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  • Prognostic Efficacy of Homocysteine and high-sensitivity C-Reactive Protein on Neurological Outcome in Subarachnoid Hemorrhage: A Case for Reverse Epidemiology Paradox?

    Final Number:

    SS Dhandapani M.Ch.; H Singh; A Srinivasan; Manju Dhandapani M.Sc., M.A; KK Mukherjee; SK Gupta; SN Mathuriya

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: Homocysteine(tHcy) and high-sensitivity C-reactive protein(hs-CRP) have been assessed over past few decades for their profound impact on vascular diseases, but have not been evaluated together in subarachnoid hemorrhage(SAH). This study was to compare their prognostic efficacy on neurological outcome following SAH.

    Methods: Admission plasma tHcy and serum hs-CRP were evaluated in 92 patients of SAH, and prospectively studied in relation to various factors and GOS at three months. Univariate and multivariate analyses were performed using SPSS21.

    Results: tHcy was significantly higher following SAH compared to matched controls (median[IQR]: 25.7[17.3-35.9] vs. 14.0[9.8-17.6] µmol/L, p<0.001), whereas hs-CRP did not show significant difference. Both of these differed significantly with respect to age. But systemic disease, WFNS and Fisher grades did not have significant impact on their levels. tHcy was significantly lower among patients who died (median[IQR]: 16.0[14.4-20.6] vs. 29.7[21.8-40.2] µmol/L, p<0.001) and those with unfavorable outcome (GOS 1-3) (median[IQR]: 21.6[14.5-28.2] vs. 30.3[20.4-40.7] µmol/L, p=0.004) compared to others, with significant continuous positive correlation between tHcy and GOS (p=0.002). hs-CRP had non-significant inverse correlation with GOS, featuring higher levels among those who developed unfavorable outcome. The beneficial association of tHcy on outcome was homogeneous with no significant subgroup difference. Multivariate analysis using binary logistic regression adjusting for the effects of age, systemic disease, WFNS grade, Fisher grade, site of aneurysm, clipping or coiling, revealed higher tHcy to have significant independent association with both survival (p=0.01) and favorable outcome (p=0.04), while higher hs-CRP had non-significant tendency towards unfavorable outcome (p=0.08).

    Conclusions: Higher homocysteine levels following SAH appear to have significant association with both survival and favorable neurological outcome, independent of other known prognostic factors, exemplifying “reverse epidemiology paradox” in SAH.

    Patient Care: tHcy may be useful as a prognostic biomarker in SAH, and therapeutic modulation of Hcy metabolism may be helpful to enhance outcome after SAH.

    Learning Objectives: To be able to: 1)Describe the prognostic relevance of tHcy and hs-CRP in patients with SAH, 2)Discuss the mechanisms of classical epidemiology and reverse epidemiology of tHcy, 3)Discuss the protective association of tHcy levels on Neurological outcome after SAH.


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