Coronary artery disease & its prevention

this article discusses about coronary artery disease, its symptoms, presentations, risk factors, pathophysiology in short and primary prevention. this article is intended to present to a group of physicians in various disciplines other than cardiology.

1. CORONARY ARTERY DISEASE & ITS PREVENTION DR MD ASHRAF UDDIN CHOWDHURY FCPS (MEDCINE), MD (CARDIOLOGY) CENTRAL POLICE HOSPITAL DHAKA

2. CORONARY ARTERY DISEASE Coronary artery disease is the most common form of heart disease in all over the world. A narrowing of the coronary arteries prevents adequate blood supply to the heart muscle in this condition. Usually caused by atherosclerosis, it may progress to the point where the heart muscle is damaged due to lack of blood supply. Such damage may result in infarction, arrhythmias, and heart failure.

3. CORONARY ARTERY DISEASE IS ALSO KNOWN AS; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) CORONARY ATHEROSCLEROSIS CORONARY HEART DISEASE ISCHAEMIC HEART DISEASE

4. CORONARY ATHEROSCLEROSIS CORONARY ATHEROSCLEROSIS is the abnormal accumulation of lipid or fatty substances or fatty atheroma (plaque) in the lumen of coronary artery

5. RISK FACTORS Non Modifiable Modifiable

6. MODIFIABLE Atherogenic dyslipidaemia Cigarette smoking, tobacco use Hypertension Diabetes mellitus Physical inactivity or sedentary lifestyle Obesity

7. NON MODIFIABLE Family history of premature CAD in first degree relatives. Increasing age Gender(male) Race(non white populations)

8. Emerging risk factors: Metabolic syndrome High Triglyceride Apo Lipoprotein B Dietary trans fat intake Poor oral health Fibrinogen Homocysteine Urine microalbuminuria / creatinine ratio (CKD) High sensitivity CRP Impaired fasting glucose

9. Synergy of risk factors : The CAD death risk in men who smoke, have DBP>90 mm Hg, TC>250 mg/dl, the actual risk is more than all the three risk factors are added Thus there is multiplicative effect of multiple risk factors acting in concert. Also control of one risk factor provides substantial benefit in persons with multiple risk factors

10. PATHOPHYSIOLOGY Normal arterial wall has three layers: Intima - limited by internal elastic lamina Media- between internal and external elastic lamina Adventitia Intima is the site at which the atherosclerotic lesions form

11. PATHOPHYSIOLOGY ?? ETIOLOGICAL FACTORS INJURY TO THE ENDOTHELIAL CELL LINING THE ARTERY INFLAMMATION AND IMMUNE REACTIONS LDL Oxidation: acts as free radicals and Initiates Inflammatory Process Oxidized LDL enters the artery intima & there is ACCUMULATION OF LIPIDS IN THE INTIMA OF ARTERIAL WALL

12. T LYMPHOCYTES AND MONOCYTES THAT BECOMES AS MACROPHAGES INFILTRATE THE AREA TO INGEST THE LIPIDS AND BECOME FOAM CELL PROLIFERATION OF SMOOTH MUSCLE CELLS WITH IN THE VESSEL FORMATION OF FIBROUS CAP OVER FATTY CORE (ATHEROMA) PROTRUSION OF ATHEROMA IN TO THE LUMEN OF VESSEL

13. NARROWING AND OBSTRUCTION IF CAP IS THIN THE LIPID CORE MAY GROW CAUSING IT TO RUPTURE HEMORRHAGE INTO PLAQUE ALLOWING THROMBUS TO DEVOLOP THROMBUS OBSTRUCT THE BLOOD FLOW LEADING TO SUDDEN CARDIAC DEATH OR MYOCARDIAL INFARCTION ANGINA AND OTHER SYMPTOMS

14. The process of atherosclerosis begins in childhood and has clinical manifestations in late adulthood The process develops over years to decades and progression is not linear and smooth but discontinuous with periods of quiescence and rapid evolution.

15. IHD – Clinical Spectrum Chronic Stable Angina Silent Ischemia Mixed Angina Microvascular Angina (Syndrome X) Stunned & Hibernating Acute Unstable Angina Acute Myocardial Infarction (NSTEMI, STEMI) Sudden Cardiac Death Prinzmetal Angina 18

16. ANGINA PECTORIS Angina pectoris is a clinical syndrome usually characterized by central chest pain, discomfort or breathlessness that is precipitated by exertion or any stress and promptly relieved by rest or nitrate. It may occur when there is imbalance between myocardial oxygen supply and demand. Coronary atheroma is the commonest cause of angina.

17. Variant angina Also called prinzmetal angina. Pain at rest with reversible ST segment elevation thought to be caused by coronary artery vasospasm

18. 21 Prolonged bouts of chest pain at rest with EKG ST seg. elevation. PRINZMETAL OR VARIANT ANGINA A = Marked transitory ST Elevation during a bout of severe chest pain B = Thirty min. after A (Normal EKG) Pathophysiology: profound spasm of one of the three major epicardial coronary arteries.

19. Microvascular angina Also known as syndrome X Patient have chest pain with ECG change In this condition stress test (ETT) is positive But does not have any blockage in epicardial coronary artery in angiogram. The pain is due to blockage or spasm in cardiac microvasculature.

20. 23 Pathophysiology: Dynamic small vessel constriction (vasospasm) (positive stress testing)

21. Silent ischaemia Objective evidence of ischaemia (such as electrocardiographic changes with a stress test) but patient has no symptoms Commonly seen in diabetic patients.

22. Is the objective evidence-ST segment shifts- of myocardial ischemia which is not associated with angina or angina equivalents. 25 Silent Ischemia ST seg. depression Iceberg’s sign Angina

23. ANGINA PAIN FEATURES Squeezing burning tightening aching pain or discomfort across chest The pain often spread to neck, jaw, arms, shoulders, throat, back or even teeth Angina pain starts with exertion which is mostly predictable . It is relieved with rest or after taking nitrate .

24. ACUTE CORONARY SYNDROME(ACS) ACS is a term that encompasses both unstable angina and Myocardial Infarction (MI). After rupture of an ulcerated or fissured plaque, there is a dynamic process whereby degree of obstruction may either increase leading to complete vessel occlusion and MI, or regress due to endogenous fibrinolysis .

25. Unstable angina New onset or rapidly worsening angina or angina on minimal exertion or angina at rest in the absence of myocardial damage. Also called preinfarction angina Symptoms occur frequently and last longer than stable angina Pain may occur at rest . The culprit lesion is usually an ulcerated or fissured atheromatous plaque with adherent platelet rich thrombus and local coronary artery spasm.

26. MYOCARDIAL INFARCTION Myocardial infarction refers to the dynamic process in which a region of the heart experience a severe prolonged lack of oxygen supply due to complete occlusion of coronary artery with subsequent necrosis or death to myocardial tissue . The process of infarction progress over several hours.

27. Progression of coronary plaque over time Clinical Findings 32 Acute Coronary Syndromes Sudden Cardiac Death Acute silent occlusive process Angina pectoris Thrombogenic risk factors Atherogenic risk factors Endothelial dysfunction 20 years 60 years Age

28. IS CORONARY ARTERY DISEASE PREVENTABLE? WHAT CAN WE DO TO PREVENT CAD?

29. Lifestyle changes / Health behaviours Lifestyle changes that may be useful in coronary disease include: Smoking cessation Exercise Healthy diet Stress management Weight control / Obesity reduction

30. Control of risk factors Control of Hypertension Control of diabetes Management for dyslipidaemia

31. Stress Psychosocial factors associated with CAD risk: Type A personality Hostility/Anger Depression/Anxiety 3 to 4 times increased risk of death in first year following MI

32. Stress Influence CAD risk via 2 main mechanisms: Catacholamine release increased BP increased HR vasoconstriction increased O 2 demand Decreased adherence to lifestyle modification recommendations

33. Healthy Diet Diets high in fruits, vegetables, whole grains, fish and unsaturated fatty acids have lower risk for CAD

34. Good and Bad Cholesterol Actually , some cholesterol is necessary for proper body function. But dietary saturated fat and cholesterol both raise levels of LDL "bad" cholesterol . High levels of LDL cholesterol can cause plaque to build up in arteries, leading to heart disease and stroke. HDL is a "good" cholesterol in that it helps eliminate bad cholesterol from blood . It is possible to lower LDL cholesterol and raise HDL cholesterol with diet.

35. Serve Up Heart-Healthy Food When it comes to fruits and vegetables , pick up the pace! Multiple servings throughout the day can help lower LDL "bad " cholesterol. Moreover, these foods have antioxidants that can be beneficial. Also, eating more vegetables and fruits often results in eating fewer high-fat foods. This can lower blood pressure promote weight loss.

36. Think Fish For Heart Health Fish is generally exceptionally heart healthy because it is high in healthy omega-3 fatty acids and low in saturated fat. It is the omega-3 fatty acids that help lower blood levels of triglycerides. Especially emphasize fatty fish. Keep in mind that deep oil frying of any food diminishes the health benefits.

37. Start the Day With Whole Grains Oatmeal or whole-grain cereal have fiber and complex carbohydrates that help to feel fuller for longer, so a person is less inclined to overeat later in the day. These breakfasts help reduce LDL "bad" cholesterol and can help with our weight control .

38. Go Nuts for Cardiovascular Health Nuts help to lower cholesterol because they are high in monounsaturated fat . This form of fat lowers LDL "bad" cholesterol while maintaining HDL "good" cholesterol levels. This can lower the risk of heart disease. Only eat a handful, though, because nuts are high in calories, especially if they are coated in sugar or chocolate.

39. Unsaturated Fats Protect the Heart Our daily fat needs are only about a third of our daily calories. However, the form of fat makes a difference. Unsaturated fats (in canola, olive, and sunflower oils ) lower LDL "bad" cholesterol levels. Saturated fats (in butter and palm oil) and trans fats increase LDL cholesterol . All fats have calories. Moderation is the key.

40. Eat More Beans, Fewer Potatoes Carbohydrates are important for energy production. However, there are differences in the quality of carbohydrates, too. Whole grains like beans , quinoa, whole-wheat pasta, and brown rice are high in fiber that can help lower cholesterol. Whole grains also keep you feeling full longer. The carbohydrates in pastries, white rice, white bread, and potatoes boost blood sugar levels rapidly. This can lead you to feel hungry sooner, potentially leading to overeating.

41. Obesity Body Mass Index (BMI) Measured in weight in Kg /height in m 2 BMI Targets Underweight <18.5 Normal 18.5-24.9 Overweight 25.0-29.9 Obese >30 Definition of central obesity in South asians : – Waist circumference of Men >90cm or 36 inches, Women >80cm or 32 inches

42. Sedentary Lifestyle & Exercise Regular exercise- at least 30 minutes , 3 or 4 times a week. Physical activity reduces the risk of CAD through: Improved balance between myocardial O 2 supply and demand Decreased platelet aggregation Decreased susceptibility to malignant ventricular arrhythmias Improved endothelial tone Beneficial effect on other CAD risk factors ( ie . diabetes, dyslipidaemia, hypertension, obesity, stress)

43. Blood pressure target Normal <120 / 80 Prehypertensive (120/80 to 139/89 mm Hg) Stage 1 (140/90 to 159/99 mm Hg) Stage 2 (≥160/100 mm Hg) *JNC 7

44. Lipid Targets for CAD Primary Targets for very high risk patients *: LDL-C < 1.8mmol/L (70 mg/dl) or <50% reduction (< 100mg/dl in moderate risk patients) Non HDL-C ≤ 2.6 mmol /L (100 mg/dl) (< 130mg/dl in moderate risk patients) Alternate : Apolipoprotein B < 0.80 g/L Can J Cardiol 29 (2013) 151–167 . *National lipid association Annual summary 2015 *ESC guideline 2015

45. Lipid Targets for CAD Secondary Targets: (once LDL cholesterol is at goal) Total Cholesterol to High Density Lipoprotein (HDL) cholesterol ratio less than 4.0 Non HDL cholesterol < 3.5 mmol /L Triglycerides < 1.7 mmol /L (150 mg/dl) Apolipoprotein B to apolipoprotein AI ratio < 0.8 High-sensitivity C-reactive protein (CPR) < 2 mg/L Can J Cardiol 2009; 25(10): 567-579.

46. Diabetes People with diabetes have 2 to 7 times increased risk of developing CAD than people without diabetes Mechanism of atherosclerosis is unclear Endothelial damage Increased platelet aggregation Insulin promotes synthesis of lipids and uptake of lipids by smooth muscle Excess sugar in vessels damages the endothelial lining making it vulnerable to plaques and clots

47. Diabetes Careful control of blood sugar levels reduces the risk of developing the complications of diabetes Targets for diabetic control-as near normal as possible Canadian guideline: FBG 4-7 mmol /L 2 hr pc BS 5-11 mmol /L HbA1C <7

48. Emerging Risk Factors Nontraditional factors that are associated with increased risk of CAD, but a causal link has not yet been proved with certainty Poor oral health Dietary trans fat intake Homocysteine Lipoprotein A Infectious agents Adhesion molecules Cytokines Fibrinogen High sensitive C-reactive protein

49. Lifestyle interventions to reduce TC & LDL-C levels Reduce dietary saturated fat Reduce dietary trans fat Reduce dietary cholesterol Increase dietary fibres Utilize functional foods enriched with phytosterols Reduce excessive body weight Increase physical activity Utilize Soy protein products **ESC guideline on dyslipidaemia 2015

50. Drugs to lower LDL Statins – atorvastatin , rosuvastatin , simvastatin , Ezetimibe Investigational agent- evolocumab & alirocumab ( PCSK9 inhibitors )- >50% reduction in LDL-c and nonHDL -c levels

51. Lifestyle interventions to reduce TG levels Reduce excessive body weight Reduce alcohol intake Reduce intake of mono and disaccharides Reduce total amount of dietary carbohydrate Increase habitual physical activity Utilize supplements of n-3 polyunsaturated fat Replace saturated fat with mono or poly unsaturated fat. **ESC guideline on dyslipidaemia 2015

52. Drugs to lower Tg Fenofibrate Gemfibrozil , colestipol , cholestyramine etc

53. Lifestyle interventions to increase HDL-C levels Reduce dietary trans fat Increase habitual physical activity Reduce excessive body weight Reduce dietary carbohydrate and replace them with unsaturated fat . Use alcohol with moderation Prefer carbohydrate with low glycaemic index and high fibre content Quit smoking Reduce intake of mono and disaccharides **ESC guideline on dyslipidaemia 2015

54. Drugs to raise HDL-c Currently none in clinical use. Investigational agent- anacetrapib , evacetrapib , - 150% increase in HDL-c.

55. SUMMARY Control of - Dyslipidaemia, Hypertension & DM Healthy behaviours - Smoking cessation Weight control Exercise Healthy diet Stress free life

56. Important Trials that showed role of statins in CAD AVERT( atorvastatin versus revascularization treatment ) - incidence of ischaemic evects was 36% lower in atorvastatin group compared with revascularization group(PTCA) ASTEROID (a study to evaluate effects of rosuvastatin on intravascular ultrasound derived coronary atheroma burden)– 9.1% reduction in atheroma volume in heavy plaque burden area of coronary artery. JUPITER (Justification for the use of statins in primary prevention: an intervention trial evaluating rosuvastatin )– this trial was stopped prematurely as it was seen unequivocally rosuvastatin reduces morbidity and mortality than placebo in primary prevention. SATURN - study of coronary atheroma by intravascular ultrasound: effects of rosuvastatin versus atorvastatin . Both were effective in reducing coronary atheroma .

57. Thank you all !!

58. This presentation was prepared for a group of physicians working in various disciplines in a large generalhospital . Very often they ask me whether he or she have CAD and what they should do to avert this deadly disease. Here I have discussed how to diagnose coronary artery disease clinically, its pathophysiology in short and how to prevent it (primary prevention). Investigations and management was not discussed in this presentation. If anyone find this presentation helpful, I shall be very happy. I convey my thanks to people who made some of these slides, pictures and also thanks in advance to those who intend to use these. Thanking you, Dr md ashraf uddin chowdhury FCPS, MD (Cardiology) Clinical and interventional cardiologist. [email protected]