Assessing atherosclerotic risk for long term preventive treatment

Transcription

1 Assessing atherosclerotic risk for long term preventive treatment Donald A. Smith, MD, MPH Endocrinologist, Clinical Lipidologist Associate Professor of Medicine and Preventive Medicine Icahn School of Medicine at Mount Sinai Director, Lipids and Metabolism Mount Sinai Heart March 2016 Mount Sinai Department of Medicine Disclosure I receive financial support from the following company or companies related to the products listed below. These relationships may lead to bias in my presentation. Entity Sanofi- Regeneron Type(s) of relationship(s) PI Product name(s) Alirocumab PCSK9 inhibitor Relevant disease(s) or condition(s) High LDLC Amgen CoPI Evolocumab High LDLC CHD onset as function of lifetime LDLC exposure Nl human lifespan 90+ yrs Nordestgaard BJ et al. European Atherosclerosis Society Consensus Panel. Eur Heart J 2013: 34: a 1

2 ATP-III: Estimate of 10-Year Risk for Women (Framingham Point Scores) Age, y Points Systolic BP If If mm Hg Untreated Treated < HDL mg/dl Points <40 2 Total Age Age Age Age Age Cholesterol < Age Age Age Age Age Nonsmoker Smoker Point Total 10-Year Risk, % <9 < Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: Primary and Secondary Prevention Goals Risk Category LDL-C Goal (mg/dl) Non HDL-C Goal (mg/dl) Coronary, peripheral, carotid < 70 <100 vascular disease CHD risk equivalent < 100 < 130 (10-y risk for CHD 20%) Multiple (2+) risk factors and < 130 < y risk 20% *Secondary goals for patients with TG 200 mg/dl 0-1 Risk factor < 160 < 190 NCEP ATP III. JAMA. 2001;285:

3 Trends in LDL-Cholesterol Quest n = 250 X 10 6 Samples, 150 X 10 6 Patients Kaufman HW et al. PLoS ONE 8(5): e Efficacy Intensive LDL-C Lowering in Patients with Low Baseline LDLC Meta-analysis RCT of major vascular events > 1000 subjects (n = 169,138) and > 2 yrs Rx of more vs less intense statin Rx For each 39 mg/dl reduction in LDLC Those with baseline LDLC < 77 mg/dl, 29% further reduction MVE (p= 0.007) Those with baseline LDLC < 70 mg/dl 37% further reduction MVE (p = 0.004) Cholesterol Treatment Trialists Collaboration Lancet 2010; 376 : ACC/AHA 2014 Guidelines Moderate to High Dose Statin therapy for 4 patient groups Those with history of atherosclerotic events (Acute coronary syndromes, MI, stable angina, coronary/other arterial revascularizations, stroke, TIA, peripheral arterial disease) Age with LDLC > 190 mg/dl Age with diabetes and LDLC > 70 Age and 10-year ASCVD risk >7.5 Ann Intern Med. 2014; 160: J Am Coll Cardiol. 2014; 63:

4 High dose Rosuva (Crestor) Statins levels mg Atorva Moderate dose Rosuva (Crestor) 5 10 Atorva Simva Prava Lovastatin 40 Fluva (Lescol) XL 40 bid or XL 80 Pitava (Livalo) 2-4 Low dose any lower dose than moderate Ann Intern Med. 2014; 160: J Am Coll Cardiol. 2014; 63: Now another proven drug to lower LDLC and risk IMPROVE-IT 18,144 patients hospitalized for ACS previous 10 days Randomized simvastatin 40 + ezetimibe 10 vs simvastatin 40 + PBO FU q 4 months for 7 years Endpoint: CV death, MI, hosp for UA, revascularization, CVA CP Cannon et al. NEJM 2015; 6/4/15 4

5 ASCVD Risk Calculator 5 NHLBI-sponsored longitudinal population-based cohorts* of African American and non-hispanic white men and women with 12 year follow-up data N= 25,000 F/M 14,000/11,000 Wh/AA 20,500/4500 Estimates risk for first adjudicated MI, CHD death, fatal or nonfatal stroke in those yrs age Age, sex, race, smoking status, total cholesterol, HDL cholesterol, SBP, antihypertensive therapy, and diabetes *Atherosclerosis Risk in Communities (ARIC) Cardiovascular Health Study (CHS) Coronary Artery Risk Development in Young Adults (CARDIA) Framingham Original and Offspring Study cohorts. 5

6 ASCVD Risk Calculator 6

7 Overestimation of risk % Ridker PM and Cook NR. Lancet: 2013; 382: Overestimation of risk why? Improved lifestyles in the newer cohorts compared with 25 years ago Newer cohorts may have started statins prior to the end of the follow up period, e.g., RN s, MD s May have missed some ASCVD events without more frequent surveillance system 7

8 Excellent estimation of risk with good event detection REGARDS: Reasons for Geographic and Racial Differences in Stroke Overall n 10,997 No DM LDLC No statins > 65 on Medicare 3333 No DM LDLC No statins Muntner P et al. JAMA 2014; Predicted percentage of groups years with > 7.5% risk hard ASCVD event in 10 yr Race Gender % with predicted risk White non Hispanic Men 45 Women 22 African American Men 55 Women 34 Hispanic Men 42 Women 19 Other Men 40 Women 19 Goff DC, Lloyd-Jones DM, Bennett, G, et al. J Am Coll Cardiol. 2014: Depending on risk, and after discussion and dietary trial to assess LDLC reduction, simply start moderate or high dose statins ASCVD risk reduction by high dose statins outweighs excess risk for diabetes in secondary prevention, and those with 10 yr risk > 7.5% And for moderate dose statins in those with 10 yr risk > 5% and < 7.5% Other factors may be considered in risk assessment: LDL-C > 160 FH of premature CHD Father/brother < 55, Mother/sister < 65 Lifetime ASCVD risk hs CRP > 2.0 mg/l Coronary artery calcification score > 300 Agatston units Ankle brachial index < 0.9 8

9 Can Imaging More adequately assess when to begin preventive lipid-altering medications? Electron Beam CT for Coronary Calcium Score Scan Modes (Calcium)- ECG triggered step volume Table Motion Single View EBCT 9

10 St. Francis Heart Study Natural History Study N = 4500 in Queens and on Nassau Counties CACS < 80 th percentile or > 80 th percentile and assigned to PBO years 70% men No CHD LDL-C mg/dl men; LDL-C women mg/dl N = 1817 with baseline CV risk factor measures Follow up 4.3 years Guerci AD. American College of Cardiology Scientific Sessions. Mar 31-Apr 2, 2003: Chicago, IL. St. Francis Heart Study N = 122 > one CV event: CV death, MI (43), CVA (5), CABG/PCI (62), PVD revasc (12) RR for CV event CACS > 100 vs < 100: 9.5 ROC area from Framingham risk factors: 0.71 p < 0.01 from CACS: 0.81 Age, gender, LDL-C and HDL-C still associated with events after correcting for CACS Guerci AD. American College of Cardiology Scientific Sessions. Mar 31-Apr 2, 2003: Chicago, IL. St. Francis Heart Study Coronary Calcium Score RR for CV event > Guerci AD. American College of Cardiology Scientific Sessions. Mar 31-Apr 2, 2003: Chicago, IL. 10

11 Calcium score St. Francis Heart Study Calcium score and 10 yr CV risk Positive predictive value (%) 10 yr MI, CHD death prediction > > yr MI, CHD death, revasc Guerci AD. American College of Cardiology Scientific Sessions. Mar 31-Apr 2, 2003: Chicago, IL. St. Francis Heart Study Natural History Study Conclusions: for ages 50 to 70 years CCS adds to CV event risk prediction given by Framingham score CCS scores > 200 are approaching coronary disease risk equivalency Guerci AD. American College of Cardiology Scientific Sessions. Mar 31-Apr 2, 2003: Chicago, IL. Coronary Calcium Scoring at Mount Sinai Generally perform this age 40+ EPIC order: CT Cardiac/Heart Coronary Calcium Score Some insurances will pay otherwise $ CT Slice Scanner: 0.5 msv radiation Yearly exposure: 3 msv Mammogram: msv 11

12 Electron Beam CT Coronary Artery Calcium Scores in 35,246 Self-referred Asymptomatic Individuals Age < > 74 Men (%ile) (n=25,251) Women(%ile) (n=9995) Hoff JA et al. Am J Cardiol 2001; 87: Multi-Ethnic Study of Atherosclerosis (MESA) 6814 M/F years without CVD 6 communities: Baltimore, Chicago, Forsyth County NC, Los Angeles, St. Paul, northern NYC 38% white, 28% black, 22% Hispanic and 12% Chinese Yeboah J et al. JAMA 2012: 308: MESA Standard Risk Factors Baseline collection 7/2000-8/2002 FU: through 5/2011 Persons with diabetes excluded since CHD equivalent Smoking 1+ cigarettes last 30 days BP: average 2 nd and 3 rd seated readings HTN - SBP 140+ or DBP 90+ TC, HDLC fasting, Friedwald equation hs CRP Dade Behring FH CHD Parent, sibling or children with fatal or non fatal MI 12

13 MESA New testable Risk Factors Ankle-brachial index cuffed Doppler appearance SBP bilat brachial, dp and post tib positions Coronary artery calcification score CAC Brachial flow-mediated dilation FMD Carotid intimal medial thickness IMT Incident CHD: MI, CHD death, Resuscitated cardiac arrest Incident CVD: probable/definite angina if + coron revasc, stroke, CVD death MESA Hazard Ratio s Yeboah J et al. JAMA 2012: 308:

14 MESA ROC curves Yeboah J et al. JAMA 2012: 308: MESA NRI Net Reclassification Improvement Yeboah J et al. JAMA 2012: 308: DB 47 yr old newsman Father died MI age /HCTZ25 Lp(a) 48 (nl < 20 mg/dl) Hypertension 2008 (age 43) on Losartan Age Year TC TG HDLC LDLC TC/HDLC Non HDLC Meds Taking Csty 2pks Nspan Lip 10 Nspan Crest 5 Nspan Crest 10 Diagnosis? Agree with this current therapy? 14

15 DB 47 yr old newsman Father died MI age /HCTZ25 Lp(a) 48 (nl < 20 mg/dl) Hypertension 2008 (age 43) on Losartan Age Year TC TG HDLC LDLC TC/HDL C Non HDLC Meds Taking Csty 2pks Nspan Lip 10 Nspan Crest 5 Nspan Crest 10 Age 47 11/2013 Coronary Artery Calcium Score = th percentile (Intermediate risk) Average score for 65-69yr old American Male. 11/2013 Agree with this current therapy now? RM 59 yr old female school teacher Father died MI 52 Stopped social smoking 1986 White coat hypertension at home 130/85 max 5 3 tall 180 lbs BMI 31.9 BP 173/ Coronary artery calcium score 5 75 th %ile 2013 Coronary artery calcium score th %ile By late 70 s untreated will have CACS 400 = coronary risk equivalent By ASCVD equation, no need for statin 15

16 10 yr CHD risk with CACS = 7.9% 10 yr CHD risk with RF s only = 4.9% CACS increased her risk Add 1-2% CVA risk and 10 yr risk = 8.9% + risk SL 56 year old male Type 2 diabetes since age 50 Neg FH of MI or CHD SBP 124 off anti-hypertensives Total cholesterol 239, HDLC 38, on no meds 16

17 But. Coronary artery calcium score: Zero 10 yr CHD risk with CACS = 3.9% 10 yr CHD risk with RF s only = 9.6% CACS decreased his risk Add 1-2% CVA risk and 10 yr ASCVD risk = % KC 74 yr old white woman High Lp(a) and sister has the same Stopped 15 yr pack smoking 30 yrs ago Father died MI age 80 Sister 65 just had MI and stent, she is frightened Intolerant of five statins: lethargy, nausea, aches 17

18 Age 73: Coronary calcium score st %ile 10 yr CHD risk with CACS = 5.8% 10 yr CHD risk without CACS = 6.0% About the same Add 1-2% CVA risk and 10 yr ASCVD risk = % 18

19 Carotid US: carotid plaques in both R and L internal carotid arteries 20-39% stenoses What recommend? Carotid US: carotid plaques in both R and L internal carotid arteries with 20-39% stenoses What recommend? Ezetimibe 10 mg per day to decrease LDLC 20% Diet: low saturated fat, increased soluble fiber Risk Assessment for ASCVD Standard Framingham risk factors very helpful and often sufficient New ASCVD risk calculator excellent for helping decide on when to possibly start statins Adding coronary risk calcification score improves in the MESA calculator improves accuracy of prediction 19