An observational study to establish the cardiovascular-renal-metabolism comorbidity epidemiology and healthcare utilisation in England

Date of ISAC Approval: 
Lay Summary: 
The widespread presence of heart and kidney (cardiorenal) diseases in patients with type 2 diabetes mellitus has led to a broader disease management goal of reducing adverse clinical complications and death in these patients. The likely course of development of cardiorenal conditions is very important. This has a substantial impact on the choice of medications used to treat type 2 diabetes and the intensity of blood sugar control measures required to achieve optimum levels. In a time of emerging treatment options for type 2 diabetes that may offer benefits but also pose risks based on the precise combination of heart and kidney conditions, there is an increasing need to understand the interactions between diabetes and these combinations of diseases in clinical practice. Work to date include associations between type 2 diabetes and mainly diseases affecting the heart and blood vessels, otherwise known as cardiovascular diseases. However, this does not take into account kidney disease as an established risk factor for complications, including how disease progression pathways may increase risks of cardiorenal disease, death and impact health care resource use in these patients. Therefore, to provide answers to these specific questions, this study will use administrative healthcare records to describe populations of patients with unique combinations and patterns of appearance of cardiorenal diseases over time in order to establish their association with adverse clinical outcomes and death.
Technical Summary: 
It is increasingly being recognised there are commonalities between cardiovascular, renal and metabolic (CaReMe) diseases with clinical overlap between these diseases and their associated complications.1, 2 Although these relationships between disorders are increasingly being elucidated there is often under-recognition by health care professionals and patients and this contributes to patients being managed for conditions in isolation.3 These relationships are increasingly important as therapies develop that could address multiple aspects of disease outcomes and may be used across this spectrum of disorders. Using a cohort of prevalent T2D patients, we will examine the incidence of cardiorenal diseases, their patterns of appearance over time, and subsequent association with adverse clinical outcomes such as cardiovascular (CV) and all-cause mortality. This study will utilise the CPRD Aurum database and the study period will begin on 1 April 2007 and will end on 31 March 2019. Each of the clinical outcomes of interest will be described separately. Event rates and 95% CIs will be reported as both incidence risks and incidence rates. Survival distributions utilising Kaplan-Meir method will describe time to cardiorenal disease progression, time to CV- and all-cause mortality. Relative risks and risk factors associated with outcomes will be estimated using Cox proportional hazard models. In addition, we aim to further highlight the impact of comorbidities on health care resource utilisation. Using a cohort of incident T2D patients, we will examine the care pathways of the patients to describe health resource use including GP consultations, laboratory tests or measurements, medication, referrals to specialist and hospital admissions. Such evidence will be used to highlight any unmet treatment needs and inform the current literature gap in this area.
Health Outcomes to be Measured: 
The study outcomes are aligned to the core objectives of this study and described in two work packages (WP). WP1 - Development of cardiorenal events in 'cardiorenal disease-free' T2D patients Primary outcomes include first hospitalisations for heart failure (HF) chronic kidney disease (CKD) peripheral artery disease (PAD), myocardial infarction (MI) and Stroke (cardiorenal events) in 'cardiorenal diseases-free' T2D population. Secondary outcomes include manifestations of cardiorenal events, CV mortality and all-cause mortality following hospitalisation for specified diseases; associated risk factors. WP2 - Healthcare resource utilisation (HRU) Supplementary outcomes include proportions of T2D patients with unique combinations of cardiorenal events, health care resource use and monetised costs of resource use; resources include disease management services in the clinical guideline, e.g., GP consultations, laboratory tests or measurements, medications, hospitalisations, etc.

Jil Billy Mamza - Chief Investigator - Astra Zeneca Ltd - UK Headquarters
Dr Amitava Banerjee - Collaborator - University College London (UCL)
Betina Blak - Collaborator - Astra Zeneca Ltd - UK Headquarters
Dr George Godfrey - Collaborator - Astra Zeneca Ltd - UK Headquarters
Jil Billy Mamza - Corresponding Applicant - Astra Zeneca Ltd - UK Headquarters
Dr Johan Bodegård - Collaborator - Astra Zeneca Inc - USA
Mr Mike Ford - Collaborator - Astra Zeneca Ltd - UK Headquarters
Dr Rob Hastings - Collaborator - Astra Zeneca Ltd - UK Headquarters
Ms Rui Qi Zhang - Collaborator - Astra Zeneca Ltd - UK Headquarters
Tamsin Morris - Collaborator - Astra Zeneca Ltd - UK Headquarters
Una Rigney - Collaborator - Astra Zeneca Ltd - UK Headquarters

HES A&E;HES Admitted;HES Outpatient;ONS;Patient IMD;Practice IMD (Standard)