HYPERTENSION The Ongoing Journey Prof. Sverre E. Kjeldsen, MD, - PowerPoint PPT Presentation

Patient Centered Meeting, Vienna, November 1, 2029 HYPERTENSION «The Ongoing Journey» Prof. Sverre E. Kjeldsen, MD, DrMedSci Department of Cardiology Oslo University Hospital Ullevaal, Oslo, Norway Past-President of the European Society of Hypertension Editor-in-Chief Blood Pressure Adjunct Professor of CV Medicine, University of Michigan

Purpose of this presentation: A. How to empower the patients ’ interacting challenges: - smoking, eating and drinking – how to celebrate health? - anxiety, stress and hypertension B. Intensive sport C. Nailing the moving target D. Follow up- structured - office unattended BPM - home BPM - ABPM - to who and how to read the results E. Interactive example – 1 case throughout

MCQ - anxiety, stress and hypertension Which method has been used IN A LONGITUDINAL STUDY (18 yrs.) to relate autonomic «stress» to high BP? • 1) Muscle sympathetic nerve activity • 2) Renal noradrenaline spillover rate • 3) Heart rate variability by Holter assessment • 4) Plasma noradrenaline in arterial blood

Mental Stress Test: 18-yr. Reproducibility SBP r=0.79 ADR r=0.62 SBP 2.examination SBP at 1.examination Hassellund S, Kjeldsen SE et al. Hypertension 2010; 55: 131-136

Arterial Plasma Noradrenaline During Mental Stress Predicts Future BP Resting SBP at 18-Year Follow-Up P =.004 140 SBP (mm Hg) 135 130 125 120 1 2 3 Arterial noradrenaline tertile at baseline during mental stress test Flaa A, Kjeldsen SE et al. Hypertension . 2008;32:336-341.

69 Year Old Male Patient (1) History: • Previous office worker, retired at 67, married • History of hypertension over many years • PCI x 3 2007-2015 (RDP and LAD) • Serum creatinine ca. 140 μmol/L • Ejection fraction 45% by echocardiography and NT-pro-BNP 640 ng/L in February 2016

69 Year Old Male Patient (2) Problem: • Sudden onset palpitations at New Years’ Eve with worsening end of January – early February 2019 • No typical angina pectoris • No typical dyspnoe, no syncope • Admitted to hospital on February 4, 2019

69 Year Old Male Patient (3) Findings: Normal body built (185 cm, 85 kg) • BP 172/92 mmHg upon admittance • HR 108 beats/min and unregular • Light jugular vein distention • Left sided pleural effusion (X-ray: small amounts) • Cardiac systolic murmur (grade 2 of 6) • No ankel oedema

69 Year Old Male Patient (4) • ECG: Atrial fibrillation, old inferior infarction and left ventricular hypertrophy by Cornell Product criteria (2560 mm x msec) • Echocardiography: Reduced posteromedial and anteroseptal wall motion, EF 40 - 45%, LV diameter diastole/systole = 5.6/5.0 cm, LA diameter = 4.7 cm, aortic valve V max. = 2.7 m/s and mean gradient 22 mmHg

LIFE: Patient Recruitment ECG-Criterion (n=9192) Both 10 % Cornell Product Sokolow-Lyon 68 % 22 % The Cornell Product criterion The Cornell Product criterion The Sokolow- -Lyon criterion Lyon criterion The Sokolow o R aVL + S V3 + 6 + QRS duration * R V5 + S V1 > 2.440 mm x msek > 38 mm Dahlöf B, Kjeldsen SE et al. Hypertension 1998;32:989-997. 10

Atrial fibrillation

Atrial fibrillation

69 Year Old Male Patient (6) Medication upon admittance: • Acetylsalicylic acid 75 mg x 1 • Simvastatin 40 mg x 1 • Furosemide (retard formula) 60 mg x 1 • Nifedipine (retard formula) 30 mg x 1 • Valsartan 40 mg x 2

69 Year Old Male Patient (7) Diagnostic Assessments: • Atrial fibrillation (new onset) Yes • Coronary disease Yes • Renal failure Yes • Moderat aortic stenosis Yes • Hypertensive heart disease Yes • Heart failure No

Framingham Criteria for Heart Failure MINOR CRITERIA* MAJOR CRITERIA FINDINGS CLINICAL Night cough  Paroxysmal nocturnal dyspnea or  orthopnea Dyspnea on ordinary exertion  Jugular venous distention Bilateral ankle edema   Pulmonary rales Hepatomegaly   Ventricular S 3 gallop  Hepatojugular reflux  Diuresis 10 lbs/5kg in response to diuretic;  clinical improvement in congestive symptoms DIAGNOSTIC FINDINGS Acute pulmonary edema on chest Pleural effusion or pulmonary vascular   x-ray engorgement or redistribution on x-ray PCWP ≥ 20 mmHg PCWP 16-19 mmHg   LVEF ≤ 35 LVEF 36-44   CI 2,0 – 2,4 CI < 2,0   Evidence of severe valvular heart disease Evidence of moderate valvular heart   disease Pulmonary edema or visceral congestion on  autopsy * Minor cirteria will be accepted only if they can not be attributed to another disease process

Discussion When Making Rounds Day 1 Question Response • Can I smoke? • Of course not • Can I drink (alcohol)? • Be careful • Can I exercise? • Yes, in due time • What kind of diet do you • Mediterranean diet with extra recommend? olive oil and nuts, pleanty of seafood, poultry, vegetables, fruit, avoid red meat • Yes, of course • Is statin good for me? • Be careful • Salt intake?

LIFE: Individual Endpoint Rates by Smoking Status Drug Groups Combined, Rates per 1000 Years of Follow-Up Cardiovascular Death Stroke Myocardial Infarction 20 *** *** *** 20 25 * *** 20 ** * 15 15 * * * 15 * 10 10 * 10 5 5 5 0 0 0 Never 1-5/d Previous 6-10/d 11-20/d >20/d (n = 4656) (n = 428) (n = 3033) (n = 454) (n = 435) (n = 182) * P < 0.05, ** P < 0.01, *** P < 0.001 for Adjusted Hazard Ratios vs. Never-Smokers Adjusted for alcohol consumption, exercise, gender, and age Reims HM, Oparil S, Kjeldsen SE et al . Blood Press 2004;13:376 Journal of Hypertension 2003, 21:1011 – 1053

LIFE: Individual Endpoint Rates by Alcohol Consumption Drug Groups Combined Endpoint rates (1/1000 yrs) according to reported weekly alcohol consumption. Cardiovascular Death Myocardial Infarction Stroke 14 18 10 * 9 16 12 * 8 14 10 7 12 6 8 10 ** 5 8 6 4 ** 6 3 4 4 2 2 2 1 0 0 0 8-10 Weekly alcohol consumption: None 1-4 5-7 >10 * P < 0.05, ** P < 0.01 for hazard ratios vs. non-drinkers Adjusted for smoking, exercise, gender, age, and race Reims HM,Kjeldsen SE, Brady WE et al . J Hum Hypertens 2004;18:381 Journal of Hypertension 2003, 21:1011 – 1053

American Journal of Hypertension Advance Access Published May 31, 2016 Doi: 10.1093/ajh/hpw054

Primary End Point: Nonfatal MI and Fatal CHD Atorvastatin 10 mg Number of events 100 4 Placebo Number of events 154 Cumulative Incidence (%) 36% 3 reduction 2 1 HR = 0.64 (0.50-0.83) p=0.0005 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Years Sever P, Kjeldsen SE et al. Lancet 2003 Journal of Hypertension 2003, 21:1011 – 1053

Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men CV-Death: HR 0.41 (0.20-0.84), p= 0.013 Q1 vs Q4 Death: HR 0.54 (0.32-0.89), p= 0.015 Q1 vs Q4 Journal of Hypertension 2003, 21:1011 – 1053 Sandvik L. et al. N Engl J Med 1993; 328: 533-7.

Effect of Dietary Counselling on Blood Pressure and Arterial Plasma Catecholamines in Primary Hypertension Beckmann SL, Os I, Kjeldsen SE, Eide I, Westheim A, Hjermann I. Am J Hypertens 1995; 8: 704-711

69 Year Old Male Patient (8) Treatment first 2 days in hospital: • Increase furosemide to 80 mg x 1, • Increased valsartan to 160 mg x 1 • Started metoprolol (increasing dosage) • DC nifedipine 30 mg x 1 • Changed simvastatin to atorvastatin • Low-molcular heparin s.c. • Started warfarin

69 Year Old Male Patient (9) BP development during first week in hospital: Date 4.2 5.2 6.2 7.2 8.2 SBP mmHg 162 150 170 170 162 Diastolic BP ranging from 60 to 80 mmHg Heart rate between 95 and 55 beats/min (atrial fibrillation)

69 Year Old Male Patient (10) Treatment from about day 5 in hospital: • ASA + warfarin (choice of the patient) • Atorvastatin 40 mg x 1 • Furosemide 80 mg x 1 • Valsartan 160 mg x 1 • Metoprolol (retard formula) 100 mg x 1 • Amlodipine 5 mg x 1

LIFE: Primary Composite Endpoint 0.16 Intention-to-Treat 0.14 Atenolol 0.12 Endpoint Rate 0.10 Losartan 0.08 Driven by 25% lower 0.06 stroke rate on losartan 0.04 Adjusted Risk Reduction 13·0%, p=0·021 0.02 Unadjusted Risk Reduction 14·6%, p=0·009 0.00 Study Day 0 180 360 540 720 900 1080 1260 1440 1620 1800 1980 Study Month 0 6 12 18 24 30 36 42 48 54 60 66 Losartan (n) 4605 4524 4460 4392 4312 4247 4189 4110 4045 3895 1888 901 Atenolol (n) 4588 4494 4414 4349 4289 4205 4135 4066 3992 3821 1854 876 Dahlöf B, Devereux RB, Kjeldsen SE & al. Lancet 2002

VALUE: Primary Composite Cardiac Endpoint 14 Valsartan-based regimen Proportion of Patients 12 With First Event (%) Amlodipine-based regimen 10 8 6 4 HR = 1.03; 95% CI = 0.94 – 1.14; P = 0.49 2 0 0 6 12 18 24 30 36 42 48 54 60 66 Time (months) Number at risk 7649 7459 7407 7250 7085 6906 6732 6536 6349 5911 3765 1474 Valsartan Amlodipine 7596 7469 7424 7267 7117 6955 6772 6576 6391 5959 3725 1474 Julius S, Kjeldsen SE, Weber M et al. Lancet . June 2004;363.