Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study.

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.

Influence of age, sex and vitamin status on fasting and post-methionine load plasma homocysteine levels.

BACKGROUND AND OBJECTIVES: To investigate the effects of age, sex and vitamin status on total plasma homocysteine (tHCy), both after fasting (FtHCy) and two hours post-methionine load (PML-tHCy). The secondary aim was to determine the reference values for FtHCy and PML-tHCy. DESIGN AND METHODS: A cohort of apparently healthy volunteers underwent blood sampling for FtHCy, PML-tHCy, creatinine, serum folate, vitamin B12 and vitamin B6 (pyridoxal-5-phosphate, PLP). RESULTS: In 147 subjects (M/F= 82/65, age range: 14-94 years), FtHCy was significantly higher in men than in women. In men, age and folate levels explained 20.5% and 19.0% of FtHCy variance, respectively. In women, age and vitamin B12 accounted for 22.6% and 17.8% of FtHCy variance, respectively. PML-tHCy was similar in men and women. PML-tHCy was negatively correlated with folate in both sexes, and with vitamin B12 and age in women only. Folate accounted for 20% of the variance of PML-tHCy in men, while in women vitamin B12 and PLP explained 40% and 20% of variance of PML-tHCy, respectively. The reference values of FtHCy and PML-tHCy were: 19.63 and 40.18 mol/L, respectively, for men under 45 years, 14.26 and 28.31 mol/L, respectively, for women under 45 years, 28.38 and 36.48 mol/L for men above 45 years, and 22.49 and 44.06 mol/L for women above 45 years. INTERPRETATION AND CONCLUSIONS: Age, gender and vitamin status influence both FtHCy and PML-tHCy in normal subjects. Reference values should be calculated according to age and sex.

Homocysteine and psychological traits: a study in obesity.

OBJECTIVE: Total serum homocysteine is a risk factor for cardiovascular disease in the general population. Further, homocysteine might be the link between psychological traits (namely anger and hostility) and cardiovascular disease, mediated by stressful events and sympathetic nervous tone. METHODS: We measured total plasma homocysteine levels and psychological traits in 205 obese individuals entering a weight-reduction program (162 females; age range, 17-64 years; body mass index, 37.7 +/- 6.2 kg/m(2), mean +/- standard deviation). Psychometric assessment was performed with three self-administered questionnaires (Symptom Checklist 90, composed of nine subscales including Hostility/Anger and Depression scales; Beck Depression Inventory; and Binge Eating Scale). RESULTS: Homocysteine levels were moderately increased in obese individuals when compared with the normal population and higher in males (median, 12.9 micromol/L; range, 6.9-26.3) than in females (9.8; 4.6-24.6; P < 0.0002), but not different in relation to the severity of obesity. Serum folate and vitamin B12 were normal. Psychometric testing showed pathologic data in up to 50% of patients and the Anger/Hostility scale was positive in 24%, mainly female, subjects. There were no differences in psychological traits in relation to the severity of obesity. Homocysteine did not correlate with Symptom Checklist 90 values or other values of psychometric testing. CONCLUSIONS: In obese persons, psychological traits are not major determinants of total homocysteine. A different response to stressful events, not simply mediated by sympathetic nervous tone, might be present in obesity.

Biological Determinants of Fasting and Postload Plasma Homocysteine Levels in Healthy Italian Subjects.

Genetic and nutritional factors are determinants of total plasma homocysteine (tHCy) whose increased levels play a pathogenic role in atherothrombosis and cardiovascular disease. This study investigated the influence of sex, age, creatinine, serum folate, vitamin B12 and vitamin B6 (pyridoxal- 5-phosphate, PLP) on fasting (FtHCy) and two hour postmethionine loading levels of tHCy in 147 apparently healthy subjects (M/F= 82/65, age range: 14-94 y). FtHCy was higher in men than women (9.89 vs 8.00 µmol/L, p< 0.01). In males, the main determinants of FtHCy were age and folate levels, respectively explaining 20.5% and 19.0% of FtHCy variance. In women, besides age (22.6%), vitamin B12 (17.8%) rather than folate was a major determinant of FtHCy. Two hour postload tHCy, expressed both as absolute value (PML) and as the difference between 2 hour postload tHCy and FtHCy (delta tHCy) was negatively correlated with folate in both sexes, and with vitamin B12 and age in women only. In males folate was the main determinant, explaining 20% of the variance of postload values, while in females vitamin B12 and PLP were predominant, explaining respectively 40% and 20% of that variance. Age was not among the main determinants of postload values in either sex. These results demonstrate that age and vitamin status differently influence both the fasting and the postmethionine plasma homocysteine levels in normal subjects.