期刊
CIRCULATION
卷 127, 期 9, 页码 988-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.112.000682
关键词
atherosclerosis; immunology; kidney; metabolomics; risk factors
资金
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000040, UL1 RR024156]
- Leducq Foundation
- Swedish Medical Research Council
- Swedish Heart and Lung Foundation
- Medical Faculty of Lund University
- Skane University Hospital
- Albert Pahlsson Research Foundation
- Crafoord Foundation
- Ernhold Lundstroms Research Foundation
- Region Skane
- Hulda and Conrad Mossfelt Foundation
- Southwest Skanes Diabetes Foundation
- King Gustaf V and Queen Victoria Foundation
- Lennart Hanssons Memorial Fund
- Knut and Alice Wallenberg Foundation
- Marianne and Marcus Wallenberg Foundation
- National Institutes of Health [HL 98280, DK 081572]
- Novo Nordisk Fonden [NNF13OC0005339] Funding Source: researchfish
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.)
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