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Cohort studies suggest that long-term exposure to higher levels of outdoor air pollution increases risk of developing cardiovascular disease. One suggested mechanism is that air pollution, especially particulate matter, induces systemic inflammation, thereby increasing the risk of developing long-term pathologic changes in the cardiovascular system, We aimed to examine the association between long-term exposure to higher levels of air pollution and chronic systemic inflammation.We examined the relationship between 2 markers of systemic inflammation (fibrinogen and C-reactive protein) and measures of outdoor air pollution estimated for each postcode sector of residence, using models incorporating information on pollutant emissions from multiple sources, and atmospheric dispersion and processing, in 3 representative cross-sectional studies of the English population in 1994, 1998, and 2003. These included about 25,000 adults with fibrinogen measurements and 17,000 adults with C-reactive protein measurements. We used multilevel linear regression modeling and pooled the results from the 3 surveys using meta-analysis.We found no associations between concentrations of fibrinogen or C-reactive protein and measures of outdoor air pollution (particulate matter <10 μm in diameter (PM10), nitrogen dioxide, sulfur dioxide, and ozone). Specifically, we found, for each 1-μg/m3 increase in PM10 concentration, a change in fibrinogen concentrations of -0.08% (95% confidence interval = 0.25-0.10) and in C-reactive protein concentrations of 0.14% (95% confidence interval = 1.00-1.30).Our findings do not support the hypothesis that the association between outdoor air pollution exposure and later cardiovascular disease is mediated by chronic systemic inflammation. [ABSTRACT FROM AUTHOR]

Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents.1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles ∗1A, ∗1B, ∗2, ∗4, ∗5, ∗9 and ∗12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years.No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the ∗1B carriers (WT1B) (OR=2.23 (1.16, 4.27) for current versus ex); ∗1A homozygotes (WT1A) were also at slightly higher risk (OR=1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups.CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory ‘occupancy’ model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption. [ABSTRACT FROM AUTHOR]

Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers.A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci.Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (∗5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18.This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed. [ABSTRACT FROM AUTHOR]

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/m, 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.

Objective: To examine the association between cardiovascular risk factors and retinal arteriolar tortuosity in a multi-ethnic child population., Methods and Results: Cross sectional study of 986 UK primary school children of South Asian, black African Caribbean, and white European origin aged 10 to 11 years. Anthropometric measurements and retinal imaging were carried out and a fasting blood sample collected. Digital images of retinal arterioles were analyzed using a validated semiautomated measure of tortuosity. Associations between tortuosity and cardiometabolic risk factors were analyzed using multi-level linear regression, adjusted for gender, age, ethnicity, arteriole branch status, month, and school. Levels of arteriolar tortuosity were similar in boys and girls and in different ethnic groups. Retinal arteriolar tortuosity was positively associated with levels of triglyceride, total and LDL cholesterol, and systolic and diastolic blood pressure. One standard deviation increases in these risk factors were associated with 3.7% (95% CI: 1.2%, 6.4%), 3.3% (0.9%, 5.8%), 3.1% (0.6%, 5.6%), 2.0% (-0.3%, 4.2%), and 2.3% (0.1%, 4.6%) increases in tortuosity, respectively. Adiposity, insulin resistance, and blood glucose showed no associations with tortuosity., Conclusions: Established cardiovascular risk factors, strongly linked to coronary heart disease in adulthood, may influence retinal arteriolar tortuosity at the end of the first decade of life.