Robert A. Elton

Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene

The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54. Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina. There was no significant relation with vitamin A. Smoking was a confounding factor. The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking. Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight. The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02). These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E.

Particulate air pollution and the blood

BACKGROUND Particulate air pollution has been associated with excess deaths from, and increases in hospital admissions for, cardiovascular disease among older people. A study was undertaken to determine whether this may be a consequence of alterations in the blood, secondary to pulmonary inflammation caused by the action of fine particles on alveolar cells, by repeatedly measuring haematological factors in older people and relating them to measurements of exposure to airborne particles. METHODS One hundred and twelve individuals aged 60+ years in two UK cities provided repeated blood samples over 18 months, 108 providing the maximum of 12 samples. Estimates of individual exposure to particles of less than 10 μm diameter (PM10), derived from a mathematical model based on activity diaries and comparative measurements of PM10 at multiple sites and during a variety of activities, were made for each three day period prior to blood sampling. The relationships between blood values and estimates of both personal exposure and city centre measurements of PM10 were investigated by analysis of covariance, adjusting for city, season, temperature, and repeated individual measurements. RESULTS Estimated personal exposure to PM10 over the previous three days showed negative correlations with haemoglobin concentration, packed cell volume (PCV), and red blood cell count (p<0.001), and with platelets and factor VII levels (p<0.05). The changes in red cell indices persisted after adjustment for plasma albumin in a sample of 60 of the subjects. City centre PM10 measurements over three days also showed negative correlations with haemoglobin and red cell count (p<0.001) and with PCV and fibrinogen (p<0.05), the relationship with haemoglobin persisting after adjustment for albumin. C reactive protein levels showed a positive association with city centre measurements of PM10 (p<0.01). Based on a linear relationship, the estimated change in haemoglobin associated with an alteration in particle concentration of 100 μg/m3 is estimated to have been 0.44 g/dl (95% CI 0.62 to 0.26) for personal PM10 and 0.73 g/dl (95% CI 1.11 to 0.36) for city centre PM10 measurements. CONCLUSIONS This investigation is the first to estimate personal exposures to PM10 and to demonstrate associations between haematological indices and air pollution. The changes in haemoglobin adjusted for albumin suggest that inhalation of some component of PM10may cause sequestration of red cells in the circulation. We propose that an action of such particles either on lung endothelial cells or on erythrocytes themselves may be responsible for changing red cell adhesiveness. Peripheral sequestration of red cells offers an explanation for the observed cardiovascular effects of particulate air pollution.

LINOLEIC AND EICOSAPENTAENOIC ACIDS IN ADIPOSE TISSUE AND PLATELETS AND RISK OF CORONARY HEART DISEASE

The relation between the fatty-acid composition of adipose tissue and platelet membranes and the estimated relative risk of coronary heart disease (CHD) was examined in a case-control study of new angina pectoris (AP) and first acute myocardial infarction (AMI). There were progressive inverse relations between adipose linoleic acid and platelet-membrane eicosapentaenoic acid and the estimated relative risk of AP. These relations were statistically independent of each other and traditional CHD risk factors. For AMI there was a progressive inverse relation between adipose linoleic acid and the estimated relative risk, but it was confounded by smoking habit. Smokers consume less linoleic acid than non-smokers. Although eicosapentaenoic acid in platelet membranes was lower in AMI patients than in controls, this difference was not significant. The estimated proportionate increase in risk of AP, independent of other CHD risk factors, was 1.2 (1.1-1.3) for a 1% decrease in linoleic acid or a 0.1% decrease in eicosapentaenoic acid.

Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease

Haemostatic and rheological factors may predict cardiovascular disease. We studied patients with intermittent claudication to see if the progression of peripheral arterial disease and the risks of coronary events could be predicted by baseline packed cell volume, plasma fibrinogen, blood and plasma viscosites, von Willebrand factor antigen, cross-linked fibrin degradation products (XLFDP), urinary fibrinopeptide A, and plasma leucocyte elastase. In 617 patients with claudication followed up for one year, baseline XLFDP was related most strongly to coronary events, relative risk 4.4 (95% CI 1.3-19.0) between top and bottom quintiles. Plasma fibrinogen was the strongest independent predictor of death from coronary disease. XLFDP was the only factor, in addition to age and cigarette smoking, that was independently associated (p = 0.008) with deterioration in peripheral arterial disease. We conclude that, in patients with peripheral arterial disease, plasma concentration of XLFDP, a measure of ongoing fibrin formation and degradation, is a strong predictor of both disease progression and future coronary risk. These results accord with the hypothesis that fibrin formation contributes to progression of coronary and peripheral atherosclerosis.

ADIPOSE TISSUE AND PLATELET FATTY ACIDS AND CORONARY HEART DISEASE IN SCOTTISH MEN

The relation between coronary heart disease (CHD) and fatty acid composition of adipose tissue and platelets was examined in a random sample of 448 middle-aged Scottish men. The linoleic acid (18:2n6) content in adipose tissue of 28 men with previously unidentified CHD was significantly lower than that in the rest of the group. Platelet linoleic and other fatty acids were not significantly different in men with new CHD. Fatty acid content of adipose tissue reflects long-term dietary intake, and a 7-day weighed dietary record in a random sub-sample of 164 men confirmed that intake of linoleic acid in 10 of the 28 new CHD cases was significantly lower than in the healthy men. In a multiple logistic analysis adipose tissue linoleic acid, age, high density lipoprotein cholesterol, and weight/height index each made an independent contribution to the explanation of new CHD. When all fatty acids were included in a second regression analysis, low concentrations of dihomo-gamma-linolenic (20:3n6) acid in adipose tissue showed a more significant relation with new CHD than did linoleic acid.

Transcutaneous oxygen levels in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a potentially blinding disease of preterm infants. 21 days of computer-recorded transcutaneous oxygen (TcPO2) data were compared in 31 infants with stage 3 or greater ROP and 38 infants with no ROP or stage 1 or 2. In a multiple logistic regression adjusted for significant perinatal factors (birthweight, gestation, and intraventricular haemorrhage), babies with stage 3 or higher ROP showed an increased variability of TcPO2 in week 1 (p < 0.01) and 2 (p = 0.012) but not week 3. Variability of TcPO2 in the first 2 weeks of life is a significant predictor of severe ROP.

ABO blood group, secretor state, and susceptibility to recurrent urinary tract infection in women.

ABO blood group and secretor state was determined in 319 women with recurrent urinary tract infection and compared with those of a control group of 334 women of similar age ranges. Women of blood groups B and AB who are non-secretors of blood group substances showed a significant relative risk of recurrent urinary tract infection of 3.12 (95% confidence limits, 1.49 and 6.52) in comparison with other types. This appears to be a genuine example of synergy in which absence of anti-B isohaemagglutinin and secretor substances combines to give an increased risk of recurrent urinary tract infection. Determination of blood group and secretor state may provide additional information in identifying those at risk.

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.

Urban air pollution and cardiopulmonary ill health : a 14.5 year time series study

OBJECTIVES: To examine possible associations between daily concentrations of urban air pollutants and hospital emergency admissions and mortality due to cardiac and pulmonary disease. METHODS: A time series study was conducted in the City of Edinburgh, which has a population of about 450,000. Poisson log linear regression models were used to investigate the relation of the daily event rate with daily air pollution concentrations of sulphur dioxide (SO2) and black smoke from 1981 to 1995, and of nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and particulate matter (PM10) from 1992 to 1995. Adjustments were made for seasonal and weekday variation, daily temperature, and wind speed. RESULTS: The most significant findings were positive associations over the period 1981-95 between black smoke as a mean of the previous three days and daily all cause mortality in people aged > or = 65, and respiratory mortality also in this age group (3.9% increase in mortality for a 10 micrograms/m3 increment in black smoke). For hospital emergency admissions between 1992 and 1995 the two most significant findings (p < 0.05) were for cardiovascular admissions of people aged > or = 65 which showed a positive association with PM10 as a mean of the 3 previous days, and a negative association with O3 as a mean of the previous three days. Analyses of outcomes based on linkage with previous cardiorespiratory emergency admissions did not show substantially different results. CONCLUSION: These data suggest that in the City of Edinburgh, after correction for confounders, there was a small but significant association between concentrations of black smoke and respiratory mortality in the older age group, probably attributable to higher pollution levels in the early part of the study period. There were also generally weak and variable associations between day to day changes in concentrations of urban air pollutants at a single central point and emergency hospital admission rates from cardiac and respiratory disease.

Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life.

OBJECTIVES We aimed to: (1) assess the association of average, low, high and variable mean blood pressure (mbp) on death and the common morbidities of very low birthweight infants, and in doing so, (2) to derive representative reference ranges for mbp in very low birthweight infants. STUDY DESIGN This five year retrospective study assessed 1 min computer recordings of intra-arterial mbp in 232 very low birthweight infants over the first 7 days of life in a tertiary NICU. Four measures of mbp were assessed: average, variability, maximum (per time period), and percentage of time with a mean blood pressure less than the infants gestation. Correlation was made with death and the development of intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP). RESULTS The mbp increased with increasing birthweight and postnatal age (though with a slight decrease on days 6 and 7). Birthweight, gestation and colloid support (adjusted for birthweight and gestation) were the only factors significantly associated with mbp. IVH was predominantly associated with a low and variable mbp on the day IVH was noted or the day before. PVL and ROP were not associated with blood pressure. CONCLUSIONS These reference ranges include more infants and data than previously published and relate mbp in this cohort to morbidity and mortality. They could assist clinicians in judging appropriate mbp for birthweight.