Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin

Heart. 2020 Jul;106(14):1073-1079. doi: 10.1136/heartjnl-2019-316165. Epub 2020 May 12.


Objectives: Oxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ-mediated immune activation and coronary artery disease risk. We examined the influence of serum lipid parameters and Vit-A on the risk association between neopterin and incident acute myocardial infarction (AMI).

Methods: We included 4130 patients with suspected stable angina pectoris (SAP), of whom 80% received lipid-lowering treatment with statins. Risk associations between plasma neopterin and AMI are given as HRs per SD increase in log-transformed neopterin.

Results: During a median follow-up of 7.5 years, 530 (12.8%) patients experienced an AMI. In age-adjusted and sex-adjusted analysis, plasma neopterin was positively associated with incident AMI (HR (95% CI) per SD: 1.26 (1.17 to 1.35)). However, the estimates were most pronounced in patients with serum low-density lipoprotein cholesterol (LDL-C) or apolipoprotein (apo) B100 below-median (HR (95% CI) per SD: 1.35 (1.24 to 1.48) and 1.42 (1.27 to 1.58), respectively; both pinteraction ≤0.03). We also observed a particularly strong risk association in those with above-median Vit-A (HR (95% CI) per SD: 1.32 (1.21 to 1.44); pinteraction=0.03). The estimates were slightly modified after multivariable adjustment.

Conclusions: In patients with suspected SAP, the majority of whom receiving statin therapy, high plasma neopterin was associated with increased risk of AMI particularly among those with low LDL-C and apoB100 or high Vit-A levels. The particularly strong relationship of plasma neopterin with residual cardiovascular risk in patients with low lipid levels should be further investigated.

Keywords: acute myocardial infarction; coronary artery disease; epidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Clinical Trials as Topic
  • Databases, Factual
  • Dyslipidemias / blood*
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy
  • Dyslipidemias / epidemiology
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Incidence
  • Lipids / blood*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Neopterin / blood*
  • Norway / epidemiology
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Time Factors
  • Vitamin A / blood*


  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Vitamin A
  • Neopterin