A review of homocysteine and heart failure.

Chronic heart failure (CHF) is a major public health problem causing considerable morbidity and mortality. Recently, plasma homocysteine (HCY) has been suggested to be increased in CHF patients potentially representing a newly recognized risk marker. This manuscript reviews the existing literature regarding hyperhomocysteinemia (HHCY) and CHF. Clinical data indicate that HHCY is associated with an increased incidence of CHF as well as with the severity of the disease. Mechanistic studies of HHCY and CHF are rare. However, preliminary results suggest that HHCY causes adverse cardiac remodelling characterized by interstitial and perivascular fibrosis resulting in increased myocardial stiffness. In addition, HHCY seems to affect the pump function of the myocardium. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodelling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium as well as NO independent vascular effects are involved. In conclusion, HHCY might be a potential aetiological factor in CHF. Future studies need to clarify the mechanistic role of HHCY in CHF as a useful paradigm with most interesting therapeutic implications, because HCY lowering therapy could favourably influence the prognosis in CHF patients.