Heterogeneity in randomized controlled trials of long chain (fish) omega-3 fatty acids in restenosis, secondary prevention and ventricular arrhythmias.

Randomized controlled trials of marine omega-3 fatty acid supplementation in relation to coronary heart disease (CHD) have inconsistent outcomes, yet public health messages are uniformly positive. Originally, fish were seen as a low saturated fat protein source, and later as a valuable source of omega-3 fatty acids. Early trials indicated that increased fish oil consumption prevented restenosis after coronary angioplasty. Later trials demonstrated that fish oils prolonged life post myocardial infarction (MI). Currently, the potential antiarrhythmic effects of fish derived omega-3 fatty acids are seen as the primary reason for cardiac benefits, as suggested by one trial with compliant subjects with implantable cardioverter defibrillators (ICDs), and sudden death reduction in a post MI trial. However, the earlier benefits of EPA and DHA on restenosis have only been confirmed in a subgroup in a recent meta-analysis. Newer data indicate that fish oils may increase CHD events in men with angina. Furthermore, in two of three trials in patients with ICDs and a history of ventricular arrhythmias, fish oils showed no significant benefit or even increased the risk of appropriate ICD discharge. Certain groups of individuals may benefit from long-chain omega-3 fatty acids while others, including men with angina and some individuals with a history of ventricular arrhythmia, may not. Due to significant heterogeneity in the response to fish oils, further studies are required before making widespread recommendations for all groups to increase consumption of fish and fish oil.

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis.

BACKGROUND: A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials. METHODS: We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible. RESULTS: We identified 3 trials of 1-2 years' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56-0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92-1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007). CONCLUSION: These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia.

Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel.

The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.

Left ventricular systolic dysfunction and atrial fibrillation in older people in the community--a need for screening?

BACKGROUND: Heart failure and stroke are major causes of morbidity and mortality in older people. Angiotensin converting enzyme inhibitors improve symptoms and survival in left ventricular systolic dysfunction. Anticoagulants are effective in stroke prevention in atrial fibrillation with aspirin being a less effective alternative. OBJECTIVES: To determine the prevalence of left ventricular systolic dysfunction, health services utilisation and prescribing of diuretics and angiotensin converting enzyme inhibitors in left ventricular systolic dysfunction, and the prevalence of atrial fibrillation and anti-platelet/thrombotic therapy in atrial fibrillation in older people in the community. METHODS: 500 subjects were drawn by two-stage random sampling from 5,002 subjects aged 70 years and over living at home. Subjects were screened for atrial fibrillation and left ventricular systolic dysfunction using electrocardiography and echocardiography. RESULTS: The population prevalence amongst older people of left ventricular systolic dysfunction was 9.8% and of atrial fibrillation 7.8%. More than two-thirds of those with left ventricular systolic dysfunction were not on angiotensin converting enzyme inhibitors. Of those in atrial fibrillation, 35% were taking aspirin, 24% were taking warfarin and 41% were on neither aspirin nor warfarin. Nearly 90% of older people in the community have had contact with their general practitioner over the past year, and over half of those with left ventricular systolic dysfunction have had contact with hospital-based services over the past 2 years. CONCLUSIONS: Left ventricular systolic dysfunction is under-treated in older people in the community. Despite the high level of contact with hospital and community-based services, the majority of those with systolic left ventricular dysfunction are not on angiotensin converting enzyme inhibitors and a significant proportion of those in atrial fibrillation are not on any treatment for stroke prevention.

Inhaler technique in older people in the community.

BACKGROUND: Good inhaler technique and medication concordance is important for symptom and disease control in chronic airways disease. OBJECTIVES: Establish the prevalence of inhaler use; the main inhaler devices used by older people at home; their ability to use the inhalers they have been prescribed; and the relationship between perceived ease of use and actual performance. DESIGN: Cross-sectional population based study. SUBJECTS: Subjects aged 70 years and over living at home. METHODS: 500 subjects were randomly selected from 5002 subjects aged 70 years and over living at home. Inhalers used over the previous 24 hours were identified by a nurse on home visit. Those with cognitive impairment were excluded. Inhaler system was assessed and graded by a doctor as acceptable (perfect or minor errors) or unacceptable (major errors), using previously published criteria. Perceived ease of use of the device was rated as easy, moderate or difficult. RESULTS: 423 subjects participated in the study. The population prevalence of inhaler use was 15.8% (12.0, 19.7). Of the 91 inhaler devices used, 39 (42.8%) were metered dose inhalers, 34 (37.4%) were metered dose inhalers with large volume spacers, and 18 (19.8%) were breath-actuated devices. Thirty-two subjects (82.1%) using metered dose inhalers had an acceptable technique compared with 33 (97.1%) of those using metered dose inhalers with large volume spacers and 13 (72.2%) of those using breath-actuated devices (P < 0.05). Up to three quarters of inhalers were considered easy to use but 12% of subjects who rated their inhaler device as being easy to use made major errors. CONCLUSION: Metered dose inhaler was the most frequently prescribed inhaler and was used correctly by most subjects especially in combination with large volume spacers. Major errors were more common with breath-actuated devices. Inhaler technique should be checked as patients' perception of their inhaler skills correlates poorly with actual performance.

Advice to eat fish and mood: a randomised controlled trial in men with angina.

People with high intake of fish have lower reported rates of depression and a small trial in psychiatric patients suggested that fish oil supplements reduced episodes of depression and mania. As part of a factorial trial of interventions to reduce mortality in angina 452 men were randomised to advice to eat more fatty fish or no fish advice. Maxepa fish oil capsules were supplied to men who found the fish unpalatable. Fish intake and mood were assessed at baseline and six months. Most men (83%) had mood assessed using the Derogatis Stress Profile at baseline and follow-up. Self reported intake of fish was higher in the fish advice group at six months. There was, however, no difference in depression or anxiety in those allocated to receive fish advice. After controlling for baseline mood, the difference in depression score between those randomised to fish advice and those not was 1.29 (95% CI -0.29 to 2.88) and the difference in anxiety was 0.82 (95% CI -0.57 to 2.22) with positive differences indicating more depression or anxiety in those allocated to the fish arm. This trial provides no evidence that increased fatty fish intake in people without depressive symptoms has any substantial effect on mood.

Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial.

BACKGROUND: Low folate status and elevated plasma homocysteine are associated with increased risk of neural tube defects and cardiovascular disease. Homocysteine responses to folate may be influenced by genetic variants in folate metabolism. OBJECTIVE: We determined the effect of folate-enhancing dietary interventions on plasma folate and plasma total homocysteine (tHcy) with respect to the methylenetetrahydrofolate reductase 677C-->T genotype. DESIGN: A total of 126 healthy subjects (42 TT, 42 CT, and 42 CC genotypes) completed 3 dietary interventions (4 mo each) in random order: 1) exclusion diet (avoidance of folic acid-fortified foods and ingestion of a placebo daily), 2) folate-rich diet (increased intake of fortified and naturally folate-rich foods to achieve 400 microg folate/d), and 3) supplement (exclusion diet plus a folate supplement of 400 microg/d). RESULTS: Plasma folate was higher (P < or = 0.001) and plasma tHcy lower (P < or = 0.001) after the folate-rich and supplement interventions than after the exclusion diet. Plasma folate was significantly greater after supplementation than after the folate-rich diet, but there was no significant difference in tHcy concentration (P = 0.72). TT homozygotes had higher plasma tHcy (14.5 compared with 8.9 micromol/L, P < or = 0.001) and lower plasma folate (14.8 compared with 19.0 nmol/L, P < or = 0.01) than did subjects with the CC genotype after the exclusion diet. CT heterozygotes had intermediate concentrations. The trend toward higher tHcy in TT homozygotes persisted throughout the study but was less marked with increasing folate intake (TT compared with CC after supplementation, P = 0.097). CONCLUSIONS: A folate-rich diet including folic acid-fortified foods or low-dose supplements effectively increases folate status. TT homozygotes require higher folate intakes than do individuals with the CT or CC genotype to achieve similar tHcy concentrations but are responsive to folate intervention.

Mortality in British vegetarians.

OBJECTIVE: To compare the mortality of British vegetarians and non-vegetarians. DESIGN: Analysis of original data from two prospective studies each including a large proportion of vegetarians--the Oxford Vegetarian Study and the Health Food Shoppers Study. Standardised mortality ratios (SMRs) compared with the population of England and Wales were calculated from deaths before age 90 for vegetarians and non-vegetarians in each study. Death rate ratios (DRRs) for vegetarians compared with non-vegetarians within each study were calculated for each of 14 major causes of death. SETTING: UK. SUBJECTS: Twenty-one thousand men and women aged 16-89 years at recruitment, including more than 8,000 vegetarians. RESULTS: SMRs for all causes of death were significantly below the reference level of 100 in both studies: 52 (95% confidence interval (CI) 49-56) based on 1,131 deaths in the Oxford Vegetarian Study and 59 (57-61) based on 2,346 deaths in the Health Food Shoppers Study. For all causes of death, the DRR for vegetarians compared with non-vegetarians was close to one in both studies: 1.01 (95% CI 0.89-1.14) in the Oxford Vegetarian Study, 1.03 (0.95-1.13) in the Health Food Shoppers Study. CONCLUSIONS: British vegetarians have low mortality compared with the general population. Their death rates are similar to those of comparable non-vegetarians, suggesting that much of this benefit may be attributed to non-dietary lifestyle factors such as a low prevalence of smoking and a generally high socio-economic status, or to aspects of the diet other than the avoidance of meat and fish.

Nutritional advice to increase soluble fibre intake does not change plasma folate or homocysteine in men with angina: a randomised controlled trial.

OBJECTIVE: To study the effect of advice to increase dietary soluble fibre, including fruit and vegetables, on plasma folate and homocysteine in men with angina. DESIGN: Data were collected on a subset of subjects from the Diet and Angina Randomised Trial (DART II). In a randomised (2 x 2) factorial design, subjects received advice on either, neither or both interventions to: (1) increase soluble fibre intake to 8.0 g day(-1) (fruit, vegetables and oats); (2) increase oily fish intake to 2 portions week(-1). Those who received soluble fibre advice were compared with those who did not. Subjects were genotyped for C677T variant 5,10-methylenetetrahydrofolate reductase (MTHFR). SETTING/SUBJECTS: Seven hundred and fifty-three male angina patients were recruited from general practice. RESULTS: Plasma homocysteine concentrations were at the upper end of the normal range (median 11.5, 25% 9.4, 75% 14.0 micromol l(-1)). Baseline intake of fruit and vegetables was positively correlated with plasma folate (r(s) = 0.29, P < 0.01). Smokers had lower intakes of fruit and vegetables, lower plasma folate and higher homocysteine (all P < 0.01). Homozygotes for variant MTHFR had higher homocysteine concentrations at low plasma folate (P < 0.01). Reported intakes of fruit and vegetables and estimated dietary folate increased in the intervention group (ca. +75 g day(-1), P < 0.01 and ca. +20 g day(-1), P < 0.05, respectively). However, neither plasma folate (baseline/follow-up 4.5 vs. 4.4 microg l(-1), P = 0.40) nor homocysteine (baseline/follow-up 11.7 vs. 11.7 micromol l(-1), P = 0.31) changed. CONCLUSIONS: Plasma homocysteine, a cardiovascular risk factor, is influenced by MTHFR genotype, plasma folate and smoking status. Dietary advice successfully led to changes in fruit and vegetable intake, but not to changes in plasma folate or homocysteine, possibly because the fruits and vegetables that were chosen were not those richest in folate.