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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.

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Lancet 2007; 370: 1829-39

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Lancet 2007 370 1829 39

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

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

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

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


Ihd mortality 33 744 deaths versus usual total cholesterol

IHD mortality (33 744 deaths) versus usual total cholesterol

Age at

risk

1 mmol/L 

total cholesterol

15% risk

80-89

256

128

18% risk

70-79

64

28% risk

60-69

32

42% risk

50-59

16

56% risk

Hazard ratio

(floating absolute risks & 95% CI)

40-49

8

4

2

1

0·5

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-by-agesex-hettrend.ctrl: 24-SEP-2007 14:47:08.14


Ihd mortality 33 744 deaths versus usual total cholesterol by age and sex

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

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)

Hazard ratio (& 95% CI)

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

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-by-agesex-hettrend.ctrl: 24-SEP-2007 14:47:08.14


Ihd mortality 33 744 deaths versus usual total cholesterol by baseline sbp

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

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

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-effectmod-slopes.ctrl: 24-SEP-2007 14:47:13.34


Ihd mortality 33 744 deaths versus usual total cholesterol by smoking status

0·6

0·8

1·0

0·4

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

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

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-effectmod-slopes.ctrl: 24-SEP-2007 14:47:13.34


Ihd mortality 33 744 deaths versus usual total cholesterol by bmi

0·4

0·6

0·8

1·0

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

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)

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-effectmod-slopes.ctrl: 24-SEP-2007 14:47:13.34


Lancet 2007 370 1829 39

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

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

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

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

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-hdletc-by-age-mg.ctrl: 24-SEP-2007 14:47:15.78


Ihd mortality 3020 deaths versus usual hdl cholesterol

IHD mortality (3020 deaths) versus usual HDL cholesterol

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

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

1

40-59

63%  risk

0·5

1·0

1·5

Usual HDL cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-hdletc-by-age-mg.ctrl: 24-SEP-2007 14:47:15.78


Ihd mortality 3020 deaths versus usual non hdl cholesterol

70-89

27%  risk

60-69

34%  risk

40-59

43%  risk

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

Age at

risk:

1 mmol/L 

non-HDL

128

64

32

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

2

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

1

0·5

3

4

5

6

Usual non-HDL cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-hdletc-by-age-mg.ctrl: 24-SEP-2007 14:47:15.78


Ihd mortality 3020 deaths versus usual total hdl cholesterol

128

64

32

16

8

4

2

1

0·5

3

4

5

6

7

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

Age at

risk

1.33 units 

total/HDL

70-89

31%  risk

40  risk

60-69

Hazard ratio

(floating absolute risks & 95% CI)

40-59

44%  risk

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Usual total/HDL cholesterol

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-hdletc-by-age-mg.ctrl: 24-SEP-2007 14:47:15.78


Stroke mortality 11 663 deaths versus usual total cholesterol by age

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

64

Age at risk: HR (95% CI)

per 1mmol/L :

80-89 1.06 (1.00-1.13)

32

16

70-79 1.04 (0.99-1.09)

8

Hazard ratio

(floating absolute risks & 95% CI)

4

60-69 1.02 (0.97-1.08)

Hazard ratio (& 95% CI)

2

40-59 0.90 (0.84-0.97)

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]stroke-by-agecause-trend.ctrl: 24-SEP-2007 14:47:18.56


Stroke mortality 11 663 deaths versus usual total cholesterol by type and age

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

Hazard ratio (& 95% CI)

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

UDV3:[VEP.PSC.FIGURES.TCHOL.OCT07]fig4-ppt.ctrl: 17-OCT-2007 13:42:15.33


Stroke mortality 11 663 deaths versus usual total cholesterol by baseline sbp

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

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

Hazard ratio (& 95% CI)

<145

42% risk

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]STROKE-BY-SBPCAUSE-TREND.CTRL: 24-SEP-2007 14:47:21.45


Stroke mortality 16 497 deaths versus usual total cholesterol by baseline sbp

Stroke mortality (16 497 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

Hazard ratio (& 95% CI) for

1 mmol/L lower usual total cholesterol

UDV3:[VEP.PSC.FIGURES.TCHOL.OCT07]fig5-ppt.CTRL: 17-OCT-2007 12:23:09.75


Lancet 2007 370 1829 39

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

128

HR (95%CI)

per 1.33 units 

total/HDL

64

32

70-89

years

70-89

70-89 years

70-89

70-89

70-89

years

0.95 (0.83-1.10)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

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

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]stroke-thing4.ctrl: 24-SEP-2007 14:47:23.91


Stroke mortality 914 deaths versus usual hdl cholesterol

Stroke mortality (914 deaths) versus usual 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

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

2

40-69 years

1.04 (0.89-1.23)

1

0·5

1·0

1·5

Usual HDL

(mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]stroke-thing4.ctrl: 24-SEP-2007 14:47:23.91


Stroke mortality 914 deaths versus usual non hdl cholesterol

Stroke mortality (914 deaths) versus usual non-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

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

2

40-69 years

0.96 (0.83-1.12)

1

0·5

3

4

5

6

Usual non-HDL

(mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]stroke-thing4.ctrl: 24-SEP-2007 14:47:23.91


Stroke mortality 914 deaths versus usual total hdl cholesterol

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

128

HR (95%CI)

per 1.33 units 

total/HDL

64

32

70-89 years

0.95 (0.83-1.10)

16

8

Hazard ratio

(floating absolute risks & 95% CI)

4

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

2

40-69 years

0.86 (0.74-0.99)

1

0·5

3

4

5

6

7

Usual total/HDL

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]stroke-thing4.ctrl: 24-SEP-2007 14:47:23.91


Conclusions total cholesterol ihd mortality

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

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

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

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


Selected web material

Selected WEB material


Ihd mortality 33 744 deaths versus usual total cholesterol by sbp

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

Baseline SBP

(mmHg):

8

185+

165-184

145-164

4

<145

Hazard ratio

(floating absolute risks & 95% CI)

2

Hazard ratio (& 95% CI)

1

4·0

5·0

6·0

7·0

8·0

Usual total cholesterol (mmol/L)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-BY-SBPCAUSE-TREND.CTRL: 24-SEP-2007 14:47:42.31


Lancet 2007 370 1829 39

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

(a)

(b)

Baseline HDL

(mmol/L)

<1·25

<1·25

4

1·25+

1·25+

2

Baseline non-HDL

(mmol/L)

5+

5+

Hazard ratio (& 95% CI)

Hazard ratio (& 95% CI)

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)

UDV3:[VEP.PSC.FIGURES.TCHOL.240907]ihd-hdl-ndl.ctrl: 24-SEP-2007 17:19:17.65


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