Sverre E. Kjeldsen

Bio: Sverre E. Kjeldsen is an academic researcher from University of Oslo. The author has contributed to research in topics: Blood pressure & Left ventricular hypertrophy. The author has an hindex of 94, co-authored 735 publications receiving 89059 citations. Previous affiliations of Sverre E. Kjeldsen include University of Michigan & Cornell University.

Heart failure with preserved ejection fraction

Abstract: Heart failure with preserved ejection fraction (HFpEF) is a complex clinical condition. Initially called diastolic heart failure, it soon became clear that this condition is more than the opposite side of systolic heart failure. It is increasingly prevalent and lethal. Currently, HFpEF represents more than 50% of heart failure cases and shares a 90-day mortality and readmission rate similar to heart failure with reduced ejection fraction. Heart failure with preserved ejection fraction is best considered to be a systemic disease. From a cardiovascular standpoint, it is not just a stiff ventricle. A stiff ventricle combined with a stiff arterial and venous system account for the clinical manifestations of flash pulmonary edema and the marked changes in renal function or systemic blood pressure with minor changes in fluid volume status. No effective pharmacologic treatments are avail able for patients with HFpEF, but an approach to the musculoskeletal system has merit: the functional limitations and exercise intolerance that patients experience are largely due to abnormalities of peripheral vascular function and skeletal muscle dysfunction. Regular exercise training has strong objective evidence to support its use to improve quality of life and functional capacity for patients with HFpEF. This clinical review summarizes the current evidence on the pathophysiologic aspects, diagnosis, and management of HFpEF.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH).

Abstract: DOCUMENT REVIEWERS Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Anthony Heagerty (UK), Slavomira Filipova (Slovak Republic), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

Genetic variation and predicted phenotypes in cyp2c9, cyp2c19, cyp3a4, cyp3a5 and cyp2d6 genes among 552 patients with uncontrolled treated hypertension

Abstract: Objective: Altered drug metabolism may be a contributing factor to uncontrolled hypertension. Beta-blockers, alpha-blockers, calcium antagonists and angiotensin receptor blockers undergo hepatic metabolism by cytochrome P450 (CYP) enzymes. Genetic variation can contribute to interindividual variation, lack of treatment response or side effects with discontinuation of treatment. We aimed to determine common CYP gene variations in patients with treated but uncontrolled hypertension and to compare the distribution with the prevalence in the overall Caucasian population. Design and method: In this national multicenter study we mapped CYP2D6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in 552 patients prescribed > = 2 antihypertensive agents and with systolic daytime ambulatory blood pressure (ABPM) > = 135 mmHg. On the (MALDI-TOF) MassARRAY analyzer, single nucleotide variants and small insertions/deletions (indels) were investigated with the VeriDose Core Panel and CYP2D6 copy-number variation with the VeriDose CYP2D6 CNV Panel (Agena Biosciences). Each allele is associated with either normal, decreased, absent, increased or unknown enzyme function based on activity scores defined by the The Clinical Pharmacogenetics Implementation Consortium (CPIC) and describe function and phenotypes for genes (IM = Intermediate metabolizer, PM = poor metabolizer, RM = rapid metabolizer and UM = ultra-rapid metabolizer). Results: 94% of patients were Caucasian. Mean daytime ABPM was 146/84 mmHg (135-190/55-106 mmHg), median age 63 (26-86) years and 35% were female. The distributions of the predicted phenotypes (illustrated in colors in Figure) for each enzyme did not differ from that reported in Caucasian population by The Pharmacogenomics Knowledgebase (PharmGK) (gray). 11% had normal phenotype in all five enzymes whereas 49% had > = 2 enzymes affected by gene variants. Conclusions: The phenotype distribution of five relevant CYP genes in patients with uncontrolled hypertension did not differ from the general Caucasian population. Dosing guidelines based on CYP2D6 genotype currently exist for metoprolol, but for other antihypertensive drugs further investigation is needed. The low proportion of patients with five normal enzymes and the high proportion with > = 2 enzymes affected suggest that pharmacogenetic CYP-testing may be useful for individualizing drug treatment in patients with uncontrolled hypertension.

Revisiting the pre-hypertension debate: Increasing evidence for treatment – or not?

Abstract: The editors of Blood Pressure , although accepting the paper by Reed et al. (1) for publication inasmuch as it is nicely reviewing many studies showing high cardiovascular risk associated with pre-hypertension and high normal blood pressure, would like to extend the reservation expressed by Gordon T. McInnes in his letter response to the editors. We herewith in the paragraph below repeat the abstract written by Gordon T. McInnes in 2009 (3).

Valuable lessons from VALUE.

Abstract: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which was started in 1997 by including the first patient by September 10 and closed-out by December 5, 2003, is one of the major outcome trials investigating angiotensin II type 1 receptor antagonism in hypertension [1–3]. The study compared treatment with valsartan with that of the calcium antagonist amlodipine, and the Executive Committee has now published the main outcome data from the 15313 randomized patients from 31 countries as well as their interpretations of the results [4, 5]. The main hypothesis in VALUE was that there would be a 12.5% incidence of cardiac morbidity and mortality in the amlodipine group and a 10.6% incidence in the valsartan group, i.e. a reduction by 15%, during the course of the follow-up of the hypertensive cohort with increased risks [4]. The study was event driven and the initial anticipation was that at least 1450 valid endpoints should occur in the cohort. At study closure, the primary composite cardiac mortality and morbidity endpoint had occurred in 1599 patients [4]. Secondary endpoints in VALUE were cardiac morbidity, cardiac mortality, total mortality, stroke morbidity or mortality, fatal and nonfatal myocardial infarction, fatal or worsening of heart failure, or new-onset diabetes mellitus [4]. The final results of VALUE showed that the primary composite cardiac outcome (RR 1.04; 95% CI 0.94–1.15, p = 0.49 valsartan vs amlodipine), did not differ between the treatment groups [4]. Thus, VALUE demonstrated no difference in its primary endpoint (i.e. time to first cardiac event), and was not able to demonstrate superiority of valsartan compared to amlodipine. As for pre-specified secondary outcomes, there were 19% more myocardial infarctions overall, more strokes in the valsartan group initially but not overall at study end [4] and a trend for less heart failure on valsartan. Interestingly, new-onset diabetes was reduced by 33% in the valsartan group [4]. What is clear from the published results of VALUE is that inferior blood pressure control was achieved in the valsartan group as compared with its comparator. This was achieved in spite of the ambition to reach below the 140/90 mmHg target by either valsartan (80–160 mg) or amlodipine (5 or 10 mg), which could be combined with HCTZ as well as other allowed drug combinations [1–4]. During the course of the trial, gradually larger proportions of the treated patient cohort achieved blood pressure targets, and after 30 months of treatment, 62% of all patients had reached the systolic target of 140 mmHg and 90% of patients had reached the diastolic target of below 90 mmHg [2, 3]. However, in the final analysis, it became clear that in patients randomized to starting treatment with amlodipine, there was a more rapid initial fall as well as more extensive reduction in systolic as well as diastolic blood pressures. Although this was not reflected in differences in the primary composite cardiac endpoint at study end, the discrepancy in blood pressure reduction between treatments was reflected in subcomponents of the primary endpoint, i.e. there were more myocardial infarctions overall. Furthermore, the blood pressure difference also influenced the most important of the secondary outcomes of the study in terms of more strokes initially but not overall at study end [4]. Despite lower blood pressures on amlodipine, valsartan prevented new-onset diabetes better and tended to prevent development of heart failure. So, what important messages can we extract from VALUE? Firstly, the trial failed to show its primary goal, i.e. a superiority of valsartan in lowering the composite cardiac endpoint in relation to its comparator amlodipine. On the contrary, the inferior initial blood pressure control by valsartan was reflected by more myocardial infarctions as well as strokes. From the results of the angiotensin II type 1 receptor cardiovascular outcome trials in hypertensives performed so far, we know from the LIFE study [6] that losartan lowers stroke morbidity and mortality compared with atenolol, and from the SCOPE trial that candesartan lowers the incidence of non-fatal strokes [7]. Certainly, so far, a mixed result for the group. As regards the calcium antagonist as comparator in VALUE, the amlodipine benefit on myocardial infarction was partially related to more effective lowering of blood pressure. It may also be speculated whether anti-ischaemic and antiangina properties may have played a role, particularly in light of no difference in fatal myocardial infarction. The trend in favour of valsartan over amlodipine regarding heart failure, and the benefit in preventing new-onset diabetes adds to previous data with inhibitors of RAS. What will be the immediate aftermath of VALUE? Certainly a discussion on which are optimal doses for valsartan in the treatment of hypertension, as well as a debate on whether or not there are true differences between the agents within the group of angiotensin II type 1 receptor blockers, or whether differences between agents in outcome trials so far merely reflect the design of the studies as well as the way they were in fact carried out.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON