Vascular Diseases

Overview: Selected Slides

Deaths in 2010 (millions)

Change between 2000-10

World 10.1 -17%

Total deaths and change in vascular death rates <70 years, 2000 and

2010, World

MEN • Ischemic heart: 0.45 M

- 0.37 M had prior history • Stroke: 0.2 M

WOMEN • Ischemic heart: 0.2 M - 0.16 M had prior history • Stroke: 0.15 M

Deaths from: heart failure (50,000), Rheumatic (10,000)

INDIA: 1.0 M vascular disease deaths at ages 30-69 years

Source: Gupta et al, forthcoming

Vascular mortality by level of education, ages 30-69 years

Source: Gupta a et al, in press

Changing vascular mortality: prevention & treatment

Tobacco (smoker @ 3x non-smoker risk)

Blood lipids* Blood pressure*

Obesity

* Secondary prevention: high annual risk ÷ 3 by long-term statin, BP lowering & aspirin

How important is blood pressure to vascular death?

20 mmHg systolic BP halves vascular mortality at 35-69

Prospective Studies Collaboration (1 million adults)

PSC, Lancet 2002; 360: 1903

Age 20 mm↓Hg

80-89 31% ↓ risk

70-79 40% ↓ risk

60-69 46% ↓

50-59 50% ↓ risk

40-49 51% ↓ risk

120 140 160 180

C

HD

mor

talit

y (&

95%

CI)

256

128

64

16 32

1

2

4

8

Usual systolic BP (mmHg)

34,000 heart attack deaths at ages 40-89: age-specific risks vs. usual SBP

20 mmHg halves risk

risk

PSC, Lancet 2002; 360:1903

120 140 160 180

St

roke

mor

talit

y (&

95%

CI)

Age 20 mm↓Hg 80-89 33% ↓ risk 70-79 50% ↓ risk

60-69 57% ↓ risk 50-59 62% ↓ risk

(40-49 64% ↓ risk)

256

64

32

16

8

4

2

1

128

Usual systolic BP (mmHg)

11,000 stroke deaths at ages 40-89: age-specific risks vs. usual SBP

20 mmHg halves risk

PSC, Lancet 2002; 360:1903

How important are blood lipids?

Good statin regimen reduces LDL cholesterol by 2 mmol/L

and vascular risk by 40%

(Non-vascular mortality is unaffected)

CTT, Lancet; online Nov 9, 2010

Absolute effects on MAJOR VASCULAR EVENTS of lowering LDL cholesterol with STATIN therapy

0 1 2 3 4 5

0 5

10

15

20

LDL cholesterol, mmol/L

Five

yea

r ris

k of

a m

ajor

va

scul

ar e

vent

, %

Control

Combined evidence: 33% relative risk reduction

per 1.5 mmol/L (since 0.79 x 0.84 = 0.67)

21% relative risk reduction per mmol/L Statin

16% relative risk reduction per 0.5 mmol/L More statin

Or: ~40% relative risk reduction

per 2 mmol/L

CTT collaborative meta-analysis, cancer incidence: 14 statin trials, 400,000 p.-years, no apparent hazard

How important is obesity to vascular mortality?

If overweight, 10 units BMI about halves MI & stroke

PSC, Lancet 2009; 373: 1083

All-cause mortality and BMI

15 20 25 30 35 40 50 4

8

16

32

64

Annual deaths

per 1000

Baseline BMI (kg/m2)

Adjusted for age, smoking and study; 1st 5 years of follow-up excluded

Male

Female

Fig 2, Lancet 2009; XX; XX-XX

& 95% CI (floated so matches PSC rate at

ages 35-79)

Male Female

2

4

6

8

10

12

14

0

2

4

6

8

10

12

14

0 15 20 25 30 35 50 15 20 25 30 35 50

Vascular

Respiratory

Cancer (lung, mouth, pharynx, larynx, oes.)

Vascular

Resp.

Main mortality categories and BMI

Cancer (other specified)

Baseline BMI (kg/m2)

Cancer (lung, mouth, pharynx larynx, oes.)

Cancer (other specified)

Fig 5, Lancet 2009; XX; XX-XX Adjusted for age, smoking and study; 1st 5 years of follow-up excluded

Annual deaths

per 1000

& 95% CI (floated so matches EU rate at

ages 35-79)

IHD and stroke mortality and BMI

15 20 25 30 35 40 50 0·5

1

2

4

8 IHD

Stroke

Adjusted for age, sex, smoking and study; 1st 5 years of follow-up excluded Fig 3, Lancet 2009; XX; XX-XX

Baseline BMI (kg/m2)

Annual deaths

per 1000

& 95% CI (floated so matches PSC rate at

ages 35-79)

All-cause mortality and BMI, by smoking

15 20 25 30 35 50 0

5

10

15

20

25

30

Baseline BMI (kg/m2)

Current cigarette smoker

Never smoked regularly

Adjusted for age, sex and study; 1st 5 years of follow-up excluded Fig 6, Lancet 2009; XX; XX-XX

Annual deaths

per 1000

& 95% CI (floated so matches EU rate at

ages 35-79) (N.B. Vertical separation of

curves underestimates effects of lifelong cigarette smoking)

Vascular death at ages 35-69,

UK 2005: 7% Male,

3% Female

Male rate 7.5 / 1000

(25% dead)

Female rate 4.5 / 1000

(15% dead)

Male

Female

BMI and vascular disease: main mechanisms known, and largely reversible

Hazards largely or wholly accounted for by blood pressure, cholesterol and diabetes

More body fat causes:

Higher blood

pressure

Higher “bad”

cholesterol

More likelihood of

diabetes

Each makes vascular death more likely

Lower “good”

cholesterol

Source: Peto et al, 2006

40 50 60 70 80 90 100

Yearly dots

BMI, kg/m2

30-35 (~32) 40-50 (~43)

0

20

40

60

80

100

Age (years)

% su

rviv

al fr

om a

ge 3

5

Never- smokers

Cigarette smokers

Prospective Studies Collaboration (males)

0

20

40

60

80

100

40 50 60 70 80 90 100

Male British Doctors’ Study

Yearly dots

Low-mortality BMI

Severe obesity

22½-25 (~24)

10 years

Moderate obesity

Life expectancy loss of 3 years with moderate obesity and

10 years with smoking 2 kg/m2 extra BMI (if overweight) or

10% smoking prevalence shortens life by ~1 yr

Source: Peto, Whitlock, Jha, NEJM, 2010

Changing vascular mortality: secondary (2ry) prevention

•Long-term drug treatment of high risk:

statin, BP lowering & aspirin in 1 pill

•Particularly relevant to 2ry prevention in middle age with good quality of life: 10-

year recurrence risk is 1/6, not 1/2

Patients already diagnosed with a stroke or heart attack (MI): prevent recurrence by

combining 3-4 generics in 1 daily pill Randomised Trial result: annual comparison rate of stroke/MI Aspirin vs nothing 5% vs 7% Aspirin + (BP lowering vs not) 3% vs 5% BP lowering + aspirin + (statin vs not) 2% vs 3%

10-year risk: 50% if untreated vs 16% with 3 drugs For every 20M on treatment, prevent 1M events / yr

Change drug approval process in G-7 & BRICS:

Let any combination of generics be approved for effects of each drug if it is 1. made to Good Manufacturing Practice; 2. shown to have bioavailability & shelf-life

Particularly important for vascular disease

control