E. S. Limb

Temperature and risk factors for ischaemic heart disease in the Caerphilly prospective study.

OBJECTIVE--To examine the associations between air temperature and risk factors for ischaemic heart disease. METHOD--Data on risk factors are available from up to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures were obtained from the Meteorological Office. Relations between these were examined by regression. RESULTS--The coldest month of the year has a mean temperature that is 16 degrees C lower than that in the warmest month. A fall in temperature of this magnitude is associated with higher blood pressures (by 3-5 mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08 mmol/l). The most important effects however, seem to be on the haemostatic system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also raised. Platelet count is increased by 30% of a standard deviation and the sensitivity of platelets in whole blood to adenosine diphosphate is increased by cold. CONCLUSIONS--These effects on haemostasis, together with the effect on blood pressure, could explain a large part of the increase in ischaemic heart disease in the winter but are unlikely to explain much of the difference in mortality within different areas of England and Wales.

Risk factors for respiratory morbidity in infancy after very premature birth

Objectives: To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors. Design: Prospective follow up study. Setting: The United Kingdom oscillation study. Patients: 492 infants, all born before 29 weeks gestation. Interventions: Structured questionnaires were completed by local paediatricians when the infants were seen in outpatients at 6 and 12 months of age corrected for prematurity. Main outcome measures: Cough, wheeze, and treatment requirements and the composite measure of respiratory morbidity (cough, frequent cough, cough without infection, wheeze, frequent wheeze, wheeze without infection, and use of chest medicine) and their relation to 13 possible explanatory variables. Results: At 6 and 12 months of corrected age, 27% of the infants coughed and 6% had frequent (more than once a week) cough, and 20% and 3% respectively had wheeze or frequent wheeze. At 6 and 12 months, 14% of infants had taken bronchodilators and 8% inhaled steroids. After adjustment for multiple outcome testing, four factors were associated with increased respiratory morbidity: male sex, oxygen dependency at 36 weeks postmenstrual age, having older siblings aged less than 5 years, and living in rented accommodation. Conclusions: Male infants are particularly vulnerable to respiratory morbidity in infancy after very premature birth. It is important to identify a safe and effective strategy to prevent chronic oxygen dependency.

Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years

Background: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. Objective: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. Methods: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. Results: Paediatricians’ forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26–28 weeks. Conclusions: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

Objective: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. Design: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. Patients: A total of 185 infants with a median gestational age of 26 (range 23–28) weeks. Results: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. Conclusion: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Inter-relationships between haemostatic tests and the effects of some dietary determinants in the Caerphilly cohort of older men

Inter-relationships between fibrinogen, platelets and other haemostatic factors were examined in 1030 men aged 55–99 years. Fasting blood was taken and used for cell counts, platelet counts and platelet parameters, aggregation of platelets to ADP by a whole blood method and a filter test of platelet activation. Plasma fibrinogen, von Willebrand factor, factor VII and plasma viscosity were measured by standard methods. A stressed bleeding time was conducted on the forearm of the arm not used for venepuncture. Variability within the laboratory and short-term intra-subject variation were examined and found to be acceptably small. The effect of age on the tests was modest, except for von Willebrand factor which increased by about 50% of a SD for every 10 years of age. Cholesterol and triglyceride levels had small effects on the platelet tests and a large effect on factor VII. A number of dietary and life-style determinants were examined: smokers had increased levels of fibrinogen, viscosity and white cell count and reduced bleeding times. Alcohol drinkers showed reduced platelet activity and have lower levels of fibrinogen, von Willebrand factor and white cell count. Men who took fish oil capsules had substantially increased bleeding times and lower levels of von Willebrand factor and men who took capsules containing an extract of garlic showed reduced platelet retention in the filter test.

Shear-induced Filter Blockage. A Population Based Appraisal of a Method for the Assessment of Platelet, White Cell and von Willebrand Factor Interactions

Blood behaviour under shear-stress is assessed by a filter method in the Caerphilly Prospective Heart Study. Associations with haemostatic and lifestyle factors in 941 men aged 55 to 69 years are reported. The importance of platelets in filter blockage is confirmed, and roles for white cells and plasma viscosity in determining flow prior to blockage are identified. The aspect of platelet activity involved in blockage appears to be independent of mechanisms mediated by cyclo-oxygenase and adenosine diphosphate. von Willebrand factor however is associated with filter blockage, probably as an inter-platelet ligand. Fibrinogen is not required for blockage. Men regularly consuming alcohol or garlic supplements show reduced blockage, and biochemical mechanisms are suggested which might explain these associations. No effects of aspirin, smoking or consumption of fish oil supplements were noted. Shear-induced filter blockage is a simple method for measuring complex flow-dependent interactions of haemostatic factors. Its application in a wide range of investigations, including epidemiological studies, would appear to be appropriate.