Inflammation Alters Relationship Between High‐Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW‐CKD

BACKGROUND: The function of high‐density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high‐density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . METHODS AND RESULTS: In total, 1864 patients from the prospective KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high‐density lipoprotein cholesterol (HDL‐C) level. Presence of inflammation was defined by hs‐CRP (high‐sensitivity C‐reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person‐years of follow‐up, overall incidence of the primary outcome was 15.8 per 1000 person‐years. In multivariable Cox analysis after adjusting for confounders, HDL‐C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL‐C for risk of extended major adverse cardiovascular events (P=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL‐C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50–1.82), 0.95 (0.50–1.82), and 0.42 (0.19–0.95), respectively, compared with HDL‐C of 40 to 49 mg/dL. However, the significant association for HDL‐C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL‐C groups (HRs [95% CIs], 0.73 [0.37–1.43], 1.24 [0.59–2.61], and 1.56 [0.71–3.45], respectively), but without statistical significance. CONCLUSIONS: The association between HDL‐C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.