Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3651347
- author
- Ganda, Anjali ; Magnusson, Martin LU ; Yvan-Charvet, Laurent ; Hedblad, Bo LU ; Engström, Gunnar LU ; Ai, Ding ; Wang, Thomas J. ; Gerszten, Robert E. ; Melander, Olle LU and Tall, Alan R.
- organization
- publishing date
- 2013
- 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<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}}, }