Imperial College London

ProfessorPeterSever

Faculty of MedicineNational Heart & Lung Institute

Professor of Clinical Pharmacology & Therapeutics
 
 
 
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Contact

 

+44 (0)20 7594 1099p.sever

 
 
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Assistant

 

Mrs Yvonne Green +44 (0)20 7594 1100

 
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Location

 

333ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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899 results found

Wang J-G, Palmer BF, Vogel Anderson K, Sever Pet al., 2023, Amlodipine in the current management of hypertension., Journal of Clinical Hypertension, ISSN: 1524-6175

Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which amlodipine, a dihydropyridine, has unique characteristics that distinguish it from other drugs within this class. This review aims to provide an updated overview of the evidence supporting the use of amlodipine over the past 30 years and highlights its cardiovascular benefits in current hypertension management. Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35-50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg. Amlodipine is cost effective and predicted to be cost saving when compared with usual care.

Journal article

Girerd N, Levy D, Duarte K, Ferreira JP, Ballantyne C, Collier T, Pizard A, Björkman J, Butler J, Clark A, Cleland JG, Delles C, Diez J, González A, Hazebroek M, Ho J, Huby A-C, Hwang S-J, Latini R, Mariottoni B, Mebazaa A, Pellicori P, Sattar N, Sever P, Staessen JA, Verdonschot J, Heymans S, Rossignol P, Zannad Fet al., 2023, Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study., Circ Heart Fail, Vol: 16

BACKGROUND: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. METHODS: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). RESULTS: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C-index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%-14.7%) in ARIC, 5.9% (2.6%-9.2%) in FHS, and 7.5% (5.4%-9.5%) in HOMAGE cohort, all P<0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis). CONCLUSIONS: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Journal article

Sever P, Gupta A, Whiteley W, Godec T, Rostamian S, Mackay J, Poulter N, Whitehouse Aet al., 2023, THE ASCOT LEGACY COHORT: THE LONG-TERM EFFECTS OF BLOOD PRESSURE AND BLOOD PRESSURE VARIABILITY ON CARDIOVASCULAR AND RENAL OUTCOMES, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E67-E68, ISSN: 0263-6352

Conference paper

Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu K-HH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao J-H, Matsuda F, Jang H-M, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu C-M, Hung Y-J, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim H-N, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukolet al., 2022, Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis., Genome Biol, Vol: 23

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Journal article

Kulkarni S, Glover M, Kapil V, Abrams SML, Partridge S, McCormack T, Sever P, Delles C, Wilkinson IBet al., 2022, Management of hypertensive crisis: British and Irish Hypertension Society Position document, Journal of Human Hypertension, ISSN: 0950-9240

Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.

Journal article

Collaborat CTTC, Reith C, Baigent C, Blackwell L, Emberson J, Spata E, Davies K, Halls H, Holland L, Wilson K, Armitage J, Harper C, Preiss D, Roddick A, Keech A, Simes J, Collins R, Fulcher J, Herrington WG, Kirby A, Mihaylova B, O'Connell R, Banks E, Blastland M, Evans S, Temple R, Weissberg P, Wittes J, Blazing M, Braunwald E, de Lemos J, Murphy S, Pedersen TR, Pfeffer M, White H, Wiviott S, Clearfield M, Downs JR, Gotto Jr A, Weis S, Fellstroem B, Holdaas H, Jardine A, Gordon D, Davis B, Furberg C, Grimm R, Pressel S, Probstfield J, Rahman M, Simpson Let al., 2022, Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials, LANCET, Vol: 400, Pages: 832-845, ISSN: 0140-6736

Journal article

Judah G, Wingfield D, Dryden S, Sun Q, Chang M, Mackay J, Sever Pet al., 2022, Adherence to antihypertensive drugs: measuring self-reported and objective levels of adherence and reasons for non-adherence in UK patients with hypertension, Publisher: SPRINGERNATURE, Pages: 7-7, ISSN: 0950-9240

Conference paper

Rostamian S, Godec T, Gupta A, Whiteley WN, Mackay J, Whitehouse A, Sever Pet al., 2022, Systolic blood pressure variability is a major risk factor for renal outcomes in hypertensive patients: Evidence from the 20-year follow-up of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), Publisher: SPRINGERNATURE, Pages: 21-21, ISSN: 0950-9240

Conference paper

Nazarzadeh M, Bidel Z, Canoy D, Copland E, Bennett DA, Dehghan A, Davey Smith G, Holman RR, Woodward M, Gupta A, Adler AI, Wamil M, Sattar N, Cushman WC, McManus RJ, Teo K, Davis BR, Chalmers J, Pepine CJ, Rahimi K, Blood Pressure Lowering Treatment Trialists' Collaborationet al., 2022, Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis, The Lancet Diabetes and Endocrinology, Vol: 10, Pages: 645-654, ISSN: 2213-8595

BACKGROUND: Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. METHODS: We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and th

Journal article

Rostamian S, Godec T, Gupta AK, Whiteley W, Mackay J, Whitehouse A, Sever Pet al., 2022, Visit-To-Visit Blood Pressure Variability Is A Major Risk Factor For Renal Outcomes In Hypertensive Patients: Evidence From The 20-Year Follow-Up Of The AngloScandinavian Cardiac Outcomes Trial (ASCOT), Hypertension Scientific Sessions of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0194-911X

Conference paper

Fagundes A, Morrow DA, Oyama K, Furtado RHM, Zelniker TA, Tang M, Kuder JF, Murphy SA, Hamer A, Keech AC, Sever P, Giugliano RP, Sabatine MS, Bergmark BAet al., 2022, Biomarker prediction of complex coronary revascularization procedures in the FOURIER trial, Journal of the American College of Cardiology, Vol: 80, Pages: 887-897, ISSN: 0735-1097

BackgroundBiomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.ObjectivesWe examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.MethodsFOURIER was a randomized trial of the proprotein convertase subtilisin–kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro–B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL).ResultsWhen patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each).ConclusionsA biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk cor

Journal article

Ramdas S, Judd J, Graham SE, Kanoni S, Wang Y, Surakka I, Wenz B, Clarke SL, Chesi A, Wells A, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu K-HH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao J-H, Matsuda F, Jang H-M, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Lee W-J, Hsiung CA, Warren HR, Ramirez J, Bork-Jensen J, Karhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Mollehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Schonherr S, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Le P, Feitosa MF, Wojczynski MK, Hemerich D, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Noah TL, Verma A, Slieker RC, Lo KS, Zilhao NR, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Emmel C, Schmidt B, Smyth LJ, Canadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kahonen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Sankareswaran A, Irvin MR, Oldmeadow C, Kim H-N, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lores-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukolaet al., 2022, A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 109, Pages: 1366-1387, ISSN: 0002-9297

Journal article

Oggero S, Godec T, van Gorp R, Pinto AL, Schurgers LJ, Reutelingsperger C, Sever P, Norling LV, Perretti M, Gupta Aet al., 2022, Role of plasma extracellular vesicles in prediction of cardiovascular risk and alterations in response to statin therapy in hypertensive patients., Journal of Hypertension, Vol: 40, ISSN: 0263-6352

BACKGROUND: Rapid and accurate new biomarkers to predict risk of cardiovascular disease (CVD) are essential. The utility of extracellular vesicles in predicting the CVD risk is postulated, yet it remains unknown whether their expression is altered in response to statin therapy. METHODS: We performed in-vitro studies with human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (hVSMC), and conducted a nested case-control study (nCCS) in hypertensive patients (n = 40) randomized to either atorvastatin or placebo in the ASCOT-LLA. Cases had a major adverse cardiovascular event or death (MACE) during 3.5 years of follow-up (median) from the time of extracellular vesicle characterization while controls, matched for age and duration of treatment, remained event-free. Conditional logistic regression models determined the risk of MACE. Additionally, the relationship of extracellular vesicle levels with statin therapy was assessed. RESULTS: Added to HUVEC, extracellular vesicles increased neutrophil recruitment, and to hVSMC, aggravated calcification and proliferation. In the nCCS, compared with controls, cases (i.e. with MACE) had preceding higher levels of CD14+ and CD14+/CD41+ extracellular vesicles (P = 0.009 and P = 0.012, respectively) and a significant reduction in the median size of the vesicles (P = 0.037). On matched analysis, higher CD14+ extracellular vesicles were associated with a 3.7-fold increased risk of MACE (P = 0.032). Patients treated with atorvastatin (vs. placebo) had both reduced size of extracellular vesicles and the proportion of CD146+ extracellular vesicles (P = 0.034 and P = 0.020, respectively). CONCLUSION AND RELEVANCE: These pilot analyses suggest a mechanistic role for extracellular vesicles in the development of CVD, with significant and differential changes in extracellular vesicles amongst those at risk of MACE, and those on atorvastatin therapy.

Journal article

Rastogi T, Ho FK, Rossignol P, Merkling T, Butler J, Clark A, Collier T, Delles C, Jukema JW, Heymans S, Latini R, Mebazaa A, Pellicori P, Sever P, Staessen JA, Thijs L, Cleland JG, Sattar N, Zannad F, Girerd Net al., 2022, Comparing and contrasting risk factors for heart failure in patients with and without history of myocardial infarction: data from HOMAGE and the UK Biobank, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 24, Pages: 976-984, ISSN: 1388-9842

Journal article

Cappuccio FP, Campbell NRC, He FJ, Jacobson MF, MacGregor GA, Antman E, Appel LJ, Arcand J, Blanco-Metzler A, Cook NR, Guichon JR, L'Abbe MR, Lackland DT, Lang T, McLean RM, Miglinas M, Mitchell I, Sacks FM, Sever PS, Stampfer M, Strazzullo P, Sunman W, Webster J, Whelton PK, Willett Wet al., 2022, Sodium and health: old myths and a controversy based on denial, Current Nutrition Reports, Vol: 11, Pages: 172-184, ISSN: 2161-3311

Journal article

Korthauer LE, Giugliano RP, Guo J, Sabatine MS, Sever P, Keech A, Atar D, Kurtz C, Ruff CT, Mach F, Ott BRet al., 2022, No association between APOE genotype and lipid lowering with cognitive function in a randomized controlled trial of evolocumab, PLOS ONE, Vol: 17, ISSN: 1932-6203

Journal article

Sever PP, 2022, Nocebo affects after COVID-19 vaccination, The Lancet Regional Health - Europe, Vol: 12, Pages: 1-2, ISSN: 2666-7762

Journal article

Pavey H, Kulkarni S, Wood A, Ben-Shlomo Y, Sever P, McEniery C, Wilkinson Iet al., 2022, Primary hypertension, anti-hypertensive medications and the risk of severe COVID-19 in UK Biobank., PLoS One, Vol: 17, Pages: 1-14, ISSN: 1932-6203

Hypertension appears to be one of the commonest comorbidities in COVID-19 patients, although whether hypertensive individuals have a higher risk of severe COVID-19 compared with non-hypertensives is unclear. It is also unclear whether the absolute level of systolic blood pressure, or the type of anti-hypertensive medication is related to this risk. Analyses were conducted using data from the UK Biobank and linked health records. Logistic regression models were fitted to assess the impact of hypertension, systolic blood pressure (SBP) and medications on the risk of severe COVID-19. 16,134 individuals tested positive for severe acute respiratory syndrome-coronavirus, 22% (n = 3,584) developed severe COVID-19 and 40% (n = 6,517) were hypertensive. Hypertension was associated with 22% higher odds of severe COVID-19 (Odds ratio (OR) 1.22; 95% confidence interval (CI) 1.12, 1.33), compared with normotension after adjusting for confounding variables. In those taking anti-hypertensive medications, elevated SBP showed a dose-response relationship with severe COVID-19 (150-159mmHg versus 120-129mmHg (OR 1.91; 95% CI 1.44, 2.53), &gt;180+mmHg versus 120-129mmHg (OR 1.93; 95% CI 1.06, 3.51)). SBP &lt;120mmHg was associated with greater odds of severe COVID-19 (OR 1.40; 95% CI 1.11, 1.78). Angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers were not associated with altered risk of severe COVID-19. Hypertension is an important risk factor for COVID-19. A better understanding of the underlying mechanisms is warranted in case of more severe strains or other viruses in the future.

Journal article

Oyama K, Giugliano RP, Tang M, Bonaca MP, Saver JL, Murphy SA, Ruzza A, Keech AC, Sever PS, Sabatine MS, Bergmark BAet al., 2021, Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 4821-4829, ISSN: 0195-668X

Journal article

Graham SE, Clarke SL, Wu K-HH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao J-H, Matsuda F, Jang H-M, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Karhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Mollehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Phuong L, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Canadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kahonen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Irvin MR, Oldmeadow C, Kim H-N, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lores-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung Y-J, Chen S, Liu F, Yaet al., 2021, The power of genetic diversity in genome-wide association studies of lipids, NATURE, Vol: 600, Pages: 675-+, ISSN: 0028-0836

Journal article

Marston NA, Giugliano RP, Park J-G, Ruzza A, Sever PS, Keech AC, Sabatine MSet al., 2021, Cardiovascular Benefit of Lowering Low-Density Lipoprotein Cholesterol Below 40 mg/dL, CIRCULATION, Vol: 144, Pages: 1732-1734, ISSN: 0009-7322

Journal article

Mujaj B, Zhang Z-Y, Yang W-Y, Thijs L, Wei F-F, Verhamme P, Delles C, Butler J, Sever P, Latini R, Cleland JGF, Zannad F, Staessen JAet al., 2021, Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis, ESC HEART FAILURE, Vol: 9, Pages: 685-694, ISSN: 2055-5822

Journal article

Keech AC, Oyama K, Sever PS, Tang M, Murphy SA, Hirayama A, Lu C, Tay L, Deedwania PC, Siu C-W, Pineda AL, Choi D, Charng M-J, Amerena J, Ahmad WAW, Chopra VK, Pedersen TR, Giugliano RP, Sabatine MSet al., 2021, Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects - A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial -, CIRCULATION JOURNAL, Vol: 85, Pages: 2063-+, ISSN: 1346-9843

Journal article

Ratneswaren A, Shah ASV, Thom SA, Sharp ASP, Francis DF, Stanton AV, Poulter NR, Sever PS, Hughes AD, Mayet Jet al., 2021, Tissue Doppler E prime velocity and E/E prime predict 19-year cardiovascular mortality in hypertension, Publisher: OXFORD UNIV PRESS, Pages: 2336-2336, ISSN: 0195-668X

Conference paper

Marston NA, Giugliano RP, Park JG, Ruzza A, Sever PS, Keech AC, Sabatine MSet al., 2021, Cardiovascular benefit of lowering LDL-C below 1 mmol/L (40 mg/dl), Publisher: OXFORD UNIV PRESS, Pages: 2585-2585, ISSN: 0195-668X

Conference paper

Oyama K, Giugliano R, Tang M, Bonaca M, Saver J, Murphy S, Ruzza A, Sever P, Sabatine M, Bergmark Bet al., 2021, Acute arterial events across all vascular territories in the FOURIER trial, Publisher: OXFORD UNIV PRESS, Pages: 2947-2947, ISSN: 0195-668X

Conference paper

Whiteley WN, Gupta AK, Godec T, Rostamian S, Whitehouse A, Mackay J, Sever PSet al., 2021, Long-Term Incidence of Stroke and Dementia in ASCOT, STROKE, Vol: 52, Pages: 3088-3096, ISSN: 0039-2499

Journal article

Howard J, Wood F, Finegold J, Nowbar A, Thompson DM, Arnold A, Rajkumar C, Connolly S, Cegla J, Stride C, Sever P, Northon C, Thom S, Shun-Shin M, Francis Det al., 2021, Side effect patterns in a crossover trial of statin, placebo and no treatment, Journal of the American College of Cardiology, Vol: 78, Pages: 1210-1222, ISSN: 0735-1097

BackgroundMost people who begin statins abandon them, most commonly because of side-effects. ObjectivesAssess daily symptom scores on statin, placebo and no treatment in participants who had abandoned statins.MethodsParticipants received 12 one-month medication bottles, 4 containing atorvastatin 20mg, 4 placebo and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the nocebo ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. Results60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% confidence interval 4.7 to 11.3) in no-tablet months. It was higher in statin months (16.3, 13.0 to 19.6, p<0.001), but also in placebo months (15.4, 12.1 to 18.7, p<0.001), with no difference between the two (p=0.388). The corresponding nocebo ratio was 0.90.In the individual-patient daily data, neither symptom intensity on starting (odds ratio 1.02, 95% CI 0.98 to 1.06, p=0.28) nor extent of symptom relief on stopping (1.01, 95% CI 0.98 to 1.05, p=0.48) distinguished between statin and placebo.Stopping was no more frequent for statin than placebo (p=0.173), and subsequent symptom relief was similar between statin and placebo.6 months after the trial, 30/60 (50%) of participants were back taking statins. ConclusionsThe majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo.

Journal article

Rahimi K, Bidel Z, Nazarzadeh M, Copland E, Canoy D, Wamil M, Majert J, McManus RJ, Chalmers J, Davis BR, Pepine CJ, Teo KKet al., 2021, Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis, The Lancet, Vol: 398, Pages: 1053-1064, ISSN: 0140-6736

BackgroundThe effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.MethodsWe did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.FindingsWe included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and

Journal article

Sever P, Gouni-Berthold I, Keech A, Giugliano R, Pedersen TR, Im K, Wang H, Knusel B, Sabatine MS, O'Donoghue MLet al., 2021, LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial., European Journal of Preventive Cardiology, Vol: 28, Pages: 805-812, ISSN: 2047-4873

AIMS: Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor. METHODS AND RESULTS: FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan-Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72-0.96, Q2 0.88, 0.76-1.01, Q3 0.82, 0.71-0.95, Q4 0.86, 0.74-1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61-0.89), Q2 0.83 (0.69-1.00), Q3 0.78 (0.65-0.94), Q4 0.82 (0.69-0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan-Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69-0.95) and 0.74 (0.61-0.90), respectively) compared with men (0.86 (0.80-0.94) and 0.81 (0.73-0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, ther

Journal article

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