Homocysteine studies

Brevick A, Vollset S, Tell G, Refsum H, Ueland P, Locken E, Drevon C and Andersen L. 2005. Plasma concentration of folate as a biomarker for the intake of fruit and vegetables the Hordaland Homocysteine Study. Am J Clin Nutr 81 434 139. 

Nygird 0, Refsum H, Ueland PM, Stensvold I, Nordrehaug JE, Kv le G, Vollset SE. (1997). Coffee consumption and plasma total homocysteine the Hordaland Homocysteine Study. Am J Clin Nutr. 65(1) 136-43. 

Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke a meta-analysis. JAMA 288 2015-2022... 

Many studies published during the last few decades have suggested that hyperhomocysteinemia is a risk factor for coronary artery disease (CAD), stroke, and thromboembolic disease. The Homocysteine Studies Collaboration metaanalysis of 30 studies concluded that elevated tHcy is a moderate risk factor for ischemic heart disease a level 3 xmol/L lower reduces the risk with an odds ratio of 0.89 (95% Cl = 0.83-0.96). The same was true for homocysteine as a risk factor for stroke (odds ratio = 0.81 95%5CI = 0.69-0.95) (6). A meta-analysis of 40 studies of the MTHFR 677 C > T polymorphism demonstrated a mildly increased risk of coronary heart disease with an odds ratio of 1. 16 (95% Cl = 1.05-1.28) (25). 

Like cholesterol, tHcy appears to be a graded risk factor, and even mild hyperhomocysteinemia confers an increased risk of cardiovascular events. A meta-analysis concluded that a 25% elevation in plasma tHcy (about 3 ftmol/L) is predictive of about a 10% increased risk of myocardial infarction and a 20% increased risk of stroke (Homocysteine Studies Collaboration, 2002). 

VoUset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, et al. Plasma total homocysteine, pregnancy complications, and adverse outcomes the Hordaland Homocysteine Study. Am J Clin Nutr 2000 71 962-8. 

BjeUand I, TeU GS, VoUset SE, Refsun H, Ueland PM. Folate, vitamin B12, homocysteine and the MTHFR 677C -> T polymorphism in anxiety and depression the Hordaland Homocysteine Study Arch Gen Psychiatr 2003 60 618-626. 

To assess the relationship of Hey concentrations with vascular disease risk, a meta-analysis of observational studies was carried out, showing that elevated Hey is at most a modest independent predictor of ischemic heart disease and stroke risk in healthy populations. Studies of the impact on disease risk of genetic variants that affect blood Hey concentrations will help determine whether Hey is causally related to vascular disease, as may large randomized trials of the effects on ischemic heart disease and stroke of vitamin supplementation to lower blood Hey concentrations (Homocysteine Studies Collaboration 2002). 

In order to estimate reliably the associations of homocysteine with CHD and stroke outcomes, individual participant data were collected from all observational studies of homocysteine with CHD and stroke outcomes for the Homocysteine Studies Collaboration (Homocysteine Studies Collaboration 2002). With individual participant data, the Homocysteine Studies Collaboration meta-analysis was able to examine the shape and strength of association of homocysteine with vascular disease after adjustment for bias and confounding due to other risk factors (Homocysteine Studies Collaboration 2002). After excluding individuals with prior disease at enrolment and adjustment for smoking, blood pressure and cholesterol, a 25% lower usual i.e. longterm) homocysteine concentration (about 3 pmol/L, a difference typically achieved by folic add supplementation in populations without mandatory fortification of grain products with folic acid) was associated with an 11% (95% Cl 4-17%) lower risk of CHD and a 19% (5-31%) lower risk of stroke (Homocysteine Studies Collaboration 2002). 

The subsequent evidence from the Homocysteine Studies Collaboration meta-analysis demonstrated the importance of homocysteine for cardiovascular risk was much less extreme than had been previously believed (Table 45.1). The Homocysteine Studies Collaboration meta-analysis did not adjust for the effects of creatinine, as these data were not available, and so was unable to assess the extent to which the assodation of homocysteine with vascular disease could have been confounded by renal function. 

Homocysteine Studies Collaboration 5073 25% lower usual tHcy ->10% lower CHD risk in prospective studies... 

Although the observational studies suggested modest associations of homocysteine with risk of vascular disease that were biologically plausible, such studies could not establish if these associations were causal. The randomized trials assessed the effectiveness of dietary supplementation with B vitamins to lower homocysteine levels on risk of cardiovascular morbidity and mortality. The initial trials were designed in the mid-1990s before the results of the Homocysteine Studies Collaboration meta-analysis (Homocysteine Studies Collaboration 2002) were reported in 2002. Consequently, few of the individual trials had sufficient statistical power to confirm or refute the 10% difference in... 

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