Global Causes of Death 2011 “ The inescapable conclusion is that an epidemic of • NCDs cause 64% (35 million) of global deaths premature CV disease is developing, the brunt of • 80% (28 million) are in LMICs • NCDs will cost the world $47 trillion over the next 20 years which will be borne by low and middle income • CVD is responsible for around one third of all deaths worldwide countries ” .
CVD Prevention Opportunity! Genetic Environmental Clinical Events Age (yrs) Fetus 0 20 40 60
Forecasting Future CVD Costs in USA 900 800 Billions 2008 $ 700 600 500 400 300 200 >20% of cost of car from Indirect Direct 100 0 staff health insurance 2026 2024 2010 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2025 2027 2029 2030 2011 2028 Heidenreich Circ 2011; 123: 933-944
Modifiable Risk Factors: Prevention Opportunity Age 15152 MI patients in 52 countries 3 Gender Odds Ratio 2 Smoking 1 BP 0 Diabetes Cholesterol 9 RFs accounted for 90% of MI in men and 94% in women INTERHEART Lancet 2004
New Lancet Statin Efficacy and Safety Study 30 5 trials with LDL Proportional reduction in major CV event rate (95% CI) reduction at 1year >1.1 mmol/L (average: 1.4 mmol/L) 17 trials with LDL reduction at 1year <1.1 mmol/L (average: 0.9 mmol/L) 20 10 5 trials with further LDl reduction (average: 0.5 mmol/L) 0 0 0.5 1.0 1.5 Mean 1-year LDLC difference Between treatment groups (mmol/L) Lancet September 2016
Very Low Levels of Atherogenic Lipoproteins and the Risk for CV Events A Meta-Analysis of Statin Trials Matthijs Boekholdt J Am Coll Cardiol 2014; 64: 485 – 94
Evolocumab in Hyperlipidemia as Add-On Therapy (DESCARTES Study) Blom NEJM 2014; 370: 1809-1819
Residual Risk in TNT Study Increased Risk RR Range Older age 1.13 1.04-1.23 Increased BMI 1.09 1.02-1.17 Male Sex 1.33 1.07-1.65 Increased BP 1.38 1.17-1.63 DM 1.33 1.11-1.60 Baseline ApoB 1.19 1.11-1.28 BUN 1.10 1.03-1.17 + Current smoking, CVD and CCB use Decreased Risk RR Range High dose statin 0.82 0.70-0.94 Aspirin 0.67 0.56-0.81 Baseline ApoA-1 0.91 0.84-0.99 Mora Circ 2012; 125: 1979-1987
Lifetime Atherosclerosis Management Treat to Lower Levels Treat multiple Risk Factors Start Earlier
Most of us have Arterial Disease! 100 85% Atherosclerosis (%) 80 71% 60% 60 37% 40 17% 20 0 <20 20-29 30-39 40-49 ≥50 Age (years) 32 Year Old Female Tuzcu Circ 2001 103:2075-10
Framingham Heart Study :Lifetime Risk Men Women 0.7 69% 0.7 ≥2 Major RFs Adjusted Cumulative Incidence 1 Major RF 0.6 0.6 ≥ Elevated RF ≥ Not Elevated RF All Optimal RFs 50% 50% 0.5 0.5 46% 0.4 0.4 39% 36% 0.3 0.3 27% 0.2 0.2 0.1 0.1 8% 5% 0 0 50 60 70 80 90 60 70 90 50 80 Attained Age Lloyd-Jones Circ. 2006; 113: 791-798
LDL Cholesterol and Coronary Heart Disease among Black Subjects by PCSK9 142X or PCSK9 679X Allele No Nonsense 12 Mutation Coronary Heart Disease (%) 50 th Percentile (n=3278) 30 P=0.008 Frequency (%) 20 8 88% 10 0 0 50 100 150 200 250 300 PCSK9 142X 4 or PCSK9 679X 28% (N=85) 30 20 0 No Yes 10 Exposure to CV RFs over time is key PCSK9 142X or PCSK9 679X 0 0 Compound interest from early management 50 100 150 200 250 300 Cohen NEJM 2006; 354:1264-72 LDL Cholesterol in Black Subjects (mg/dl )
Benefit from Lifetime Lower LDLc Ference J Am Coll Cardiol. 2015; 65: 1552 – 61
LDL EXposure is Key! Effect of Lower LDL-C Mediated by Polymorphisms in NPC1L1, HMGCR, or Both Ference J Am Coll Cardiol 2015; 65: 1552 – 61
Trial Support for Lower LDLc Irrespective of Approach Silverman JAMA 2016; 316: 1289-1297
Long Term Benefits From LDLc Lowering Past Trial Duration Ford Circ 2016; 133: 1073-1080
HOPE-3 Studies: NEJM April 2016 “ Because of the short follow up of trial the probable life time benefit of continuous treatment is much larger than the benefit observed during trials ” “ The size of the intermediate risk population eligible for primary prevention is enormous. Three quarters of Salim Yousef men over 55 and women over 60 would be eligible based on HOPE-3 criteria ”
Study Population and Exposures Study sample: 102,773 persons (age 27 - 100 years) enrolled in one of 14 prospective cohort or case-control studies LDL-C genetic score: 46 polymorphisms associated primarily with lower LDL-C at genome-wide level of significance SBP genetic score: 33 polymorphisms associated with lower SBP at genome-wide level of significance Genetic scores used as both the instrument of randomization and the instrument of exposure B. Ference (Plymouth, US), FP 3163 ESC 2016
Combined Effect of LDL-C and SBP on Cardiovascular Events N = 14,368 Major Vascular Events B. Ference (Plymouth, US), FP 3163
Effect of 1 mmol/L lower LDL-C & 10 mmHg lower SBP on Major Cardiovascular Events 0 0.25 0.75 0.50 1.00 SBP and LDL-C have independent, multiplicative and cumulative effects on CVD risk B. Ference (Plymouth, US), FP 3163
Conclusions LDL-C and SBP have independent, multiplicative and cumulative causal effects on risk of CV events Because their effects are multiplicative and cumulative over time, long-term exposure to combination of modestly lower LDL-C and SBP has the potential to dramatically reduce the lifetime risk of CVD CV events are largely preventable and CVD prevention can be substantially improved and simplified by designing programs that promote long-term exposure to combination of lower LDL-C and lower SBP beginning in early adulthood
Managing CVD Risk with an Integrated Approach Olsen Lancet September 23 2016
CVD Prediction and Prevention Knowledge Communication Empowerment
ESC CV Prevention Guidelines 2012 Disenfranchises the Young, especially Women! European Heart Journal 2012; 33: 1635-1701
Short Term v. Lifetime Risk in USA Non-smoking men <45yrs All women <65yrs <10% 10yr CHD Risk Marma Circ 2009;120:384-390 56% of US adults (87,000,000) have low (<10%) 10yr and high lifetime (≥39%) risk Marma Circ Cardiothoracic Qual Outcomes 2010;3:8-14
New Cholesterol Guidelines to a Population-Based Sample 56 million people Mostly Elderly Men! Pencina NEJM 2014; 370: 1422-31
JBS3 Lifetime Risk Calculator Heart March 2014 and www.jbs3risk.com
Impact of Heart Age Tool on Modifiable CVRFs 3153 subjects (47% male), Mean Age 46yrs, 12m FU 2 1.0 4 8 2.0 2.0 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 P<0.001 0.8 1 3 6 1.5 1.5 Systolic Blood Pressure (mmHg) 0.6 Total cholesterol (mg/dl) 4 2 1.0 1.0 0 Current smoking (%^) 0.4 Glucose (mg/dl) Heart Age (yrs) 1 2 0.5 0.5 Weight (kg) 0.2 -1 0.0 0 0 0.0 0.0 -2 -0.2 -2 -1 -0.5 -0.5 -0.4 -3 -2 -4 -1.0 -1.0 -0.6 -4 -0.8 -3 -6 -1.5 -1.5 -1.0 -5 -8 -4 -2.0 -2.0 Control FR Lopez-Gonzalez European Journal of Preventive Cardiology 2015: 22; 389 – 396 HA
Heart Age NHS Calculator: 14/02/15-13/04/16 Total starts: 2,115,568 Total completes: 882,260 Patel BMJ Open 2016 Today
World Heart Day: PHE Launch 29/09/16
CV RF lowering and Dementia Risk? What ’ s Good for the Heart is Good for the Brain!
Mid LifeCV RFs and Dementia Risk Factors CV composite Score 2.5 8845 HMO patients 2.0 Age 40-43 yrs Hazard Factor 1.5 1.0 0.5 0 1 2 3 4 Whitmer Neurology 2005; 64: 277-281
Multidomain Treatment and Cognitive Decline: FINGER Trial Ngandu Lancet 2015; 385: 2255-2263
National Initiative for Preventable Dementia Based on CV Risk Factor Reduction
Familial Hypercholesterolaemia IMT difference between FH and sibs against age 0.08 Δ IMT (mm) FH v. siblings 0.06 0.04 0.02 0 -0.02 -0.04 8 10 16 18 12 14 Age (years)
Juonala NEJM 2011; 365: 1876-1885
Digital Health: Empowerment ?
Revolution in the Delivery of Medicine Early Management / Digital Systems Wellness Illness Ageing
Integrated Approach to CV Risk Olsen Lancet September 23 2016
CVD Prevention: Some Thoughts… Early intervention for lifetime gain. Novel treatment approaches Better communication especially with the young Empowerment including use of innovative technology Political / legislative interventions Doctors need to play a major role in all of these!
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