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Clusterin/apolipoprotein J is independently associated with survival in patients with chronic heart failure
Lorenz Koller1, Bernhard Richter1, Max-Paul Winter1
1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria.
Insights
Decreasing levels of Clusterin (CLU) may indicate worsening chronic heart failure (HF). Lower CLU levels predict higher mortality risk in HF patients, suggesting CLU as a promising prognostic biomarker.
Area of Science:
- Biochemistry
- Cardiology
- Biomarker Discovery
Background:
- Clusterin/apolipoprotein J (CLU) is a glycoprotein with known cytoprotective properties.
- Experimental studies suggest CLU can prevent myocardial injury.
- Decreased CLU levels are hypothesized to correlate with chronic heart failure (HF) progression.
Purpose of the Study:
- To investigate the prognostic value of plasma CLU in patients diagnosed with HF.
- To determine if CLU levels can predict mortality risk in chronic HF patients.
Main Methods:
- Plasma CLU levels were measured in a cohort of 318 patients with chronic HF.
- The findings were validated in a second cohort of 346 patients with advanced HF.
- Survival analysis was performed, assessing mortality and cardiovascular events during follow-up.
Main Results:
- CLU was identified as an inverse predictor of all-cause mortality (HR 0.75) and cardiovascular mortality (HR 0.67).
- These associations remained significant after adjusting for established HF risk factors.
- Validation in the second cohort confirmed CLU as an independent prognosticator in chronic HF.
Conclusions:
- Evidence suggests CLU consumption is involved in HF pathophysiology.
- CLU shows potential as a novel and promising prognostic biomarker for patients with chronic HF.
Background:
Clusterin/apolipoprotein J (CLU) is a ubiquitous expressed glycoprotein with cytoprotective properties capable to prevent myocardial injury in experimental studies. We hypothesized that decreasing levels of CLU might be involved in progression of chronic heart failure (HF) and therefore represent a potential biomarker for prognosis in this vulnerable group of patient.
Objective:
We aimed to determine the prognostic value of plasma CLU in patients with HF.
Methods:
Plasma CLU levels were determined in a prospectively recruited cohort comprising 318 patients with chronic HF and validated in a second cohort comprising 346 patients with advanced HF.
Results:
During a median follow-up time of 3.2 years (interquartile range 2.0-4.9), 119 patients (37.3%) deceased including 83 patients (26.1%), who died from cardiovascular events. CLU was an inverse predictor of mortality with a crude hazard ratio (HR) per increase of 1 standard deviation (1 SD) of 0.75 (95% confidence interval [CI]: 0.62 to 0.9, P = .002) and specifically cardiovascular mortality with an HR per 1 SD of 0.67 (95% CI: 0.53-0.84, P < .001). CLU remained significantly associated with cardiovascular mortality after comprehensive adjustment for established HF-related risk factors and potential confounders with an adjusted HR per 1 SD of 0.79 (95% CI: 0.63-0.99, P = .042). Validation in the second cohort yielded similar results and confirmed CLU as independent prognosticator in patients with chronic HF.
Conclusion:
Our results point toward an ongoing consumption of CLU involved in the complex pathophysiology of HF and suggest CLU as novel and promising biomarker for prognosis in patients with chronic HF.