HYPERTENSION The Ongoing Journey Prof. Sverre E. Kjeldsen, MD, [PDF]

SLIDE 1

Patient Centered Meeting, Vienna, November 1, 2029

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

HYPERTENSION

«The Ongoing Journey»

SLIDE 2

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

SLIDE 3

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

SLIDE 4

Mental Stress Test: 18-yr. Reproducibility

SBP r=0.79 ADR r=0.62

Hassellund S, Kjeldsen SE et al. Hypertension 2010; 55: 131-136

SBP at 1.examination SBP 2.examination

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Arterial Plasma Noradrenaline During Mental Stress Predicts Future BP

Resting SBP at 18-Year Follow-Up

1 2 3 120 125 130 135 140

SBP (mm Hg) Arterial noradrenaline tertile at baseline during mental stress test P=.004

Flaa A, Kjeldsen SE et al. Hypertension. 2008;32:336-341.

SLIDE 6

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

SLIDE 7

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

SLIDE 8

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

SLIDE 9

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

SLIDE 10

10

10 % 22 % 68 %

LIFE: Patient Recruitment ECG-Criterion (n=9192)

Both Cornell Product Sokolow-Lyon

Dahlöf B, Kjeldsen SE et al. Hypertension 1998;32:989-997.

The Cornell Product criterion The Cornell Product criterion

QRS duration > 2.440 mm x msek RaVL + SV3 + 6+ *

> 38 mm

The Sokolow The Sokolow-

Lyon criterion

Lyon criterion

RV5 + SV1

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Atrial fibrillation

SLIDE 12

Atrial fibrillation

SLIDE 13

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

SLIDE 14

69 Year Old Male Patient (7)

Diagnostic Assessments:

Atrial fibrillation (new onset)
Coronary disease
Renal failure
Moderat aortic stenosis
Hypertensive heart disease
Heart failure

Yes Yes Yes Yes Yes No

SLIDE 15

Framingham Criteria for Heart Failure

MAJOR CRITERIA

CLINICAL



Paroxysmal nocturnal dyspnea or

rthopnea



Jugular venous distention



Pulmonary rales



Ventricular S3 gallop



Hepatojugular reflux



Diuresis 10 lbs/5kg in response to diuretic; clinical improvement in congestive symptoms

DIAGNOSTIC



Acute pulmonary edema on chest x-ray



PCWP ≥ 20 mmHg



LVEF ≤ 35



CI < 2,0



Evidence of severe valvular heart disease



Pulmonary edema or visceral congestion on autopsy

MINOR CRITERIA*

FINDINGS



Night cough



Dyspnea on ordinary exertion



Bilateral ankle edema



Hepatomegaly

FINDINGS



Pleural effusion or pulmonary vascular engorgement or redistribution on x-ray



PCWP 16-19 mmHg



LVEF 36-44



CI 2,0 – 2,4



Evidence of moderate valvular heart disease

* Minor cirteria will be accepted only if they

can not be attributed to another disease process

SLIDE 16

Discussion When Making Rounds Day 1

Question

Can I smoke?
Can I drink (alcohol)?
Can I exercise?
What kind of diet do you

recommend?

Is statin good for me?
Salt intake?

Response

Of course not
Be careful
Yes, in due time
Mediterranean diet with extra
live oil and nuts, pleanty of

seafood, poultry, vegetables, fruit, avoid red meat

Yes, of course
Be careful

SLIDE 17

Journal of Hypertension 2003, 21:1011–1053

*P < 0.05, **P < 0.01, ***P < 0.001 for Adjusted Hazard Ratios vs. Never-Smokers

Adjusted for alcohol consumption, exercise, gender, and age

Cardiovascular Death Myocardial Infarction Stroke

5 10 15 20 25

* * ** ***

5 10 15 20

* *** *** *

5 10 15 20

* * *** *

Never Previous 1-5/d 6-10/d 11-20/d >20/d (n = 4656) (n = 3033) (n = 454) (n = 428) (n = 435) (n = 182)

LIFE: Individual Endpoint Rates by Smoking Status

Drug Groups Combined, Rates per 1000 Years of Follow-Up

Reims HM, Oparil S, Kjeldsen SE et al. Blood Press 2004;13:376

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Journal of Hypertension 2003, 21:1011–1053

LIFE: Individual Endpoint Rates by Alcohol Consumption

*P < 0.05, ** P < 0.01 for hazard ratios vs. non-drinkers

Adjusted for smoking, exercise, gender, age, and race

Endpoint rates (1/1000 yrs) according to reported weekly alcohol consumption.

2 4 6 8 10 12 14 Cardiovascular Death 2 4 6 8 10 12 14 16 18 Stroke 1 2 3 4 5 6 7 8 9 10 Myocardial Infarction

* * ** **

Drug Groups Combined

None 1-4 5-7 >10 8-10 Weekly alcohol consumption:

Reims HM,Kjeldsen SE, Brady WE et al. J Hum Hypertens 2004;18:381

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American Journal of Hypertension Advance Access Published May 31, 2016

Doi: 10.1093/ajh/hpw054

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Journal of Hypertension 2003, 21:1011–1053

1 2 3 4 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Years Cumulative Incidence (%)

36% reduction

Primary End Point: Nonfatal MI and Fatal CHD

HR = 0.64 (0.50-0.83) Atorvastatin 10 mg Number of events 100 Placebo Number of events 154 p=0.0005

Sever P, Kjeldsen SE et al. Lancet 2003

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Journal of Hypertension 2003, 21:1011–1053

Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men

Sandvik L. et al. N Engl J Med 1993; 328: 533-7. 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

SLIDE 22

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

SLIDE 23

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

SLIDE 24

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)

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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

SLIDE 26

LIFE: Primary Composite Endpoint

180 360 540 720 900 1080 1260 1440 1620 1800 1980 Study Day 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16

Endpoint Rate

Intention-to-Treat

Losartan Atenolol

Study Month 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

Adjusted Risk Reduction 13·0%, p=0·021 Unadjusted Risk Reduction 14·6%, p=0·009

Dahlöf B, Devereux RB, Kjeldsen SE & al. Lancet 2002

Driven by 25% lower stroke rate on losartan

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VALUE: Primary Composite Cardiac Endpoint

14 12 10 8 6 4 2 Time (months) 6 12 18 24 30 36 42 48 54 60 66 Proportion of Patients With First Event (%) Valsartan-based regimen Amlodipine-based regimen

HR = 1.03; 95% CI = 0.94–1.14; P = 0.49

Julius S, Kjeldsen SE, Weber M et al. Lancet. June 2004;363. Number at risk Valsartan Amlodipine

7596 7649 7469 7459 7424 7407 7267 7250 7117 7085 6772 6732 6955 6906 6576 6536 5959 5911 3725 3765 1474 1474 6391 6349

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ASCOT-BPLA: Reductions Observed in Most Primary, Secondary, and Tertiary End Points

Amlodipine  perindopril better Atenolol  bendroflumethiazide better

0.50 0.70 1.00 1.45

Primary Nonfatal MI (incl silent) + fatal CHD Secondary Nonfatal MI (exc. silent) + fatal CHD Total coronary end point Total CV events and procedures All-cause mortality CV mortality Fatal and nonfatal stroke Fatal and nonfatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Post hoc Primary end point + coronary revasc procs CV death + MI + stroke

2.00

Unadjusted Hazard Ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-.078) 0.85 (0.75-0.97) 0.86 (0.77-0.96) 0.84 (0.76-0.92)

Dahlöf B, Kjeldsen SE et al for the ASCOT Investigators. Lancet 2005

SLIDE 29

Kaplan Meier for Primary Endpoint

Cumulative event rate

Jamerson K et al. New Engl J Med 2008; 359: 2417-28.

20% Risk Reduction

Time to 1st CV morbidity/mortality (days)

p = 0

ACEI / HCTZ CCB / ACEI 650 526

.0 02

HR (95% CI): 0.80 (0.72, 0.90)

SLIDE 30

2018 ESC/ESH Guidelines for the management of arterial hypertension European Heart Journal (2018) doi:10.1093/eurheartj/ehy339 www.escardio.org/guidelines www.escardio.org/guidelines

The core algorithm is also appropriate for most patients with HMOD, cerebrovascular disease, diabetes, or PAD

Core drug-treatment strategy for uncomplicated hypertension

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69 Year Old Male Patient (11)

BP development during 2. week in hospital:

Date 9.2 10.2 11.2 12.2 13.2 SBP mmHg 160 160 165 160 150

Diastolic BP ranging from 70 to 90 mmHg Heart rate between 90 and 40 beats/min (atrial fibrillation)

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69 Year Old Male Patient (12)

CT angiography of abdominal aorta 10.2:

Infrarenal aneurysm with maximal diameter =

4.8 cm (increased from 4.4 cm in 2018)

More aggressive antihypertensive treatment

indicated also from this point of view

What should be his treatment target for systolic BP?

< 120 mmHg? < 130 mmHg? < 140 mmHg?

SLIDE 33

MCQ: What would be the most useful method to ensure BP control?

1. Follow office BP only
2. Take 24-hour ambulatory BP once/year
3. Teach the patient to do home BP
4. Introduce unattended automated office BP

SLIDE 34

Home BP Measurement

SLIDE 35

Unattended Automatic Office Blood Pressure Measurement

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69 Year Old Male Patient (13)

Problems with choices of antihypertensives:

Beta-blocker: bradycardia on increasing the dose further
CCB: potentially not good in atrial fibrillation
ACEI and ARB: problems with further increase in

creatinine to 176 µmol/L on 10.2

Thiazide not very effective with the renal failure
α-blocker: may cause fluid retenion and precipitate heart

failure

Centrally acting agent: no endpoint documentation
Aldosteron antagonist: potentially a problem with the renal

function and potassium

SLIDE 37

Reduced First Occurence of Incident Atrial Fibrillation With ARB: the VALUE Trial

Schmieder RE, Kjeldsen SE, Julius SE et al. J Hypertens 2008; 26: 403-411.

SLIDE 38

Cumulative Event Rates for Hospitalized/ Fatal Heart Failure by ALLHAT Treatment Group

ALLHAT

Cumulative Event Rate Years 1 2 3 4 5 6 7 .02 .04 .06 .08 .1

Doxazosin Chlorthalidone Amlodipine Lisinopril

The diuretic group had the lower incidence of HF Curves diverged very early Is it diuretic withdrawal?

JAMA 2001, JAMA 2002

SLIDE 39

69 Year Old Male Patient (14)

Antihypertensive treatment at discharge:

Furosemide 80 mg x 1
Metoprolol (retard formula) 100 mg x 1
Amlodipine 10 mg x 1
Valsartan 160 mg x 1
Eplerenone 25 mg x 1

SLIDE 40

69 Year Old Male Patient (15)

Further treatment:

Control SBP < 130 mmHg
Protect renal function and follow K+
Avoid too slow heart rate (PM or ICD?)
Ultrasound of abdominal aorta
INR target 2.0 – 2.5
Electro regularization

SLIDE 41

69 Year Old Male Patient (16)

Follow-up visits during summer and fall:
Systolic BP < 130 mmHg but not < 120 mmHg
Creatinine remained < 180 µmol/L
Potassium acceptable (4.7 – 5.1 mmol/l)
PM not needed; CRT/ICD not indicated
Electroconversion successfully performed in

April and sinusrhythm maintained

Ultrasound of abdominal aorta due in November
Repeat ECG and echocardiography yearly

SLIDE 42

Sinus rhythm

SLIDE 43

Sinus rhythm

SLIDE 44

Regression of ECG LVH and Outcome: Treatment-Adjusted Cox Models*

* Adjusted for treatment effect only; hazard ratios calculated for a 1 SD decrease in Cornell product and Sokolow-Lyon voltage

0.6 1 1.5 Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) Hazard Ratio (95% CI) p<0.001 p<0.001 p=0.005 p=0.002 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 Composite Endpoint CV Mortality Myocardial Infarction Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Stroke Cornell Product SL Voltage

Okin P , Kjeldsen SE et al. JAMA 2004

SLIDE 45

29

New Onset CHF Stratified by Time-Varying Presence

r Absence of Cornell Voltage Duration Product LVH

12 24 36 48 60 Month 0.00 0.01 0.02 0.03 0.04 0.05 0.06 Endpoint Rate

 2440 (n=3027, 4070, 4207) >2440 (n=5712, 4493, 3963)

m954pn133CPpooled Oct. 13, 2005

CP LVH+ CP LVH-

* n= number of patients in each group at baseline, 2 and 4 years of LIFE Adapted from Okin et al.: Ann Intern Med 2007;(revision pending).

Absolute increase in CHF 2% over 5 years associated with LVH

147:311-319.

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46

LV Geometric Patterns During 2 Years Treatment in LIFE

10 20 30 40 50 60 Normal Geometry Concentric Remodel Eccentric LVH Concentric LVH Baseline 12 Months 24 Months

Prevalence (%)

Devereux RB et al: JAMA 2004 P<0.001 P<0.001 P<0.001

SLIDE 47

6 12 18 24 30 36 42 48 54 60 2 4 6 8 10 12 14

Composite End Point Stratified by Time-Varying Presence

f Echocardiographic Ventricular Hypertrophy*

Devereux RB et al., JAMA 2004; 292: 2350

Left ventricular hypertrophy defined as LVMI > 116.0 in men and > 104.0 in women. Patients with LVH at baseline are counted in the “LVH absent” group at the time at which their LVH regresses. * Adjusted for treatment, baseline LVMI, baseline & treatment BP

Month End point rate (%)

LVH Present LVH Absent

No. at risk

LVH + LVH - 635 281 332 532 230 580 12153 M

SLIDE 48

2018 ESC/ESH Guidelines for the management of arterial hypertension European Heart Journal (2018) doi:10.1093/eurheartj/ehy339 www.escardio.org/guidelines www.escardio.org/guidelines

Marker of HMOD Sensitivity to changes Reproducibility and operator independence Time to changes Prognostic value

f the change

LVH by ECG Low High Moderate (> 6 months) Yes LVH by echocardiogram Moderate Moderate Moderate (> 6 months) Yes LVH by CMR High High Moderate (> 6 months) No data eGFR Moderate High Very slow (years) Yes Urinary albumin excretion High Moderate Fast (weeks to months) Moderate Carotid IMT Very low Low Slow (> 12 months) No PWV High Low Fast (weeks to months) Limited data Ankle−brachial index Low Moderate Slow (> 12 months) Moderate