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Peer-reviewedCC BYAtherosclerosis Plus

Arginine and homoarginine as predictors of cardiovascular mortality in chronic coronary syndrome

  • Silje Kjellevold Storesund1
  • Iman Karaji1
  • Adrian McCann2
  • Gard Frodahl Tveitevåg Svingen3
  • Per Magne Ueland4
  • Mai Tone Lønnebakken1
  • Ottar Nygård1
  • Eva Ringdal Pedersen5
5 affiliations
  1. 1Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway
  2. 2Bevital A/S, Bergen, Norway
  3. 3Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
  4. 4Department of Clinical Science, University of Bergen, Bergen, Norway; Bevital A/S, Bergen, Norway
  5. 5Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Corresponding author. Department of Heart Disease, Haukeland University Hospital, 5021, Bergen, Norway.
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Abstract

Background and aims: Arginine (Arg) and homoarginine (hArg) are related to the nitric oxide pathway, which is important for vascular function. We investigated if serum concentrations of Arg and hArg predicted long-term cardiovascular disease (CVD) mortality in patients with chronic coronary syndrome (CCS), and whether associations differed between non-obstructive coronary artery disease (NOCAD) and obstructive coronary artery disease (OCAD). Methods and results: We included 4164 patients undergoing invasive coronary angiography for suspected CCS. Associations with CVD mortality were assessed using multivariable Cox regression, reporting hazard ratios (HRs) per standard deviation increase in log-transformed concentrations. During a median follow-up of 14.1 years, 586 (14.1%) patients died from CVD. Serum hArg was inversely associated with CVD mortality [HR (95% CI): 0.81 (0.74–0.88)] as was serum Arg [HR (95% CI): 0.90 (0.83–0.98)]. However, in Fine–Gray competing risk analyses, the association of serum Arg with CVD mortality was no longer statistically significant, whereas the inverse association for serum hArg persisted. Addition of serum hArg to the clinical model increased the C-statistic from 0.771 to 0.776, indicating a modest improvement in discrimination. In exploratory subgroup analyses, the association between serum hArg and CVD mortality was stronger in NOCAD than OCAD [0.54 (0.40–0.73) vs. 0.84 (0.77–0.92); P for interaction = 0.037]. Conclusion: Serum Arg and hArg were inversely associated with long-term CVD mortality in patients with CCS. However, the association of serum hArg was more robust than that of serum Arg. The stronger association observed in NOCAD requires independent validation.

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Cite

BibTeXRIS
BibTeX
@article{storesund2026arginine,
  title = {{Arginine and homoarginine as predictors of cardiovascular mortality in chronic coronary syndrome}},
  author = {Silje Kjellevold Storesund and Iman Karaji and Adrian McCann and Gard Frodahl Tveitevåg Svingen and Per Magne Ueland and Mai Tone Lønnebakken and Ottar Nygård and Eva Ringdal Pedersen},
  journal = {Atherosclerosis Plus},
  year = {2026},
  month = oct,
  doi = {10.1016/j.athplu.2026.100621},
  url = {https://doi.org/10.1016/j.athplu.2026.100621},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Arginine and homoarginine as predictors of cardiovascular mortality in chronic coronary syndrome
AU  - Silje Kjellevold Storesund
AU  - Iman Karaji
AU  - Adrian McCann
AU  - Gard Frodahl Tveitevåg Svingen
AU  - Per Magne Ueland
AU  - Mai Tone Lønnebakken
AU  - Ottar Nygård
AU  - Eva Ringdal Pedersen
PY  - 2026
DA  - 2026/10/23
JO  - Atherosclerosis Plus
DO  - 10.1016/j.athplu.2026.100621
UR  - https://doi.org/10.1016/j.athplu.2026.100621
AB  - Background and aims: Arginine (Arg) and homoarginine (hArg) are related to the nitric oxide pathway, which is important for vascular function. We investigated if serum concentrations of Arg and hArg predicted long-term cardiovascular disease (CVD) mortality in patients with chronic coronary syndrome (CCS), and whether associations differed between non-obstructive coronary artery disease (NOCAD) and obstructive coronary artery disease (OCAD). Methods and results: We included 4164 patients undergoing invasive coronary angiography for suspected CCS. Associations with CVD mortality were assessed using multivariable Cox regression, reporting hazard ratios (HRs) per standard deviation increase in log-transformed concentrations. During a median follow-up of 14.1 years, 586 (14.1%) patients died from CVD. Serum hArg was inversely associated with CVD mortality [HR (95% CI): 0.81 (0.74–0.88)] as was serum Arg [HR (95% CI): 0.90 (0.83–0.98)]. However, in Fine–Gray competing risk analyses, the association of serum Arg with CVD mortality was no longer statistically significant, whereas the inverse association for serum hArg persisted. Addition of serum hArg to the clinical model increased the C-statistic from 0.771 to 0.776, indicating a modest improvement in discrimination. In exploratory subgroup analyses, the association between serum hArg and CVD mortality was stronger in NOCAD than OCAD [0.54 (0.40–0.73) vs. 0.84 (0.77–0.92); P for interaction = 0.037]. Conclusion: Serum Arg and hArg were inversely associated with long-term CVD mortality in patients with CCS. However, the association of serum hArg was more robust than that of serum Arg. The stronger association observed in NOCAD requires independent validation.
SN  - 2667-0895
SN  - 2667-0909
ER  -