Global Causes of Death 2011 The inescapable conclusion is that an - - PowerPoint PPT Presentation

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Global Causes of Death 2011 The inescapable conclusion is that an - - PowerPoint PPT Presentation

Mar 23, 2023 388 likes •803 views

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

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SLIDE 1

Global Causes of Death

  • NCDs cause 64% (35 million) of global deaths
  • 80% (28 million) are in LMICs
  • NCDs will cost the world $47 trillion over the next 20 years
  • CVD is responsible for around one third of all deaths worldwide

2011

“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”.

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SLIDE 2

20 40 60 Age (yrs)

Clinical Events

Genetic Environmental

Fetus

CVD Prevention Opportunity!

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SLIDE 3

Forecasting Future CVD Costs in USA

Heidenreich Circ 2011; 123: 933-944

900

Billions 2008 $

2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030

700 600 500 400 300 200 100 800

Indirect Direct

>20% of cost of car from staff health insurance

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SLIDE 4

Modifiable Risk Factors: Prevention Opportunity

INTERHEART Lancet 2004

1 2 3

Odds Ratio

9 RFs accounted for 90% of MI in men and 94% in women

Age Gender Smoking Cholesterol BP Diabetes 15152 MI patients in 52 countries

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SLIDE 5

New Lancet Statin Efficacy and Safety Study

Mean 1-year LDLC difference Between treatment groups (mmol/L) 30 20 10 0.5 1.0 1.5 Proportional reduction in major CV event rate (95% CI)

5 trials with LDL 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) 5 trials with further LDl reduction (average: 0.5 mmol/L)

Lancet September 2016

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SLIDE 6

Matthijs Boekholdt J Am Coll Cardiol 2014; 64: 485–94

Very Low Levels of Atherogenic Lipoproteins and the Risk for CV Events

A Meta-Analysis of Statin Trials

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SLIDE 7

Evolocumab in Hyperlipidemia as Add-On Therapy (DESCARTES Study)

Blom NEJM 2014; 370: 1809-1819

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SLIDE 8

Residual Risk in TNT Study

Mora Circ 2012; 125: 1979-1987

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

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SLIDE 9

Lifetime Atherosclerosis Management

 Treat to Lower Levels

 Treat multiple Risk Factors  Start Earlier

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SLIDE 10

Tuzcu Circ 2001 103:2075-10

32 Year Old Female

100

Atherosclerosis (%)

17% 37% 60% 85% 71% 20 40 60 80 <20 20-29 30-39 40-49 ≥50

Age (years)

Most of us have Arterial Disease!

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SLIDE 11

Framingham Heart Study :Lifetime Risk

Adjusted Cumulative Incidence 50% 39% 27%

Attained Age

0.7 0.6 0.5 0.4 0.3 0.2 0.1 50 60 70 80 90

69% 50% 46% 36% 5%

0.7 0.6 0.5 0.4 0.3 0.2 0.1 50 60 70 80 90

8%

≥2 Major RFs 1 Major RF ≥ Elevated RF ≥ Not Elevated RF All Optimal RFs

Men Women

Lloyd-Jones Circ. 2006; 113: 791-798

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SLIDE 12

LDL Cholesterol and Coronary Heart Disease among Black Subjects by PCSK9142X or PCSK9679X Allele

LDL Cholesterol in Black Subjects (mg/dl)

PCSK9142X or PCSK9679X

300 30 20 10 0 0 50 100 150 200 250 300 No Nonsense Mutation (n=3278)

50th Percentile

Frequency (%)

PCSK9142X

  • r PCSK9679X

(N=85) 30 20 10 0 0 50 100 150 200 250

Cohen NEJM 2006; 354:1264-72

28%

Coronary Heart Disease (%)

No Yes

P=0.008

12 8 4

88%

 Exposure to CV RFs over time is key  Compound interest from early management

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SLIDE 13

Ference J Am Coll Cardiol. 2015; 65: 1552–61

Benefit from Lifetime Lower LDLc

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SLIDE 14

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

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SLIDE 15

Silverman JAMA 2016; 316: 1289-1297

Trial Support for Lower LDLc Irrespective of Approach

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SLIDE 16

Ford Circ 2016; 133: 1073-1080

Long Term Benefits From LDLc Lowering Past Trial Duration

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SLIDE 17

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

men over 55 and women over 60 would be eligible based on HOPE-3 criteria”

Salim Yousef

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SLIDE 18

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
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SLIDE 19

Combined Effect of LDL-C and SBP

  • n Cardiovascular Events
  • B. Ference (Plymouth, US), FP 3163

N = 14,368 Major Vascular Events

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SLIDE 20
  • B. Ference (Plymouth, US), FP 3163

Effect of 1 mmol/L lower LDL-C & 10 mmHg lower SBP on Major Cardiovascular Events

SBP and LDL-C have independent, multiplicative and cumulative effects on CVD risk

0.25 0.50 0.75 1.00

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SLIDE 21

Conclusions

LDL-C and SBP have independent, multiplicative

and cumulative causal effects on risk of CV events

 Because their effects are multiplicative and cumulative

  • ver 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

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SLIDE 22

Olsen Lancet September 23 2016

Managing CVD Risk with an Integrated Approach

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SLIDE 23

Knowledge Communication

CVD Prediction and Prevention

Empowerment

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SLIDE 24

European Heart Journal 2012; 33: 1635-1701

ESC CV Prevention Guidelines 2012

Disenfranchises the Young, especially Women!

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SLIDE 25

Non-smoking men <45yrs All women <65yrs <10% 10yr CHD Risk 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 Marma Circ 2009;120:384-390

Short Term v. Lifetime Risk in USA

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SLIDE 26

New Cholesterol Guidelines to a Population-Based Sample

Pencina NEJM 2014; 370: 1422-31

56 million people Mostly Elderly Men!

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SLIDE 27

JBS3 Lifetime Risk Calculator

Heart March 2014 and www.jbs3risk.com

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SLIDE 28

Systolic Blood Pressure (mmHg)

P<0.001

2 1

  • 1
  • 2
  • 3
  • 4
  • 5

Weight (kg)

P<0.001

1.0 0.8 0.6 0.2

  • 0.2
  • 0.4
  • 0.8
  • 1.0

0.4 0.0

  • 0.6

Glucose (mg/dl)

P<0.001

4 3 2 1

  • 2
  • 3
  • 4
  • 1

Total cholesterol (mg/dl)

P<0.001

8 6 4 2

  • 4
  • 6
  • 8
  • 2

Current smoking (%^)

P<0.001

2.0 1.5 1.0 0.5 0.0

  • 1.0
  • 1.5
  • 2.0
  • 0.5

Heart Age (yrs)

P<0.001

2.0 1.5 1.0 0.5 0.0

  • 1.0
  • 1.5
  • 2.0
  • 0.5

Impact of Heart Age Tool on Modifiable CVRFs

3153 subjects (47% male), Mean Age 46yrs, 12m FU

Lopez-Gonzalez European Journal of Preventive Cardiology 2015: 22; 389–396

Control FR HA

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SLIDE 29

Heart Age NHS Calculator: 14/02/15-13/04/16

Total starts: 2,115,568 Total completes: 882,260

Patel BMJ Open 2016 Today

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SLIDE 30

World Heart Day: PHE Launch 29/09/16

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SLIDE 31

What’s Good for the Heart is Good for the Brain!

CV RF lowering and Dementia Risk?

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SLIDE 32

Whitmer Neurology 2005; 64: 277-281

Mid LifeCV RFs and Dementia

2.5 2.0 1.5 1.0 0.5

1 2 3 4

Hazard Factor

Risk Factors CV composite Score

8845 HMO patients Age 40-43 yrs

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SLIDE 33

Multidomain Treatment and Cognitive Decline: FINGER Trial

Ngandu Lancet 2015; 385: 2255-2263

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SLIDE 34

National Initiative for Preventable Dementia Based on CV Risk Factor Reduction

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SLIDE 35

Familial Hypercholesterolaemia

IMT difference between FH and sibs against age

  • 0.04
  • 0.02

0.02 0.04 0.06 0.08

Δ IMT (mm) FH v. siblings Age (years)

8 10 12 14 16 18

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SLIDE 36

Juonala NEJM 2011; 365: 1876-1885

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SLIDE 37

Digital Health: Empowerment ?

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SLIDE 38

Early Management / Digital Systems Wellness Illness Ageing

Revolution in the Delivery of Medicine

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SLIDE 39

Olsen Lancet September 23 2016

Integrated Approach to CV Risk

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SLIDE 40

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!