title: Mild renal dysfunction and metabolites tied to low HDL cholesterol are associated with monocytosis and atherosclerosis.
abstract: BACKGROUND
  The number of circulating blood monocytes impacts atherosclerotic lesion size, and in mouse models, elevated levels of high-density lipoprotein cholesterol suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced high-density lipoprotein levels, high blood monocyte counts, and accelerated atherosclerosis.
  
  
  RESULTS
  To test whether mild renal dysfunction is associated with an increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmö Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (P=0.02). Cystatin C levels were positively and plasma high-density lipoprotein cholesterol levels negatively associated with monocyte counts at baseline, after adjustment for traditional risk factors. Several amino acid metabolites tied to low levels of high-density lipoprotein cholesterol and insulin resistance measured in a subset of individuals (n=752) by use of liquid chromatography-mass spectrometry were independently associated with a 22% to 34% increased risk of being in the top quartile of monocytes (P<0.05).
  
  
  CONCLUSIONS
  A low high-density lipoprotein cholesterol, insulin resistance phenotype occurs in subjects with mild renal dysfunction and is associated with elevated monocytes and atherosclerosis. High blood monocyte counts may represent a previously unrecognized mechanism underlying the strong relationship between cystatin C and cardiovascular risk.
authors: Division of Nephrology, College of Physicians & Surgeons, Columbia University, PH4-124, 622 W 168th St, New York, NY 10032, USA. ag355@columbia.edu
authors: Anjali
authors: A
authors: Ganda
authors: Martin
authors: M
authors: Magnusson
authors: Laurent
authors: L
authors: Yvan-Charvet
authors: Bo
authors: B
authors: Hedblad
authors: Gunnar
authors: G
authors: Engström
authors: Ding
authors: D
authors: Ai
authors: Thomas J
authors: TJ
authors: Wang
authors: Robert E
authors: RE
authors: Gerszten
authors: Olle
authors: O
authors: Melander
authors: Alan R
authors: AR
authors: Tall
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D007677:Kidney Function Tests; D007964:Leukocytosis / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL
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