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.

Blood pressure control--slowly getting there through new strategies?

Abstract: Current global estimates indicate that more than 25% of the adult population has diagnosed or undiagnosed hypertension (1), and as a consequence of that, cardiovascular disease and stroke is emerging as a major contributor to the global burden of death and disability (2,3). Also alarming is that the prevalence of hypertension is increasing (1), so that by 2025, the expected number of hypertensive patients in the world will be more than 1.5 billion. The majority of hypertensive patients today remain insufficiently controlled (4) and if current strategies of practice do not change, the majority of these 1.5 billion people will remain insufficiently controlled for their hypertension (5). Clearly, drastic measures have to be taken to improve the current situation and there is an urgent need to prepare health service providers as well as physicians for a global scenario containing even larger patient cohorts, possessing even more complicated and deranged risk-factor profiles to bring under control. While the prevalence of hypertension in the community is alarming, even more disturbing is how badly blood pressure (BP) is controlled in patients who are known to be hypertensive. Increased efforts and an extended use of combination therapies are vital to reach BP goals of v140/ 90 mmHg in patients with uncomplicated hypertension and v130/80 mmHg in those with hypertension and diabetes or renal disease (6). The severity of hypertension and presence of underlying comorbidity should guide the clinician in choosing the optimal type and dosage of antihypertensive therapy. For most patients, treatment does not bring any immediate or subjective benefits to them but rather causes inconvenience, medication-related side-effects and substantial costs. All of these factors influence compliance and the risk of suboptimal treatment results. Treatment failure may also be related to suboptimal drug therapy with low doses, inappropriate or wrong dose schedules, or suboptimal use of available treatment combinations. For a proportion of patients with hypertension, a stepwise approach either starting with one substance or with a fixed low-dose combination is adequate. A majority of patients with arterial hypertension do not reach BP goals with one antihypertensive drug alone, since patients with higher initial BP demonstrate remarkably lower responder rates to monotherapy (7). Combination therapy therefore has to be used in a majority of patients with moderate or severe hypertension. In fact, only about 5–25% of such patients can be effectively treated with a monotherapy (8,10). Further, in such patient groups, treatment with not two concomitant medications but three or more substances is required (8–10). As a consequence of this, it may be advantageous for some of these patients to initiate their treatment with a fixed combination within a therapeutic range of components, thereby achieving BP goals more rapidly. Accordingly, the 2003 ESH/ESC Guidelines (11) recommends that drug therapy should be started gradually either with monotherapy or with a ‘‘lowdose’’ combination, irrespective of initial BP levels; the JNC 7 report states that most patients with ‘‘stage 2’’ hypertension (systolic BP>160 mmHg or diastolic BP>100 mmHg) will require a combination therapy. There is no recommendation in the current guidelines on special patient groups to be considered for a first-line combination therapy, and in the ESH/ESC Guidelines (11), first-line combination treatment covers both sub-therapeutic and low therapeutic doses of the mono-components. In Blood Pressure. 2007; 16: 68–71

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.

Abstract: DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

Antihypertensive Therapy Benefits: Pleiotropic Versus Blood Pressure-Dependent Mechanisms

Abstract: The accumulated evidence from numerous trials in many thousands of individuals with high blood pressure indicates that, compared with placebo or control therapy, antihypertensive drug treatment reduces the risk of stroke, coronary heart disease and progression of renal impairment. Benefits are seen in systolic and diastolic hypertension, in mild-to-moderate hypertension, in all age groups, and they appear to be constant in proportion across the blood pressure range. People at all levels of risk benefit; therefore, the bigger the absolute risk, the greater the absolute benefit. A comprehensive meta-analysis of the results of 147 randomized trials involving 464,000 people in the context of epidemiological data from 958,000 people indicated that the proportional reduction in cardiovascular disease events is the same or similar regardless of pretreatment blood pressure and the presence or absence of cardiovascular disease. Thus, whatever the risk level, comorbidity, or special groups, the most important thing is to lower blood pressure properly. All the different common antihypertensive drugs and most drug combinations can be used if well tolerated.

Abstract 1881: Association of New-Onset Left Bundle Branch Block with Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy: The LIFE study

Abstract: Background : Whether new-onset left bundle branch block (LBBB) is associated with increased cardiovascular morbidity and mortality in treated hypertensive patients is unknown. Object : To assess cardiovascular morbidity and mortality associated with new-onset LBBB in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study among hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH). Methods: Hypertensive patients with LVH by Cornell voltage-duration product or Sokolow-Lyon voltage criteria on screening electrocardiograms were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. electrocardiograms were read at a central laboratory; Minnesota code 7.1 identified LBBB. Only participants without LBBB on LIFE study baseline electrocardiograms were included in the current study. Results : The electrocardiograms in LIFE study annual follow-up evaluations identified 296 patients (143 or 48.3% women) with and 8277 patients (4458 or 53.9% women) without new-onset LBBB. New-onset LBBB was associated with older age (70.0±6.2 vs. 67.3±7.0 years), higher sex-adjusted Cornell voltage (30.7±7.9 vs. 27.2±7.1) and higher prevalence of cardiovascular disease (35.8% vs. 24.2%)(all p Conclusion: Among hypertensive patients with electrocardiographic LVH, new-onset LBBB independently identifies those at increased risk of developing subsequent congestive heart failure and myocardial infarction.

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