CV risk management: When to start intervening in CVD? Prof. - - PowerPoint PPT Presentation

Practical challenges in CV risk management: When to start intervening in CVD?

• Prof. Drapkina O.M., Eliashevich S.O.

The National Research Center for Preventive Medicine Ministry of Healthcare, Russian Federation

The ESC Guidelines 2016

• The ESC Guidelines represent the

views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.

• However, the ESC Guidelines do

not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient.

Two whales and intuition

LDL-C level The total CV risk

?

Recommendations for risk estimation

SCORE chart: 10-year risk of fatal cardiovascular disease in populations of countries at high cardiovascular risk

Simple principles of risk assessment

Persons with

• documented CVD
• type 1 or type 2 diabetes
• very high levels of individual risk factors
• chronic kidney disease (CKD)

are automatically at very high or high total CV risk. No risk estimation models are needed for them; they all need active management of all risk factors.

The additional impact of HDL-C on risk estimation for women in populations at high cardiovascular disease risk

Relative risk chart, derived from SCORE

A particular problem relates to young people with high levels of risk factors; a low absolute risk may conceal a very high relative risk requiring intensive lifestyle advice. To motivate young people not to delay changing their unhealthy lifestyle, an estimate of their relative risk, illustrating that lifestyle changes can reduce relative risk substantially, may be helpful. ESC,2016

Low and moderate risk categories

• The heterogeneity of low and moderate risk group (SCORE 0 – 5%)
• The details should be in focus

The pilot study The aim:

to assess criteria of the low-risk group heterogeneity (SCORE<1%)

%

Inclusion criteria: low-risk persons (SCORE <1%) aging 18 to 60 years; intima-media thickness <0.9 mm (according to ultrasound examination of the brachiocephalic arteries). Exclusion criteria: smoking over 1 year before the study, atherosclerosis-related cardiovascular pathologies; lipid-lowering therapy within 6 weeks; secondary arterial hypertension; thyroid pathologies; severe concomitant diseases (cardiac, respiratory, renal, and liver insufficiency, cancer, mental illness); pregnancy and lactation.

n = 80 Group I Patients with abdominal obesity (AO) n=48 Group II Patients without signs of AO n=32

The detected criteria of the low-risk group heterogeneity

10 20 30 40 50 60 CRITERIA mLDL-C hsCRP level General obesity Central obesity

• Central obesity (60% of patients)
• General obesity (44 % of patients)
• hs CRP level (≥ 3 mg/l among 60% of patients)
• mLDL-C

%

Prevalence of Overweight, % (BMI 25.0–29.99 kg/m2)

According to WHO, 2014. http://apps.who.int/bmi/index.jsp

REGISTERS

10 20 30 40 50 60

%

Курение НФА ИПС НПОФ Повышенное АД Повышенный ХС Ожирение Повышенная глюкоза Женщины, N=11386 Мужчины, N=6919 Всего, N=18305

ABP – arterial blood pressure; TC – total cholesterol; LFA – low physical activity; ESI – excessive salt intake; PIFV – poor intake of fruit and vegetables

HIGH PREVALENCE OF THE MAIN RISK FACTORS OF NONCOMMUNICABLE DISEASES

National Research Center for Preventive Medicine

11,8 26,9 26,4 30,8 5 10 15 20 25 30 35 НПВ (1993) ЭССЕ (2013) % Мужчины Женщины

Growth of Prevalence of Arterial Hypertension in Men (n = 19,600, 12 regions)

43 36,1 47,7 48,6 41,4 38,6 10 20 30 40 50 60 1993 2003 2013 % Мужчины Женщины

Growth of Obesity Prevalence

Smoke LPA ESI PIFV AH TC obesity high glucose

Female Male Total

• Increase in liver free fatty acids inflow
• (VLDL )
• Glucose utilization in peripheral tissues  … 

hyperinsulinemia

• SMC proliferation with phenotypic changes Fasting

hypertriglyceridemia  HDL, LDL

Visceral obesity

“Multifaced” Metabolic Syndrome

Bonora E., Targher G. Increased risk of cardiovascular disease and chronic kidney disease in NAFLD. Nature Reviews Gastroenterology & Hepatology 2012: 9, 372–381.

Metabolic syndrome Visceral adiposopathy Insulin resistance Dyslipidemia NAFLD Hypertension Thrombophilia Hyperinsulinemia Hyperglycemia Oxidative stress Fatty tissue regulation disorder

Examples of risk modifiers that are likely to have reclassification potential

Nontraditional markers of cardiovascular disease risk

Routine assessment of circulating or urinary biomarkers is not recommended for refinement of CVD risk stratification (III class, B level).

How to catch an «athero» ASAP?

Biochemistry Ultrasound/ IMT CT/MRI/ fusion/ ±contrast Invasive (including intravascular US) Arterial stiffness/ functional tests (FMD)

Young patients (and usually their physicians too) prefer to avoid it due to possible complications fair accuracy (but not 100 %) …BUT… …BUT… Dedicated, Limited availability, Distrustful [on early stages] You are able to see an “virtual plaque” Cheap, Allow risk stratification, Prognostic significance, etc… …BUT… Indirect methods!! Sometimes so early, that it will have not had come into play? …BUT… Too late? Not reliable? Distrustful? … Simple, cheap, and very fast, Prognostic Significance and… YOU CAN SEE IT!

The purpose

• to develop novel reliable non-

invasive method of very early atherosclerotic lesions assessment.

Enrolled patients

• 10 patients with advanced symptomatic atherosclerosis

(affected both cerebral, coronary, and carotid arteries);

• 11 patients with subclinical atherosclerosis (by duplex

sonography or invasive tests);

• 10 patients with no evidence of atherosclerosis (assessed

by duplex sonography and CT-angio/coronarography), normal intima-media thickness, but presented with dyslipidemia, smoking, and obesity; and

• 8 comparable healthy controls.

! Risk !

Patients characteristics

Group / Parameter

• 1. Healthy

controls

• 2. Pts with

risk factors

• 3. Subclinical

athero-s

• 4. Advanced

athero-s Mean age, years 53 ± 8 52 ± 6 52 ± 4 50± 3 Mean blood pressure, mm Hg < 130 and 80 * 147 and 85 149 and 87 151 and 89** Myocardium mass (by Deveraux), gr 170 ± 16 * 230 ± 32 239 ± 24 288 ± 29** Score risk (ESC), % < 1 % * 4 ± 2 7 ± 4 > 15**

* - p < 0,05 for comparison between groups 1 and (2 and 3) ** - p < 0,05 for comparison between groups 4 and (2 and 3)

Methods (1)

• Comprehensive clinical assessment
• Careful BP monitoring (blood pressure monitoring)
• Full blood biochemistry (including lipids, CRP, etc)
• ECG (including stress-test)
• Echocardiography with tissue doppler
• Microalbuminuria
• CT-angio / coronary angiography (In particular patients)

Methods (2)

• Flow-mediated

dilation with parallel dual (US + photoplethysmo- grapic) assessment

• Vascular stiffness

(RI, SI, Alx, etc) evaluation

Cuff (forearm disposition) Photoplethysmograpic sensor Ultrasound transducer

Methods: carotid ultrasound (1)

• High-resolution B-mode ultrasound imaging of common

carotid artery structure and its pulse-motion (M-mode) were obtained in uniform regimen by single operator.

• Then gray-scale arterial wall images were 10-fold enlarged

using fractal-based algorithm. After that shear stress, viscosity, stiffness and dimensions of common carotid artery layers (intima, media, adventitia) were assessed. Echo-heterogeneity of media and endothelium were evaluated by computed analysis with 3D-reconstruction of arterial wall. 

Echo-heterogeneity of media

E-hm = (maximal media echogenicity – minimal media echogenicity) / 256 (levels in gray-scale) x 100 %

10 % 23 % IMT=0 .84 mm IMT=0 .67 mm

3D-reconstruction

• f the CCA wall

0.5 mm 0.5 mm

1 2 3 4

5 10 15 20 25 30 35 40 E-hm,% FMD,% IMT,mm

11,7 13 6,5 20,1 9 8,5 27,8 4 11 38,9 3 12

Healthy controls, SCORE < 1 % Patients with risk factors, SCORE 4 % Subclinical atherosclerosis, SCORE 7 % Advanced atherosclerosis, SCORE > 15 %

* * * * * * * - p < 0,05

x 10 -1

E-hm, %

10 20 30 40 50 1.5 2.0 2.5 3.0 3.5 4.0

LDL-cholesterol, mg/dl

• healthy controls

E-hm, %

10 20 30 40 50

LDL-cholesterol, mg/dl

• healthy controls
• patients with risk factors

1.5 2.0 2.5 3.0 3.5 4.0

E-hm threshold of 15 % permitted us to differentiate healthy controls from high-risk patients without overt atherosclerosis

E-hm, %

10 20 30 40 50

r = 0.7, p < 0.05 LDL-cholesterol, mg/dl

• healthy controls
• patients with risk factors
• subclinical atherosclerosis

1.5 2.0 2.5 3.0 3.5 4.0

E-hm, %

10 20 30 40 50

r = 0.7, p < 0.05 LDL-cholesterol, mg/dl

• healthy controls
• patients with risk factors
• subclinical atherosclerosis
• advanced atherosclerosis

1.5 2.0 2.5 3.0 3.5 4.0

For IMT and LDL-cholesterol r = 0.4, p < 0.05

Study limitations

• Small sample
• Non-blinded, operator-dependent study, performed by

single operator

• Difficulties associated with different ultrasound device

application

• Morphological verification (autopsy) still in process
• Unknown prognostic significance

Conclusion

• Media echo-heterogeneity tightly correlates with LDL-cholesterol

(r = 0.7, p < 0.05) and the threshold of 15 % allows to distinguish healthy controls from high-risk patients without overt atherosclerosis.

• The novel ultrasound postprocessing method of non-invasive

subtle evaluation of common carotid artery intima and media characteristics might be used to catch atherosclerotic lesions at the earliest stage.

Treatment goals for LDL-C

I class, B level I class, B level IIa class, C level

1.8 mmol/l or a reduction of at least 50% 2.6 mmol/l or a reduction of at least 50% 3 mmol/l

Very high-risk High-risk Low and moderate risk

LDL-C is recommended as the primary target for treatment (I class, A level).

LDL-C

Possible intervention strategies as a function

• f total cardiovascular risk and LDL-C level

One goal, but different ways of achievement …

Low and moderate risk LDL-C ≤ 3 mmol/l

Lifestyle modifications Drug therapy Lifestyle modifications plus drug therapy AHA/ACC guidelines have a wider indication for statin therapy than ESC guidelines

The primary prevention

• The absolute benefit from statin treatment may be less evident in patients in

primary prevention, who are typically at lower risk.

• In Cochrane analysis (2013): all-cause mortality was reduced by 14%, CVD events by

27%, fatal and non-fatal coronary events by 27% and stroke by 22% per 1 mmol/L (40 mg/dL) LDL-C reduction.

• However, it should be emphasized that in subjects with lower risk, the absolute risk

reduction is also lower.

• Thus statin use should be considered for primary prevention at high CV risk

It is sad but true

Predictors of non-adherence with statins have been identified and include their use in individuals for primary prevention as compared with their use in patients with disease or with multiple risk factors, lower income, being elderly, complex polypharmacy, cost and forgetfulness due to a lack of symptoms and psychological co-morbidities.

CAC score improves coronary and CV risk assessment: More Evidence

• Medscape. Sep 26, 2016.

3745 individuals without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003 59 (8) years of age, 47% men Prospective study, a mean follow-up 10.4 years

Mahabadi AA, Mohlenkamp S. Lehmann N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines. JACC: Cardiovasc Imaging 2016

The aim of this study was to assess the difference in indication for statin therapy by ESC versus AHA/ACC guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort.

Statin Eligibility According to ESC and AHA/ACC Guidelines

CAC-Stratified Coronary and Cardiovascular Event Rate

Difference in Event Rate by CAC Score in Subjects With Potential Statin Therapy

Coronary Calcium Scores Can Help Some 'Intermediate-Risk' Patients Avoid Statins