Iain M. Carey

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Parental smoking and spirometric indices in children

BACKGROUND A systematic quantitative review was conducted of the evidence relating parental smoking to spirometric indices in children. METHODS An electronic search of the Embase and Medline databases was completed in April 1997 and identified 692 articles from which we included four studies in neonates, 42 cross-sectional studies in school aged children (22 were included in a meta-analysis), and six longitudinal studies of lung function development. RESULTS In a pooled analyses of 21 surveys of school aged children the percentage reduction in forced expiratory volume in one second (FEV1) in children exposed to parental smoking compared with those not exposed was 1.4% (95% CI 1.0 to 1.9). Effects were greater on mid expiratory flow rates (5.0% reduction, 95% CI 3.3 to 6.6) and end expiratory flow rates (4.3% reduction, 95% CI 3.1 to 5.5). Adjustment for potential confounding variables had little effect on the estimates. A number of studies reported clear evidence of exposure response. Where exposure was explicitly identified it was usually maternal smoking. Two studies in neonates have reported effects of prenatal exposure to maternal smoking. Of five cross sectional studies that compared effects of perinatal exposure (retrospectively assessed) with current exposure to maternal smoking in later childhood, the three largest concluded that the major effect was in utero or neonatal exposure. Longitudinal studies suggest a small effect of current exposure on growth in lung function, but with some heterogeneity between studies. CONCLUSIONS Maternal smoking is associated with small but statistically significant deficits in FEV1 and other spirometric indices in school aged children. This is almost certainly a causal relationship. Much of the effect may be due to maternal smoking during pregnancy.

Home environment and severe asthma in adolescence: a population based case-control study

Abstract Objective: To investigate the effects of the home environment on the risk of severe asthma during adolescence. Design: A questionnaire based case-control study drawn from a cross sectional survey of allergic diseases among secondary school pupils in Sheffield in 1991. Subjects: 763 children whose parents had reported that over the previous 12 months they had suffered either 12 or more wheezing attacks or a speech limiting attack of wheeze. A further 763 children were frequency matched for age and school class to act as controls. Analysis was restricted to 486 affected children and 475 others born between 1975 and 1980 who had lived at their present address for more than three years. Results: Independent associations with severe wheeze were seen for non-feather bedding, especially foam pillows (odds ratio 2.78; 95% confidence interval 1.89 to 4.17), and the ownership of furry pets now (1.51; 1.04 to 2.20) and at birth (1.70; 1.20 to 2.40). These estimates were derived from subjects whose parents denied making changes in the bedroom or avoiding having a pet because of allergy. Parental smoking, use of gas for cooking, age of mattress, and mould growth in the childs bedroom were not significantly associated with wheezing. Conclusions: Either our study questionnaire failed to detect the avoidance or removal of feather bedding by allergic families or there is some undetermined hazard related to foam pillows. Synthetic bedding and furry pets were both widespreadin this population and may represent remediable causes of childhood asthma.

Trends in the prevalence of diagnosed atrial fibrillation, its treatment with anticoagulation and predictors of such treatment in UK primary care

Objectives: To examine trends in the prevalence of diagnosed atrial fibrillation (AF), its treatment with oral anticoagulants between 1994 and 2003, and predictors of anticoagulant treatment in 2003. Methods: Analysis of electronic data from 131 general practices (about one million registered patients annually) contributing to the DIN-LINK database. Results: From 1994 to 2003 the prevalence of “active” AF rose from 0.78% to 1.31% in men and from 0.79% to 1.15% in women. The proportion of patients with AF taking anticoagulants rose from 25% to 53% in men and from 21% to 40% in women. Most others received antiplatelets. The likelihood of receiving anticoagulants was greater for men and with increasing stroke risk. It decreased sharply with age after 75 years. Socioeconomic status, urbanisation and region had no influence. Non-steroidal anti-inflammatory drugs, antiplatelet drugs and ulcer healing drugs were associated with reduced likelihood of receiving anticoagulants, as were peptic ulcers, chronic gut disorders, anaemias, psychoses and poor compliance. Anticoagulant treatment was associated with several cardiovascular co-morbidities and drugs, possibly due to secondary care treatment. Nevertheless, only 56.5% of patients at very high risk of stroke were taking anticoagulants in 2003, whereas 38.2% of patients at low risk of stroke received anticoagulants. Conclusions: This study confirms previously observed trends of increasing AF prevalence and warfarin treatment. Many patients who may benefit from anticoagulation still do not receive it, whereas others at lower risk of stroke do. The lower likelihood of women receiving anticoagulants is of particular concern.

Evolution of statin prescribing 1994–2001: a case of agism but not of sexism?

Objective: To study trends in the use of lipid lowering drugs in the UK, and to assess which patient factors influence prescribing. Methods: Routinely collected computerised medical data were analysed from 142 general practices across England and Wales that provide data for the Doctors’ Independent Network database. Subjects included were people aged 35 years or more with treated ischaemic heart disease, averaging annually over 30 000. The temporal trend from 1994 to 2001 in prescription of lipid lowering drugs and daily statin dose and the odds ratios (ORs) for receiving a statin prescription in 1998 were examined. Results: Lipid lowering drug prescribing increased greatly over time, entirely because of statins, so that in 2001 56.3% of men and 41.1% of women with ischaemic heart disease received lipid lowering drugs. However, 33% of these patients were on a < 20 mg simvastatin daily equivalent. In 1998 the OR for receiving a statin fell from 1 at age 55–64 to 0.64 at 65–74 and 0.16 at 75–84 years. The age effect was similar in those without major comorbidity. Revascularised patients were much more likely to receive a statin than those with angina (OR 3.92, 95% confidence interval (CI) 3.57 to 4.31). Men were more likely to receive a statin than women (OR 1.62, 95% CI 1.54 to 1.71) but this difference disappeared after adjustment for age and severity of disease (OR 1.06). Geographical region had little effect but there was a very weak socioeconomic gradient. Conclusions: Although prescribing has increased, many patients who may benefit from lipid lowering drugs either do not receive it or are undertreated, possibly because of lack of awareness of the relative potency of the different statins. Patients with angina and the elderly are less likely to receive treatment that may prevent a coronary event.

Mortality Associations with Long-Term Exposure to Outdoor Air Pollution in a National English Cohort

RATIONALE Cohort evidence linking long-term exposure to outdoor particulate air pollution and mortality has come largely from the United States. There is relatively little evidence from nationally representative cohorts in other countries. OBJECTIVES To investigate the relationship between long-term exposure to a range of pollutants and causes of death in a national English cohort. METHODS A total of 835,607 patients aged 40-89 years registered with 205 general practices were followed from 2003-2007. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter less than 10 (PM(10)) and less than 2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)), ozone, and sulfur dioxide (SO(2)) at 1 km(2) resolution, estimated from emission-based models, were linked to residential postcode. Deaths (n = 83,103) were ascertained from linkage to death certificates, and hazard ratios (HRs) for all- and cause-specific mortality for pollutants were estimated for interquartile pollutant changes from Cox models adjusting for age, sex, smoking, body mass index, and area-level socioeconomic status markers. MEASUREMENTS AND MAIN RESULTS Residential concentrations of all pollutants except ozone were positively associated with all-cause mortality (HR, 1.02, 1.03, and 1.04 for PM(2.5), NO(2), and SO(2), respectively). Associations for PM(2.5), NO(2), and SO(2) were larger for respiratory deaths (HR, 1.09 each) and lung cancer (HR, 1.02, 1.06, and 1.05) but nearer unity for cardiovascular deaths (1.00, 1.00, and 1.04). CONCLUSIONS These results strengthen the evidence linking long-term ambient air pollution exposure to increased all-cause mortality. However, the stronger associations with respiratory mortality are not consistent with most US studies in which associations with cardiovascular causes of death tend to predominate.

Long-term exposure to outdoor air pollution and incidence of cardiovascular diseases.

Background: Evidence based largely on US cohorts suggests that long-term exposure to fine particulate matter is associated with cardiovascular mortality. There is less evidence for other pollutants and for cardiovascular morbidity. By using a cohort of 836,557 patients age 40 to 89 years registered with 205 English general practices in 2003, we investigated relationships between ambient outdoor air pollution and incident myocardial infarction, stroke, arrhythmia, and heart failure over a 5-year period. Methods: Events were identified from primary care records, hospital admissions, and death certificates. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter <10 (PM10) and <2.5 microns, nitrogen dioxide (NO2), ozone, and sulfur dioxide at a 1 × 1 km resolution were derived from emission-based models and linked to residential postcode. Analyses were performed using Cox proportional hazards models adjusting for relevant confounders, including social and economic deprivation and smoking. Results: While evidence was weak for relationships with myocardial infarction, stroke, or arrhythmia, we found consistent associations between pollutant concentrations and incident cases of heart failure. An interquartile range change in PM10 and in NO2 (3.0 and 10.7 µg/m3, respectively) both produced a hazard ratio of 1.06 (95% confidence interval = 1.01–1.11) after adjustment for confounders. There was some evidence that these effects were greater in more affluent areas. Conclusions: This study of an English national cohort found evidence linking long-term exposure to particulate matter and NO2 with the development of heart failure. We did not, however, replicate associations for other cardiovascular outcomes that have been reported elsewhere.

Does β‐adrenoceptor blocker therapy improve cancer survival? Findings from a population‐based retrospective cohort study

AIMS To examine the effect of β-adrenoceptor blocker treatment on cancer survival. METHODS In a UK primary care database, we compared patients with a new cancer diagnosis receiving β-adrenoceptor blockers regularly (n= 1406) with patients receiving other antihypertensive medication (n= 2056). RESULTS Compared with cancer patients receiving other antihypertensive medication, patients receiving β-adrenoceptor blocker therapy experienced slightly poorer survival (HR = 1.18, 95% CI 1.04, 1.33 for all β-adrenoceptor blockers; HR = 1.21, 95% CI 0.94, 1.55 for non-selective β-adrenoceptor blockers). This poorer overall survival was explained by patients with pancreatic and prostate cancer with no evidence of an effect on survival for patients with lung, breast or colorectal cancer. Analysis in a cancer-free matched parallel cohort did not suggest selection bias masked a beneficial effect. CONCLUSION Our study does not support the hypothesis that β-adrenoceptor blockers improve survival for common cancers.

The effects of environmental tobacco smoke exposure on lung function in a longitudinal study of British adults.

Small effects of environmental tobacco smoke exposure on lung function have been demonstrated in many studies of children, but fewer studies have examined adults in this respect. We examined these relations in a 7-year longitudinal study of 1,623 British adults, age 18-73 years, who were nonsmokers throughout. Outcome was measured by forced expiratory volume in 1 second (FEV1) adjusted for sex, age, and height. Exposure was assessed by asking subjects whether they lived with a smoker (at both the initial and the follow-up studies) and by salivary cotinine measurements (follow-up study only). Cross-sectionally, subjects exposed at home showed tiny FEV1 deficits at both studies of -4 ml [95% confidence limits (CL) = -31, 23] and -5 ml (95% CL = -32, 22), respectively. Cotinine adjusted for potential confounders showed a stronger association with FEV1, with the highest quintile showing a -105-ml deficit (95% CL = -174, -37) in comparison with the lowest. Longitudinally, no clear relation was apparent between change in FEV1 and average exposure or change in exposure. These results indicate that environmental tobacco smoke is associated with small deficits in adult lung function, consistent with our meta-analysis estimate of a 2.7% deficit in exposed nonsmoking adults. The relations seen with cotinine but not with household exposure may reflect the importance of exposure outside the home.

Trends in secondary prevention of ischaemic heart disease in the UK 1994-2005: use of individual and combination treatment

Background: Statins, antiplatelet drugs, β-blockers and ACE inhibitors may produce marked benefits in secondary prevention of ischaemic heart disease (IHD), especially in combination. Objective: To examine trends in treatment and factors associated with treatment using a population-based general practice database. Design: Analysis of routinely collected computerised data from 201 general practices using iSOFT software contributing to the DIN-LINK database. Setting and patients: Subjects aged ⩾35 years and registered with the practices; on average, 30 000 men and 21 000 women with IHD each year. Main outcome measure: Percentage of subjects with IHD receiving individual drugs and combined treatment in any given year. Results: Between 1994 and 2005 use of drugs for secondary prevention increased markedly. By 2005, 80% of men and 70% of women were receiving a statin, 75% and 74% were receiving antiplatelet drugs, 55% and 48% were receiving β-blockers and 57% and 51% were receiving an ACE inhibitor; 55% of men and 46% of women were receiving a statin, antiplatelet drug and either β-blocker or ACE inhibitor, of whom just under half were receiving all four classes of drug. Gender differences were largely explained by more severe disease in men. In 2005, subjects less likely to receive combination therapy were older, had not had a myocardial infarction or revascularisation, and lacked comorbidities such as diabetes or hypertension. Conclusions: Despite high levels of statin and antiplatelet prescribing, opportunities exist for increasing the benefits of secondary prevention, especially through the wider use of combined treatments. Future targets could usefully include combination therapy.