Lancet 2007 370 1829 39
This presentation is the property of its rightful owner.
Sponsored Links
1 / 27

Lancet 2007; 370: 1829-39 PowerPoint PPT Presentation


  • 277 Views
  • Uploaded on
  • Presentation posted in: General

Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370: 1829-39. Prospective Studies Collaboration .

Download Presentation

Lancet 2007; 370: 1829-39

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Blood cholesterol and vascular mortality by age, sex and blood pressure:a meta-analysis of individual datafrom 61 prospective studieswith 55 000 vascular deaths

Lancet 2007; 370: 1829-39


Prospective Studies Collaboration

  • Established chiefly to investigate associations of blood pressure and cholesterol with cause-specific mortality

  • Individual data on 900 000 participants without any previous history of vascular disease from 61 prospective cohort studies

  • > 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12 000 stroke, 10 000 other)

  • 150 000 participants from 23 studies also had HDL cholesterol (5000 vascular deaths)


Collaborators and investigators

Atherosclerosis Risk in Communities (ARIC): L Chambless; Belgian Inter-university Research on Nutrition and Health (BIRNH): G De Backer, D De Bacquer, M Kornitzer; British Regional Heart Study (BRHS): P Whincup, SG Wannamethee, R Morris; British United Provident Association (BUPA):N Wald, J Morris, M Law; Busselton: M Knuiman, H Bartholomew; Caerphilly and Speedwell: G Davey Smith, P Sweetnam, P Elwood, J Yarnell; Cardiovascular Health Study (CHS): R Kronmal; CB Project: D Kromhout; Charleston: S Sutherland, J Keil; Copenhagen City Heart Study: G Jensen, P Schnohr; Evans County: C Hames (deceased), A Tyroler; Finnish Mobile Clinic Survey (FMCS): A Aromaa, P Knekt, A Reunanen; Finrisk: J Tuomilehto, P Jousilahti, E Vartiainen, P Puska; Flemish Study on Environment, Genes and Health (FLEMENGHO): T Kuznetsova, T Richart, J Staessen, L Thijs; Research Centre for Prevention and Health (Glostrup Population Studies): T Jorgensen,T Thomsen; Honolulu Heart Program: D Sharp, JD Curb; Ikawa, Noichi and Kyowa: H Iso, S Sato, A Kitamura, Y Naito; Imperial College, London and Oxon Clinical Epidemiology Limited: N Qizilbash; Centre d'Investigations Preventives et Cliniques (IPC), Paris: A Benetos, L Guize; Israeli Ischaemic Heart Disease Study: U Goldbourt; Japan Railways: M Tomita, Y Nishimoto, T Murayama; Lipid Research Clinics Follow-up Study (LRC): M Criqui, C Davis; Midspan Collaborative Study: C Hart, G Davey-Smith, D Hole, C Gillis; Minnesota Heart Health Project (MHHP) and Minnesota Heart Survey (MHS): D Jacobs, H Blackburn, R Luepker; Multiple Risk Factor Intervention Trial (MRFIT): J Neaton, L Eberly; First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS): C Cox; NHLBI Framingham Heart Study: D Levy, R D'Agostino, H Silbershatz; Norwegian Counties Study: A Tverdal, R Selmer; Northwick Park Heart Study (NPHS): T Meade, K Garrow, J Cooper; Nurses’ Health Study: F Speizer, M Stampfer; Occupational Groups (OG), Rome: A Menotti, A Spagnolo; Ohasama: I Tsuji, Y Imai, T Ohkubo, S Hisamichi; Oslo: L Haheim, I Holme, I Hjermann, P Leren; Paris Prospective Study: P Ducimetiere, J Empana; Perth: K Jamrozik, R Broadhurst; Prospective Cardiovascular Munster Study (PROCAM): G Assmann, H Schulte; Prospective Study of Women in Gothenburg: C Bengtsson, C Björkelund, L Lissner; Puerto Rico Health Heart Program (PRHHP): P Sorlie, M Garcia-Palmieri; Rancho Bernado: E Barrett-Connor, M Criqui, R Langer; RenfrewandPaisley study: C Hart, G Davey Smith, D Hole; Saitama Cohort Study: K Nakachi, K Imai; Seven Cities China: X Fang, S Li; Seven Countries (SC) Croatia: R Buzina; SC Finland: A Nissinen; SC Greece (Greek Islands Study): C Aravanis, A Dontas, A Kafatos; SC Italy: A Menotti; SC Japan: H Adachi, H Toshima, T Imaizumi; SC Netherlands: D Kromhout; SC Serbia: S Nedeljkovic, M Ostojic; Shanghai: Z Chen; Scottish Heart Health Study (SHHS): H Tunstall-Pedoe; Shibata: T Nakayama, N Yoshiike, T Yokoyama, C Date, H Tanaka; Tecumseh: J Keller; Tromso: K Bonaa, E Arnesen; United Kingdom Heart Disease Prevention Project (UKHDPP): H Tunstall-Pedoe; US Health Professionals Follow-up Study: E Rimm; US Physicians’ Health Study: M Gaziano, JE Buring, C Hennekens; Värmland: S Törnberg, J Carstensen; Whitehall: M Shipley, D Leon, M Marmot; Clinical Trial Service Unit (CTSU): J Armitage, C Baigent, Z Chen, R Clarke, R Collins, J Emberson, J Halsey, M Landray, S Lewington, A Palmer (deceased), S Parish, R Peto, P Sherliker, G Whitlock.

Steering Committee — S Lewington (coordinator and statistician), S MacMahon (chair), R Peto (statistician), A Aromaa, C Baigent, J Carstensen, Z Chen, R Clarke, R Collins, S Duffy, D Kromhout, J Neaton, N Qizilbash, A Rodgers, S Tominaga, S Törnberg, H Tunstall-Pedoe, G Whitlock.


Analysis

  • Cox regression adjusted for age, sex & study

  • Hazard ratios are presented as floating absolute risks (does not alter values but adds appropriate confidence interval to every group, including even reference group)

  • Adjustment for regression dilution bias makes relationship with usual values about 50% steeperthan that with measured values


256

128

64

32

16

Hazard ratio

(floating absolute risks & 95% CI)

8

4

2

1

0·5

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

IHD mortality (33 744 deaths) versus usual total cholesterol

Age at

risk

1 mmol/L 

total cholesterol

15% risk

80-89

18% risk

70-79

28% risk

60-69

42% risk

50-59

56% risk

40-49


Age at

risk

Sex

No. of

deaths

80-89

Men

2919

Women

2707

0·85 (0·82-0·89)

Total

5626

70-79

Men

7372

Women

3457

Total

10 829

0·82 (0·80-0·85)

60-69

Men

8594

Women

1825

Total

10 419

0·72 (0·69-0·74)

50-59

Men

5001

Women

560

Total

5561

0·58 (0·56-0·61)

40-49

Men

1191

Women

118

Total

1309

0·44 (0·42-0·48)

0·4

0·6

0·8

1·0

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

IHD mortality (33 744 deaths) versus usual total cholesterolby age and sex


Age at

risk

SBP

(mmHg)

No. of

deaths

70-89

165+

7634

0·82 (0·79-0·84)

145-164

4645

0·79 (0·76-0·82)

<145

4176

0·76 (0·73-0·79)

60-69

165+

3174

0·81 (0·78-0·84)

145-164

3027

0·73 (0·70-0·76)

<145

4218

0·68 (0·65-0·70)

40-59

165+

1364

0·66 (0·62-0·70)

145-164

1908

0·62 (0·59-0·65)

<145

3598

0·53 (0·51-0·55)

0·4

0·6

0·8

1·0

Hazard ratio (& 95% CI) for

mmol/L lower usual total cholesterol

IHD mortality (33 744 deaths) versus usual total cholesterolby baseline SBP


Age at

risk

Smoking

status

No. of

deaths

70-89

2730

Current cig

0·74 (0·71-0·78)

Other

11 168

0·80 (0·78-0·82)

2557

Never

smoker

0·77 (0·74-0·81)

60-69

3911

Current cig

0·70 (0·68-0·73)

Other

5170

0·71 (0·68-0·74)

1338

Never

smoker

0·71 (0·67-0·76)

40-59

3612

Current cig

0·58 (0·56-0·60)

Other

2608

0·54 (0·52-0·57)

650

0·59 (0·54-0·64)

Never

smoker

0·6

0·8

1·0

0·4

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

IHD mortality (33 744 deaths) versus usual total cholesterolby smoking status


Age at

risk

BMI

(kg/m2)

No. of

deaths

70-89

30+

2369

0·77 (0·73-0·81)

25-29

7198

0·78 (0·75-0·80)

<25

6736

0·79 (0·76-0·81)

60-69

30+

1518

0·74 (0·70-0·79)

25-29

4679

0·72 (0·69-0·74)

<25

4123

0·70 (0·68-0·73)

40-59

30+

827

0·62 (0·57-0·67)

25-29

3105

0·56 (0·54-0·59)

<25

2881

0·55 (0·53-0·58)

0·4

0·6

0·8

1·0

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

IHD mortality (33 744 deaths) versus usual total cholesterolby BMI


1.33 units 

total/HDL

128

31% 

70-89

years

70-89

years

64

32

70-89

years

60-69

40% 

60-69

16

Hazard ratio

(floating absolute risks & 95% CI)

8

40-59

44% 

60-69

40-59

4

2

1

40-59

0·5

1·0

1·5

3

4

5

6

3

4

5

6

7

Usual HDL

(mmol/L)

Usual non-HDL

(mmol/L)

Usual total/HDL

IHD mortality (3020 deaths) versus usual(a) HDL cholesterol; (b) non-HDL cholesterol; and (c) total/HDL cholesterolby age at risk


128

Age at

risk:

0.33 mmol/L 

HDL

64

70-89

35%  risk

32

16

8

Hazard ratio

(floating absolute risks & 95% CI)

83%  risk

60-69

4

2

1

40-59

63%  risk

0·5

1·0

1·5

Usual HDL cholesterol (mmol/L)

IHD mortality (3020 deaths) versus usual HDL cholesterol


Age at

risk:

1 mmol/L 

non-HDL

128

70-89

27%  risk

64

32

60-69

34%  risk

16

8

Hazard ratio

(floating absolute risks & 95% CI)

40-59

43%  risk

4

2

1

0·5

3

4

5

6

Usual non-HDL cholesterol (mmol/L)

IHD mortality (3020 deaths) versus usual non-HDL cholesterol


Age at

risk

1.33 

total/HDL

70-89

31%  risk

128

64

40  risk

60-69

32

16

Hazard ratio

(floating absolute risks & 95% CI)

8

40-59

44%  risk

4

2

1

0·5

3

4

5

6

7

Usual total/HDL cholesterol

IHD mortality (3020 deaths) versus usual total/HDL cholesterol


64

Age at risk: HR (95% CI)

per 1mmol/L 

80-89 1.10 (1.05-1.16)

32

16

70-79 1.15 (1.09-1.20)

8

Hazard ratio

(floating absolute risks & 95% CI)

4

60-69 0.94 (0.90-0.99)

2

40-59 0.84 (0.78-0.91)

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

Stroke mortality (11 663 deaths) versus usual total cholesterol by age


Stroke

subtype

Age at

risk

No. of

deaths

Total

stroke

80-89

2632

1·06 (1·00-1·13)

70-79

4311

1·04 (0·99-1·09)

60-69

2938

1·02 (0·97-1·08)

Test for trend: 12 = 9.3 (P=0.002)

40-59

1782

0·90 (0·84-0·97)

Haemorrhagic

stroke

80-89

422

1·06 (0·90-1·25)

70-79

915

1·18 (1·06-1·31)

60-69

743

1·09 (0·97-1·23)

Test for trend: 12 = 4.3 (P=0.04)

40-59

620

0·92 (0·81-1·04)

Ischaemic

stroke

80-89

519

1·09 (0·95-1·26)

70-79

850

1·06 (0·95-1·17)

60-69

540

0·89 (0·79-1·01)

Test for trend: 12 = 15.1 (P=0.0001)

40-59

225

0·73 (0·61-0·87)

0·6

0·8

1·0

1·2

1·4

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

Stroke mortality (11 663 deaths) versus usual total cholesterolby type and age


8

Baseline SBP

(mmHg):

1 mmol/L 

total cholesterol

185+

10% risk

4

Hazard ratio

(floating absolute risks & 95% CI)

15% risk

165-184

2

145-164

7% risk

<145

42% risk

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

Stroke mortality (11 663 deaths) versus usual total cholesterolby baseline SBP


Stroke

subtype

SBP

(mmHg)

No. of

deaths

Total

stroke

185+

2473

1·10 (1·05-1·16)

165-184

2498

1·15 (1·09-1·20)

145-164

3092

1·07 (1·02-1·12)

125-144

2562

0·94 (0·90-0·99)

Test for trend:12 = 53·2 (p<0·0001)

<125

1038

0·84 (0·78-0·91)

Haemorrhagic

stroke

185+

662

1·16 (1·05-1·27)

165-184

631

1·30 (1·18-1·43)

145-164

674

1·12 (1·03-1·23)

125-144

528

1·01 (0·90-1·13)

<125

205

0·83 (0·71-0·98)

Test for trend: 12 = 15·7 (p=0·0001)

Ischaemic

stroke

185+

476

0·99 (0·89-1·11)

165-184

439

1·13 (1·01-1·26)

145-164

574

1·00 (0·91-1·11)

125-144

433

0·92 (0·82-1·03)

Test for trend: 12 = 8.9 (p=0·003)

<125

212

0·78 (0·67-0·90)

0·6

0·8

1·0

1·4

1·2

Stroke mortality (16 497 deaths) versus usual total cholesterolby baseline SBP

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol


128

HR (95%CI)

per 1.33 

total/HDL

64

32

70-89

years

70-89

70-89

70-89 years

70-89

years

70-89

0.95 (0.83-1.10)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

2

40-69

40-69

0.86 (0.74-0.99)

1

40-69

40-69

40-69

40-69

0·5

3

4

5

6

1·0

1·5

3

4

5

6

7

Usual non-HDL

(mmol/L)

Usual HDL

(mmol/L)

Usual total/HDL

Stroke mortality (914 deaths) versus usual:(a) HDL cholesterol; (b) non-HDL cholesterol; and (c) total/HDL cholesterol


128

HR (95%CI) per

0.33 mmol/L  HDL

64

32

70-89 years

1.02 (0.88-1.17)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

2

40-69 years

1.04 (0.89-1.23)

1

0·5

1·0

1·5

Usual HDL (mmol/L)

Stroke mortality (914 deaths) versus usual HDL cholesterol


128

HR (95%CI) per

1 mmol/L  non-HDL

64

32

70-89 years

1.05 (0.91-1.20)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

2

40-69 years

0.96 (0.83-1.12)

1

0·5

3

4

5

6

Usual non-HDL (mmol/L)

Stroke mortality (914 deaths) versus usual non-HDL cholesterol


128

HR (95%CI)

per 1.33 

total/HDL

64

32

70-89 years

0.95 (0.83-1.10)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

2

40-69 years

0.86 (0.74-0.99)

1

0·5

3

4

5

6

7

Usual total/HDL

Stroke mortality (914 deaths) versus usual total/HDL cholesterol


Conclusions:Total cholesterol & IHD mortality

  • Total cholesterol is a major risk factor for IHD both in middle and in old age

  • There is no threshold level of total cholesterol in the range commonly occurring in Western populations below which lower cholesterol is not associated with lower IHD mortality

  • There are no important sex differences in the relative effects of total cholesterol on vascular mortality

  • The joint relative effects of total cholesterol and blood pressure are approximately additive (rather than multiplicative)


Conclusions:HDL, non-HDL cholesterol & IHD mortality

  • The joint relative effects of HDL and non-HDL cholesterol are approximately independent and additive

  • HDL cholesterol adds worthwhile predictive information beyond either total or non-HDL cholesterol

  • The ratio of total/HDL cholesterol is statistically twice as informative as total cholesterol alone


Conclusions:Total cholesterol & stroke mortality

  • A positive relationship with ischaemic and total stroke mortality was seen only in middle age and only in those with below-average blood pressure

  • At older ages and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality

  • There is conclusive evidence from randomised trials that statins substantially reduce stroke rates in a wide range of patients

  • The contrast between these statistically reliable observational epidemiological results and the statistically reliable randomised trial results is substantial and invites further research


Web material


Baseline SBP

(mmHg):

8

185+

165-184

145-164

4

<145

Hazard ratio

(floating absolute risks & 95% CI)

2

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

IHD mortality (33 744 deaths) versus usual total cholesterol by SBP


IHD mortality (3020 deaths) versus:usual HDL cholesterol by baseline non-HDL cholesterolusual non-HDL cholesterol by baseline HDL cholesterol

Baseline HDL

(mmol/L)

<1·25

<1·25

4

1·25+

1·25+

Hazard ratio

(floating absolute risks & 95% CI)

2

Baseline non-HDL

(mmol/L)

5+

5+

1

<5

<5

0·5

1·0

1·5

3·0

4·0

5·0

6·0

Usual HDL cholesterol (mmol/L)

Usual non-HDL cholesterol (mmol/L)


  • Login