Plasma S-adenosylhomocysteine: A potential risk marker for cerebral venous thrombosis.

BACKGROUND: Despite a plethora of studies suggesting that hyperhomocysteinemia is associated with an increased risk for arterial and venous thrombosis, there is paucity of data on the role of the S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine (Hcy) as a risk predictor for cerebral venous thrombosis (CVT). METHOD: We estimated fasting plasma concentrations of total homocysteine (tHcy), SAH and S-adenosylmethionine (SAM), in 185 CVT patients and 248 healthy controls, by reverse-phase high performance liquid chromatography coupled with coulometric electrochemical detection. RESULTS: Fasting tHcy, SAH and SAM were significantly higher in patients compared with controls. Increased tHcy and SAH concentrations were associated with 4.54-fold (95% CI, 2.74-7.53) and 35.77-fold (95% CI, 19.45-65.79) increase in risk for CVT, respectively. Receiver operating characteristic (ROC) curve analysis showed that the area under curve, sensitivity and specificity was higher for SAH compared to tHcy. Further, discriminant analysis to distinguish between tHcy and SAH showed that SAH had a significantly higher percentage classification, with lower Wilk's lambda and higher χ(2), compared to tHcy. CONCLUSION: Increased plasma SAH may be a more sensitive risk marker for CVT than plasma tHcy.

Hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T polymorphism in cerebral veno-sinus thrombosis.

There is limited data on the role of hyperhomocysteinemia as a risk factor for cerebral veno-sinus thrombosis (CVT) in Indians. We examined the association between plasma homocysteine (Hcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and CVT in 185 patients with aseptic CVT (puerperal 80 and nonpuerperal 105) and 248 healthy controls (puerperal 67 and nonpuerperal 181). Fasting Hcy was higher in patients compared to controls (20.25 ± 5.97 vs 9.81 ± 5.19 µmol/L, P < .001) and associated with 4.54-fold (95% confidence interval [CI]: 2.74-7.53) increase in risk of CVT. Risk was higher in puerperal (odds ratio [OR]: 8.7, 95% CI: 2.73-26.91) compared to nonpuerperal CVT (OR: 3.82, 95% CI: 2.09-6.96). Plasma Hcy was higher in MTHFR 677TT compared to 677CT and 677CC genotypes (34.44 ± 32.8 vs 25.81 ± 33.3 vs 18.50 ± 23.7 µmol/L, respectively, P < .001), but the risk associated with MTHFR 677TT was insignificant (OR: 1.91, 95% CI: 0.53-7.06). We conclude that hyperhomocysteinemia is a risk marker for Indian patients with aseptic CVT. MTHFR 677TT genotype is not linked with CVT but is a determinant of plasma Hcy.

Homocysteine, folate and vitamin B(12) in puerperal cerebral venous thrombosis.

BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia (hyper-Hcy) is a known risk factor for venous thrombosis, but few studies document the risk in puerperal cerebral venous thrombosis (CVT). Nutritional folate and vitamin B(12) deficiency can cause hyper-Hcy and pregnancy may contribute to this deficiency. We studied the association of plasma total homocysteine (tHcy), folate and vitamin B(12) levels with puerperal CVT through a case-control study. METHODS: Sixty women with puerperal CVT and 64 healthy puerperal controls were recruited. Plasma fasting tHcy was estimated by high pressure liquid chromatography using coulometric electrochemical detection. Vitamin B(12) and folate were measured by radioimmunoassay. Risk of puerperal CVT was estimated for each of the three variables. RESULTS: Adjusted odds ratio for the risk of puerperal CVT with hyper-Hcy (>90th percentile) was 10.8 (95% CI: 4.0-29.4; adjusted for vitamin B(12) and folate levels). Low folate and vitamin B(12) levels (<10th percentile) did not increase the risk for puerperal CVT. There was a significant inverse correlation between folate and tHcy levels (rho=-0.471, p<0.001). CONCLUSIONS: Hyperhomocysteinemia is associated with an increased risk of puerperal CVT occurring in Indian women and low folate levels contribute significantly to hyper-Hcy. Regular antenatal folate and vitamin B(12) supplementation is likely to lower puerperal tHcy levels, but its clinical benefit needs to be tested by large therapeutic trials.