Omega 3 fatty acids for prevention and treatment of cardiovascular disease.

BACKGROUND: It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. OBJECTIVES: To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. SEARCH STRATEGY: Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. SELECTION CRITERIA: RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. DATA COLLECTION AND ANALYSIS: Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. MAIN RESULTS: Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. REVIEWERS' CONCLUSIONS: It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health. There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo.

Serum total homocysteine and coronary heart disease: prospective study in middle aged men.

OBJECTIVES: To examine the prospective relation between total homocysteine and major coronary heart disease events. DESIGN: A nested case-control study carried out within the British regional heart study, a prospective investigation of cardiovascular disease in men aged 40-59 years at entry. Serum total homocysteine concentrations were analysed retrospectively and blindly in baseline samples from 386 cases who had a myocardial infarct during 12.8 years of follow up and from 454 controls, frequency matched by age and town. RESULTS: Geometric mean serum total homocysteine was slightly higher in cases (14.2 micromol/l) than in controls (13.5 micromol/l), a proportional difference of 5.5% (95% confidence interval (CI) -0.02% to 10.8%, p = 0.06). Age adjusted risk of myocardial infarction increased weakly with log total homocysteine concentration; a 1 SD increase in log total homocysteine (equivalent to a 47% increase in total homo cysteine) was associated with an increase in odds of myocardial infarction of 1.15 (95% CI 1.00 to 1. 32; p = 0.05). The relation was particularly marked in the top fifth of the total homocysteine distribution (values >16.5 micromol/l), which had an odds ratio of 1.77 (95% CI 1.28 to 2.42) compared with lower levels. Adjustment for other risk factors had little effect on these findings. Total homocysteine concentrations more than 16.5 micromol/l accounted for 13% of the attributable risk of myocardial infarction in this study population. Serum total homocysteine among control subjects varied between towns and was correlated with town standardised mortality ratios for coronary heart disease (r = 0.43, p = 0.08). CONCLUSIONS: Serum total homocysteine is prospectively related to increased coronary risk and may also be related to geographical variation in coronary risk within Britain. These results strengthen the case for trials of total homocysteine reduction with folate.

Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.

Moderate hyperhomocysteinaemia is common in the general population and has been linked with cardiovascular disease. However, there are no data from prospective, population-based studies. We examined the association between serum total homocysteine (tHcy) concentration and stroke in a nested case-control study within the British Regional Heart Study cohort. Between 1978 and 1980 serum was saved from 5661 men, aged 40-59 years, randomly selected from the population of one general practice in each of 18 towns in the UK. During follow-up to December, 1991, there were 141 incident cases of stroke among men with no history of stroke at screening. Serum tHcy was measured in 107 cases and 118 control men (matched for age-group and town, without a history of stroke at screening, who did not develop a stroke or myocardial infarction during follow-up). tHcy concentrations were significantly higher in cases than controls (geometric mean 13.7 [95% CI 12.7-14.8] vs 11.9 [11.3-12.6] mumol/L; p = 0.004). There was a graded increase in the relative risk of stroke in the second, third, and fourth quarters of the tHcy distribution (odds ratios 1.3, 1.9, 2.8; trend p = 0.005) relative to the first. Adjustment for age-group, town, social class, body-mass index, hypertensive status, cigarette smoking, forced expiratory volume, packed-cell volume, alcohol intake, diabetes, high-density-lipoprotein cholesterol, and serum creatinine did not attenuate the association. These findings suggest that tHcy is a strong and independent risk factor for stroke.

Acute abdominal pain and appendicitis in north east Thailand.

In a survey of emergency admissions to hospital in rural Thailand, acute appendicitis was the commonest cause of acute abdominal pain. Estimates of the incidence of appendicitis, in two series comprising a total of 356 patients, at 3.2 and 3.7 per 10,000 population per year, were relatively high compared with reports from other warm climate countries. In comparison with 1825 cases in studies sponsored by the Organisation Mondiale de Gastroenterologie (OMGE), Thai patients with acute appendicitis were older, presented late and experienced more complications than those in 14 other countries. In Khon Kaen only 2-3% of the cases were children aged 0-9 years, compared with 9-26% in the OMGE series. In patients admitted to hospital with acute abdominal pain in Thailand, acute appendicitis was diagnosed more often than non-specific abdominal pain. The converse was true in the OMGE series. This may reflect the longer distances travelled to hospital by many patients and delays between onset of symptoms and admission to hospital. Acute appendicitis was the commonest definitive diagnosis in both series. This survey indicates that relatively high rates of acute appendicitis may occur in populations eating traditional diets. The results are consistent with the recently described hypothesis of an infective aetiology and increases in appendicitis rates may be expected in people born since the introduction of improvements in environmental sanitation. Further studies are needed to examine trends in the incidence of appendicitis in populations eating traditional diets with both high and low fibre content and to investigate the significance of changing social and environmental factors.

Normal values for range of shoulder abduction in men and women aged over 65 years.

The range of movement of the shoulder in abduction at 45 degrees of flexion was objectively measured using a standard technique in a demographically representative survey of 1000 men and women living in their own homes. Sampling was stratified to obtain approximately equal numbers of those aged 65-74 years and those aged 75 and over. The response rate was 80%. Normal values for shoulder abduction grouped by age and sex are presented as frequency distributions, means and deciles. Information about health problems was also recorded in the survey; the prevalences of these problems and their associations with shoulder abduction have been investigated. Women had significantly lower values for shoulder abduction than men. For both sexes values were on average about 30 degrees lower than those found in younger adults, and about half of the elderly group had values below 120 degrees. The prevalence of specified health problems was high with only 3% of the older group and 6% of the younger group being free from all the specified health problems. There was a significant independent negative association between shoulder abduction and both age and reported health. The associations were more marked in women than in men. This was so for both a cumulated 14-item health index and selected individual health items which included arthritis, lack of mobility and incontinence. The decile values for shoulder abduction for women without these health problems are presented. This provides more appropriate normal data for them; it is more normally distributed and reduces the percentage with a shoulder abduction less than 120 degrees to 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Flexibility of the shoulder joint measured as range of abduction in a large representative sample of men and women over 65 years of age.

In a representative survey of 1000 elderly men and women aged over 65 years living in their own homes, assessments have been made of flexibility measured as range of shoulder abduction in addition to health status, psychological well-being and reported customary activity. The results for shoulder abduction were approximately normally distributed and the mean values (+/- 1 standard deviation) were as follows: - in men aged 65-74 years, 129 (+/- 14) degrees and aged over 74 years, 121 (+/- 19) degrees; in women aged 65-74 years, 124 (+/- 19) degrees and aged over 74 years, 114 (+/- 22) degrees. These mean values are about 30 degrees less than those accepted for younger subjects. Nearly half the distribution falls below the accepted threshold level of 120 degrees for adequate function. There were significant effects of sex and age (P less than 0.001); women had poorer flexibility and the reduction with age amounted to 10 degrees per decade. Multiple regression analysis showed that the effect of age was accounted for in part by health, strength and customary use. The effects of use were most marked in those with some disability. This suggests that maintained or increased use could offset some of the age-related loss of the range of shoulder movement.

Falls by elderly people at home: prevalence and associated factors.

Of 1042 individuals aged 65 years and over who were successfully interviewed in a community survey of health and physical activity, 35% (n = 356) reported one or more falls in the preceding year. Although the overall ratio of female fallers to male fallers was 2.7:1, this ratio approached unity with advancing age. Mobility was significantly impaired in those reporting falls. Asked to provide a reason for their falls, 53% reported tripping, 8% dizziness and 6% reported blackouts. A further 19% were unable to give a reason. There was no association between falls and the use of diuretics, antihypertensives or tranquilizers, but a significant association between falls and the use of hypnotics and antidepressants was found. Discriminant analysis of selected medical and anthropometric variables indicated that handgrip strength in the dominant hand and reported symptoms of arthritis, giddiness and foot difficulties were most influential in predicting reports of recent falls.

Levels of customary physical activity among the old and the very old living at home.

With an activity inventory designed specifically for use among elderly people, detailed profiles of customary physical activity were obtained from 507 old (aged 65-74 years) and 535 very old (aged 75 years and over) individuals randomly sampled from the community. Participation in four categories of activity was assessed: outdoor productive activities; indoor productive activities; leisure activities; and walking. Customary engagement in many activities was found to be low, age (old versus very old) and sex being among the most important determinants of participation. The method of assessment is described, and activity profiles normative for older age groups are presented.

Low dose beta blockade in acute stroke ("BEST" trial): an evaluation.

The beta blocker stroke ("BEST") trial was designed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke. Three hundred and two conscious patients with clinically diagnosed hemispheric strokes sustained within the past 48 hours were randomly assigned to receive atenolol, propranolol, or matching placebo capsules for three weeks. More early deaths occurred among the patients allocated to receive beta blockers, but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups. By contrast, the outcome in a further 60 patients, who had been taking beta blockers at the time of their stroke but were otherwise similar to the patients in the trial, was considerably better, suggesting that prior treatment with beta blockers might be protective. The search for an effective medical treatment for acute stroke must continue. The approach used here, in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome, allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost.

The pragmatic approach to stroke trial design: stroke register, pilot trial, assessment of neurological then functional outcome.

Assessment of the results of medical intervention in acute stroke presents particular difficulties. Firstly the condition is extremely variable both in its clinical presentation and in its underlying pathology. Secondly, extreme care must be taken over the methods used to assess outcome. A reduction in mortality is no indication of success if there is a consequent increase in the number of survivors with extreme disability. Nor is it valid to compare functional or neurological outcome in survivors, since differences in mortality between treatment groups may upset the balancing effect of initial randomisation. Furthermore, overall 'neurological scores' are of dubious validity when the progress of patients with different patterns of disability has to be compared. Despite these difficulties a pragmatic approach can be used in which the design and conduct of a stroke trial closely resemble the normal clinical situation. This requires a knowledge of the range and natural history of stroke cases seen, best obtained from a stroke register. A pilot trial is then needed to assess the extent of variation in outcome and thus to estimate the numbers needed for the main study. The latter should then be conducted in two stages. Initially 'neurological benefit' should be assessed by counting the number of individual neurological signs which show improvement or deterioration in patients in each treatment group. Finally, a simple functional end-point should be compared in large numbers of patients with death being treated as equivalent to the worst possible non-fatal outcome. These principles are now being applied in a large, double-blind, placebo-controlled trial of low-dose beta-blockers in conscious stroke victims.

Depression after stroke: a hospital treatment survey.

Treatment with anti-depressant drugs of 61 inpatients admitted on account of stroke was studied. Eighteen patients (30%) were being so treated. Only 5 patients (17%) with dysphasia were being treated with anti-depressant drugs compared with 13 patients (41%) without dysphasia (P less than 0.05). Dosage levels used were generally low and only one patient had been referred for a psychiatric opinion. We suggest that the difference in anti-depressant usage is because dysphasic patients are more difficult to assess and therefore less likely to have depressive symptoms recognized and treatment given. We also think that psychiatric referral should be used more often for assessment of stroke patients and for advice about treatment.