CV Risk: A novel early intervention strategy to prevent cardiovascular disease John Deanfield, MD. University College London United Kingdom

Transcription

1 CV Risk: A novel early intervention strategy to prevent cardiovascular disease John Deanfield, MD University College London United Kingdom

2 Death / 100,000 population Death Rates from All Circulatory Disease in England A fall of 55% since baseline Immortality Guaranteed by 2026 Target: 40% minimum reduction from B/L Progress target Source: ONS (ICD ; ICD10 I00-I99)

3 CVD Dominates Global NCD deaths < 70 years (2008) CVD

4 CVD Prevention: Challenge! The human race has had long experience and a fine tradition in surviving adversity; we now face a task for which we have little experience, the task of surviving prosperity Alan Gregg ( ) Rockefeller Foundation

5 CVD Prevention Opportunity! Genetic Environmental Clinical Events Fetus Age (yrs)

6 Billions 2008 $ Forecasting Future CVD in USA Indirect Direct Heidenreich Circ 2011; 123:

7 Coronary Heart Disease Mortality in Beijing Extra deaths Attributable to Risk Factor Changes Cholesterol 77% Diabetes 19% BMI 4% Smoking 1% 642 fewer deaths by treatments AMI treatments 41% Hypertension treatment 24% Secondary prevetion 11% Heart failure 10% Aspirin for Angina 10% Angina: CABG & PTCA 2% Critchley J. Circulation, 2004;110:

8 Lancet Editorial 2011 Global Trends in Adult CV Disease The inescapable conclusion is that an epidemic of premature CV disease is developing, the brunt of which will be borne by low and middle income countries. the gains of recent years are likely to be overshadowed by the sheer volume of CV disease that will accrue from untreated RFs.

9 Odds Ratio Modifiable Risk Factors: Prevention Opportunity Age MI patients in 52 countries Gender Smoking BP Diabetes Cholesterol 9 RFs accounted for 90% of MI in men and 94% in women INTERHEART Lancet 2004

10 Atherosclerosis: Investing in your Arteries Early Intervention for Lifetime Risk Reduction

11 Prevalence of Atherosclerosis in the Young Atherosclerosis (%) % % 71% 40 37% 20 17% 32 Year Old Female 0 < Age (years) Tuzcu Circ :

12 Mean maximum carotid IMT (mm) CV Risk Factors in Childhood and Carotid IMT in Adults Risk factors measured at ages 12-18yrs No. of risk factors or P<0.001 P< Men Women Raitakari et al JAMA 2003;290;

13 Adjusted Cumulative Incidence Framingham Heart Study :Lifetime Risk Men 69% 50% 46% 36% Women 2 Major RFs 1 Major RF Elevated RF Not Elevated RF All Optimal RFs 50% 39% % % Attained Age % Lloyd-Jones Circ. 2006; 113:

14 Frequency (%) LDL Cholesterol and Coronary Heart Disease among Black Subjects by PCSK9 142X or PCSK9 679X Allele Coronary Heart Disease (%) th Percentile P= % % LDL Cholesterol in Black Subjects (mg/dl) 0 No Yes PCSK9 142X or PCSK9 679X Cohen NEJM 2006; 354:

15 CHD Impact of Early vs Late LDL Lowering Mendelian Randomisation Studies of 9 Polymorphisms in 6 Genes Ference J Am Coll Cardiol 2012; 60:

16 Opportunity for Lifetime Management of CVD Risk Exposure to risk factors over time is key Early intervention pays long term dividends

17 Cholesterol Lowering and Major Vascular events 90,056 pts in 14 Statin trials Endpoint (Yr) RR (CI) ( ) ( ) ( ( ) ( ) ( ) Trend test: 2 1 = 13.9; p= Treatment Control better better Cholsterol treatments trialists collaborators Lancet, 2005; 366:

18 Benefit Even at Low Risk? Cholesterol Treatment Trialists, Lancet 2012

19 Hazards of Smoking and Benefits of Smoking Cessation 113,752 w and 88,496 m aged 25y in US NHIS Jha N Engl J Med 2013; 368:

20 Joint British Societies (JBS)3: March 26th 2014 Early intervention pays long term dividends Investing in Your Arteries!

21 Mean Δ IMT (mm) Familial Hyper Cholesterolaemia Statins in FH Children 208 FH children (8-18 yrs) 1/500 of population = 12,000 in Central and NE London < 200 detected 50% chance of MI by 50yrs CCA P=0.06 Placebo Statin Rodenburg J Circ

22 Δ IMT (mm) FH v. siblings Familial Hypercholesterolaemia IMT difference between FH and sibs against age Age (years)

23 ACE inhibitor arm AdDIT: intervention in adolescent diabetes : ACR and cimt Statin arm atorvastatin placebo quinapril quinapril atorvastatin placebo placebo placebo

24 CV Effects of Smoking Ban in Public Places Study IRR (95% CI) % Weight Helena Pueblo New York Indiana Ohio Saskatoon Piedmont Rome Naples Trieste Scotland Overall (% CI) 0.60 (0.39, 0.92) 0.30 (0.25, 0.35) 0.98 (0.97, 0.99) 0.48 (0.24, 0.96) 0.81 ( ) 0.91 (0.80, 1.02) 1.08 (1.05, 1.12) 1.02 (0.98, 1.05) 1.09 (1.00, 1.19) 0.83 (0.79, 0.87) 0.83 (0.77, 0.92) Meyers et al JACC 54;

25 Passive Smoking in the Young Frey JACC 2012; 59: Young Finns CDAH Study Juonala ATVB 2012; 32; Meyers JACC 2009; 54:

26 Blood pressure (mm Hg) Cholesterol (mmol/l) ALSPAC: Vascular Risk Factors at 9-11 yrs v. BMI Systolic 4 Non-HDL Cholesterol Diastolic 60 1 HDL Cholesterol BMI (Kg/m 2 ) BMI (Kg/m 2 )

27 Childhood Obesity and Premature Death Glucose Intolerance 1 v. 4 th quartile 73% higher deaths Childhood Hypertension 1 v. 4 th quartile 57% higher deaths Franks NEJM ;

28 Juonala NEJM 2011; 365:

29 No. of excess events No. of excess events Potential Benefit of CV RF treatment in Obesity Excess Total CHD Events Excess Deaths from CHD Average projection Treatment for DBP and LDL Treatment for DBP, LDL and HDL Average projection Treatment for DBP and LDL Treatment for DBP, LDL and HDL Year Year Bibbins-Domingo NEJM 2007; 357:

30 Proportion of published cost-effectiveness ratios Cost Effectiveness of Preventive Interventions Environmental intervention Non-clinical, person-directed intervention Clinical intervention Costsaving <10,000 10,000 to <50,000 50,000 to <100, ,000 to <250, ,000 to <1,000,000 >1,000,000 Increases cost and worsens health Chokshi NEJM 2012;367:295-6

31 Taxation of Food and Drink Sugar, rum and tobacco are commodities which are nowhere necessaries of life, which are become objects of almost universal consumption, and which are therefore extremely proper subjects of taxation. Adam Smith, The Wealth of Nations, 1776 Brownell NEJM 2009;360:

32 CV disease is preventable Life-long Rx likely to be cost-effective and often cost saving Circulation 2011;124:

33 It should be the function of medicine to have people die young as late as possible Ernest L. Wynder M.D.

34 CV Prevention- Long way to go! Lifetime management of CV RFs Better communication with public, especially young Novel approaches to individual and population RF lowering Political and legislative interventions Doctors need to have a major role in leading health programmes and promoting societal change