Type of Evidence | Extent to Which It Offers Support | Comment |
---|---|---|
Inborn errors | +++ 2-213 | Untreated, these patients suffer or even die of vascular disease; treatment prevents or delays vascular events |
Retrospective and cross-sectional studies | 2-213 | Due to the fact that blood sampling occurs after the event, the effect of CHD on tHcy concentrations cannot be excluded |
Prospective studies with healthy subjects | 2-213 | Evidence is stronger in older subjects and in studies with a short follow-up period |
Prospective studies with high-risk subjects | ++ | In these types of studies it cannot be excluded that the increased levels of tHcy are a marker of the degree of vascular disease |
Prospective studies with venous thrombosis | 2-213 | These studies indicate that the tHcy concentration may predominantly be a thrombogenic factor, although the number of prospective studies is small |
MTHFR 677C>T genotype | 2-213 | Lack of evidence that the 677TT genotype is associated with CHD may be a power problem |
Mechanism of action | ++ | Especially the relationship with endothelial function seems plausible |
Intervention trials with intermediate endpoints | +++ | Beneficial effects could also be the result of folic acid |
↵2-213 , indicates minor support; ++++, indicates strong support.