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Le NN, Frater I, Lip S, Padmanabhan S. Hypertension precision medicine: the promise and pitfalls of pharmacogenomics. Pharmacogenomics 2025:1-24. [PMID: 40421951 DOI: 10.1080/14622416.2025.2504865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 05/08/2025] [Indexed: 05/28/2025] Open
Abstract
Pharmacogenomics (PGx) has the potential to revolutionize hypertension management by tailoring antihypertensive therapy based on genetic profiles. Despite significant advances in genomic research, the clinical translation of PGx in hypertension remains challenging due to genetic complexity, variability in drug response, and implementation barriers. This review explores the genetic basis of hypertension, highlighting key pharmacogenomic markers that influence antihypertensive metabolism and efficacy, including CYP2D6, CYP3A4, UMOD, and ACE polymorphisms. We also examine the role of Mendelian randomization, polygenic risk scores in drug development and stratifying hypertension treatment response. While PGx offers opportunities for personalized medicine - such as reducing trial-and-error prescribing and improving adherence - several obstacles hinder its widespread adoption. These include limited clinical actionability, lack of large-scale randomized controlled trials, cost constraints, and concerns about equity and accessibility. Furthermore, drug-gene interactions and phenoconversion add complexity to implementation. Emerging technologies, including artificial intelligence-driven prescribing, microbiome integration, and pharmacoepigenomics, may enhance PGx precision in hypertension management. However, further research, clinical validation, and policy frameworks are necessary before PGx can be routinely incorporated into hypertension care. This review critically evaluates both the promise and limitations of PGx in hypertension, offering insights into the future of precision medicine in cardiovascular health.
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Affiliation(s)
- Nhu Ngoc Le
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, UK
| | - Iain Frater
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, UK
| | - Stefanie Lip
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, UK
| | - Sandosh Padmanabhan
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, UK
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Maheshwari A, Gupta R, Verma N, Narasingan SN, Singh RB, Saboo B, Kumar CHV, Gupta A, Srivastava MK, Gupta A, Srivastava S, Aggarwal A, Tewari A, Ansari S, Patni B, Agarwal D, Sattur GB, Rodrigues L, Pareek KK, Yeolekar M, Banerjee S, Sreenivasamurthy L, Das MK, Joshi S, Vajpeyee S, Muthusamy VV, Muruganathan A. Position statement on hypertension by Indian Society of Hypertension, 2023. J Hum Hypertens 2024; 38:736-744. [PMID: 39367179 DOI: 10.1038/s41371-024-00960-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 07/25/2024] [Accepted: 09/18/2024] [Indexed: 10/06/2024]
Abstract
The Indian Society of Hypertension (InSH) highlights the urgency for India-specific guidelines on hypertension management. Hypertension affects over one billion people worldwide, with India bearing a significant burden due to its population, diversity, and demographics. In India, hypertension affects 21% of women and 24% of men, while pre-hypertension affects 39% of women and 49% of men. The prevalence of hypertension increases in the population with obesity. Even 7% of school-going children in India have hypertension, especially in urban and overweight children. However, awareness and control of hypertension in India are inadequate. Only 57% of women and 38% of men have been diagnosed with hypertension; among them, only a fraction receive appropriate medication. The overall control of hypertension stands at 15%, with regional variations. Hypertension significantly contributes to cardiovascular and renal diseases, and better detection and treatment could reduce their impact in India. At the total population level, reducing systolic blood pressure (SBP) by 2 mm Hg may significantly affect cardiovascular disease. Considering the unique challenges faced in India, the InSH stresses the importance of a tailored approach to hypertension management. They plan to disseminate guidelines through practitioner training and patient awareness campaigns. These guidelines will cover screening, diagnosis, management, handling hypertension with other conditions, long-term follow-up, and patient education. In conclusion, this position paper calls for immediate action to improve hypertension management in India and alleviate the associated disease burden and mortality.
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Affiliation(s)
- Anuj Maheshwari
- Hind Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
| | - Rajeev Gupta
- Eternal Heart Care Centre and Research Institute, Jaipur, Rajasthan, India
| | - Narsingh Verma
- King George Medical University, Lucknow, Uttar Pradesh, India
| | | | - Ram B Singh
- Halberg Hospital and Research Institute, Moradabad, Uttar Pradesh, India
| | - Banshi Saboo
- Dia Care, Diabetes Care, and Hormone Clinic, Ahmedabad, Gujarat, India
| | | | | | | | - Amit Gupta
- Centre For Diabetes Care, Noida, Uttar Pradesh, India
| | - Saurabh Srivastava
- Government Institute of Medical Sciences, Greater Noida, Uttar Pradesh, India
| | - Amitesh Aggarwal
- University College of Medical Sciences and GTB Hospital, Delhi, India
| | - Ajoy Tewari
- Hind Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Sajid Ansari
- Hind Institute of Medical Sciences & S.S Heart Care Centre, Lucknow, Uttar Pradesh, India
| | - Bijay Patni
- Diabetes Wellness Care, Kolkata, West Bengal, India
| | | | - G B Sattur
- Sattur Medical Care, Hubli, Karnataka, India
| | - Lily Rodrigues
- Stride Hospitals & Maheshwara Medical College, Hyderabad, Telangana, India
| | - K K Pareek
- S. N. Pareek Hospital, Kota, Rajasthan, India
| | - Murar Yeolekar
- K J Somaiya Medical College & Hospital, Mumbai, Maharashtra, India
| | - Samar Banerjee
- Vivekananda Institute of Medical Sciences, Kolkata, West Bengal, India
| | | | - M K Das
- C.K. Birla Hospitals (BMB/CMRI), Kolkata, West Bengal, India
| | - Shashank Joshi
- Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India
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Hu Y, Huerta J, Cordella N, Mishuris RG, Paschalidis IC. Personalized hypertension treatment recommendations by a data-driven model. BMC Med Inform Decis Mak 2023; 23:44. [PMID: 36859187 PMCID: PMC9979505 DOI: 10.1186/s12911-023-02137-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 02/09/2023] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND Hypertension is a prevalent cardiovascular disease with severe longer-term implications. Conventional management based on clinical guidelines does not facilitate personalized treatment that accounts for a richer set of patient characteristics. METHODS Records from 1/1/2012 to 1/1/2020 at the Boston Medical Center were used, selecting patients with either a hypertension diagnosis or meeting diagnostic criteria (≥ 130 mmHg systolic or ≥ 90 mmHg diastolic, n = 42,752). Models were developed to recommend a class of antihypertensive medications for each patient based on their characteristics. Regression immunized against outliers was combined with a nearest neighbor approach to associate with each patient an affinity group of other patients. This group was then used to make predictions of future Systolic Blood Pressure (SBP) under each prescription type. For each patient, we leveraged these predictions to select the class of medication that minimized their future predicted SBP. RESULTS The proposed model, built with a distributionally robust learning procedure, leads to a reduction of 14.28 mmHg in SBP, on average. This reduction is 70.30% larger than the reduction achieved by the standard-of-care and 7.08% better than the corresponding reduction achieved by the 2nd best model which uses ordinary least squares regression. All derived models outperform following the previous prescription or the current ground truth prescription in the record. We randomly sampled and manually reviewed 350 patient records; 87.71% of these model-generated prescription recommendations passed a sanity check by clinicians. CONCLUSION Our data-driven approach for personalized hypertension treatment yielded significant improvement compared to the standard-of-care. The model implied potential benefits of computationally deprescribing and can support situations with clinical equipoise.
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Affiliation(s)
- Yang Hu
- Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, 8 Saint Mary's St., Boston, MA, 02215, USA
| | - Jasmine Huerta
- Department of Medicine, Boston Medical Center, School of Medicine, Boston University, Boston, MA, USA
| | - Nicholas Cordella
- Department of Medicine, Boston Medical Center, School of Medicine, Boston University, Boston, MA, USA
| | - Rebecca G Mishuris
- Department of Medicine, Boston Medical Center, School of Medicine, Boston University, Boston, MA, USA
| | - Ioannis Ch Paschalidis
- Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, 8 Saint Mary's St., Boston, MA, 02215, USA.
- Department of Biomedical Engineering, Faculty of Computing & Data Sciences, Hariri Institute for Computing and Computational Science & Engineering, Boston University, 8 Saint Mary's St., Boston, MA, 02215, USA.
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Lip S, Dempster G, Jain S, Brooksbank K, Ghouri N, McCallum L, Padmanabhan S. Underrepresentation of ethnic minorities in hypertension research-a survey of enablers and barriers among South Asian and African communities in Glasgow. Trials 2022; 23:609. [PMID: 35906700 PMCID: PMC9335986 DOI: 10.1186/s13063-022-06542-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 07/12/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hypertension is the biggest contributor to the global cardiovascular burden with evidence for ethnic differences in treatment response and outcomes. Under-representation of ethnic minorities in clinical research is well known, and despite wide-ranging public engagement events by the Glasgow Blood Pressure Clinic team, there was a lack of participation of ethnic minorities in both engagement activities and clinical trials conducted by them. This study aims to explore the awareness and knowledge of hypertension and the facilitators and barriers to participation in hypertension clinical research among South Asian (SA) and African (AFR) communities in Glasgow. METHODS A survey questionnaire was co-developed with representatives from South Asian (SA) and African (AFR) patients and community members in Glasgow to understand awareness and knowledge of hypertension and enablers and barriers to participation in clinical research. The survey was distributed to adults (aged > 18) years of SA or AFR ancestry at public engagement events at venues that were frequently visited by these two communities in Glasgow. RESULTS The survey response rate was 337 (67.4%) consisting of 242 (71.8%) South Asian (SA) and 56 (16.9%) African (AFR) respondents. Thirty-nine questionnaires were excluded because of incompletion. Most of the respondents were not born in the UK and were in the 35-53-year group (AFR 29 (51%), SA 113 (47%)). The proportion living in the most deprived (SIMD 1) and least deprived (SIMD 5) was respectively 26 (12.4%) and 34 (16.2%) for SA and 20 (42.6%) and 2 (4.3%) for AFR. There was a considerable recognition that treatment needs to be ethnicity-specific (SA/AFR = 107 (48%)/23 (45.1%)) and that current cardiovascular disease treatment guidelines were not tailored for different ethnicities 84 (38.5%)/23 (45.1%). The key enablers encouraging research participation are enhanced health information, conducting aspects of their clinical research visits/appointments at a location they frequently visited and allowing a family member to accompany them. Barriers included concerns about the use of personal information and side effects of the new treatment. CONCLUSION Our survey confirmed enablers and barriers to ethnic minority participation in research. We find improving and evolving awareness and beliefs among the ethnic minority population including community leaders. Thus, continual review of researchers' beliefs and attitudes is also essential to ensure engagement activities keep up with these changing perceptions.
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Affiliation(s)
- Stefanie Lip
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Georgia Dempster
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Sahil Jain
- Department of Rheumatology and General Internal Medicine, Queen Elizabeth University Hospital, Glasgow, UK
| | - Katriona Brooksbank
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Nazim Ghouri
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Linsay McCallum
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Sandosh Padmanabhan
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
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Initial combination therapy for hypertension in patients of African ancestry: a systematic review and meta-analysis. J Hypertens 2022; 40:629-640. [PMID: 35132041 DOI: 10.1097/hjh.0000000000003074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We systematically reviewed randomized controlled trials (RCTs) that consider the effect of initial dual antihypertensive combination treatment on blood pressure (BP), morbidity, or mortality in hypertensive African ancestry adults, using the methodology of the Cochrane Collaboration. Main outcomes were difference in means (continuous data) and risk ratio (dichotomous data).We retrieved 1728 reports yielding 13 RCTs of 4 weeks to 3 years duration (median 8 weeks) in 3843 patients. Systolic BP was significantly higher on β-adrenergic blocker vs. other combinations, 3.80 [0.82;6.78] mmHg, but comparable for other combinations. Hypokalemia and hyperglycemia occurred with calcium channel blocker (CCB) + diuretics > diuretics + angiotensin converting enzyme inhibitor (ACEI)/angiotensin-II-type-1-receptor antagonist (ARB) > CCB + ACEI/ARB. An RCT including high-risk patients reported combined morbidity/mortality for hydrochlorothiazide (mg) 25 + benazepril 40 vs. amlodipine 10 + benazepril 40 of respectively 8.9% vs. 6.6% (n = 1414, risk ratio 1.35 [0.94;1.94]; all patients, N = 11 506, 1.23 [1.11;1.37]).We conclude that limited evidence supports CCB + ACEI rather than HCT + ACEI as first-line initial combination therapy in African ancestry patients with hypertension. PROSPERO CRD42021238529.
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Jeon I, Kim YK, Song I, Yoon DY, Huh KY, Jin X, Yu K, Lee S, Kumagai Y, Jang I. The necessary conduct: Exploratory multiregional clinical trials in East Asia. Clin Transl Sci 2021; 14:2399-2407. [PMID: 34397152 PMCID: PMC8604233 DOI: 10.1111/cts.13106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/25/2021] [Indexed: 12/01/2022] Open
Abstract
Various studies have highlighted the importance of ethnic differences. The consideration of ethnic differences in the field of individualized pharmacotherapy is imperative. Therefore, various organizations and networks across countries should aim to conduct multicountry and multiregional clinical trials (MRCTs). If there is solid evidence available to evaluate the existence of ethnic differences between the same regional areas, it will lead to an increase in the efficiency of drug development. The purpose of this paper was to compare the approval dosing regimen among four Asian countries (Korea, Japan, China, and Taiwan) and elucidate the readiness and current status of the implementation of the International Conference on Harmonization (ICH) E17 guidelines on MRCTs. Reducing unnecessary clinical trials via multinational clinical trials in East Asian countries is also suggested. The approved dosing regimens for some drugs in the four Asian countries were similar; however, some differences might be caused by differences in legislation, even though there were no ethnic differences. This indicates that there are several roles to be expected of the Asia Clinical Pharmacology study network for exploratory MRCTs, which would lead to the accumulation of evidence for MRCTs, ultimately accelerating the efficiency of drug development in East Asian countries. The exposure of the new treatment to the necessary patients through collaborative research coordination and simultaneous multinational subject recruitment would serve its role in providing East Asia with specific personalized medicine with a high treatment success rate.
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Affiliation(s)
- Inseung Jeon
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Yu Kyong Kim
- Department of Clinical Pharmacology and TherapeuticsChungbuk National University College of Medicine and HospitalCheongjuKorea
| | - Ildae Song
- Department of Pharmaceutical Science and TechnologyKyungsung UniversityBusanKorea
- Kitasato Clinical Research CenterKitasato University School of MedicineKanagawaJapan
| | - Deok Yong Yoon
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Ki Young Huh
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Xuanyou Jin
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Kyung‐Sang Yu
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - SeungHwan Lee
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Yuji Kumagai
- Kitasato Clinical Research CenterKitasato University School of MedicineKanagawaJapan
| | - In‐Jin Jang
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
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Prasad GVR, Bhamidi V. Managing cardiovascular disease risk in South Asian kidney transplant recipients. World J Transplant 2021; 11:147-160. [PMID: 34164291 PMCID: PMC8218347 DOI: 10.5500/wjt.v11.i6.147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/12/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
South Asians (SA) are at higher cardiovascular risk than other ethnic groups, and SA kidney transplant recipients (SA KTR) are no exception. SA KTR experience increased major adverse cardiovascular events both early and late post-transplantation. Cardiovascular risk management should therefore begin well before transplantation. SA candidates may require aggressive screening for pre-transplant cardiovascular disease (CVD) due to their ethnicity and comorbidities. Recording SA ethnicity during the pre-transplant evaluation may enable programs to better assess cardiovascular risk, thus allowing for earlier targeted peri- and post-transplant intervention to improve cardiovascular outcomes. Diabetes remains the most prominent post-transplant cardiovascular risk factor in SA KTR. Diabetes also clusters with other metabolic syndrome components including lower high-density lipoprotein cholesterol, higher triglycerides, hypertension, and central obesity in this population. Dyslipidemia, metabolic syndrome, and obesity are all significant CVD risk factors in SA KTR, and contribute to increased insulin resistance. Novel biomarkers such as adiponectin, apolipoprotein B, and lipoprotein (a) may be especially important to study in SA KTR. Focused interventions to improve health behaviors involving diet and exercise may especially benefit SA KTR. However, there are few interventional clinical trials specific to the SA population, and none are specific to SA KTR. In all cases, understanding the nuances of managing SA KTR as a distinct post-transplant group, while still screening for and managing each CVD risk factor individually in all patients may help improve the long-term success of all kidney transplant programs catering to multi-ethnic populations.
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Affiliation(s)
- G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
| | - Vaishnavi Bhamidi
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, ON, Canada
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Hypertension management in 2030: a kaleidoscopic view. J Hum Hypertens 2021; 35:812-817. [PMID: 33139827 PMCID: PMC7605343 DOI: 10.1038/s41371-020-00438-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/04/2020] [Accepted: 10/20/2020] [Indexed: 01/31/2023]
Abstract
The last decade has witnessed the healthcare system going paperless with increased use of electronic healthcare records. Artificial intelligence tools including smartphones and smart watches have changed the landscape of day-to-day lives. Digitisation, decentralisation of healthcare and empowerment of allied healthcare providers and patients themselves have made shared clinical decision-making a reality. The year 2020 quickly turned into an unprecedented time in our lives with the entry of COVID-19. Amidst a pandemic, healthcare systems rapidly adapted and transformed, and changes that otherwise would have taken a decade, took a mere few weeks (Webster, Lancet 395:1180-1, 2020). This essay reviews evidence of transformation in the realm of hypertension management, namely diagnosis, lifestyle changes, therapeutics and prevention of hypertension at both individual and population levels, and presents an extrapolation of how this transformation might shape the next decade.
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Sinnott SJ, Douglas IJ, Smeeth L, Williamson E, Tomlinson LA. First line drug treatment for hypertension and reductions in blood pressure according to age and ethnicity: cohort study in UK primary care. BMJ 2020; 371:m4080. [PMID: 33208355 PMCID: PMC7670766 DOI: 10.1136/bmj.m4080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2020] [Indexed: 01/13/2023]
Abstract
OBJECTIVE To study whether treatment recommendations based on age and ethnicity according to United Kingdom (UK) clinical guidelines for hypertension translate to blood pressure reductions in current routine clinical care. DESIGN Observational cohort study. SETTING UK primary care, from 1 January 2007 to 31 December 2017. PARTICIPANTS New users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), calcium channel blockers (CCB), and thiazides. MAIN OUTCOME MEASURES Change in systolic blood pressure in new users of ACEI/ARB versus CCB, stratified by age (< v ≥55) and ethnicity (black v non-black), from baseline to 12, 26, and 52 week follow-up. Secondary analyses included comparisons of new users of CCB with those of thiazides. A negative outcome (herpes zoster) was used to detect residual confounding and a series of positive outcomes (expected drug effects) was used to determine whether the study design could identify expected associations. RESULTS During one year of follow-up, 87 440 new users of ACEI/ARB, 67 274 new users of CCB, and 22 040 new users of thiazides were included (median 4 (interquartile range 2-6) blood pressure measurements per user). For non-black people who did not have diabetes and who were younger than 55, CCB use was associated with a larger reduction in systolic blood pressure of 1.69 mm Hg (99% confidence interval -2.52 to -0.86) relative to ACEI/ARB use at 12 weeks, and a reduction of 0.40 mm Hg (-0.98 to 0.18) in those aged 55 and older. In subgroup analyses using six finer age categories of non-black people who did not have diabetes, CCB use versus ACEI/ARB use was associated with a larger reduction in systolic blood pressure only in people aged 75 and older. Among people who did not have diabetes, systolic blood pressure decreased more with CCB use than with ACEI/ARB use in black people (reduction difference 2.15 mm Hg (-6.17 to 1.87)); the corresponding reduction difference was 0.98 mm Hg (-1.49 to -0.47) in non-black people. CONCLUSIONS Similar reductions in blood pressure were found to be associated with new use of CCB as with new use of ACEI/ARB in non-black people who did not have diabetes, both in those who were aged younger than 55 and those aged 55 and older. For black people without diabetes, CCB new use was associated with numerically greater reductions in blood pressure than ACEI/ARB compared with non-black people without diabetes, but the confidence intervals were overlapping for the two groups. These results suggest that the current UK algorithmic approach to first line antihypertensive treatment might not lead to greater reductions in blood pressure. Specific indications could be considered in treatment recommendations.
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Affiliation(s)
- Sarah-Jo Sinnott
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
| | - Ian J Douglas
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
| | - Liam Smeeth
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
| | - Elizabeth Williamson
- Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
| | - Laurie A Tomlinson
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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Van Tassell JC, Shimbo D, Hess R, Kittles R, Wilson JG, Jorde LB, Li M, Lange LA, Lange EM, Muntner P, Bress AP. Association of West African ancestry and blood pressure control among African Americans taking antihypertensive medication in the Jackson Heart Study. J Clin Hypertens (Greenwich) 2020; 22:157-166. [PMID: 32049421 PMCID: PMC7219977 DOI: 10.1111/jch.13824] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 12/24/2019] [Accepted: 12/31/2019] [Indexed: 01/05/2023]
Abstract
African Americans have a wide range of continental genetic ancestry. It is unclear whether racial differences in blood pressure (BP) control are related to ancestral background. The authors analyzed data from the Jackson Heart Study, a cohort exclusively comprised of self-identified African Americans, to assess the association between estimated West African ancestry (WAA) and BP control (systolic and diastolic BP < 140/90 mm Hg). Three nested modified Poisson regression models were used to calculate prevalence ratios for BP control associated with the three upper quartiles, separately, vs the lowest quartile of West African ancestry. The authors analyzed data from 1658 participants with hypertension who reported taking all of their antihypertensive medications in the previous 24 hours. WAA was estimated using 389 ancestry informative markers and categorized into quartiles (Q1: <73.7%, Q2: >73.7%-81.0%, Q3: >81.0%-86.3%, and Q4: >86.3%). The proportion of participants with controlled BP in the lowest-to-highest WAA quartile was 75.2%, 76.1%, 76.6%, and 74.4%. The prevalence ratios (95% CI) for controlled BP comparing Q2, Q3, and Q4 to Q1 of WAA were 1.00 (0.93-1.08), 1.02 (0.94-1.10), and 0.99 (0.91-1.07), respectively. Among African Americans in the Jackson Heart Study taking antihypertensive medication, BP control rates did not differ across quartiles of WAA.
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Affiliation(s)
| | - Daichi Shimbo
- Department of MedicineColumbia UniversityNew YorkNew York
| | - Rachel Hess
- Division of Health System Innovation and ResearchDepartment of Population Health SciencesUniversity of UtahSalt Lake CityUtah
| | - Rick Kittles
- Division of Health EquitiesDepartment of Population SciencesCity of HopeDuarteCalifornia
| | - James G. Wilson
- Department of Physiology and BiophysicsUniversity of MississippiJacksonMississippi
| | - Lynn B. Jorde
- Department of Human GeneticsUniversity of Utah School of MedicineSalt Lake CityUtah
| | - Man Li
- Division of Nephrology & HypertensionDepartment of Internal MedicineUniversity of UtahSalt Lake CityUtah
| | - Leslie A. Lange
- Division of Biomedical Informatics and Personalized MedicineDepartment of MedicineUniversity of Colorado, Anschutz Medical CampusAuroraColorado
| | - Ethan M. Lange
- Division of Biomedical Informatics and Personalized MedicineDepartment of MedicineUniversity of Colorado, Anschutz Medical CampusAuroraColorado
| | - Paul Muntner
- Department of EpidemiologyUniversity of Alabama at BirminghamBirminghamAlabama
| | - Adam P. Bress
- Division of Health System Innovation and ResearchDepartment of Population Health SciencesUniversity of UtahSalt Lake CityUtah
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Wych J, Grayling MJ, Mander AP. Sample size re-estimation in crossover trials: application to the AIM HY-INFORM study. Trials 2019; 20:665. [PMID: 31791376 PMCID: PMC6889633 DOI: 10.1186/s13063-019-3724-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 09/13/2019] [Indexed: 11/10/2022] Open
Abstract
Background Crossover designs are commonly utilised in randomised controlled trials investigating treatments for long-term chronic illnesses. One problem with this design is its inherent repeated measures necessitate the availability of an estimate of the within-person standard deviation (SD) to perform a sample size calculation, which may be rarely available at the design stage of a trial. Interim sample size re-estimation designs can be used to help alleviate this issue by adapting the sample size mid-way through the trial, using accrued information in a statistically robust way. Methods The AIM HY-INFORM study is part of the Informative Markers in Hypertension (AIM HY) Programme and comprises two crossover trials, each with a planned recruitment of 600 participants. The objective of the study is to test whether blood pressure response to first line antihypertensive treatment depends on ethnicity. An interim analysis is planned to reassess the assumptions of the planned sample size for the study. The aims of this paper are: (1) to provide a formula for sample size re-estimation in both crossover trials; and (2) to present a simulation study of the planned interim analysis to investigate alternative within-person SDs to that assumed. Results The AIM HY-INFORM protocol sample size calculation fixes the within-person SD to be 8 mmHg, giving > 90% power for a primary treatment effect of 4 mmHg. Using the method developed here and simulating the interim sample size reassessment, if we were to see a larger within-person SD of 9 mmHg at interim, 640 participants for 90% power 90% of the time in the three-period three-treatment design would be required. Similarly, in the four-period four-treatment crossover design, 602 participants would be required. Conclusions The formulas presented here provide a method for re-estimating the sample size in crossover trials. In the context of the AIM HY-INFORM study, simulating the interim analysis allows us to explore the results of a possible increase in the within-person SD from that assumed. Simulations show that without increasing the planned sample size of 600 participants, we can reasonably still expect to achieve 80% power with a small increase in the within-person SD from that assumed. Trial registration ClinicalTrials.gov, NCT02847338. Registered on 28 July 2016.
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Affiliation(s)
- Julie Wych
- Medical Research Council Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.
| | - Michael J Grayling
- Medical Research Council Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.,Institute of Health & Society, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK
| | - Adrian P Mander
- Medical Research Council Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.,Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, 7th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK
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McNally RJ, Morselli F, Farukh B, Chowienczyk PJ, Faconti L. A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective. Br J Clin Pharmacol 2019; 85:2707-2713. [PMID: 31471972 PMCID: PMC6955404 DOI: 10.1111/bcp.14109] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 08/07/2019] [Accepted: 08/24/2019] [Indexed: 01/02/2023] Open
Abstract
Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.
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Affiliation(s)
- Ryan J. McNally
- British Heart Foundation CentreKing's College LondonLondonUK
| | - Franca Morselli
- British Heart Foundation CentreKing's College LondonLondonUK
| | - Bushra Farukh
- British Heart Foundation CentreKing's College LondonLondonUK
| | | | - Luca Faconti
- British Heart Foundation CentreKing's College LondonLondonUK
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Das R, Upadhyai P. An Ancestry Informative Marker Set Which Recapitulates the Known Fine Structure of Populations in South Asia. Genome Biol Evol 2018; 10:2408-2416. [PMID: 30184103 PMCID: PMC6143162 DOI: 10.1093/gbe/evy182] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2018] [Indexed: 12/16/2022] Open
Abstract
The inference of genomic ancestry using ancestry informative markers (AIMs) can be useful for a range of studies in evolutionary genetics, biomedical research, and forensic analyses. However, the determination of AIMs for highly admixed populations with complex ancestries has remained a formidable challenge. Given the immense genetic heterogeneity and unique population structure of the Indian subcontinent, here we sought to derive AIMs that would yield a cohesive and faithful understanding of South Asian genetic origins. To discern the most optimal strategy for extracting AIMs for South Asians we compared three commonly used AIMs-determining methods namely, Infocalc, FST, and Smart Principal Component Analysis with ADMIXTURE, using previously published whole genome data from the Indian subcontinent. Our findings suggest that the Infocalc approach is likely most suitable for delineation of South Asian AIMs. In particular, Infocalc-2,000 (N = 2,000) appeared as the most informative South Asian AIMs panel that recapitulated the finer structure within South Asian genomes with high degree of sensitivity and precision, whereas a negative control with an equivalent number of randomly selected markers when used to interrogate the South Asian populations, failed to do so. We discuss the utility of all approaches under evaluation for AIMs derivation and interpreting South Asian genomic ancestries. Notably, this is the first report of an AIMs panel for South Asian ancestry inference. Overall these findings may aid in developing cost-effective resources for large-scale demographic analyses and foster expansion of our knowledge of human origins and disease, in the South Asian context.
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Affiliation(s)
- Ranajit Das
- Manipal Centre for Natural Sciences (MCNS), Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Priyanka Upadhyai
- Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
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