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Original research
Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin
  1. Indu Dhar1,
  2. Sumia Siddique2,
  3. Eva R Pedersen3,
  4. Gard F T Svingen3,
  5. Vegard Lysne1,3,
  6. Thomas Olsen4,
  7. Dennis W Nilsen5,6,
  8. Jan Erik Nordrehaug5,6,
  9. Øivind Midttun7,
  10. Per M Ueland7,
  11. Grethe S Tell8,9,
  12. Ottar K Nygård1,3
  1. 1 Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway
  2. 2 Faculty of Medicine, University of Bergen, Bergen, Norway
  3. 3 Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
  4. 4 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  5. 5 Department of Cardiology, Stavanger University Hospital, Stavanger, Norway
  6. 6 Department of Clinical Science, University of Bergen, Bergen, Norway
  7. 7 Bevital AS, Bergen, Norway
  8. 8 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  9. 9 Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway
  1. Correspondence to Dr Indu Dhar, Department of Clinical Science, University of Bergen, Bergen N‐5021, Norway; Indu.Dhar{at}


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.

  • coronary artery disease
  • acute myocardial infarction
  • epidemiology

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  • Correction notice Since the online publication of this article, the author name 'Dennis W Nilsen' has been updated as the middle initial was incorrectly linked to the surname.

  • Contributors OKN and ID designed research; ID analysed the data, performed analysis, wrote the manuscript and had primary responsibility for the final content; ID, SS, ERP, GFTS, VL, TO, DWN, JEN, ØM, PMU, GST and OKN conducted research. All authors critically reviewed and revised the manuscript. OKN and ID are the guarantors.

  • Funding Funding was provided by the University of Bergen, the Department of Heart Disease at Haukeland University Hospital, the Western Norway Regional Health Authority, and the Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen, Norway.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was performed according to the Declaration of Helsinki, and was approved by the Regional Medical and Health Ethics committee, the Norwegian Medicines Agency and the Norwegian Data Inspectorate.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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