Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.

BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors. METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. RESULTS: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

Outcomes of undernutrition in patients in the community with cancer or cardiovascular disease.

Public health concern has tended to focus on the dangers of obesity, but there is evidence that undernutrition may also pose a risk to physical and mental well-being, particularly in those who are already ill. Using the General Practice Research Database (see office for Population Censuses and Surveys, 1995), we followed up 10,128 men and women aged 18 years and over who had been diagnosed with cancer or cardiovascular disease to examine whether nutritional status, as indicated by BMI, affected rates of use of health care resources and mortality. In both diagnostic groups, patients with a BMI below 20 kg/m2 had higher rates of consultation with GP, higher rates of prescription and higher death rates during the follow-up period compared with those with a BMI of 20-< 25 kg/m2. In men and women with cardiovascular disease, poor nutritional status was associated with a sharply increased risk of hospital admission. Patients whose BMI was 30-< 40 kg/m2 also tended to have increased rates of GP consultation and prescription, and if they were under the age of 65 years, they had an increased risk of death. The results of the present study suggest that in men and women with cancer or cardiovascular disease, even minor degrees of undernutrition are associated with a marked increase in morbidity and mortality.

Mortality from Parkinson's disease and other causes in men who were prisoners of war in the Far East.

BACKGROUND: During World War II, more than 140000 Allied prisoners of war (POWs) were held captive by the Japanese in conditions of extreme privation. There have been concerns that the survivors are at increased risk of degenerative neurological disorders, especially Parkinson's disease. We assembled a cohort of British ex-POWs and analysed their mortality in a 46-year follow-up study. METHODS: Using records held by the War Pensions Agency, we abstracted data on 11915 British former POWs. 11134 men were traced, and observed numbers of deaths between 1952 and 1997 were compared with those expected from national rates for the male population of England and Wales. Standardised mortality ratios (SMR) were calculated. FINDINGS: Overall, mortality was lower than expected (7474 deaths vs 8796.2 expected; SMR 0.85 [95% CI 0.83-0.87]). Death rates from Parkinson's disease among the former POWs were slightly below the national average, though this difference was not statistically significant (35 deaths vs 43.2 expected; SMR 0.81 [0.56-1.13]). A similar pattern was seen for other degenerative neurological disorders (motorneuron disease 0.62 [0.31-1.11], multiple sclerosis 0.88 [0.42-1.61], and dementia 0.88 [0.68-1.11]). The former POWs had significantly lower than expected mortality from all major causes of death (ischaemic heart disease 0.81 [0.78-0.85], cerebrovascular disease 0.88 [0.81-0.95], all malignant neoplasms 0.92 [0.88-0.95], and respiratory disease 0.79 [0.74-0.85]). They also had below average rates of death from tuberculosis (0.44 [0.26-0.71]) and suicide (0.77 [0.57-1.02]), though the latter relation was not statistically significant. Mortality from diseases of the liver was increased (chronic liver disease and cirrhosis 1.68 [1.28-2.17], primary carcinoma of the liver 2.42 [1.75-3.26]). INTERPRETATION: There is little evidence that men who were POWs in the Far East have higher rates of death than the male population generally. The only exception is diseases of the liver, which may be due to infection with hepatitis B or C virus during captivity. Death-certification data cannot provide a complete picture of physical and mental health, but the period of severe malnutrition, frequent infections, exhaustion, and intense psychological stress seems not to have increased susceptibility to neurodegenerative disease.

Gender differences in the healthy worker effect among synthetic vitreous fiber workers.

The aim of this study was to determine whether the healthy worker effect and its component parts operate similarly for women and men. A cohort of workers from 14 synthetic vitreous fiber factories in seven countries, employed for at least 1 year between 1933 and 1977 and followed up to the early 1990s, included 375 deaths and 53,608 person-years among females and 2,568 deaths and 210,073 person-years among males. Standardized mortality ratios for all-cause and circulatory diseases were adjusted for country, age, calendar time, and gender. In addition, internal comparisons were adjusted for time since hire and employment status. The analyses addressed the following: 1) the healthy hire effect, 2) the time since hire effect, and 3) the healthy worker survivor effect. In this cohort, an overall healthy worker effect was not present in either gender. The healthy hire effect, based on standardized mortality ratios for years 1-4 since hire, was observed in males (standardized mortality ratio (SMR) = 0.8; 95% confidence interval (CI): 0.7, 1.0) but was less in females (SMR = 0.9; 95% CI: 0.5, 1.6). The relative risks increased slightly with time since hire in males but not in females. Higher mortality ratios were seen among those leaving employment than among those who remained actively employed; however, this effect was substantially greater for women (relative risk (RR) = 3.4; 95% CI: 1.8, 6.3) than men (RR = 1.8; 95% CI: 1.5, 2.1). The gender difference for active versus inactive status was stronger up to age 60 (men: RR = 1.7; 95% CI: 1.4, 2.0; women: RR = 3.6; 95% CI: 1.8, 7.1) than above that age. In conclusion, it appears that there is a stronger selection of healthy men than women into the workforce, while health-related selection out of the workforce is stronger for women than men.

Catch-up growth in childhood and death from coronary heart disease: longitudinal study.

OBJECTIVE: To examine whether catch-up growth during childhood modifies the increased risk of death from coronary heart disease that is associated with reduced intrauterine growth. DESIGN: Follow up study of men whose body size at birth was recorded and who had an average of 10 measurements taken of their height and weight through childhood. SETTING: Helsinki, Finland. SUBJECTS: 3641 men who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki. MAIN OUTCOME MEASURES: Hazard ratios for death from coronary heart disease. RESULTS: Death from coronary heart disease was associated with low birth weight and, more strongly, with a low ponderal index at birth. Men who died from coronary heart disease had an above average body mass index at all ages from 7 to 15 years. In a simultaneous regression the hazard ratio for death from the disease increased by 14% (95% confidence interval 8% to 19%; P<0.0001) for each unit (kg/m3) decrease in ponderal index at birth and by 22% (10% to 36%; P=0.0001) for each unit (kg/m2) increase in body mass index at 11 years of age. Body mass index in childhood was strongly related to maternal body mass index, which in turn was related to coronary heart disease. The extent of crowding in the home during childhood, although related to body mass index in childhood, was not related to later coronary heart disease. CONCLUSION: The highest death rates from coronary heart disease occurred in boys who were thin at birth but whose weight caught up so that they had an average or above average body mass from the age of 7 years. Death from coronary heart disease may be a consequence of poor prenatal nutrition followed by improved postnatal nutrition.

Effects of ergotamine on myocardial blood flow in migraineurs without evidence of atherosclerotic coronary artery disease.

The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic (dipyridamole) myocardial blood flow (MBF), measured with positron emission tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind, randomized, placebo controlled, crossover study. Ergotamine produced a 27% reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1); p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs 2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2 +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting vasoconstriction of the coronary microcirculation.

Effect of nutritional status on use of health care resources by patients with chronic disease living in the community.

The prevalence of malnutrition in patients with chronic disease living in the community in the UK is around 8%. Whether such patients experience greater morbidity and mortality or make increased use of health care resources is unknown. The aim of this study was to investigate how the use of health care resources by patients with chronic disorders of the respiratory, gastrointestinal and neurological systems varied by nutritional status. We used longitudinal data, collected since 1987, which formed part of the General Practice Research Database in the UK. Subjects were 11 357 men and women aged 18 years or over. Main outcomes were consultation rates in general practice, prescription rates, hospital referral rates, hospital admission rates and mortality. Consultation and prescription rates were lowest amongst patients whose body mass index (BMI) was between 20 and 25. Rates were higher in patients whose BMI was below 20, or 25 and above. There was no statistically significant relation between rate of hospital outpatient referral and nutritional status, but both hospital admission rate and mortality were greatest in those people whose BMIs were below 20 and declined as BMIs increased. In patients with differential use of health care resources in both primary care and hospital practice, and with differences in mortality.

Cancer mortality among man-made vitreous fiber production workers.

We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.

Cancer mortality among local authority pest control officers in England and Wales.

OBJECTIVE: To examine cancer mortality by tumour site among local authority pest control officers. METHODS: Prospective mortality study, and follow up to the end of 1994, of 1485 male pest control officers aged between 17 and 69 and employed in 296 local authorities in England and Wales for at least six months between January 1980 and April 1984. Observed numbers of deaths were compared with those expected on the basis of the rates for relevant calendar year, cause, sex, and age specific groups for England and Wales. RESULTS: 200 deaths occurred during the follow up period of which 65 were certified as due to malignant neoplasms. No tumour type showed significantly more deaths than expected. Total all cause, lung cancer, and respiratory disease mortality were significantly lower than expected. CONCLUSIONS: 15 year follow up of a group of men handling a wide range of pesticides did not show any significant risk of cancer. This may be partially explained by the healthy worker effect and also the limited power of the study to detect significant increases in the less common tumours. Further long term follow up of this cohort will continue. Chemical control of pests that can cause human disease and can contaminate food and water has been, and will continue to be, a major public health measure. It is important to ensure that the health of those applying pesticides is not at excess risk. Negative results are important.

Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people.

OBJECTIVES: To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. DESIGN: A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. SETTING: Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS: 730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. RESULTS: Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. CONCLUSION: In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease.

Pooled reanalysis of cancer mortality among five cohorts of workers in wood-related industries.

OBJECTIVES: To provide more information regarding the risk of cancer associated with wood dust, a pooled reanalysis of data from five cohort studies was performed. METHODS: The combined cohort consisted of 28,704 persons from five studies: British furniture workers, members of the union representing furniture workers in the United States, two cohorts of plywood workers, and one of wood model makers, among whom 7665 deaths occurred. Pooled analyses were carried out for all of the cohorts combined, the two furniture worker cohorts combined, and the two plywood workers cohorts combined. RESULTS: Significant excesses of nasal [observed 11, standardized mortality ratio (SMR) 3.1, 95% confidence interval (95% CI) 1.6-5.6] and nasopharyngeal (observed 9, SMR 2.4, 95% CI 1.1-4.5) cancer were observed. That for nasal cancer appeared to be associated with exposure to wood dust but was based solely on cases from the British furniture worker cohort, while that of nasopharyngeal cancer was observed for furniture and plywood workers and was associated with both high and low probability of wood dust exposure. Some support for an excess risk of multiple myeloma was also observed but was less clearly associated with wood dust exposure. No excesses of lung, larynx, stomach, or colon cancer were found to be associated with any surrogate indicators of wood dust exposure. CONCLUSIONS: Workers exposed to wood dust may have an excess risk of nasopharyngeal cancer and multiple myeloma in addition to sinonasal cancer. The limitations of this study would tend to obscure relationships, rather than create false positive findings.

Weight gain in infancy and cancer of the ovary.

The geographic association between ovarian cancer and tall stature suggests a link with rapid growth in early childhood. Among 5585 women born in Hertfordshire, UK, 41 who died from ovarian cancer had had a high rate of weight gain in infancy. Whereas their mean birthweight was the same as that of the other women, their mean weight at 1 year was higher (22.3 pounds [10.1 kg] vs 21.4 pounds [9.7 kg], p = 0.01). These observations are consistent with the hypothesis that ovarian cancer is linked to altered patterns of gonadotropin release established in utero when the fetal hypothalamus is imprinted.

Early growth and death from cardiovascular disease in women.

OBJECTIVE: To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. DESIGN: Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. SETTING: Hertfordshire, England. SUBJECTS: 5585 women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES: Standardised mortality ratios for cardiovascular disease. RESULTS: Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. CONCLUSION: Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.

A cohort study of workers exposed to formaldehyde in the British chemical industry: an update.

A cohort study of workers exposed to formaldehyde in the British chemical industry in any one of six factories has been extended after the earlier published report in 1984. A further eight years of follow up to the end of 1989 have been included for the originally reported 7660 workers first employed before 1965, and a first follow up to the same date has been carried out for 6357 workers first employed since 1964. Extensive checking of the database has taken place including records at the factories, the MRC Environmental Epidemiology Unit, and the National Health Service Central Register. The updated findings include one death from nasal cancer compared with 1.7 expected in this number of men during the follow up period--which gives no support to the original hypothesis based on animal experimental data that formaldehyde may be a nasal carcinogen in humans. There have been no cases of nasopharyngeal cancer in the cohort compared with an estimated 1.3 expected--which gives no support to the findings in a similarly designed study in the United States of an excess of cancers of the nasopharynx associated with exposure to formaldehyde. There has been a slight excess of about 12% for lung cancer with 402 deaths compared with about 359 expected. This is similar to that found in the United States study, but higher than we reported earlier before the checking procedures and extended follow up. Further analysis gives no definitive indication of this excess of lung cancer being clearly related to formaldehyde exposure, and the increase is within that generally thought consistent with possible confounding effects of cigarette smoking (although no data are available on this point).

Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.

OBJECTIVE: To examine whether method of infant feeding is associated with adult serum lipid concentrations and mortality from ischaemic heart disease. DESIGN: Follow up study of men born during 1911-30. SETTING: Hertfordshire, England. SUBJECTS: 5718 men, for 5471 of whom information on infant feeding had been recorded by health visitors and 1314 of whom had died. 485 of the men born during 1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN OUTCOME MEASURES: Death from ischaemic heart disease; serum cholesterol and apolipoprotein concentrations. RESULTS: 474 men had died from ischaemic heart disease. Standardised mortality ratios were 97 (95% confidence interval 81 to 115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to 90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who had been breast and bottle fed. Compared with men weaned before one year men not weaned had higher mean serum concentrations of total cholesterol (6.9 (not weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6 mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also had a high standardised mortality ratio for ischaemic heart disease (95; 68 to 130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In all feeding groups serum apolipoprotein B concentrations were lower in men with higher birth weight and weight at 1 year. CONCLUSIONS: Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.

Fetal and infant growth and impaired glucose tolerance at age 64.

OBJECTIVE: To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN: Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING: Hertfordshire, England. SUBJECTS: 468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS: 93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS: Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

OBJECTIVE: To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN: Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING: Hertfordshire, England. SUBJECTS: 5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES: Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS: 55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS: Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.

A mortality follow-up study of pottery workers: preliminary findings on lung cancer.

The possible association between exposure to low levels of silica and lung cancer was investigated by following up pottery workers included in a survey conducted in 1970-71 of respiratory disease among such workers. The initial results show that, among men under the age of 60 at the time of the original survey, mortality has been similar to that expected, but that there was an excess of lung cancer of over 30% even after allowance had been made for cigarette smoking and place of residence. There were no particular excesses of lung cancer by product group or job group. However, there was some indication that lung cancer risk increased with estimated cumulative exposure to respirable quartz. These findings do suggest an association between lung cancer and the low levels of silica found in potteries, and the follow-up will therefore be continued and a more detailed analysis of the data carried out.

Weight in infancy and death from ischaemic heart disease.

Environmental influences that impair growth and development in early life may be risk factors for ischaemic heart disease. To test this hypothesis, 5654 men born during 1911-30 were traced. They were born in six districts of Hertfordshire, England, and their weights in infancy were recorded. 92.4% were breast fed. Men with the lowest weights at birth and at one year had the highest death rates from ischaemic heart disease. The standardised mortality ratios fell from 111 in men who weighed 18 pounds (8.2 kg) or less at one year to 42 in those who weighed 27 pounds (12.3 kg) or more. Measures that promote prenatal and postnatal growth may reduce deaths from ischaemic heart disease. Promotion of postnatal growth may be especially important in boys who weigh below 7.5 pounds (3.4 kg) at birth.