Relationships between the Serum Cholesterol Levels, Production of Monocyte Proinflammatory Cytokines and Long-term Prognosis in Patients with Chronic Heart Failure

Abstract

Objective Low serum cholesterol is associated with a poor prognosis in patients with chronic heart failure (CHF). However, the relationships between the serum cholesterol level, production of monocyte proinflammatory cytokines and long-term prognosis in CHF patients remain unclear. Methods A total of 95 CHF patients who had not been treated with statins and had a mean left ventricular ejection fraction of 26.0±6.0% were examined. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured and expressed as the mean ± SD (pg/mL/10 6 PBMCs). Results The production of monocyte TNF-α and IL-6 was found to be significantly and negatively associated with the serum low-density lipoprotein (LDL)-cholesterol level (TNF-α: r=-0.515, p<0.001, IL-6: r= -0.419, p<0.001). During a median follow-up of 66.0 months, 49 patients developed cardiac events, including 21 cardiac deaths and 28 readmissions for worsening CHF. A multivariate Cox hazard analysis showed that a monocyte TNF-α level of ! 4.9 pg/mL/10 6 PBMCs [hazard ratio (HR) 187.38, 95% confidence interval (CI) 7. 92-4,434.94, p=0.001] and LDL-cholesterol level of <120 mg/dL (HR 9.41, 95% CI 1.02-86.66, p=0.048) were independently associated with the incidence of cardiac events. Conclusion Low LDL-cholesterol and the upregulation of monocyte proinflammatory cytokine production are both significantly and independently associated with poor outcomes in CHF patients.

Nutritional Status is Associated with Inflammation and Predicts a Poor Outcome in Patients with Chronic Heart Failure

“…PEM and inflammation are also strongly associated with one another and may each independently contribute to hypoalbuminemia and cachexia in patients with CHF 1) . These data suggest that malnutrition associated with inflammation may contribute to the pathogenesis and development of p 0.001) 23) . These data suggest that the upregulation of monocyte TNF-production may be, in part, because of increases in LPS from the plasma.…”

“…In our previous study, the endotoxin (LPS) levels were measured in 20 normal subjects and 40 patients with CHF 23) . The endotoxin levels in patients with CHF (median: 30.5 pg/mL, range: 11.0 -95.2 pg/mL) were significantly higher than those observed in normal subjects (median: 11.8 pg/mL; range 10.2 -18.9 pg/mL, p 0.001).…”

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

“…The pro-inflammatory profile becomes strategic throughout the lifespan (8)(9)(10)(11) -an increase of cytokine secretion, also thought to be associated with the influence of CMV-infection, may be at least partly responsible for age-associated degenerative disorders (12)(13)(14)(15)(16). Previous studies usually investigated individual roles of different cytokines, inflammatory mediators or metabolic factors in the age-related physiological alterations (17)(18)(19)(20)(21). With growing numbers of biomarkers, however, it may become difficult to interpret results and translate them into useful information.…”

Relationship among IL-6, LDL cholesterol and lipid peroxidation

“…Previous studies reported a significant reduction in serum cholesterol levels during episodes of acute myocardial infarction (AMI) [2], as a result of major surgery, and during acute infections [3]. The significant inverse correlation between cholesterol and interleukin-6 (IL-6) [4] might suggest an active role of IL-6 in changes in serum lipoprotein levels. This effect on serum total cholesterol (TC) was also observed after systemic infusion of cytokines in animal models [5].…”