Trends of Cardiovascular Diseases in Recent Decades in Taiwan³造中.pdf · 高三酸甘油脂血症之臨床意義與治療 Chau-Chung Wu (吳造中), M.D., Ph.D. Department of

高三酸甘油脂血症之臨床意義與治療

Chau-Chung Wu (吳造中), M.D., Ph.D.

Department of Internal Medicine (Cardiology Section)National Taiwan University Hospital

Taipei, Taiwan

Lipoproteins in Human Plasma

Correlation with Lipoprotein Major Lipid Atherosclerosis

Chylomicron TG No

VLDL TG Minimal

IDL TG

C Direct

LDL C Direct

HDL C Inverse

Lp(a) C Unclear

“Remnants” TG

C Direct

Dense LDL C Direct

Selected Characteristics

Relative Size of Plasma

Lipoproteins According to Their Hydrated Density

Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed.,

Clinical event data Clinical

event data

Statin trialsStatin trials

The Evolution of Clinical Event Data

Non-Statin trialsNon-Statin trialsCholesterolhypothesisCholesterolhypothesis

EpidemiologyEpidemiology

Very high cholesterol with CHD or MI

Moderate high cholesterol in high risk CHD or MI

Normal cholesterol with CHD or MI

High cholesterol with NO CHD or MI

No history of CHD or MI, average TC and LDL-C, but below average HDL-C

4S

LIPID, PLAC I / II, KAPS, REGRESS

CARE

WOSCOPS

AFCAPS/TexCAPS

The Pyramid of Statin TrialsRelative Size of the Various Segments

of the PopulationMIRACL, Risk-HIAAcute Coronary Syndrome

Low to moderate cholesterol without CHD or MI

ASCOT-LLT, CARDS

HPS

Trial WOSCOPS AFCAPS/ TexCAPS

HPS ASPEN 4S LIPID CARE TNTTotal

TNTMet S

TNTDiabetes

N 6.595 6.505 20.536 2.410 4.444 9.014 4.159 10.001 5.584 1.501

LDL-C -26% -27% -29% -29% -36% -25% -28% -21% -24% -20%

82%72%

80%75%75%

62%73%73%

62%69%

Results from statin outcome trials show the existence of significant residual CV risk

Adapted from Libby P, J Am Coll Cardiol 2005;46:1225-1228

Res

idua

l Maj

or C

oron

ary

Eve

nts

(%)

Low HDL-C

High TG

Theatherogenic

triad

Atherogenic dyslipidemia - The atherogenic triad

Expert Panel on Detection, Evaluation,and Treatment of High Blood Cholesterol in Adults JAMA 2001;285:2486-2497

High LDL-C

High sd LDL-C

0

1

2

3

4

Copenhagen Male StudyRelative risk for ischemic heart disease (IHD) during8 years according to level of fasting TG

Rel

ativ

e R

isk

of IH

D

From: J. Jeppesen et. al. Circulation 97:1029-1036, 1998

1.01.5

2.2

TG Level (Thirds)

0.88(0.44-1.09)

78

1.33(1.10-1.59)

117

2.45(1.60-22.4)

217

(mmol/L)

(mg/dl)

P < .05

P < .001

Adjusted for:AgeLDL-CHDL-CAlcohol useTobaccoPhysical activityBMISBP/DBPHTNNIDDMGlycosuriaLow social class

Prospective Cardiovascular Münster Study (PROCAM)

CHD Risk According to Triglycerides and LDL/HDL Cholesterol Ratio

Inci

denc

e (p

er 1

,000

in 6

yea

rs)

Taken from Lipid Metabolism Disorders and Coronary Heart Disease, G. Assmann, Editor, MMV Medizin Verlag, Munich 1993

Triglycerides< 200 mg/dl

LDL Cholesterol / HDL Cholesterol

0

50

100

150

200

250*

116

24 31

245

* This bar represents 5% of the subjects in which 25% of the CHD events occurred.

Triglycerides

200 mg/dl

2.3 mmol/L)

5.0 > 5.0

Interrelation Between Atherosclerosis and Insulin Resistance

HypertensionHypertension

ObesityObesity

HyperinsulinemiaHyperinsulinemia

DiabetesDiabetes

HypertriglyceridemiaHypertriglyceridemia

Small, dense LDLSmall, dense LDL

Low HDLLow HDL

HypercoagulabilityHypercoagulability

Insulin Resistance

InsulinInsulin ResistanceResistance AtherosclerosisAtherosclerosis

Atherosclerosis

(hepatic(hepatic lipase)lipase)

Mechanisms Relating Insulin Resistance and Dyslipidemia

Fat CellsFat Cells LiverLiver

KidneyKidneyInsulinInsulin

IRIR XX

(CETP)(CETP)

CECE

TGTG

Apo BApo B

VLDLVLDL

(CETP)(CETP)

VLDLVLDL HDLHDL

(lipoprotein or hepatic lipase)(lipoprotein or hepatic lipase)

SDSD LDLLDLLDLLDL

TGTGApo AApo A--11

TGTGCECE

FFAFFA

Accumulation of chylomicron remnants

Accumulation of VLDL remnants

Generation of small, dense LDL-C

Association with low HDL-C

Increased coagulability

- plasminogen activator inhibitor (PAI-1)

- factor VIIc

- Activation of prothrombin to thrombin

Hypertriglyceridemia and CHD Risk: Associated Abnormalities

FirstFirst--line agentsline agents

HMG CoA HMG CoA reductasereductase inhibitorinhibitor

FibricFibric acid derivativeacid derivative

SecondSecond--line agentsline agents

Bile acid binding resinsBile acid binding resins

Nicotinic acidNicotinic acid

Pharmacologic Agents for Treatment of Dyslipidemia

American Diabetes Association. Diabetes Care 2000;23(suppl 1):S57-S60.

In diabetic patients, nicotinic acid should be restricted to

Action of Fibrate --- Activate PPARαto improve Lipid Profile1. Activate LPL gene, LPL↑ , TG↓

2. Apo AI/AII↑, Hepatic secretion of HDL↑

3. Inhibit Apo CIII, VLDL → large LDL↑

Fenofibrate

Increased degradation of triglyceride-rich lipoproteins

PPAR

Increase of LPL gene expression

Triglycerides

Increased production

of LPL

Fenofibrate increases LPL gene expression

Decrease TG-rich lipoproteins

Lowering TG Effect

-60%

-50%

-40%

-30%

-20%

-10%

0%

S20 vs Feno M P20 vs Feno M A10 vs Feno M

% c

hang

e

StatinFenofibrate

Type IIB patients1 Type IIB patients2 Type IIB patients3

N = 45 N = 152 N = 84

1) Steinmetz A et al,J Cardiovasc Pharmacol 1996;27:563-570 2) Ducobu J et al, J Cardiovasc Pharmacol, 2003; 41:60-67

3) Ooi TC et al, Arterioscler Thromb 1997; 17:1793-1799

P < 0.05P < 0.001 P < 0.0001

Fenofibrate to increase HDL

20

30

40

50

Qualitative effect of fenofibrate and atorvastatin on lipid profile

Exp Clin Endocrinol Diabetes 2004, 112:241-247

Small dense LDL

P=0.028*

P=0.028*P=0.173 P=0. 753

Fibrate mechanisms of actionFibrate

PPAR

Reverse

cholesterol transport

LDL particle size

HDL synthesis

Inflammation

Triglycerides

Established role of fibratesRaising HDL & lowering TG

1. Rubins HB et al. N Engl J Med 1999;341:410–82. Frick MH et al. N Engl J Med 1987; 317: 1237–453. Diabetes Atherosclerosis Intervention Study Investigators. Lancet 2001; 357: 905–104. The BIP Study Group. Circulation 2000; 102–21

VA-HIT1

-41% CHD Deathp = 0.02

BIP4

-29% MIp = 0.02

DAIS3

-23% CV EventsNS

HHS2

-78% CHDp = 0.002

HDL

TG

Sd-LDL

VA-HIT StudyLipid entrance criteria:Lipid entrance criteria:

HDL 40 mg/dl

LDL 140 mg/dl

TG 300 mg/dl

Endpoints:Endpoints:Primary endpoint: nonfatal MI or CHD deathnonfatal MI or CHD deathSecondary endpoint: death, stroke and other CV death, stroke and other CV

events / proceduresevents / proceduresRubins HB, et al. N Engl J Med 1999 Aug 5;341(6):410-8

VA-HIT Study% change in lipid at 1 year% change in lipid at 1 year

Gemfibrozil Group Placebo GroupPlacebo Group

TC TC 2.8 %2.8 % 2.1 %2.1 %

HDL HDL 7.5 % 7.5 % 1.8 %1.8 %

TG TG 24.5 %24.5 % 9.6 %9.6 %Rubins HB, et al. N Engl J Med 1999 Aug 5;341(6):410-8

VA-HIT - Mean On-treatment Lipid Levels

171

116

32.5

176170

115

34.5

122

0

20

40

60

80

100

120

140

160

180

200

TC LDL-C HDL-C TG

Mea

n Pl

asm

a Le

vel (

mg/

dL) Placebo

Gemfibrozil

*P< 0.001, difference betweentreatment and placebo groups

*

*

*

VA-HIT StudyPrimary Endpoints by Treatment GroupPrimary Endpoints by Treatment Group

PlaceboPlacebo Gemfibrozil RRR%RRR% 95%CI95%CI P valueP valuen=1267 n=1267 n=1264

CHD death/Nonfatal MI 274 (21.6%) 219 (17.3%) 22 7~35 0.005

CHD death CHD death 118 (9.3%) 93 (7.4%) 118 (9.3%) 93 (7.4%) 22 --2~41 0.0732~41 0.073

Nonfatal MI 183 (14.4%) 145 (11.6%) 183 (14.4%) 145 (11.6%) 22 3~37 3~37 0.024

Rubins HB, et al. N Engl J Med 1999 Aug 5;341(6):410-8

Downs et al: JAMA 1998;279:1615–1622

Risk Reduction in a Population With Low HDL-C:

AFCAPS/ TexCAPS—Study Design

6605 men and women without CHD

Cholesterol 4.7–6.8 mmol/L (182–263 mg/dL)

HDL-C

–32% –33%

–0

–10

–20

–30

–40

–50

Downs et al: JAMA 1998;279:1615–1622

Risk Reduction in a Population With Low HDL-C: AFCAPS/TexCAPS —

Results Summary

All risk reductions are P

Effect of Treatment on Lipids and Fibrinogen in BIP Study

(The BIP Study Group, Circulation. 2000;102:21.)

http://circ.ahajournals.org/content/vol102/issue1/images/large/hc2604227001.jpeg

Cumulative probability of the primary end point in BIP Study



Trial VA-HIT BIP AFCAPS/TexCAPS

Drug Gemfibrozil Bezafibrate LovastatinIndication 2nd prevention 2nd prevention 1st preventionDuration (years) 5.2 6.2 5.2Primary endpoint Non-fatal MI/CAD deathMI/sudden death 1st major coronaryPatient characteristicsAge (years) 64 60 58No. (men/women) 2531/0 2825/265 5608/99Diabetes (%) 25 10 3Hypertension 57 32 22Current smokers (%) 20 12 12Total cholesterol (mmol/1) 4.5 5.6 5.7Triglyceride (mmol/1) 1.8 1.6 1.8LDL cholesterol (mmol/1) 2.9 3.9 3.9HDL cholesterol (mmol/1) 0.8 0.9 0.9Outcome variablesTotal cholesterol -6 -4 - 18TriglyceHde (%) -31 - 21 - 15LDL cholesterol -4 -6 - 25HDL cholesterol +6 +18 +6RR red. in 1st endpoint (%) - 22 -9 - 37AR red. in 1st endpoint (%) -4.4 -1.4 -4.1NNT to prevent event 23 a 24

Comparison of recent clinical endpoint trials employing a fibrate in patients with low plasma HDL cholesterol levels

Comparison of Baseline Lipids in Secondary Prevention Trial

LDL-C (mg/dl) HDL-C (mg/dl)

190 4S 4745

170 4341

150 LIPID CARE 39LIPID 37

130 CARE BIP 3533

110 VA-HIT VA-HIT 31

4S

Rubins HB, et al. N Engl J Med 1999 Aug 5;341(6):410-8

AFCAPS/TexCAPS

Kaplan-Meier curves for the

primary end point in subgroups of

patients with baseline TG < 200 and > 200 mg/dL.



Helsinki Heart Study – baseline triglycerides and HDL-C

HDL-C

42 mg/dlHDL-C

42 mg/dl

CH

D in

cide

nce

per 1

000

pers

on –

year

s

Triglycerides (mg/dL)Manninen et al. Circulation 1992;85:37

20

16

12

8

4

0

200 > 200

200 > 200

GemfibrozilPlacebo

Minimum lumendiameter

0.00

-0.02

-0.04

-0.06

-0.08

-0.10

mm

-40%

Prog

ress

ion

of C

AD

Prog

ress

ion

of C

AD

Lancet 2001; 357: 905-910

% Change

Percent stenosis

4.00

2.00

0.00

-42%

Mean Segment Diameter

0.00

-0.02

-0.04

-0.06

-0.08

-0.10mm

-25%

p = 0.029p = 0.029 p = 0.020p = 0.020 p = 0.171p = 0.171

PlaceboFenofibrate

Fenofibrate treatment decreases theprogression of atherosclerosis in type 2

diabetic patients

Trial nMajor CVD event rate (%)

RRR (%) p-Valuecontrol drug

Primary prevention

HHS1Overall: 4,081 41.4 27.3 34

FIELD: Fenofibrate Intervention and Event Lowering in Diabetes

Randomized, double-blind, international studyPatients with Type 2 diabetesage: 50 – 75 yearshigh risk of CHD (n = 8500)primary and secondary prevention

Comparison of treatment with fenofibrate or placebo (average 5 years treatment)Principal study outcome: the effect of lipid modification, by micronized fenofibrate,

on CHD mortality among all randomized patients

9,795 Patients

Fenofibrate 200 mg/day, n = 4,895

Placebo, n = 4,900

Average Follow-up:

5 Yearsand 500

CHD Events

FIELD Study Investigators. Lancet 2005, e-publication November 14

Study Design5-year double blind, placebo controlled study against a background of usual care, including the option to add other lipid-modifying therapies

Results: compliance and statin use

Drop-outsHR = 1.01

95% CI = (0.93 –1.11)p=0.76

Drop-insHR = 0.47

95% CI = (0.44 – 0.51)P

-6.9% -5.8%

-21.9%

1.2%

-30

-25

-20

-15

-10

-5

0

5

10

TC LDL-C HDL-C TG

Per

cent

age

Cha

nge

From

Bas

elin

e at

clo

se o

ut(c

orre

cted

for p

lace

bo e

ffect

)

Lipid Effects of Fenofibrate at Study Close (full cohort)

Primary End Point : CHD Events (Non fatal MI + CHD Death)

Years from randomisation

Cum

ulat

ive

risk

(%)

0 1 2 3 4 5 6

0

2

4

6

8

10

Placebo 4900 4835 4741 4646 4547 2541 837Fenofibrate 4895 4837 4745 4664 4555 2553 850

PlaceboFenofibrate

HR = 0.8995% CI = (0.75 – 1.05)

p=0.16

Outcomes adjusted for statin useFenofibrate Treatment Effect

Relative Risk Reduction (95% CI)

P

CHD EventsUnadjusted 11% (-5 to 25) 0.16Adjusted for statin use* 19% (4 to 32) 0.01

Total CVD EventsUnadjusted 11% (1 to 20) 0.035Adjusted for statin use* 15% (5 to 24) 0.004* Non-randomised comparison adjusting for on-study statin use

Scott R et al Circulation 2007;116:II-838 Abstract 3691*HDL-c: 200 mg/dL

17.8

13.5

0.74(0.59-0.92)

P=0.01

Highest therapeutical benefit of fenofibrate in patients with elevated TG and low HDL cholesterol

(FIELD study)

PControl

Risk Reduction (%)0 5 10 15 20 25 30 35

Albuminuria

Retinopathy

Fenofibrate: Effective on Microvascular and Peripheral Vascular Disease

Effects independent of the degree of glycemic control (HbA1c),concomitant medications or reduction in blood pressure!

15%P =0.002

30%P

1,450 1,450

1,450 1,450

ACCORD: NIH/NHLBI Trial Action to Control CardiOvascular Risk in Diabetes

Simvastatin 20 mg

Intensive glycemic control

Standard glycemic control

Does a therapeutic strategy that targets HbA1c < 6% reduce the rate of CVD compared with a target of < 7.5%?

Does combination therapy with a fibrate plus a statin reduce CVD more than statin therapy alone?

http://www.clinicaltrials.gov/ct/gui/show

Simvastatin 20 mg + Fenofibrate 160 mg

140

150

160

170

180

190

200

0 1 2 3 4 5 6 7

mg/

dl

Years Post-Randomization

Mean Total Cholesterol

FenoPlacebo

N = 5483 5180 4988 4783 5250 3377 1668 491

60

70

80

90

100

110

120

0 1 2 3 4 5 6 7

mg/

dl


Mean LDL-C

FenoPlacebo

N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491

37

38

39

40

41

42

0 1 2 3 4 5 6 7

mg/

dl


Mean HDL-C

FenoPlacebo

N = 5483 5180 4988 4783 5250 3377 1668 491 N = 5483 5180 4988 4783 5250 3377 1668 491

110

120

130

140

150

160

170

0 1 2 3 4 5 6 7

mg/

dl


Median Triglycerides

FenoPlacebo

N = 5432 5180 4988 4783 5250 3377 1668 491

ACCORD Lipid Profile

ACCORD Study

Primary Outcome By Treatment Group and Baseline Subgroups

Trial(Drug)

Primary Endpoint: Entire Cohort (P-value)

Lipid Subgroup Criterion

Primary Endpoint: Subgroup

HHS (Gemfibrozil) -34% (0.02)

TG > 200 mg/dlLDL-C/HDL-C > 5.0 -71%

BIP (Bezafibrate) -7.3% (0.24)

TG > 200 mg/dl-39.5%

FIELD(Fenofibrate) -11% (0.16)

TG > 204 mg/dlHDL-C < 42 mg/dl -27%

ACCORD(Fenofibrate) -8% (0.32)

TG > 204 mg/dlHDL-C < 34 mg/dl -31%

Niacin (Nicotinic Acid)

83

The Nicotinic Acid Receptor GPR109A (PUMA-G or HM74A)

86

Combination Niacin Extended-Release/ Lovastatin vs Monotherapy with Atorvastatin or

SimvastatinPercent Change from Baseline

Week 8 Week 12Niacin ER/L 1000/40 mg A 10 mg

Niacin ER/L 1000/40 mg S 20 mg

LDL-C –39%* –38% –42%* –35%HDL-C +20%** +3% +19%** +8%Triglyceride –30%** –20% –36%** –15%Lipoprotein(a) –16%** +5% –20%** –1%

Bays H et al. Am J Cardiol 2003;91:667-672.

**P

ARBITER 6–HALTS TrialThe patients who had CAD or equivalent, who were receiving long-term statin therapy, and in whom an LDL- C

Mean Percent Changes in Cholesterol and Triglyceride Levels over the 14-month Study Period among the 208

Patients Who Completed the Study

Taylor, et al. N Engl J Med 2009;361.

Changes in the Mean Carotid Intima–Media Thickness over the 14-Month Study Period

Taylor, et al. N Engl J Med 2009;361.

Conventional WisdomTreatment Assumptions in CAD Mx:1. Patients with symptomatic CAD and

chronic angina who have significant coronary stenoses “need” revascularization

2. Revascularization is required to improve prognosis

3. PCI is less invasive than CABG surgery (i.e., is safer) and, therefore, should be selected.

Stable CAD: PCI vs Conservative Medical ManagementMeta-analysis of 11 randomized trials; N = 2,950

DeathCardiac death or MI

Nonfatal MICABG

PCI

Katritsis DG et al. Circulation. 2005;111:2906-12.

0 1 2

P

0.680.280.120.820.34

Risk ratio(95% Cl)

Favors PCI Favors Medical Management

PCI + Optimal Medical Therapy

will be Superior to

Optimal Medical Therapy Alone

Hypothesis of COURAGE Study

Survival Free of Death from Any Cause and Myocardial Infarction (COURAGE)

Number at RiskMedical Therapy 1138 1017 959 834 638 408 192 30PCI 1149 1013 952 833 637 417 200 35

Years0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

Optimal Medical Therapy (OMT)

Hazard ratio: 1.0595% CI (0.87-1.27)P = 0.62

7

Optimal Medical Therapy in COURAGEPharmacologic

Anti-platelet: aspirin; clopidogrel in accordance with established practice standardsLipid-lowering agents: simvastatin ±

ezetimibe or ER niacin ±

fenofibrateACE Inhibitor or ARB: lisinopril or losartanBeta-blocker: long-acting metoprololCalcium channel blocker: amlodipineNitrate: isosorbide 5-mononitrate

Applied to Both Arms by Protocol and Case-Managed

Published NEJM 11/15/2011 (online)Published NEJM 11/15/2011 (online)

AIMAIM--HIGH TrialHIGH TrialAAtherothrombosistherothrombosis IIntervention in ntervention in MMetabolic Syndrome with Low etabolic Syndrome with Low

HHDL/High Triglycerides and DL/High Triglycerides and IImpact onmpact on GGlobal lobal HHealth Outcomesealth Outcomes

Adjust simva to LDL 40 – 80

mg/dL

Adjust simva to LDL 40 – 80

mg/dL

Study DesignStudy Design

Months Relative to RandomizationMonths Relative to Randomization--22 --11 00 11 22 33 66 1212

Open-Label Run- In: Up-Titrate Niacin from 500mg to

2,000mg/day

4-8 weeks

Open-Label Run- In: Up-Titrate Niacin from 500mg to

2,000mg/day

4-8 weeksFollow to end

of study

Follow to end

of study

ER Niacin ER Niacin + 40+ 40--80 mg/day 80 mg/day simvastatinsimvastatin

PlaceboPlacebo + 40+ 40--80 mg/day 80 mg/day simvastatinsimvastatin

R

HDLHDL--C at Baseline & FollowC at Baseline & Follow--upup

*

Triglycerides at Baseline and FollowTriglycerides at Baseline and Follow--upup

LDLLDL--C at Baseline & FollowC at Baseline & Follow--upup

P < 0.001 *

Time (years)Time (years)

Cum

ulat

ive

% w

ith P

rimar

y O

utco

me

Cum

ulat

ive

% w

ith P

rimar

y O

utco

me

00

1010

2020

3030

4040

5050

00 11 22 33 44

MonotherapyMonotherapyCombination TherapyCombination Therapy

HR 1.02, 95% CI 0.87, 1,21HR 1.02, 95% CI 0.87, 1,21LogLog--rank P value= 0.79rank P value= 0.79

N at riskN at riskMonotherapyMonotherapy

Combination TherapyCombination Therapy

1696169617181718

1581158116061606

1381138113661366

910910903903

436436428428

Primary OutcomePrimary Outcome

16.2%

16.4%

Wei‐Hsian Yin, Chau‐Chung Wu, Jaw‐Wen Chen, on behalf of

the T‐SPARCLE Registry Investigators

Taiwanese Secondary Prevention for patients with AtheRosCLErotic

disease (T‐

SPARCLE) Registry (2009‐2011)

AIM of The Study

The study attempts to register and follow up a large population of patients receiving

secondary prevention therapy for the CVD to define the current status of lipid lowering therapy in

Taiwan the effects of lipid‐lowering therapy on CVD morbidity

and mortality during a follow up of 5 years.

Outcome study in relation to lipid control in Taiwan insufficient !!

Inclusion criteriaMale or female patients with stable symptomatic atherosclerotic

diseases aged > 18 years. The definition of coronary atherosclerosis: (1) the presence of

significant coronary artery occlusion of >50% in diameter by cardiac catheterization examination, (2) having history of myocardial

infarction (MI) as evidenced by ECG or hospitalization, or (3) angina patient showing ischemic ECG changes or positive response to stress test.

Cerebral vascular disease, defined as: cerebral infarction, intra‐ cerebral hemorrhage (excluding intra‐cerebral hemorrhage associated

with trauma or other diseases), and transient ischemic attack whose carotid artery ultrasound confirms atheromatous

change with more

than 70% blockage. Peripheral atherosclerosis with symptoms of ischemia and confirmed

by Doppler ultrasound or angiography.

T‐SPARCLE 參加研究中心分布圖

新北市

北榮(603)

振興(602)

台大(507)

馬偕(474)

北市醫 ‐

仁愛(110)

北市醫 –

和平(106) 林長(110)

中榮(300)中山(115)

成大(665)

市南(317)

高醫(300)

義大(221)

亞東(131)

14 Centers4,561 patients

3,486 eligible for

analysis

Patient characteristics and biochemistry

124

Factors Mean

Mean systolic BP (N=3,264) 133 mmHg

Mean diastolic BP (N=3,240) 76 mmHg

Mean pulse rate (N=2,607) 75 bpm

Mean waist (N=3,110) 94 cm

Mean hip (N=3,034) 101 cm

Mean WHR (N=3,038) 0.93

Mean height (N=3,329) 163 cm

Mean weight (N=3,357) 70 kg

Factors Mean

Total choleterol (N=3,486) 175 mg/dL

HDL cholesterol (N=3,486) 46 mg/dL

LDL cholesterol (N=3,486) 101 mg/dL

Triglycerides (N=3,486) 140 mg/dL

AC sugar (N=3,080) 118 m/dL

HbA1c (N=1,750) 7.3%

Creatinine (N=3,057) 1.13 mg/dL

GPT (N=2,695) 29 mg/dL

CPK (N=1,450) 132 mg/dL

Proportion of patients attaining their lipid goals

%

126

Treatment to the Target by Drugs (I)

127

Multivariate Analysis of Factors Associated with LDL Target Achievement

128

Multivariate Analysis of Factors Associated with TG Target Achievement

Management of High TGPrimary Management

Control underlying conditions (ex. Hypothyroidism, DM, Nephrotic syndrome, Chronic liver disease, Cushing’s syndrome, etc.)

Control body weightInstitute diet (increase the ratio of MUFA/SFA and complex CH2 O)Institute regular exerciseRestrict alcohol in selected patientsAvoid concurrent agents that increase TG (b-blocker, estrogen,

steroids, and diurectics)Drug Therapy

Fibrate: Helsinki, VA-HIT, BIP, DAIS, FIELD, UKLDS StatinNicotinic acidn-3 free fatty acid (fish oil)Combination therapyThe indications for the proper use of these drugs have not been

satisfactorily defined.

謝謝聆聽謝謝聆聽敬請賜教敬請賜教

chauchungwu@[email protected]

高三酸甘油脂血症之臨床意義與治療 Lipoproteins in Human PlasmaThe Evolution of Clinical Event Data投影片編號 7Benefits of lowering LDL投影片編號 9Atherogenic dyslipidemia �- The atherogenic triadCopenhagen Male StudyProspective Cardiovascular �Münster Study (PROCAM)Interrelation Between Atherosclerosis and Insulin ResistanceMechanisms Relating Insulin Resistance and DyslipidemiaHypertriglyceridemia and CHD Risk: Associated AbnormalitiesPharmacologic Agents for Treatment of DyslipidemiaAction of Fibrate --- Activate PPARαto improve Lipid ProfileFenofibrate increases LPL gene expressionLowering TG EffectFenofibrate to increase HDLQualitative effect of fenofibrate and �atorvastatin on lipid profileFibrate mechanisms of action投影片編號 48VA-HIT StudyVA-HIT Study投影片編號 51VA-HIT StudyRisk Reduction in a Population �With Low HDL-C: �AFCAPS/ TexCAPS—Study DesignRisk Reduction in a Population With �Low HDL-C: AFCAPS/ TexCAPS —�Results Summary投影片編號 55投影片編號 56投影片編號 57投影片編號 58投影片編號 59Helsinki Heart Study –�baseline triglycerides and HDL-C投影片編號 61投影片編號 62FIELD: Fenofibrate Intervention and Event Lowering in DiabetesStudy DesignResults: compliance and statin use投影片編號 66Primary End Point : CHD Events �(Non fatal MI + CHD Death) Outcomes adjusted for statin use投影片編號 71投影片編號 72Fenofibrate: Effective on Microvascular and Peripheral Vascular DiseaseACCORD: NIH/NHLBI Trial Action to Control CardiOvascular Risk in Diabetes投影片編號 77投影片編號 79投影片編號 80投影片編號 81投影片編號 82Niacin (Nicotinic Acid)The Nicotinic Acid Receptor GPR109A (PUMA-G or HM74A)投影片編號 87Combination Niacin Extended-Release/ Lovastatin vs Monotherapy with Atorvastatin or SimvastatinCombination Niacin Extended-Release/Lovastatin Compared with Statin AloneARBITER 6–HALTS TrialMean Percent Changes in Cholesterol and Triglyceride Levels over the 14-month Study Period among the 208 Patients Who Completed the StudyChanges in the Mean Carotid Intima–Media Thickness over the 14-Month Study PeriodConventional WisdomStable CAD: PCI vs Conservative�Medical Management投影片編號 97Survival Free of Death from Any Cause and Myocardial Infarction (COURAGE)投影片編號 101Published NEJM 11/15/2011 (online)AIM-HIGH TrialStudy DesignHDL-C at Baseline & Follow-upTriglycerides at Baseline and Follow-upLDL-C at Baseline & Follow-up投影片編號 114投影片編號 120AIM of The StudyInclusion criteriaT-SPARCLE 參加研究中心分布圖Patient characteristics and biochemistryProportion of patients �attaining their lipid goals投影片編號 126投影片編號 127投影片編號 128Management of High TG投影片編號 130

Documents

Trends of Cardiovascular Diseases in Recent Decades in Taiwan³造中.pdf · 高三酸甘油脂血症之臨床 意義與治療 Chau-Chung Wu (吳造中), M.D., Ph.D. Department of

Trends of Cardiovascular Diseases in Recent Decades in Taiwan³造中.pdf · 高三酸甘油脂血症之臨床意義與治療 Chau-Chung Wu (吳造中), M.D., Ph.D. Department of