Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease

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Abstract

Background: Monocyte chemoattractant protein-1 ­(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = –0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4–2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0–2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1–2.3]) after adjusting for CV risk factors. Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.

Original languageEnglish (US)
Pages (from-to)395-405
Number of pages11
JournalAmerican Journal of Nephrology
DOIs
StateAccepted/In press - Jun 6 2018

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Chemokine CCL2
Chronic Renal Insufficiency
Kidney Diseases
Glomerular Filtration Rate
Albuminuria
Blood Proteins
Pulse Wave Analysis
Atherosclerotic Plaques
Acute Coronary Syndrome
Monocytes
Cause of Death
Atherosclerosis
Coronary Vessels

Keywords

  • Albuminuria
  • Biomarkers
  • Cardiovascular
  • Chronic kidney disease
  • Death
  • Inflammation
  • Monocyte chemoattractant protein-1
  • Outcomes

ASJC Scopus subject areas

  • Nephrology

Cite this

@article{29555658a0924a6f96e042296d63f429,
title = "Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease",
abstract = "Background: Monocyte chemoattractant protein-1 ­(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8{\%}) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = –0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7{\%}) deaths and 168 (6.4{\%}) atherosclerotic events in the non-CKD vs. 97 (34.0{\%}) deaths and 62 (27.9{\%}) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4–2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0–2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1–2.3]) after adjusting for CV risk factors. Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.",
keywords = "Albuminuria, Biomarkers, Cardiovascular, Chronic kidney disease, Death, Inflammation, Monocyte chemoattractant protein-1, Outcomes",
author = "Gregg, {Lucile Parker} and Tio, {Maria Clarissa} and Xilong Li and Huet, {Beverley A} and {de Lemos}, {James A} and Hedayati, {S S}",
year = "2018",
month = "6",
day = "6",
doi = "10.1159/000488806",
language = "English (US)",
pages = "395--405",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease

AU - Gregg, Lucile Parker

AU - Tio, Maria Clarissa

AU - Li, Xilong

AU - Huet, Beverley A

AU - de Lemos, James A

AU - Hedayati, S S

PY - 2018/6/6

Y1 - 2018/6/6

N2 - Background: Monocyte chemoattractant protein-1 ­(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = –0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4–2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0–2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1–2.3]) after adjusting for CV risk factors. Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.

AB - Background: Monocyte chemoattractant protein-1 ­(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = –0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4–2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0–2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1–2.3]) after adjusting for CV risk factors. Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.

KW - Albuminuria

KW - Biomarkers

KW - Cardiovascular

KW - Chronic kidney disease

KW - Death

KW - Inflammation

KW - Monocyte chemoattractant protein-1

KW - Outcomes

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DO - 10.1159/000488806

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JO - American Journal of Nephrology

JF - American Journal of Nephrology

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