Cardiovascular prevention 2015

Prof Dr Johan De Sutter

AZ Maria Middelares Gent

Universiteit Gent

Many chronic diseases are inter-related with common comorbidities

Diabetes

Cardiovascular Diseases (CVD)

Kidney Diseases (CKD)

Hypertension

Cancers

Liver Diseases

Respiratory Diseases (Asthma, COPD etc.)

Allergic Diseases

www.alliancechronicdiseases.org

Many prevalent chronic diseases share common risk factors (Indicative table)

CVD Hypertension Diabetes Cancer CKD Liver Disease

Respiratory Disease

Allergic Disease

Poor nutrition habits

x x x x x x x

Tobacco use X x x x x x

Obesity x x x x

x x x

Physical inactivity

x x x x x x x x

Alcohol consumption

x x

x x x

Environmental factors

x x x x

www.alliancechronicdiseases.org

Change in cardiovascular disease deaths 1990-2013

Cardiovascular disease deaths wordwide between 1990 and 2013 : 41% ↑

Due to

Population growth : 25% ↑

Aging of the population : 55% ↑

Despite

Age-specific CV death rate : 39% ↓

Change in cardiovascular disease deaths 1990-2013

Cardiovascular disease as death cause in Belgium (1998-2011 ICD-10)

0

5

10

15

20

25

30

35

40

45

50

1998 1999 2000 2003 2004 2005 2006 2007 2008 2009 2010 2011

men

women

%

2011 : cardiovascular disease 31%, cancer 29%, respiratory disease : 10%

Procentuele verdeling van de verschillende

hart- en vaataandoeningen Vlaams Gewest 2011

Treatment or changes in risk factors ?

Who is at very high cardiovascular risk ?

• Documented cardiovascular disease – Coronary disease (ACS, PCI, CABG,…)

– Stroke

– Peripheral arterial disease

• Diabetes type 1 or 2 with 1 or more CV risk factors and/or target organ damage

• Severe kidney disease (GFR<30 ml/min/1,73 m²)

• SCORE risk ≥ 10%

SCORE chart: 10 year risk of fatal CV disease

The risk-age concept

310

270

230

190

(mg/dl)

Who is at high cardiovascular risk

• Strongly elevated risk factor

– Familial hypercholesterolemia (LDL cholesterol ≥ 190 mg/dl)

– Severe hypertension (≥ 180/110 mmHg)

• Diabetes type 1 or 2 without CV risk factors or target organ damage

• Moderate kidney disease (GFR 30-59 ml/min/1,73m²)

• SCORE risk 5-10%

Who is at moderate/low cardiovascular risk ?

• Moderate risk : SCORE risk 1-5%

Risk can be further evaluated based on other risk factors

• HDL/triglycerids/Lp(A)/…

• Familial history of premature CV disease

• Psychosocial risk factors

• Sedentary behaviour/central obesity

• ….

• Low risk : SCORE risk < 1%

The ABC of cardiovascular prevention

Avoid tobacco

The ABC of cardiovascular prevention

Avoid tobacco Be more active

Minimum recommended:

75 min vigorous intensity/week

or

180 min moderate intensity/week

Physical activiy and cause-specific mortality

Minimum recommended:

75 min vigorous intensity/week

or

180 min moderate intensity/week

The ABC of cardiovascular prevention

Avoid tobacco Be more active

Choose good nutrition

PREDIMED study, NEJM 2013

Characteristics of a healthy diet

www.alliancechronicdiseases.org

Ezatti et al, NEJM 2013

ESC hypertension guidelines 2013

Initiation of lifestyle changes and medication

Choice of antihypertensive drugs

ESC hypertension guidelines 2013

COME STAI study

• 10.078 consecutive hypertension patients, seen by 516 general practicioners in Belgium and Luxemburg in 2013

• Medication : – 43% 1 medication

– 46% 2 or more medictions

• 55% systolic blood pressure >140 mmHg

• Treatment intensification only in 34% of patients with systolic blood pressure > 140 mmHg !

Van de Borne et al, Journal of Hypertension 2014

CTT collaborators, Lancet 2005 and 2008

CTT collaborators, Lancet 2005 and 2008

Recommended target levels

Total cholesterol (mg/dl) LDL cholesterol (mg/dl)

Low to moderate CV risk High CV risk Very high CV risk

< 190 mg/dl < 175 mg/dl < 150 mg/dl

< 115 mg/dl < 100 mg/dl < 70 mg/dl or > 50% ↓

Intervention strategies as a function of total CV risk and LDL levels

8000 CAD patients evaluated in 2012

Cardioprotective medication in patients with coronary artery disease

*: Belgium (Gent) : ACE or ARB : 45%

*

Control of risk factors in patients with coronary artery disease

Effects of cardiac rehabilitation

Duration of FU HR (95%CI)

Mortality

Cardiovascular mortality

MI (fatal/nonfatal)

CABG

PCI

Hospital readmissions

> 12 months

> 12 months

> 12 months

> 12 months

> 12 months

6-12 months

0,87 (0,75-0,99)

0,74 (0,63-0,87)

0,97 (0,82-1,15)

0,93 (0,68-1,27)

0,89 (0,66-1,19)

0,69 (0,51-0,93)

47 studies (RCT) – 10.794 patients (mostly male, middle aged and lower risk

post AMI or CABG)

Cochrane Review 2011

Controversial issues

• Risk stratification : can we improve it ?

• Statins in elderly patients ?

• Statins and diabetes ?

• Statins not for all patients ?

• Statin intolerance : how to treat it ?

How to improve the overall performance of lipid treatment guidelines ?

• Improvement of risk scores for primary prevention – More focus on age- and gender specific risk thresholds ?

– Incorporation of biomarkers (inflammation, neurohormonal markers, new lipid markers, …) ?

– Incorporation of non-invasive imaging markers (coronary calcium, intima media thickness, …) ?

– Incorporation of other risk factors (exercise capacity, BMI, waist… ) ?

• The poly pill approach

• Treatment based on results of randomized controlled trials

Age and gender specific 10-years risk thresholds ?

• 3685 adults, average age 57 years, from the Framingham Offspring Study, with no CVD at baseline

• Overall: 47% met criteria for statin therapy, based on 7,5% risk threshold

• But – 40-55 years : poor PPV for men (48%) and women (36%); 5% risk

threshold appears to have better PPV

– 66-75 years : very poor NPV (3%); 15-20% risk threshold appears to have better NPV

Navar-Boggan AM et al, JACC 2015 (in press)

Non-invasive imaging

Coronary calcifications

(CT) Intima media thickness

(Echo)

NON-INVASIVE MARKERS OF SUBCLINICAL ATHEROSCLEROSIS FOR

PREDICTING A PRIMARY CARDIOVASCULAR EVENT: A RAPID SYSTEMATIC

REVIEW

Key messages

Coronary artery calcium score provided the highest incremental

predictive value, with a CNRI ranging from 22% to 55%. The added value

of the ankle-brachial index, aortic pulse wave velocity and carotid plaque

in risk reclassification was lower than for coronary calcium (CNRI around

15%).

The clinical benefit of integrating these 4 markers into the Framingham

risk score or to SCORE was not formally assessed in studies.

Economic evaluations were only identified for one marker: coronary

artery calcium. The studies showed highly unstable results, sensitive to a

number of assumptions, and in particularly to those relating to the price

and efficacy of preventive treatments.

KCE report april 2015

Ridker et al, JACC 2015;65:942-8

Ridker et al, JACC 2015;65:942-8

Ridker et al, JACC 2015;65:942-8

Controversial issues

• Risk stratification : can we improve it ?

• Statins in elderly patients ?

• Statins and diabetes ?

• Statins not for all patients ?

• Statin intolerance : how to treat it ?

• ….

• Ideally, treatment of hypercholesterolemia for patients at risk

for CVD should start before they turn 80 years old

• No RCT evidence exists to guide statin initiation after age 80 years

• Decisions to use statins in older individuals are made individually and are not supported by high quality evidence

Controversial issues

• Risk stratification : can we improve it ?

• Statins in elderly patients ?

• Statins and diabetes ?

• Statins not for all patients ?

• Statin intolerance : how to treat it ?

• ….

Major vascular event and

prior diabetes Events (%)

Treatment Control RR (CI)

0·78 (0·69 - 0·87) 0·77 (0·73 - 0·81) 0·77 (0·74 - 0·80)

0·75 (0·64 - 0·88) 0·76 (0·72 - 0·81) 0·76 (0·73 - 0·80)

0·79 (0·67 - 0·93) 0·84 (0·76 - 0·93) 0·83 (0·77 - 0·88)

0·79 (0·72 - 0·86) 0·79 (0·76 - 0·82) 0·79 (0·77 - 0·81)

0·5 1·0 1·5

Major coronary event 776 (8·3) 979 (10·5)

2561 (7·2) 3441 (9·6) Any major coronary event 3337 (7·4) 4420 (9·8)

Stroke 407 (4·4) 501 (5·4) 933 (2·7) 1116 (3·2)

Any stroke 1340 (3·0) 1617 (3·7)

Coronary revascularization Diabetes 491 (5·2) 627 (6·7) No diabetes 2129 (6·0) 2807 (7·9) Any coronary revascularization 2620 (5·8) 3434 (7·6)

Major vascular event 1465 (15·6) 1782 (19·2) 4889 (13·7) 6212 (17·4)

Any major vascular event 6354 (14·1) 7994 (17·8)

Diabetes No diabetes

Diabetes No diabetes

Diabetes No diabetes

RR (95% CI) RR (99% CI)

Effects on MAJOR VASCULAR EVENTS, per mmol/L reduction in LDL

cholesterol, among participants with diabetes

CTT collaborators, Lancet 2005 and 2008

Statins : benefits versus new-onset diabetes

5,4 fewer CHD deaths or

nonfatal MI per 255 patients

treated for 4 years per

1 mmol/L LDL-C reduction

1 additional case of

diabetes per 255 patients

treated for 4 years

CTT collaborators, Lancet 2008 and Sattar et al, Lancet 2010

Controversial issues

• Risk stratification : can we improve it ?

• Statins in elderly patients ?

• Statins and diabetes ?

• Statins not for all patients ?

• Statin intolerance : how to treat it ?

• ….

Statins have no proven benefit for…

• Patients with heart failure and LVEF<40%

– No effect on hard CV endpoints

• Patients with aortic valve stenosis

– No effect on aortic valve stenosis progression

• Patients with severe kidney disease

– No effect on hard CV endpoints

Controversial issues

• Risk stratification : can we improve it ?

• Statins in elderly patients ?

• Statins and diabetes ?

• Statins not for all patients ?

• Statin intolerance : how to treat it ?

• ….