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Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Heart failure (HF) is a complex disease, almost as common in women as in men. Nonetheless, HF clinical presentation, prognosis, and aetiology vary by sex. This review summarizes the current state of sex‐sensitive issues related to HF drugs included in treatment guidelines and suggests future directions for improved care. Heart failure presentation differs between female and male patients: females more often show with hypertensive aetiology and the preserved ejection fraction phenotype, while men more often show ischaemic aetiology and the reduced ejection fraction phenotype. Yet the HF clinical guidelines in Europe, the United States, and Canada do not reflect the sexual dimorphism. Further, in randomized clinical trials of HF medication, women are largely underrepresented, typically consisting of ≥70% men. Given the knowledge that some adverse drug reactions, such as torsade de pointes and angiotensin‐converting enzyme inhibitor‐induced cough, occur more frequently in women, we emphasize the need to test medications thoroughly in both sexes and explore sexual dimorphisms. To better represent all of the targeted patient population and provide better care for all, two kinds of change must come about: recruitment methods to randomized clinical trial samples need to evolve and the participation needs to seem more attractive to women.

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The COVID-19 pandemic has spread uncertainty, promoted psychological distress, and fueled interpersonal conflict. The concomitant upsurge in endorsement of COVID-19 conspiracy theories is worrisome because they are associated with both non-adherence to public health guidelines and intention to commit violence. This study investigates associations between endorsement of COVID-19 conspiracy theories, support for violent radicalization (VR) and psychological distress among young adults in Canada. We hypothesized that (a) endorsement of COVID-19 conspiracy theories is positively associated with support for VR, and (b) psychological distress modifies the relationship between COVID-19 conspiracy theories and support for VR. A total of 6003 participants aged 18–35 years old residing in four major Canadian cities completed an online survey between 16 October 2020 and 17 November 2020, that included questions about endorsement of COVID-19 conspiracy theories, support for VR, psychological distress, and socio-economic status. Endorsement of conspiracy theories was associated with support for VR in multivariate regression (β = 0.88, 95% confidence interval (CI) 0.80–0.96). There is a significant interaction effect between endorsement of COVID-19 conspiracy theories and psychological distress (β = 0.49, 95% CI 0.40–0.57). The magnitude of the association was stronger in individuals reporting high psychological distress (β = 1.36, 95% CI 1.26–1.46) compared to those reporting low psychological distress (β = 0.47, 95% CI 0.35–0.59). The association between endorsement of COVID-19 conspiracy theories and VR represents a public health challenge requiring immediate attention. The interaction with psychological distress suggests that policy efforts should combine communication and psychological strategies to mitigate the legitimation of violence.

IntroductionExperimental and epidemiological studies have reported associations between air pollution exposure, in particular related to vehicle exhaust, and cardiovascular disease. A potential pathophysiological pathway is pollution-induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and GSTCD, may contribute to determining individual susceptibility to air pollution as a promoter of coronary vulnerability.AimsWe aimed to investigate effects of long-term traffic-related air pollution exposure, as well as variants in GSTP1, GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension. In addition, we studied whether air pollution effects were modified by the investigated genetic variants.MethodsGenotype data at 7 single nucleotide polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD genes, as well as air pollution exposure estimates, were available for 119 AMI cases and 1310 randomly selected population controls. Population control individuals with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or on daily antihypertensive medication were defined as hypertensive (n = 468). Individual air pollution exposure levels were modeled as annual means of NO2 (marker of vehicle exhaust pollutants) using central monitoring data and dispersion models, linking to participants' home addresses.ResultsAir pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04–3.03) per 10 µg/m3 of long-term NO2 exposure. Three GSTP1 SNPs were significantly associated with hypertension. The effect of air pollution on risk of AMI varied by genotype strata, although the suggested interaction was not significant. We saw no obvious interaction between genetic variants in the GST genes and air pollution exposure for hypertension.ConclusionAir pollution exposure entails an increased risk of AMI, and this risk differed over genotype strata for variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically-significantly.

ObjectivesTo investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region.DesignCross-sectional results from a cohort study.SettingThe adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001–2008 in Gothenburg, Sweden. Exposure was expressed as the distance from participants’ residential address to the nearest road with dense traffic (>10 000 vehicles per day) or very dense traffic (>30 000 vehicles per day). The exposure categories were: low (>500 m; reference), medium (75–500 m) or high (<75 m).ParticipantsThe source population was a population-based cohort of adults (n=6153). The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates.Outcome measuresForced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination. The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status.ResultsWe identified a significant dose–response trend between exposure category and FEV1 (p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates. High exposure was associated with lower FEV1 (−1.0%, 95% CI −2.5% to 0.5%) and lower FVC (−0.9%, 95% CI −2.2% to 0.4%). The effect appeared to be stronger in women. In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (−4.5%, 95% CI −8.8% to −0.1%).ConclusionsHigh traffic exposure at the residential address was associated with lower than predicted FEV1 and FVC lung function compared with living further away in a large general population cohort. There were particular effects on women and individuals with obstructive disease.

Background: Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways. Objective: It was the aim of this study to identify differences in the phospholipid composition of PEx from smokers and non-smokers. Methods: PEx from 12 smokers and 13 non-smokers was collected using a system developed in-house. PEx was analysed using time-of-flight secondary ion mass spectrometry, and the mass spectral data were evaluated using multivariate analysis. Orthogonal partial least squares (OPLS) was used to relate smoking status, lung function and pack years to the chemical composition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. Results: There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. Conclusion: The chemical composition of PEx differs between smokers and non-smokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.