Title: Long-term cardiovascular outcomes among survivors of critical illness
Funder: Department of Health and Social Care

Abstract: Research questions What is the incidence of major adverse cardiovascular events (MACE) after ICU care in the UK? What is the association between pre-ICU (baseline) risk, acute illnesses, cardiovascular therapies, and MACE events? Can we predict which patients will experience MACE events up to several years after leaving ICU?Background Critical illness may be associated with a considerable increase in fatal and non-fatal major adverse cardiovascular events (MACE, predominantly strokes and myocardial infarctions), for years after an ICU admission. Using a combination of existing and novel databases, I will study associations between patient factors, ICU care and long-term MACE events in very large numbers of patients. Aim The aim of my fellowship is to understand the associations between baseline cardiovascular risk, the disease resulting in ICU admission and therapies on ICU with subsequent MACE events. This would allow targeted primary and secondary preventative treatments. Objectives Systematically review the existing literature Determine the incidence of MACE events following care on UK ICUs using the RISK-II database Build a new database containing cardiovascular risk factors at ICU admission, the admission diagnosis, cardiovascular therapies on ICU and long term (including MACE) outcomes Use this database to determine the associations between these risk factors and future MACE events Examine the associations found to identify potential ways to reduce future MACE events and build a predictive model of future MACE events.Methods After a systematic literature review, I will undertake a new analysis of the NIHR funded RISK-II database (14/19/06). This contains details from the ICNARC Case Mix Program[4], as well as mortality, cause of death and Hospital Episode Statistics (HES) data for nearly a million admissions to nearly all UK ICUs since 2006. I will determine the incidence of MACE events post ICU care and compare this to age and sex matched figures from national statistics. I will create a new database containing highly detailed physiological and treatment data from computerised information systems (CIS) on 3 different local ICUs. These data will be linked to HES, ONS (Office of National Statistics) databases and the National Cardiovascular Outcomes Research (NICOR) databases. This will allow the associations between long-term MACE events, baseline risk, disease process and cardiovascular therapies to be studied in unprecedented detail. I will also use causal inference techniques to further analyse the response of the effect variable when the cause is changed. Using this novel dataset, I will develop and test techniques to identify patients at greatest risk of MACE events to 2 years post ICU care. Timelines The literature review will be complete by month 6, with RISK-II analysis delivered in the first year. Database construction and linkage will occupy the second year with analysis and write-up of the thesis taking place in the third. The new database will also serve as a data source for my post-doctoral research. Impact and dissemination I will publish open access papers quantifying the problem and describing associations between MACE events and ICU treatment. I will present at European specialist meetings and engage ICU ex-patient groups.

Lay abstract: Background Intensive care units (ICU) support critically ill patients who would otherwise succumb to their illnesses. Historically the benefit of ICU care to patients has been measured as survival. However, over the last three decades, survival of patients admitted to ICU has improved markedly, so more attention is being focussed on the long-term health problems related to ICU care in survivors. Many of these problems significantly affect patients' lives. The associations to the ICU stay are poorly understood, partly because they can occur many years later.I will study one important group of conditions that are common after treatment on an ICU - strokes and diseases of the heart and blood vessels. There is evidence from other countries that these may be more common after care on an ICU.The high number of strokes and heart attacks after ICU care may result from the patients underlying illnesses and also the long-term effects of ICU treatments for low blood pressure and circulation during critical illness.Currently we are unable to identify which patients are at risk of heart attacks and strokes. We need to understand who is at risk. There are well-established treatments to avoid these conditions in the community. This research will help decide who should be considered for these treatments after critical illness. Aim The aim of my fellowship will be to find out which patients are at risk of heart attacks/strokes up to several years after discharge from an ICU. I will also study how much the treatment the patients received on ICU contributes to this risk. Objectives Conduct a detailed review of what has been written in this area Find out how many patients suffer strokes/heart attacks after ICU care in the UK Work out which diseases and ICU treatments make heart attacks/strokes more likely Determine which patients are at greatest risk of heart attacks/strokes up to several years after leaving ICUDesign and methods We will use a ~1 million-patient database of patients treated on all UK ICUs since 2006 (RISK-II) to find out how many have had heart attacks/strokes after ICU care. We will use UK government statistics to find out how many heart attacks/strokes occur in patients not admitted to ICUs as a comparator. I will need to create a new database to look at which patients are more likely to get heart attacks/strokes after ICU care, as the RISK-II database does not contain details on management whilst on ICU. ICUs are technologically advanced areas in hospitals, and patients' vital signs, treatments and blood tests are often electronically recorded as part of normal care.By linking these highly detailed ICU records with NHS long-term follow-up data, we can unpick what factors increase patients' long-term risks and identify patients at highest risk of having heart attacks/strokes years after ICU care. Patient and public involvement All my ICU projects benefit from advice and help from our Oxford ICU Patients' Forum, who are very familiar with record-based research. For this project, I have developed a PPI strategy with help from our Research Design Service and presented it to the Forum, who were very supportive, expressing surprise that this research was not done routinely.Dissemination I will publish the results in scientific papers freely available on the internet. I will work with the charity 'ICUsteps', the Intensive Care Society's patient group, and our local ICU group to publicise results to ex-patients. We will share our findings through talks at conferences, social media, interviews and press releases.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR;STROKE