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Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality. We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta-analysis to combine estimates of the association between differences in SBP between arms and each outcome. We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36·9 mm Hg (95% CI 35·4–38·4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8·8, 95% CI 3·6–21·2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2·5, 95% CI 1·6–3·8; sensitivity 15%, 9–23; specificity 96%, 94–98); pre-existing cerebrovascular disease (five cohorts; RR 1·6, 1·1–2·4; sensitivity 8%, 2–26; specificity 93%, 86–97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1·7, 95% CI 1·1–2·5) and all-cause mortality (HR 1·6, 1·1–2·3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2·4, 1·5–3·9; sensitivity 32%, 23–41; specificity 91%, 86–94). A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of 15 mm Hg or more could be a useful indicator of risk of vascular disease and death. Royal College of General Practitioners, South West GP Trust, and Peninsula Collaboration for Leadership in Applied Health Research and Care.

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8–17 years in 2009–2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term.

Organogermanium, especially poly‐trans‐[(2‐carboxyethyl)germasesquioxane] (Ge‐132), has been known to enhance immune‐modulatory activities. However, the in vivo and in vitro evidence accumulated over the last 20 years reveals that Ge‐132 has unique but underappreciated multi‐functional properties that have a potential positive effect for the cardiovascular system. A hydrolysate of Ge‐132, monomeric 3‐(trihydroxygermyl)propanoic acid, forms a complex with a vicinal diol structure (i.e., having two adjacent hydroxyl groups such as the cis‐diol and catechol groups) that exists in ribose (e.g., adenosine triphosphate), catecholamine (e.g., adrenaline), and saccharide (e.g., glucose). Additionally, Ge‐132 enhances macrophage phagocytosis and the heme catabolic pathway by upregulating key enzymes that are responsible for producing cytoprotective molecules such as biliverdin and bilirubin during the process. These multi‐functional properties exert pleiotropic physiological effects after an oral intake of Ge‐132 such as anti‐oxidation, anti‐inflammation, anti‐hypertensive, anti‐glycation, and erythrocyte lifecycle enhancement, all of which appear to assist the cardiovascular system. Of those effects, the effects on the lifecycle of erythrocyte may have an important implication for maintaining optimal vascular function, augmenting the availability of oxygen by enhancing the elimination of senescent, and damaged erythrocytes as well as promoting erythropoiesis. Human studies are warranted to determine whether these beneficial effects observed in previous studies are translated into humans.

Background Hypertension is a highly prevalent condition, with optimal treatment to BP targets conferring significant gains in terms of cardiovascular outcomes. Understanding why some patients do not achieve BP targets would be enhanced through greater understanding of their health-related quality of life (HRQoL). However, the only English language disease-specific instruments for measurement of HRQoL in hypertension have not been validated in accordance with accepted standards. It is proposed that the Spanish MINICHAL instrument for the assessment of HRQoL in hypertension could be translated, adapted and validated for use in the United Kingdom. The aim of the study was therefore to complete this process. Methods The MINICHAL authors were contacted and the original instrument obtained. This was then translated into English by two independent English-speakers, with these versions then reconciled, before back-translation and subsequent production of a 2nd reconciled version. Thereafter, a final version was produced after cognitive debriefing, for administration and psychometric analysis in the target population of patients living in the Exeter area (Southwest UK) aged 18–80 years with treatment-naïve grade II-III hypertension, before, during and after 18 weeks’ intensive treatment. Results The English-language instrument was administered to 30 individuals (median age: 58.5 years, 53% male). Psychometric analysis demonstrated a floor effect, though no ceiling effect. Internal consistency for both state of mind (StM) and somatic manifestations (SM) dimensions of the instrument were acceptable (Cronbach’s alpha = 0.81 and 0.75), as was test–retest reliability (ICC = 0.717 and 0.961) and construct validity, which was measured through co-administration with the EQ-5D-5L and Bulpitt-Fletcher instruments. No significant associations were found between scores and patient characteristics known to affect HRQoL. The EQ-5D-5L instrument found an improvement in HRQoL following treatment, with the StM and SM dimensions of the English language MINICHAL trending to support this (d = 0.32 and 0.02 respectively). Conclusions The present study details the successful English translation and validation of the MINICHAL instrument for use in individuals with hypertension. The data reported also supports an improvement in HRQoL with rapid treatment of grade II-III hypertension, a strategy which has been recommended by contemporaneous European guidelines. Trial registration ISRCTN registry number: 57475376 (assigned 25/06/2015).

Allergic bronchopulmonary aspergillosis (ABPA) is a well-known complication in children and young people with cystic fibrosis (CF) and without treatment causes structural lung damage. We performed a longitudinal observational study to identify clinical risk factors for ABPA in a cohort of children and young people with CF aged 8 to 17 years at baseline. Anonymised annual review UK CF Registry data from 2009 to 2019 for patients aged 8–17 years in 2009 were collected, with lung transplant recipients excluded. Baseline characteristics are presented for the whole group and cross-sectional comparisons made according to the presence of ABPA or not in 2009. Longitudinal analysis from 2009 to 2019 was completed on the group without ABPA in 2009 to identify predictors for the subsequent development of ABPA using a complementary log–log regression model. In 2009, there were 1612 patients, of which 1420 were ABPA-negative and 192 ABPA-positive. Aspergillus colonisation (p = 0.01) and IV antibiotic use (p < 0.0001) were associated with having ABPA in 2009. Longitudinal analysis of the group without ABPA in 2009 identified male gender, younger age, lower lung function, Pseudomonas aeruginosa infection, and Aspergillus colonisation to be significantly associated with the development of ABPA (p < 0.0001). Ivacaftor was significantly associated with reduced ABPA (OR 0.46, p = 0.01) but not lumacaftor/ivacaftor (OR 0.64, p = 0.28). Chronic oral macrolide use was significantly associated with increased risk of development of ABPA (OR 1.30, p < 0.0001). This study shows that lower lung function, Aspergillus colonisation, and Pseudomonas aeruginosa infection in children with CF were associated with the development of ABPA, highlighting the need for enhanced surveillance in these patients. This is the first study to show a protective association of ivacaftor and ABPA.

Background Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis. Methods We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment. Results We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m 2 , p < 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p < 0.001), mid-circumferential strain (− 20.8 ± 4.9 to − 19.1 ± 3.7, p = 0.02), apical circumferential strain (− 26.0 ± 5.3 to − 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003). Conclusions LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes. Trial registration : ISRCTN registry number: 57475376 (assigned 25/06/2015).

ObjectiveTransient ischaemic attacks (TIA) and minor strokes are important risk factors for further vascular events. We explored the role of albumin creatinine ratio (ACR) in improving risk prediction after a first event.SettingRapid access stroke clinics in the UK.Participants2202 patients attending with TIA or minor stroke diagnosed by the attending stroke physician, able to provide a urine sample to evaluate ACR using a near-patient testing device.Primary and secondary outcomesPrimary outcome was major adverse cardiac events (MACE: recurrent stroke, myocardial infarction or cardiovascular death) at 90 days. The key secondary outcome was to determine whether urinary ACR could contribute to a risk prediction tool for use in a clinic setting.Results151 MACE occurred in 144 participants within 90 days. Participants with MACE had higher ACR than those without. A composite score awarding a point each for age >80 years, previous stroke/TIA and presence of microalbuminuria identified those at low risk and high risk. 90% of patients were at low risk (scoring 0 or 1). Their 90-day risk of MACE was 5.7%. Of the remaining ‘high-risk’ population (scoring 2 or 3) 12.4% experienced MACE over 90 days (p<0.001 compared with the low-risk population). The need for acute admission in the first 7 days was twofold elevated in the high-risk group compared with the low-risk group (3.23% vs 1.43%; p=0.05). These findings were validated in an independent historic sample.ConclusionA risk score comprising age, previous stroke/TIA and microalbuminuria predicts future MACE while identifying those at low risk of a recurrent event. This tool shows promise in the risk stratification of patients to avoid the admission of low-risk patients.

Aims Parameters derived from reservoir‐excess pressure analysis have been demonstrated to predict cardiovascular events. Thus, altered reservoir‐excess pressure parameters could have a detrimental effect on highly‐perfused organs like the heart. We aimed to cross‐sectionally determine whether reservoir‐excess pressure parameters were associated with N‐terminal pro‐brain‐type natriuretic peptide (NT‐proBNP) in older adults. Methods We studied 868 older adults with diverse cardiovascular risk. Reservoir‐excess pressure parameters were obtained through radial artery tonometry including reservoir pressure integral, peak reservoir pressure, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC). Plasma levels of NT‐proBNP, as a biomarker of cardiac overload, were analysed by the Proximity Extension Assay technology. Results Multivariable linear regression analyses revealed that all reservoir‐excess pressure parameters studied were associated with NT‐proBNP after adjusting for age and sex. After further adjustments for conventional cardiovascular risk factors, INTXSP [β = 0.191 (95% confidence interval, CI: 0.099, 0.283), P < 0.001], SRC [β = −0.080 (95% CI: −0.141, −0.019), P = 0.010] and DRC [β = 0.138 (95% CI: 0.073, 0.202), P < 0.001] remained associated with NT‐proBNP. Sensitivity analysis found that there were occasions where the association between SRC and NT‐proBNP was attenuated, but both INTXSP and DRC remained consistently associated with NT‐proBNP. Conclusions The observed associations between reservoir‐excess pressure parameters and NT‐proBNP suggest that altered reservoir‐excess pressure parameters may reflect an increased load inflicted on the left ventricular cardiomyocytes and could have a potential to be utilized in the clinical setting for cardiovascular risk stratification.

Abstract Purpose It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on the cardiovascular (CV) system or whether its association with cardiovascular events (CVEs) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVEs. Methods In 269 patients with a high prevalence of diabetes, dyslipidemia, and hypertension, the carotid intima-media thickness, ankle–brachial index (ABI), reactive hyperemic index, carotid–femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, and cardiac index were measured. Results 132 patients had carotid plaque, 31 ABI < 0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index, and 115 a history of CVEs. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5 [4.4] vs 7.6 [2.8] μmol/L; adjusted P = .001) and ABI < 0.9 (10.4 [3.8] vs 7.9 [3.4] μmol/L; adjusted P = .001) than in those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial, and LV pump function. Within markers of CV organ damage, only LVH was associated with a history of CVEs. Conclusion This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVEs and suggests that LVH may represent 1 of the pathophysiologic links between Hcy and CV risk.

Breast conserving surgery (BCS) for breast cancer aims for optimal oncological results with minimal tissue excision. Positive margins due to insufficient resection results in significant numbers of patients requiring re‐excision, which could be resolved with intra‐operative margin analysis (IMA). High wavenumber (HWN) Raman Spectroscopy (RS) examines the difference in protein/lipid environment and water content in tissues. Fluorescence from haemoglobin and blue dye surgical pigments (commonly present in excised breast tissue) can confound HWN RS. We present a Raman system with 785 nm excitation laser and indium gallium arsenide camera capable of quantifying changes in water content in different environments (protein‐rich and lipid‐rich) by measuring the water/total area ratio (W/TAR) of the HWN spectrum. We demonstrate that haemoglobin and blue dye do not adversely affect water content analysis by the W/TAR calculation. Measurement of paired tumour/non‐tumour human breast tissue specimens showed the biochemical differences between tissues, and spectral analysis with W/TAR demonstrated large differences in water content and that our Raman system can accurately differentiate between tumour and non‐tumour tissue, even in the presence of surgical pigments. This provides proof of principle that this Raman system is suitable for further investigation with a view to providing IMA in the clinical environment. We demonstrate the biochemical differences in malignant human breast tissue and spectral analysis of water content differentiates between tumour and non‐tumour tissue, even in the presence of surgical pigments. We present a Raman system with the potential to provide IMA in the clinical environment.