Highlights
- •Some discrete monocyte subsets predict cardiovascular outcomes, but monocytes have now been redefined as a continuum.
- •We tested whether shift of monocytes along their continuum provides incremental prognostic information.
- •We found that shift of monocyte subsets along their continuum predicted adverse cardiovascular outcomes more than their frequency.
- •These data illustrate how the concept of monocyte continuum can be used to model cardiovascular risk.
Abstract
Background and aims
Distribution of monocyte subsets has been shown to predict cardiovascular outcomes.
However, monocytes form a continuum and categorization into discrete subsets may be
an oversimplification. We herein aimed at establishing whether distribution of monocytes
based on CD14 and CD16 fluorescence intensity provides incremental and complementary
information on cardiovascular outcomes beyond enumeration of traditional subsets.
Methods
A cohort of 227 patients at high cardiovascular risk was characterized at baseline
and followed for a median of 4 years. We quantified monocytes subsets by flow cytometry
based on CD14 and CD16 expression and evaluated the continuous distribution of CD14
and CD16 fluorescence within each subset.
Results
A consistent shift toward higher CD16 fluorescence intensity within each monocyte
subset was observed in patients with type 2 diabetes, despite no change in their frequencies.
Patients with coronary artery disease (CAD) at baseline showed a doubling of CD14++CD16+ intermediate monocytes and a shift of non-classical and classical monocytes towards
intermediates ones. During follow-up, cardiovascular death or cardiovascular events
occurred in 26 patients, who showed monocyte skewing similar to those of patients
with baseline CAD. In fully adjusted Cox proportional hazard regression models, higher
CD16 expression on classical monocytes, but not the level of intermediate monocytes
or other subsets, independently predicted adverse cardiovascular outcomes.
Conclusions
Shift of monocyte subsets along the CD14/CD16 continuum, more than their frequencies,
predicted adverse cardiovascular outcomes. This finding illustrates how the concept
of monocyte continuum can be used to model the cardiovascular risk.
Keywords
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Article info
Publication history
Published online: September 29, 2017
Accepted:
September 28,
2017
Received in revised form:
September 20,
2017
Received:
June 18,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
