The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.

OBJECTIVE: An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism. DESIGN AND SETTING: Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel. PATIENTS: THcy was determined in a total of 1150 cases and 1753 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype. RESULTS: High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies. CONCLUSIONS: Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study.

OBJECTIVE: Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mug of folic acid or 40 mg of pyridoxine supplementation might eliminate. DESIGN: Randomised, blinded study with two consecutive trial periods. SETTING: Free living population. Volunteers. SUBJECTS: A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y. INTERVENTIONS: (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mug folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks. MAIN OUTCOME MEASURES: The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period. RESULTS: Coffee abstention resulted in a tHcy decrease of 1.04 mumol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mumol/l was observed in the folic acid group whereas an increase of 1.26 mumol/l was observed in the placebo group, the difference was 1.43 mumol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. CONCLUSIONS: Supplementation of 200 mug folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect.

Filtered coffee raises serum cholesterol: results from a controlled study.

OBJECTIVE: Earlier studies and trials have shown a serum cholesterol raising effect of unfiltered coffee, which is reduced by about 80% in filtered coffee. Recent cross-sectional studies and trials, however, have indicated that filtered coffee may have a more pronounced serum cholesterol raising effect than previously anticipated. The objective of this controlled study was to assess the effects of the intake and abstention of filtered brewed coffee on blood lipids. DESIGN: A prospective, controlled study with four consecutive trial periods. The first and third periods were 3 weeks of total coffee abstention. The second and fourth periods consisted of 4 weeks with the subjects consuming 600 ml filter brewed coffee/day. SETTING: Free-living population. Volunteers. SUBJECTS: A total of 121 healthy, nonsmoking men and women aged 29-65 y. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum total cholesterol, serum HDL cholesterol, serum triglycerides, serum lipoprotein (a) (Lp(a)), blood pressure and heart rate. RESULTS: The two coffee abstention periods were associated with a decline in serum cholesterol of 0.22 mmol/l (95% CI -0.31, -0.13) and 0.36 mmol/l (95% CI -0.46, -0.26), respectively. Filtered coffee/day 600 ml increased serum cholesterol by 0.25 mmol/l (95% CI 0.15, 0.36) and 0.15 mmol/l (95% CI 0.04, 0.26) during the two coffee drinking periods. CONCLUSIONS: Coffee abstention for 3 weeks decreased total serum cholesterol by 0.22-0.36 mmol/l. A volume of 600 ml (about four cups) of filtered coffee/day during 4 weeks raised total serum cholesterol by 0.15-0.25 mmol/l.

High fruit intake may reduce mortality among middle-aged and elderly men. The Study of Men Born in 1913.

OBJECTIVE: A number of long-term population-based studies have tried to study fruit and vegetable consumption in relation to cardiovascular disease, cancer and total mortality. Few of these studies are based on randomly selected population samples. The aim of the study was to investigate the long-term effect of fruit and vegetable consumption on mortality, cardiovascular disease, cardiovascular death, cancer morbidity and cancer death among middle-aged and elderly men. DESIGN: Prospective cohort study. SETTING: General community. The Study of Men Born in 1913. SUBJECTS: 792 men at age 54 who participated in a screening examination in 1967. MAIN OUTCOME MEASURES: A food frequency questionnaire was used to obtain information of the dietary habits in 730 of the men (92%). All men were followed up with repeated examinations until the age of 80. RESULTS: Cardiovascular as well as total mortality was significantly lower among men with high fruit consumption in univariate analysis. There was no correlation between fruit or vegetable consumption in relation to cancer incidence, cancer death and cardiovascular disease. In multivariate survival analysis where smoking, cholesterol and hypertension were taken into account, there was a significantly lower mortality among men with a high fruit consumption during 16 y follow up until the age of 70 (P=0.042), but this finding was no longer statistically significant during 26 y follow-up at the age of 80 (P=0.051). CONCLUSIONS: Daily fruit consumption seems to have positive effect on long-term survival independently of other traditional cardiovascular risk factors like smoking, hypertension and cholesterol. SPONSORSHIP: This study was supported by grants from the Swedish Medical Research Council (K98-274-06276-17) King Gustav V and Queen Victoria's Foundation, and the Göteborg University.