Colin Edwards Cardiologist Waitemata Health and Auckland Heart Group

Transcription

1 Colin Edwards Cardiologist Waitemata Health and Auckland Heart Group June 2015

2 Disclosures PFIZER LECTURE SERIES

3 Concepts in CV Risk Assessment Framingham Risk Atheroma Imaging Lifetime CV Risk 4 cases Lipid Management current and future treatment

4 ACUTE CORONARY SYNDROME Disease Process- atherosclerosis Learn more about the prevention ACS PLAQUE FORMATION New Zealand (year 2000) Cardiovascular deaths: 4402 (35%) Cancer deaths: 4120 (30%) Most common cause of death in men under 65 years. Fighting a War against atherosclerosis TCFA PLAQUE RUPTURE

5 Predictors of Plaque Rupture? Total Plaque Burden Lesion Severity Thin Cap Fibrous Atheroma

6 To eradicate atherosclerosis as the number 1 killer of mankind! Atherosclerosis starts in childhood-if not earlier Screening and management of CV risk factors should also start in childhood

7 Start Screening Circulation 2001

8 CV RISK PREDICTION Total up a patients CV risk factors AND The more CV risk factors present.the greater the 5 or 10 year risk of having a stroke or heart attack Degree of intervention is determined by number of risk factors ANALOGY WHAT IS YOUR RISK OF HAVE A CAR SMASH..? If you drive carefully low but not nil If you drive fast. It is higher but not definite. If you drive fast and drink alcohol once again higher but still not definite.

9 AIMS OF CV RISK PREDICTION ADD 5 % - FAMILY HX OF EARLY CAD - MAORI OR PACIFIC ISLAND OR INDIAN

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11 CASE 1 Mrs JE 61 year old phlebotomist Referral from Orthopaedics cardiac clearance prior to THJR. Vague chest pain- OFTEN at rest. Not exercising much due osteo-arthritis. CV RISK Female 61 yrs Yes No Hypertension x-140/75mmhg Diabetes Mellitus x T Chol HDL LDL TG Ratio Smoker 9mmol/l 1.9mmo/l 6 mmol/l 2.5mmol/l 4.7 mmol/l Family history x-mother 65 brother CABG 50yrs FATHER- 94 yrs cancer x-never

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13 LDL 3mmol/l Booked a dobutamine stress echo- risk stratification prior to hip surgery.

14 Admitted to hospital with rest pain while waiting for DSE. CORONARY ANGIOGRAM: minor plaque

15 EXPECTED A HIGHER CORONARY PLAQUE BURDEN-? HDL is protective

16 CASE 2 65 year old female Exertional chest pain particularly after food. Relieved by GTN and rest. Lasts about 2 min CASE 2 YES NO CV RISK Female age 65 yrs Diabetes mellitus Hypertension Smoker T Chol HDL Chol LDL Chol TG Ratio Family hx Mild 150/80mmHg 5 mmol/l 1.4 mmol/l 3.1 mmol/l 1 mmol/l 3.5 x x x

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19 EXERCISE TEST: Positive

20 Coronary Angiography Severe 3 VD Far more extensive CAD than expected! Not sure why. Must have a very atherogenic LDL particle In-patient CABG

21 Similar Framingham CV Risk similar atheroma burden Shouldn t the pt with higher LDL have more atheroma?

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23 CASE 1

24 CASE 1 CASE 2 LDL-C 6 mmol/l

25 POSSIBLE EXPLAINATIONS Enviromental component- Exercise, diet, stress, passive smoking etc. etc... Atherosclerosis at a molecular level Process is dependant on multiple factors- LDL, adhesion molecules, IL s, inflammatory markers, genetic factors Genetics of atherosclerosis: Complex, no single gene, may be multiple +ve family hx of early CAD- CV risk 2-3 fold

26 HOW CAN WE IMPROVE ACCURACY OF CV RISK ASSESSMENT COMBINE FRAMINGHAM RISK WITH ATHEROMA IMAGING PERSONALISED CV RISK ASSESSMENT

27 1) Confirms the presence or absence of coronary plaque 2) Predictors of plaque rupture - severity of stenosis - plaque burden - thin cap Radiation dose is down-1 to 5mSv

28 CALCIUM SCORE Non-contrast scan. Agatston score- X area of each calcified lesion with the peak density (HU) of the plaque. Normal varies for age and sex- zero is a good figure to have. PREDICTION OF CORONARY DISEASE EVENTS Relative Risk Calcium score- independent predictor of CV events Motivational to patient and treating Physician-better adherence and Risk Factor modification >600 Calcium Score Recommended for Intermediate Risk pts (asymptomatic)

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31 Case 4- Pearl : 46 year female, pharmacy technician Chest pain intermittently for 2 yrs- seen at A + E twice and told it was atypical. Female age 46 yrs Diabetes mellitus Hypertension Smoker Total Chol HDL Chol LDL Chol TG Ratio Family hx YES NO x x x x

32 Severe episode of CP during a ward round radiating into her jaw. Very unwell, clammy, collapsed taken to emergency department

33 CORONARY ANGIOGRAPHY Widow maker Severe LMS stenosis Inpatient coronary bypass surgery FRS failed this pt! CTCA

34 CASE 3- Jimmy 33 year old obese bus driver, single, flatting Saw GP- driving medical asymptomatic-denied chest pain or breathlessness PM/SH-nil Meds-nil Family history: Father and grandfather had MI s in their 50 s. Social hx: poor diet-take outs, never exercises, non-smoker CV Risk: Male 33 yrs Yes No Hypertension 125/80mmHg Weight-137 kg Waist Circumference-140cm Diabetes Smoker Fasting glucose 5.4mmol/l x T Chol HDL Chol LDL Chol TG Ratio 6.2 mmol/l 0.65 mmol/l 5.1 mmol/l 3.0 mmol/l 9.5 Family Hx X

35 ? 33 years SHORTCOMINGS OF FRS 1. Better suited for assessing CV risk in older age groups 2. Family hx (NZ guidelines add 5%)

36 ? Start statin-so young, pt not keen 12 months later-haemorrhoids Gained WT-140kg Waist circumference-143cm

37 2 years later Presented to his GP complaining of L sided chest pain tearing in nature radiated to neck and jaw persistent x 45 minutes Clammy, vomited Acute infero-posterior ST elevation MI Ambulance NSH Primary angioplasty (PAMI)

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39 Framingham risk score didn t serve this pt well Probably has a familial dyslipidemic syndrome. Should have started a statin, ±fibrate when 1 st seen. Atheroma imaging

40 LIPID MANAGEMENT: LDL-C 5.1mmol/l Goal 1- LDL Target mmol/l

41 5-80mg/d 5-80mg/d 10-80mg/d 10-40mg/d

42 Hepatic cholesterol Direct GIT Cholesterol

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44 MANAGEMENT: Atorvastatin-start at 80mg/d + Ezetrol 10mg/d 3 months later T Chol 3.8mmol/l HDL Chol 0.65mmol/l LDL Chol 2.0 mmol/l TG 2.0 mmol/l Ratio 5.8 Residual Risk: LDL targets achieved, but HDL LOW These pts have further events? Do we need to attend to HDL

45 ? Triple therapy Ideally want HDL>1mmol/l Atorvastatin 80mg Ezetrol 10mg/d Nicotinic acid or fibrate

46 Exciting New Lipid Lowering Therapy CETP Inhibitors Anacetrapib, Evacetrapib PCSK9 inhibitors - Alirocumab

47 CETP Inhibitors

48 CETP-Lipid Effects

49 CETP Inhibitors

50 PCSK9 -inhibitors PCSK9 is a protein produced in the liver. Binds LDL-CHOL R complex Facilitates receptor internalization and destruction PCSK9-Inhibitor Humanised monoclonal Ab Administered every 2-4 weeks LDL receptor number and LDL

51 ODYSSEY LONG TERM Trial design: Participants with heterozygous familial hypercholesterolemia or high CV risk on statin therapy were randomized to alirocumab 150 mg SQ injection every 2 weeks (n = 1,553) vs. placebo SQ injection every 2 weeks (n = 788) % Alirocumab Placebo (p < ) Percent change in LDL-C from baseline to 24 weeks Results From baseline to 24 weeks, the change in LDL-C: -61% for alirocumab compared with 0.8% for placebo (p < ) This reduction was maintained to 52 weeks; LDL-C: 53 mg/dl with alirocumab vs. 123 mg/dl with placebo Conclusions Among participants with heterozygous familial hypercholesterolemia or high CV risk, alirocumab resulted in a large reduction in LDL- C compared with placebo, which was maintained to 52 weeks Presented by Dr. Jennifer Robinson at ESC 2014

52 Large plaque burden + good stent Atorvastatin 80mg Ezetrol 10mg/d Aspirin 100mg/d Clopidogrel 75mg/d Sore back Very concerned clinician Who wants to add a 5 th toxin

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54 Exercise 30 min 5 d/week BMI-24 BP<130/80mmHg HbA1c < 7%

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56 Circulation 2006;113;

57 Motivates the patient and physician to normalise risk factors Gain 11 years of life Circulation 2006;113;

58 Personalised CV Risk Assessment Framingham Risk Personalised CV risk l Lifetime CV Risk Atheroma Imaging and CV Risk

59 Process of coronary atherosclerosis starts in childhood- primary prevention should also start in childhood. Framingham risk is a good start. Important to normalise all risk factors- in order to reduce LIFETIME CV RISK Shortcomings- doesn t cater for the young pt not that good for high risk families/populations Use lifetime risk models e.g. QRISK Atheroma imaging-low radiation, good prognostic data, motivational for pt and physician

60 THANKS Colin Edwards