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- Materials and Methods
©2012 Wiley Periodicals, Inc.
Heat shock protein 60 (HSP60) is a mitochondrial protein constitutively expressed in the majority of cells, and its expression is up-regulated by a variety of stressors. In heart failure, HSP60 is released from cardiomyocytes. The authors speculate that increased serum HSP60 (sHSP60) may be related to the severity of heart failure. This investigation sought to assess the association between sHSP60 and the composite end point of death/readmission in patients with acute heart failure (AHF). A total of 132 consecutive patients were admitted for AHF. The independent association between sHSP60 and the end point was assessed with Cox regression. During a median follow-up of 7 months (interquartile range, 3–14), 35 (26.5%) deaths, 40 (30.3%) readmissions, and 65 (49.2%) deaths/readmission were identified. Patients who exhibited the outcome showed higher median sHSP60 values (6.15 ng/mL [8.49] vs 4.71 ng/mL [7.55] P=.010). A monotonic increase in the incidence of the composite end point was observed when moving from lower to higher tertile (4.74, 4.76, and 6.98 per 10 patients-years of follow-up, P for trend <.001). After adjusting for established risk factors, only patients in the upper tertile showed an increased risk of death/readmission (hazard ratio, 2.63; 95% confidence interval, 1.29–5.37; P=.008). In patients with AHF, high sHSP60 was related to a higher risk for subsequent death/readmission for AHF.
Heat shock protein 60 (HSP60) is an intracellular protein constitutively expressed in the majority of cells. Although primarily located inside the mitochondria, 15% to 20% of HSP60 has been found in the cytosol.1,2 Its expression is up-regulated by a variety of stressors such as infection, anoxia, oxidative stress, and inflammation. It has a protective role against stress-induced injury by maintaining cellular homeostasis and 3-dimensional structure of proteins.1–4 HSP60 has been reported to translocate to the myocardial cell surface before being released into the plasma in patients with heart failure (HF).5,6 In fact, increased levels of HSP60 in plasma membrane and serum HSP60 (sHSP60) in rat and human failing hearts have paradoxically been associated with an increase in myocardial apoptosis (measured by caspase activation and DNA fragmentation) and immune modulation due to its antigenic role.7,8
Detectable sHSP60 levels have been reported in healthy control human patients9,10 and patients with cardiovascular diseases (diabetes and coronary heart disease).11–14 Various studies have shown that sHSP60 levels have been associated with unfavorable psychosocial measures (socioeconomic status, psychological distress, and social isolation), proinflammatory status (increase of tumor necrosis factor α [TNF-α]),9 atherosclerosis burden,12 endothelial dysfunction (flow-mediated vasodilatation assessment), and higher risk of coronary heart disease,10–14 suggesting an important role in the activation of vascular cells and the immune system.
In patients with advanced chronic heart failure (CHF), sHSP60 was related to the severity of the disease and associated with a high risk of cardiac events.15 Nevertheless, no studies have examined the clinical implications of sHSP60 during an acute phase of the disease. Therefore, we sought in this study to evaluate whether sHSP60 was associated with the risk of the composite end point of death/readmission for acute heart failure (AHF) in a nonselected sample of patients admitted for AHF.