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 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 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 60 % 50 40 (n = 19,600, 12 regions) Женщины, Female N=11386 Мужчины, Male N=6919 Total Всего, N=18305 30 20 10 0 Smoke Курение LPA НФА ESI ИПС PIFV НПОФ AH Повышенное TC Повышенный obesity Ожирение high glucose Повышенная 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 Prevalence of Arterial Hypertension in Men 60 Мужчины Женщины 35 48,6 30 50 47,7 43 41,4 25 38,6 40 36,1 20 % 30 % 15 20 10 Growth of Obesity Prevalence Мужчины Женщины 30,8 26,4 26,9 11,8 10 5 0 1993 2003 2013 0 НПВ (1993) ЭССЕ (2013) National Research Center for Preventive Medicine
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 Thrombophilia Fatty tissue regulation disorder Hyperinsulinemia NAFLD Metabolic syndrome Visceral adiposopathy Insulin resistance Oxidative stress Hyperglycemia Hypertension 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 stiffness/ functional tests (FMD) Biochemistry Ultrasound/ IMT CT/MRI/ fusion/ ±contrast Invasive (including intravascular US) Cheap, Allow risk stratification, Prognostic significance, etc BUT Sometimes so early, that it will have not had come into play? Indirect methods!! Simple, cheap, and very fast, Prognostic Significance and YOU CAN SEE IT! BUT Too late? Not reliable? Distrustful? You are able to see an virtual plaque BUT Dedicated, Limited availability, Distrustful [on early stages] fair accuracy (but not 100 %) BUT Young patients (and usually their physicians too) prefer to avoid it due to possible complications
The purpose to develop novel reliable noninvasive method of very early atherosclerotic lesions assessment.
! Risk! 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.
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 Score risk (ESC), % 170 ± 16 * 230 ± 32 239 ± 24 288 ± 29** < 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 + photoplethysmograpic) assessment Vascular stiffness (RI, SI, Alx, etc) evaluation Ultrasound transducer Cuff (forearm disposition) Photoplethysmograpic 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=0.84 mm IMT=0.67 mm 23 % 10 % 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
40 35 30 38,9 * 27,8 * * * * 25 20 15 10 5 0 * - p < 0,05 20,1 * 13 11,7 E-hm,% FMD,% 3 4 8,5 9 6,5 IMT,mm x 10-1 11 12 4 SCORE 3 7 % Patients 2 with risk factors, SCORE 4 % Healthy 1 controls, SCORE < 1 % Advanced atherosclerosis, SCORE > 15 % Subclinical atherosclerosis,
LDL-cholesterol, mg/dl 4.0 3.5 - healthy controls 3.0 2.5 2.0 1.5 10 20 30 40 50 E-hm, %
LDL-cholesterol, mg/dl 4.0 3.5 - healthy controls - patients with risk factors 3.0 2.5 2.0 E-hm threshold of 15 % permitted us to differentiate healthy controls from high-risk patients without overt atherosclerosis 1.5 10 20 30 40 50 E-hm, %
LDL-cholesterol, mg/dl 4.0 3.5 3.0 - healthy controls - patients with risk factors - subclinical atherosclerosis 2.5 2.0 r = 0.7, p < 0.05 1.5 10 20 30 40 50 E-hm, %
LDL-cholesterol, mg/dl 4.0 3.5 3.0 - healthy controls - patients with risk factors - subclinical atherosclerosis - advanced atherosclerosis 2.5 2.0 1.5 r = 0.7, p < 0.05 For IMT and LDL-cholesterol r = 0.4, p < 0.05 10 20 30 40 50 E-hm, %
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 LDL-C is recommended as the primary target for treatment (I class, A level). LDL-C I class, B level 3 mmol/l Low and moderate risk I class, B level 2.6 mmol/l or a reduction of at least 50% High-risk IIa class, C level 1.8 mmol/l or a reduction of at least 50% Very high-risk
Possible intervention strategies as a function of 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. 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. 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
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