Monocyte heterogeneity in obesity and subclinical atherosclerosis.

AIMS: Monocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis. METHODS AND RESULTS: We assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14(++)CD16(-) and CD16(+) cells, which we further subdivided into CD14(++)CD16(+) and CD14((+))CD16(+) cells. Body mass index was significantly correlated with carotid IMT. High CD16(+) monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16(+) monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16(+) monocyte numbers in obesity may partly explain the association between obesity and IMT. CONCLUSION: Our results reveal a significant univariate association between CD16(+) monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16(+) monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.

Haemodialysis-induced transient CD16+ monocytopenia and cardiovascular outcome.

BACKGROUND: Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intra-dialytic leukopenia due to endothelial adherence. After the introduction of biocompatible membranes, only CD16(+) (i.e. CD14(++)CD16(+) and CD14((+))CD16(+)) monocytes showed an impressive transient intra-dialytic decrease. Presently, it is unclear whether this CD16(+) monocyte drop is detrimental. We investigated whether a prominent intra-dialytic decrease of CD16(+) monocytes predicts future cardiovascular (CV) events. METHODS: We measured leukocyte and monocyte subpopulations in 70 patients before and 10 min after haemodialysis initiation. Patients were stratified by their intra-dialytic CD14(++)CD16(+) monocyte drop (pre-defined major drop: decline of cell counts at 10 min to <50% of pre-dialytic values; pre-defined minor drop: decline to values >50% of pre-dialytic counts). Patients were followed up for 42 +/- 2 months; endpoints were CV events and death. RESULTS: Patients with a minor CD14(++)CD16(+) monocyte drop had more CV events than patients with a major drop. In multivariate analysis, a minor CD14(++)CD16(+) monocyte drop was the strongest independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192-4.854)]. CONCLUSIONS: These data refute the assumption that a prominent intra-dialytic decrease of CD14(++)CD16(+) monocytes is detrimental. Instead, a minor cell drop could mirror CD14(++)CD16(+) monocyte dysfunction, with inadequate migratory reaction towards an immunologic stimulus posed by membrane and tubing contact.

Does clopidogrel rather than aspirin plus a proton-pump inhibitor reduce the frequency of gastrointestinal complications after cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether clopidogrel rather than aspirin plus a proton-pump inhibitor reduce the frequency of gastrointestinal complications after cardiac surgery. Altogether 40 publications were identified using the below-mentioned search and all the papers reference lists were searched. Six papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that clopidogrel causes fewer gastrointestinal complications than aspirin in those patients with no previous history of gastric or duodenal ulceration with a number needed to treat of around 200 to prevent an episode of bleeding per year. However, in those patients with a previous history of gastrointestinal complications, clopidogrel alone is not a safer alternative than aspirin alone. Either aspirin or clopidogrel combined with a proton pump inhibitor are equally effective for these patients.