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Welcome

Welcome. Please Note. Only SMS will be sent in future for CMEs Postal / courier invitation will not be sent Make sure you give us your Mobile No. Confirm your participation by SMS Reply to our SMS – To know you received Make sure to send your name in your reply

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Welcome

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  1. Welcome www.drsarma.in

  2. Please Note • Only SMS will be sent in future for CMEs • Postal / courier invitation will not be sent • Make sure you give us your Mobile No. • Confirm your participation by SMS • Reply to our SMS – To know you received • Make sure to send your name in your reply • Mark this No. as Dr Sarma 98940 60593 • Bring along any other interested doctors • Give your e-mail ID. Create one, if not having www.drsarma.in

  3. Coronary Heart Disease (CHD) - Risk Approach Dr.R.V.S.N.Sarma., M.D. www.drsarma.in

  4. Over view of this CME Session One • CHD Prevention is the Mantra • Over view of atherosclerosis • Risk Factors in detail Session Two • Patient evaluation - what tests to do • Risk scoring tools • Management of risk factors • Take home messages www.drsarma.in

  5. Very Alarming Indeed !! • India is the Diabetic capital of the world • Indians have one of highest rates of CAD • Indian CAD is malignant in its onslaught • Obesity in India is 3 fold compared to 1970 It is high time, all of us collectively do what ever best is possible to prevent worsening ! www.drsarma.in

  6. Coronary Artery Disease - CAD Cerebro Vascular Disease – CVD Peripheral Vascular Disease – PVD Reno Vascular Disease - MRD At the end of the show there are only two exits Cardio Vascular Diseases - CVD All Other Causes of Death Exit 1 Exit 2 50% 50% www.drsarma.in

  7. CHD – THE VOLCANO www.drsarma.in

  8. Treatment Advances in CAD • Thrombolysis – Rx. Algorithms • ICU care – Defibrillators, Ventilators, IABP • Coronary Angiogram, CT Angio, STS • Primary PTCA – Stents, Elective PTCA • Rescue Angioplasty – Drug Eluted Stents • CABG – Beating Heart Surgery • MRV, Angiogenesis - Stem Cell Research • Remember, all the above are prohibitively expensive and not accessible to all • Benefit the lucky few patients who survived until the hospital door • They are at best palliative; not curative www.drsarma.in

  9. CAD Scenario • Out 100 cases of MI • 20 persons die – what ever we do or not ! - blessed ones ! • Of these – 14/20 (2/3) die even before they see us – lucky • Pre hospital mortality – very sacred souls !! • Remaining – 6/20 (1/3) – die in spite of us • Some more may perish – because of us – iatrogenic causes • 2 – 3% SCD – Sudden Cardiac deaths – exemplary !!! • 1/3 cases of MI are silent MIs – ↑ Risk of death • Among the 80 survivors – Reinfarction rates of > 30% • Re-stenosis and failure of PTCA around 25% • 10% of survivors – LVDF and CHF – chronic invalids So, once we are a patient of MI, we are permanent patients +/- invalidity !!! www.drsarma.in

  10. Samudrae saanta kallole Snatum itcchati mooda dhi When the waves stop, then Shall I bathe, thinks the fool How foolish we are all !! www.drsarma.in

  11. Samudrae saanta kallole Snatum itcchati mooda dhi Samsaare saanta kallole Jnanam icchati durmati When the waves stop, then Shall I bathe, thinks the fool Sans turbulance I am when, Then shall I strive for wisdom How foolish we are all !! www.drsarma.in

  12. Samudrae saanta kallole Snatum itcchati mooda dhi Samsaare saanta kallole Jnanam icchati durmati Sareerae hrid rogapeeditae Roginah kaankshati rakshati When the waves stop, then Shall I bathe, thinks the fool Sans turbulance I am when, Then shall I strive for wisdom The CAD strikes my heart when Then, shall I crave for prevention How foolish we are all !! www.drsarma.in

  13. How to win the battle of CHD • Coronary care units cannot answer all callers • PTCA and CABG are not always feasible • Are affordable by and available to only some • Why make a valiant attempt to save the myocardium after all the damage is done • Why not protect our tiny blood pipes by adopting preventive strategies at low cost ! Prevention is the only best weapon Need to identify those at greater risk Target them early to forestall damage www.drsarma.in

  14. Prevention is the key • CVD - Is it preventable ?? - Very much Yes. • The risk assessment must start very early • At the age of 20 years itself • Healthy life style and hearty eating habits • Regular physical exercise from young age • Maintaining ideal weight and hour glass waist • Avoiding tobacco and reducing alcohol • There are enough guidelines – Implementation ? www.drsarma.in

  15. } The Progressive Development of Cardiovascular Disease Intervene here Risk Factors Endothelial Dysfunction Atherosclerosis CAD Myocardial Ischemia Coronary Thrombosis Myocardial Infarction Arrhythmia & Muscle Loss Remodeling Ventricular Dilation Congestive Heart Failure End stage Heart Disease www.drsarma.in

  16. Continuum Risk for a CHD Event Post MI/Angina Secondary Prevention Other Atherosclerotic Manifestations Subclinical Atherosclerosis PrimaryPrevention Multiple Risk Factors Low Risk www.drsarma.in Courtesy of CD Furberg.

  17. Note the individual Endothelial Cells www.drsarma.in

  18. www.drsarma.in

  19. Endothelial Apoptosis Apoptosed Normal www.drsarma.in

  20. The Universal Damage The Essential Components Genes Coronary Risk Factors Endothelial Dysfunction NO ↑ Inflammation ↑ Thrombosis Coronary Heart Disease The Nature (Genetic) conspires with the Nurture (Acquired) www.drsarma.in

  21. www.drsarma.in (L-NMMA) =N(G)-mono-methyl-L-arginine

  22. Regulatory Functions of the EndotheliumNormal Dysfunction Vasodilation Vasoconstriction NO, PGI2, EDHF, BK, C-NP ROS, ET-1, TxA2, A-II, PGH2 Thrombolysis Thrombosis tPA, Protein C, TF-I, vWF PAI-1, TF-α, Tx-A2 Platelet Disaggregation NO, PGI2 Adhesion Molecules CAMs, P,E Selectins Antiproliferation NO, PGI2, TGF-, Hep Growth Factors ET-1, A-II, PDGF, ILGF, ILs Inflammation ROS, NF-B Lipolysis www.drsarma.in LPL Vogel R

  23. Progression of Atherosclerosis www.drsarma.in

  24. Role of LDL in Inflammation LDL readily enter the artery wall where they may be modified Vessel Lumen LDL Nitric Oxide (NO) Policing the Endothelium Endothelium LDL Hydrolysis of Phosphatidylcholineto Lysophosphatidylcholine Oxidation of Lipidsand ApoB Aggregation Other Chemical Modifications Modified LDL Intima Modified LDL is Proinflammatory Steinberg D et al. N Engl J Med 1989;320:915-924.

  25. Modified LDL Stimulate Expression of MCP-1 in Endothelial Cells Vessel Lumen Monocyte LDL Endothelium MCP-1 LDL Monocyte Chemotactic Protein 1 – MCP 1 Modified LDL Intima Navab M et al. J Clin Invest 1991;88:2039-2046.

  26. Differentiation of Monocytes into Macrophages Vessel Lumen Monocyte LDL Endothelium MCP-1 LDL Intima Modified LDL Monocyte Chemotactic Protein 1 – MCP 1 Modified LDL PromoteDifferentiation ofMonocytes intoMacrophages Macrophage Steinberg D et al. N Engl J Med 1989;320:915-924.

  27. Modified LDL Induces Macrophages to Release Cytokines - Stimulate Adhesion Molecule Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Cytokines Modified LDL Intima Macrophage Nathan CF. J Clin Invest 1987;79:319-326.

  28. Recruitment of Blood Monocytes by Endothelial Cell Adhesion Molecules Rolling Monocyte Vessel Lumen Sticking Transmigration VCAM-1 ICAM-1 Endothelium E-Selectin MCP-1 Intima Charo IF. Curr Opin Lipidol 1992;3:335-343.

  29. Macrophages Express Receptors that take up Modified LDL Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Modified LDL Taken up by Macrophage Intima Macrophage Foam Cell Steinberg D et al. N Engl J Med 1989;320:915-924.

  30. Macrophages and Foam Cells Express Growth Factors and Proteinases Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Intima Modified LDL Growth FactorsMetalloproteinases Cytokines Cell ProliferationMatrix Degradation Macrophage Foam Cell Ross R. N Engl J Med 1999;340:115-126.

  31. The Remnants of VLDL and Chylomicrons are also Proinflammatory Vessel Lumen Monocyte Remnant Lipoproteins AdhesionMolecules Endothelium MCP-1 Remnants Intima ModifiedRemnants Cytokines Growth FactorsMetalloproteinases Cell ProliferationMatrix Degradation Macrophage Foam Cell Doi H et al. Circulation 2000;102:670-676.

  32. Vulnerable Atherosclerotic Plaque Non-Vulnerable Atherosclerotic Plaque Pathogenesis of ACS www.drsarma.in

  33. Atherosclerosis A Progressive Process PlaqueRupture/Fissure &Thrombosis Occlusive AtheroscleroticPlaque FattyStreak FibrousPlaque Unstable Angina Normal MI Coronary Death Stroke Effort Angina Claudication Critical Leg Ischemia Clinically Silent Increasing Age www.drsarma.in Courtesy of P Ganz.

  34. Intima Lipidcore Fibrouscap Lumen Media –T lymphocyte – Macrophagefoam cell (tissue factor+) – “Activated” intimal SMC (HLA-DR+) –Normal medial SMC The Anatomy of Atherosclerotic Plaque www.drsarma.in Libby P. Lancet.1996;348:S4-S7.

  35. The Matrix Skeleton of UnstableCoronary Artery Plaque Fissures in the fibrous cap www.drsarma.in Davies MJ. Circulation. 1996;94:2013-2020.

  36. CHD Risk Factors – So Many ? • Malaria – One causative parasite • Tuberculosis – One definite bacterium • HIV and AIDS – One deadly virus • But for CHD – No one specific cause • It is a non communicable disease • It is multi factorial in its causation • The more ignorant we are about the causation, the more risk factors we seek and try to explain www.drsarma.in

  37. CHD – Makers and Markers The Makers – Risk Factors • Non Modifiable – The tough six • Modifiable – The conventional six • Modifiable – The contributing six The Markers – Surrogate tests • We rarely care – The simple six • We barely know – The complex six • We hardly need – The experimental six www.drsarma.in

  38. CHD Risk Factors - Makers • If non modifiable – why study them ? • Non Modifiable – The Tough Six • Age • Gender • Ethnicity • Family H/o of premature CHD • Phenotype B • Type A personality (partly modifiable) www.drsarma.in

  39. CHD Risk Factors - Makers • If modifiable – why not control them ? • Modifiable – The Conventional Six • Diabetes Mellitus • Dyslipidemia • Hypertension • Smoking / tobacco • Over weight and Obesity • Physical inactivity www.drsarma.in

  40. CHD Risk Factors - Makers • Modifiable – The contributing six • hs-CRP • Lp(a) • sLDL • Endothelial dysfunction • Apo B / Apo A1 ratio • Homocysteine www.drsarma.in

  41. CHD Risk Factors - Markers • We rarely care to identify – The simple six • WC – Waist Circumference – Are we tailors? • ED – Erectile Dysfunction; ED = ED • ABI – Ankle Brachial Index, IC, Pedal pulse • PP – Pulse Pressure – Importance of ISH • MAU – Micro Albuminuria – Dip stick test • LVH – By Echocardiography, ECG, CXR www.drsarma.in

  42. CHD Risk Factors - Markers • We barely know & test – The complex six • ABPM – Dippers & Non Dippers • FMD – Brachial Flow Mediated Dilatation • PCOS – Polycystic Ovarian Syndrome - USG • CIMT – Carotid Intima Media Thickness • FFAG – Florescence Fundus Angiography • STS – Stress Thallium Scan – for perfusion study www.drsarma.in

  43. CHD Risk Factors - Markers • We hardly need to test – The experimental six • C Peptide – Measure of Insulin Resistance • Uric Acid – Surrogate for Inflammation • Fibrinogen – Surrogate for coagulability • PAI 1 – Plasminogen Activator Inhibitor 1 • Inflam. markers – sICAM, ICAM. SAA, IL-6, MMP • Sub fractions – of LDL and HDL, IVUS www.drsarma.in

  44. CHD Risk Equivalents • Diabetes Mellitus • Peripheral Vascular Disease (PVD) • Framingham risk score of > 20% • Carotid artery disease – • Stroke, TIA • > 50% Narrowing, Carotid Bruit • Abdominal Aortic Aneurysm (AAA) Adult Treatment Panel III. NIH publication 01-3095. www.drsarma.in

  45. Non Modifiable Risk factors • Age • Gender • Ethnicity • Family H/o of premature CHD • Phenotype B • Type A personality www.drsarma.in

  46. Non Modifiable Risk factors • Age • Gender • Ethnicity • Family H/o of premature CHD • Phenotype B • Type A personality www.drsarma.in

  47. CHD risk increases as age advances Men > 45 and women > 55 – high risk CAD-I is 10 years younger Men suffer CAD 10 years early Increased longevity – Aging population Increased duration of risk exposure Multiplicity of risk factors occurs Treatment responses are blunted Age and CAD www.drsarma.in

  48. Non Modifiable Risk factors • Age • Gender • Ethnicity • Family H/o of premature CHD • Phenotype B • Type A personality www.drsarma.in

  49. CAD is ‘Disease of the Men’ – a myth Women CAD presents atypically Silent MI more common; 10 yrs later First attack mortality more common CAD deaths are twice those from all Ca DM is a more powerful risk factor for ♀ ↑ TG, LDL and ↓ HDL are common in ♀ Physical inactivity, Abd. obesity is more Gender and CAD www.drsarma.in

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