Biomedical subjects

Per M Ueland

Publications and source records attributed to Per M Ueland.

29 records · Page 2Linked to original sources

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↗

PubMed2004

Facts and recommendations about total homocysteine determinations: an expert opinion.

BACKGROUND: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. METHODS: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. OUTCOME: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

Blood Specimen Collection↗

PubMed2003

Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation.

OBJECTIVE: Betaine is a substrate in the betaine-homocysteine methyltransferase reaction, converting homocysteine to methionine. There are only sparse data on plasma betaine as a determinant of the plasma total homocysteine (tHcy) concentration. METHODS AND RESULTS: Ninety patients undergoing coronary angiography were randomized into 4 groups administered oral: (1) folic acid (0.8 mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg); (2) folic acid and vitamin B12; (3) vitamin B6 alone; or (4) placebo. Nonfasting blood samples were collected at baseline and 3, 14, and 28 days and 3, 6, and 12 months after treatment start. A 4-hour methionine-loading test (0.1 g/kg) was performed at baseline and after 3 months. At baseline, median (interquartile range) plasma betaine was 36.9 micromol/L (range: 30.3 to 46.8) and was increased by 15% after methionine loading. The postmethionine load (PML) increase in tHcy was inversely related to plasma betaine (beta=-0.29, P=0.02) and even more strongly to PML betaine (beta=-0.47, P<0.001). After 3 months of intervention, the relation between the PML increase in tHcy and PML betaine was weakened (beta=-0.33, P=0.007). CONCLUSIONS: Plasma betaine is a strong determinant of the PML increase in tHcy in subjects not supplemented with B-vitamins.

Administration, Oral↗

PubMed2003

Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project.

BACKGROUND: Homozygotes for the thermolabile mutation (TT genotype) of the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated plasma concentrations of the cardiovascular disease risk factor homocysteine, particularly if folate depleted. OBJECTIVE: We examined the relations between thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease risk. DESIGN: This was a case-control comparison in 711 vascular disease cases and 747 controls from 9 European countries. RESULTS: The TT genotype was associated with higher homocysteine and lower plasma folate than the CC and CT genotypes in both cases and controls and a nonsignificant increase in vascular disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT genotype in cases was not significantly different from that in controls (12.8% compared with 10.8%). After adjustment for traditional risk factors, the TT genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of vascular disease. This risk was attenuated after further adjustment for homocysteine. In subgroups with homocysteine concentrations >or= 9 micro mol/L, risk tended to be higher in CC than in TT subjects. However, CC subjects were characterized by a higher prevalence of the conventional risk factors associated with both elevated plasma homocysteine and serum creatinine. After adjustment, the risk of vascular disease associated with each genotype was not significantly different. CONCLUSIONS: There was a strong graded association between homocysteine and vascular risk in all genotypes. MTHFR genotype is a key determinant of plasma total homocysteine concentrations. The initially nonsignificant risk estimate associated with the TT genotype was strengthened after adjustment for conventional cardiovascular disease risk factors but was attenuated after adjustment for plasma folate and total homocysteine. The modest risk increase conferred by the TT genotype is mediated mainly by increased total homocysteine and low plasma folate concentrations.

Adult↗

PubMed2003

Plasma total cysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine Study.

BACKGROUND: Total homocysteine (tHcy) is associated with pregnancy complications and adverse pregnancy outcomes. The associations of plasma total cysteine (tCys) with such outcomes have not been investigated in large populations. OBJECTIVE: We investigated the association between plasma tCys and pregnancy complications, congenital malformations, and other adverse pregnancy outcomes. DESIGN: The plasma tCys concentrations of 5883 women aged 40-42 y that were measured in 1992-1993 during a cardiovascular health screening were compared with the outcomes and complications of 14492 pregnancies in the same women that were registered in the Medical Birth Registry of Norway from 1967 to 1996. RESULTS: After adjustment for parity, mother's age, tHcy, total cholesterol, body mass index, smoking, and coffee drinking, high plasma tCys concentrations (above the 95th percentile) were associated with significantly higher risks of preeclampsia [n = 342; odds ratio (OR): 1.6; 95% CI: 1.1, 2.4; P = 0.03], premature delivery (n = 774; OR: 1.8; 95% CI: 1.3, 2.5; P = 0.001), and very low birth weight (n = 175; OR: 2.0; 95% CI: 1.1, 3.9; P = 0.03) than were lower plasma tCys concentrations. tCys was not associated with the risk of placental abruption. High tCys concentrations showed a weak association with congenital malformations and stillbirths with birth weight <1500 g. The associations were independent of the tHcy concentrations. CONCLUSION: High tCys concentrations were associated with risks of preeclampsia, premature delivery, and low birth weight.

Abruptio Placentae↗

PubMed2003

Screening for vitamin B-12 and folate deficiency in older persons.

BACKGROUND: Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency. OBJECTIVE: We assessed the prevalence of vitamin B-12 and folate deficiency in a population-based study (n = 1562) of older persons living in Oxford City, United Kingdom. DESIGN: We postulated that, as vitamin B-12 or folate concentrations declined from adequate to impaired levels, tHcy (or MMA) concentrations would increase. Individuals were classified as being at high risk of vitamin B-12 deficiency if they had low vitamin B-12 (< 150 pmol/L) or borderline vitamin B-12 (150-200 pmol/L) accompanied by elevated MMA (> 0.35 micromol/L) or tHcy (> 15.0 micromol/L). Individuals were classified as being at high risk of folate deficiency if they had low folate (< 5 nmol/L) or borderline folate (5-7 nmol/L) accompanied by elevated tHcy (> 15 micromol/L). RESULTS: Cutoffs of 15.0 micro mol/L for tHcy and 0.35 micro mol/L for MMA identified persons with normal or elevated concentrations. Among persons aged 65-74 and >or= 75 y, respectively, approximately 10% and 20% were at high risk of vitamin B-12 deficiency. About 10% and 20%, respectively, were also at high risk of folate deficiency. About 10% of persons with vitamin B-12 deficiency also had folate deficiency. CONCLUSION: Use of tHcy or MMA among older persons with borderline vitamin concentrations may identify those at high risk of vitamin B-12 deficiency who should be considered for treatment.

Age Factors↗

PubMed2003

Predictors of change in plasma total cysteine: longitudinal findings from the Hordaland homocysteine study.

BACKGROUND: Total cysteine (tCys) in plasma has recently been linked to cardiovascular risk and is also associated with cardiovascular risk factors, including body mass index (BMI) and cholesterol. Changes and predictors of change in tCys concentrations over a mean follow-up time of 6.0 (5.2-7.2) years were assessed in this study. METHODS: Baseline data from the Hordaland Homocysteine Study recorded in 1992-1993 included tCys, total homocysteine (tHcy), and various lifestyle and cardiovascular risk factors. In 1998-1999, the same measurements were repeated in 3,732 individuals born in 1950-1951 and 3,339 individuals born in 1925-1927. Most of the statistical analyses were done separately in the four age and sex groups. RESULTS: The overall mean values of tCys were higher at follow-up [mean (SD), 296 (41) micro mol/L] than at baseline [278 (36.5) micro mol/L]; P <0.0001. The mean percentage of increase in tCys in the different age and sex groups ranged from 4.9% to 8.5%. There was a significant correlation between the tCys values measured on the two occasions (Spearman correlation coefficient, 0.55-0.59 in the different age and sex groups; P <0.0001). The change in tCys correlated with changes in BMI, cholesterol, and diastolic blood pressure in the younger age group, whereas only changes in BMI predicted changes in tCys in the older age group. CONCLUSIONS: tCys increased in the 6 years between the two measurements. Factors related to the baseline tCys values, including BMI and the change in BMI, predicted the tCys changes over time.

Adult↗

PubMed2003

Plasma total cysteine, mortality, and cardiovascular disease hospitalizations: the Hordaland Homocysteine Study.

BACKGROUND: We have previously reported a positive association between tHcy and mortality and cardiovascular disease (CVD) hospitalizations in the Hordaland Homocysteine Study cohort. Using the same data set, we assessed the relationship between plasma total cysteine (tCys) and mortality from all causes and from cardiovascular and noncardiovascular conditions, and the association between tCys and the risk of hospitalizations from CVD. METHODS: We measured plasma tCys in blood samples from 12,595 men and women 40-42 years of age and from 4766 men and women 65-67 years of age, collected as part of the Hordaland Homocysteine Study in the year 1992-1993. Follow-up data on mortality were collected through 1999. Data on CVD hospitalizations were collected from hospital records up to May 31, 1998. RESULTS: After a follow-up time of 6.6-7.6 years, there were a total of 610 deaths, of which 243 were cardiovascular deaths and 367 were noncardiovascular deaths. There was no association between tCys and all-cause, cardiovascular, or noncardiovascular mortality. When we used tCys values <247.6 micromol/L (lowest quartile) as the reference category, the adjusted mortality ratio (MR) for all-cause mortality at tCys concentrations of 247.6-270.79, 270.8-295.79, and > or =295.8 micromol/L (highest quartile) were 1.0, 0.9, and 1.0, respectively. The adjusted MRs for cardiovascular mortality were 1.0, 1.1, and 1.1, respectively. There were no associations between tCys and 1275 CVD hospitalizations, except that tCys was significantly associated with hospitalizations from coronary artery bypass grafting. CONCLUSION: Plasma tCys is not associated with mortality or CVD hospitalizations.

Adult↗

PubMed2002

Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) level is a risk factor for occlusive disease in the coronary, cerebral, and peripheral vessels and is related to several lifestyle factors associated with cardiovascular disease (CVD). OBJECTIVE: To examine the association of a single tHcy measurement on subsequent hospitalizations due to CVD. METHODS: A population-based prospective cohort study was conducted from April 1, 1992, to May 31, 1998 (mean follow-up, 5.3 years) in western Norway. The study included 17 361 individuals aged 40 to 42 or 65 to 67 years at baseline. Main outcome measure was CVD as the main hospital discharge diagnosis or coronary revascularization procedures (denoted "CVD hospitalizations") during follow-up (n = 1275). RESULTS: At baseline, participants with preexisting CVD had higher mean tHcy values than individuals without CVD. Risk of CVD hospitalizations increased significantly with increasing baseline tHcy only in the oldest age group. Here, multiple risk factor-adjusted hospitalization rate ratios in 5 tHcy categories (<9, 9-11.9, 12-14.9, 15-19.9, and >or=20 micromol/L [to convert tHcy to milligrams per liter, divide by 7.397]) were as follows: 1 (reference level), 1.00, 1.34, 1.67, and 1.94, respectively (P for trend <.001). The relation between tHcy level and CVD hospitalizations was significantly stronger among individuals with preexisting CVD than those without (hospitalization rate ratio per 5-micromol/L tHcy increment, 1.29 vs 1.10; P for interaction,.02). CONCLUSIONS: Plasma tHcy level is a strong predictor of CVD hospitalizations only in elderly individuals, and especially among those with preexisting CVD. Our findings are compatible with the theory that tHcy interacts with conventional CVD risk factors to provoke the acute event of CVD.

Adult↗

PubMed2002

Homocysteine levels in men and women of different ethnic and cultural background living in England.

This population-based cross-sectional study in South London looks at the total homocysteine (tHcy) levels in groups of different ethnic background and the possible role of environmental factors and the 677C-->T genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR). Fasting plasma tHcy was measured in 1392 men and women, age 40-59 years; 475 were white, 465 of African origin (of whom 180 were West Africans and 280 Caribbeans) and 452 South Asian (of whom 222 were Hindus and 167 Muslims). The homozygous MTHFR TT variant had observed frequencies of 0.10 in whites, 0.01 in people of African origin and 0.02 in South Asians (P<0.001). tHcy levels were 16% (95% CI 8-26) higher amongst TT than CC. tHcy levels were 25% (21-29) higher in men than women. Levels were significantly higher in South Asians than whites (8% [3-13]). Vegetarians had higher levels than non-vegetarians (25% [18-33]). These differences were present after adjustments for age, sex, smoking, body mass index (BMI), MTHFR 677C-->T polymorphism and socio-economic status. Compared with whites (10.0 [9.7-10.3] micromol/l), and allowing for confounders, Hindus had significantly higher levels of tHcy (12.1 [11.6-12.6] micromol/l). This difference was attenuated by the inclusion of vegetarianism in the model (11.3 [10.8-11.9] micromol/l). In contrast Muslims had similar tHcy levels to whites while both West Africans and Caribbeans had slightly lower levels, though differences were not significant. The reported higher levels of tHcy in South Asians are due to high levels amongst Hindus only. They are in part accounted for by their vegetarianism. These differences in tHcy are large enough to be important contributors to the risk of vascular disease and may be preventable by simple targeted population strategies.

Adult↗

PubMedDate not supplied

Folate and depression.

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Depressive Disorder↗