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PubMed2005

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003-2004).

Hypertension is a modifiable risk factor for cardiovascular disease, but its aetiology has not been fully elucidated. Recently, attention has been focused on the direct relations of plasma homocysteine (Hcy) to blood pressure (BP). The purpose of this study was to determine the relationship of Hcy with BP and other cardiovascular disease risk factors. This population-based study was a part of the Cardiovascular Risk Factors Survey and has been designed and conducted based on the methodology of the MONICA/WHO Project. A total of 1214 people aged 25-64 years were recruited using cluster sampling and assessed regarding standardized methods. BP was measured in seated position after a 10-min rest period. Blood samples were gathered and analysed according to standard methods. Variables were assessed in 1191 participants (416 men; 775 women). Mean age was higher in hypertensives compared to normotensives (P < 0.001). Mean Hcy was higher in hypertensives, but significant only in men (P < 0.031). Concurrent effects of Hcy, folate and vitamin B12 on hypertension indicated that Hcy acts as a risk factor and folate and vitamin B12 as protective factors; however, after adjustment, just vitamin B12 remained as a protective factor. Although we detected a simple correlation of Hcy with BP in Iranian adults, this relationship was no longer significant after applying an adjustment. In light of our observations, it is likely that the increased Hcy levels reported in hypertensive persons are concomitant rather than a precursor of hypertension.

Adult↗
PubMed1997

Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study.

The health consequences of coffee drinking remain controversial. We report on an association between coffee consumption and the concentration of total homocysteine (tHcy) in plasma, a risk factor for cardiovascular disease and for adverse pregnancy outcome. The study population consisted of 7589 men and 8585 women 40-67 y of age and with no history of hypertension, diabetes, ischemic heart disease, or cerebrovascular disease. They were recruited from Hordaland county of western Norway in 1992-1993. Daily use of coffee was reported by 89.1% of the participants, of whom 94.9% used caffeinated filtered coffee. There was a marked positive dose-response relation between coffee consumption and plasma tHcy, which was stronger than the relation between coffee and total serum cholesterol. In 40-42-y-old men, mean tHcy was 10.1 mumol/L for nonusers and 12.0 mumol/L for drinkers of > or = 9 cups of coffee/d. Corresponding tHcy concentrations in 40-42-y-old women were 8.2 and 10.5 mumol/L, respectively. Although coffee drinking was associated with smoking and lower intake of vitamin supplements and fruit and vegetables, the coffee-tHcy association was only moderately reduced after these variables were adjusted for. The combination of cigarette smoking and high coffee intake was associated with particularly high tHcy concentrations. A strong inverse relation between tea and tHcy concentration in univariate analysis was substantially attenuated after smoking and coffee drinking were adjusted for. The results of the present report should promote future studies on tHcy as a possible mediator of adverse clinical effects related to heavy coffee consumption.

Adult↗
PubMed2000

Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study.

BACKGROUND: Total homocysteine (tHcy) measured in serum or plasma is a marker of folate status and a risk factor for cardiovascular disease. OBJECTIVE: Our objective was to investigate associations between tHcy and complications and adverse outcomes of pregnancy. DESIGN: Plasma tHcy values measured in 1992-1993 in 5883 women aged 40-42 y were compared with outcomes and complications of 14492 pregnancies in the same women that were reported to the Medical Birth Registry of Norway from 1967 to 1996. RESULTS: When we compared the upper with the lower quartile of plasma tHcy, the adjusted risk for preeclampsia was 32% higher [odds ratio (OR): 1. 32; 95% CI: 0.98, 1.77; P for trend = 0.02], that for prematurity was 38% higher (OR: 1.38; 95% CI: 1.09, 1.75; P for trend = 0.005), and that for very low birth weight was 101% higher (OR: 2.01; 95% CI: 1.23, 3.27; P for trend = 0.003). These associations were stronger during the years closest to the tHcy determination (1980-1996), when there was also a significant relation between tHcy concentration and stillbirth (OR: 2.03; 95% CI: 0.98, 4.21; P for trend = 0.02). Neural tube defects and clubfoot had significant associations with plasma tHcy. Placental abruption had no relation with tHcy quartile, but the adjusted OR when tHcy concentrations >15 micromol/L were compared with lower values was 3.13 (95% CI: 1.63, 6. 03; P = 0.001). CONCLUSION: Elevated tHcy concentration is associated with common pregnancy complications and adverse pregnancy outcomes.

Abruptio Placentae↗
PubMed2001

Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study.

BACKGROUND: Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality. OBJECTIVE: Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality. DESIGN: This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway. RESULTS: During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular and 1.3, 2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%) increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in noncancer, noncardiovascular mortality (33 deaths). CONCLUSION: Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65-72-y-olds. These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease.

Adult↗
PubMed2004

Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study.

BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors. OBJECTIVE: We examined whether changes in lifestyle influence tHcy over time. DESIGN: A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y). RESULTS: During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 micromol/L, respectively. Among the younger and older age groups, those who started to take vitamin supplements during follow-up had significant reductions in tHcy concentrations of 0.42 (95% CI: -0.65, -0.20) and 0.41 (-0.78, -0.03) micromol/L, respectively. In the younger subjects who quit smoking, tHcy concentrations decreased 0.54 (-0.91, -0.16) micromol/L. Weight changes were inversely related to tHcy. Both baseline history of cardiovascular disease or hypertension and cardiovascular events during follow-up were significantly associated with changes in tHcy. CONCLUSIONS: Changes in lifestyle factors over time influence tHcy concentrations. These changes are modest when compared with the strong associations between tHcy and lifestyle factors in cross-sectional studies.

Adult↗
PubMed1995

Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and peripheral vascular disease.

Elevated total homocysteine (Hcy) in plasma is an independent risk factor for early-onset vascular disease in the coronary, cerebral, and peripheral arteries. Different forms of Hcy, and their relation to other aminothiols in plasma, have not been investigated in patients with vascular disease. We therefore investigated 65 patients (35 men and 30 women) operated on for peripheral arterial disease at < 50 years of age and 65 age- and sex-matched control subjects. Total, reduced, oxidized, and protein-bound Hcy, cysteine (Cys), and cysteinylglycine (CysGly) were measured 0 to 11 years (mean, 6 years) postoperatively, in the fasting state, and after a standard methionine loading dose that caused a transient increase in reduced, oxidized, and protein-bound Hcy. All forms of Hcy and Cys, except reduced Cys, were higher in fasting patients than fasting control subjects. A similar difference between the groups was observed after methionine loading. The levels of most Hcy forms both during fasting and after methionine loading were related to smoking, but multivariate analysis showed that the difference between patients and control subjects could not be explained by smoking alone. Notably, reduced Cys and the reduced/total ratio for Cys were significantly higher in control subjects than in patients, both during fasting and after methionine loading. In both groups, the redox status and protein binding of the various aminothiols in plasma were interactive, as demonstrated by positive correlations between their reduced/total ratios and by a decrease in protein-bound Cys when protein-bound Hcy was elevated during methionine loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Serum levels of total homocysteine, homocysteine metabolites and of advanced glycation end-products (AGEs) in patients after renal transplantation.

AIMS: Hyperhomocysteinemia has been described as an independent risk factor for cardiovascular diseases (CVD) influencing patient outcome. Advanced glycation end-products (AGEs) are involved in the pathogenesis of vascular damage in uremia. This study was undertaken to assess whether high serum levels of total homocysteine (tHcy) with its metabolites methylmalonic acid (MMA), methylcitric acid (MCA) and cystathionine (CYSTA) as well as elevated serum concentrations of the AGEs pentosidine and Nepsilon-carboxymethyllysine (CML) are independent risk factors for CVD, left ventricular hypertrophy (LVH) or hypertension as well as kidney dysfunction in renal transplant recipients (RTR). METHODS: Serum levels of tHCy, MMA, MCA and CYSTA were measured by a gas chromatographic-mass spectrometric assay, pentosidine by HPLC and CML using an ELISA assay. RESULTS: All measured parameters were significantly higher in RTRs than in healthy subjects (p < 0.0001). The levels of pentosidine and CML as well as of tHcy and its metabolites correlated significantly with each other, but not with those ofMMA and CYSTA. Significant correlations were also found between pentosidine and tHcy, MMA or MCA as well as between CML, MMA and MCA, respectively. Acute or chronic rejection did not influence these values. No significant differences were observed between patients with or without CVD or with hypertension. In RTRs with LVH, only the tHcy levels were significantly higher than in those RTRs without LVH (p = 0.006). Logistic regression analysis revealed an independent influence of tHcy on the presence of LVH. CONCLUSION: These results may indicate an association between high tHcy values and LVH. Further investigation is needed to determine whether a reduction of tHcy and Hcy metabolites and/or AGE serum concentrations would significantly improve patient outcome after undergoing renal transplantation.

Adult↗
PubMed1999

[Hyperhomocysteinemia in CAPD patients: peritoneal transport of total homocysteine at peritoneal equilibration test and daily elimination of total homocysteine].

Peritoneal equilibration tests (PET) were performed in patients on continuous ambulatory and automated peritoneal dialysis (CAPD, APD) to evaluate the peritoneal transport capabilities for total homocysteine (tHcy) and other amino acids. Forty-five patients (24 males, 21 females, 50.6 +/- 12.8 years old) maintained on PD for 43.4 +/- 30.3 months participated in the study. PET revealed a markedly lower dialysate to plasma (D/P) ratio of tHcy at 4 hours (0.148 +/- 0.047) than those of other amino acids. A significant positive correlation between the D/P ratio of tHcy and the D/P ratio of creatinine was found, as well as between the D/P ratio of tHcy and the D/P ratio of albumin. The most significant positive correlation was found between dialysate and plasma levels of tHcy at 4 hours. There was no difference in the D/P ratio of tHcy between patients with D/P ratios of creatinine higher than the sample median of 0.68 and with D/P ratios of creatinine below 0.68, while the D/P ratios of other amino acids except threonine in the former patients tended to be higher than those of the latter patients. The D/P ratio of tHcy in patients with serum levels of albumin higher than 4.0 g/dl was significantly higher than that in patients with a ratio less than the sample median of 3.9 g/dl, whereas there were no significant differences in the D/P ratios of other amino acids. These observations suggest that the dialysate level of tHcy is primarily affected by the plasma level of tHcy, and that protein-bound Hcy mainly regulates the D/P ratio of tHcy. Daily peritoneal elimination of tHcy in 20 PD patients was 40.6 +/- 28.4 micromol. A significant positive correlation between the elimination of tHcy and plasma level of tHcy was also found. Daily elimination of tHcy in 7 patients with APD tended to be lower than that in 13 patients with CAPD. These findings indicate that the daily peritoneal elimination of tHcy does not compensate for the daily amount of tHcy metabolized in normal kidney, and that other therapies, such as folic acid administration, are required to improve hyperhomocysteinemia in patients on PD.

Adult↗
PubMed2004

[Homocysteine--an underestimated atheromatosis risk factor. Do sex hormones influence homocysteine concentrations?].

Recent data on the atherogenic effect of elevated concentrations of homocysteine (Hcy) and a review of published results on the influence of sex hormones, especially estrogens, on plasma Hcy levels are presented. Epidemiological data show that hyperhomocysteinemia as well as a mild elevation in plasma Hcy levels significantly increase cardiovascular risk. Some results do not support this relationship. Recently it was established that onset of menopause and decreases in serum estrogen levels probably increase serum Hcy concentrations. The majority of investigation, based on observational studies and the results of one randomized, double-blind placebo-controlled study, showed that use of estrogen and hormonal replacement therapy lowered HCY concentration. It has been observed that the decrease in Hcy level was greater the higher its concentrations before treatment. These results are in contrast with those of another randomized double-blind placebo-controlled study which showed that the Hcy concentration does not depend on menopause and does not change after hormonal treatment. Individual data showed that dehydroepiandrosterone, an adrenal steroid, probably lowers Hcy level. There were no correlations between serum Hcy concentration and insulin concentration, body mass, and type of obesity. The hypotheses about the influence of sex hormones on Hcy concentration are not clear and need further investigation.

Atherosclerosis↗
PubMed1986

Determination of in vivo protein binding of homocysteine and its relation to free homocysteine in the liver and other tissues of the rat.

Low concentrations (0.5-6 nmol/g) of homocysteine (Hcy) have recently been demonstrated in acid extracts of various tissues of the mouse and rat (Ueland, P.M., Helland, S., Broch, O.-J., and Schanche, J.-S. (1984) J. Biol. Chem. 259, 2360-2364). This is referred to as free Hcy in tissues. This paper describes a method for the determination of protein-bound Hcy, which involves precipitation and washing of tissue protein with ammonium sulfate, release of Hcy from native proteins in the presence of dithioerythritol, and determination of free Hcy by a sensitive radioenzymic assay. Both free and bound Hcy decreased markedly in rat tissues within a few seconds following death of the animal. The amount of protein-bound Hcy was highest in liver, somewhat lower in kidney, brain, heart, lung, and spleen. The ratio between free and bound Hcy was between 1 and 2 in most tissues, except in cerebellum, containing a large excess of free Hcy (free/bound ratio of 18). Free Hcy was almost exclusively localized to the soluble fraction of rat liver, whereas protein-bound Hcy was about equally distributed between this fraction and the microsomes. Isolated rat hepatocytes contained free and protein-bound Hcy in proportions observed in whole liver, but a large amount of Hcy was exported into the extracellular medium. The half-lives, as determined from pulse-chase experiments with [35S] methionine, were 53 s for S-adenosylmethionine, 2 s for S-adenosylhomocysteine and 3 s for Hcy (free and bound regarded as a single pool). Furthermore, isotope equilibrium between these metabolites and between free and bound Hcy throughout the rapid chase period suggests the turnover rates of S-adenosylhomocysteine and Hcy to be production rate limited, and the dissociation rate of the Hcy-protein complex may greatly exceed the turnover rate of Hcy. Thus, the half-lives of Hcy are such that participation of both free and bound Hcy in metabolic regulation is feasible.

Adenine↗