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血脂 相关 剩留血管风险的治疗策略 PowerPoint PPT Presentation


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血脂 相关 剩留血管风险的治疗策略. 何为剩留血管事件风险?. 尽管很多患者接受了当前心血管疾病的标准治疗,包括降低 LDL-C 达标,加强控制血压和血糖等 ,但仍剩留明显的大血管事件和微血管并发症风险 。 此定义由 R 3 i 国际指导委员会委员发布。. 血脂相关剩留血管事件风险的治疗策略. 1, 他汀时代的剩留大血管事件风险 2, 血脂相关因素与剩留大血管事件风险 3, 他汀时代的小或微血管事件风险 4, 致 AS 血脂异常与 小或微血管事件风险 5, 剩留血管事件风险的治疗策略. 他汀临床试验中剩留的心血管风险. Patients Experiencing

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血脂 相关 剩留血管风险的治疗策略

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LDL-C

R3i


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1,

2,

3,

4,AS

5,


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Patients Experiencing

Major CHD Events, %

4S1

LIPID2

CARE3

HPS4

WOSCOPS5

AFCAPS/

TexCAPS6

N

4444

9014

4159

20,536

6595

6605

LDL

35%

25%

28%

29%

26%

25%

Secondary

High Risk

Primary

4S, Scandinavian Simvastatin Survival Study; HPS, Heart Protection Study; WOSCOPS, West of Scotland Coronary Prevention Study; AFCAPS/TexCAPS, Air Force/Texas Coronary Atherosclerosis Prevention Study.

14S Group. Lancet. 1994;344:1383-1389; 2LIPID Study Group. N Engl J Med. 1998;339:1349-1357; 3Sacks FM et al. N Engl J Med. 1996;335:1001-1009. 4HPS Collaborative Group. Lancet. 2002;360:7-22; 5Shepherd J et al. N Engl J Med. 1995;333:1301-1307; 6Downs JR et al. JAMA. 1998;279:1615-1622.


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84%

88%

80%

Patients Experiencing

Major CVD Events, %

PROVE IT-TIMI 222

TNT4

IDEAL3

4162

N

8888

10,001

LDL-C,* mg/dL

95

62

104

81

101

77

PROVE IT-TIMI 22, Pravastatin or Atorvastatin Evaluation and Infection TherapyThrombolysis In Myocardial Infarction 22; IDEAL, Incremental Decrease in End Points Through Aggressive Lipid Lowering; TNT, Treating to New Targets.

*Mean or median LDL-C after treatment.

1Superko HR. Br J Cardiol. 2006;13:131-136; 2Cannon CP et al. N Engl J Med. 2004;350:1495-1504; 3Pedersen TR et al. JAMA. 2005;294:2437-2445; 4LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.


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1,

2,

3,

4,AS

5,


Care and lipid

CARE and LIPID

Slope = 0.018

P = 0.02

Placebo

N = 13,173

Pravastatin

CVD Event Rate*

Slope = 0.029

P < 0.001

< 98

99-126

127-158

159-207

> 207

TG Level, mg/dL

*CHD death, nonfatal MI, CABG, PTCA.

CARE, Cholesterol and Recurrent Events; LIPID, long-term Intervention with Pravastatin in Ischemic Disease.

Reprinted from Sacks FM et al. Circulation. 2000;102:1893-1900, with permission from Lippincott Williams & Wilkins (www.lww.com).


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PROVE IT-TIMI 22 study: LDL-C <70 mg/dL (1.8 mmol/L) , TG 200 mg/dL (2.3 mmol/L) 56% MIACS1

1 Miller M et al. J Am Coll Cardiol 2008;51:724-30.


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Groups

CHD Cases

N = 262,525

Duration of follow-up

5902

10 years

< 10 years

4256

Sex

Male

7728

Female

1994

Fasting status

Fasting

7484

Nonfasting

2674

Adjusted for HDL

Yes

4469

No

5689

1.72 (1.561.90)

1

2

1.5

CHD Risk Ratio* (95% CI)

*Individuals in top vs bottom third of usual log-TG values, adjusted for at least age, sex, smoking status, lipid concentrations, and blood pressure (most).

Reprinted from Sarwar N et al. Circulation. 2007;115:450-458, with permission from Lippincott Williams & Wilkins (www.lww.com).


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HDL-C

TNT study:LDL-C (<70 mg/dL or 1.8 mmol/L)1HDL-CCV HDL-C39%(HR: 0.61, 95% CI: 0.38-0.97)

1 Barter P et al. TNT sub-analysis. N Engl J Med 2007;357:1301-10.


Hdl c chd

HDL-CCHD

PROCAM LDL-CHDL-C1

<31

31-45

45-59

60

1.Assmann G ,et al.Eur Heart J.Suppl 2006;8(suppl F):F40-6


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LDL

Small, dense

LDL

TG

(60%)

2

HDL-C


Tg hdl c ldl c

TG/HDL-CLDL-C

  • TGHDL-C

  • TGHDL-C

  • NCEP ATPIII 2004HDL-C2

1Grundy SM. Circulation. 2002;106:2526-2529.

2Grundy SM et al. Circulation. 2004;110:227-239.


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1,

2,

3,

4,AS

5,


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1.Sanohu S, et al. J Am Soc Nephrol 2006;17:2006-16

2.Tonelli M, et al. Circulation.2005;112:171-8

3.Shepherd J, et al. Clin J Am Soc Nephrol 2007;2:1131-9

4.Colhoun HM, et al. Lancet .2004;364:685-96

5.Gaede P,et al.N Engl J Med. 2003;348:383-93

  • 1-3

  • 4,5


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1,

2,

3,

4,


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    • -6-31-6

    • 7

    • 50%28,9

    • 10

    • HDL-C/HDL-CTG11-14

    • 4284740-7568%15


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2004 ATP III NECP

TG/HDL

2005 2004

2005 IDF 2

LDL-C>2.3mmol/l(>200mg/dl)

2007 ESC/EASD 2

LDL-C>2mmol/L(177mg/dL),

2008 ADA 2

TG<150mg/dl(1.7mmol/l)HDL-C>40mg/dl(1.0mmol/l)>50mg/dl(1.3mmol/l)

2008 2007

2008NICE 2

TG>4.5mmol/l(400mg/dl)

2TG2.3-4.5mmol/l(200-400mg/dl)


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-

  • 2007- 2

  • LDL-C

  • :TG150199mg/dl; TG>200mg/dlTGTG>=5.65mmol/L(500mg/dl) TG

  • HDL: VAHITHDLCLDLC

2007

22007-

2

LDL-CLDL-CTG>1.5mmol/LHDL-C1.1mmol/L4.5mmol/L

2

2007


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PPAR-

1.Gross B, Staels B. Best Pract Res Clin Endoorinol Metab.2007;21:687-710

2.Duez H, et al. Arterioscler Thromb Vasc Biol. 2005;25:585-91

3.Ooi TC et al. Arterioscler Thromb Vasc Biol.1997;17:1793-9

4.Davidson MH, et al.Clin cardiol. 2006:29:268-73

5.Ducobu et al. J Cardiovasc Pharmacol.2003;41:60-7

6.Helly et al. Atherosclerosis.1995;115:S94

7.Grundy SM,Am J Cardiol.2005;95:462-8

    • TG30-50% 1,2

    • HDL-C5-15% 1,2

    • ApoCIII17-35% 3,4

    • LDL-C17-22% 5,6 () 31%7


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LDL

HDL

LDL

+++

+

+

+

++

+

+++

++

++

++

Farnier M. Am J Cardiovasc Drugs 2003;3:169-78


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20mg

20mg 160mg

+19

+10

(SAFARI )

(n=618)

-20

-26

-31

-43

S.M. Grundy et al., Am. J. Cardiol., 95: 462-468, 2005

+22

(n=120)

+9

-30

-50

-40

-46

Athyros et al. Diab. Care 25:1198-1202, 2002


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  • 221

    10 mg/dn=72

    200 mg/dn=68

    10mg/d+ 200mg/dn=81

    6

20052332


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LDL-C

TC

HDL-C

TG

10mg(n = 72)

200mg (n = 68)

200mg

10mg(n = 81)

  • P0.05

6%

*p < 0.001

-56

20052332


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70

60

50

40

30

20

10

0

OR 10.84 (95% CI 8.44 to 13.95)

59.6

p < 0.0000001

5.5

Alsheikh-Ali et al. Am J Cardiol 2004;94:935-8


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Davidson MH. Expert Opin Drug Saf 2006;5(1):145-56.


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-:

Pan et al. J Clin Pharmacol 2000;40:316-23.Backman et al. Clin Pharmacol Ther 2000;68:122-9.Kyrklund et al. Clin Pharmacol Ther 2001;69:340-5.Backman et al. Clin Pharmacol Ther 2002;72:685-91.Davidson et al. Am J Cardiol 2002;90 (suppl):50K-60K. Prueksaritanont et al. Drug Metab Dispos 2002;30:1280-7.Martin et al. Clin Ther 2003; 25: 459-71.


Action to control cardiovascular risk in diabetes accord

Action to Control CardiOvascular Risk in Diabetes (ACCORD)

    • (HbA1C, N = 10000)

      • : 8.0%

      • : 6.0%

    • LDL (N = 5800), ACCORD:

      • 20-40mg*

      • 20-40mg* 160mg

    • (N = 4200)

      • : SPB < 130 mmHg

      • : SPB < 120 mmHg

  • : CV(CV,MI,)

2008

?

* According to patients LDL-c level and CVD history.


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5

(4)

ACCORD Lipid

(%)

CK:

ULN:

ALT:

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.


Field

FIELD:

FIELD


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  • CK5


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  • Cr>2.0mg/dL)

  • >80


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TGHDL-C

ACCORD


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!


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