Coronary Artery Disease **CAD Risk Stratification** Dr. Joseph A Akamah 2016

OBJECTIVES To describe the burden of CAD To discuss the risk factors for CAD To discuss the role of global risk scores To discuss the role of clinical, stress testing, calcium score and CTA in risk stratification

Worldwide Causes of Mortality World Health Organization

Distribution of CVD deaths: Males vrs Females

Chart 22-2 The 16 leading diagnoses for direct health expenditures, United States, 2007 (in billions of dollars) Roger, V. L. et al. Circulation 2011;123:e18-e209

AHA Heart Disease and Stroke Statistics — 2008

Breakdown of Deaths Due to Cardiovascular Disease Focus on problem areas to maximize preventive measures Circulation. 2011;123:e18-e209

It is all about Atherosclerosis! Lipid accumulation and modification. Endothelial dysfunction. Inflammation.

The biology of the artery wall in the atherogenesis. O’Brien KD, Chait A. Med Clin North Am 1994;78:41-67.

The Endothelium

Endothelial Dysfunction

Inflammation: Concept of Vulnerable and Stable Plaques Characteristics of Vulnerable Plague Large Lipid Core High Macrophage Density/Activity Low SMC Density Thin Cap-Disorganized Collagen High TF Content

CAD Risk Factors Modifiable Nonmodifiable Increasing Age Male gender Tobacco Use Elevated LDL cholesterol Low HDL cholesterol High Triglycerides High blood pressure Diabetes Physical Inactivity Obesity Diet high in Saturated fat Social Stress: Poverty, Social Isolation, Stressful life Alcohol 1 to 2 drinks may lead to 30% (reduce) Medications Increasing Age Male gender Family history of premature CHD Ethnic Group/Race

INTERHEART Study Included population in 52 countries Identified 9 risk factors responsible for 90% of the CVD risk: Smoking Dyslipidemia Hypertension Diabetes Obesity Diet Physical activity Alcohol consumption Psychosocial factors. Lancet. 2004;364: 937-952.l

Natural History of Coronary Artery Disease Death MI Unstable Angina Stable angina Atherosclerosis Risk Factors PREVENTION

Comparison of risk factors considered in the overall cardiovascular risk scores Framingham SCORE PROCAM (Men) Reynolds (Men) Risk factors Age, sex, total cholesterol, HDL, smoking, sBP, antihypertensive medication Age, sex, total cholesterol – HDL ratio, smoking, sBP Age, LDL, HDL, smoking, diabetes, sBP, triglycerides, family history Age, total cholesterol, CRP, family history of MI at age <60 years Electronic address http://hp2010.nhlbihi.net/atp iii/calculator. http://www. heartscore.org http://www.chdtaskforce.co m/coronary_risk_assessme nt.html http://www.reynoldsrisk score.org/

CAD Pathophysiology 2 asymptomatic stable angina progressive angina The patient’s risk is usually a function of four types of patient characteristics CAD typically cycles in and out of clinically defined phases asymptomatic stable angina progressive angina unstable angina acute MI Functioning of the LV. (EF) Anatomic extent and severity of atherosclerotic involvement of the coronary tree. Evidence of a recent coronary plaque rupture (ACS) General health and noncoronary comorbidity.

Clinical Classification of Chest Pain Typical angina (definite) Substernal chest discomfort with a characteristic quality and duration of 3-15 minutes Provoked by exertion or emotional stress(Predictable) Relieved by rest or NTG or absence of stressor Atypical angina (probable) Meets 2 of the above characteristics. NonAngina chest pain Meets one or none of the typical anginal characteristics. Sharp pain, Pricking, lasting seconds, hours, days

Pretest Probability of Coronary Artery Disease by Age, Gender, and Symptoms Age (Y) Gender Typical/ Definite Angina Pectoris Atypical/ Probable Angina Pectoris Nonanginal Chest Pain Asymptomatic 30-39 Men Women Intermediate Very low Low 40-49 High 50-59 60-69

Prevalence (%) of Coronary Artery Disease According to Sex, Age, and Symptom Age Range Symptoms None Nonanginal Chest Pain Atypical Angina Typical Angina Male 30-39 2 5 22 70 40-49 6 14 46 87 50-59 10 59 92 60-69 12 28 67 94 Female <1 1 4 26 3 13 55 8 32 79 19 54 91 Diamond GA, Forrester JS. N Engl J Med 1979;300:1350-8.

Nomogram showing the probability of severe (three-vessel or left main) coronary disease based on a five-point score. One point is awarded for each of the following variables: male gender typical angina history and ECG evidence of MI diabetes and use of insulin Each curve shows the probability of severe coronary disease as a function of age Hubbard BL, Gibbons RJ, et alArch Intern Med 1992;152:309-12.

Clinicals: EPIDEMIOLOGY CHEST PAIN Typical Angina, Atypical Angina or Nonanginal Age Gender BAYES’ THEOREM Past Experience + Present Observation = Future Interpretation DIAMOND AND FORRESTER 1 mm ST-Segment Depression Varies According To Type of Chest Pain and Pretest Probability Information Gained is 5X more In Atypical Angina Than Patients Without Symptoms and 2.5X that of Patients with Typical Angina SENSITIVITY AND SPECIFICITY PREDICTIVE VALUE AND RELATIVE RISK

Sensitivity and Specificity Sensitivity: among those with disease, the proportion with a positive test (true positive) Specificity: among those without disease, the proportion with a negative test (true negative) Positive Predictive Value: among those with a positive test, the proportion that has the disease Negative Predictive Value: among those with a negative test, the proportion that does not have the disease Likelihood Ratio: the ratio of the probability of a certain test result in people with the disease to the probability in people without the disease

Brown KA, Rowen M. Impact of antianginal medications, peak heart rate and stress level on the prognostic value of a normal exercise myocardial perfusion imaging study. J Nucl Med 1993;34:1467-71

Incremental Prognostic Value of Clinical, Exercise, Myocardial Perfusion Imaging, and Cardiac Catheterization Data Iskandrian AS, et al. J Am Coll Cardiol 1993;22:665-70. Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease.

Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900-6.

DECISIONS

Three Groups based on Cardiac Mortality High Risk >3% per year Intermediate Risk 1-3% per year Low Risk <1% per year

Non-Invasive Risk Stratification

Low risk

STRESS TEST: REAL WORLD Why do you STRESS about Stress Testing? Is the stress test necessary? Is the reason purpose of Diagnosis? effectiveness of Therapy? risk stratification? To begin exercise program? Help define what treatment plan? Is any form of imaging required for localization of Ischemic segment? Which imaging modality? Which stress test modality is better for your px: exercise or pharmacology? What type of (exercise) stress works better for a given form of imaging?

Stress Testing An exercise ECG may be considered for cardiovascular risk assessment in intermediate-risk asymptomatic adults (including sedentary adults considering starting a vigorous exercise program), particularly when attention is paid to non-ECG markers such as exercise capacity Stress echocardiography is not indicated for cardiovascular risk assessment in low- or intermediate-risk asymptomatic adults

Stress Testing Stress MPI may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes or symptomatic adults with a strong family history of CHD or when previous risk assessment testing suggests high risk of CHD, such as a CAC score of 400 or greater Stress MPI is not indicated for cardiovascular risk assessment in low- or intermediate-risk asymptomatic adults. (Exercise or pharmacologic stress MPI is primarily used and studied for its role in advanced cardiac valuation of symptoms suspected of representing CHD and/or estimation of prognosis in patients with known CAD.)

Perform if Indicated Use a Global Risk Assessment Instrument (Global risk scores) (I) Family history of atherothrombotic CVD should be obtained for cardiovascular risk assessment in all asymptomatic adults (I) Measurement of hemoglobin A1C may be reasonable for cardiovascular risk assessment in asymptomatic adults without a diagnosis of diabetes (IIa) Urinary Albumin Excretion IIa for DM/HTN, IIb for Intermediate risk

Perform if Indicated Measurement of ABI is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk IIa Measurement of carotid artery IMT is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (IIa) ECG: IIa for HTN/DM and IIb if no HTN/DM ECHO: IIb for HTN and III if no HTN

Do Not Perform if Asymptomatic (Class III) Genotype testing for CHD risk assessment in asymptomatic adults is not recommended Lipoprotein and Apolipoprotein Assessments: No benefit Measurement of natriuretic peptides is not recommended for CHD risk assessment in asymptomatic adults Coronary CT Angiogram Cardiac MRI

Recommendations for Measurement of C-Reactive Protein Class IIa In men 50 years of age or older or women 60 years of age or older with LDL cholesterol less than 130 mg/dL; not on lipid-lowering, hormone replacement, or immunosuppressant therapy; without clinical CHD, diabetes, chronic kidney disease, severe inflammatory conditions, or contraindications to statins, measurement of CRP can be useful in the selection of patients for statin therapy. Class IIb In asymptomatic intermediate-risk men 50 years of age or younger or women 60 years of age or younger, measurement of CRP may be reasonable for cardiovascular risk assessment.22,115 (Level of Evidence: B) Class III: No Benefit In asymptomatic high-risk adults, measurement of CRP is not recommended for cardiovascular risk assessment.116 (Level of Evidence: B) In low-risk men younger than 50 years of age or women 60 years of age or younger, measurement of CRP is not recommended for cardiovascular risk assessment.22,115 (Level of Evidence: B)

Computed Tomography for Coronary Calcium Measurement of CAC is reasonable for cardiovascular risk assessment in Asymptomatic adults at intermediate risk (10% to 20% 10-year risk). (Class IIa) Asymptomatic adults with diabetes, 40 years of age and older (Class IIa) Measurement of CAC may be reasonable for cardiovascular risk assessment in persons at low to intermediate risk (6% to 10% 10-year risk) (Class IIb) Class III: No Benefit Persons at low risk (<6% 10-year risk) should not undergo CAC measurement for cardiovascular risk assessment.18,348,351 (Level of Evidence: B)

Coronary angiography –stable CAD Chronic CAD who have lifestyle-limiting angina despite medical therapy Markedly positive results on noninvasive stress testing Successful resuscitation from sudden cardiac death Documented ventricular tachycardia Maybe considered patients with nonspecific chest pain who have had recurrent hospitalizations, in order to completely exclude CAD as a cause for the current symptoms.

KEY MESSAGES Concept of Risk Stratification: Dynamic Process Pre-Op Risk Stratification New Angina Chronic stable Angina Assess Effectiveness of Therapy Assess Progression ACS: NSTEMI and UA STEMI Other Considerations Females Diabetics Presence or absence of Co-morbidities

Strategies used for CAD Risk Stratification KEY MESSAGES Clinical Noninvasive Tests Electrocardiography Echocardiography Stress ECG Stress Test + Echocardiography Stress Test + Nuclear Myocardial Imaging Viability Studies MPI SPECT (Single Isotope or Dual Isotope) PET Cardiac MR Cardiac CT Angiography Invasive

KEY MESSAGES The decision to order a specific stress test is based upon: The pretest probability of CAD; The ability of the patient to exercise; The findings on the resting electrocardiogram (ECG) The presence of comorbid conditions such as reactive airways disease

Diagnosis of Coronary Artery Disease

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