Do elevated neutrophil and monocyte counts indicate myeloid immune activation and higher cardiovascular risk?

Circulating myeloid cells are primary cellular mediators of systemic inflammation, and their elevation in the blood is directly tied to cardiovascular pathology.

Mechanistic pathways of myeloid activation

• Myeloid-biased hematopoiesis: Chronic systemic inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), act directly on hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. This signaling drives HSPCs out of quiescence and biases their differentiation toward the myeloid lineage.
• Trained innate immunity: Recurrent metabolic or inflammatory stimuli trigger trained immunity in myeloid progenitors, yielding an expanded circulating pool of hyperresponsive, pro-inflammatory neutrophils and monocytes.
• Inflammatory amplification: Once activated, these circulating cells release cytokines that stimulate hepatic synthesis of high-sensitivity C-reactive protein (hs-CRP), sustaining a cycle of low-grade systemic inflammation.

Clinical evidence and cardiovascular risk

• Elevated risk metrics: Elevated absolute neutrophil counts (ANC) and absolute monocyte counts (AMC) are strong, independent predictors of cardiovascular disease (CVD). Prospective cohort data show that higher neutrophil counts correlate with a 32% increase in CVD incidence and a 71% increase in CVD mortality.
• Predictive cellular indices: Combining these cellular markers into integrated metrics, such as the Systemic Inflammation Response Index (SIRI; calculated as neutrophils × monocytes / lymphocytes), provides superior prognostic value. Large-scale evaluations, including UK Biobank analyses, demonstrate that elevated SIRI independently predicts myocardial infarction, stroke, heart failure, and cardiovascular mortality in a clear dose-response relationship.

Bottom line

• Absolute elevations in circulating neutrophils and monocytes directly reflect myeloid-biased hematopoiesis and trained innate immunity. Both individually and when integrated into composite indices like SIRI, these cellular markers serve as highly reliable, independent predictors of chronic low-grade systemic inflammation and elevated cardiovascular risk.