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Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis

Ganda, Anjali ; Magnusson, Martin LU orcid ; Yvan-Charvet, Laurent ; Hedblad, Bo LU ; Engström, Gunnar LU ; Ai, Ding ; Wang, Thomas J. ; Gerszten, Robert E. ; Melander, Olle LU orcid and Tall, Alan R. (2013) In Circulation 127(9). p.988-996
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 Malmo Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of... (More)
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 Malmo 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. (Circulation. 2013; 127: 988-996.) (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, immunology, kidney, metabolomics, risk factors
in
Circulation
volume
127
issue
9
pages
988 - 996
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000315804800013
  • scopus:84874652279
  • pmid:23378299
ISSN
1524-4539
DOI
10.1161/CIRCULATIONAHA.112.000682
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Hypertension and Cardiovascular Disease (013242540), Cardio-vascular Epidemiology (013241610)
id
172ac8a8-a47a-45a6-94e8-d2d13f88a038 (old id 3651347)
date added to LUP
2016-04-01 14:16:35
date last changed
2024-01-10 01:18:00
@article{172ac8a8-a47a-45a6-94e8-d2d13f88a038,
  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 Malmo 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&lt;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. (Circulation. 2013; 127: 988-996.)}},
  author       = {{Ganda, Anjali and Magnusson, Martin and Yvan-Charvet, Laurent and Hedblad, Bo and Engström, Gunnar and Ai, Ding and Wang, Thomas J. and Gerszten, Robert E. and Melander, Olle and Tall, Alan R.}},
  issn         = {{1524-4539}},
  keywords     = {{atherosclerosis; immunology; kidney; metabolomics; risk factors}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{988--996}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Circulation}},
  title        = {{Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis}},
  url          = {{http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000682}},
  doi          = {{10.1161/CIRCULATIONAHA.112.000682}},
  volume       = {{127}},
  year         = {{2013}},
}