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Biomedical subjects

M R Law

Publications and source records attributed to M R Law.

At least 55 records · Page 3Linked to original sources
PubMed1994

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?

OBJECTIVE: To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. DESIGN: Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). MAIN OUTCOME MEASURE: Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. RESULTS: For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. CONCLUSIONS: The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

Adult↗
PubMed1994

Assessing possible hazards of reducing serum cholesterol.

OBJECTIVE: To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN: Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES: Excess cause specific mortality associated with low or lowered serum cholesterol concentration. RESULTS: The only cause of death attributable to low serum cholesterol concentration was haemorrhagic stroke. The excess risk was associated only with concentrations below about 5 mmol/l (relative risk 1.9, 95% confidence interval 1.4 to 2.5), affecting about 6% of people in Western populations. For noncirculatory causes of death there was a pronounced difference between cohort studies of employed men, likely to be healthy at recruitment, and cohort studies of subjects in community settings, necessarily including some with existing disease. The employed cohorts showed no excess mortality. The community cohorts showed associations between low cholesterol concentration and lung cancer, haemopoietic cancers, suicide, chronic bronchitis, and chronic liver and bowel disease; these were most satisfactorily explained by early disease or by factors that cause the disease lowering serum cholesterol concentration (depression causes suicide and lowers cholesterol concentration, for example). In the randomised trials nine deaths (from a total of 687 deaths not due to ischaemic heart disease in treated subjects) were attributed to known adverse effects of the specific treatments, but otherwise there was no evidence of an increased mortality from any cause arising from reduction in cholesterol concentration. CONCLUSIONS: There is no evidence that low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. This risk affects only those people with a very low concentration and even in these will be outweighed by the benefits from the low risk of ischaemic heart disease.

Accidents↗
PubMed1994

Serum albumin and mortality in the BUPA study. British United Provident Association.

In the British United Provident Association (BUPA) study, a prospective observational study of 21,520 men, the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls, each matched to a case by age (within 1 year) and date of attendance (within 3 months). There was little overall difference (mean case-control difference = -0.11 milligram, P > 0.2) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality. Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases. An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre-clinical cancer lowering both serum albumin itself and serum cholesterol, with which albumin was associated. There was an association of chronic respiratory, neurological, renal, liver and gut diseases with low serum albumin (case-control difference = -1.19 milligram, P < 0.001) consistent with the effect of pre-clinical disease lowering serum albumin. Other causes of death showed no association with albumin. Our data do not support a cause and effect association of low serum albumin and mortality.

Accidents↗
PubMed1994

An ecological study of serum cholesterol and ischaemic heart disease between 1950 and 1990.

OBJECTIVE: (i) To carry out a quantitative analysis of the average serum cholesterol levels in different countries in relationship to the ischaemic heart disease (IHD) mortality in these countries. (ii) To examine changes in serum cholesterol levels over time in different countries. DESIGN: Analysis of published surveys measuring average serum cholesterol in specified communities in different countries. SETTING: The original cholesterol surveys were mainly in occupational and residential settings. RESULTS: Survey data allowed estimation of average serum cholesterol levels during specified time periods for 17 countries; estimates in men aged 40-59 years varied from 3.8 mmol/l (rural China) to 7.0 mmol/l (Finland). Variation in serum cholesterol accounted for 80% of the tenfold range in risk of IHD across countries. A difference in total (or LDL) cholesterol of 0.6 mmol/l between countries was associated with an average difference in IHD mortality of 37% at age 55-64 years. Repeat surveys showed that serum cholesterol reductions of the order of 0.6 mmol/l have occurred in some communities over about 5-10 years. CONCLUSIONS: Variation in serum cholesterol explains four-fifths of the geographical variation in IHD mortality. Reductions in cholesterol of about 0.6 mmol/l (10%) have been achieved in some Western communities or countries over periods of a few years, a change that is associated with a decrease in IHD mortality of over one-third.

Adult↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? I--Analysis of observational data among populations.

OBJECTIVE: To estimate the quantitative relation between blood pressure and sodium intake. DESIGN: Data were analysed from published reports of blood pressure and sodium intake for 24 different communities (47 000 people) throughout the world. MAIN OUTCOME MEASURE: Difference in blood pressure for a 100 mmol/24 h difference in sodium intake. Allowance was made for differences in blood pressure between economically developed and undeveloped communities to minimise overestimation of the association through confounding with other determinants of blood pressure. RESULTS: Blood pressure was higher on average in the developed communities, but the association with sodium intake was similar in both types of community. A difference in sodium intake of 100 mmol/24 h was associated with an average difference in systolic blood pressure that ranged from 5 mm Hg at age 15-19 years to 10 mm Hg at age 60-69. The differences in diastolic blood pressure were about half as great. The standard deviation of blood pressure increased with sodium intake implying that the association of blood pressure with sodium intake in individuals was related to the initial blood pressure--the higher the blood pressure the greater the expected reduction in blood pressure for the same reduction in sodium intake. For example, at age 60-69 the estimated systolic blood pressure reduction in response to a 100 mmol/24 h reduction in sodium intake was on average 10 mm Hg but varied from 6 mm Hg for those on the fifth blood pressure centile to 15 mm Hg for those on the 95th centile. CONCLUSIONS: The association of blood pressure with sodium intake is substantially larger than is generally appreciated and increases with age and initial blood pressure.

Adolescent↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? II--Analysis of observational data within populations.

OBJECTIVE: To determine whether the estimates of the size of the association between blood pressure and sodium intake derived from studies of individuals within populations can be quantitatively reconciled with our estimates derived from comparisons of the average blood pressure and sodium intake between different populations. DESIGN: Examination of data from 14 published studies that correlated blood pressure recordings in individuals against measurements of their 24 hour sodium intake (within population studies). MAIN OUTCOME MEASURE: Comparison of observed differences in blood pressure per 100 mmol/24 h difference in sodium intake in each within population study with predicted differences calculated from the between population data, after allowing for the underestimation of the true association of blood pressure with sodium intake caused by the large day to day variation in 24 hour sodium intake within individuals. RESULTS: The underestimation bias inherent in the within populations studies reduced the regression slope of blood pressure on single measures of 24 hour sodium intake to between a half and a quarter of the true value (for example, in one study from 6.0 to 2.4 mm Hg/100 mmol/24 h). Estimates from between population comparisons of the regression slope of blood pressure on sodium intake, after adjustment to take this underestimation bias into account, were similar to the values actually observed in the within population studies. CONCLUSION: The within population studies confirm our estimates from between population comparisons of the magnitude of the association between blood pressure and sodium intake.

Adolescent↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction.

OBJECTIVE: To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN: Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE: Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS: In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS: The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.

Adult↗
PubMed1991

Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies.

Data were analyzed from 33 prospective studies to assess the evidence for a long-term association of low serum cholesterol with cancer. In subjects with cancer diagnosed within two years of the cholesterol measurement or causing death within five years (n = 4,661), the level of serum cholesterol was on average lower than in controls by 0.18 (SE = 0.02) mmol/l in men and 0.11 (SE = 0.04) mmol/l in women; this effect can be attributed to preclinical cancer. For cancers presenting after these intervals (n = 22,030), the average differences were smaller but statistically significant (0.04 [SE = 0.01] mmol/1 [P less than 0.001) in men, and 0.03 [SE = 0.01] mmol/1 [P = 0.005] in women), equivalent to about a 15 percent increase in cancer incidence in the lowest cholesterol quintile. This cannot be attributed entirely to preclinical cancer. In men, there was significant (P = 0.01) heterogeneity between studies as to the extent of a long-term association. The heterogeneity could be substantially explained by socioeconomic status, the association being pronounced in studies of manual workers but absent in studies of professional men. The overall long-term association was attributable mainly to lung cancer in men, and partly to hemopoietic cancers (representing prolongation of survival by treatment). Colon cancer and other cancers unrelated to smoking showed no long-term association with low cholesterol. The data collectively do not justify concern that lowering serum cholesterol to reduce ischemic heart-disease risk might cause cancer. The long-term association with lung cancer is probably caused by smoking and we propose a mechanism.

Cholesterol↗
PubMed1991

Dietary salt and blood pressure.

We have previously shown that the association between salt intake and blood pressure is large and of substantial public health importance. Analysis of the average blood pressure and average sodium intake in different communities yielded estimates of the decrease in blood pressure for a given reduction in dietary sodium according to age and blood pressure centile that successfully predicted both the association between sodium and blood pressure in observational studies and the reduction in blood pressure obtained in trials of dietary salt reduction. Here we consider the validity of criticisms of the appraisal. The fact that the observed blood pressure reductions in individual trials closely mirrored predicted values for individuals trials that varied widely (from 2.6 to 25.2 mmHg systolic according to age, existing blood pressure and the extent of salt restriction) renders bias implausible since it would be too great a coincidence for a source of error to reproduce such close matching. If the analysis is restricted to trials that avoided possible bias because (1) the high- and low-salt diets were otherwise identical, (2) the order of the diet avoided regression to the mean or (3) the trials were double-blind with diets that were otherwise identical and the order was random, the matching between observed and predicted blood pressure reductions is equally close. Our results are consistent with the Intersalt study. A reduction in dietary salt could be a simple change, yet the reduction in mortality would be large.

Adolescent↗
PubMed1990

Is routine vitamin E administration justified in very low-birthweight infants?

Analysis of nine randomised controlled trials of prophylactic vitamin E supplementation in very low-birthweight infants (less than 1500g) showed no statistically significant reduction in the incidence of acute retinopathy of prematurity. There was a significant reduction (49 per cent) in the incidence of intraventricular haemorrhage, but no clear evidence for a corresponding reduction in intracerebral haemorrhage and no reduction in the incidence of haemorrhage confined to the germinal matrix. By combining the estimated reduction with the known incidence of long-term neurological disability associated with intracranial haemorrhage alone, it was shown that only 1.5 per cent (point estimate) and not more than about 4 per cent of all very low-birthweight infants are likely to benefit from routine vitamin E supplementation. In view of this, and data suggesting toxicity of vitamin E at concentrations close to those considered therapeutic, the routine use of vitamin E in very low-birthweight infants is not justified on present evidence. Only large randomised trials can establish whether currently used vitamin E preparations do more good than harm.

Cerebral Hemorrhage↗
PubMed1989

Serum cholesterol and subsequent risk of cancer: results from the BUPA study.

In the BUPA study, a prospective study of 22,000 men attending a screening centre in London, the mean serum cholesterol level of the 267 men who developed cancer was 6.66 mmol l-1, not significantly different from the mean level of 6.72 mmol l-1 among the 525 unaffected controls matched for age, smoking history and the calendar quarter of their attendance at the screening centre. There was, however, a significant difference in serum cholesterol levels among men who were diagnosed as having cancer less than 2 years after the date of blood collection (6.49 mmol l-1 for the 116 cancer subjects and 6.78 mmol l-1 for the 224 controls (P = 0.02)) but not in men who developed cancer 2-11 years after blood collection (6.79 mmol l-1 for the 151 cancer subjects and 6.68 mmol l-1 for the 301 controls). The observation that the association between low serum cholesterol and cancer was confined to men in whom a diagnosis of cancer was made within 2 years after the date of blood collection suggests that the low serum cholesterol is a metabolic consequence rather than a precursor of the cancer. Our results, which are consistent with the majority of other published studies, indicate that a low serum cholesterol is not a cause of cancer.

Adult↗