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

Ganda A, Magnusson M, Yvan-Charvet L, Hedblad B, Engström G, Ai D, Wang TJ, Gerszten RE, Melander O, Tall AR
Circulation. 2013 127 (9): 988-96

PMID: 23378299 · PMCID: PMC4074592 · DOI:10.1161/CIRCULATIONAHA.112.000682

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.

MeSH Terms (16)

Aged Atherosclerosis Case-Control Studies Cholesterol, HDL Cohort Studies Cross-Sectional Studies Female Humans Kidney Diseases Kidney Function Tests Leukocytosis Male Middle Aged Monocytes Prospective Studies Risk Factors

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