Addressing global disparities in blood pressure control : perspectives of the International Society of Hypertension
- Authors: Schutte, Aletta , Jafar, Tazeen , Poulter, Neil , Damasceno, Albertino , Khan, Nadia , Nilsson, Peter , Alsaid, Jafar , Neupane, Dinesh , Kario, Kazuomi , Beheiry, Hind , Brouwers, Sofie , Burger, Dylan , Charchar, Fadi , Cho, Myeong-Chan , Guzik, Tomasz , Haji Al-Saedi, Ghazi , Ishaq, Muhammad , Itoh, Hiroshi , Jones, Erika , Khan, Taskeen , Kokubo, Yoshihiro , Kotruchin, Praew , Muxfeldt, Elizabeth , Odili, Augustine , Patil, Mansi , Ralapanawa, Udaya , Romero, Cesar , Schlaich, Markus , Shehab, Abdulla , Mooi, Ching
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cardiovascular Research Vol. 119, no. 2 (2023), p. 381-409
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- Description: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics
- Authors: Xu, Xiaoguang , Eales, James , Jiang, Xiao , Sanderson, Eleanor , Drzal, Maciej , Saluja, Sushant , Scannali, David , Williams, Bryan , Morris, Andrew , Guzik, Tomasz , Charchar, Fadi , Holmes, Michael , Tomaszewski, Maciej
- Date: 2022
- Type: Text , Journal article
- Relation: Cardiovascular research Vol. 118, no. 15 (2022), p. 3151-3161
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- Description: AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in
Human Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
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- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications
- Authors: Tomaszewski, Maciej , Morris, Andrew , Howson, Joanna , Franceschini, Nora , Eales, James , Xu, Xiaoguang , Dikalov, Sergey , Guzik, Tomasz , Humphreys, Benjamin , Harrap, Stephen , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Kidney International Vol. 102, no. 3 (2022), p. 492-505
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- Description: Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. © 2022 International Society of Nephrology