Cardiovascular Risk Assessment Using Risk Scores in Primary Prevention. Khurram Nasir, MD MPH

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1 Cardiovascular Risk Assessment Using Risk Scores in Primary Prevention Khurram Nasir, MD MPH

2 Cardiovascular Risk Assessment Using Risk Scores in Primary Prevention Khurram Nasir, MD MPH MSc Associate Professor of Medicine (Section of Cardiovascular Medicine) Director Population Health & Health Systems Research Center for Outcomes Research and Evaluation Yale University School of Medicine

3 Burden of Cardiovascular Disease n Cardiovascular disease accounts for nearly 1/3 of all deaths worldwide n In USA 800,000 have an first acute myocardial infarction. n Cardiovascular disease estimated to have cost the U.S. health care system more than $400 billion in n First manifestation of CHD in 40-60% is a myocardial infarction or sudden death.

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5 How Cardiovascular Disease Became Our Biggest Threat in The Last Century? n : Infectious diseases was the leading cause of death in the United States, and the average life expectancy was only 47 in 1930 n Sanitation, TB & Pneumonia Control, Penicillin significantly improved outcomes n 1945: 1 out of every 3 men in the United States developed CVD in their 50 s with majority of dying in 60 s n 1946: 44% of deaths in the US could be attributed to cardiovascular disease. That was an increase of about 20% since 1940

6 Concept of cardiovascular risk factors Age Sex Hypertension Hyperlipidemia Smoking Diabetes Kannel et al, Ann Intern Med 1961

7 Statins: Journey from Discovery to Established Role in Primary Prevention n 1960: Block & Lynen establish reduction of HMG-CoA is the major point of regulation on the pathway to cholesterol n 1971: Akira Endo, a Japanese biochemist began the search for cholesterol lowering drug. n 1984: Coronary Primary Prevention Trial demonstrated cholesterol lowering could significantly reduce the risk of heart attacks and angina Table 2. Summary of Landmark Statin Primary Prevention Clinical Trials Trial Drug Study Population Duration of Follow-up, y Baseline LDL-C, mg/dl %Changein LDL-C vs Control Results NNT WOSCOPS Pravachol 40 mg/d vs placebo 6595; men only, hyperlipidemia % TC 20%, MI/CHD death 31%, death 22% 42 AFCAPS/TexCAPS Lovastatin mg/d vs placebo 6605; men 84.9%, women 15.1%; hyperlipidemia % MI/UA/sudden cardiac death 38%, event rate in women 50 MEGA Pravastatin mg/d vs diet 7832; men 31.5%, women 68.5%; hyperlipidemia % TC 11%, MI/UA/sudden cardiac death/coronary revascularization 33% 119 ASCOT-LLA Atorvastatin 10 mg/d vs placebo ; men 81.2%, women 18.8%; hypertension with >3CVDriskfactors % Nonfatal MI, CHD-related death 36% 99 JUPITER Rosuvastatin 20 mg/d vs placebo ; men 61.8%, women 38.2%; healthy people with CRP >2.0 mg/l, LDL <130 mg/dl % hs-crp 37%, MI/stroke/arterial revascularization/ua/cv death 44% 25 at 5 y

8 Framingham Based Risk Scores is Incorporated in National Guidelines to Use for Assessing Risk of Developing CVD & Management with statins in Asymptomatic Individuals

9 How do we classify Asymptomatic Individuals Based on FRS? n <10%: Low Risk n Reassurance n Avoid further risk assessments for 5 years. n >20% : High Risk n Candidates for aggressive management with LDL goals of <100 mg/dl and aspirin n 10-20%: Intermediate Risk n Do not qualify for the most intensive risk factor interventions n Candidate for pharmacotherapy if LDL>160 mg/dl

10 Case Study n Name: WJC n Age: 55 years old male n Profession: Former chief executive n Social: No Cigarette use n Blood pressure is 128/84 mm Hg after treatment with hydrochlorothiazide n Total cholesterol level is 188 mg/dl n LDL Cholesterol 129 mg/dl n HDL cholesterol level is 42 mg/dl. n No family history of coronary artery disease.

11 2003: How Good are Traditional Strategies in Estimating CHD risk?? 222 patients with 1 st acute MI, no prior CAD men <55 y/o (75%), women <65 (25%), no DM 10% 18% 72% High Risk Intermediate Risk Low Risk Akosah Et al, JACC 2003:

12 Significant overlap in risk factors in with and without CHD Framingham Heart Study 26-Year Follow-up No CHD CHD Total Cholesterol (mg/dl) Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.

13 Are we Focusing too much on What s Your Cholesterol?

14 Most People who Develop Heart Attacks have Normal LDL Values Heart attack with normal LDL Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines Of 136,905 patients hospitalized with CAD, more than 75% had LDL levels below 130 mg/dl 23% had LDL-C < 70 mg/dl Sachdeva et al. AHJ, Vol 157, Jan 2009

15 Age is a big factor in FRS! Age/sex/smoking RFs to Exceed 20% 10-Year Risk 35 male NS CAN T (TC>320, HDL-c<20, SBP>200) 35 female NS CAN T (TC>320, HDL-c<20, SBP>200) 35 male smoker TC >275, HDL-c<40, SBP> female smoker TC >300, HDL-c<40, SBP> male NS TC >320, HDL-c<30, SBP> female NS CAN T (TC>320, HDL-c<20, SBP>200) 45 male smoker TC>240, HDL-c<40, SBP> female smoker TC>300, HDL-c<40, SBP>170

16 Is there a Gender & Age Bias? 100% 80% Men 60% 40% 20% 0% % of men aged & 92% aged are at least intermediate risk Age (years) 100% <10% 10-20% >20% Women 80% 60% 40% 20% 0% % women aged & 9% aged are at least intermediate risk Age (years) Ford ES et al, JACC 2004 <10% 10-20% >20%

17 Family History of CHD is not Considered in Framingham Risk Stratification!!!!

18 Coronary Artery Calcification and Family History of Premature Coronary Heart Disease Sibling History Is More Strongly Associated Than Parental History Khurram Nasir, MD, MPH; Erin Donnelly Michos, MD; John A. Rumberger, MD, PhD; Joel B. Braunstein, MD, MBA; Wendy S. Post, MD, MS; Matthew J. Budoff, MD; Roger S. Blumenthal, MD asymptomatic individuals (69% men; mean age: 52 9 years). CAC> Rf 1 RF 2 RF >=3 No FamHx of CHD FamHx of Premature CHD (Parent) FamHx of Premature CHD (Sibling)

19 Family History of Premature Coronary Heart Disease and Coronary Artery Calcification Multi-Ethnic Study of Atherosclerosis (MESA) 40 Khurram Nasir, MD, MPH; Matthew J. Budoff, MD; Nathan D. Wong, PhD; Maren Scheuner, PhD; David Herrington, MD, MHS; Donna K. Arnett, PhD; Moyses Szklo, MD, DrPH; Philip Greenland, MD; Roger S. Blumenthal, MD Advanced CAC FamHx of Premature CHD among all ethnic groups considered Low risk 10 Caucasians African Americans Hispanics Chinese American No FamHx of CHD FamHx of Premature CHD

20 Journal of the American College of Cardiology Ó 2014 The Expert Panel Members Published by Elsevier Inc. Vol. 63, No. 25, 2014 ISSN /$ PRACTICE GUIDELINE 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults q A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Endorsed by the American Academy of Physician Assistants, American Association of Cardiovascular and Pulmonary Rehabilitation, American Pharmacists Association, American Society for Preventive Cardiology, Association of Black Cardiologists, Preventive Cardiovascular Nurses Association, and WomenHeart: The National Coalition for Women With Heart Disease

21 2013 New Atherosclerotic CVD Risk & cholesterol guidelines: Worth the wait? n GROUP 1: PEOPLE WITH CLINICAL ASCVD n GROUP 2: PEOPLE WITH LDL-C 190 n GROUP 3: DIABETES, AGE 40 75, LDL-C , NO CLINICAL ASCVD n GROUP 4: AGE 40 75, LDL-C , NO ASCVD, BUT 10-YEAR RISK 7.5%

22 Cholesterol Treatment in Primary Prevention

23 ournal of the American College of Cardiology Vol. 63, No. 25, by the American College of Cardiology Foundation ISSN /$36.0 ublished by Elsevier Inc. Viewpoint Headed in the Right Direction But at Risk for Miscalculation A Critical Appraisal of the 2013 ACC/AHA Risk Assessment Guidelines Nivee P. Amin, MD, MHS,* Seth S. Martin, MD,* Michael J. Blaha, MD, MPH,* Khurram Nasir, MD, MPH,*y Roger S. Blumenthal, MD,* Erin D. Michos, MD, MHS* Baltimore, Maryland; and Miami Beach, Florida Tradeoffs with Cholesterol Management Guidelines in Primary Prevention Settings

24 ORIGINAL RESEARCH Annals of Internal Medicine An Analysis of Calibration and Discrimination Among Multiple Cardiovascular Risk Scores in a Modern Multiethnic Cohort Andrew P. DeFilippis, MD, MSc*; Rebekah Young, PhD*; Christopher J. Carrubba, MD; John W. McEvoy, MB, BCh, BAO; Matthew J. Budoff, MD; Roger S. Blumenthal, MD; Richard A. Kronmal, PhD; Robyn L. McClelland, PhD; Khurram Nasir, MD, MPH; and Michael J. Blaha, MD, MPH Risk Score, % Participants, n Predicted Events, n (%) Observed Events, Including CMS Data, n (%) (2.8) 21 (2.3) (6.2) 16 (3.1) (8.7) 15 (3.6) (17.1) 124 (9.3) Total (10.1) 176 (5.5) Systematic overestimation of risk is a significant concern if it leads to prescription of statin therapy among groups in which actual risk scores are lower than predicted. (Paul Ridker)

25 Background Original Article Quantifying the Utility of Taking Pills for Cardiovascular Prevention Robert Hutchins, MD, MPH; Anthony J. Viera, MD, MPH; Stacey L. Sheridan, MD, MPH; Michael P. Pignone, MD, MPH Circ Cardiovasc Qual Outcomes March 2015 Two third patients averse to taking long term medication unless at high risk and substantial benefit

26 What Does it Mean for Stakeholder? PHYSICIAN ACCURATE RISK ASSESSMENT HEALTH SYSTEM PATIENT

27 Current Dilemma: How do we go along in identifying the low risk individual prior to a clinical event? 1. To Invest in Future We Must Learn From Our History! 2. Cholesterol bases testing substantially underestimate risk especially in young and women 3. 50% event happen in those with normal LDL 4. Risk score pendulum shifted from under to over estimation 5. Predictors of disease are uncertain in this group

28 Strategies that compete with the absolute risk approach.

29 Need additional information? Non invasive Low risk Cost effective High sensitivity and specificity

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31 AHA/ACC Special Report Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease Donald M. Lloyd-Jones, MD, ScM, FACC, FAHA; Lynne T. Braun, PhD, CNP, FAHA; Chiadi E. Ndumele, MD, PhD, FAHA; Sidney C. Smith, Jr, MD, MACC, FAHA; Laurence S. Sperling, MD, FACC, FAHA; Salim S. Virani, MD, PhD, FACC, FAHA; Roger S. Blumenthal, MD, FACC, FAHA Published Online Ahead of Print November 10, 2018 in Circulation and JACC

32 Refining Risk Estimates for Individual Patients Estimate Absolute 10-year ASCVD Risk Low Risk 0 - <5% Borderline Risk 5% - <7.5% Intermediate Risk 7.5% - <20% High Risk 20% Clinician-patient discussion considering risk-enhancing factors and net benefit of therapy Lifestyle modification Lifestyle and drug therapy

33 Performance of Pooled Cohort Equations in Diverse Population Samples: Predictable Broad US Clinical Population High SES, engaged patients Over- Estimate Risk Reasonable Calibration Low SES, HIV, Inflammatory dz Under- Estimate Risk Estimated 10-y ASCVD Risk Clinician-Patient Discussion

34 Refining Risk Estimates for Individual Patients Risk-Enhancing Factors for Clinician Patient Risk Discussion Family history of premature ASCVD; (males, age <55 y; females, age <65 y) Primary hypercholesterolemia (LDL-C, mg/dl [ mmol/l]; non-hdl-c mg/dl [ mmol/l])* Metabolic syndrome (increased waist circumference, elevated triglycerides [>175 mg/dl], elevated blood pressure, elevated glucose, and low HDL-C [<40 mg/dl in men; <50 in women mg/dl] are factors; tally of 3 makes the diagnosis) Chronic kidney disease (egfr ml/min/1.73 m 2 with or without albuminuria, not treated with dialysis or kidney transplantation) Chronic inflammatory conditions such as psoriasis, RA, or HIV/AIDS History of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk such as pre-eclampsia High-risk race/ethnicities (e.g. South Asian ancestry) Lipid/biomarkers: Associated with increased ASCVD risk -Persistently* elevated, primary hypertriglyceridemia ( ³175mg/dL); -If measured: o Elevated high-sensitivity C-reactive protein ( 2.0 mg/l o Elevated Lp(a) A relative indication for its measurement is family history of premature ASCVD. An Lp(a) 50 mg/dl or 125 nmol/l constitutes a risk enhancing factor especially at higher levels of Lp(a) o Elevated apob ³130 mg/dl - A relative indication for its measurement would be triglyceride 200 mg/dl. A level 130 mg/dl corresponds to an LDL-C >160 mg/dl and constitutes a risk enhancing factor o ABI (ABI) <0.9

35 Refining Risk Estimates for Individual Patients Estimate Absolute 10-year ASCVD Risk Low Risk 0 - <5% Borderline Risk 5% - <7.5% Intermediate Risk 7.5% - <20% High Risk 20% Clinician-patient discussion considering risk-enhancing factors and net benefit of therapy If uncertainty or patient indecision remains, consider CAC score and revise decision based on results Lifestyle modification Lifestyle and drug therapy

36 High Risk Conditions that Don t Need Risk Calculation Familial Hypercholesterolemia Diabetes Mellitus, years

37 TAKE HOME MESSAGE Emphasize a heart-healthy lifestyle Assess ASCVD risk as starting point for discussion regarding statin use years: Lifetime risk estimation years: 10 year ASCVD risk; If years, diabetes à moderate intensity statin If years, no diabetes and intermediate risk ( %) -strong evidence for benefit with statins based on multiple RCTs Clinician-patient risk discussion occurs before statin Rx -Enhancing factors personalize a risk decision re statins -When a risk decision uncertain, coronary artery calcium score can target statin use to those most likely to benefit.