Relevance of plasma levels of free homocysteine and methionine as risk predictors for ischemic stroke in the young.

BACKGROUND & AIMS: The debated vascular risk potential of total homocysteine (tHcy), due to failed clinical trials designed on B vitamin supplementation, raises many possible explanations like the higher risk potential of the deleterious, free form of homocysteine (fHcy) or, the unchecked confounding effects of B-vitamins in tHcy-based association studies. Additionally, the cardiovascular risk probability of altered status of the homocysteine precursor, methionine (tMet) could shed light on the causality of association between tHcy and cardiovascular diseases. Hence, we aimed to evaluate the risk associations of elevated plasma levels of tHcy, fHcy and low levels of tMet with premature, ischemic stroke. METHODS: We recruited 171 young, ischemic stroke patients (aged ≤45 years) and 249 age- and gender-matched healthy controls. Plasma levels of fHcy, tHcy, tMet and vitamin B6 were estimated using HPLC coupled with coulometric electrochemical detection. Plasma levels of vitamin B12 and folate were estimated by radioimmunoassay. RESULTS: Elevated fHcy (>2.9 µmol/L) was independently and strongly associated with the risk of premature, ischemic stroke (OR = 9.62, 95% CI = 3.51-26.40). On the contrary, association between premature ischemic stroke and elevated tHcy (>15.0 µmol/L) was found to attenuate when adjusted for vitamin B6 values (OR = 0.24, 95%, CI = 0.03-1.69). Interestingly, compromised B6-status (<59.2 nmol/l) was found to confer high risk of premature ischemic stroke (OR = 170.80, 95% CI = 58.22-501.06). We could not establish any significant correlation between fHcy and B-vitamin levels (P > 0.05). Low tMet (<13.86 µmol/L) was also not significantly associated with premature, ischemic stroke (OR = 2.53, 95% CI = 0.613-10.38). CONCLUSION: Our results indicate significant but not-correlated, independent associations of fHcy and vitamin B6 with risk of premature, ischemic stroke. However, the causality of these associations need prospective and large scale validations. Further, our findings highlight the crucial confounding effects of B-vitamins on risk association between tHcy and premature ischemic stroke.

Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine) Treatment.

Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine) describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory) (mean age 39.26 ± 9.88 years; male 43, female 7) were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I) or Ayurveda treatment (Group II) for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS). Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F = 8.16, P = 0.007, F = 9.73, P = 0.004, F = 13.51, and P = 0.001, resp.). The BRS too increased following the treatment period (F = 10.129, P = 0.004). Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted.

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.