Significance of hyperhomocysteinemia

Moderate hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular (CVD) and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy. Elderly persons have a high prevalence of HHCY. Vitamin deficiency is by far the most common cause of HHCY. Retrospective and prospective studies emphasize a causal relationship between HHCY and the CVD risk. Some vitamin intervention trials, however, did not lower the risk of CVD. From power calculation one can conclude that these trials may not involve sufficient numbers of patients to assure statistically valid conclusions. Re-analysis of the VISP study (excluding renal failure and vitamin B12 status tampering factors), however, detected a 21% decrease in the risk of stroke. This number has been confirmed by results from the HOPE 2 vitamin intervention trial. Folic acid enrichment of grain products in the US and Canada has led to a significant decline of stroke mortality, since 1998 annually 12900 fewer stroke deaths in the US and 2800 fewer stroke deaths in Canada. Despite negative results from secondary prevention trials regarding the CVD risk reduction there is convincing evidence about the effectiveness of B-vitamin supplementation in lowering the stroke risk. The overall decline in stroke risk calculated in meta-analysis from prospective studies and found in intervention trials is around 20%. Additionally, HHCY was recently linked to the occurrence and severity of chronic heart failure. HHCY is also a risk factor for osteoporotic fractures and vitamin treatment lowered the fracture risk significantly. Furthermore, there is a correlation between HHCY and cognitive disorders or Alzheimer's disease. HHCY is a predictive parameter for the decline in cognitive function. Hypomethylation is among the central mechanisms through which HHCY acts cytotoxically. HHCY and low folate are causal factors for pregnancy complications. In addition to the recommended folate supplementation, vitamin B12 supplementation could further decrease pregnancy complications. Determination of homocysteine plasma concentration should be part of the individual risk profile, especially for elderly subjects who are at risk for CVD, neurodegenerative diseases or osteoporotic fractures.