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The Maker and Marker of Cardio Vascular Ill Health

ENDOTHELIAL DYSFUNCTION = ED. The Maker and Marker of Cardio Vascular Ill Health. Prof. Dr. R.V.S.N. Sarma, M.D., M.Sc., (Canada), RCGP, FCGP, FIMSA, FRCP (Glasgow) Visiting Professor of Internal Medicine and Cardiology Senior Consultant Physician & Cardio-metabolic Specialist.

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The Maker and Marker of Cardio Vascular Ill Health

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  1. ENDOTHELIAL DYSFUNCTION = ED The Maker and Marker ofCardio Vascular Ill Health Prof. Dr. R.V.S.N. Sarma, M.D., M.Sc., (Canada), RCGP, FCGP, FIMSA, FRCP (Glasgow) Visiting Professor of Internal Medicine and Cardiology Senior Consultant Physician & Cardio-metabolic Specialist Visit us at: www.drsarma.in

  2. Heaven and Hell Sutton-Osler-Rendu-Weber-Syndrome (HHT) Nuclei in tail tip of MF of Mansonella ozzardi Tsutsugamushi fever – a scrub typus Diabetes Mellitus, Hypertension, Dyslipidemia Metabolic Syndrome, Cardiometabolic Risk The new paradigm shift in CMR Management

  3. We are always on the top • Saare jehan se achchaa ……. Hindustan hamara… • Saare jehan se oonchaa ……. T2DM hamara hamara… • Saare jehan se jyaadaa ……. CVD hamara hamara… CADI is phenomenon

  4. Coronary Artery Disease - CAD Cerebro Vascular Disease – CVD Peripheral Arterial Disease – PAD Chronic Kidney Disease - CKD At the end of the show there are only two exits Cardio Vascular Mortality - CVM All other causes of Mortality Exit 1 Exit 2 50% 50% www.drsarma.in

  5. Note the individual Endothelial Cells

  6. Endothelial Apoptosis Apoptosed Normal

  7. The Vascular Endothelium • The inner lining of our bloods vessels is the Endothelium • It plays a central role in regulating the vasomotor tone & • Local homeostasis & control of the coagulation process • Endothelial cells have ‘Sensors’ and release ‘Mediators’ • ‘Mediators’ are the functional molecules on the cell surface

  8. Vascular Endothelial Mediators Include the following • Nitric oxide (NO) • Cycloxygenase (CxO) • Endothelin-1 (ET-1) • Endothelium Depolarisation Factor (EDF) • And many others - thus • It is the largest endocrine gland

  9. ED and NO ↓ NO deficiency in the vessel wall promotes • Inflammation • Oxidation of lipoproteins • Smooth muscle proliferation • Accumulation of lipid rich material • Platelet activation and thrombus formation Finally results in atherosclerosis.

  10. Coronary Arteries Epicardial Artery Diameter  with ACh CBF  with ACh Epicardial Artery Diameter  with Adenosine Forearm Brachial Artery Diameter  with Arterial Occlusion FMD Forearm Blood Flow with ACh Clinical Methods for Assessing Endothelium-dependent Dilation

  11. Brachial Artery Flow-Mediated VasodilationBaseline 5 Minutes Post-Occlusion Blood Pressure Cuff Occlusion – 1 Minute Release 3.6 mm 3.1 mm

  12. Genes CV Risk Factors Endothelial Dysfunction NO ↑ Inflammation ↑ Thrombosis Cardio vascular Diseases Genetics Load the Gun – ButRemember – Environment pulls the trigger The Universal Damage

  13. Constrictors/ Growth Promoters Dilators/ Growth Inhibitors Angiotensin II Catecholamines Endothelin-1 ROS Cytokines EDCF Nitric Oxide Prostacyclin Bradykinin EDHF Vascular tone and structure Imbalance in Factors Affecting Vascular Tone and Structure Nephron destruction and renal failure EDHF= endothelium-derived hyperpolarizing factors ROS= reactive oxygen species EDCF= endothelium-derived constricting factors www.hypertensiononline.org

  14. Endothelial Regulatory Functions Vasodilation Vasoconstriction NO, PGI2, EDHF, BK, C-NP ROS, ET-1, TxA2, A-II, PGH2 Thrombolysis Thrombosis Endothelial Dysfunction, Inflammation Prothrombotic state, Vasoconstriction Platelet havoc, SMC proliferation tPA, Protein C, TF-I, vonWF PAI-1, TF, Tx-A2 Platelet Disaggregation NO, PGI2 Adhesion Molecules CAMs, Selectins Antiproliferation NO, PGI2, TGF-, Hep Growth Factors, ET-1, A-II, PDGF, bFGF, ILGF, IL Lipolysis Inflammation ROS, NF-B LPL

  15. Oxidative Stress: Endothelial Dysfunction and CAD/Renal Risk Factors Homocysteine Estrogen deficiency Smoking LDL Diabetes Hypertension O2Endothelial Cells and  H2O2 Vascular Smooth Muscle Endothelial Dysfunction Lipid deposition Thrombosis Apoptosis VSMC growth Leukocyte adhesion Vasoconstriction

  16. Today’s Thinking DIABETOLOGIST IS DEAD !! Cardio Metabologist Is Born !! The Islet, Vol 3, No2, May 2005

  17. Diabetes is No More Sweet From Blood Sugar to Blood Vessel

  18. IR,  Insulin Dyslipidemia IGT, IFG Increased CV Risk ED, ED Hypertension Pro Thrombotic Visceral obesity Pro Inflammatory

  19. Mirrors of CV Ill Health • Diabetes Mellitus (DM = CAD) • Hypertension, Isolated Systolic Hypertension • Pulse Pressure, Mean Arterial Pressure (MAP) • Metabolic syndrome, Waist Circumference • Left Ventricular Hypertrophy, TMT, CIMT • ABI (Ankle Brachial Index), Intermittent claudication • Micro albuminuria (MAU), H/o Smoking • hs-CRP, Serum Fibrinogen, Serum Amyloid  (SAA) • Erectile Dysfunction (ED) = ED • Retinopathy, Microangiopathy, OSA, PCOD, NAFLD

  20. Our Treasure in the Tummy

  21. Albumin Creatinine Ratio (ACR) Spot urine only (no 24 hour urine) Urine Microalbumin in mg/liter Urine creatinine in mg/deciliter ACR calculation : Urine MAU in mg/l 60 Urine Creatinine mg/dl120 X 100 = X 100 = 50

  22. Pulse Wave Record Ankle Brachial Index

  23. Isn’t it Enough ?

  24. Its not just your Legs !! ………. . Its your life

  25. Now we know why the titanic sank !! CHRONIC KIDNEY DISEASE – CKDA Silent Killer < 0.5 % 5- 10%

  26. Today’s Watch Word MDRD Formula based on Serum Creatinine, Age, Gender, Ethnicity

  27. Gender Bias in Treatment of Women “… The community has viewed women’s health almost with a ‘bikini’ approach, looking essentially at the breast and reproductive system, and almost ignoring the rest of the woman as part of women’s health ….”Nanette Wenger, MD Chief of Cardiology, Grady Hospital Professor of Medicine, Emory University Atlanta, Georgia www.drsarma.in

  28. Erectile Dysfunction Penis is the barometer of Endothelial Health Erectile Dysfunction is a mirror of Cardiovascular Risk ED = ED

  29. Vascular Protection for CMR • Atorvastatin (Lipid management) • ASA (Acetyl Salicylic Acid) – (enteric coated) • ACE inhibitors or ARBs • A1c control (Glycemic control) • Blood pressure goal (<130/80) • Control of Nephropathy, Proteinuria (MAU) • Cigarette smoking cessation • Weight and waist management • Physical Activity – at least 2 km/d x 5 d

  30. Drug May Cause ED • Beta blockers, Levodopa, Phenytoin • Thiazide diuretics, spironolactone, CAHI • SSRIs, TCA, MAOI, Disulfiram • Phenothiazines, Risperidone, Carbamazepine • LH-RH, estrogens • Gemfibrozil, Clofibrate • H2 Antagonists, Allopurinol, Indomethacin

  31. Television watching became even more convenient with Sony’s introduction of a new remote controlled remote control – Tokyo News line www.drsarma.in

  32. This how we walk the dog !

  33. Evolution or Devolution ?

  34. 20000 B.C. 2012 Paleolithic sup. age Neolithic age 19th century 21st century Processed foods Hunting-gathering subsistence Animal fats ­ and glucides Dietary fibre ¯ High level of Sedentary physical activity life Thrifty genotype Susceptibility genotype Where are we heading ?? Technology has changed a lot the way we live But, we have not altered our lifestyle Journal of internal medicine 2003:254(2):114-25

  35. யாகாவார் ஆயினும் நாகாக்க காவாக்கால்சோகாப்பர் சொல்லிழுக்குப் பட்டு Anything else you may be careless to guard, but not the tongue; for, even a slightest slip of it, sure drowns you in misery. యాకావార్ ఆయిణుమ్ నాకాక్క కావాక్కాల్ సోగాప్పర్ సొల్లిళుక్కు ప్పట్టు.

  36. The Ultimate Call Trividham narakasya idam dwaram nasanam atmanah Kamah krodhah tadha lobhah tasmaat yaetat triam tyajaeth BG 16:21 Trividham narakasya idam dwaram nasanam sareerinah sharkara lavanam tadha tailam tasmaat yaetat triam tyajaeth CADI Call

  37. The Almighty is Only ONE Govind bolo, Gopal bolo Shiv dev bolo, Ram naam bolo Allah, Malik, Yesu, Naanak Ye naam saare jeevan sahare Jo naam chaaho O naam bolo Laekin Prem se maano Dhyaan se jaano Worship Govind or Gopal or Lord Shiva or Ram’s name Allah, Maalik, Yesu & Naanak In journey of life, All Do help Whatever Form you are fond of Please take refuge in Him But, do that with love and With perfect focus & attention!

  38. All these Mean Only ONE CAD bolo, CKD bolo PAD (PED) bolo CVD bolo Ye naam saare ek hi bimaari Jo naam dekho Sub naam poocho, Lekin Jaldee hi jaano Aagae hi pakado Call it CAD or CKD Call it PED, Call it CVD All of them are but one Malady Whatever form of them U see Don’t ignore other circuits pl Verily investigate early and Start the risk modification !!

  39. Thank You All

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