Dr Jeremy Sayer Consultant Cardiologist St. Bartholomew s Hospital
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1 Your Heart Would you get Standard Rates? Dr Jeremy Sayer Consultant Cardiologist St. Bartholomew s Hospital Freitag, 28. Mai 2010 Page 1
2 Summary Cardiovascular Risk Estimation of cardiovascular risk Further risk assessment ECG, Exercise ECG, EBCT, MSCT The Future Hypercholesterolaemia Valvular Disorders The natural history Cardiomopathy HCM, LVH or Athlete s Heart? Ventriclular ectopics Should you worry? Freitag, 28. Mai 2010 Page 2
3 Heart disease in UK Men Women Causes of deaths, 2003, United Kingdom Freitag, 28. Mai 2010 Page 3
4 Freitag, 28. Mai 2010 Page 4
5 Pathology Freitag, 28. Mai 2010 Page 5
6 Vessel wall Atheroma Coronary artery plaque and its consequences Lumen Area of infarction Left ventricular cavity Clot Freitag, 28. Mai 2010 Page 6
7 Risk factors for Coronary Artery Disease Age Fibrinogen Lipoprotein (a) Alcohol Gender Obesity C-reactive protein Homocysteine Personality D-dimer Hypercholesterolaemia Serum amyloid Depression Hypertension Smoking Diabetes Inactivity Stress Family history Interleukin-6 Soft water Freitag, 28. Mai 2010 Page 7
8 Risk factors for Coronary Artery Disease Markers Fibrinogen Lipoprotein (a) C-reactive protein Homocysteine D-dimer Serum amyloid Interleukin-6 Freitag, 28. Mai 2010 Page 8
9 Risk factors for Coronary Artery Disease Those difficult to measure Personality Depression Inactivity Soft water Freitag, 28. Mai 2010 Page 9
10 Risk factors for Coronary Artery Disease Standard measures Age Gender Obesity Hypercholesterolaemia Hypertension Smoking Diabetes Family history Freitag, 28. Mai 2010 Page 10
11 Levels of risk associated with smoking, hypertension and hypercholesterolaemia Hypertension (SBP 195 mmhg) x3 X4.5 x9 x16 Smoking X1.6 x6 x4 Serum cholesterol level (8.5 mmol/l, 330 mg/dl) (Adapted from Poulter et al, 1993) Freitag, 28. Mai 2010
12 Estimated 10 year risk (%) of coronary artery disease in a 55 year old Data from the Framingham Study. Am J Hypertens 1994;7:75 Freitag, 28. Mai 2010 Page 12
13 Calculation of CHD Risk Freitag, 28. Mai 2010 Page 13
14 Case 1 a typical 55 year old male 55 year old Smoker Blood pressure 160 mmhg Cholesterol 7.5mmol/l Family history The persons depicted in this presentation are entirely fictitious. Any resemblance to people living or dead is purely coincidental Freitag, 28. Mai 2010 Page 14
15 Case 1 a typical 55 year old male 55 year old Smoker Blood pressure 160 mmhg Cholesterol 7.5mmol/l (Family history) Freitag, 28. Mai 2010 Page 15
16 Case 2 a healthy 40 year old male 40 year old Non smoker Blood pressure 120 mmhg Cholesterol 4.2mmol/l No family history Freitag, 28. Mai 2010 Page 16
17 Case 2 a healthy 40 year old male 40 year old Non smoker Blood pressure 120 mmhg Cholesterol 4.2mmol/l No family history Freitag, 28. Mai 2010 Page 17
18 Case 3 single risk factor 40 year old Non smoker Blood pressure 120 mmhg Cholesterol 7.5mmol/l No family history Freitag, 28. Mai 2010 Page 18
19 Case 3 single risk factor 40 year old Non smoker Blood pressure 120 mmhg Cholesterol 7.5mmol/l No family history Freitag, 28. Mai 2010 Page 19
20 Case 4 mildly raised risk factors 40 year old Smoker Blood pressure 145 mmhg Cholesterol 5.4mmol/l No family history Freitag, 28. Mai 2010 Page 20
21 Case 4 mildly raised risk factors 40 year old Smoker Blood pressure 145 mmhg Cholesterol 5.4mmol/l No family history Freitag, 28. Mai 2010 Page 21
22 Further Risk Stratification Freitag, 28. Mai 2010 Page 22
23 Further Risk Assessment The Resting ECG Freitag, 28. Mai 2010 Page 23
24 Further Risk Assessment Sensitivity and Specificity True positive (TP) Abnormal test in individual with disease False positive (FP) Abnormal test in individual without disease True negative (TN) Normal test in individual without disease False negative (FN) Normal test in individual with disease Sensitivity Specificity % with disease who have an abnormal result (TP/TP + FN) % without disease who have an normal result (TN/TN + FP) Freitag, 28. Mai 2010 Page 24
25 Normal ECG Normal in 50% on patients with chronic stable angina Freitag, 28. Mai 2010 Page 25
26 Further Risk Assessment The Exercise ECG Sensitivity 50-60% Specificity ~ 70% Freitag, 28. Mai 2010 Page 26
27 Outcome of 25,927 asymptomatic men undergoing ETT Freitag, 28. Mai 2010 Page 27
28 Further Risk Assessment Myocardial Perfusion Scanning Freitag, 28. Mai 2010
29 Further Risk Assessment Myocardial Perfusion Scanning Freitag, 28. Mai 2010 Page 29
30 diagnosis/stress_test ecg_6.html Comparison of Noninvasive Exercise Tests: Meta-analyses Study Test N (% female) Sensitivity Specificity ECG 2456 (34%) 52% 71% Fleischmann 11 SPECT 3237 (30%) 87% 64% ECG 3721 (100%) 61% 70% Kwok 12 (gender-specific) SPECT 842 (100%) 78% 64% SPECT 1249 (44%) 77% 69% AHRQ 62 (gender-specific) Freitag, 28. Mai 2010 Page 30
31 Further Risk Assessment Coronary Angiography Forssmann 1929 Right heart catheter Freitag, 28. Mai 2010
32 Further Risk Assessment Coronary Angiography Freitag, 28. Mai 2010 Page 32
33 Intravascular Ultrasound (IVUS) IVUS image of inside a coronary artery. IC=IVUS catheter, L=lumen, P=plaque Freitag, 28. Mai 2010 Page 33
34 Intravascular Ultrasound (IVUS) Angiogram IVUS Image Nissen SE et al. JAMA 2004; 291(9) Freitag, 28. Mai 2010 Page 34
35 Further Risk Assessment Electron Beam CT and Calcium Scoring Calcification of the left anterior descending coronary artery (large arrow) and left circumflex coronary artery (small arrow) Freitag, 28. Mai 2010 Page 35
36 Test Sensitivity (%) Specificity (%) Stress ECG EBCT Cardiac Catheterisation Adapted from Am J Cardiac Imaging 1996;10:180-6 Freitag, 28. Mai 2010 Page 36
37 Further Risk Assessment Multi-slice CT Freitag, 28. Mai 2010 Page 37
38 Further Risk Assessment Cardiac MR Freitag, 28. Mai 2010 Page 38
39 The Activated Endothelium activated endothelium cytokines (eg. IL-1, TNF- ) CELLULAR ADHESION MOLECULES chemokines (eg.mcp-1, IL-8) growth factors (eg. PDGF, FGF) attracts monocytes and T lymphocytes which adhere to endothelial cells induces cell proliferation and a prothrombic state Adapted from Koenig W. Eur Heart J 1999;1(Suppl T);T Freitag, 28. Mai 2010 Page 39
40 Relative Risk Relative Risk Relative Risk Relative Risk Markers of Inflammation in the Prediction of Cardiovascular Disease in Women High Medium Low Low Medium High High Medium Low Low Medium High Total Cholesterol Total Cholesterol High Medium Low Low Medium High High Medium Low Low Medium High Total Cholesterol Total Cholesterol hs-crp, high-sensitivity C-reactive protein; SAA, serum amyloid A; sicam, serum intracellular adhesion molecule; IL, interleukin. Ridker PM, et al. N Engl J Med. 2000;342: (with permission) Freitag, 28. Mai 2010 Page 40
41 Hypercholesterolaemia and IHD Freitag, 28. Mai 2010 Page 41
42 Freitag, 28. Mai 2010
43 Exogenous Pathway of Lipid Metabolism Chylomicron Skeletal muscle Adipose tissue Intestine FFA LP lipase Chylomicron remnant Dietary triglycerides and cholesterol Liver Remnant receptor to atheroma Freitag, 28. Mai 2010 Page 43
44 Endogenous Pathway of Lipid Metabolism LPL Lipoprotein lipase LDL receptor Liver LP LDL L HL HL IDL LP HL Small L VLDL LP HL Large L VLDL Hepatic lipase Freitag, 28. Mai 2010 Page 44
45 Reverse Cholesterol Transport Cell membrane SRB1 Liver FC ABCA1 CE CE LCAT CETP HDL HDL3 TG LDL receptor VLDL, IDL, LDL Peripheral tissues FC Free cholesterol TG Triglycerides CE Cholesterol esters LCAT Lecithin cholesterol acyl transferase CETP Cholesteryl ester transfer protein Freitag, 28. Mai 2010 Page 45
46 Classification of Dyslipidaemias Fredrickson (WHO) Classification Phenotype Lipoprotein Serum Serum Atherogenicity Prevalence elevated cholesterol triglyceride I Chylomicrons Normal to None seen Rare IIa LDL Normal +++ Common IIb LDL and VLDL +++ Common III IDL +++ Intermediate IV VLDL Normal to + Common V VLDL and Normal to + Rare chylomicrons LDL low-density lipoprotein; IDL intermediate-density lipoprotein; VLDL very low-density lipoprotein. (High-density lipoprotein (HDL) cholesterol levels are not considered in the Fredrickson classification.) (Adapted from Yeshurun et al., 1995) Freitag, 28. Mai 2010
47 (a) Achilles tendon xanthoma; (b) tendon xanthomata on the dorsum of a hand (heterozygous familial hypercholesterolaemia); and (c) planar xanthoma in the antecubital fossa (homozygous familial hypercholesterolaemia). Courtesy of Professor PN Durrington. Freitag, 28. Mai 2010 Page 47
48 Freitag, 28. Mai 2010 Page 48
49 Number of prescriptions (000's) Prescriptions used in the prevention and treatment of diseases of the circulatory system, selected BNF paragraphs, , England Anti-arrhythmic drugs Antiplatelet drugs Antihypertensive therapy Lipid lowering drugs Year Freitag, 28. Mai 2010 Page 49
50 Freitag, 28. Mai 2010 Page 50
51 Freitag, 28. Mai 2010 Page 51
52 ..and the rest... Freitag, 28. Mai 2010 Page 52
53 Valve Disease Freitag, 28. Mai 2010 Page 53
54 Mitral Regurgitation Freitag, 28. Mai 2010 Page 54
55 Aortic valve Disease Freitag, 28. Mai 2010 Page 55
56 Mild and moderate aortic stenosis Natural history and risk stratification by echocardiography European Heart Journal (2004) 25, Freitag, 28. Mai 2010 Page 56
57 Aortic Regurgitation BONOW ET AL., ACC/AHA TASK FORCE REPORT JACC Vol. 32, No. 5, November 1998: Freitag, 28. Mai 2010 Page 57
58 Left Ventricular Hypertrophy, Hypertrophic Cardiomyopathy and Athletes Heart Freitag, 28. Mai 2010 Page 58
59 Left Ventricular Dimensions and Athletes Heart Relative impact of different types of sports training on left ventricular (LV) cavity dimension and wall thickness (expressed as a percentage of maximum) Freitag, 28. Mai 2010 Page 59
60 Left Ventricular Dimensions and Athletes Heart Distribution of LV dimensions in trained athletes N Engl J Med 1991; 324: Freitag, 28. Mai 2010 Page 60
61 Ventricular ectopics Freitag, 28. Mai 2010 Page 61
62 Freitag, 28. Mai 2010 Page 62
63 Freitag, 28. Mai 2010 Page 63
64 THANK YOU Freitag, 28. Mai 2010 Page 64
65 ADDITIONAL SLIDES Freitag, 28. Mai 2010 Page 65
66 DEFINITION OF MYOCARDIAL INFARCTION Freitag, 28. Mai 2010 Page 66
67 Definition of Myocardial Infarction World Health Organisation (WHO) definition: Two out of three of Typical symptoms Typical enzyme rise Typical ECG (with the development of Q waves) Freitag, 28. Mai 2010 Page 67
68 Definitions of Myocardial Infarction Pathological diagnosis - loss of cardiac myocytes (necrosis) by prolonged ischaemia WHO 2 out of 3 of Typical symptoms Enzyme rise Typical ECG pattern European Heart Journal (2000) 21, doi: /euhj , available online at on Consensus Document Myocardial infarction redefined A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction The Joint European Society of Cardiology/American College of Cardiology Committee** Freitag, 28. Mai 2010 Page 68
69 SUMMARY Definition of MI Criteria for acute, evolving or recent MI Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: (1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: (a) ischemic symptoms; (b) development of Q waves (c) ECG changes indicative of ischemia (ST segment elevation or depression) (d) coronary artery intervention (e.g., coronary angioplasty). (2) Pathologic findings of an acute MI. Criteria for established MI Any one of the following criteria satisfies the diagnosis for established MI: (1) Development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myo-cardialnecrosis may have normalized, depending on the length of time that has passed since the infarct developed. (2) Pathologic findings of a healed or healing MI. Troponin levels Myocardial necrosis is detected if Maximal concentration of troponin T or I exceeds the decision limit (99th percentile of the values for a reference control group) on at least one occasion during the first 24 h after the index clinical event Implications Identification of more infarcts (but this would seem reasonable since any rise in Troponin is associated with adverse outcome) Allows appropriate secondary prevention in more cases Excludes previously mislabelled infarcts Social implications - HGV licenses, pilots licenses, life insurance, psychological Freitag, 28. Mai 2010 Page 69
70 Cardiac Troponins TnC TnT TnI 100% specific for myocardial damage Released within first few hours Peak at 12-24hours TnT detectable up to 14 days TnI detectable up to 5-7 days Allow quantification of infarct size Prognostic indicators Guide therapy Actin Tropomyosin Sensitivity Specificity CK AST TnT Components of Cardiac Muscle Freitag, 28. Mai 2010 Page 70
71 Cardiac death or MI (%) CHD - Troponins Risk Stratification in Unstable Angina Role of Troponin T > < Time from inclusion (days) Cumulative risk of cardiac death or MI based on Tropnin T levels ( g/l) Freitag, 28. Mai 2010 Page 71
72 Cardiac death/mi (%) CHD - Troponins Risk Stratification in Unstable Angina Role of Troponin T and ECG Changes Lindahl. Circulation 1996;93: ST+T ST T ECG at rest <0.06 g/l >0.18 g/l g/l TnT Five-months risk of cardiac death or MI in relation to resting ECG and tropnin T levels during the first 24h in the FRISC trial Freitag, 28. Mai 2010 Page 72
73 Cardiac death/mi (%) CHD - Troponins Risk Stratification in Unstable Angina Role of Troponin T and Exercise Testing Lindahl. Eur Heart J 1997;18: > <0.16 Troponin T ( g/l) High risk High risk ETT Intermediate risk ETT Low risk ETT Five-months risk of cardiac death or MI in relation to exercise test response and tropnin T levels during the first 24h in the FRISC trial Freitag, 28. Mai 2010 Page 73
74 CHD - definition Acute Coronary Syndrome No ST Elevation ST Elevation Unstable Angina Myocardial Infarction NSTEMI NonQWMI QWMI Freitag, 28. Mai 2010 Page 74
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