome data will be used to build improved risk models for CAD.

ETHICS AND DISSEMINATION

The study protocol has been approved by the human research ethics committee of North Shore Local Health District in Sydney, Australia. All findings will be published in peer-reviewed journals or at scientific conferences.

TRIAL REGISTRATION NUMBER

ACTRN12618001322224.