Cardiovascular risk factor appraisal art or science?

Cardiovascular risk factor appraisal art or science? Prof. Philip MacCarthy BSc MBChB (Hons) PhD FRCP Consultant Cardiologist Bupa Cromwell Hospital Clinics: Wednesday & Friday PM/Evening

What are we trying to achieve?

CVD Mortality in England (all <75 yrs) BHF Heart Stats (2012) http://www.bhf.org.uk/publications/view-publication.aspx?ps=1002097

Causes of Death (England, <75 yrs) (Source: Living Well for Longer [ONS data], 2013) Source: www.statistics.gov.uk/ statbase/product.asp?vlnk=6725

CVD.. 200k deaths pa (1:3 of all) 4.9m adults have CVD (11.7% of population) 1.4m hospital admissions in 2010/11 65% were patients under 75 yrs >50% were emergencies CVD costs NHS & UK economy 30bn pa. Prevalence increases with deprivation - Inequalities Services for the prevention of CV Disease NICE Commissioning Guide 45. March 2012

UK causes of Years of Life Lost (both sexes, all ages) 1990-2010 Global Burden of Disease Study. Lancet 2013;381:997-1020 259 diseases and injuries & 67 risk factors

History

The Framingham Heart Study Data collection started in 1948 Bi-annual follow up First CVD risk equation: Truett et al. 1967 > 20 groups of regression equations between 1967 and 2008 Modified Anderson et al 1991 used in UK

Framingham - Anderson Data collected 1968-75 5573 men and women followed up for 12 years Six regression equations published in 1991

Risk factors used to calculate the Anderson Framingham risk score -age and sex -diastolic and systolic BP -total:hdl cholesterol ratio -diabetes (Y/N) -cigarette smoking (Y/N) -LVH (Y/N) Absolute CVD Risk over 10 years

Different versions and coloured charts New Zealand cardiovascular risk prediction charts

Limitations of Framingham BP treatment Family History Deprivation Ethnicity Generalisability Statistical validity Face validity Improvements were needed

A new era of CV risk prediction

SCORE Systematic Coronary Risk Evaluation 2003 205,178 men and women from 12 European cohort studies

SCORE better than Framingham? BP treatment Family History Deprivation Ethnicity Generalisability? Statistical validity Face validity SCORE No No No No Yes No

ASSIGN - ASSessing cardiovascular risk, using SIGN guidelines Scottish Heart and Health Extended Cohort (SHHEC) 6540 men, 6757 women Classic risk factors plus Deprivation Family history Shifts treatment towards the socially deprived compared to Framingham

ASSIGN better than Framingham? SCORE ASSIGN BP treatment No No Family History No Yes Deprivation No Yes Ethnicity No No Generalisability?? Statistical validity Yes Yes Face validity No No

The evolution of QRISK

QRISK1 and QRISK2 Electronic patient record Cohort analysis based on large validated GP database (QResearch) Contains individual patient level data 15 year study period 1993 to 2008 First diagnosis of CVD (including CVD death) QRISK1 Deprivation Family History BMI On BP treatment NO Ethnicity

QRISK 1 QRISK algorithm derived from Derivation cohort 1.28 million patients Validated in the Validation cohort 0.61 million patients QRISK out-performed Framingham and ASSSIGN

QRISK1 - better than Framingham? SCORE ASSIGN QRISK1 BP treatment No No Yes Family History No Yes Yes Deprivation No Yes Yes Ethnicity No No No Generalisability?? Yes Statistical validity Yes Yes Yes Face validity No No Yes

QRISK2 Included ONS deaths linkage Included additional variables 2.3 million people (>16 million person yrs) Self-assigned ethnicity

Age-standardised incidence of CVD by deprivation 12 10 8 6 4 2 Q1 (affluent) Q2 Q3 Q4 Q5 (deprived) 0 females males

Age-standardised incidence of CVD by Ethnicity per 1000 pyrs 25 20 15 10 % White Indian Pakistani Bangladeshi Other Asian Black Caribbean 5 Black African Chinese 0 Females Males Other

Framingham over-predicts QRISK underpredicts Collins and Altman, BMJ 2009;339:2584

QRISK2 better than Framingham? SCORE ASSIGN QRISK1 QRISK2 BP treatment No No Yes Yes Family History No Yes Yes Yes Deprivation No Yes Yes Yes Ethnicity No No No Yes Reproducibility Yes Yes Yes Yes Generalisability?? Yes Yes Statistical validity Yes Yes Yes Yes Face validity No No Yes Yes

How to apply QRisk2 in practice

How to apply QRisk2 in practice

Future developments of QRISK2 A living evidence base

JBS3

http://www.jbs3risk.com Heart 2014;100:ii1-ii67

NICE guidance for statin use

Case study 1 Young female with significant risk factors Effect of intensive risk factor modification 35-year-old female smoker Systolic BP of 160mmHg TC of 7.0mmol/L, HDL of 1.4mmol/L (non-hdl of 5.6mmol/L) Family history of premature CVD

Estimated average survival without a CV event

Estimated average survival without a CV event

Effect of intensive risk factor modification

Effect of intensive risk factor modification

Shortfalls of CV risk scores Not tailored to individual patients Differing views on lifestyle/medications Not completely accurate Is 10yr risk the correct metric? Should be used in the context of clinical common sense!

Further refinement of CV risk Functional testing eg. Exercise ECG/echo Cardiac CT Ca++ scoring/ct angiography PLAC test Genetic testing Other parameters hs-crp, fibrinogen, LP(a)

Lipoprotein-associated phospholipase A2 PLAC test

Predictive value of Lp-PLA2 activity

Cardiac CT Calcium scoring Detrano et al, NEJM 2008;358:1336

Case Study 2 44yr old Asian Goldman Sachs Executive Slim. Asymptomatic. Non-diabetic. Strong FHx of premature IHD Total cholesterol 7.8 LDL 5.46 HDL 1.23 Non-smoker BP 100/60

JBS3

Case study 2 Rx: Atorvastatin 10mg od

CT coronary angiography

Case study 3 50yr old man. Management Consultant. Asymptomatic CV RF: Strong FHx of IHD (Father/Uncle CABG, Mother PCI), HTn on Lisinopril Total Cholesterol: 5.5 HDL: 1.3 LDL: 3.9

Case study 3

CT Coronary Angiogram Ca++ score 48 (50-75 th centile) 50-70% stenosis in proximal LAD Stress Echocardiogram Reversible ischaemia in LAD territory

Physiologically-guided PCI-LAD

Case study 4 56yr old male. Asymptomatic. Strong FHx of IHD Father MI 61yrs Paternal GF MI 60yrs Uncle fatal MI 60yrs Total cholesterol now controlled with statin TC 4.1, LDL 2.0

Screening history 2014 Exercise ECG ST depression at peak workload. No symptoms. 2014 CTCA Ca++ score 276. Prox LAD stenosis 2014 Invasive cor angio Moderate LMS/LAD disease 2014 Stress echo negative at good workload

Screening history March 2016 repeat stress echo ischaemia at high workload (12 55 ) referred to me. Invasive coronary angiogram with a view to pressure wire assessment

Angiogram 70% 80% 70% Distal LMS/Ostial LAD Underwent CABG x 3

Case study 5 The brother of Case study 4! Asymptomatic Frightened by the story of his brother asked local Cardiologist to screen him for CAD Stress echo negative at high workload. Told not to worry and take a statin (TC 4.0, LDL 2.3, HDL 1.1 on rosuvastatin 5mg) Came to me for second opinion

Case study 5 - screening Cardiac CT Ca++ score 932 dense calcification in LMS, prox and mid-lad. 80th centile. No angiogram performed. Invasive coronary angiogram at patient s (and brother s) insistence!

Coronary angiogram 95% Mid-LAD stenosis PCI LAD with drug-eluting stent

What do we do with asymptomatic coronary disease?

The FAME 2 Trial

FAME 2 De Bruyne et al, NEJM 2014;371:1208

Conclusions Cardiovascular risk predictors are useful tools but only form a framework for management Risk scores should be performed in the context of individual patients CV risk factor management can be enhanced by an individual approach and further tests (CT, PLAC) The evidence base for management of completely asymptomatic CAD is lacking

Thank you! How to refer? Call 0800 783 9229