dislipidemia dan risiko stroke nov 2011.pdf

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DISLIPIDEMIA DAN RISIKO DISLIPIDEMIA DAN RISIKO STROKESTROKESTROKESTROKE

Oleh:Oleh:Dr Sugianto, SpS, Mkes, PhDDr Sugianto, SpS, Mkes, PhD

Abnormal dari serum lipids (trygliserid, cholesterol, Low Density Lipoprotein / LDL , dan high density lipoprotein/ HDL) secara jelas sebagai faktor risikolipoprotein/ HDL) secara jelas sebagai faktor risiko atherosclerotic, terutama penyakit coronair.

Study dengan memakai ultrasound teknologi t k t t l h l t l t LDL h l t lmenetapkan total cholesterol atau LDL cholesterol

secara langsung dan HDL cholesterol berhubungan dengan extracranial carotid atherosclerosis dan penebalan plaque pada intima-media. p p q p

Tiga prospective studies pada pria menunjukkan peningkatan ischemic stroke dengan total cholesterol diatas 240 270 mg/dldiatas 240-270 mg/dl.

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Asia Pacific Cohort studies, 352.033 individu didapatkan 25% kenaikan pada ischemic stroke untuk setiap kenaikan 1 mmol/L (38 7 mg/dl) pada total

DislipidemiaDislipidemiasetiap kenaikan 1-mmol/L (38.7 mg/dl) pada total cholesterol.(Zang, 2003).

Project Eurostroke (22.183 subjects, 34% wanita) ditemukan kenaikan risiko 6% infarcht cerebri setiap kenaikan 1-mmol/L kenaikan total cholesterol. (Bots, 2002).

Project pada wanita Amerika ( 24.343 wanita dengan risiko ) di dapatkan kenaikan 25% ischemic stroke fatal pada setiap kenaikan 1-mmol/L total cholesterol (Horenstein, 2002)

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Lebih dari 28 juta orang Amerika memiliki beberapa Lebih dari 28 juta orang Amerika memiliki beberapa bentuk penyakit kardiovaskuler (Minin, 2006). Hasil medis dengan penurunan produktivitas dan g p pbiaya sekitar $ 431.800.000.000 di Amerika Serikat pada tahun 2007 (Mackay,2004). Menurunkan lowdensity lipoprotein (LDL) kadar kolesterol mengurangi tingkat penyakit jantung koroner (PJK) dan stroke iskemik (Baigent C, 2005)

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Dyslipidemia is a broad term that refers to a Dyslipidemia is a broad term that refers to a number of lipid disorders.Most (80%) lipid disorders are related to diet and Most (80%) lipid disorders are related to diet and lifestyle, although familial disorders (20%) are important as wellp

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The basic categories of dyslipidemias include: elevated low-density lipoprotein cholesterol (LDL-C), y p p ( ),low high-density lipoprotein cholesterol (HDL-C),excess lipoprotein(a), hypertriglyceridemia, atherogenic dyslipidemia, and mixed lipid disorders.(Eaton CB, 2005)

HDL-C dan Stroke7

Studi kohort berbasis populasi selama 10-tahun menunjukkan bahwa laki-laki Jepang dan perempuan dengan tingkat HDL-C rendah (30 mg / d [0 8 l / ]) f k d d k ddL [0,78 mmol / L]), signifikan didapatkan pada stroke, khususnya stroke iskemik. (Yoshiyuki. 2003)

HDL-C dan Stroke8

In the Northern Manhattan Stroke Study (NOMASS) In the Northern Manhattan Stroke Study (NOMASS) that involved a multiethnic community, higher HDL-cholesterol levels were also associated with reduced risk of ischemic stroke (Sacco RL, 2001)Five prospective cohort studies included in a p psystematic review found a decreased risk of stroke ranging from 11% to 15% for each 10 mg/dLincrease in HDL cholesterol

Trigliseride g9

The Copenhagen City Heart Study, a prospective, populationbased cohort study composed of p p y papproximately 14 000 persons, found that elevated nonfasting triglyceride levels increased the risk of ischemic stroke in both men and women.

Why is low HDL-C important to MACROvascular residual risk?MACROvascular residual risk?

HDL has a number of anti-atherogenic effectsHDL has a number of anti atherogenic effectsRole in reverse cholesterol transportAntioxidant effectsInhibition of adhesion molecule expression Inhibition of platelet activationProstacyclin stabilizationPromotion of NO production

f flPrevention of inflammation

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Challenges in secondary stroke prevention: prevalence ofmultiple metabolic risk factors, including abnormal glycaemia,in ischaemic stroke and transient ischaemic attack

D. P. Scott, J. R. Greenfield, V. Bramah, J. Alford, C. Bennett, R. Markus and L. V. Campbell

Secondary prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA) mandates identification and treatment of multiple metabolic risk factors.(TIA) mandates identification and treatment of multiple metabolic risk factors. The aim was to determine the prevalence of abnormal glycaemia, hypertension and dyslipidaemia in patients presenting to an Acute Stroke Unit of a tertiary referral teaching hospital with IS or TIA.

Internal Medicine Journal 40 (2010) 275–280

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Almost half the patients admitted with IS/TIA to our institution p /over a 17-month period were hyperglycaemic. This finding is important for three reasons. First, glucose level on admission has been shown to predict the extent of cerebral infarction, as well as post-stroke recovery and function. ( Parsons MW, 2002 )and function. ( Parsons MW, 2002 )Second, it demonstrates that a significant proportion of patients admitted with stroke may have, or be at risk of developing, diabetes, which has been shown to increase the risk of recurrent stroke by 35% in patients with establishedcerebrovascular disease. (Berthet K, 2004)( , )

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Third, as hyperglycaemia coexisted with both hypertension and dyslipidaemia with one-third of yp y ppatients admitted with stroke, this group is at further increased risk of recurrent stroke and othermacrovascular disease and requires intensive and aggressive risk factor modification.

Multiple metabolic risk factors

Prevalence of diabetes/impaired fasting glucose (IFG)/post-stroke dysglycaemiaDiabetes 2%glucose (IFG)/post-stroke dysglycaemia,hypertension and dyslipidaemia in theirvarious combinations in the study cohort.

n = 224

13%2%

30%

n 224

33%

30%

4% 12%33%

14Hypertension Dyslipidaemia

Current standards of care fail to adequately address this changing risk factor profilethis changing risk factor profile

Despite efficacy of current standards of care, including achievement of low density Despite efficacy of current standards of care, including achievement of low density lipoprotein cholesterol (LDL-C) goals, patients remain exposed to a high risk of:

MACROvascular events 1,2

• Myocardial infarction• Stroke

MICROvascular complications of diabetes 3

• RetinopathyRetinopathy• Nephropathy• Neuropathy

1 Baigent C et al Lancet 2005;366:1267 78

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1.Baigent C et al. Lancet 2005;366:1267-78

2.Cholesterol Treatment Trialist” (CTT) Collaborators, Kearney PM et al. Lancet 2008;371:117-25

3.Gaede P et al. Engl J Med 2003;348:383-393

Ischemic• Transient ischemic attack• Ischemic stroke

Ischemic sudden death

• Angina pectoris (stable, unstable)• Myocardial infarction

• Claudication

• Critical limb ischemia rest pain gangrene• Critical limb ischemia, rest pain, gangrene, amputation

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Risk Factors

Smoking

Fatty StreakFatty Streak

Smoking

Hypertension

Hyperlipidemia

Others(diabetes, coagulation abnormalities,homocysteinemia, etc.)y )

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Aterosklerosis adalah dianggap sebagai respon Aterosklerosis adalah dianggap sebagai respon terhadap inflamasi selular dan molekuler,inisiasi awal yang telah terjadidalam dekade kedua kehidupan. Tahap pertama dalam proses atherogenesis adalah disfungsi endotel. Ini terjadi, di zona bifurkasi arteri dan zona aliran turbulen mana penurunan produksi oksida nitrit oksid

t j di d d t l yang terjadi pada endotel

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Sebagian besar penelitian epidemiologi tidak menemukan g p p ghubungan yang konsisten antara tingkat kolesterol dan risiko stroke secara keseluruhanB b li i l h k h b i if Beberapa penelitian, telah menemukan hubungan positif antara total dan low-density lipoprotein (LDL) kolesterol dan resiko stroke iskemik [Larry, 2006]Peningkatan high density lipoprotein (HDL) kadar kolesterol berkaitan dengan penurunan risiko stroke iskemik pada pria d it d t d di t k l kdan wanita, pada orang tua, dan di antara kelompok-kelompok ras dan etnis yang berbeda [Sacco, 2001].

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Dalam sebuah tinjauan terbaru dan meta-analisis dari 42 jpercobaan acak mengevaluasi terapi statin untuk pencegahan stroke (N = 121.285), resiko relatif dikumpulkan terapi statin untuk semua stroke adalah 0 84 (95% CI 0 79 0 91) [Regan untuk semua stroke adalah 0,84 (95% CI, 0,79-0,91) [Regan, 2008] .Sebelas percobaan melaporkan kejadian stroke hemoragik (total 54.334 = N; risiko relatif 0,94; 95% CI, 0,68-1,30) dan 21 uji coba melaporkan pada stroke fatal (total 82.278 = N; risiko relatif 0 99 95% CI 0 80 1 21) risiko relatif, 0,99, 95% CI, 0,80-1,21) .

National Cholesterol Educational Program and the Adult Treatment Panel (NCEP-ATP III)Adult Treatment Panel (NCEP-ATP III)

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Normal <150 mg/dl (1.7 mmol/l)Borderline high 150–199 mg/dl (1.7–2.2 mmol/l)High 200–499 mg/dl (2.2–5.6 mmol/l)Very high ≥500 mg/dl (≥5.6 mmol/l)

Mechanisms by which hypertriglyceridemia may contribute ISmay contribute IS

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Promotion of atherosclerosisPromotion of atherosclerosisEndothelial dysfunctionOxidative stress due to lipid-derived free radicalspImpairment of endothelial-dependent vasodilatationAssociation with elevation of the markers of atherosclerosis(C-reactive protein, fibrinogen levels and circulating adhesion Molecules)

Mechanisms by which hypertriglyceridemia may contribute ISmay contribute IS

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Promotion of thrombogenicityPromotion of thrombogenicityElevated plasma viscosityElevated plasma fibrinogen levelsLowered fibrinolytic activityElevated levels of clotting factor Xc compared to normolipidemic controlsElevated fibrinogen levels

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Hipertrigliseridemia postprandial pada penderita Hipertrigliseridemia postprandial pada penderita diabetes ditemukan disfungsi endotel, stres oksidatif akibat radikal bebas, dan kerusakan ,pada endotelium (Anderson 2001)Mekanisme lain yang potensial dengan y g p ghypertriglyceridemia berkontribusi untuk aterosklerosis adalah melalui kerjasama dengan peningkatan protein C-reaktif (CRP).

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Hipertrigliseridemia juga dapat menyebabkan Hipertrigliseridemia juga dapat menyebabkan penyakit serebrovaskular melalui dampaknya pada trombosis. Efek ini dihasilkan oleh perubahan thrombogenic sistem koagulasi serta peningkatan viskositas plasmaHyperviscosity dapat mengakibatkan iskemia jaringan akibat gangguan microcirculatory, kerusakan

d d t li d k d i k t pada endotelium , dan kecenderungan meningkat menjadi trombosis (Rosenson, 2001)

CHOLESTEROL

??

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Stroke is one of the most costly diseases in the ycommunity both from a humanitarian and economic point of viewT k h d dTo prevent recurrent stroke events, the standardstrategy today aims at reducing the risk factors involved in atherosclerosis, heart disease and metabolic ,disorders.The risk for a recurrent stroke has been reported to be b t 4% i th fi t th d b t 12% i th fi t about 4% in the first month and about 12% in the first

year after stroke onset with the first period after the event being the most vulnerable

Summary of Recommendations (AHA Guidelines) for primary stroke preventionfor primary stroke prevention

Non Modifiable :Non Modifiable :Age Sex Race

L Bi h i h G i f E h i iLow Birth weight Genetic factors Ethnicity

Well documented & modifiable RFLess well documented or potentially modifiable RF

Goldstein LB .A Primer on Stroke Prevention Treatment Willey Blackwell 2009

Summary of Recommendations (AHA Guidelines) for primary stroke preventionfor primary stroke prevention

WWell documentedell documented and Mand Modifiable RFodifiable RFWWell documented ell documented and Mand Modifiable RFodifiable RF

Hypertension ( I, A) Asymptomatic Carotid Stenosisyp ( , ) y p

Cigarette Smoking ( I, B) Oral contraceptive use (III,B/C)

Diabetes ( I, A) Diet and Nutrition

D li id i ( I A )D li id i ( I A ) Ph i l I ti itDyslipidemia ( I , A )Dyslipidemia ( I , A ) Physical Inactivity

Atrial Fibrillation Obesity and Body Fat Distribution

Other Cardiac Conditions

Sickle Cell Disease


Summary of Recommendations (AHA Guidelines) Summary of Recommendations (AHA Guidelines) for primary stroke preventionfor primary stroke preventionfor primary stroke preventionfor primary stroke prevention

Less well documented or potentially modifiableLess well documented or potentially modifiable RF& modifiable RF

Metabolic syndrome Alcohol abuse (IIb, B)y ( , )

Drug abuse (IIb,C) Oral contraceptive use (III,B/C)

Sleep disordered breathing (IIb,C) Migraine

H h t i i (IIb C) El t d L ( ) (IIb C)Hyperhomocysteinemia (IIb,C) Elevated Lp(a) (IIb,C)

Elevated lipoprotein phospholipaseA2

Hypercoagulability

Inflammation (IIa,B) Infection

Aspirin for primary stroke prev(III,a)


Proposed structure for consideration for modifiable stroke risk factorrisk factor

1. First –tier factors• The “Big three” factors

a. Hypertensionb. Diabetesc. Cigarette smokingOth fi t ti f t• Other first tier factorsa. Heart diseaseb Atrial fibrillationb. Atrial fibrillationc. LVH

Goldstein BL. A Primer on Stroke Prevention Treatment Willey Blackwell 2009

Proposed structure for consideration for modifiable stroke risk factorrisk factor

2. Second–tier factors• Risk factors for risk factors.exp:

a Obesity & body fat distriba. Obesity & body fat distribb. Physical inactivity

• Risk factors important to control.expD li id ia. Dyslipidemia

b. Metabolic syndrome• Risk factors important in special populations

a. Asymptomatic carotid stenosisb. Post menopausal hormone therapyc Sickle cell diseasec. Sickle cell disease

• Risk factors with smaller effect or questionable effectGoldstein BL. A Primer on stroke Prevention Treatment. Willey Blackwell.2009

Paul Coverdell National Acute Stroke RegistrySurveillance 2005–2007Surveillance 2005–2007

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The most common risk factors :The most common risk factors :history of hypertension (72.7%), history of hyperlipidemia (33.8%), history of hyperlipidemia (33.8%), previous stroke or TIA (30.9%), history of diabetes (28.2%), y ( ),previous myocardial infarction or history of coronary artery diseasen(24.7%), cigarette smoking (17.7%), and history of atrialfibrillation (15.1%)

Paul Coverdell National Acute Stroke Registry, Georgia, Illinois, Massachusetts, and North Carolina, 2005–2007Illinois, Massachusetts, and North Carolina, 2005 2007

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Total(N = 56 969)

Georgia(N = 13 047)

Illinois(N = 10 257)

Massachusetts(N =

North Carolina(N = 56,969) 13,047) 10,257) (N =

16,984)(N = 16,681)

Hemorrhagic 7,839 (13.8) 2,615 (20.0) 1,620 (15.8) 894 (5.3) 2,710 (16.2)

I h i 32 014 (56 2) 7 884 (60 4) 4 228 (41 2) 11 873 (69 9) 8 029 (48 1)Ischemic 32,014 (56.2) 7,884 (60.4) 4,228 (41.2) 11,873 (69.9) 8,029 (48.1)

Ill defined 4,158 (7.3) 162 (1.2) 1,749 (17.1) 250 (1.5) 1,997 (12.0)

Transient IA 12,320 (21.6) 2,289 (17.5) 2,511 (24.5) 3,760 (22.1) 3,760 (22.5)

Paul Coverdell National Acute Stroke RegistrySurveillance 2005–2007Surveillance 2005–2007

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The most common combinations of risk factors :Hypertension and dyslipidemia (28.5%),hypertension and diabetes (23.8%), hypertension and previous stroke or TIA (24.4%),hypertension and previous myocardial infarction or historyhypertension and previous myocardial infarction or historyof coronary artery disease (20.0%). The combination of hypertension, diabetes, and ypdyslipidemia, three components of metabolic syndrome, occurred in 11.0% of patients.

Modifiable Risk Factors for Ischemic Stroke

Factor Prevalence % Relative Risk

Hypertension 25 40 3 5Hypertension 25-40 3-5

Elevated total cholesterol level( >240 mg/dl [6.21

6 – 40 1,81,8--2.62.6

( 240 mg/dl [6.21 mmol/L])

Smoking 25 1,5

Physical inactivity 25 2 7Physical inactivity 25 2,7

Obesity 18 1.8-2.4

Asymptomic carotid stenosis

2/8 2stenosis(>50%)

Alcohol consumption (>5 drinks/d)

2-5 1.6drinks/d)

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Stroke prognosisStroke prognosisp gp g

Death : within : 1 mth : 25% 6 mth : 30%1 yr : 50%

Prognosis worse : ICH and SAH : 1mth mortality : 50%

Early mortality : most : neurological deterioration + aspiration

L t d th di di t k li tiLater death : cardiac disease or stroke complication

Lancet 2008;371 :1612

AHA/ ASA G id liAHA/ ASA Guideline

Guidelines for the Primary Prevention of Stroke

A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationAmerican Heart Association/American Stroke AssociationThe American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.

Larry B. Goldstein, MD, FAHA, Chair; Cheryl D. Bushnell, MD, MHS, FAHA, Co-Chair;Robert J. Adams, MS, MD, FAHA; Lawrence J. Appel, MD, MPH, FAHA;Lynne T. Braun, PhD, CNP, FAHA; Seemant Chaturvedi, MD, FAHA; Mark A. Creager, MD, FAHA; Antonio Culebras, MD, FAHA; Robert H. Eckel, MD, FAHA; Robert G. Hart, MD, FAHA;J dith A Hi h MD MS FAHA Vi i i J H d PhD FAHA Ed d C J h MD MSJudith A. Hinchey, MD, MS, FAHA; Virginia J. Howard, PhD, FAHA; Edward C. Jauch, MD, MS, FAHA; Steven R. Levine, MD, FAHA; James F. Meschia, MD, FAHA; Wesley S. Moore, MD, FAHA; J.V. (Ian) Nixon, MD, FAHA; Thomas A. Pearson, MD, FAHA

Stroke 2011;42;517-584; originally published online Dec 2 2010;

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Stroke 2011;42;517 584; originally published online Dec 2, 2010;

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Stroke remains a major healthcare problem. Approximately j p pp y795 000 people in the United States have a stroke each year, of which about 610 000 are a first attack; and 6.4 million Americans are stroke survivorsAmericans are stroke survivorsStroke is also a leading cause of functional impairments, with 20% of survivors requiring institutional care after 3 months and 15% to 30% being permanently disabled (Lloyd-Jones D, 2010)St k i lif h i t th t ff t t l t kStroke is a life-changing event that affects not only strokepatients themselves but their family members and caregiversas well.

Generally Nonmodifiable Risk Factors44

Age, y Prevalence of first stroke

(percent per 100 000)

18–44 0.5

45–64 2.445 64 2.4

65–74 7.6

75 11.2

I id f fi k ( 1000)1†Incidence of first stroke (per 1000)1†

White men White women Black Men Black women

45–54 1.4 1.0 3.5* 2.9

55–64 2.9 1.6 4.9 4.6

65–74 7.7 4.2 10.4 9.8

75–84 13.5 11.3 23.3* 13.5

85 32.1 16.5 24.7* 21.8


Sex (age adjusted) Prevalence (percent per 100 000)Men: 2.9Women: 2.3

Low birth weight 2 for birth weight 2500 g vs 4000 gThe odds of stroke were more than double for those with birth weights of 2500 g compared with those weighing 4000 g

Race/ethnicity (age adjusted) Prevalence (percent per 100 000)/ y ( g j ) (p p )Asian: 1.8Blacks: 4.6Hispanics: 1.9pWhites: 2.4


Genetic Factors

A meta-analysis of cohort studies showed that a positive family history of stroke increases risk of stroke by approximately 30% [odds ratio (OR), 1.3; 95% CI, 1.2 to 1.5, P0.00001].

The odds of both monozygotic twins having strokes are 1.65-fold higher than those for dizygotic twins

Correlation Between Cholesterol And Ischemic StrokeIschemic Stroke

MRFIT: Stroke mortality for 6 years (n=350,977)

6

8

ratio

Subarachnoid hemorrhage

Intracranial hemorrhage

y y ( , )

4

6

d d

eath

Non-hemorrhagic

2

adju

sted

0Age

< 160 160-199 200-239 240-279 >280

Iso et al. N engl J Med. 1989;320:904-

Serum cholesterol (mg/dl)

Inconsitent - weak association

CHOLESTEROLAND

Inconsitent weak association

Chol ↓ with STATIN → incidence ↓in high risk & pts with di b li t k /TIA STROKE noncardioembolic stroke /TIA

Statin tx : most important advance in stroke prev ft ASA ti HTafter ASA, anti HT

Amarenco P, Labreuche J. Lancet Neurol 2009;8;453-463

Recommendations of the NCEP-ATP III( National Cholesterol Educational Program and the Adult Treatment Panel)( National Cholesterol Educational Program and the Adult Treatment Panel)

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Management of factors contributing to Management of factors contributing to hypertriglyceridemia

Obesity and overweightPhysical inactivityCigarette smokingExcess alcohol intakeHigh carbohydrate diets (>60% of energy intake)M b li d 2 di bMetabolic syndrome or type 2 diabetes

Recommendations of the NCEP-ATP III( National Cholesterol Educational Program and the Adult Treatment Panel)( National Cholesterol Educational Program and the Adult Treatment Panel)

51

Management of factors contributing to Management of factors contributing to hypertriglyceridemia

Chronic renal failureNephrotic syndromeMedications (corticosteroids, estrogens, retinoids and high-dose-blockers)Genetic disorders (familial combined hyperlipidemia, familial hypertriglyceridemia and familial familial hypertriglyceridemia and familial dysbetalipoproteinemia)

Recommendations of the NCEP-ATP III52

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins): 7–30% dreduction

Lovastatin 20–80 mg dailyPravastatin 20–80 mg dailySimvastatin 20–80 mg dailySimvastatin 20 80 mg dailyFluvastatin 20–80 mg dailyAtorvastatin 10–80 mg daily

Nicotinic acid: 20–50% reductionImmediate-release (crystalline) nicotinic acid 1.5–4.5 g dailyExtended-release nicotinic acid 1–2 g daily NiaspanSustained-release nicotinic acid 1–2 g daily

Fibric acids: 20–50% reductionGemfibrozil 600 mg twice dailyFenofibrate 200 mg dailyClofibrate 1 000 mg twice dailyClofibrate 1,000 mg twice daily

Treatment with an HMG-CoA reductase inhibitor

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Treatment with an HMG CoA reductase inhibitor(statin) medication in addition to therapeutic lifestyle changes with LDL-cholesterol goals as y g greflected in the NCEP guidelines is recommended for primary prevention of ischemic stroke in patientswith coronary heart disease or certain high-riskconditions such as diabetes (Class I; Level of E id A)Evidence A)

Pengaruh Statin pada strokeg p54

Stroke Prevention by Aggressive Reduction in Cholesterol y ggLevels(SPARCL) studi [Amarenco, 2006] adalah yang pertama, dirancang khusus untuk menyelidiki pengaruh penurunan kadar kolesterol dengan statin dalam pencegahan stroke sekunderkolesterol dengan statin dalam pencegahan stroke sekunderPada 4.731 pasien yang mengalami stroke atau TIA dalam waktu 1-6 bulan sebelum masuk studi atorvastatin 80 mg secara acak atau plasebo, dengan jangka waktu rata-rata 4,9 tahun. Penelitian ini menunjukkan manfaat atorvastatin 80 mg pada reduksi stroke berulang (16% pengurangan risiko mg pada reduksi stroke berulang (16% pengurangan risiko relatif).

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Population-based 10-year cohort study showed that Population based 10 year cohort study showed that Japanese men and women with low HDL-C levels (30 mg/dL [0.78 mmol/L]) had significantly and( g/ / ) g yindependently higher risk of stroke, especially ischemic stroke. (Yoshiyuki. 2003)

Statins, Fibrates and Lipids Statins, Fibrates and Lipids

LDL-CLDL C

HDL-CSTATINS FIBRATES

TG

56LDL-C: Low density lipoprotein cholesterol (BAD Cholesterol)HDL-C: High density lipoprotein cholesterol (GOOD Cholesterol)TG: Triglycerides

Combination therapies to achieve greater or more comprehensive improvements in lipoprotein profiles

Statin and fenofibrate (↓↓ LDL, ↑HDL, ↓↓ ↓ TG)

Statin and nicotinic acid (↓↓↓ LDL, ↑↑HDL, ↓↓ TG)

Statin and omega-3 (↓↓ TG, no effect on HDL and LDL)

Statin and ezetimibe (↓↓↓ LDL no major effect on HDL and TG)Statin and ezetimibe (↓↓↓ LDL, no major effect on HDL and TG)

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood C ( ) C ( )

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Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002;106(25):3143-421Farnier M et al. Eur Heart J. 2005 May;26(9):897-905 Farnier et al. Am Heart J 2007; 153: 335-338Athyros VG et al. Diabetes Care. 2002;25(7):1198-202. Athyros VG et al. Diabetes Care. 2002;25(7):1198-202.

Guidelines for the Diagnosis and Management of Dyslipidemias 2008Dyslipidemias 2008

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Secara umum, kombinasi dari statin dan fibrates Secara umum, kombinasi dari statin dan fibrates tidak disarankanJika kombinasi ini harus digunakan, lebih aman Jika kombinasi ini harus digunakan, lebih aman fenofibrate dari gemfibrozilJika gemfibrozil digunakan, dosis statin harus Jika gemfibrozil digunakan, dosis statin harus dijaga rendah

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Peningkatan kadar TG, dosis statin yang lebih tinggi g , y g ggdiperlukan. Untuk peningkatan moderat LDL-C pada pasien dengan peningkatan TG, niacin (Niaspan) adalah pengobatan alternatif Secara umum statin tidak boleh digunakan sendiri alternatif. Secara umum, statin tidak boleh digunakan sendiri pada pasien dengan TG> 500 mg / dL.Ezetimibe menghambat penyerapan kolesterol usus. Statin dipertimbangkan terapi lini pertama untuk pasien yang membutuhkan penurunan LDL-C. Gunakan dalam kombinasi ezetimibe dengan statin untuk pasien (LDL-C) tidak turun ezetimibe dengan statin untuk pasien (LDL-C) tidak turun dengan statin.

Medication-Specific Treatment Recommendations

TG Level RX Goal Start and maximize

Then add or switch to

< 499 LDL-C < 70 atorvastatin 40-80 mg, simvastatin 40-80 mg or

Add Niaspan 1000-2000 mg daily

Vytorin 20-80/10 mg**

> 500 LDL-C < 70 andHDL C < 100

Niaspan 2000 mg, 3 fi h il

Add Niaspan, 3 fi h il non-HDL-C < 100 omega-3 fish oils

4 g orfenofibrate 200 mg

omega-3 fish oils, fenofibrate,or statin

g

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Statins Azetidinone Nicotinic Acid FibratesStatins Azetidinone Nicotinic Acid Fibrates

Medications atorvastatin (Lipitor)fluvastatin

ezetimibe niacin(Niaspan)niacin/lovasta

gemfibrozilfenofibrate(Lofibra, fluvastatin

lovastatinpravastatinrosuvastatin*(C )

niacin/lovastatin(Advicor)30niacin/simvast

i

(Lofibra, Tricor,Antara)

Crestor)simvastatin

atin(Simcor)30

Lipid EffectsLDL C

lower 18-60% lower 17-23% lower 10-25% lower 5-20%(may raise)LDL-C

HDL-CTG

raise 5-15%lower 7-30%

raise 2%lower 4-11%

raise 15-35%lower 20-50%

(may raise)raise 10-20%lower 20-50%

Major Use elevated LDL- elevated LDL - moderately TG > 400 M j U vC, mild tomoderatelyelevated TG,

ildl l

vC

yelevatedLDL-C, elevated TG,l HDL C

G 00mg/dL

mildly lowHDL-C

low HDL-C

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Statins Azetidinone Nicotinic Acid FibratesStatins Azetidinone Nicotinic Acid Fibrates

Contraindication- Absolute

liver disease,pregnancyconcomitant

severe liver disease

liver disease,pregnancygout,

pregnancy28liver or severerenal disease, Absolute

- Relativeconcomitant useof fibric acidderivatives

gout, hyperuricemia

renal disease, gallstones

Major Side Effects

myopathy, myalgia,abdominal pain

well tolerated bymost

flushing,abdominal pain, gout,hyperglycemi

dyspepsia, gallstonepain, hepatotoxicitypain,

hepatotoxicityhyperglycemia, hepatotoxicity,ulcers

hepatotoxicity

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Summaryy64

Dyslipidemia is a modifiable stroke risk factorDyslipidemia is a modifiable stroke risk factorPrior statin treatment is associated with lower strokeseverity and better outcomes in acute ischemic severity and better outcomes in acute ischemic stroke patients.The ongoing cross-risk after ischemic stroke for The ongoing cross risk after ischemic stroke for further ischemic vascular complications stresses the importance of long-term control of theatherothrombotic disease process.

dislipidemia dan risiko stroke nov 2011.pdf

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