This meta-analysis of observational studies suggests that elevated homocysteine is at most a modest independent predictor of IHD and stroke risk in healthy populations. Studies of the impact on disease risk of genetic variants that affect blood homocysteine concentrations will help determine whether homocysteine is causally related to vascular disease, as may large randomized trials of the effects on IHD and stroke of vitamin supplementation to lower blood homocysteine concentrations.

Reduced, oxidized and protein-bound forms of homocysteine (Hcy), cysteine and cysteinylglycine in plasma interact via redox and disulphide exchange reactions, and these aminothiol species comprise a dynamic system referred to as redox thiol status. Notably, in plasma reduced cysteine is the most abundant low molecular weight sulfhydryl compound. Elevation of plasma Hcy (hyperhomocysteinemia) causes changes in redox thiol status. Protein-bound Hcy increases up to a maximum capacity of about 140 micromol/L, and there is a concurrent displacement of protein-bound cysteine. When the Hcy binding approaches saturation, free oxidized and reduced Hcy show a substantial increase. The resulting increase in reduced/total ratio for Hcy causes a parallel change in this ratio for the other aminothiols. These dynamics were observed during both chronic hyperhomocysteinemia (due to cobalamin deficiency or homocystinuria) and acute hyperhomocysteinemia (induced by methionine or Hcy loading). In addition, changes in redox thiol status have been observed in patients with vascular disease (decreased reduced/total ratio for cysteine), renal failure (low reduced/total ratio for aminothiols) or HIV infection (high level of reduced Hcy), which suggest primary imbalance between prooxidant and antioxidant processes in these patients. In conclusion, redox thiol status is a dynamic system which is probably linked to the extracellular antioxidant defence system. This must be taken into account when designing future experimental or epidemiological studies on Hcy and cardiovascular disease.

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Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.

Predictive power, for total and vascular mortality, of selected indices measured at baseline in the British National Diet and Nutrition Survey (community-living subset) of People Aged 65 Years and Over was tested. Mortality status and its primary and underlying causes were recorded for 1100 (mean age 76·7 (SD 7·5) years, 50·2 % females) respondents from the baseline survey in 1994-5 until September 2008. Follow-up data analyses focussed especially on known predictors of vascular disease risk, together with intakes and status indices of selected nutrients known to affect, or to be affected by, these predictors. Total mortality was significantly predicted by hazard ratios of baseline plasma concentrations (per SD) of total homocysteine (tHcy) (95 % CI) 1·19 (1·11, 1·27), pyridoxal phosphate 0·90 (0·81, 1·00), pyridoxic acid 1·10 (1·03, 1·19), a 1 -antichymotrypsin 1·21 (1·13, 1·29), fibrinogen 1·14 (1·05, 1·23), creatinine 1·20 (1·10, 1·31) and glycosylated Hb 1·23 (1·14, 1·32), and by dietary intakes of energy 0·87 (0·80, 0·96) and protein 0·86 (0·77, 0·97). Prediction patterns and significance were similar for primary-cause vascular mortality. The traditional risk predictors plasma total and HDL cholesterol were not significant mortality predictors in this age group, nor were the known tHcy-regulating nutrients, folate and vitamin B 12 (intakes and status indices). Model adjustment for known risk predictors resulted in the loss of significance for some of the afore-mentioned indices; however, tHcy 1·34 (1·04, 1·73) remained a significant predictor for vascular mortality. Thus, total and primary vascular mortality is predicted by energy and protein intakes, and by biochemical indices including tHcy, independent of serum folate or vitamin B 12 .

We found little evidence of an effect of the child's MTHFR or FVL alleles on the risk of preeclampsia. Our estimates of effects of maternal MTHFR and FVL alleles were consistent with estimates from case-control studies. The case-parent triad design may be a useful tool for studies of pregnancy complications such as preeclampsia.

CBZ therapy may be associated with low folate and high p-tHcy levels.