The National Research Center for Preventive Medicine Ministry of Healthcare, Russian Federation Practical challenges in CV risk management: When to start intervening in CVD? Prof. Drapkina O.M., Eliashevich S.O.
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 The total CV risk LDL-C level ?
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 Group II Patients with abdominal obesity (AO) Patients without signs of AO n=48 n=32
The detected criteria of the low-risk group heterogeneity • Central obesity (60% of patients) • General obesity (44 % of patients) • hs CRP level (≥ 3 mg /l among 60% of patients) • mLDL-C CRITERIA % 0 10 20 30 40 50 60 mLDL-C hsCRP level General obesity Central obesity
REGISTERS Prevalence of Overweight, % (BMI 25.0 – 29.99 kg/m 2 ) According to WHO, 2014. http://apps.who.int/bmi/index.jsp
HIGH PREVALENCE OF THE MAIN RISK FACTORS OF NONCOMMUNICABLE DISEASES (n = 19,600, 12 regions) % 60 Женщины, N=11386 Female Мужчины, N=6919 Male 50 Total Всего, N=18305 40 30 20 10 0 Курение НФА ИПС НПОФ Повышенное Повышенный Ожирение Повышенная Smoke LPA ESI PIFV AH TC obesity high glucose АД ХС глюкоза ABP – arterial blood pressure; TC – total cholesterol; LFA – low physical activity; ESI – excessive salt intake; PIFV – poor intake of fruit and vegetables Growth of Obesity Prevalence Growth of Prevalence of Arterial Hypertension in Men Мужчины Женщины Мужчины Женщины 35 60 30,8 30 48,6 26,9 47,7 26,4 50 43 25 41,4 38,6 40 36,1 20 % % 30 15 11,8 10 20 5 10 0 0 НПВ (1993) ЭССЕ (2013) National Research Center for Preventive Medicine 1993 2003 2013
Visceral obesity • Increase in liver free fatty acids inflow • (VLDL ) • Glucose utilization in peripheral tissues … hyperinsulinemia • SMC proliferation with phenotypic changes Fasting hypertriglyceridemia HDL , LDL
“ Multifaced ” Metabolic Syndrome Hyperinsulinemia Thrombophilia Fatty tissue regulation disorder Metabolic syndrome Visceral adiposopathy Oxidative stress NAFLD Insulin resistance Hypertension Hyperglycemia Dyslipidemia Bonora E., Targher G. Increased risk of cardiovascular disease and chronic kidney disease in NAFLD. Nature Reviews Gastroenterology & Hepatology 2012: 9, 372 – 381.
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? Arterial Invasive Biochemistry Ultrasound/ CT/MRI/ stiffness/ (including IMT fusion/ functional intravascular ±contrast tests (FMD) US) fair accuracy (but You are able to Simple, Cheap, Allow risk not 100 %) see an “virtual stratification, Prognostic cheap, and plaque” very fast, significance, etc… Prognostic …BUT… …BUT… …BUT… Significance Sometimes so early, that it will and… Young patients Dedicated, have not had come into play? YOU CAN SEE (and usually their Limited Indirect methods!! IT! physicians too) availability, prefer to avoid it Distrustful …BUT… due to possible [on early complications stages] Too late? Not reliable? Distrustful? …
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 / 1. Healthy 2. Pts with 3. Subclinical 4. Advanced Parameter controls risk factors athero-s athero-s 53 ± 8 52 ± 6 52 ± 4 50 ± 3 Mean age, years Mean blood < 130 and 147 and 85 149 and 87 151 and 89** pressure, mm Hg 80 * 170 ± 16 * 230 ± 32 239 ± 24 288 ± 29** Myocardium mass (by Deveraux), gr 4 ± 2 7 ± 4 Score risk (ESC), < 1 % * > 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 Ultrasound transducer Cuff (forearm Photoplethysmograpic disposition) sensor
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 IMT=0 IMT=0 .84 .67 mm mm 10 % 23 % E-hm = (maximal media echogenicity – minimal media echogenicity) / 256 (levels in gray-scale) x 100 %
0.5 mm 0.5 mm 3D-reconstruction of the CCA wall
38,9 * * * * 40 27,8 35 * 30 25 * 20,1 12 20 11 Advanced 3 atherosclerosis, 15 13 4 SCORE > 15 % 8,5 9 11,7 10 4 Subclinical atherosclerosis, SCORE 7 % 3 6,5 5 Patients with risk factors, 2 0 SCORE 4 % Healthy controls, 1 E-hm,% SCORE < 1 % FMD,% IMT,mm x 10 -1 * - p < 0,05
LDL-cholesterol, mg/dl 4.0 - healthy controls 3.5 3.0 2.5 2.0 1.5 E-hm, % 10 20 30 40 50
LDL-cholesterol, mg/dl 4.0 - healthy controls 3.5 - patients with risk factors 3.0 E-hm threshold of 15 % permitted us to differentiate 2.5 healthy controls from high-risk patients without overt atherosclerosis 2.0 1.5 E-hm, % 10 20 30 40 50
LDL-cholesterol, mg/dl 4.0 - healthy controls 3.5 - patients with risk factors - subclinical atherosclerosis 3.0 2.5 r = 0.7, p < 0.05 2.0 1.5 E-hm, % 10 20 30 40 50
LDL-cholesterol, mg/dl 4.0 - healthy controls 3.5 - patients with risk factors - subclinical atherosclerosis - advanced atherosclerosis 3.0 2.5 r = 0.7, p < 0.05 2.0 For IMT and LDL-cholesterol 1.5 r = 0.4, p < 0.05 E-hm, % 10 20 30 40 50
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