HDL Cholesterol and CVD Mortality in Hemodialysis Patients
HDL Cholesterol and CVD Mortality in Hemodialysis Patients
Background High-density lipoprotein (HDL) confers protection against atherosclerosis by several different mechanisms. Although in the general population, increasing levels of HDL are associated with reduced cardiovascular (CV) mortality, this association is not well known in patients with chronic disease states such as end-stage renal disease. We hypothesize that the association of serum HDL concentration and its ratio to total cholesterol with all-cause and CV mortality in hemodialysis patients is different from the general population.
Methods A 3-year (July 2004 to June 2007) cohort of 33 109 chronic hemodialysis patients was studied in the USA in the dialysis clinics where lipid profile was measured in at least 50% of all outpatients of the clinic during a given calendar quarter. Cox proportional hazard models were adjusted for demographics and case–mix variables and cubic splines were plotted.
Results Higher HDL concentrations up to 50 mg/dL were associated with better overall survival, while HDL at 60 mg/dL and above was associated with a rise in all-cause and CV mortality. All-cause and CV mortality hazard ratio was 1.28 (1.20–1.38) and 1.08 (1.01–1.16) for HDL <30 mg/dL and 1.05 (1.00–1.10) and 1.08 (1.00–1.16) for HDL ≥ 60 mg/dL, respectively (reference: HDL: 30–<60 mg/dL).
Conclusions In contrast to the general population, low total cholesterol to HDL ratio was associated with higher mortality in hemodialysis patients. A U-shaped association between HDL cholesterol level and all-cause and CV mortality exists in hemodialysis patients with HDL between 50 and <60 mg/dL exhibiting the best survival. The underlying mechanisms responsible for these seemingly paradoxical associations await further investigation.
End-stage renal disease (ESRD) is associated with accelerated atherosclerosis and a marked increase in cardiovascular (CV) mortality. Several factors are involved in the pathogenesis of atherosclerosis and CV disease in chronic kidney disease (CKD). These include oxidative stress, inflammation, hypertension, endothelial dysfunction, vascular calcification and dyslipidemia. Monocyte adhesion, infiltration and differentiation into macrophages and their ultimate conversion to foam cells are the primary steps in plaque formation. Foam cell formation is the result of increased uptake of oxidized or otherwise modified low-density lipoprotein (LDL) and remnant lipoproteins by macrophages in the artery wall. High-density lipoprotein (HDL) protects against plaque formation and progression via reverse cholesterol transport (RCT) and prevention or reversal of LDL oxidation. Therefore, it is not surprising that in the general population, increasing HDL cholesterol concentrations are associated with decreased atherosclerosis burden and reduced CV mortality. In addition to its role in RCT, HDL serves as a potent antioxidant, anti-inflammatory and antithrombotic factor. Indeed, recent studies have found that HDL function and activity are equally important in preventing CV disease and predicting CV mortality.
Plasma apolipoprotein A-I, the principal apolipoprotein constituent of HDL and HDL cholesterol content are commonly reduced in ESRD. The reduction in plasma HDL can clearly lead to increased cholesterol influx and diminished RCT and thereby promote atherosclerosis. The available data on the role of plasma HDL concentration in predicting CV mortality in patients with ESRD is limited. The present study was therefore designed to determine the relationship between plasma HDL concentration and CV and overall mortality in the ESRD patients maintained on hemodialysis. To this end, we examined a large national database of maintenance hemodialysis (MHD) patients of the contemporary origin with somewhat uniform practice patterns and with highly standardized laboratory values that were all measured in a single laboratory.
Abstract and Introduction
Abstract
Background High-density lipoprotein (HDL) confers protection against atherosclerosis by several different mechanisms. Although in the general population, increasing levels of HDL are associated with reduced cardiovascular (CV) mortality, this association is not well known in patients with chronic disease states such as end-stage renal disease. We hypothesize that the association of serum HDL concentration and its ratio to total cholesterol with all-cause and CV mortality in hemodialysis patients is different from the general population.
Methods A 3-year (July 2004 to June 2007) cohort of 33 109 chronic hemodialysis patients was studied in the USA in the dialysis clinics where lipid profile was measured in at least 50% of all outpatients of the clinic during a given calendar quarter. Cox proportional hazard models were adjusted for demographics and case–mix variables and cubic splines were plotted.
Results Higher HDL concentrations up to 50 mg/dL were associated with better overall survival, while HDL at 60 mg/dL and above was associated with a rise in all-cause and CV mortality. All-cause and CV mortality hazard ratio was 1.28 (1.20–1.38) and 1.08 (1.01–1.16) for HDL <30 mg/dL and 1.05 (1.00–1.10) and 1.08 (1.00–1.16) for HDL ≥ 60 mg/dL, respectively (reference: HDL: 30–<60 mg/dL).
Conclusions In contrast to the general population, low total cholesterol to HDL ratio was associated with higher mortality in hemodialysis patients. A U-shaped association between HDL cholesterol level and all-cause and CV mortality exists in hemodialysis patients with HDL between 50 and <60 mg/dL exhibiting the best survival. The underlying mechanisms responsible for these seemingly paradoxical associations await further investigation.
Introduction
End-stage renal disease (ESRD) is associated with accelerated atherosclerosis and a marked increase in cardiovascular (CV) mortality. Several factors are involved in the pathogenesis of atherosclerosis and CV disease in chronic kidney disease (CKD). These include oxidative stress, inflammation, hypertension, endothelial dysfunction, vascular calcification and dyslipidemia. Monocyte adhesion, infiltration and differentiation into macrophages and their ultimate conversion to foam cells are the primary steps in plaque formation. Foam cell formation is the result of increased uptake of oxidized or otherwise modified low-density lipoprotein (LDL) and remnant lipoproteins by macrophages in the artery wall. High-density lipoprotein (HDL) protects against plaque formation and progression via reverse cholesterol transport (RCT) and prevention or reversal of LDL oxidation. Therefore, it is not surprising that in the general population, increasing HDL cholesterol concentrations are associated with decreased atherosclerosis burden and reduced CV mortality. In addition to its role in RCT, HDL serves as a potent antioxidant, anti-inflammatory and antithrombotic factor. Indeed, recent studies have found that HDL function and activity are equally important in preventing CV disease and predicting CV mortality.
Plasma apolipoprotein A-I, the principal apolipoprotein constituent of HDL and HDL cholesterol content are commonly reduced in ESRD. The reduction in plasma HDL can clearly lead to increased cholesterol influx and diminished RCT and thereby promote atherosclerosis. The available data on the role of plasma HDL concentration in predicting CV mortality in patients with ESRD is limited. The present study was therefore designed to determine the relationship between plasma HDL concentration and CV and overall mortality in the ESRD patients maintained on hemodialysis. To this end, we examined a large national database of maintenance hemodialysis (MHD) patients of the contemporary origin with somewhat uniform practice patterns and with highly standardized laboratory values that were all measured in a single laboratory.
