Relationship Between Serum Homocysteine Levels and Long-Term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction

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Relationship Between Serum Homocysteine Levels and Long-Term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction

Cardiovascular diseases remain a leading cause of global mortality, with ST-segment elevation myocardial infarction (STEMI) representing a critical manifestation of acute coronary occlusion. Despite advancements in treatment, residual risk stratification remains challenging. Homocysteine (HCY), a sulfur-containing amino acid linked to atherosclerotic processes, has been proposed as a potential biomarker for adverse outcomes. This study investigates the prognostic value of serum HCY levels in patients with STEMI, focusing on both short- and long-term clinical outcomes.

Study Design and Methodology

Patient Population

A retrospective cohort of 419 consecutive STEMI patients admitted to Xuanwu Hospital, Capital Medical University (Beijing, China) between March 2010 and December 2015 was analyzed. STEMI diagnosis required two of the following: prolonged chest pain (>20 minutes), ST-segment elevation on electrocardiogram, or elevated cardiac biomarkers (troponin or CK-MB). Exclusion criteria included folic acid supplementation, prior STEMI, coronary revascularization, or active inflammatory conditions.

HCY Measurement and Group Stratification

Serum HCY levels were measured within 24 hours of admission using enzymatic cycling assays. Patients were divided into high HCY (H-HCY, ≥14.4 µmol/L, median value) and low HCY (L-HCY, 60 years).

Clinical Endpoints

  • In-hospital outcomes: All-cause mortality.
  • Long-term outcomes: Major adverse cardiovascular and cerebrovascular events (MACCE), including death, nonfatal MI, stroke, heart failure, and revascularization.

Statistical Analysis

Baseline characteristics were compared using Student’s t-test, Mann-Whitney U test, or Chi-squared tests. Multivariate logistic and Cox regression models adjusted for covariates (age, hypertension, Killip class, etc.) evaluated HCY’s predictive value. Kaplan-Meier curves assessed survival differences, and receiver operating characteristic (ROC) analysis determined HCY’s discriminative power in elderly patients.

Key Findings

Baseline Characteristics

The H-HCY group (n=208) exhibited distinct demographic and biochemical profiles compared to the L-HCY group (n=211):

  • Demographics: Higher proportion of males (84.6% vs. 75.4%, P=0.018) and fewer diabetics (20.2% vs. 35.5%, P<0.001).
  • Biomarkers: Elevated white blood cell counts (10.95 vs. 9.83 ×10⁹/L, P<0.001), creatinine (730 vs. 660 mg/L, P<0.001), and uric acid (363.34 vs. 311.58 µmol/L, P<0.001).
  • Medications: Lower calcium channel blocker use (16.8% vs. 28.0%, P=0.005).
    No significant differences existed in angiographic severity (Gensini scores: 40.5 vs. 48.0, P=0.377) or treatment strategies (primary PCI rates: 53.4% vs. 55.0%, P=0.741).

In-Hospital Outcomes

  • Mortality rates were comparable between H-HCY and L-HCY groups (4.8% vs. 3.3%, P=0.440).
  • Independent predictors of in-hospital mortality included age (OR:1.114, 95% CI:1.045–1.188, P=0.001), Killip class (OR:3.340, 95% CI:1.693–6.591, P=0.001), and white blood cell count (OR:1.376, 95% CI:1.130–1.675, P=0.001). HCY levels showed no association (OR:0.970, P=0.387).

Long-Term Outcomes

During a median follow-up of 35.8 months:

  • MACCE occurred in 24.2% of H-HCY and 16.2% of L-HCY patients (P=0.120).
  • Hypertension (HR:1.881, 95% CI:1.178–3.005, P=0.008) and higher Killip class (HR:1.923, 95% CI:1.419–2.607, P<0.001) independently predicted MACCE, but HCY did not (HR:1.007, P=0.507).

Age-Stratified Subgroup Analysis

  • Patients ≤60 years (n=190): Younger patients had more males (93.2% vs. 69.0%, P<0.001), smokers (78.9% vs. 51.1%, P<0.001), and lower Killip class (37.9% vs. 66.8% ≥Killip II, P<0.001). HCY did not predict MACCE (HR:0.972, P=0.233).
  • Patients >60 years (n=229): Elderly patients had higher GRACE scores (173.02 vs. 128.34, P<0.001) and creatinine levels (710 vs. 665 mg/L, P<0.001). Elevated HCY independently predicted MACCE (HR:1.036, 95% CI:1.011–1.062, P=0.005), with a ROC-derived cutoff of 14.05 µmol/L (AUC:0.662, sensitivity:74%, specificity:56%).

Discussion

HCY and STEMI Prognosis

While HCY has been implicated in endothelial dysfunction and oxidative stress, this study found no independent association between HCY levels and outcomes in the overall STEMI cohort. This aligns with prior mixed evidence in acute coronary syndromes, where traditional risk factors (age, hypertension, Killip class) dominate prognosis. However, the age-specific analysis revealed HCY’s predictive utility in elderly patients, likely reflecting compounded effects of renal impairment and chronic vascular damage in this subgroup.

Mechanistic Considerations

HCY’s role in atherosclerosis involves promoting inflammation, platelet activation, and endothelial injury. However, acute STEMI pathophysiology—driven by plaque rupture and thrombotic occlusion—may overshadow HCY’s subtler contributions. In elderly patients, prolonged exposure to elevated HCY, coupled with age-related declines in renal function and metabolic resilience, likely amplifies its adverse effects.

Clinical Implications

  • Risk Stratification: HCY measurement may enhance risk assessment in elderly STEMI patients, complementing traditional markers like GRACE scores.
  • Therapeutic Targeting: Despite HCY’s association with outcomes, trials of folic acid/B-vitamin supplementation have not reduced cardiovascular events, suggesting HCY may be a marker rather than a modifiable risk factor.

Conclusion

This study underscores the limited prognostic value of serum HCY in unselected STEMI populations but highlights its utility in elderly patients. Hypertension, Killip class, and renal function remain central to risk stratification, while HCY’s role appears context-dependent, meriting further investigation in age-specific cohorts.

DOI: https://doi.org/10.1097/CM9.0000000000000159

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