Association of low plasma antioxidant levels with all-cause mortality and coronary events in healthy middle-aged men from France and Northern Ireland in the PRIME study.

BACKGROUND: The main underlying risk factors associated with coronary heart disease (CHD) are modifiable and oxidative injury and systemic inflammatory damage represent key aetiological factors associated with the development and progression of CHD and premature mortality. OBJECTIVE: To examine associations of plasma antioxidant status with all-cause mortality and fatal or non-fatal cardiovascular events. DESIGN: The PRIME study prospectively evaluated 9709 men aged 50-59 years between 1991 and 1993 in Northern Ireland and France who were free of CHD at recruitment and followed annually for deaths and cardiovascular events for 10 years. Serum concentrations of vitamin C, retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography. Baseline conventional risk factors were considered, as well as socioeconomic differences and lifestyle behaviours including diet, smoking habit, physical activity, and alcohol consumption through Cox regression analyses. RESULTS: At 10 years, there were 538 deaths from any cause and 440 fatal or non-fatal cardiovascular events. After adjustment for country, age, systolic blood pressure, diabetes, body mass index, cholesterol, high density lipoprotein cholesterol, triglycerides, height, total physical activity, alcohol consumption and smoking habit, higher levels of all antioxidants were associated with significantly lower risk of all-cause mortality, with the exception of γ-tocopherol. Only retinol was significantly associated with decreased risk of cardiovascular events in a fully adjusted model. CONCLUSIONS: Low antioxidant levels contribute to the gradient of all-cause mortality and cardiovascular incidence independent of lifestyle behaviours and traditional cardiovascular and socioeconomic risk factors.

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial.

PURPOSE: Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels. METHODS: A randomised, double-blind, factorial design, intervention study was carried out on 132 men with mildly elevated homocysteine levels, allocated to four groups (a) B vitamins alone--1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin daily, (b) antioxidants alone--150 mg ascorbic acid, 67 mg vitamin E, 9 mg ß-carotene daily, (c) B vitamins with antioxidant vitamins, or (d) placebo. A total of 101 men completed the study to 8 weeks. RESULTS: When the percentage of baseline ADMA and CRP was examined at 8 weeks, no statistically significant differences were observed between the four groups (p = 0.21 and p = 0.90, respectively). Similar non-significant results were observed when analysis was stratified based on baseline CRP levels (<1.0 mg/L, p = 0.10; ≥1.0 mg/L, p = 0.64) and smoking status (all p ≥ 0.05). CONCLUSIONS: Supplementation with moderate doses of B vitamins and/or antioxidants did not alter either ADMA or CRP concentrations in these middle-aged, apparently healthy men with mildly elevated homocysteine levels.

Thiol and cardiovascular risk factor status in a male northern Irish population.

OBJECTIVES: Raised plasma homocysteine is a risk factor for cardiovascular disease (CVD). Cysteine has also been associated with CVD risk. In this study, we investigated the association between known CVD risk factors, dietary factors, and total plasma cysteine, cysteinyl-glycine, and homocysteine. METHODS: The study group was 765 male workers aged between 30-49 years. The dietary habits of the subjects were recorded using a food frequency questionnaire. Body mass index (BMI), smoking status, and blood pressure were assessed, and fasting blood samples were taken for analysis of serum concentrations of vitamins, lipids, total plasma cysteine, cysteinyl-glycine, and homocysteine, and genotyping for the methylenetetrahydrofolate reductase (MTHFR) polymorphism. RESULTS: In multivariable analyses, cysteine was significantly positively associated with age and negatively associated with serum vitamin B12 and serum vitamin B6, while cysteinyl-glycine was significantly positively associated with BMI. Homocysteine (tHcy) was significantly negatively associated with serum folate, serum vitamin B12, and fruit and vegetable intake, and also depended on the MTHFR 677C>T genotype. CONCLUSIONS: Our data show a significant relationship between age, serum levels of B-vitamins and cysteine, and BMI and cysteinyl-glycine. In agreement with other studies, we also confirm an association between tHcy, serum folate and vitamin B12, MTHFR genotype, and fruit and vegetable intake. Further investigation into the role of these thiols and their determinants in CVD is required.

Low plasma retinol predicts coronary events in healthy middle-aged men: the PRIME Study.

The role of plasma retinol and carotenoids in coronary heart disease (CHD) remains unclear. The PRIME Study prospectively evaluated these in France and Northern Ireland in 9758 men aged 50-59 years who were free of CHD at baseline. After five years' follow-up 150 incident cases of CHD (non-fatal myocardial infarction and fatal CHD) were compared with 285 controls matched for age, date of blood collection and study centre. Geometric means of major carotenoids did not differ significantly between cases and controls (P>0.05), whereas the absolute and lipid-standardized plasma retinol levels were 9% lower in cases than controls in both countries (P<0.002), without correlation with carotenoids. After adjusting for risk factors, the relative risks (RRs) of CHD in the first four quintiles of retinol distribution in controls (< or =601, -683, -760, and -846 microg/l) were 2.65 (P=0.0009), 1.70, 1.03, and 1.12 (all P>0.05) respectively, relative to the top quintile (retinol > or =846 microg/l; linear trend P=0.0001). The 10th percentile of lipid-standardized retinol (< or =544 microg/l) predicted an RR of 4.7 (P<0.001). The risk associated with low retinol was comparable to strong risk factors (e.g. HDL-cholesterol, Interleukin-6) and behaved additively. In conclusion, plasma retinol levels of < 601 microg/l in a fifth of middle-aged European men place them at an approximately threefold RR of developing CHD. Thus the intake of vitamin A might be too low in middle-aged men. These findings must be confirmed.