S. E. Vollset

Total homocysteine and cardiovascular disease

Abstract. Nygård O, Vollset SE, Refsum H, Brattström L, Ueland PM (University of Bergen, Norway; County Hospital, Kalmar, Sweden). Total homocysteine and cardiovascular disease (Review). J Intern Med 1999; 246: 425–454.

Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: the Hordaland Homocysteine Study

BACKGROUND Limited information is available on the association between vitamin B-12 status and intake from different dietary sources. OBJECTIVE We investigated the relation of dietary intake of different food items with plasma vitamin B-12 concentrations in the general population. DESIGN A cross-sectional, population-based study of 5937 subjects in 2 age groups (47-49 and 71-74 y) from the Hordaland Homocysteine Study in Norway was conducted by using a food-frequency questionnaire and measurements of plasma vitamin B-12 concentrations. RESULTS A significant difference in plasma vitamin B-12 concentrations was observed with increasing total vitamin B-12 intake. A plateau was reached at an intake of approximately 10 microg/d. Plasma vitamin B-12 was associated with intakes of increasing amounts of vitamin B-12 from dairy products or fish (P for trend <0.001 for both) but not with intakes of vitamin B-12 from meat or eggs. For the same content of vitamin B-12, intake from dairy products led to the greatest increase in plasma vitamin B-12. Total intake of vitamin B-12, particularly from milk and fish, decreased the risk of vitamin B-12 concentrations <200 pmol/L and impaired vitamin B-12 function (vitamin B-12 <200 pmol/L and methylmalonic acid >0.27 micromol/L) in the total group and in 71-74-y-old subjects. CONCLUSIONS Dietary intake of dairy products and fish are significant contributors to plasma vitamin B-12 and may improve plasma vitamin B-12 status. Vitamin B-12 appears to be more bioavailable from dairy products; guidelines for improving vitamin B-12 status should take this into consideration.

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations

BackgroundHyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD.ObjectivesTo estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD.DesignCross-sectional data on 12 541 men and 12 948 women aged 20+ y were used from nine European studies.ResultsThe prevalence of isolated HHCY was 8.5% in subjects aged 20–40 y, 4.7% in subjects aged 40–60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20–40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years).ConclusionsA substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

Homocysteine‐lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease

Objectives.  A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine‐lowering B‐vitamin therapy, as used in the Western Norway B‐vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis.

A community‐based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study

Circulating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine pathway. We measured neopterin, tryptophan, kynurenine, anthranilic acid, kynurenic acid, 3‐hydroxykynurenine, 3‐hydroxyanthranilic acid and xanthurenic acid in plasma in two age groups, 45–46 years (n = 3723) and 70–72 years (n = 3329). Differences across categories of the potential determinants, including age, gender, renal function, body mass index (BMI), smoking and physical activity, were tested by Mann–Whitney U‐test and multiple linear regression including age group, gender, renal function and lifestyle factors. In this multivariate model, neopterin, KTR and most kynurenines were 20–30% higher in the older group, whereas tryptophan was 7% lower. Men had 6–19% higher concentrations of tryptophan and most kynurenines than women of the same age. Compared to the fourth age‐specific estimated glomerular filtration rate (eGFR) quartile, the first quartile was associated with higher concentrations of neopterin (25%) and KTR (24%) and 18–36% higher concentrations of kynurenines, except 3‐hydroxyanthranilic acid. Additionally, KTR, tryptophan and all kynurenines, except anthranilic acid, were 2–8% higher in overweight and 3–17% higher in obese, than in normal‐weight individuals. Heavy smokers had 4–14% lower levels of tryptophan and most kynurenines than non‐smokers. Age and renal function were the strongest determinants of plasma neopterin, KTR and most kynurenines. These findings are relevant for the design and interpretation of studies investigating the role of plasma neopterin, KTR and kynurenines in chronic diseases.

Distribution and determinants of serum creatinine in the general population: the Hordaland Health Study

Background: Serum creatinine is a well-recognized risk factor for cardiovascular disease (CVD) and is also a rough measure of glomerular filtration rate. The purpose of the present study was to investigate determinants of serum creatinine in the general population. Methods: The participants were recruited as a part of the Hordaland Health Study, and included 6952 men aged 41-49 years, 8218 women aged 41-49 years, 1470 men aged 71-74 years and 1865 women aged 71-74 years. Data on lifestyle factors, medical history and medication were obtained through questionnaires. Body size and blood pressure measurements as well as non-fasting blood samples were obtained during a health examination. Determinants of serum creatinine were identified using multiple linear and logistic regression analyses. Results: Male and older participants had higher levels of serum creatinine than female and middle-aged participants. For older participants, creatinine was associated with serum triglycerides, CVD, upper-arm circumference and use of antihypertensive drugs as well as inversely associated with cigarette smoking. For middle-aged participants, creatinine was associated with upper-arm circumference, serum lipids and physical exercise, as well as inversely associated with smoking and alcohol intake. The associations with CVD risk factors were much stronger for older participants than for middle-aged participants and most associations were significant after adjustments as well as present within the reference range of serum creatinine. Conclusions: In this general population sample, high serum creatinine levels were associated with risk factors for CVD. These associations were stronger in older subjects, whereas in middle-aged subjects lifestyle variables were relatively more important.

A 3‐month double‐blind cross‐over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure

Abstract. The non‐sulfhydryl selective angiotensin‐converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post‐infarction (6–24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double‐blind cross‐over design with 3‐month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin‐converting enzyme inhibitors may be superior to diuretics as first‐choice therapy in symptomatic mild heart failure.

Homocysteine and its relation to B‐vitamins in Graves’ disease before and after treatment: effect modification by smoking

Abstract. Nedrebø BG, Hustad S, Schneede J, Ueland PM, Vollset SE, Holm PI, Aanderud S, Lien EA (University of Bergen; Haukeland University Hospital, Bergen; and Haugesund Hospital, Haugesund; Norway). Homocysteine and its relation to B‐vitamins in Graves’ disease before and after treatment: effect modification by smoking. J Intern Med 2003; 254: 504–512.

Plasma sulfur amino acids and stearoyl-CoA desaturase activity in two caucasian populations☆

In rats, dietary restriction of the cysteine precursor methionine suppresses hepatic stearoyl-CoA desaturase (SCD)-1 expression and activity, whereas cysteine supplementation reverses these effects. In 2 independent cohorts: Hordaland Health Study (HUSK; N=2021, aged 71-74y), Norway, and Hoorn study (N=686, aged 50-87y), Netherlands, we examined the cross-sectional associations of plasma sulfur-containing compounds (SCC; methionine, S-adenosylmethionine, S-adenosylhomocysteine, homocysteine, cystathionine, total cysteine (tCys), glutathione and cysteinylglycine) with SCD-16 index (16:1n-7/16:0), estimated from fatty acid profiles of total plasma or serum lipids. Only tCys was consistently associated with SCD-16 index after adjustments for sex and age (HUSK: partial r=0.14; Hoorn: partial r=0.11, P<0.001 for both), and after further adjustments for other SCC, body fat, diet, exercise and plasma lipids (HUSK: partial r=0.07, P=0.004; Hoorn: partial r=0.12, P=0.013). Together with animal data showing an effect of dietary cysteine on SCD1, our results suggest a role for cysteine in SCD1 regulation in humans.

Association of plasma neopterin with risk of an inpatient hospital diagnosis of atrial fibrillation: results from two prospective cohort studies

Link between inflammation and atrial fibrillation (AF) has been increasingly recognized. Neopterin, a biomarker of cellular immune activation, may be associated with incident AF.