Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 µm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m2 resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 µg/m3 change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue.

Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort.

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.

Statin use after first myocardial infarction in UK men and women from 1997 to 2006: Who started and who continued treatment?

BACKGROUND AND AIMS: To examine trends in initiation and continuation of statin treatment after myocardial infarction (MI) and their determinants, during a period of increasing usage. METHODS AND RESULTS: 9367 patients aged 30-84 with a first Myocardial Infarction (MI) in 1997-2006 were identified in DIN-LINK, an anonymised, UK primary care database. We assessed statin initiation (prescription within 6 months of MI) and continued therapy (% covered by a prescription on a given day of those prescribed a statin within 6 months). The influences of co-morbidities and socio-economic deprivation (Index of Multiple Deprivation) were examined. Statin initiation increased from 37% for MIs in 1997 to 92% in 2006. Continuation at 1 year remained stable over successive cohorts at approximately 80%, settling to about 76% in patients with 5-10 years follow up. Younger age, affluence, revascularisation in 6 months after MI, and absence of congestive heart failure, predicted higher initiation and continuation; a diagnosis of hypertension or diabetes predicted higher initiation, while smoking was associated with poorer continuation. Men had higher initiation and continued therapy, but these effects were largely explained by their younger age. Type of statin initially prescribed did not influence continued usage. CONCLUSION: Statin use after MI increased markedly between 1997 and 2006, whilst continued therapy remained high and stable. Importantly, first choice of statin had no effect on continuation. Whilst the high current levels of initiation may have reached a ceiling, increasing continuation rates among smokers, older patients and those from lower socio-economic groups, should remain a priority.

Antipsychotic prescribing to older people living in care homes and the community in England and Wales.

OBJECTIVE: Excessive use of antipsychotic medication by older people is an international concern, but there is limited comparative information on their use in different residential settings. This paper describes and compares antipsychotic prescribing to older people in care homes and the community in England and Wales. METHOD: Analysis of a primary care database (THIN) with 403 259 community and 10 387 care home residents aged 65-104 years in 2008-9. RESULTS: 3677 (0.9%) patients in the community and 2173 (20.9%) in care homes (20.5% in residential homes, 21.7% in nursing homes) received an antipsychotic medication prescription in the last 90 days. Most patients had received prescriptions for more than three months and 60% of prescriptions were for atypical antipsychotics. In patients without severe mental illness, 2367 (0.6%) patients in the community and 1765 (18.2%) in care homes received antipsychotic medication; such prescribing was common for patients with recorded dementia (30.2% in care home, 10.1% in the community). In care homes, younger age and living in the North of England predicted prescribing, but care home type did not. In the community, female gender, increasing age, living in a deprived area and the North predicted prescribing. CONCLUSIONS: Despite safety concerns, antipsychotic prescribing is markedly higher in care homes than in the community, and strongly associated with dementia in both settings. In England and Wales, we estimate that 54 000 older care home patients and 50 000 community patients receive antipsychotic medication without a diagnosis of severe mental illness with important implications for health and social services.

Blood pressure recording bias during a period when the Quality and Outcomes Framework was introduced.

The 2004 UK Quality and Outcomes Framework (QOF) remunerates general practitioners for achieving a target blood pressure (BP) of 150 mm Hg in 2000-2001, and only 19% in 2004-2005. However, there was a trend towards recording systolic values just below, rather than just above the 150 cut-off. In 2000-2001, 2.3% of patients had 148-149 recorded and 1.8% had 151-152. In 2004-2005, the figures were 4.2 and 1.3%, respectively. By smoothing the distribution we estimate that the true percentage of patients with SBP>150 mm Hg in 2004-2005 was 23%, rather than the 19% recorded. Moreover, patients with a recorded SBP=148-149 were more likely to have a recorded diastolic BP

Persistency with medical treatment for glaucoma and ocular hypertension in the United Kingdom: 1994-2005.

PURPOSE: To examine trends and demographic factors affecting persistence with ocular hypotensive therapy, from a period before prostaglandins were available to when they were the most common therapy. METHODS: Computerised patient records from 94 general practices across the United Kingdom, identified 5670 registered patients newly prescribed an ocular hypotensive drug (1993-2005). Persistence was defined as continuing therapy without a 90-day gap in prescription for (i) any ocular hypotensive and (ii) initial monotherapy. Time to failure with the treatment was compared using proportional hazard analyses, adjusted for age, gender, practice, year of initial treatment, and a sociodemographic indicator. Study findings were set in the context of a review of the literature. RESULTS: Percentage persistent at 1-year rose after 1997 when prostaglandins were introduced; from 61% in 1994-1996 to 70% in 2002-2004. Persistence with any treatment did not differ between those initiated on beta-blockers compared to prostaglandins (1.05, 95% CI 0.93-1.17). However, 20% of subjects initiated on beta-blockers received a prostaglandin by 1 year. Conversely, 8% of those initiated on prostaglandins received a beta-blocker. When failure with initial therapy was considered, beta-blockers appeared worse (1.35, 95% CI 1.21-1.50); this was consistent with findings from six studies in the review (1.40, 95% CI 1.34-1.46). Neither gender nor social factors were associated with persistence, but younger subjects (35-64 years) were significantly more likely to fail as were those over 85 years. CONCLUSIONS: Introduction of prostaglandins may explain an improvement in persistence over a decade. However, whether the higher cost of initiating patients on prostaglandins is justified remains questionable unless clinically indicated.

Infections presenting for clinical care in early life and later risk of hay fever in two UK birth cohorts.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect against hay fever (HF). We investigated infections during infancy in relation to HF, including rarer ones not previously researched in this context, while examining the role of potential confounding variables. METHODS: From birth cohorts derived within the General Practice Research Database (GPRD) and Doctors Independent Network (DIN) database of computerized patient records from UK general practice, we selected 3549 case-control pairs, matched for practice, age, sex and control follow-up to case diagnosis. Conditional logistic regressions were fitted for each of 30 infections; behavioural problems (BP) acted as a control condition unrelated to HF. Odds ratios (OR), adjusted for consultation frequency were pooled across the databases using fixed effect models. We also adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS: Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media in infancy were each related with a moderately increased risk of HF in both databases, as were BP. These associations were lost on adjustment for consultation frequency. Only bronchiolitis was significantly associated with a reduced pooled risk of HF after adjustment for consultations (OR = 0.8). Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had strong or consistent associations with HF after adjustment for consultation frequency. Except for bronchiolitis, possibly a chance finding, none of the clinically apparent infections considered appear to have an important role in allergy prevention.

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

BACKGROUND: Statins, antiplatelet drugs, beta-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 >or=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 beta-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 beta-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.

Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year. METHODS: Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases. RESULTS: There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98). CONCLUSION: Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.

The epidemiology of medical treatment for glaucoma and ocular hypertension in the United Kingdom: 1994 to 2003.

AIMS: To study trends in the prevalence of being treated for glaucoma and ocular hypertension from 1994 to 2003, and to examine factors determining treatment in 2002. METHODS: Computerised data (the DIN-LINK database) from 131 general practices across the United Kingdom, in which half a million patients aged 40 years or more were registered annually, were used. On average 10 000 patients were treated for glaucoma and ocular hypertension annually. RESULTS: Prevalence of being treated for glaucoma and ocular hypertension increased from 1.7% in 1994 to 2.3% in 2003. Those aged 85 years or more were 13 times (95% CI 12.2 to 13.8) more likely to be treated than those aged 40-64 years. Men were more likely to be treated than women (OR 1.24, 95% CI 1.19 to 1.28). Subjects "hard pressed" were less likely to be treated than "wealthy achievers" (OR 0.92, 95% CI 0.86 to 0.99). While use of topical beta blocker only medications has declined since 1995, use of topical prostaglandins and combination therapies has increased. In 2003, use of prostaglandins overtook beta blocker only medications. CONCLUSION: Prevalence of being treated for glaucoma has increased over time, and rises with age. Differences in treatment by sex and social status could be explained by use of or access to health care or by underlying prevalence of disease. Trends in treated glaucoma emphasise the shift from use of topical beta blockers to newer therapies.

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.

Timing of routine immunisations and subsequent hay fever risk.

BACKGROUND: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy. AIMS: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk. METHODS: Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression. RESULTS: Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations. CONCLUSIONS: Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.

A comparison of the recording of 30 common childhood conditions in the Doctor's Independent Network and General Practice Research Databases.

In this article we compare the recording of 30 common childhood conditions in two general practice databases of anonymised computerised medical records based on fundamentally different systems--the Doctor's Independent Network (DIN) database (Torex system) and the General Practice Research Database (GPRD) (In Practice Systems). Analysing the records of all children born 1990-1993 and followed for 5 years we found comparable results for most conditions, but differences between the hierarchical structures of the diagnostic coding systems (Read in DIN, OXMIS in GPRD) led to some differences between the databases. Practice variation was marked, but comparable between databases. Variation was greatest in conditions that are poorly defined clinically.

Early-life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors' Independent Network.

BACKGROUND: Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting. OBJECTIVE: To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis. METHODS: Nested case-control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model. RESULTS: The pooled odds ratio for hayfever was 1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever. CONCLUSION: These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.

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.

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Do children who become autistic consult more often after MMR vaccination?

A close temporal association has been reported between the measles, mumps, and rubella (MMR) vaccination and dramatic behavioural decline in children subsequently diagnosed as autistic. We hypothesised that such a decline would be reflected in increased consultations with the child's general practitioner. The Doctor's Independent Network database was used to examine whether children subsequently diagnosed as autistic consulted more frequently than controls after MMR vaccination. No difference in consulting behaviour was seen in the six months post MMR. Any dramatic effect of MMR on behaviour seems unlikely.

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.

Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years.

Factors operating in fetal life or during childhood may be important in determining fibrinogen and factor VII concentrations in adult life, and particularly in explaining social gradients in cardiovascular disease risk. In 1994, the authors measured fibrinogen and factor VIIc levels in 641 children aged 10-11 years (61% response rate) from schools in five towns in England and Wales. Birth weight was obtained by maternal recall, and other data on measures of fetal growth were obtained from birth records. Fibrinogen levels were higher in girls (258.8 mg/dl) than in boys (245.4 mg/dl) (95% confidence interval (CI) for difference: 5.5, 21.5). Fibrinogen and factor VIIc levels were linearly related to adiposity, rising by 37.1 mg/dl (95% CI: 24.7, 49.5) and 13.0% of standard (95% CI: 6.3, 19.7), respectively, between the bottom and top quintiles of ponderal index (weight (kg)/height (m)3). Fibrinogen was independently related to heart rate (p < 0.001) and was negatively but nonsignificantly related to measures of physical activity. Factor VIIc was positively correlated with total cholesterol (p < 0.001). No relations were found with measures of fetal growth or social class. These data do not support the concept that fibrinogen or factor VII levels are determined in utero or by social factors in childhood. Adiposity and physical training appear to be the important determinants of fibrinogen and factor VII levels in childhood.