Vascular Diseases. Overview: Selected Slides

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1 Vascular Diseases Overview: Selected Slides

2 Total deaths and change in vascular death rates <70 years, 2000 and 2010, World Deaths in 2010 (millions) Change between World %

3 INDIA: 1.0 M vascular disease deaths at ages years MEN Ischemic heart: 0.45 M M had prior history Stroke: 0.2 M WOMEN Ischemic heart: 0.2 M M had prior history Stroke: 0.15 M Deaths from: heart failure (50,000), Rheumatic (10,000) Source: Gupta et al, forthcoming

4 Vascular mortality by level of education, ages years Source: Gupta a et al, in press

5 Changing vascular mortality: prevention & treatment Tobacco 3x non-smoker risk) Blood lipids* Blood pressure* Obesity * Secondary prevention: high annual risk 3 by long-term statin, BP lowering & aspirin

6 How important is blood pressure to vascular death? 20 mmhg systolic BP halves vascular mortality at Prospective Studies Collaboration (1 million adults) PSC, Lancet 2002; 360: 1903

7 34,000 heart attack deaths at ages 40-89: age-specific risks vs. usual SBP CHD mortality (& 95% CI) Age 20 mm Hg % risk % risk % risk % risk % risk mmhg halves risk Usual systolic BP (mmhg) PSC, Lancet 2002; 360:1903

8 11,000 stroke deaths at ages 40-89: age-specific risks vs. usual SBP Stroke mortality (& 95% CI) Age 20 mm Hg % risk % risk % risk % risk ( % risk) 20 mmhg halves risk Usual systolic BP (mmhg) PSC, Lancet 2002; 360:1903

9 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

10 Absolute effects on MAJOR VASCULAR EVENTS of lowering LDL cholesterol with STATIN therapy Five year risk of a major vascular event, % More statin Statin Combined evidence: 33% relative risk reduction per 1.5 mmol/l (since 0.79 x 0.84 = 0.67) Control 21% relative risk reduction per mmol/l 16% relative risk reduction per 0.5 mmol/l Or: ~40% relative risk reduction per 2 mmol/l LDL cholesterol, mmol/l

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

12 How important is obesity to vascular mortality? If overweight, 10 units BMI about halves MI & stroke PSC, Lancet 2009; 373: 1083

13 All-cause mortality and BMI 64 Annual deaths per 1000 & 95% CI (floated so matches PSC rate at ages 35-79) Male Female Baseline BMI (kg/m 2 ) Adjusted for age, smoking and study; 1 st 5 years of follow-up excluded Fig 2, Lancet 2009; XX; XX-XX

14 Main mortality categories and BMI 14 Male 14 Female 12 Vascular 12 Annual deaths per & 95% CI (floated so matches EU rate at ages 35-79) Adjusted for age, smoking and study; 1 st 5 years of follow-up excluded Cancer (other specified) 4 Cancer (lung, mouth, pharynx, larynx, oes.) 2 Respiratory Baseline BMI (kg/m 2 ) Resp. Vascular Cancer (other specified) Cancer (lung, mouth, pharynx larynx, oes.) Fig 5, Lancet 2009; XX; XX-XX

15 IHD and stroke mortality and BMI 8 IHD Annual deaths per 1000 & 95% CI (floated so matches PSC rate at ages 35-79) Stroke Baseline BMI (kg/m 2 ) Adjusted for age, sex, smoking and study; 1 st 5 years of follow-up excluded Fig 3, Lancet 2009; XX; XX-XX

16 All-cause mortality and BMI, by Annual deaths per 1000 & 95% CI (floated so matches EU rate at ages 35-79) smoking Current cigarette smoker Never smoked regularly (N.B. Vertical separation of curves underestimates effects of lifelong cigarette smoking) Baseline BMI (kg/m 2 ) Adjusted for age, sex and study; 1 st 5 years of follow-up excluded Fig 6, Lancet 2009; XX; XX-XX

17 Male rate 7.5 / 1000 (25% dead) Male Female rate 4.5 / 1000 (15% dead) Female Vascular death at ages 35-69, UK 2005: 7% Male, 3% Female

18 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 Lower good cholesterol More likelihood of diabetes Each makes vascular death more likely Source: Peto et al, 2006

19 Life expectancy loss of 3 years with moderate obesity and 10 years with smoking 2 kg/m 2 extra BMI (if overweight) or 10% smoking prevalence shortens life by ~1 yr Prospective Studies Collaboration (males) Male British Doctors Study % survival from age Severe obesity BMI, kg/m 2 22½-25 (~24) (~32) (~43) Moderate obesity Low-mortality BMI Yearly dots Cigarette smokers Neversmokers 10 years Yearly dots Age (years) Source: Peto, Whitlock, Jha, NEJM, 2010

20 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

21 Patients already diagnosed with a stroke or heart attack (MI): prevent recurrence by combining 3-4 generics in 1 daily pill Randomised comparison Trial result: annual 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

22 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

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