HDL Cholesterol Is Not Associated with Lower Mortality in Patients with Kidney Dysfunction

Abstract

In the general population, HDL cholesterol (HDL-C) is associated with reduced cardiovascular events. However, recent experimental data suggest that the vascular effects of HDL can be heterogeneous. We examined the association of HDL-C with all-cause and cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health study comprising 3307 patients undergoing coronary angiography. Patients were followed for a median of 9.9 years. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C (eGFR creat-cys ) equation. The effect of increasing HDL-C serum levels was assessed using Cox proportional hazard models. In participants with normal kidney function (eGFR.90 ml/min per 1.73 m 2 ), higher HDL-C was associated with reduced risk of [P=0.60]). Moreover, Cox regression analyses revealed interaction between HDL-C and eGFR in predicting all-cause and cardiovascular mortality (P=0.04 and P=0.02, respectively). We confirmed a lack of association between higher HDL-C and lower mortality in an independent cohort of patients with definite CKD (P=0.63). In summary, higher HDL-C levels did not associate with reduced mortality risk and coronary artery disease severity in patients with reduced kidney function. Indeed, abnormal HDL function might confound the outcome of HDL-targeted therapies in these patients.

Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties

“…Recent studies have shown an association of HDL-cholesterol levels as predictors of CKD progression, but not with CVD risk. [40][41][42] This is in line with our findings that KTx good patients have higher HDL-cholesterol levels compared with KTx poor patients (Table 1), which is likely a consequence of recovered renal function. A major finding of our study is that functional properties of HDL remain compromised after renal transplantation, shown by substantial impairments in both KTx groups similar to patients with ESRD.…”

Molecular mechanisms of disorders of lipid metabolism in chronic kidney disease

“…In fact, there is evidence that increased oxidized ApoAI levels are associated with a high risk of cardiovascular mortality in hemodialysis patients (120). The clinical significance of the above mentioned abnormalities are highlighted in recent studies that have shown the association of elevated serum HDL cholesterol levels with improved CV mortality is significantly diminished in patients with reduced estimated GFR (121). In addition, we have shown that in patients with ESRD on maintenance hemodialysis, reduced serum triglyceride to HDL ratio and elevated serum HDL cholesterol levels were paradoxically associated with increased CV and all-cause mortality (122).…”

“…A recent study in a large cohort of U.S. veterans found that the lowest and highest deciles of serum HDL cholesterol levels were associated with significantly increased risks of incidence and progression of CKD (123). Hence, elevated serum HDL cholesterol concentrations are not necessarily associated with improved outcomes in patients with CKD (121). This combined with the fact that HDL from patients with CKD/ESRD on maintenance hemodialysis has been shown to have impaired reverse cholesterol transport capabilities that can lead to HDL dysfunction and account for the paradoxical associations of serum HDL level with outcomes noted in epidemiologic studies (124,125).…”

HDL in Children with CKD Promotes Endothelial Dysfunction and an Abnormal Vascular Phenotype

“…26 HDL is a complex particle and blood levels of HDL cholesterol do not reflect its diverse vascular protective functions. In CKD, HDL carries a distinct protein cargo with acute phase protein serum amyloid A1, apoCIII, and lipoprotein-associated phospholipase A2.…”