Mild renal dysfunction and metabolites tied to low HDL cholesterol are associated with monocytosis and atherosclerosis

Anjali Ganda, Martin Magnusson, Laurent Yvan-Charvet, Bo Hedblad, Gunnar Engström, Ding Ai, Thomas J. Wang, Robert E. Gerszten, Olle Melander, Alan R. Tall

Research output: Contribution to journalArticle

37 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)988-996
Number of pages9
JournalCirculation
Volume127
Issue number9
DOIs
StatePublished - Mar 5 2013
Externally publishedYes

Keywords

  • atherosclerosis
  • immunology
  • kidney
  • metabolomics
  • risk factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Ganda, A., Magnusson, M., Yvan-Charvet, L., Hedblad, B., Engström, G., Ai, D., Wang, T. J., Gerszten, R. E., Melander, O., & Tall, A. R. (2013). Mild renal dysfunction and metabolites tied to low HDL cholesterol are associated with monocytosis and atherosclerosis. Circulation, 127(9), 988-996. https://doi.org/10.1161/CIRCULATIONAHA.112.000682