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Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD
Affiliation:1. Medical and Surgical Sciences Dept., University of Bologna, Italy;2. Department of Cardiology, Toranomon Hospital, Tokyo, Japan;3. Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO, United States;4. Department of Cardiology, Cardiovascular Center, St. Luke''s International Hospital, Tokyo, Japan.
Abstract:
Background and aimsThe optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake.Methods and resultsA total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression.During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality.ConclusionsThis study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.
Keywords:Cardiovascular event  Chronic kidney disease  Kidney outcome  Low-density lipoprotein cholesterol  Mortality  ASCVD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0040"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Atherosclerotic cardiovascular disease  AUC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0050"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Area under the receiver-operating characteristics curves  BMI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0060"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Body mass index  CAD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Coronary artery disease  CI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Confidence intervals  CKD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Chronic kidney disease  CVD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Cardiovascular disease  CVE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0120a"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Cardiovascular event  DM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0120"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Diabetes mellitus  eGFR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0130a"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  estimated glomerular filtration rate  ESA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0130b"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  European Atheroscloerosis Society  ESKD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0130"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  End-stage kidney disease  HDL-C"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0140a"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  high-density lipoprotein cholesterol  HR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0140s"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Hazard ration  hs-CRP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0140d"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  high sensitivity C-reactive protein  IDI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0140"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Integrated discrimination improvement  LDL-C"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0160a"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  low-density lipoprotein cholesterol  MACE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0160s"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  major adverse cardiovascular events  NRI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0160"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Net reclassification improvement  RASB"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0170a"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  renin-angiotensin system blocker  RCT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0170s"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  randomized controlled trial  SHARP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0170"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Study of Heart and Renal Protection  uACR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0170x"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  urine albumin-creatinine ration  uPCR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0170z"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  urine protein-creatinine ratio
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