Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales.

BACKGROUND/OBJECTIVE: Familial Hypercholesterolaemia (FH) is caused by mutations in genes of the Low Density Lipoprotein (LDL) receptor pathway. A definitive diagnosis of FH can be made by the demonstration of a pathogenic mutation. The Wales FH service has developed scoring criteria to guide selection of patients for DNA testing, for those referred to clinics with hypercholesterolaemia. The criteria are based on a modification of the Dutch Lipid Clinic scoring criteria and utilise a combination of lipid values, physical signs, personal and family history of premature cardiovascular disease. They are intended to provide clinical guidance and enable resources to be targeted in a cost effective manner. METHODS: 623 patients who presented to lipid clinics across Wales had DNA testing following application of these criteria. RESULTS: The proportion of patients with a pathogenic mutation ranged from 4% in those scoring 5 or less up to 85% in those scoring 15 or more. LDL-cholesterol was the strongest discriminatory factor. Scores gained from physical signs, family history, coronary heart disease, and triglycerides also showed a gradient in mutation pick-up rate according to the score. CONCLUSION: These criteria provide a useful tool to guide selection of patients for DNA testing when applied by health professionals who have clinical experience of FH.

A randomized controlled trial of the effect of school food and dining room modifications on classroom behaviour in secondary school children.

BACKGROUND/OBJECTIVES: Adequate nutrition is considered important for learning, but there is little robust research on the association between diet and learning in school-aged children in industrialized countries. This study investigated the effect of tailored modifications to the food and dining experience in secondary schools on learning-related behaviours. SUBJECTS/METHODS: In 2008, 12 co-educational secondary schools in England were recruited. Schools were randomly allocated to receive a tailored action plan and support to modify their food provision and dining environment over a 15-week period (intervention or to control). Learning-related behaviours were systematically observed during post-lunchtime classes at all schools. Observations were made by trained observers using a validated protocol to determine whether pupils were 'on-task' (concentrating and alert) or 'off-task' (disruptive or disengaged). RESULTS: In total, 156 pupils were observed (control n = 58, intervention n = 98) at baseline (12,210 and 20,560 observations, control and intervention, respectively) and at follow-up (16,846 and 23,462, respectively). On-task and off-task behaviours were similar across treatment groups at baseline. At follow-up, intervention group pupils were 18% more likely to be on-task (odds ratio (OR) 1.18, 95% confidence interval ((95% CI) 1.05-1.33) and 14% less likely to be off-task (OR 0.86, 95% CI 0.75-0.98) compared with control group pupils. CONCLUSIONS: This study suggests that modifying food provision and the dining environment can improve learning-related behaviours of secondary school pupils in the post-lunch period. This finding supports ongoing investment and interventions by local authorities across the United Kingdom to improve school food and lunchtime dining facilities.

Effect of a pilot community intervention on fruit and vegetable intakes: use of FACET (Five-a-day Community Evaluation Tool).

BACKGROUND: In 2001 the UK Department of Health funded pilot community-based interventions to improve fruit and vegetable intakes in five economically deprived areas of England. The effectiveness of the programme and the use of a brief tool for evaluating community interventions are reported here. METHODS: Data on intakes of and beliefs about fruit and vegetables were collected by a short postal questionnaire (FACET--Five-a-day Community Evaluation Tool) simultaneously from 810 individuals living in the pilot communities and 270 individuals who were participating in an unrelated observational study (controls). Data were collected before and after a 12-month intervention period. Quantitative dietary data derived from 7-day food diaries available for control subjects were used to assess the ability of the FACET questionnaire to estimate fruit and vegetable intakes. RESULTS: Compared with controls, the intervention group significantly increased their knowledge of the 5-a-day optimum (P<0.01) and reported increased access to fruits and vegetables (P<0.001). Overall, the intervention had no demonstrable effect on total fruit and vegetable intakes as measured by FACET. However, smoking habit strongly predicted change in fruit and vegetable intakes (P<0.01) in the intervention group. Opposite trends were observed in the two groups, with 'smokers' and 'non-smokers' in the intervention and control groups respectively reducing their fruit and vegetable intakes. The FACET questionnaire agreed with food diary estimates of fruit and vegetable intakes in 56% of cases. CONCLUSIONS: Community-based interventions can produce important changes in knowledge of and access to fruit and vegetables. However, in this study change in fruit and vegetable intakes was strongly influenced by smoking habit. This bias needs to be considered in planning future intervention and evaluation programmes. The FACET questionnaire provides acceptable estimates of fruit and vegetable intakes which may be used for grading intake in large community-based projects.

The long-term effect of dietary advice on the diet of men with angina: the diet and angina randomized trial.

INTRODUCTION: The long-term effects on diet of dietary advice to eat fruit and vegetables or fatty fish are not well described. MATERIALS AND METHODS: From 1990 to 1996 3114 men aged 37-70 with treated angina were recruited from general practices in South Wales. A dietitian randomly allocated the eligible men to receive advice to eat more fruit and vegetables, or advice to eat more fatty fish, or both these types of advice or neither. In 2000, a brief self-completion questionnaire was sent to a sample of 1191 of the men known to be alive at the end of March 1999. RESULTS: The questionnaire was returned by 944 of the 1036 men alive at the time the questionnaire was sent. Those given fish advice were consuming more fatty fish but the difference was modest 21.9 g day(-1) vs. 14.0 g day(-1) (P < 0.01). The differences in fruit and vegetables intake between those given fruit advice and those not given fruit advice were small 373.2 g day(-1) vs. 351.7 g day(-1) (P = 0.05). DISCUSSION: Men of this age group may be particularly resistant to fruit and vegetables advice; population-based interventions or interventions targeted at women might be more effective.

Is 'five-a-day' an effective way of increasing fruit and vegetable intakes?

OBJECTIVES: To assess whether the amount of fruits and vegetables consumed depends on the serving size or on how often fruits and vegetables are eaten. DESIGN: Estimation of the weight of serving sizes and the number of fruits and vegetables eaten daily, using a validated food diary method. SETTING: Free-living men and women participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: Two hundred and sixty-nine men and women sampled from EPIC-Norfolk to participate in a study of simple methods of assessing fruit and vegetable intakes. RESULTS: The average portion of all fruits and vegetables measured was 87 g, close to the standard portion size of 80 g used as the basis of '5-a-day' recommendations. There was a wide variation; the average portion size for baked beans was 147 g while for lettuce it was 26 g. The 20th and 80th percentiles also showed a large range, e.g. 39-72 g for carrots and 60-150 g for strawberries. Women ate more fruit than did men but fewer vegetables, so the total amount of fruit and vegetables eaten by men and women was the same. High consumers of fruits and vegetables (> or =400 g day(-1)) ate them approximately 5 times a day whilst low consumers (<400 g day(-1)) ate them less often (approximately 3 servings per day, P<0.01). Portion size differed little between high and low consumers. CONCLUSIONS: Frequency of intake is more important than portion size when distinguishing between high and low consumption of fruits and vegetables. Therefore, to increase intakes, low consumers should eat fruits and vegetables more often. This endorses the '5-a-day' healthy eating message.

Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage.

BACKGROUND: Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. OBJECTIVE: To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. DESIGN: A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. RESULTS: Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. CONCLUSIONS: In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.

Lack of benefit of dietary advice to men with angina: results of a controlled trial.

OBJECTIVE: To see whether mortality among men with angina can be reduced by dietary advice. DESIGN: A randomized controlled factorial trial. SETTING: Male patients of general practitioners in south Wales. SUBJECTS: A total of 3114 men under 70 y of age with angina. INTERVENTIONS: Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y. RESULTS: Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication. CONCLUSIONS: Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.

A comparison of the effect of advice to eat either '5-a-day' fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine.

OBJECTIVE: To assess and compare the effects of natural folate (100 micro g) with those of folic acid from fortified sources (100 micro g/day) on plasma folate and homocysteine. DESIGN: Randomized controlled trial (parallel groups). SETTING: Men and women living in South Wales, UK. SUBJECTS: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). INTERVENTIONS: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet-usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet-usual diet plus 100 microg/day folate from natural sources; (3) control-usual diet. RESULTS: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P<0.001) achieving an extra 98 microg/day (95% CI 88-108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P<0.001), but achieved a mean increase of only 50 microg/day (95% CI 34-66). Plasma folate increased (P<0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8-5.1; natural group 2.76, 95% CI 0.6-4.9. Plasma homocysteine, vitamins B(6) and B(12) were not significantly changed. CONCLUSIONS: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes.

Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype.

OBJECTIVES: We sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults. BACKGROUND: Elevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene ( approximately 12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake. METHODS: Healthy subjects (n = 126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-microg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 microg/day. RESULTS: At baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 +/- 73 microm at baseline, 110 +/- 69 microm after a high-folate diet, 114 +/- 59 microm after supplementation and 118 +/- 68 microm after placebo). Plasma von Willebrand factor antigen was unaltered. CONCLUSIONS: Optimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype.

Folate, homocysteine, endothelial function and cardiovascular disease. What is the link?

Elevated plasma homocysteine concentrations are associated with an increased risk of cardiovascular disease, but the relationship has not been proven to be causal. Folate is the strongest nutritional and pharmacological determinant of plasma homocysteine concentrations, which also interact with the genetic variation in methylenetetrahydrofolate reductase (MTHFR). Endothelial dysfunction due to reduced nitric oxide bioavailability is an early feature of vascular pathology. This can be assessed noninvasively by measurement of flow-mediated dilatation. Human studies on folic acid, homocysteine and endothelial function are reported. It is proposed that folic acid in high doses may have beneficial effects on endothelial function, which are independent of homocysteine lowering.