The document discusses cardiovascular risk factors and management. It summarizes that most heart attacks are caused by low-grade coronary artery blockages rupturing and triggering blood clots. Several risk factors can make plaques more vulnerable to rupture, such as inflammation, thin fibrous caps, and lipid-rich cores. Lifestyle changes and statin drugs are effective at reducing cardiovascular risks by lowering cholesterol levels and having additional anti-inflammatory effects. More aggressive lowering of LDL cholesterol is associated with greater reduction in heart attack risk.

1. Holistic in Risk factors and Cardiovascular Management Warong Lapanun MD. Cardiology division Bhumibol Adulyadej Hospital Emergency Medicine Lunch Symposium: 2/9/07

4. Atherosclerosis

5. Cross-section through the wall of a healthy artery with intact endothelium, intima and smooth muscle bundles (SEM)

6. Artery demonstrating endothelial erosion (SEM)

8. Intimal thickening Extralipid pool Fibrous scar

9. Atheromatous plaque

10. Plaque Rupture

11. Coronary occlusion Plaque rupture Occlusive thrombus

16. Coronary Remodeling (Adapted from Glagov et al.) Normal vessel Minimal CAD Progression Compensatory expansion maintains constant lumen Expansion overcome: lumen narrows Severe CAD Moderate CAD Glagov et al, N Engl J Med , 1987.

17. Atherosclerosis: A Progressive Process Disease progression PHASE I: Initiation PHASE II: Progression PHASE III: Complication Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis MI Stroke Critical Leg Ischemia Coronary Death Unstable Angina Libby P. Circulation. 2001;104:365-372.

18. IVUS=intravascular ultrasound Nissen S, Yock P. Circulation 2001 ; 103: 604–616 Angiogram IVUS Little evidence of disease Atheroma No evidence of disease The IVUS technique can detect angiographically ‘silent’ atheroma

19. Correlation of CT angiography of the coronary arteries with intravascular ultrasound illustrates the ability of MDCT to demonstrate calcified and non-calcified coronary plaques (Becker et al., Eur J Radiol 2000) Non-calcified, soft, lipid-rich plaque in left anterior descending artery (arrow) . The plaque was confirmed by intravascular ultrasound (Kopp et al., Radiology 2004)

21. Estimated 10-Year CHD Risk in 55-Year-Old Adults According to Levels of Various Risk Factors : Framingham Heart Study A B C D Blood Pressure (mm Hg) 120/80 140/90 140/90 140/90 Total Cholesterol (mg/dL) 200 240 240 240 HDL Cholesterol (mg/dL) 50 50 40 40 Diabetes No No Yes Yes Cigarettes No No No Yes Source: Circulation 1998;97:1837-1847.

22. CHD Mortality 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 3.77 (1.74-8.17) Follow-up, Y Cumulative Hazard (%) Yes No 866 288 852 279 834 234 292 100 The Kuopio Ischaemic Heart Disease Risk Factor Study Unadjusted Kaplan-Meier Curve No. at Risk Metabolic Syndrome Yes Metabolic Syndrome: 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 2.43 (1.64-3.61) Follow-up, Y 866 288 852 279 834 234 292 100 CVD Mortality All Cause Mortality Lakka H-M, et al. JAMA . 2002;288:2709-2716. No 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 3.55 (1.96-6.43) Follow-up, Y 866 288 852 279 834 234 292 100

27. Discharge Dx

28. Gender

31. Risk factors

32. Prevalence of RF according to gender

33. Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670 2001. http://hin.nhlbi.nih.gov/ncep_slds/menu.htm 1% decrease in LDL-C reduces CHD risk by 1% 1% increase in HDL-C reduces CHD risk by 3%

34. CHD Outcomes in Clinical Trials of LDL Cholesterol-Lowering Therapy Mean CHD CHD No. No. Person- cholesterol Incidence Mortality Intervention trials treated years reduction (%) (% change) (% change) Surgery 1 421 4,084 22 -43 -30 Sequestrants 3 1,992 14,491 9 -21 -32 Diet 6 1,200 6,356 11 -24 -21 Statins 12 17,405 89,123 20 -30 -29 Source: This table is adapted from the meta-analysis of Gordon, 2000.

36. Vessel Wall And Endothelial Cell Membrane Changes With Atherogenesis Reproduced from Mason et al. Circulation . 2004;109(suppl II):II-34, with permission. Mason et al. Am J Cardiol . 2005;96(suppl):11F.

37. Role Of Statins In ACS: Non-Lipid Effects ( Pleiotropic effects) ADP = adenosine diphosphate; CD40-L = CD40 ligand; IFN = interferon; IL = interleukin; vWF = von Willebrand factor. Reproduced from Ray and Cannon. J Thromb Thrombolysis . 2004;18:89, with permission. Cannon and Ray. Am J Cardiol . 2005;96:54F.

38. Clinical Events Correlate Directly With On-Treatment LDL-Cholesterol Levels P = placebo; S = statin. Reproduced from O'Keefe et al. J Am Coll Cardiol . 2004;43:2142, with permission. CHD Events (%) 10 9 8 7 6 5 4 3 2 1 0 -1 55 75 95 115 135 155 175 195 LDL Cholesterol (mg/dL) y = 0.0599x - 3.3952 R 2 = 0.9305 P =.0019 AFCAPS-S WOSCOPS-S ASCOT-S ASCOT-P AFCAPS-P WOSCOPS-P Primary prevention: 4-5 yr duration

39. ASCOT-LLA: Nonfatal MI And Fatal CAD Primary End Point Adapted from Sever et al. Lancet . 2003;361:1149, with permission. Sever et al. Am J Cardiol . 2005;96(suppl):39F. 2 0 1 4 3 Years 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Cumulative Incidence (%) Placebo Atorvastatin 10 mg Number of Events 36% Reduction HR = 0.64 (0.50-0.83) P =.0005 Number of Events 154 100 N=10,305

40. Effects of Lipid-Lowering Therapy on CHD Events in Statin Trials 25 20 15 10 5 0 Patients with CHD event (%) 90 110 130 150 170 190 210 S = statin-treated P = placebo-treated *Extrapolated to 5 y 4S - P CARE - P LIPID - P 4S - S WOSCOPS - S WOSCOPS - P AFCAPS - P AFCAPS - S LIPID - S CARE - S Primary prevention Simvastatin Pravastatin Lovastatin Modified from Kastelein JJP. Atherosclerosis. 1999;143(suppl 1): S17-S21. HPS - S HPS - P Atorvastatin ASCOT - S * ASCOT - P * Secondary prevention LDL-C (mg/dL)

41. PROVE IT-TIMI 22: A Major Cardiovascular Event Or Death From Any Cause Primary End Point Adapted from Cannon et al. N Engl J Med . 2004;350:1495, with permission. Ray and Cannon. Am J Cardiol . 2005;96(suppl):54F. 15 0 10 30 25 5 20 Months Of Follow-Up 0 3 9 15 21 6 12 18 24 27 30 Death Or Major Cardiovascular Event (%) Pravastatin 40 mg Atorvastatin 80 mg P =.005 Overall P =.03 n= 4,162 with CHD

43. PROVE IT-TIMI 22: A Major Cardiovascular Event Or Death From Any Cause At Different Censoring Times Reproduced from Cannon et al. N Engl J Med . 2004;350:1495, with permission. Ray and Cannon. Am J Cardiol . 2005;96(suppl):54F. Censoring Time Hazard Ratio (95% CI) Risk Reduction (%) Event Rate (%) Atorvastatin Pravastatin 30 days 90 days 180 days End of follow-up 17 1.9 2.2 18 6.3 7.7 14 12.2 14.1 16 22.4 26.3 0.50 0.75 1.0 High-Dose Atorvastatin Better Standard-Dose Pravastatin Better 1.50 1.25

44. NCEP-ATP III National Cholesterol Education Program Adult Treatment Panel III

45. Evolution of Lipid Management Guidelines ATP I (1988) ATP II (1993) ATP III (2001) Diet; low-dose, nonstatin monotherapy High-dose statin, combination therapy Low- to moderate-dose statin monotherapy Increasing aggressiveness of cholesterol-lowering therapy The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)

46. Update to ATP III: Risk Categories, LDL-C Goals Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines: Circulation . 2004;110:227-239. <160 <130 <130 <100 (optional <70) LDL-C Goal (mg/dL) > 160 > 130 > 130 > 100 Initial TLC (mg/dl) > 130 (optional 100-129) Moderately high risk: 2+ risk factors (10-year risk 10-20%) > 190 (optional 160-189) Lower risk: 0–1 risk factor >160 Moderate risk: 2+ risk factors (10-year risk  10%) > 100 (optional <100) High risk: CHD or CHD risk equivalents (10-year risk >20%) Consider drug (mg/dl) Risk Category

47. Am J Cardiol. 2004;93: 154-8

60. HDL LDL TG Total chol

73. Cardiac Emergency

78. Angina chest pain

81. AMI Definition • Chest pain • ECG • Troponin positive

82. STEMI Blood flow Chest discomfort PMVT, VF Sudden Death M. Ischemia Heart failure Cardiogenic shock Elevated +CK,Trop-T M.stunning Consequences after acute coronary artery occlusion NSTEMI ,UA Cardiovascular Research & Prevention Center, Bhumibol Adulyadej hospital

83. Wave Front Theory LAD occlusion

86. Acute antero-lateral MI

89. Extensive antero-lateral ischemia

90. Effect of thrombolytic on mortality according to admission ECG Live save per thousand FTT Collaborative group: Lancet 1994; 343

91. Applicability and Efficacy of Lysis vs PCI 0% 50% 100% 100% 50% 0% Fribrinolysis Primary angioplsty Availability Availability 10% <50% Treated > 90% TIMI 3 > 90% Treated Reocclusion Stroke 54% TIMI 3 5% 0.1% 10% Reocclusion 1% Stroke 25% Reocclusion

92. Total ischemic time A B C ER Rx <30min (lytic) <90 min (PCI) CP reperfuse microvascular epicardial

93. การคัดกรอง

95. 30-day mortality (%) Relationship between 30-day mortality and Door to Balloon time( N=522 ) Berger et al. Circulation 1999;100:14-20 P=0.001

96. PCI vs Fibrinolysis with fibrin-specific agents

102. 60 yo man, smoker, 1hr severe CP, BP 100/60

103. 58 yo lady, DM HT, syncope, sweating, CP 2/10, BP 80/60

104. V4R

106. 68 yo man, 3 hrs 8/10 CP, BP 100/60

108. Algorithm for ECG identification of the IRA in Anterior MI STE in V 1 , V 2 and V 3 STE in V1 (>2.5 mm) and AVL or RBBB with Q wave or both ST depression (<1 mm) in II, III, and AVF STE in II, III, and AVF Wrap around

109. A 63 yo lady, 3 hrs 7/10 CP Given Metalalyse + Clexane , continuing chest pain, VF x II in cath lab

115. ED :55 yo man, 3 hrs Lt. CP 5/10, less with sits forward

116. GP: 34 yo athlete, anterior CP 3/10, pt. of tenderness Fish hook

117. 60-yo man severe headache and collapsed

125. SVT after Rx with Adenosine 6mg IV

126. AF with WPW: How to Rx? Unstable : Cardioversion 100 J Stable : Amiodarone 150 mg IV

127. 34-yo lady, gen. edema 3 mo.

130. Cardiac tamponade

131. Pericardiocentesis

133. Hemopericardium

134. 23-y-old man with fever 7 day and chest pain

135. Pericardial fluid

137. Wong, T. Y. et al. N Engl J Med 2004;351:2310-2317 Examples of Mild Hypertensive Retinopathy AV nicking Focal narrowing AV nicking Copper wiring

140. Cerebral Autoregulation Mean arterial pressure (mmHg) Cerebral blood flow (ml/100 gm per min ) 50 100 150 200 150 100 50 0 Normotensive Hypertensive Strandgaard S,et al; Br Med J 1:507, 1973

145. Approach to HT crisis BP > 220/120 mmHg Headache No neurosign No target organ damage Urgency Identify the cause and Rx the cause ( panic, anxiety) Otherwise use oral anti HTagent Neurosign( encep., stroke) Retinopathy gr III, IV severe chest pain ( IHD, dissecting aneu) Pulmonary edema Cathecholamine excess ARF Emergency IV therapy Recheck in 6-24 hr

146. Question