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1. Assessing Machine Learning for Diagnostic Classification of Hypertension Types Identified by Ambulatory Blood Pressure Monitoring

Author

Tran, Tran Quoc Bao, Lip, Stefanie, du Toit, Clea, Kalaria, Tejas Kumar, Bhaskar, Ravi K., O’Neil, Alison Q., Graff, Beata, Hoffmann, Michał, Szyndler, Anna, Polonis, Katarzyna, Wolf, Jacek, Reddy, Sandeep, Narkiewicz, Krzysztof, Dasgupta, Indranil, Dominiczak, Anna F., Visweswaran, Shyam, McCallum, Linsay, and Padmanabhan, Sandosh

Published
2024
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4. Serum chloride : epidemiology and genetic dissection of a novel marker for cardiovascular risk

Author

McCallum, Linsay

Subjects
616.1, RC Internal medicine
Abstract

Chloride (Cl-) is the principal anion in the human body and is essential for the maintenance of osmotic pressure, acid-base balance, the movement of water between fluid compartments and regulation of muscular activity. The ability of the kidney to reabsorb Cl- maintains serum Cl- within a narrow range. Hyper and hypochloraemia are associated with several disease states or can be the result of drugs. Serum Cl- is frequently measured in the clinical setting and although it is useful in a number of clinical conditions, it is often overlooked. Low serum Cl- has been shown in multiple phenotypically distinct populations to be associated with adverse outcomes, in particular cardiovascular outcomes, however the mechanism by which low serum Cl- increases mortality and/or cardiovascular events and its validity within the general population is unclear. This thesis aims to validate serum Cl- as a risk predictor in large scale epidemiological studies of two large patient cohorts; identify physiological pathways that affect serum Cl- and other electrolytes through metabolome-wide association study and identify genetic determinants of serum Cl- through a genome-wide association study. Chapter 1 provides an introduction to cardiovascular disease, cardiovascular risk and the use of serum biomarkers for risk stratification. The emphasis is on salt as a risk factor with focus on the epidemiological studies of serum Cl- and adverse outcomes. In Chapter 2 , the data sources (Glasgow Blood Pressure Clinic; NHS Greater Glasgow and Clyde Safe Haven; TwinsUK; Generation Scotland Family Health Study), data application process, methods for data cleaning and the preparation of data for analysis are detailed. Statistical methods for the epidemiological studies are described. Building upon previous work investigating the association of serum chloride and mortality outcomes in the Glasgow Blood Pressure Clinic (GBPC) hypertensive population, Chapter 3 explores the association of serum chloride and cause-specific morbidity and mortality outcomes in a new dataset linking the GBPC patient data with outcome data from the NHS Scotland Information Services Division. Multivariable Cox proportional hazard (Cox-PH) modelling and Cox-PH modelling with restricted cubic spline function were used investigate the associations. In 6,133 hypertensive patients attending the GBPC, using the multivariable Cox PH model, there was an inverse association of serum Cl- with all-cause and cardiovascular mortality, death from myocardial infarction, ischaemic heart disease and stroke at 10, 20 and 30 years follow up. The relationship between serum chloride with all-cause mortality, cardiovascular mortality and death from stroke was found to be U-shaped using Cox-PH modelling with restricted cubic spline function whilst for death from myocardial infarction and ischaemic heart disease the relationship was linear. The risk of hospital admission with heart failure was inversely related to serum Cl- in the multivariable Cox-PH model at 5 and 10 years follow up and this relationship was found to be U-shaped in the Cox-PH model with restricted cubic spline function. Chapter 4 sought to validate the findings from the GBPC population in a large general population study using data from the NHS Greater Glasgow and Clyde Safe Haven. A wider range of morbidity and mortality outcomes were studied, including non-cardiovascular outcomes which share common pathophysiological processes with cardiovascular disease, using multivariable Cox-PH models. In 519,957 patients from the NHSGGC Safe Haven, lower levels of serum Cl- were associated with higher risk of all-cause, cardiovascular mortality and heart failure admissions confirming the findings from the hypertension study described in Chapter 3. In addition, lower serum Cl- is also significantly associated with the following cause-specific cardiovascular outcomes – deaths due to MI, heart failure, arrhythmia, ischaemic stroke, intracerebral haemorrhage; admissions for PVD, ischaemic stroke and intracerebral haemorrhage. Furthermore, the following non-cardiovascular outcomes are also associated with lower serum Cl- - deaths due to COPD, cancer, chronic liver disease, alcohol related liver disease, diabetes mellitus; admissions for COPD, chronic liver disease, alcohol related liver disease, diabetes mellitus and CKD. Though serum chloride is inversely associated with adverse outcomes in Chapter 4 a causal mechanism is not established. In Chapter 5 a two-pronged approach is used to attempt to further understand the relationship between serum Cl- and risk. A metabolome wide association study (MWAS) was performed in the TwinsUK cohort to discover molecular markers and pathways associated with serum electrolyte levels through metabolomic profiling. Acid–base balance and electrolyte homeostasis are intricately connected to maintain the body’s internal environment within rigidly controlled limits therefore the study of metabolomic associations of electrolytes need to be considered in the context of these homeostatic processes. Common electrolyte and acid-base patterns were mapped, based on the HCO3--centric physicochemical model and electroneutrality, to metabolite associations. Na+ and Cl‐ showed the lowest number of independent metabolite associations (10 & 17 respectively) and K+ the highest number. Serum K+ showed the most significant associations with individual fatty acid metabolites with specific enrichment in fatty acid pathways. In contrast, serum Na+ and HCO3- showed associations predominantly with amino acids. Cl- and HCO3- association signals, however, helped map patterns based on the Stewart physicochemical model of acid-base chemistry enabling novel insights into electrolyte homeostasis. The heritability of serum electrolytes was estimated in the TwinsUK cohort with serum chloride showing low heritability (A 0.04 (0-0.19)). A genome wide association study meta-analysis was performed using the TwinsUK and Generation Scotland cohorts aiming to identify novel pathways to enhance understanding of electrolyte balance and inform Mendelian randomisation studies. The study was underpowered and there were no SNPs associated with serum Cl- at the conventional genome-wide significance level < 5x10-8. Chapter 6 bring the thesis to conclusion tying together the findings of the epidemiological, genetic and metabolomic studies to pave the path for future work. Serum Cl- is validated as an independent risk predictor for both cardiovascular and non-cardiovascular morbidity and mortality outcomes in the general population.

Published
2020
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8. Assessing Machine Learning for Diagnostic Classification of Hypertension Types Identified by Ambulatory Blood Pressure Monitoring

Author

Bao Tran, Tran Quoc, primary, Lip, Stefanie, additional, du Toit, Clea, additional, Kalaria, Tejas Kumar, additional, Bhaskar, Ravi K., additional, O’Neil, Alison Q., additional, Graff, Beata, additional, Hoffmann, Michał, additional, Szyndler, Anna, additional, Polonis, Katarzyna, additional, Wolf, Jacek, additional, Reddy, Sandeep, additional, Narkiewicz, Krzysztof, additional, Dasgupta, Indranil, additional, Dominiczak, Anna F., additional, Visweswaran, Shyam, additional, McCallum, Linsay, additional, and Padmanabhan, Sandosh, additional

Published
2024
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10. Survey and Evaluation of Hypertension Machine Learning Research

Author

du Toit, Clea, primary, Tran, Tran Quoc Bao, additional, Deo, Neha, additional, Aryal, Sachin, additional, Lip, Stefanie, additional, Sykes, Robert, additional, Manandhar, Ishan, additional, Sionakidis, Aristeidis, additional, Stevenson, Leah, additional, Pattnaik, Harsha, additional, Alsanosi, Safaa, additional, Kassi, Maria, additional, Le, Ngoc, additional, Rostron, Maggie, additional, Nichol, Sarah, additional, Aman, Alisha, additional, Nawaz, Faisal, additional, Mehta, Dhruven, additional, Tummala, Ramakumar, additional, McCallum, Linsay, additional, Reddy, Sandeep, additional, Visweswaran, Shyam, additional, Kashyap, Rahul, additional, Joe, Bina, additional, and Padmanabhan, Sandosh, additional

Published
2023
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13. Unravelling the distinct effects of systolic and diastolic blood pressure using Mendelian randomisation

Author

Le, Nhu Ngoc, Tran, Tran Quoc Bao, Lip, Stefanie, McCallum, Linsay, McClure, John, Dominiczak, Anna F., Gill, Dipender, and Padmanabhan, Sandosh

Subjects
Heart Failure, Stroke, Diabetes Mellitus, Type 2, Atrial Fibrillation, Hypertension, Genetics, Humans, blood pressure, systolic, diastolic, Mendelian randomization, Blood Pressure, Genetics (clinical), Ischemic Stroke
Abstract

A true discrepancy between the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on cardiovascular (CV) outcomes remains unclear. This study performed two-sample Mendelian randomization (MR) using genetic instruments that exclusively predict SBP, DBP or both to dissect the independent effect of SBP and DBP on a range of CV outcomes. Genetic predisposition to higher SBP and DBP was associated with increased risk of coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Genetically proxied SBP exclusively was associated with CAD (OR 1.18, 95% CI: 1.03–1.36, per 10 mmHg), stroke (1.44[1.28–1.62]), ischemic stroke (1.49[1.30–1.69]), HF (1.41[1.20–1.65]), AF (1.28[1.15–1.43]), and T2DM (1.2[1.13–1.46]). Genetically proxied DBP exclusively was associated with stroke (1.21[1.06–1.37], per 5 mmHg), ischemic stroke (1.24[1.09–1.41]), stroke small-vessel (1.35[1.10–1.65]) and CAD (1.19[1.00–1.41]). Multivariable MR using exclusive SBP and DBP instruments showed the predominant effect of SBP on CAD (1.23[1.05–1.44], per 10 mmHg), stroke (1.39[1.20–1.60]), ischemic stroke (1.44[1.25–1.67]), HF (1.42[1.18–1.71]), AF (1.26[1.10–1.43]) and T2DM (1.31[1.14–1.52]). The discrepancy between effects of SBP and DBP on outcomes warrants further studies on underpinning mechanisms which may be amenable to therapeutic targeting.

Published
2022

14. Rationale and design for the LOnger-term effects of SARS-CoV-2 INfection on blood Vessels And blood pRessure (LOCHINVAR)

Author

Lip, Stefanie, McCallum, Linsay, Delles, C., McClure, John D., Guzik, Tomasz, Berry, Colin, Touyz, Rhian, and Padmanabhan, Sandosh

Abstract

Introduction: COVID-19 may lead to long-term endothelial consequences including hypertension, stroke and myocardial infarction. A pilot study ‘COVID-19 blood pressure endothelium interaction study’, which found that patients with normal blood pressure (BP) at the time of hospital admission with COVID-19 showed an 8.6 mm Hg higher BP ≥12 weeks after recovery, compared with a group without COVID-19. The ‘LOnger-term effects of SARS-CoV-2 INfection on blood Vessels And blood pRessure’(LOCHINVAR) study is designed to provide definitive evidence of the long-term impact of COVID-19 on BP.\ud \ud Methods and analysis: The LOCHINVAR study is an observational clinical phenotyping study comparing longitudinal BP change between individuals with and without COVID-19 infection. 150 participants (30–60 years) with no history of hypertension and not on BP lowering medications will be recruited to the study to attend three visits (baseline, 12 months, 18 months). Cases will be patients who were admitted to the Queen Elizabeth University Hospital (QEUH), Glasgow, UK, with suspected/confirmed COVID-19 until 31 December 2021 and who were alive at discharge. Controls will be those who have never had confirmed COVID-19 infection. All participants will undergo clinical and vascular phenotyping studies which will include 24-hour ambulatory BP monitoring systolic BP (ABPM SBP), brachial flow-mediated dilatation urine and blood samples to assess the renin-angiotensin system, vascular inflammation and immune status. The primary outcome is the change in systolic 24-hour ABPM (ABPM SBP) between the cases and controls. Sample size was calculated to detect a mean difference of 5 mm Hg ABPM SBP at 80% power.\ud \ud Ethics and dissemination: The protocol of this study has been approved by the West of Scotland Research Ethics Committee 5 (21/WS/0075), Scotland, UK. Written informed consent will be provided by all study participants. Study findings will be submitted to international peer-reviewed hypertension journals and will be presented at international scientific meetings.\ud \ud Trial registration number NCT05087290.

Published
2022

15. INVESTIGATING THE QUALITY OF MACHINE LEARNING RESEARCH AND REPORTING IN HYPERTENSION

Author

Du Toit, Clea, primary, Tran, Tran, additional, Aryal, Sachin, additional, Lip, Stefanie, additional, Manandhar, Ishan, additional, Sykes, Robert, additional, Pattnaik, Harsha, additional, Deo, Neha, additional, Alsanosi, Safaa, additional, Sionakidis, Aristeidis, additional, Ngoc Le, Nhu, additional, Mccallum, Linsay, additional, Mehta, Dhruven, additional, Kassi, Maria, additional, Rostron, Maggie, additional, Stevenson, Leah, additional, Tummala, Ramakumar, additional, Kashyap, Rahul, additional, Joe, Bina, additional, and Padmanabhan, Sandosh, additional

Published
2022
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18. Additional file 1 of Underrepresentation of ethnic minorities in hypertension research—a survey of enablers and barriers among South Asian and African communities in Glasgow

Author

Lip, Stefanie, Dempster, Georgia, Jain, Sahil, Brooksbank, Katriona, Ghouri, Nazim, McCallum, Linsay, and Padmanabhan, Sandosh

Abstract

Additional file 1. Survey of awareness and attitudes to clinical research and cardiovascular health among ethnic minorities in Glasgow.

Published
2022
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21. Vascular dysfunction and increased cardiovascular risk in hypospadias

Author

Lucas-Herald, Angela K, primary, Montezano, Augusto C, additional, Alves-Lopes, Rheure, additional, Haddow, Laura, additional, Alimussina, Malika, additional, O’Toole, Stuart, additional, Flett, Martyn, additional, Lee, Boma, additional, Amjad, S Basith, additional, Steven, Mairi, additional, Brooksbank, Katriona, additional, McCallum, Linsay, additional, Delles, Christian, additional, Padmanabhan, Sandosh, additional, Ahmed, S Faisal, additional, and Touyz, Rhian M, additional

Published
2022
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22. Predictive Accuracy and Clinical Utility of Machine Learning Prediction for Classifying Blood Pressure Status

Author

Tran, Tran Quoc Bao, primary, Lip, Stefanie, additional, du Toit, Clea, additional, Kalaria, Tejas Kumar, additional, Bhaskar, Ravi K., additional, O’Neil, Alison Q., additional, Graff, Beata, additional, Hoffmann, Michał, additional, Szyndler, Anna, additional, Polonis, Katarzyna, additional, Wolf, Jacek, additional, Reddy, Sandeep, additional, Narkiewicz, Krzysztof, additional, Dasgupta, Indranil, additional, Dominiczak, Anna F., additional, Visweswaran, Shyam, additional, McCallum, Linsay, additional, and Padmanabhan, Sandosh, additional

Published
2022
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23. Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19

Author

Touyz, Rhian M., primary, Boyd, Marcus O.E., additional, Guzik, Tomasz, additional, Padmanabhan, Sandosh, additional, McCallum, Linsay, additional, Delles, Christian, additional, Mark, Patrick B., additional, Petrie, John R., additional, Rios, Francisco, additional, Montezano, Augusto C., additional, Sykes, Robert, additional, and Berry, Colin, additional

Published
2021
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26. Abstract P265: Hypertension, Vascular Dysfunction And Downregulation Of The Renin Angiotensin System Sequelae Of COVID-19

Author

McCallum, Linsay, primary, Lip, Stefanie, additional, Rios, Francisco J, additional, Neves, Karla B, additional, Kilmartin, Jason, additional, Murray, Eleanor, additional, Reetoo, Salil, additional, Knox, Laura, additional, Rostron, Maggie, additional, Lucas-herald, Angela, additional, du Toit, Clea, additional, Guzik, Tomasz J, additional, Delles, Christian, additional, Montezano, Augusto C, additional, Dominiczak, Anna F, additional, Padmanabhan, Sandosh, additional, and Touyz, Rhian M, additional

Published
2021
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27. Abstract P259: Cardiovascular Pharmacotherapy And Covid-19

Author

Lip, Stefanie, primary, McCallum, Linsay, additional, du Toit, Clea, additional, Kilmartin, Jason, additional, Murray, Eleanor, additional, Reetoo, Salil, additional, Knox, Laura, additional, Rostron, Maggie, additional, Guzik, Tomasz J, additional, Delles, Christian, additional, Dominiczak, Anna F, additional, Touyz, Rhian M, additional, and Padmanabhan, Sandosh, additional

Published
2021
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32. THE GLOBAL AMBULATORY BLOOD PRESSURE MONITORING (ABPM) IN HEART FAILURE WITH PRESERVED EJECTION FRACTION (HF-PEF) REGISTRY. RATIONALE, DESIGN AND OBJECTIVES

Author

Camafort, Miguel, primary, Adeseye, Akintunde, additional, Barroso, Weimar Sebba, additional, Coca, Antonio, additional, Damasceno, Albertino, additional, Medina, Angel R. González, additional, Jhund, Pardeep, additional, Kario, Kazuomi, additional, Komori, Takahiro, additional, Lee, Hae -Young, additional, Lip, Stefanie, additional, López-Jaramillo, Patricio, additional, Mccallum, Linsay, additional, Ogah, Okechukwu, additional, Padmanabhan, Sandosh, additional, Pascual, Domingo, additional, Pyun, Wook -Bum, additional, Renna, Nicolas F., additional, Sierra, Cristina, additional, Valdez, Osiris, additional, Wyss, Fernando, additional, Barbosa, Eduardo, additional, Okazaki, Osamu, additional, Yoshida, Tetsuro, additional, and Sani, Mahmoud, additional

Published
2021
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37. May Measurement Month 2018 : an analysis of blood pressure screening results from the UK and the Republic of Ireland

Author

McDonnell, Barry J., Beaney, Thomas, Al Shezawi, Mahfoudha, Cockcroft, John R., Barciela, Carolina, Tay, Tricia, Keitley, James, Brady, Adrian J. B., Padmanabhan, Sandosh, McCallum, Linsay, Dolan, Eamon, O'Brien, Eoin, Tomaszewski, Maciej, Schutte, Aletta E., Poulter, Neil R., Cappuccio, Francesco, International Society of Hypertension and British, and British and Irish Hypertension Society

Subjects
RA0421, QP
Abstract

Raised blood pressure (BP) was the biggest contributor to the global burden of disease in 2017, with lack of awareness and adequate control of BP identified as the main drivers of this disease burden. In 2017, an opportunistic BP screening and awareness campaign called May Measurement Month (MMM) in the UK and Republic of Ireland (RoI) highlighted that levels of undiagnosed hypertension and uncontrolled hypertension in the community screened were approximately 23% and 40%, respectively. MMM18 was undertaken to further the campaign’s efforts to increase awareness and create an evidence base of population risk associated with high BP. MMM18 BP screenings were conducted in the community at places of worship, supermarkets, GP surgeries, workplaces, community pharmacies, gyms, and various other public places. A total of 5000 volunteers, aged 47.3 (617.2) years, 60% female were screened. Of all 5000 individuals screened, 1716 (34.3%) were hypertensive, of which only 51.3% were aware of their condition, 42.8% on antihypertensive treatment, and only 51.5% of those on medication controlled to target BP of

Published
2020

39. May Measurement Month 2018: an analysis of blood pressure screening results from the UK and the Republic of Ireland

Author

McDonnell, Barry J, primary, Beaney, Thomas, additional, Al Shezawi, Mahfoudha, additional, Cockcroft, John R, additional, Barciela, Carolina, additional, Tay, Tricia, additional, Keitley, James, additional, Brady, Adrian J B, additional, Padmanabhan, Sandosh, additional, McCallum, Linsay, additional, Dolan, Eamon, additional, O’Brien, Eoin, additional, Tomaszewski, Maciej, additional, Schutte, Aletta E, additional, Poulter, Neil R, additional, and Cappuccio, Franco P, additional

Published
2020
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41. Risk Prediction for Acute Kidney Injury in Acute Medical Admissions in the UK

Author

Blackburn, Anna, Gunda, Smita, Lopez, Berenice, Edwards, James, Spittle, Nick, Preston, Rob, Baines, Richard, Little, Jane, Falayajo, Akin, Mahmoud, Huda, Selby, Nicholas M., Shaw, Sue, Trowbridge, Stephen, Coutinho, Andrew, Samarasinghe, Yohan, Farmer, Chris, Beeson, Claire, John, Ian, Gisby, Sharon, Forni, Lui, Dachsel, Martin, Fallouh, Bassam, Ward, Emily, Sood, Bhrigu, Ostermann, Marlies, Mohanty, Manab, Robert, Stephanie, MacLaughlin, Helen, Banerjee, Anita, Wright, Kelly, Tomlinson, Laurie, Wolff, Jacob de, Laing, Chris, Prowle, John, DeFreitas, Sarah, Balasubramaniam, Gowrie, McGuinness, Daniel, Murray, John, Kanagasundaram, Suren, Harron, Camille, Magee, Brian, Harty, John, Maxwell, Peter, Morgan, Neal, Leaonard, Niall, McCarroll, Frank, Kuan, Ying, Chakarborty, Tapas, Ahmed, Aimun, Ponnusamy, Arvind, Brown, Becky, Ahmed, Shahed, Henney, Bob, Hammersley, Shirley, Obale, Begho, Nipah, Rob, Al-Sayed, Tam, Varia, Ragit, Skinner, Christopher, Young, Innes, Clark, Laura, Bassiouni, Ibrahim, Finlay, Sian, Moonie, Alasdair, Douglas, Alistair, Bell, Samira, Duthie, Fiona, Thetford, David, White, Beth, McQuarrie, Emily, McCallum, Linsay, Campbell, Iona, Millar, James, McCormick, Jenna L., Allen, Ruridh, Jamdar, Ravi, Murray, Eleanor, Hand, Malcolm, Harmouche, Ali, Fattah, Hasan, Farquhar, Fiona, Condy-Young, Helen, Morrison, Jennifer, Power, Bert, Udayaraj, Uday, Murray, Paul, Mulgrew, Chris, Boddana, Preetham, Prescott, Craig, Uniake, Mark, Bonfield, Becky, Edwards, Helena, Armstrong, Kirsty, Whitehead, Duncan, Miller, Alice, Waters, Helen, Carr, Steve, Dickenson, Steve, Subbe, Chris, Phillips, Aled, Thomas, David, Lewis, Aled, Chess, James, Price, David, Mizen, Paul, Ramasamy, Vijaya, Thomas, Mark, Hewins, Pete, Carmichael, Paul, Chand, Rob, Ramaswamy, Diwaker, Thompson, Chris, Morgan, James, Lobaz, Steven, Oh, Weng, Stoves, John, Ali, Asifa, Ali, Mansoor, Awais, Muhammed, Naudeer, Sarah, Lewington, Andy, McDonald, Suzanne, Naeem, Haroon, and Than, Nilar

Subjects
Male, medicine.medical_specialty, Kidney Function Tests, Risk Assessment, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Risk factor, Aged, Aged, 80 and over, Framingham Risk Score, business.industry, Acute kidney injury, General Medicine, Odds ratio, Acute Kidney Injury, Middle Aged, Prognosis, medicine.disease, United Kingdom, Confidence interval, Hospitalization, Logistic Models, Creatinine, Multivariate Analysis, Female, Risk assessment, business, Cohort study, Kidney disease
Abstract

Background Acute Kidney Injury (AKI) is associated with adverse outcomes; identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. This approach is advocated in national guidelines but is not well studied in acutely unwell medical patients. We therefore aimed to undertake a UK-wide study in acute medical units (AMUs) with the following aims: to define the proportion of acutely unwell medical patients who develop hospital-acquired AKI (hAKI); to determine risk factors associated with the development of hAKI; and to assess the feasibility of using these risk factors to develop an AKI risk prediction score. Methods In September 2016, a prospective multicentre cohort study across 72 UK AMUs was undertaken. Data were collected from all patients who presented over a 24-hour period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were subsequently excluded. The primary outcome was the development of h-AKI. Results 2,446 individuals were admitted to the AMUs of the 72 participating centres. 384 patients (16%) sustained AKI of whom 287 (75%) were cAKI and 97 (25%) were hAKI. After exclusions, 1,235 participants remained in whom chronic kidney disease (OR 3.08, 95% CI 1.96-4.83), diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and an elevated serum bilirubin were independently associated with development of hAKI. Multivariable model discrimination was moderate (c-statistic 0.75), and this did not support the development of a robust clinical risk prediction score. Mortality was higher in those with hAKI (adjusted OR 5.22; 95% CI 2.23-12.20). Conclusion AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. The smaller proportion of hAKI cases, only moderate discrimination of prognostic risk factor modelling and the resource implications of widespread application of an AKI clinical risk score across all AMU admissions suggests that this approach is not currently justified. More targeted risk assessment or automated methods of calculating individual risk may be more appropriate alternatives.

Published
2018

44. Rationale and Design of the Genotype-Blinded Trial of Torasemide for the Treatment of Hypertension (BHF UMOD).

Author

McCallum, Linsay, Brooksbank, Katriona, McConnachie, Alex, Aman, Alisha, Lip, Stefanie, Dawson, Jesse, MacIntyre, Iain M, MacDonald, Thomas M, Webb, David J, and Padmanabhan, Sandosh

Subjects
CLINICAL trial registries, SINGLE nucleotide polymorphisms, UROMODULIN, BLOOD pressure, HYPERTENSION
Abstract

BACKGROUND Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the uromodulin gene (UMOD) affecting uromodulin excretion and blood pressure (BP). Uromodulin is almost exclusively expressed in the thick ascending limb (TAL) of the loop of Henle and its effect on BP appears to be mediated via the TAL sodium transporter, NKCC2. Loop-diuretics block NKCC2 but are not commonly used in hypertension management. Volume overload is one of the primary drivers for uncontrolled hypertension, so targeting loop-diuretics to individuals who are more likely to respond to this drug class, using the UMOD genotype, could be an efficient precision medicine strategy. METHODS The BHF UMOD Trial is a genotype-blinded, multicenter trial comparing BP response to torasemide between individuals possessing the AA genotype of the SNP rs13333226 and those possessing the G allele. 240 participants (≥18 years) with uncontrolled BP, on ≥1 antihypertensive agent for ≥3 months, will receive treatment with Torasemide, 5 mg daily for 16 weeks. Uncontrolled BP is average home systolic BP (SBP) >135 mmHg and/or diastolic BP >85 mmHg. The primary outcome is the change in 24-hour ambulatory SBP area under the curve between baseline and end of treatment. Sample size was calculated to detect a 4 mmHg difference between groups at 90% power. Approval by West of Scotland Research Ethics Committee 5 (16/WS/0160). RESULTS The study should conclude August 2021. CONCLUSIONS If our hypothesis is confirmed, a genotype-based treatment strategy for loop diuretics would help reduce the burden of uncontrolled hypertension. CLINICAL TRIALS REGISTRATION https://clinicaltrials.gov/ct2/show/NCT03354897. [ABSTRACT FROM AUTHOR]

Published
2021
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45. May Measurement Month 2019: an analysis of blood pressure screening results from the United Kingdom and Republic of Ireland

Author

McDonnell, Barry J, Rees, Emma, Cockcroft, John R, Beaney, Thomas, Clayton, Bethan, Le Kieu, Phuong, Brady, Adrian J B, Padmanabhan, Sandosh, McCallum, Linsay, Dolan, Eamon, O’Brien, Eoin, Tomaszewski, Maciej, Schutte, Aletta E, Poulter, Neil R, and Cappuccio, Francesco P

Abstract

In the UK, heart and circulatory diseases account for 29% of all deaths (14% through coronary heart disease and 8% through stroke). In 2015, the prevalence of hypertension was 20% in the UK and 23% in the Republic of Ireland. In 2019, 14% of people registered with a UK general practice had hypertension and yet it was the attributable risk factor for around half of all deaths from coronary heart disease or stroke. We participated in May Measurement Month 2019 to increase awareness of blood pressure (BP) measurement, and to identify the proportion of undiagnosed hypertension and degree of uncontrolled hypertension in the community. The 2019 campaign set up screening sites within the community at places of worship, supermarkets, GP surgeries, workplaces, charity events, community pharmacies, gyms, and various other public places. We screened 10194 participants (mean age 51 ± 18 years, 60% women) and found that 1013 (9.9%) were on antihypertensive treatment, while 3408 (33.4%) had hypertension. Of the 3408 participants with hypertension, only 33.5% were aware of their condition despite 98.8% having previous BP measurements. In those on antihypertensive medication, only 38.2% had controlled BP (<140 and <90 mmHg). Our UK and Republic of Ireland data demonstrate concerning levels of undiagnosed hypertension and sub-optimal BP control in many individuals with a diagnosis. This evidence supports a critical need for better systematic community and primary care screening initiatives.

Published
2021
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50. Impact of treatment algorithms on the prescribing of antithrombotic therapy in patients with suspected acute coronary syndrome – a prospective audit

Author

Cameron, Alan C, McCallum, Linsay, Gardiner, Thomas, Darroch, Claire, Walters, Matthew R, and Oldroyd, Keith G

Subjects
Male, Medical Audit, Therapeutics, Middle Aged, Sensitivity and Specificity, Fibrinolytic Agents, ROC Curve, Predictive Value of Tests, Practice Guidelines as Topic, Humans, Female, Prospective Studies, Acute Coronary Syndrome, Algorithms
Abstract

Chest pain presentations are common although most patients do not have an acute coronary syndrome (ACS). We hypothesized that our local therapeutic guideline was leading to many low risk patients being inappropriately treated with potent anti-thrombotic therapy for ACS.We conducted a prospective analysis of patients presenting with suspected ACS to the Western Infirmary Glasgow over a 2 month period between 6/10/13-3/11/13 and 5/4/14-2/5/14. We collated data on demographics, investigation, initial management and final diagnosis. Patients taking warfarin were excluded. We calculated sensitivity, specificity and receiver operating characteristic (ROC) curves for our local guideline, the SIGN guideline and a new guideline proposal.We studied 202 patients of whom 112 (55%) were male with mean (SD) age 60 (15) years. Full anti-thrombotic therapy for ACS was recommended in 91 patients (45%) according to the NHS GGC guideline, 37 (18%) by the SIGN guideline and 30 (15%) by our new guideline proposal. The final diagnosis was ACS in 39 patients (19%). The current NHS GGC guideline had a sensitivity of 80%, specificity 63% and AUROC 0.71 (95% CI 0.63, 0.80). The respective values were 62%, 92% and 0.77 (95% CI 0.67, 0.86) for the SIGN guideline and 54%, 94% and 0.74 (95% CI 0.64, 0.84) for our new proposed guideline.Only one-fifth of patients who present with chest pain or suspected ACS have ACS as their final diagnosis. Our new guideline proposal is highly specific and would minimize unnecessary administration of potent anti-thrombotic therapy to low risk patients.

Published
2015

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