Air pollution, lung function and mortality: survival and mediation analyses in UK Biobank.

Background: Air pollution is associated with lower lung function, and both are associated with premature mortality and cardiovascular disease (CVD). Evidence remains scarce on the potential mediating effect of impaired lung function on the association between air pollution and mortality or CVD. Methods: We used data from UK Biobank (n∼200 000 individuals) with 8-year follow-up to mortality and incident CVD. Exposures to particulate matter <10 µm (PM10), particulate matter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were assessed by land-use regression modelling. Lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio) was measured between 2006 and 2010 and transformed to Global Lung Function Initiative (GLI) z-scores. Adjusted Cox proportional hazards and causal proportional hazards mediation analysis models were fitted, stratified by smoking status. Results: Lower FEV1 and FVC were associated with all-cause and CVD mortality, and incident CVD, with larger estimates in ever- than never-smokers (all-cause mortality hazard ratio per FEV1 GLI z-score decrease 1.29 (95% CI 1.24-1.34) for ever-smokers and 1.16 (95% CI 1.12-1.21) for never-smokers). Long-term exposure to PM2.5 or NO2 was associated with incident CVD, with similar effect sizes for ever- and never-smokers. Mediated proportions of the air pollution-all-cause mortality estimates driven by FEV1 were 18% (95% CI 2-33%) for PM2.5 and 27% (95% CI 3-51%) for NO2. Corresponding mediated proportions for incident CVD were 9% (95% CI 4-13%) for PM2.5 and 16% (95% CI 6-25%) for NO2. Conclusions: Lung function may mediate a modest proportion of associations between air pollution and mortality and CVD outcomes. Results likely reflect the extent of either shared mechanisms or direct effects relating to lower lung function caused by air pollution.

Prospective study design and data analysis in UK Biobank.

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.

Comparison of devices used to measure blood pressure, grip strength and lung function: A randomised cross-over study.

BACKGROUND: Blood pressure, grip strength and lung function are frequently assessed in longitudinal population studies, but the measurement devices used differ between studies and within studies over time. We aimed to compare measurements ascertained from different commonly used devices. METHODS: We used a randomised cross-over study. Participants were 118 men and women aged 45-74 years whose blood pressure, grip strength and lung function were assessed using two sphygmomanometers (Omron 705-CP and Omron HEM-907), four handheld dynamometers (Jamar Hydraulic, Jamar Plus+ Digital, Nottingham Electronic and Smedley) and two spirometers (Micro Medical Plus turbine and ndd Easy on-PC ultrasonic flow-sensor) with multiple measurements taken on each device. Mean differences between pairs of devices were estimated along with limits of agreement from Bland-Altman plots. Sensitivity analyses were carried out using alternative exclusion criteria and summary measures, and using multilevel models to estimate mean differences. RESULTS: The mean difference between sphygmomanometers was 3.9mmHg for systolic blood pressure (95% Confidence Interval (CI):2.5,5.2) and 1.4mmHg for diastolic blood pressure (95% CI:0.3,2.4), with the Omron HEM-907 measuring higher. For maximum grip strength, the mean difference when either one of the electronic dynamometers was compared with either the hydraulic or spring-gauge device was 4-5kg, with the electronic devices measuring higher. The differences were small when comparing the two electronic devices (difference = 0.3kg, 95% CI:-0.9,1.4), and when comparing the hydraulic and spring-gauge devices (difference = 0.2kg, 95% CI:-0.8,1.3). In all cases limits of agreement were wide. The mean difference in FEV1 between spirometers was close to zero (95% CI:-0.03,0.03), limits of agreement were reasonably narrow, but a difference of 0.47l was observed for FVC (95% CI:0.53,0.42), with the ndd Easy on-PC measuring higher. CONCLUSION: Our study highlights potentially important differences in measurement of key functions when different devices are used. These differences need to be considered when interpreting results from modelling intra-individual changes in function and when carrying out cross-study comparisons, and sensitivity analyses using correction factors may be helpful.

Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.

Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.

Aircraft noise and cardiovascular morbidity and mortality near Heathrow Airport: A case-crossover study.

Aircraft noise causes annoyance and sleep disturbance and there is some evidence of associations between long-term exposures and cardiovascular disease (CVD). We investigated short-term associations between previous day aircraft noise and cardiovascular events in a population of 6.3 million residing near Heathrow Airport using a case-crossover design and exposure data for different times of day and night. We included all recorded hospitalisations (n = 442,442) and deaths (n = 49,443) in 2014-2018 due to CVD. Conditional logistic regression was used to estimate the ORs and adjusted for NO2 concentration, temperature, and holidays. We estimated an increase in risk for 10 dB increment in noise during the previous evening (Leve OR = 1.007, 95% CI 0.999-1.015), particularly from 22:00-23:00 h (OR = 1.007, 95% CI 1.000-1.013), and the early morning hours 04:30-06:00 h (OR = 1.012, 95% CI 1.002-1.021) for all CVD admissions, but no significant associations with day-time noise. There was effect modification by age-sex, ethnicity, deprivation, and season, and some suggestion that high noise variability at night was associated with higher risks. Our findings are consistent with proposed mechanisms for short-term impacts of aircraft noise at night on CVD from experimental studies, including sleep disturbance, increases in blood pressure and stress hormone levels and impaired endothelial function.

Spatial assessment of the attributable burden of disease due to transportation noise in England.

BACKGROUND: Noise pollution from transportation is one of the leading contributors to the environmental disease burden in Europe. We provide a novel assessment of spatial variations of these health impacts within a country, using England as an example. METHODS: We estimated the burden of annoyance (highly annoyed), sleep disturbance (highly sleep disturbed), ischemic heart disease (IHD), stroke, and diabetes attributable to long-term transportation noise exposures in England for the adult population in 2018 down to local authority level (average adult population: 136,000). To derive estimates, we combined literature-informed exposure-response relationships, with population data on noise exposures, disease, and mortalities. Long-term average noise exposures from road, rail and aircraft were sourced from strategic noise mapping, with a lower exposure threshold of 50 dB (decibels) Lden and Lnight. RESULTS: 40 %, 4.5 % and 4.8 % of adults in England were exposed to road, rail, and aircraft noise exceeding 50 dB Lden. We estimated close to a hundred thousand (∼97,000) disability adjusted life years (DALY) lost due to road-traffic, ∼13,000 from railway, and âˆ¼ 17,000 from aircraft noise. This excludes some noise-outcome pairs as there were too few studies available to provide robust exposure-response estimates. Annoyance and sleep disturbance accounted for the majority of the DALYs, followed by strokes, IHD, and diabetes. London, the South East, and North West regions had the greatest number of road-traffic DALYs lost, while 63 % of all aircraft noise DALYs were found in London. The strategic noise mapping did not include all roads, which may still have significant traffic flows. In sensitivity analyses using modelled noise from all roads in London, the DALYs were 1.1x to 2.2x higher. CONCLUSION: Transportation noise exposures contribute to a significant and unequal environmental disease burden in England. Omitting minor roads from the noise exposure modelling leads to underestimation of the disease burden.

Does air pollution confound associations between environmental noise and cardiovascular outcomes? - A systematic review.

BACKGROUND: Exposure to environmental noise is associated with adverse health effects, but there is potential for confounding and interaction with air pollution, particularly where both exposures arise from the same source, such as transport. OBJECTIVES: To review evidence on confounding and interaction of air pollution in relation to associations between environmental noise and cardiovascular outcomes. METHODS: Papers were identified from similar reviews published in 2013 and 2015, from the systematic reviews supporting the WHO 2018 noise guidelines, and from a literature search covering the period 2016-2022 using Medline and PubMed databases. Additional papers were identified from colleagues. Study selection was according to PECO inclusion criteria. Studies were evaluated against the WHO checklist for risk of bias. RESULTS: 52 publications, 36 published after 2015, were identified that assessed associations between transportation noise and cardiovascular outcomes, that also considered potential confounding (49 studies) or interaction (23 studies) by air pollution. Most, but not all studies, suggested that the associations between traffic noise and cardiovascular outcomes are independent of air pollution. NO2 or PM2.5 were the most commonly included air pollutants and we observed no clear differences across air pollutants in terms of the potential confounding role. Most papers did not appear to suggest an interaction between noise and air pollution. Eight studies found the largest noise effect estimates occurring within the higher noise and air pollution exposure categories, but were not often statistically significant. CONCLUSION: Whilst air pollution does not appear to confound associations of noise and cardiovascular health, more studies on potential interactions are needed. Current methods to assess quality of evidence are not optimal when evaluating evidence on confounding or interaction.

Road Traffic Noise and Incidence of Primary Hypertension: A Prospective Analysis in UK Biobank.

Background: The quality of evidence regarding the associations between road traffic noise and hypertension is low due to the limitations of cross-sectional study design, and the role of air pollution remains to be further clarified. Objectives: The purpose of this study was to evaluate the associations of long-term road traffic noise exposure with incident primary hypertension; we conducted a prospective population-based analysis in UK Biobank. Methods: Road traffic noise was estimated at baseline residential address using the common noise assessment method model. Incident hypertension was ascertained through linkage with medical records. Cox proportional hazard models were used to estimate hazard ratios (HRs) for association in an analytical sample size of over 240,000 participants free of hypertension at baseline, adjusting for covariates determined via directed acyclic graph. Results: During a median of 8.1 years follow-up, 21,140 incident primary hypertension (International Classification of Diseases-10th Revision [ICD-10]: I10) were ascertained. The HR for a 10 dB[A] increment in mean weighted average 24-hour road traffic noise level (L den ) exposure was 1.07 (95% CI: 1.02-1.13). A dose-response relationship was found, with HR of 1.13 (95% CI: 1.03-1.25) for L den >65 dB[A] vs ≤55 dB[A] (P for trend <0.05). The associations were all robust to adjustment for fine particles (PM2.5) and nitrogen dioxide (NO2). Furthermore, high exposure to both road traffic noise and air pollution was associated with the highest hypertension risk. Conclusions: Long-term exposure to road traffic noise was associated with increased incidence of primary hypertension, and the effect estimates were stronger in presence of higher air pollution.

Environmental noise and health in low-middle-income-countries: A systematic review of epidemiological evidence.

Evidence of the health impacts from environmental noise has largely been drawn from studies in high-income countries, which has then been used to inform development of noise guidelines. It is unclear whether findings in high-income countries can be readily translated into policy contexts in low-middle-income-countries (LMICs). We conducted this systematic review to summarise noise epidemiological studies in LMICs. We conducted a literature search of studies in Medline and Web of Science published during 2009-2021, supplemented with specialist journal hand searches. Screening, data extraction, assessment of risk of bias as well as overall quality and strength of evidence were conducted following established guidelines (e.g. Navigation Guide). 58 studies were identified, 53% of which were from India, China and Bulgaria. Most (92%) were cross-sectional studies. 53% of studies assessed noise exposure based on fixed-site measurements using sound level meters and 17% from propagation-based noise models. Mean noise exposure among all studies ranged from 48 to 120 dB (Leq), with over half of the studies (52%) reporting the mean between 60 and 80 dB. The most studied health outcome was noise annoyance (43% of studies), followed by cardiovascular (17%) and mental health outcomes (17%). Studies generally reported a positive (i.e. adverse) relationship between noise exposure and annoyance. Some limited evidence based on only two studies showing that long-term noise exposure may be associated with higher prevalence of cardiovascular outcomes in adults. Findings on mental health outcomes were inconsistent across the studies. Overall, 4 studies (6%) had "probably low", 18 (31%) had "probably high" and 36 (62%) had "high" risk of bias. Quality of evidence was rated as 'low' for mental health outcomes and 'very low' for all other outcomes. Strength of evidence for each outcome was assessed as 'inadequate', highlighting high-quality epidemiological studies are urgently needed in LMICs to strengthen the evidence base.

Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.

Background: Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort. Methods: Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (µg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators. Results: Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)]. Conclusions: This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.

Assessing the health risk of living near composting facilities on lung health, fungal and bacterial disease in cystic fibrosis: a UK CF Registry study.

AIM: To explore the health risk of living near permitted composting sites (PCSs) on disease severity in children and adults with cystic fibrosis (CF) across the UK.  METHODS: A semi-individual cross-sectional study was used to examine the risk of disease severity in people with CF (pwCF) within and beyond 4 km of PCSs in the UK in 2016. All pwCF registered in the UK CF Registry were eligible for this study. Linear and Poisson regressions, adjusted for age, gender, genotype, BMI, Pseudomonas aeruginosa and deprivation, were used to quantify associations between distance to a PCS and percent predicted forced expiratory volume in one second (ppFEV1), pulmonary exacerbations (#IVdays), and fungal and bacterial infections. RESULTS: The mean age of the 9,361 pwCF (3,931 children and 5,430 adults) studied was 20.1 (SD = 14.1) years; 53.3% were male; and 49.2% were homozygous F508del. Over 10% of pwCF (n = 1,015) lived within 4 km of a PCS. We found no statistically significant difference in ppFEV1 and #IVdays/year in children. However, in adults, ppFEV1 was -1.07% lower (95% confidence interval (CI): -2.29%, 0.16%) and #IVdays/year were 1.02 day higher (95%CI: 1.01, 1.04) within 4 km of a PCS. Furthermore, there were statistically significant differences in mean ppFEV1 in CF adults with Aspergillus fumigatus (58.2.% vs 62.0%, p = 0.005) and Candida spp. (56.9% vs 59.9%, p = 0.029) residing within 4 km of a PCS. No associations were identified for allergic bronchopulmonary aspergillosis, P. aeruginosa or Staphylococcus aureus. CONCLUSIONS: This novel national study provides evidence that adults with CF living near a PCS may experience small reductions in lung function, an increased risk of pulmonary exacerbations, and more frequent fungal infections. If confirmed by studies using refined exposure assessment methods accounting for bioaerosol dispersion, these results could have important implications for the living environment of pwCF.

How to design and implement a university-based COVID-19 testing programme? An evaluation of a novel RT-LAMP COVID-19 testing programme in a UK university.

BACKGROUND: Little is known about how asymptomatic testing as a method to control transmission of COVID-19 can be implemented, and the prevalence of asymptomatic infection within university populations. The objective of this study was to investigate how to effectively set-up and implement a COVID-19 testing programme using novel reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) technology and to quantify the scale of asymptomatic infection on a university campus. METHODS: An observational study to describe the set-up and implementation of a novel COVID-19 testing programme on a UK university campus between September and December 2020. RT-LAMP testing was used to identify asymptomatic cases. RESULTS: A total of 1,673 tests were performed using RT-LAMP during the study period, of which 9 were positive for COVID-19, giving an overall positivity rate of 0.54%, equivalent to a rate in the tested population of 538 cases per 100,000 over the duration of testing. All positive tests were found to be positive on RT-PCR testing, giving a false positive rate of 0%. CONCLUSIONS: This study shows that it is possible to rapidly setup a universal university testing programme for COVID-19 in collaboration with local healthcare providers using RT-LAMP testing. Positive results were comparable to those in the local population, though with a different peak of infection. Further research to inform the design of the testing programme includes focus groups of those who underwent testing and further interrogation of the demographics of those opting to be tested to identify potential access problems or inequalities.

Differences in the risk of cardiovascular disease across ethnic groups: UK Biobank observational study.

BACKGROUND AND AIMS: To describe sociodemographic, lifestyle, environmental and traditional clinical risk factor differences between ethnic groups and to investigate the extent to which such differences confound the association between ethnic groups and the risk of cardiovascular disease (CVD) METHODS AND RESULTS: A total of 440,693 white European (55.9% women), 7305 South Asian (48.6%) and 7628 black African or Caribbean (57.7%) people were included from UK Biobank. Associations between ethnicity and cardiovascular outcomes (composite of non-fatal stroke, non-fatal myocardial infarction and CVD death) were explored using Cox-proportional hazard models. Models were adjusted for sociodemographic, lifestyle, environmental and clinical risk factors. Over a median (IQR) of 12.6 (11.8, 13.3) follow-up years, there were 22,711 (5.15%) cardiovascular events in white European, 463 (6.34%) in South Asian and 302 (3.96%) in black African or Caribbean individuals. For South Asian people, the cardiovascular hazard ratio (HR) compared to white European people was 1.28 (99% CI [1.16, 1.43]). For black African or Caribbean people, the HR was 0.80 (0.66, 0.97). The elevated risk of CVD in South Asians remained after adjusting for differences in sociodemographic, lifestyle, environmental and clinical factors, whereas the lower risk in black African or Caribbean was largely attenuated. CONCLUSIONS: South Asian, but not black African or Caribbean individuals, have a higher risk of CVD compared to white European individuals. This higher risk in South Asians was independent of sociodemographic, lifestyle, environmental and clinical factors.

Association between Noise Annoyance and Mental Health Outcomes: A Systematic Review and Meta-Analysis.

To date, most studies of noise and mental health have focused on noise exposure rather than noise annoyance. The purpose of this systematic review and meta-analysis was to evaluate whether the available evidence supports an adverse association between noise annoyance and mental health problems in people. We carried out a literature search of Web of Science, PubMed, Scopus, PsycINFO, and conference proceedings published between 2000 and 2022. Thirteen papers met the inclusion criteria. We conducted meta-analyses of noise annoyance in relation to depression, anxiety, and general mental health. In the meta-analyses, we found that depression was approximately 1.23 times greater in those who were highly noise-annoyed (N = 8 studies). We found an approximately 55% higher risk of anxiety (N = 6) in highly noise-annoyed people. For general mental health (N = 5), highly annoyed participants had an almost 119% increased risk of mental health problems as assessed by Short Form (SF) or General Household Questionnaires (GHQ), but with high heterogeneity and risk of publication bias. In conclusion, findings are suggestive of a potential link between noise annoyance and poorer mental health based on a small number of studies. More evidence is needed to confirm these findings.

Sources of particle number concentration and noise near London Gatwick Airport.

There is increasing evidence of potential health impacts from both aircraft noise and aircraft-associated ultrafine particles (UFP). Measurements of noise and UFP are however scarce near airports and so their variability and relationship are not well understood. Particle number size distributions and noise levels were measured at two locations near Gatwick airport (UK) in 2018-19 with the aim to characterize particle number concentrations (PNC) and link PNC sources, especially UFP, with noise. Positive Matrix Factorization was used on particle number size distribution to identify these sources. Mean PNC (7500-12,000 p cm-3) were similar to those measured close to a highly trafficked road in central London. Peak PNC (94,000 p cm-3) were highest at the site closer to the runway. The airport source factor contributed 17% to the PNC at both sites and the concentrations were greatest when the respective sites were downwind of the runway. However, the main source of PNC was associated with traffic emissions. At both sites noise levels were above the recommendations by the WHO (World Health Organisation). Regression models of identified UFP sources and noise suggested that the largest source of noise (LAeq-1hr) above background was associated with sources of fresh traffic and urban UFP depending on the site. Noise and UFP correlations were moderate to low suggesting that UFP are unlikely to be an important confounder in epidemiological studies of aircraft noise and health. Correlations between UFP and noise were affected by meteorological factors, which need to be considered in studies of short-term associations between aircraft noise and health.

Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals.

BACKGROUND: Impaired lung function is predictive of mortality and is a key component of chronic obstructive pulmonary disease. Lung function has a strong genetic component but is also affected by environmental factors such as increased exposure to air pollution, but the effect of their interactions is not well understood. OBJECTIVES: To identify interactions between genetic variants and air pollution measures which affect COPD risk and lung function. Additionally, to determine whether previously identified lung function genetic association signals showed evidence of interaction with air pollution, considering both individual effects and combined effects using a genetic risk score (GRS). METHODS: We conducted a genome-wide gene-air pollution interaction analysis of spirometry measures with three measures of air pollution at home address: particulate matter (PM2.5 & PM10) and nitrogen dioxide (NO2), in approximately 300,000 unrelated European individuals from UK Biobank. We explored air pollution interactions with previously identified lung function signals and determined their combined interaction effect using a GRS. RESULTS: We identified seven new genome-wide interaction signals (P<5×10-8), and a further ten suggestive interaction signals (P<5×10-7). Additionally, we found statistical evidence of interaction for FEV1/FVC between PM2.5 and previously identified lung function signal, rs10841302, near AEBP2, suggesting increased susceptibility as copies of the G allele increased (but size of the impact was small - interaction beta: -0.363 percentage points, 95% CI: -0.523, -0.203 per 5 µg/m3). There was no observed interaction between air pollutants and the weighted GRS. DISCUSSION: We carried out the largest genome-wide gene-air pollution interaction study of lung function and identified potential effects of clinically relevant size and significance. We observed up to 440 ml lower lung function for certain genotypes when exposed to mean levels of outdoor air pollution, which is approximately equivalent to nine years of average normal loss of lung function in adults.

Risk of cardiovascular mortality, stroke and coronary heart mortality associated with aircraft noise around Congonhas airport, São Paulo, Brazil: a small-area study.

BACKGROUND: Noise pollution is increasingly recognised as a public health hazard, yet limited evidence is available from low- and middle-income countries (LMIC), particularly for specific sources. Here, we investigated the association between day-night average (Ldn) aircraft noise and the risk of death due to cardiovascular disease (CVD), stroke and coronary heart disease (CHD) at small-area level around São Paulo's Congonhas airport, Brazil during the period 2011-2016. METHODS: We selected 3259 census tracts across 16 districts partially or entirely exposed to ≥50 dB aircraft noise levels around the Congonhas airport, using pre-modelled 5 dB Ldn noise  bands (≤50 dB to > 65 dB). We estimated the average noise exposure per census tract using area-weighting. Age, sex and calendar year-specific death counts for CVD, stroke and CHD were calculated by census tract, according to the residential address at time of death. We fitted Poisson regression models to quantify the risk associated with aircraft noise exposure, adjusting for age, sex, calendar year and area-level covariates including socioeconomic development, ethnicity, smoking and road traffic related noise and air pollution. RESULTS: After accounting for all covariates, areas exposed to the highest levels of noise (> 65 dB) showed a relative risk (RR) for CVD and CHD of 1.06 (95% CI: 0.94; 1.20) and 1.11 (95%CI: 0.96; 1.27), respectively, compared to those exposed to reference noise levels (≤50 dB). The RR for stroke ranged between 1.05 (95%CI: 0.95;1.16) and 0.91 (95%CI: 0.78;1.11) for all the noise levels assessed. We found a statistically significant positive trend for CVD and CHD mortality risk with increasing levels of noise (p = 0.043 and p = 0.005, respectively). No significant linear trend was found for stroke. Risk estimates were generally higher after excluding road traffic density, suggesting that road traffic air and noise pollution are potentially important confounders. CONCLUSIONS: This study provides some evidence that aircraft noise is associated with increased risk of CVD and CHD mortality in a middle-income setting. More research is needed to validate these results in other LMIC settings and to further explore the influence of residual confounding and ecological bias. Remarkably, 60% of the study population living near the Congonhas airport (~ 1.5 million) were exposed to aircraft noise levels > 50 dB, well above those recommended by the WHO (45 dB), highlighting the need for public health interventions.