CAUSES OF HYPERHOMOCYSTEINEMIA
A number of enzymes, essential cofactors, and the availability of the important cosubstrate methyltetrahydrofolate regulate plasma homocysteine concentrations. Predictably, therefore, the causes of hyperhomocysteinemia are multifactorial.
Environmental Factors
Age and Gender
Plasma tHcy increases with age in both genders, for reasons that have not been elucidated.
Decreases in cofactor levels or coexisting renal impairment often seen in older patients may be responsible, and age-dependent reductions in cystathionine ~-synthase activity may also playa part. In general, men have higher plasma levels than women. After menopause, fasting tHcy seems to increase although this has not been confirmed, and hormone replacemen therapy can lower elevated tHcy levels in postmenopausal women. Although gender differences may be explained by the effect of sex hormones on homocysteine metabolism, they may be related to higher creatinine values or the greater muscle mass of men than women. Homocysteine is decreased by up to 50% during pregnancy, returning to normal 2 - 4 d postpartum. The authors suggest several reasons for this decrease, including the hemodilution known to occur in pregnancy, or an increased demand for methionine by the fetus, leading to increased remethylation of homocysteine.
Ethnic Group
Despite a high prevalence of CHD risk factors such as hypertension, obesity, and smoking, CHD incidence rate is much lower among westernized black Africans compared with the white population. A group of 27 black men, aged 18 - 25 yr, had tHcy 46% lower than similarly aged white men. By contrast, in a study examining tHcy and B-vitamin levels in American black pre-menopausal women, who have higher rates of CAD than white women, black women had higher tHcy and lower folate examined homocysteine and CAD in the Hong Kong Chinese population. Although the evalence of hyperhomocysteinemia was similar to that in white subjects, elevated tHcy was not an independent risk factor, being associated with smoking. Serum vitamin B12 did not Mer between patients and control subjects. The observation of higher serum folate in those with elevated tHcy does not seem compatible with what is known about tHcy metabolism.
Coexistent Disease
Elevated homocysteine levels are found in a number of disease states. Impaired renal :unction is associated with hyperhomocysteinemia. There is a positive correlation between :asting plasma tHcy and serum creatinine although the mechanism is unclear. Markedly elevated homocysteine levels have also been seen in acute lymphoblastic leukemia various
cinomas (including breast, ovary and, pancreas, severe psoriasis, and diabetes mellitus.
