Information for health professionals

What is the C3 Study?

The C3 Study is a large retrospective observational cohort study of patients admitted to intensive care units between 2006 and 2023.

It has obtained approval from the Health Research Authority (HRA) under advice from the Confidentiality Advisory Group (CAG) in accordance with Section 251 of the NHS Act 2006.

The cardiovascular consequences of critical illness

The mortality of patients who survive a period of treatment on an ICU is significantly higher than an age and sex matched general population. This excess mortality risk persists for at least two years after ICU discharge. To an extent, this is to be expected as patients may have a condition that was related both to their critical illness and an increase in their long-term risk of death, such as chronic lung disease or cancer. However, there is evidence of a high rate of major adverse cardiovascular events (MACE – nonfatal stroke, nonfatal myocardial infarction, heart failure and cardiovascular death) amongst ICU survivors who had critical illnesses unrelated to cardiovascular disease.

The aim of the project is to create a powerful data resource that can be used to predict adverse cardiovascular outcomes both on and after leaving the unit. 

We hope the study will provide new knowledge about the associations between baseline cardiovascular risk, the disease resulting in ICU admission and therapies / events on ICU with subsequent MACE events, to allow the ongoing risk of these events to be determined. If we know who is at risk, then we can potentially modify known risk factors.

Study methods

We will study patients admitted to intensive care units at a selection of NHS trusts in the UK. Data will be collected and de-identified automatically using tailored software at each recruiting site. We will link these patient records with NHS Digital at source. The linkage with NHS digital will allow us to gather information from other de-identified/pseudo-anonymous databases containing information about patient outcomes including, but not limited to, Office of National Statistics (ONS), Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR).

What we hope to learn

Understanding the problem

Using our novel dataset, we will be able to describe our at-risk population in unprecedented detail, in terms of demographics, physiological performance, treatments and long-term outcomes/events both fatal and non-fatal. We will also be able to make meaningful comparisons in terms of event rates between different populations (UK, USA, Europe) and specific subgroups (sepsis, emergency surgery, trauma).

Additional analyses will include examining the relationship between poor cardiac performance during critical illness, cardiac performance assessed by echocardiography and subsequent mortality or MACE events.

Predicting risk

The rich dataset containing detailed in-ICU variables alongside long-term outcomes will will provide a unique opportunity to increase our understanding of cardiovascular risk.

Based on the best available evidence major adverse cardiovascular events occur at least 40% more often in the survivors of critical illness than a similar age and sex matched population. We hope to identify in-ICU factors that are associated with increased risk of MACE events.

Identifying high-risk patients will allow for targeted follow-up and risk-management after ICU discharge.

Furthermore, highlighting and addressing modifiable risk factors in ICU may improve long-term outcomes in this vulnerable group.