859 research outputs found

    South Asians have elevated postexercise blood pressure and myocardial oxygen consumption compared to Europeans despite equivalent resting pressure

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    This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Stroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this. METHODS AND RESULTS: A population-based sample of 147 European and 145 South Asian middle-aged men and women performed the Dundee 3-minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate-pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, -0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate-pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, -39 to 561 mm Hg/min; P=0.3]). CONCLUSION: Postexercise recovery of BP and rate-pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians.The British Heart Foundation funded this project. Drs Chaturvedi, Kooner, John Chambers, and Hughes received support from the NIHR (UK National Institute for Health Research) Biomedical Research Centre. Dr Shore received support from the Peninsula NIHR Clinical Research Facility

    The South Asian genome

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    Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

    Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

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    WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

    Non-invasive skin measurement methods and diagnostics for vitiligo: a systematic review

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    Vitiligo is a multifaceted autoimmune depigmenting disorder affecting around 0.5 to 2.0% of individuals globally. Standardizing diagnosis and therapy tracking can be arduous, as numerous clinical evaluation methods are subject to interobserver variability and may not be validated. Therefore, there is a need for diagnostic tools that are objective, dependable, and preferably non-invasive.AimsThis systematic review provides a comprehensive overview of the non-invasive objective skin measurement methods that are currently used to evaluate the diagnosis, severity, and progression of vitiligo, as well as the advantages and limitations of each technique.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used for the systematic review. Scopus, Embase, Cochrane Library, and Web of Science databases were comprehensively searched for non-invasive imaging and biophysical skin measuring methods to diagnose, evaluate the severity of, or monitor the effects of vitiligo treatment. The risk of bias in included articles was assessed using the QUADAS-2 quality assessment scale.ResultsAn extensive literature search resulted in 64 studies for analysis, describing eight imaging techniques (reflectance confocal microscopy, computer-aided imaging analysis, optical coherence tomography, infrared photography, third-harmonic generation microscopy, multiphoton microscopy, ultraviolet light photography, and visible light/digital photograph), and three biophysical approaches (dermoscopy, colorimetry, spectrometry) used in diagnosing and assessing vitiligo. Pertinent information about functionality, mechanisms of action, sensitivity, and specificity was obtained for all studies, and insights into the strengths and limitations of each diagnostic technique were addressed. Methodological study quality was adequate; however, statistical analysis was not achievable because of the variety of methods evaluated and the non-standardized reporting of diagnostic accuracy results.ConclusionsThe results of this systematic review can enhance clinical practice and research by providing a comprehensive overview of the spectrum of non-invasive imaging and biophysical techniques in vitiligo assessment. Studies with larger sample sizes and sound methodology are required to develop verified methods for use in future practice and research.Systematic review registration(PROSPERO) database, (CRD42023395996)

    Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers

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    Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff

    Subleading effects and the field range in axion inflation

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    An attractive candidate for the inflaton is an axion slowly rolling down a flat potential protected by a perturbative shift symmetry. Realisations of this idea within large field, natural and monomial inflation have been disfavoured by observations and are difficult to embed in string theory. We show that subleading, but significant non-perturbative corrections can superimpose sharp cliffs and gentle plateaus into the potential, whose overall effect is to enhance the number of e-folds of inflation. Sufficient e-folds are therefore achieved for smaller field ranges compared to the potential without such corrections. Thus, both single-field natural and monomial inflation in UV complete theories like string theory, can be restored into the favour of current observations, with distinctive signatures. Tensor modes result un-observably small, but there is a large negative running of the spectral index. Remarkably, natural inflation can be achieved with a single field whose axion decay constant is sub-Planckian.Comment: 18 pages, 15 figures; v2 references improve

    A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides

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    Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD

    A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

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    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz
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