title: 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 (eGFRcreat-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 all-cause and cardiovascular mortality and coronary artery disease severity (hazard ratio [HR], 0.51, 95% confidence interval [95% CI], 0.26-0.92 [P=0.03]; HR, 0.30, 95% CI, 0.13-0.73 [P=0.01]). Conversely, in patients with mild (eGFR=60-89 ml/min per 1.73 m(2)) and more advanced reduced kidney function (eGFR<60 ml/min per 1.73 m(2)), higher HDL-C did not associate with lower risk for mortality (eGFR=60-89 ml/min per 1.73 m(2): HR, 0.68, 95% CI, 0.45-1.04 [P=0.07]; HR, 0.84, 95% CI, 0.50-1.40 [P=0.50]; eGFR<60 ml/min per 1.73 m(2): HR, 1.18, 95% CI, 0.60-1.81 [P=0.88]; HR, 0.82, 95% CI, 0.40-1.69 [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.
authors.affiliation: Departments of Internal Medicine IV and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zewinger
authors.affiliation: Departments of Internal Medicine IV and.
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
authors.affiliation: Medical Faculty Mannheim, University of Heidelberg, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology), Mannheim, Germany;
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria;
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Division of Nephrology, Department of Internal Medicine I, University of Bonn, Bonn, Germany;
authors.forename: Rainer
authors.initials: R
authors.lastname: Woitas
authors.affiliation: Internal Medicine V, Saarland University Hospital, Homburg/Saar, Germany;
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Lepper
authors.affiliation: Departments of Internal Medicine IV and.
authors.forename: Karolin
authors.initials: K
authors.lastname: Pfahler
authors.affiliation: Departments of Internal Medicine IV and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.affiliation: Departments of Internal Medicine IV and.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.affiliation: Medical Faculty Mannheim, University of Heidelberg, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology), Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Synlab Academy, Synlab Services LLC, Mannheim, Germany; and.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Angiology, Swiss Cardiovascular Center, University Hospital Bern, Bern, Switzerland.
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.affiliation: Departments of Internal Medicine IV and danilo.fliser@uks.eu.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000401:mortality*; D008076:Cholesterol, HDL / Q000097:blood*; D017023:Coronary Angiography; D066246:ErbB Receptors / Q000097:blood / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality*
chemical_list: D008076:Cholesterol, HDL; C512478:EGFR protein, human; D066246:ErbB Receptors