??????

1
????????????????

• ????????

2
????

• ?. ??
• ??
• ?????????
• ??????

3
???????????
??????????????
4
???????????
5
???????????
6
???????????????

• ??
• TIA
• ????
• ???
• ???
• ??
• ?????

??????
????? ????? ????? ?????
??????? ??????? ???????? ????
Pepine CJ. Am J Cardiol. 19988223S-27S.
7
???????????????????
???????,??????? ???????,???????
???? ??
23? (????????)1 34? (?? TIA)1
57? (????)3 ????9?2
4? (??????MI???CHD?? )4 ????23? (?? TIA)2
?????
????
??????
??????????1??????,??????(CHD)
??????MI???CHD?? ???????MI
1. Kannel WB. J Cardiovasc Risk 1994 1 333339.
2. Wilterdink JI, Easton JD. Arch Neurol 1992
49 857863. 3. Adult Treatment Panel II.
Circulation 1994 8913331363. 4. Criqui MH et
al. N Engl J Med 1992 326 381386.
8
???????????????????????
?????IVUS?????? ???????? ????????????? ?(A.
???????)IVUS ? (B)?(C)???2??????
Rioufol et al, Circulation 2002 106 804-808.
9
???????

• ?????????????????,???????????
• ??????????????,??????????,????????????
• ?????????,??????????,????????????

10
???????????

• ???????????
• ????????????????????????????????,???????????
  ???????
• ??????LDL-C?
• ????????????????
• ?????????,??????????????????

11
??????????? Therapeutic Life-style Change, TLC
???????????????????????????????????,??????????
????? ??????????????????????,TLC??????????????
????????
12
TLC?????

• ??????????????
• ????LDL-C???
• ???????????
• ????
• ??????????
• ?????????????????
• ????????????

13
??????
???? ???? LDL-C???????
????
???? lt7???? 8-10
????? lt200mg/d 3-5
?? ??4.5kg 5-8
????
????? 5-10 g/d 3-5
???? 2 g/d 6-15
?????? 20-30
14
??????????

• ??
• ?????????LDL-C???
• ????
• ????????
• ????????

15
?????????? ????
???(g/?) ????
??????? ?? 75 g
??,?,?? ??,????
????,??
??,??,?? ?? 3-4?/?
??,??,?? ?? ?? 250 g
??,?? ????,??? ???
20 g ???,???,
????,??
?? ????, ???,??
??,??? ????
????
??,??,???

????,??? ?? 10 g
??,??
16
??????????(?) ????
??? ????
??????? ???? 400-500 g
???,????? ???? 50 g ????
????,???? ??
lt 6 g
????????? ?? ?500 g
???? ?400 g ????
??30 g ??????
???????,? ?? ???150 g ????
???,???,?
????? 45
g ???????????,?????
17
(No Transcript)
18
??????????

• ???,?????(??)??lt0.5?/??
• ?????????????
• ???????????????
• ????,????
• ???????,????
• ??????
• ?????,3/4??????????,?????????
• ????????????1-2?/??
• ????????5??
• ???1???6-8??

19
?????????

• ???????100???????????????????????????????????????
  ??????????????????
• ???????200???????????????????????????????????????
  ??????????????????????
• ????????????????????????????????????

20
????

• BMI??(??)/??(?)2
• ?? BMI ? 24
• ?? BMI ? 28
• ??
• ?? lt 2.6 ?
• ?? lt 2.4 ?

21
??????????????
????
22
???????

• ??3-5?
• ????30??
• ?????????? 170 ???
• ??????????? ??1??

????????????, ?????????????????????????
23
???????

• ??????????(????,????,???)
• ???????
• ???????
• ?????????
• ??????,????
• ?????????
• ???

24
?. ?????????

• ???????????????
• (1)??????????????
• ???????
• (2)??????????????
• ???????
• (3)??????
• ?????????????????
• (4)??????
• ?-3???

25
???????????????
TC TG LDL-C HDL-C
??? -30-40 -7-30 -18-55 5-15
??? -6-12 -20-50 -5-20 10-20
??? -5-20 -20-50 -5-25 15-35
????? -15-20 -15-30 3-5
???????? -13 -8 -20 1
???? -20-25 - -5-15 -25
?-3??? - 25-50 - 5
26
(?) ???(statins)

• ??3-??3-???????A(HMG-CoA)??????,??????????,??????L
  DL??,????LDL???,??????VLDL????

27
???????? ?????
?2/3
?1/3
28
??????

• ???????LDL-C?TC?apoB,???TG???????HDL-C
• ????????????????,?????????????????
• ???????????,???????????????????????????????

29
????????????

• ?????????
• ????
• ??????????
• ????????????PAI-1

• ?????????
• ??????????,?????,??????
• ?????????????
• ???????

• ??????
• ??????????
• ??????

??????
30
??????

• ???????LDL-C?????,?CHD???????????,????????????????
  ?(???????)?????
• ???????CHD???????,????,??????
• ??????CHD???????????,??CHD????????????CHD??,?LDL-C
  ??lt2.6mmol/L?lt1.8-2 mmol/L,???????????

31
?????????????????????
Cardiac death or nonfatal MI CHD, coronary heart
disease 4S, Scandinavian Simvastatin Survival
Study AFCAPS/TexCAPS, Air Force/Texas Coronary
Atherosclerosis Prevention Study ALERT,
Assessment of Lescol in Renal Transplantation
ASCOT, Anglo-Scandinavian Cardiac Outcomes Trial
CARE, Cholesterol and Recurrent Events HPS,
Heart Protection Study LIPID, Long-Term
Intervention With Pravastatin in Ischaemic
Disease LIPS, Lescol Intervention Prevention
Study PROSPER, Prospective Study of Pravastatin
in the Elderly at Risk WOSCOPS, West of Scotland
Coronary Prevention Study.
32
??????????

• ????(Lovastatin)
• ????(Simvastatin)
• ????(Pravastatin)
• ????(Fluvastatin)
• ?????(Atorvastatin)
• ?????(Rosuvastatin)

33
???????

• TC??30-40
• LDL-C??18-55
• HDL-C??5-15
• TG??7-30
• ??????????????,?????,TC???5,LDL-C??7

34
???????

• ???????????????????,??????????
• ?????0.6g,2?/d???TC??23,LDL-C??28.5,TG??36.5,HD
  L-C??19.6?

35
???LDL-C????
5mg 10mg 20mg 40mg 80mg
????? 38 43 48 53 58
????? 31 37 43 49 55
???? 23 27 32 37 42
???? 10 15 21 27 33
???? - 21 29 37 45
???? 15 20 24 29 33
164?????????
Law MR, et al. BMJ. 20033261-7
36
?????????????????????????
????? ??????????? ????? ??????????? ????? ??????????? ????? ??????????? ????? ??????????? ????? ??????????? ????? ???????????
????? ???? ???? ???? ???? TC LDL-C HDL-C TG
10 20 40 80 10 20 40 80 20 40 80 20 40 40 80 -22 -27 48 -1015 -27 -34 48 -1020 -32 -41 48 -1525 -37 -48 48 -2030 -42 -55 48 -2535
37
??????LDL-C??30-40????(????)
?? ??(mg/d) LDL-C??()
????? 5-10 39-45
????? 10 39
???? 20-40 35-41
???? 40 31
???? 40 34
???? 40-80 25-35
38
??????????????

• ?????,?????,?????????????????????????????????
• ?????ALT?AST???0.5-2.0,?????????????????????????
  ??????????????????????,??????????????????????????
  ???

39
??????????????

• ????????,??????????????????????????,??????(CK)????
  ??????,??CK???????????????,?CK???????????10?(10UL
  N)?????,???????????,??????????????????????????,???
  5??,?????????

40
??????????????

• ??????????????(?)??????????????????????????P-450?
  ??????(?11)???,???????????????????????????????,???
  ????????????????

41
??????????????

• ??????????????????
• ??(??gt80?)??(????)
• ????
• ?????(????????,????????)
• ???????
• ????
• ???????(gt??1??)?
• ???

42
??????????????

• ????????,??????ALT?AST?CK????????(lt??????23?),???
  ???????????????CK?????,????????????????

43
??????????????

• ???????,????????????????,?????CK?????????????????
  ?, CK??10ULN,????????? CK?????????,?????,????CK?
  ??????CK??????,???????????????

44
??????????P450???????????
CYP3A4 CYP3A4 CYP3A4 CYP2C9 CYP2C9
?? ??? ??? ??? ?? ??? ???
????? ???? ???? ??? ???? ???? ??? ???? ???? ???? ???? ??? ??? ???? ??? ??? ???? ???? ?????? ???? ???? ????? ??? ??? ????A ???? ???? ???? ??? ???? ??????? ??? ???? ?????? ???? ????? ??? ???? ??? ???? ??? ??? ?????
45
ACC/AHA/NHLBI???????????????????

• ???????????????
• ??(??80?????),?????
• ????
• ?????(??????????????DM??)
• ????????
• ????????????
• ?????????????(???????)??????????????????????????(
  ?????????)??????????
• ????????

46
(?)???

• ?????????,?????????????????a(PPARa),???????(LPL)?a
  poAI?apoAII?????,????apoCIII?????,??LPL?????,?????
  ????TG????,????TG???HDL-C??,??????????,??LDL??????
  ??????????

47
???????

• ????
• ??0.1g,3?/d?????0.2g, 1?/d
• ????0.2g, 3?/d
• ????0.6g,2?/d

48
??????????

• ????????????TC??615,LDL-C??520,??????20-50
  ,HDL-C??10-20?
• ????????????TG??????????????HDL-C??

49
(No Transcript)
50
(No Transcript)
51
????????????

• ?????????,????????????????????????????????????????
  ?????????,???????,?????????????????

52
?????????????TG?

• ??????TG lt 1.7mmol/L(150mg/dl),HDL-C
  1.04mmol/L(40mg/dl)
• ???TG???? (2.26 5.63mmol/L) (200500
  mg/dl),LDL-C???????????HDL-C???????(?HDL-C TC
  HDL-C),?????LDL-C??? 0.78mmol/L (30 mg/dl)
• ???TG?? 5.65mmol/(500mg/dl ),???????????,????
  ???TG??

53
(?)??

• ???B????, ????????????????, ???????????????????,
  ???????????????????VLDL????????????apoAI?apoAII???
  ?

54
?????????

• TC??5-20,LDL-C??5-25,TG??20-50,HDL-C??15-35
  ?
• ????????????HDL-C????TG?????????????

55
????????

• ????????????????????????,??????,??????????????????
  ??,????????????????????????????????????12 g,
  1?/d????????,?????0.3750.5g, ???? 4?????1g/d,
  ????????2g/d?

56
?????????

• ?????????????????(???)????????
• ???????????????
• ???????????????????
• ???????????,???

57
(?)?????

• ????????????,??????????????, ???????????,
  ???????????, ?????????????????????????????LDL??,??
  LDL????????LDL,?????LDL-C?????

58
?????

• ?????????????(??4-16g,?????),????(??5-20g,?????)??
  ??????TC??15-20, LDL-C??15-30HDL-C??3-5?TG
  ?????????????????????????????????????

59
?????

• ????????????????,??,???????????????????????ß?????
  TGgt4.52mmol/L(400mg/dl)??????TGgt2.26mmol(200mg/dl
  )?

60
(?)????????

• ????????????(ezetimibe),????????,???????????-?????
  ,???????????,??????????????????????????????,????LD
  L?????,???LDL????

61
????????(????) ?????????
VLDL
LDL
IDL
LDL-R
Synthesis
??
????
INTESTINE
????????????
??
?????
62
????(???) ???????
?????????? ????????

• ??????????????????????(NPC1L1)
• ???????????????? 54
• ??
• ????????????
• ?????????,????????????
• ??????TG??????????

????? Harry R. Davis, PhD.
???
???
???
?????
???????????,?????????
63
????????

• ?????10mg/d,?LDL-C???18,???????LDL-C, HDL-C?TG
  ????????,?????????????????????,??????????

64
????????????
LDL-C
HDL-C
TG
2.7
1.0
8???????()
2.9
3.7
plt0.001plt0.05plt0.01
14.0
?? ??? (n390) ?? ???? 10 mg (n379)
25.1
Gagné C et al. Am J Cardiol 2002901084-1091.
65
????????

• ??????????????,????(CK)???????3ULN???????????????
  ???????????????55,?????????,?????????????2????4??
  ?????????????????

66
(?)?????

• ????
• ?????????????,???????,????????????TC??20-25,
  LDL-C??5-15, ?HDL-C?????(??25)????????????,????
  ??????,??????????

67
?????

• ????
• ????????????
• ????????????????????????????
• ????????????????? ??????????, ????????
  ??????????QT ????,??????????QT?????????????0.5g,
  2?/d?

68
?-3???

• ?????????(EPA,C205n-3)????????(DHA,C226n-3),????
  ???????,????????-3??????? TG ?????HDL-C,
  ?TC?LDL-C???123-125?????2-4g/d?,??TG??25-30?
• ??????????????????????????????,??????????????????

69
?-3????????????????

• ?????-?VLDL-C??,??TG(20-50),?HDL-C
• ?????- ???????ICD??????MI???
• ???????-????????????
• ??????????-??????????
• ????-???????????? (2.6/1.2)
• ????-??,??1.6bpm

70
?-3???

• ???????,??23??????????????????????????????????
  CK????,????????????,??????3??, ???????????????????
  ????????????????
• ?-3?????(?????)??EPADHA?????85,?????????????????
  , 0.51g, 3?/d?

71
?????????
72
???????6??
LDL-C???
5-6
5-6
5-6
3????
???????
1st
2nd
3rd
????
?????????1? LDL-C??????5-6
Bays H et al. Expert Opin Pharmacother
20034779-90.
73
1. ????????????

• ???????????????????????,?????????????????10mg/d???
  ??10mg/d ??????????????,???LDL-C????80mg/d
  ????????????,???????????19???72?
• ????????,????????????????????????,????????,???????
  ?????,???????????????

74
2. ???????????

• ????????????,????TC?LDL-C?TG???????,HDL-C?????????
  ??????????????,???????????????????????????????????
  ?????????????,???????????????,???????????
• ???????????,?????,???????????????????????????,????
  ??,????????????????????????????????????????????

75
2. ???????????

• ????????????????????????HIV???????????????????????
  ???????,??????????????????????
• ?????,??????????????????????,??????????????????,??
  ?????????

76
??????????????

• ?????????????,??
• ???????????????
• ??non-HDL-C ??,????????
• ????????????????
• ?????,?????
• ???????????
• ??????,?CKgt????5????
• ??????????3????

77
3. ???????????

• ????,?????????HDL-C,????????????HATS????,?????????
  ,???????????,????MI,??????????????????????????????
  ?,??????????

78
3. ???????????

• ???????????????,??6??????????????????????????????
  ??????????????????????,????????CK????????????????
  ???,?????????,???????????

79
4. ?????????????

• ??????????LDL-C??,???????????????,??CHD?????,?????
  ??????,????????????????????,??????????????????????
  ?

80
5. ?????-3???????

• ???????????????????(20 mg/d)?????-3?????????TG?TC?
  apoE????????????????????????-3???????,???????????
  ???????????????????

81
???????

• 1?????
• ???????48?????,???????,?????612???????????3-6??
  ???????????,???????????????,??48????????????612?
  ?????,????????????????

82
???????

• 2??????
• ?????????????????
• ???????(AST/ALT)???????(ULN)?3?,?????????????????,
  ???????
• ?????,??????????????????????????,?CK????5
  ULN????
• ???????????????????,???????????????????,??????

83
??????????????????????/?????????
?????????????
???????????gt18mg/dL?
???
N1632
60
49
LDL lt70mg/dl
N756
62
60
LDL lt100mg/dl
N637
47
61
(??2004?ATP??????)
64
N112
LDL lt130mg/dl
22
N127
LDL lt160mg/dl
9
36
84
? ?

• ???????????????????
• ????????????,????????????
• ????????????????,??????????
• ???????????????
• ?????????????
• LDL-C??????????(????),HDL-C??HDL-C?
• ???????(????????)
• ???????????????, ???????