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

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 ∼ 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

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

Background: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. Methods: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Findings: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Interpretation: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Background Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. Methods In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. Findings Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). Interpretation Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use