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H Refsum

Publications and source records attributed to H Refsum.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2001

Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians.

BACKGROUND: In India, most people adhere to a vegetarian diet, which may lead to cobalamin deficiency. OBJECTIVE: The objective was to examine indicators of cobalamin status in Asian Indians. DESIGN: The study population included 204 men and women aged 27-55 y from Pune, Maharashtra, India, categorized into 4 groups: patients with cardiovascular disease (CVD) and diabetes, patients with CVD but no diabetes, patients with diabetes but no CVD, and healthy subjects. Data on medical history, lifestyle, and diet were obtained by interviews and questionnaires. Blood samples were collected for measurement of serum or plasma total cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) and hemetologic indexes. RESULTS: MMA, tHcy, total cobalamin, and holoTC did not differ significantly among the 4 groups; therefore, the data were pooled. Total cobalamin showed a strong inverse correlation with tHcy (r = -0.59) and MMA (r = -0.54). Forty-seven percent of the subjects had cobalamin deficiency (total cobalamin <150 pmol/L), 73% had low holoTC (<35 pmol/L), 77% had hyperhomocysteinemia (tHcy >15 micromol/L), and 73% had elevated serum MMA (>0.26 micromol/L). These indicators of impaired cobalamin status were observed in both vegetarians and nonvegetarians. Folate deficiency was rare and only 2.5% of the subjects were homozygous for the MTHFR 677C-->T polymorphism. CONCLUSIONS: About 75% of the subjects had metabolic signs of cobalamin deficiency, which was only partly explained by the vegetarian diet. If impaired cobalamin status is confirmed in other parts of India, it may have important health implications.

Adult↗
PubMed2001

Plasma total homocysteine is influenced by prandial status in humans: the Hordaland Hhomocysteine Sstudy.

Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease, adverse pregnancy outcomes and impaired cognitive function. No population-based studies on the possible influence of prandial status on tHcy have been published. The aim of this study was to investigate the variation in plasma tHcy levels in relation to time since last meal. A cross-sectional, population-based study including 18,044 individuals in Western Norway was conducted. Most subjects were in the age groups 40-42 and 65-67 y. Participants who had not eaten during the past 6 h before the blood sampling had significantly higher mean tHcy levels compared with those who had eaten; 11.7 [95% confidence interval (CI): 11.4-12.1] vs. 11.2 (95% CI: 11.1-11.3) micromol/L among men (P = 0.03) and 10.2 (95% CI: 9.9-10.6) vs. 9.7 (95% CI: 9.6-9.7) micromol/L among women (P = 0.003). In all groups except older women, tHcy concentrations were generally higher with increasing time after a meal (P-trend <0.01 in all 3 groups). These findings suggest that fasting status and time since last meal may influence levels of tHcy and should be considered in studies of tHcy as a risk factor for cardiovascular and other diseases, and when comparing tHcy values among studies.

Adult↗
PubMed2001

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

BACKGROUND: In epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of 'usual' levels of tHcy with risk of cardiovascular disease, referred to as 'regression dilution'. The aim of this report was to estimate the magnitude of regression dilution after varying intervals of follow-up. METHODS: Regression dilution ratios (RDR) for tHcy were calculated using replicate tHcy measurements obtained after 3, 6 and 8 years from the Rotterdam, Hordaland and Framingham studies, respectively, and after 3, 6, 9 and 12 years from the United Kingdom Prospective Study of type 2 Diabetes Mellitus (UKPDS). RESULTS: The RDR for tHcy decreased with increasing interval in the three population-based studies and in the UKPDS. Moreover, the rate of decline of the RDR in the population-based studies was similar to that obtained in the UKPDS. Using linear regression analysis for the population-based studies, these results suggest an RDR of 0.83 at 2 years, 0.71 at 6 years and 0.53 at 12 years. CONCLUSIONS: These results have important implications for the interpretation of prospective studies of tHcy and cardiovascular disease. Failure to correct for increasing regression dilution using lower RDRs for longer follow-up may underestimate the relative risks of cardiovascular disease associated with tHcy by about one-fifth after 2 years and one-half after 10 years.

Aged↗
PubMed2001

Determinants of cobalamin status in newborns.

OBJECTIVE: Cobalamin deficiency accompanied by bone marrow dysfunction and impaired central nervous system development has been reported in infants who were born to mothers with low cobalamin intake. We investigated the relation between cobalamin status in newborns and in their healthy mothers who consumed an omnivorous diet. METHODS: Serum cobalamin and the functional markers plasma methylmalonic acid (MMA) and total homocysteine (tHcy) were determined in 173 newborns and their mothers. Forty-five children and mothers were reinvestigated after 6 weeks. RESULTS: At birth, median (interquartile range) serum cobalamin levels were 245 (175-323) pmol/L in the mothers and 314 (238-468) pmol/L in the newborns. In the neonates, serum cobalamin, but not folate, was inversely associated with MMA and tHcy. Among maternal factors, low serum cobalamin was the strongest predictor of impaired cobalamin function (defined as low cobalamin, high tHcy, or high MMA levels) in the newborns. After 6 weeks, the maternal cobalamin levels had increased (to 421 [271-502] pmol/L), whereas the newborn levels had declined (to 230 [158-287] pmol/L). In the same interval, the infants had a marked increase in plasma MMA (from 0.29 [0.24-0.38] to 0.81 [0.37-1.68] micromol/L). At 6 weeks, parity was a strong predictor of cobalamin status in the infant. CONCLUSION: The cobalamin status in the neonatal period is strongly associated with maternal cobalamin status and parity. A reduction in serum cobalamin and an increase in metabolite levels are consistent with impaired cobalamin function in a significant portion of the infants who were born to healthy, nonvegetarian mothers.

Adult↗
PubMed2001

Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome.

Increased folate intake reduces the risk of neural tube defects, other malformations and also possibly, pregnancy complications. Increasing evidence suggests that the beneficial effect of folate may be related to improved function of methionine synthase, a vitamin B12-dependent enzyme that converts homocysteine to methionine. In India, the majority of the population adheres to a vegetarian diet known to be deficient in vitamin B12. In such a population, increased folate intake may offer minimal protection against birth defects, whereas vitamin B12 administration should be considered. In this review, is described the metabolism of and interrelations between folate, vitamin B12 and homocysteine. This is followed by a brief discussion of some of the proposed mechanisms for their biological effects in relation to birth defects and pregnancy outcome.

Congenital Abnormalities↗
PubMed2000

Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD. METHODS AND RESULTS: We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo. CONCLUSIONS: Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.

Adult↗
PubMed2000

Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men.

BACKGROUND: Reasons for the increase in mortality due to coronary heart disease (CHD) in UK Indian Asians are not well understood. In this study, we tested the hypotheses that elevated plasma homocysteine concentrations are a risk factor for CHD in Indian Asians, and explain part of their increased CHD risk, compared with Europeans. METHODS: We undertook two parallel case-control studies, one in Europeans and one in Indian Asians. We recruited 551 male cases (294 European, 257 Indian Asian) and 1025 healthy male controls (507 European, 518 Indian Asian). Fasting and post-methionine load homocysteine, vitamin B12 and folate concentrations, and conventional CHD risk factors were measured. FINDINGS: Fasting homocysteine concentrations were 8% higher (95% CI 3-14) in cases compared with controls, in both ethnic groups. The odds ratio of CHD for a 5 micromol/L increment in fasting plasma homocysteine was 1.3 (1.1-1.6) in Europeans and 1.2 (1.0-1.4) in Indian Asians. The association between fasting plasma homocysteine and CHD was independent of conventional CHD risk factors in both ethnic groups. Post-load homocysteine concentrations were not significantly different in cases compared with controls. Among the controls, fasting homocysteine concentrations were 6% (2-10) higher in Indian Asians than in Europeans. From the results we estimate that elevated homocysteine may contribute to twice as many CHD deaths in Indian Asians, compared with Europeans. The differences in homocysteine concentrations between the two ethnic groups were explained by lower vitamin B12 and folate levels in Asians. INTERPRETATION: Plasma homocysteine is a novel and independent risk factor for CHD in Indian Asians, and may contribute to their increased CHD risk. Raised homocysteine concentrations in Indian Asians may be related to their reduced vitamin B12 and folate levels, implying that the increased CHD risk in this group may be reduced by dietary vitamin supplementation.

Case-Control Studies↗
PubMed2000

Biological and environmental determinants of plasma homocysteine.

This article gives an overview over common physiological, lifestyle, and pathological conditions that may modulate the homocysteine status. The interplay of several environmental factors, including age, gender, nutrition, smoking, and coffee consumption and physical activity with commonly used drugs and prevalent diseases are described. In most cases, an abnormal homocysteine status is not caused by a single factor alone but often is the result of combined effects. We address these frequently found "clusters" of homocysteine-modulating factors. Finally, we give an overview of likely causes of hyperhomocysteinemia found in an authentic material. This material is based on 2462 routine measurements of plasma total homocysteine carried out at the Haukeland University Hospital. The data represent the total number of combined homocysteine and methylmalonic acid determinations, requested by general practitioners in Norway during February 1998.

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↗
PubMed2000

The controversy over homocysteine and cardiovascular risk.

Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebo-controlled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.

Cardiovascular Diseases↗
PubMed2000

Signs of impaired cognitive function in adolescents with marginal cobalamin status.

BACKGROUND: Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. OBJECTIVE: The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. DESIGN: Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status. RESULTS: The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14). CONCLUSION: Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

Adolescent↗
PubMed2000

Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease.

BACKGROUND/AIMS: A moderately elevated plasma concentration of the sulphur amino acid homocysteine is an independent risk factor for atherosclerotic vascular disease. Many of the risk factors associated with coronary, cerebral, and peripheral atherosclerotic vascular disease are common to retinal vascular occlusive disease but it is unclear whether elevated plasma concentrations of homocysteine are also associated with such disease. This study assessed the relation between retinal vascular occlusive disease and elevated levels of plasma total homocysteine (tHcy). METHODS: A retrospective case-control study involving hospital based controls and cases with retinal artery, central retinal vein (including hemiretinal vein), and branch retinal vein occlusions was performed. The relation between elevated tHcy, defined as a level greater than or equal to 12 micromol/l and risk of retinal vascular occlusive disease was examined. RESULTS: 87 cases of retinal vascular occlusive disease including 26 cases of retinal artery occlusion, 40 cases with central retinal vein occlusion, and 21 cases of branch retinal vein occlusion were compared with 87 age matched controls. Mean tHcy levels were higher in all disease groups and this difference was significant in patients with retinal artery occlusions (p= 0.032) and patients with central retinal vein occlusion (p=0.0001). When adjusted for known cardiovascular risk factors, tHcy was an independent risk factor for retinal vascular occlusive disease (OR 2.85 (95% CI 1.43-5.68)). CONCLUSIONS: Elevated tHcy is an independent risk factor for retinal vascular occlusive disease. Assessment of tHcy may be important in the investigation and management of patients with retinal vascular occlusive disease.

Aged↗
PubMed2000

Methylenetetrahydrofolate reductase 677 C-->T mutation and coronary heart disease risk in UK Indian Asians.

Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9. 7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 micromol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TT MTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations in CHD cases compared with controls. TT MTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; P=0.39), unlike in European whites (odds ratio, 2.1; 95% confidence interval, 1.1 to 4. 1; P=0.02). We conclude that the MTHFR 677T: mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.

Adult↗
PubMed2000

Evaluation of novel assays in clinical chemistry: quantification of plasma total homocysteine.

BACKGROUND: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries. METHODS: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance. RESULTS: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor. CONCLUSIONS: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

Fluorescence Polarization Immunoassay↗
PubMed2000

Evaluation of indicators of cobalamin deficiency defined as cobalamin-induced reduction in increased serum methylmalonic acid.

BACKGROUND: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. METHODS: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17-87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 micromol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used. RESULTS: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0. 810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information. CONCLUSIONS: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.

Adolescent↗