patient centered meeting, vienna, november 1, 2029 ... · cornell product sokolow-lyon dahlöf b,...

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»

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095896/

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

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

SBP at 1.examination

SBP 2.examination

Arterial Plasma Noradrenaline During Mental Stress Predicts Future BP

Resting SBP at 18-Year Follow-Up

1 2 3120

125

130

135

140

SB

P (

mm

Hg)

Arterial noradrenaline tertile at baseline during

mental stress test

P=.004

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


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


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


• 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

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 criterionThe Cornell Product criterion

QRS duration

> 2.440 mm x msek

RaVL + SV3 + 6+

*

o

> 38 mm

The SokolowThe Sokolow--Lyon criterion Lyon criterion

RV5 + SV1

Atrial fibrillation


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


Diagnostic Assessments:

• Atrial fibrillation (new onset)

• Coronary disease

• Renal failure

• Moderat aortic stenosis

• Hypertensive heart disease

• Heart failure

Yes

Yes

Yes

Yes

Yes

No

Framingham Criteria for Heart Failure

MAJOR CRITERIA

CLINICAL

Paroxysmal nocturnal dyspnea or orthopnea

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

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

olive oil and nuts, pleanty of

seafood, poultry, vegetables,

fruit, avoid red meat

• Yes, of course

• Be careful

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 InfarctionStroke

0

5

10

15

20

25

*

*

**

***

0

5

10

15

20

*

*** ****

0

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


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.

0

2

4

6

8

10

12

14

Cardiovascular Death

0

2

4

6

8

10

12

14

16

18

Stroke

0

1

2

3

4

5

6

7

8

9

10

Myocardial Infarction

*

*

**

**

Drug Groups Combined

None 1-4 5-7 >108-10Weekly alcohol consumption:

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

American Journal of Hypertension Advance

Access Published May 31, 2016

Doi: 10.1093/ajh/hpw054


0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve

In

cid

en

ce

(%

)

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


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

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


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


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)


Treatment from about day 5 in hospital:

• ASA + warfarin (choice of the patient)

• Atorvastatin 40 mg x 1

• Furosemide 80 mg x 1


• Metoprolol (retard formula) 100 mg x 1

• Amlodipine 5 mg x 1

LIFE: Primary Composite Endpoint

0 180 360 540 720 900 1080 1260 1440 1620 1800 1980Study Day0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0.16E

ndpoin

t R

ate

Intention-to-Treat

Losartan

Atenolol

LIFE: Primary Composite Endpoint

58

Study Month 0 6 12 18 24 30 36 42 48 54 60 66Losartan (n) 4605 4524 4460 4392 4312 4247 4189 4110 4045 3895 1888 901Atenolol (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

VALUE: Primary Composite Cardiac Endpoint

14

12

10

8

6

4

2

0

Time (months)

0 6 12 18 24 30 36 42 48 54 60 66

Pro

po

rtio

n o

f P

ati

en

ts

Wit

h F

irst

Eve

nt

(%)

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

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

Amlodipine perindopril better Atenolol bendroflumethiazide better0.50 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

Kaplan Meier for Primary Endpoint C

um

ula

tive e

vent ra

te

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 0 02 HR (95% CI): 0.80 (0.72, 0.90)

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

http://www.escardio.org/guidelines



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)


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?

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

Home BP Measurement

Unattended Automatic Office Blood Pressure Measurement


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

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.

Cumulative Event Rates for Hospitalized/ Fatal

Heart Failure by ALLHAT Treatment Group ALLHAT

Cu

mu

lative

Eve

nt

Ra

te

Years 0 1 2 3 4 5 6 7

0

.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


Antihypertensive treatment at discharge:

• Furosemide 80 mg x 1

• Metoprolol (retard formula) 100 mg x 1

• Amlodipine 10 mg x 1


• Eplerenone 25 mg x 1


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

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

Sinus rhythm

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=0.005p=0.002

p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001p<0.001

Composite Endpoint

CV Mortality

Myocardial Infarction

StrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStrokeStroke

Los925 AHA02 Orkin 1 Nov. 13, 2002

Cornell Product

SL Voltage

Okin P , Kjeldsen SE et al. JAMA 2004

29

New Onset CHF Stratified by Time-Varying Presence

or Absence of Cornell Voltage Duration Product LVH

0 12 24 36 48 60

Month

0.00

0.01

0.02

0.03

0.04

0.05

0.06

En

dp

oin

t R

ate

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

LIFEAdapted from Okin et al.: Ann Intern Med 2007;(revision pending).

Absolute increase in

CHF 2% over 5 years

associated with LVH

147:311-319.

46

LV Geometric Patterns During 2 Years Treatment in LIFE

0

10

20

30

40

50

60

Normal

Geometry

Concentric

Remodel

Eccentric

LVH

Concentric

LVH

Baseline

12 Months

24 Months

Pre

vale

nce

(%)

Devereux RB et al: JAMA 2004

P<0.001 P<0.001 P<0.001

0 6 12 18 24 30 36 42 48 54 60

0

2

4

6

8

10

12

14

Composite End Point Stratified by Time-Varying Presence

of 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

En

d p

oin

t ra

te (

%)

LVH Present

LVH Absent

No. at risk

LVH +

LVH -

635

281

332

532

230

580

12153 M

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

of 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

Follow-up of Patients with Hypertension Mediated Organ Damage (HMOD) During Drug Treatment



patient centered meeting, vienna, november 1, 2029 ... · cornell product sokolow-lyon dahlöf b,...

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