Cardiovascular

Homocysteine, cysteine and methionine are associated with 90-day prognosis in intracerebral hemorrhage patients.

TL;DR

Plasma levels of Hcy, Cys and Met are associated with 90-day prognosis after intracerebral hemorrhage, and triple combination of Hcy, Cys and Met has greater predictive value, providing a more comprehensive risk assessment of unfavorable prognosis in ICH patients.

Key Findings

ICH patients had significantly higher plasma homocysteine, cysteine, and methionine levels compared to healthy controls.

  • A total of 212 ICH patients and 215 age- and sex-matched healthy controls were enrolled in this retrospective study.
  • Plasma Hcy, Cys, and Met levels were compared between ICH patients and healthy controls.
  • The differences in all three biomarkers between groups were statistically significant.

Patients with unfavorable 90-day prognosis had higher homocysteine and cysteine levels but lower methionine levels compared to those with favorable prognosis.

  • ICH patients were categorized into favorable and unfavorable prognostic groups based on their 90-day prognosis.
  • Unfavorable prognosis patients presented higher Hcy and Cys levels.
  • Unfavorable prognosis patients presented lower Met levels.
  • This divergent pattern distinguished the prognostic groups across all three sulfur amino acid metabolites.

High plasma homocysteine was an independent risk factor for unfavorable 90-day prognosis in ICH patients.

  • Multivariate logistic regression analysis identified Hcy as an independent predictor.
  • OR = 1.235 (95% CI 1.137–1.342) for high Hcy.
  • This association remained significant after adjustment for other variables.

High plasma cysteine was an independent risk factor for unfavorable 90-day prognosis in ICH patients.

  • Multivariate logistic regression analysis identified Cys as an independent predictor.
  • OR = 1.017 (95% CI 1.008–1.025) for high Cys.
  • This association remained significant after adjustment for other variables.

Methionine exhibited a dual nonlinear (concentration-dependent) relationship with 90-day prognosis, with a protective effect observed at levels below 32.88 µmol/L.

  • Restricted Cubic Spline (RCS) analysis was used to explore the nonlinear relationship between Met and prognosis.
  • Met played a protective role at levels <32.88 µmol/L with OR = 0.924 (95% CI 0.860–0.992).
  • The dual nonlinear effect means Met's association with prognosis changes direction or magnitude at the threshold of 32.88 µmol/L.
  • Lower odds of adverse outcomes were observed for Met <32.88 µmol/L.

The combined detection of all three biomarkers (Hcy, Cys, and Met) yielded the highest predictive accuracy for 90-day ICH prognosis, superior to single and pairwise combinations.

  • ROC curve analysis was used to assess predictive efficacy of individual and combined biomarkers.
  • The combined three-biomarker model achieved AUC = 0.819.
  • This was superior to all single biomarker and pairwise biomarker combinations.
  • The predictive model was internally validated and compared with classic ICH prognostic scoring systems.
  • The authors note the model requires external prospective verification before clinical translation.

What This Means

This research suggests that three amino acid-related compounds in the blood — homocysteine (Hcy), cysteine (Cys), and methionine (Met) — are linked to how well patients recover in the 90 days after a brain bleed (intracerebral hemorrhage, or ICH). The study compared 212 ICH patients to 215 healthy individuals and found that all three compounds were elevated in ICH patients. Among the ICH patients themselves, those who had worse outcomes tended to have higher homocysteine and cysteine but lower methionine levels. Higher homocysteine and cysteine were independently associated with worse outcomes, while methionine showed a more complex relationship: at lower concentrations (below about 33 µmol/L), higher methionine was associated with better outcomes, but this protective pattern did not hold at higher concentrations. When all three biomarkers were measured together and combined into a predictive model, the accuracy in forecasting poor outcomes (measured by AUC = 0.819) was better than using any single biomarker or any two biomarkers combined, and also outperformed standard ICH scoring systems in this dataset. This suggests that measuring these three compounds together could offer a more complete picture of a patient's risk after a brain bleed. This research suggests that blood levels of homocysteine, cysteine, and methionine could potentially serve as useful prognostic tools in ICH patients. However, the authors caution that this was a single-center retrospective study and that the combined biomarker model needs to be tested in larger, prospective, and externally validated studies before it could be considered for routine clinical use.

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Citation

Fang M, Xia T, Yin Y. (2026). Homocysteine, cysteine and methionine are associated with 90-day prognosis in intracerebral hemorrhage patients.. Annals of medicine. https://doi.org/10.1080/07853890.2026.2719236