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Early and sustained acute falls in total serum cholesterol are associated with critical illness mortality in the setting of tight glycaemic control

Dark, Paul; Buchan, Ian; Warhurst, Geoff; New, John; Gibson, Martin; Baker, Pat; Rudenski, Aram; Kemp, Stephen and Brass, Andy (2007) Early and sustained acute falls in total serum cholesterol are associated with critical illness mortality in the setting of tight glycaemic control. In: 7th World Congress on Trauma, Shock, Inflammation and Sepsis - Interdisciplinary Summit on Inflammation -TSIS 2007, 13-17 March 2007, Munich, Germany. (Unpublished)

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Abstract

To determine if rapidly-falling and low total serum cholesterol are independent risk factors for death in critically ill patients with tight glycaemic control. Methods: We performed a case cohort study of patients admitted to a 16 bed University Hospital intensive care between April and July 2006. Waived consent for anonymous data was approved by the NHS Central Office for Research Ethics Committees. Tight glycaemic control is the norm during critical care in our Unit. The testing of routine blood samples for lipid biochemistry was performed every morning on each critically ill patient admitted to our intenisve care. A random effects logistic regression model of mortality was used to accommodate the repeated biochemical measures - with the patient unique number as the panel variable. All statistical analysis was carried out using Sata version 9.2 (Stata Corp, College Station, Texas, US). Results are presented as the main effect with a 95% confidence interval unless stated otherwise. Results: 223 patients were studied - 137 men (mean age 54 years) and 86 women (mean age 57 years). 163 patients survived past 28 days and 65 died, of which 60 died in the intensive care unit. Mean APACHE II score was 16.1. Total serum cholesterol levels were 0.53 (0.21 to 0.86) mmol/l lower, on average across the days of admission, in those who died within 28 days compared with survivors. Differences were not present on admission. Furthermore, a rapid early fall in cholesterol predicted death. Total cholesterol across the first two recordings after admission fell by 0.17 (0.12 to 022) mmol/l in those who survived compared with 0.37 (0.31 to 0.45) mmol/l in those who died. This difference remained statistically significant (P < 0.001) after adjustment for age and gender. In models of mortality, low cholesterol remained a consistent and significant (P = 0.001) predictor of death, irrespective of adding potential confounders or effect modifiers, including age, gender, time from admission to blood test, and proxy indicators of pre-morbid organ dysfunction. HDL-cholesterol predicted death only from the second day after admission, and then much weaker (P = 0.04) than total cholesterol. Conclusions: Our study confirms that lower total serum cholesterol is associated with higher mortality in intensive care patients, and demonstrates this for the first time under strict euglycaemic conditions. Furthermore we have show that the early rate of decline in total serum cholesterol is the most discriminating factor. We can not assert whether or not the association between mortality and cholesterol decline is causal. There is, however, emerging evidence from animal studies that cross-talk between nuclear factors may induce a positive feedback state of increasing inflammation and lowering cholesterol. Whether the cholesterol level changes are causal, or result from inflammatory mediators, is difficult to determine from observational studies; therefore we are currently exploring interventional studies in animal models. This work could lead to novel therapeutics in critical illness and challenge the use of lipid lowering therapies in patients with life-threatening inflammatory states. Therefore, until the mechanisms are better understood, it may be that any intervention that may further lower cholesterol in critically ill patients should be used with caution.

Item Type:Conference or Workshop Item (Other)
Uncontrolled Keywords:Mortality; Control; Inflammation; methods; Blood; Model; Number; analysis; Levels; Level; Difference; Models; Time; ASSOCIATION; Animal; Mechanism
Subjects:R Medicine > R Medicine (General)
Q Science > QH Natural history > QH426 Genetics
Q Science > QH Natural history > QH301 Biology
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Science > Department of Biological Sciences
Related URLs:
Refereed:No
Status:Unpublished
ID Code:331
Deposited On:20 Apr 2010 15:06
Last Modified:20 May 2011 17:13

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