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DISLIPIDEMIA DAN RISIKO STROKE


Oleh: Dr Sugianto, SpS, Mkes, PhD

Abnormal dari serum lipids (trygliserid, cholesterol, Low Density Lipoprotein / LDL , dan high density lipoprotein/ HDL) secara jelas sebagai faktor risiko atherosclerotic, terutama penyakit coronair. Study dengan memakai ultrasound teknologi menetapkan t k total t t l cholesterol h l t l atau t LDL cholesterol h l t l secara langsung dan HDL cholesterol berhubungan dengan extracranial carotid atherosclerosis dan penebalan p p plaque q p pada intima-media. Tiga prospective studies pada pria menunjukkan peningkatan ischemic stroke dengan total cholesterol diatas 240-270 240 270 mg/dl mg/dl.
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Asia Pacific Cohort studies, 352.033 individu didapatkan 25% kenaikan pada ischemic stroke untuk setiap kenaikan 1 1-mmol/L mmol/L (38 (38.7 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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Dislipidemia

Lebih dari 28 juta orang Amerika memiliki beberapa bentuk penyakit kardiovaskuler (Minin, 2006). Hasil medis dengan g penurunan p produktivitas p dan biaya 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)

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

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

HDL-C dan Stroke


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

HDL-C dan Stroke


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

Trigliseride g
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The Copenhagen City Heart Study, a prospective, populationbased p p cohort study y composed p of approximately 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?


HDL has a number of anti anti-atherogenic atherogenic effects
Role in reverse cholesterol transport Antioxidant effects Inhibition of adhesion molecule expression Inhibition of platelet activation Prostacyclin stabilization Promotion of NO production Prevention of f inflammation fl

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Challenges in secondary stroke prevention: prevalence of multiple 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. 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) 275280

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Almost half the p patients admitted with IS/TIA / to our institution 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 ) 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 established (Berthet K, , 2004) ) cerebrovascular disease. (

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

Multiple metabolic risk factors

Diabetes

2%

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

n = 224 2% 30% 13%

33% 4% 12%

Hypertension
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Dyslipidaemia

Current standards of care fail to adequately address this changing risk factor profile
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 Retinopathy Nephropathy Neuropathy

MICROvascular complications of diabetes 3


1 1. 2. 3.

Baigent C et al. Lancet 2005;366:1267-78 2005;366:1267 78 Cholesterol Treatment Trialist (CTT) Collaborators, Kearney PM et al. Lancet 2008;371:117-25 Gaede P et al. Engl J Med 2003;348:383-393

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Transient ischemic attack Ischemic stroke Angina pectoris (stable, unstable) Myocardial infarction Claudication

Ischemic sudden death

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

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Risk Factors
Fatty Streak
Smoking Hypertension Hyperlipidemia Others
(diabetes, coagulation abnormalities, y etc.) ) homocysteinemia,

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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 yang terjadi t j di pada d endotel d t l

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Sebagian g besar penelitian p epidemiologi p g tidak menemukan hubungan yang konsisten antara tingkat kolesterol dan risiko stroke secara keseluruhan B b Beberapa penelitian, li i telah l h menemukan k h hubungan b positif i if 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 wanita, dan it pada d orang tua, t d dan di antara t k kelompokl k kelompok ras dan etnis yang berbeda [Sacco, 2001].

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Dalam sebuah tinjauan j terbaru dan meta-analisis dari 42 percobaan acak mengevaluasi terapi statin untuk pencegahan stroke (N = 121.285), resiko relatif dikumpulkan terapi statin untuk semua stroke adalah 0 0,84 84 (95% CI CI, 0,79-0,91) 0 79 0 91) [Regan, [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, relatif 0 0,99, 99 95% CI CI, 0 0,80-1,21) 80 1 21) .

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National Cholesterol Educational Program and the Adult Treatment Panel (NCEP-ATP III)
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Normal <150 mg/dl (1.7 mmol/l) Borderline high 150199 mg/dl (1.72.2 mmol/l) High 200499 mg/dl (2.25.6 mmol/l) Very high 500 mg/dl (5.6 mmol/l)

Mechanisms by which hypertriglyceridemia may contribute IS


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Promotion of atherosclerosis
Endothelial dysfunction Oxidative stress due to lipid-derived p free radicals Impairment of endothelial-dependent vasodilatation Association with elevation of the markers of atherosclerosis (C-reactive protein, fibrinogen levels and circulating adhesion Molecules)

Mechanisms by which hypertriglyceridemia may contribute IS


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Promotion of thrombogenicity
Elevated plasma viscosity Elevated plasma fibrinogen levels Lowered fibrinolytic activity Elevated levels of clotting factor Xc compared to normolipidemic controls Elevated fibrinogen levels

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

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Hipertrigliseridemia juga dapat menyebabkan penyakit serebrovaskular melalui dampaknya pada trombosis. Efek ini dihasilkan oleh perubahan thrombogenic sistem koagulasi serta peningkatan viskositas plasma Hyperviscosity dapat mengakibatkan iskemia jaringan akibat gangguan microcirculatory, kerusakan pada d endotelium d t li , dan d kecenderungan k d meningkat i k t menjadi trombosis (Rosenson, 2001)

CHOLESTEROL

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Stroke is one of the most costly y diseases in the community both from a humanitarian and economic point of view T prevent recurrent stroke To k events, the h standard d d strategy 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 about b t 4% i in the th first fi t month th and d about b t 12% in i the th first fi t year after stroke onset with the first period after the event being the most vulnerable

Summary of Recommendations (AHA Guidelines) for primary stroke prevention

Non Modifiable :
Age L Birth Low Bi h weight i h Sex G Genetic i f factors Race Eh i i Ethnicity

Well documented & modifiable RF Less 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 prevention

Well documented and Modifiable Modifiable RF


Hypertension yp ( I, , A) ) Cigarette Smoking ( I, B) Diabetes ( I, A) Asymptomatic y p Carotid Stenosis Oral contraceptive use (III,B/C) Diet and Nutrition Ph i l Inactivity Physical I ti it Obesity and Body Fat Distribution

Dyslipidemia D li id i ( I , A )
Atrial Fibrillation Other Cardiac Conditions Sickle Cell Disease

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

Summary of Recommendations (AHA Guidelines) for primary stroke prevention

Less well documented or potentially modifiable RF& modifiable RF


Metabolic syndrome y Drug abuse (IIb,C) Sleep disordered breathing (IIb,C) H Hyperhomocysteinemia h t i i (IIb,C) (IIb C) Elevated lipoprotein phospholipase A2 Inflammation (IIa,B) Aspirin for primary stroke prev (III,a) Alcohol abuse ( (IIb, , B) ) Oral contraceptive use (III,B/C) Migraine El Elevated t d Lp(a) L ( ) (IIb (IIb,C) C) Hypercoagulability Infection

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

Proposed structure for consideration for modifiable stroke risk factor

1. First tier factors The Big three factors a. Hypertension b. Diabetes c. Cigarette smoking Other Oth fi first t ti tier factors f t a. Heart disease b Atrial fibrillation b. c. LVH

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

Proposed structure for consideration for modifiable stroke risk factor

2. Secondtier factors Risk factors for risk factors.exp: a Obesity & body fat distrib a. b. Physical inactivity Risk factors important to control.exp a. Dyslipidemia D li id i b. Metabolic syndrome Risk factors important in special populations a. Asymptomatic carotid stenosis b. Post menopausal hormone therapy c Sickle cell disease c. Risk factors with smaller effect or questionable effect
Goldstein BL. A Primer on stroke Prevention Treatment. Willey Blackwell.2009

Paul Coverdell National Acute Stroke Registry Surveillance 20052007


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The most common risk factors :


history

of hypertension (72.7%), history of hyperlipidemia (33.8%), previous stroke or TIA (30.9%), history y of diabetes ( (28.2%), ), previous myocardial infarction or history of coronary artery diseasen(24.7%), cigarette smoking (17.7%), and history of atrial fibrillation (15.1%)

Paul Coverdell National Acute Stroke Registry, Georgia, Illinois, Massachusetts, and North Carolina, 2005 20052007 2007
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Total (N = 56 969) 56,969)


Hemorrhagic

Georgia (N = 13 047) 13,047)

Illinois (N = 10 257) 10,257)

Massachuse tts (N = 16,984)

North Carolina (N = 16,681)

7,839 (13.8) 2,615 (20.0) 1,620 (15.8)


32 014 (56.2) 32,014 (56 2) 7,884 7 884 (60 (60.4) 4) 4,228 4 228 (41 (41.2) 2)

894 (5.3) 2,710 (16.2)


11 873 (69.9) 11,873 (69 9) 8,029 8 029 (48 (48.1) 1)

I h i Ischemic Ill defined Transient IA

4,158 (7.3)

162 (1.2) 1,749 (17.1)

250 (1.5) 1,997 (12.0)

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 Registry Surveillance 20052007


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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 history of coronary artery disease (20.0%). The combination of hypertension, yp diabetes, and dyslipidemia, three components of metabolic syndrome, occurred in 11.0% of patients.

Modifiable Risk Factors for Ischemic Stroke


Factor Hypertension Elevated total cholesterol level ( >240 240 mg/dl [6.21 mmol/L]) Smoking Physical inactivity Obesity Asymptomic carotid stenosis (>50%) Alcohol consumption (>5 drinks/d)
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Prevalence % 25 40 25-40 6 40

Relative Risk 35 3-5 1,81,8 -2.6

25 25 18 2/8

1,5 27 2,7 1.8-2.4 2

2-5

1.6

Stroke p prognosis 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 death Later d th : cardiac di disease di or stroke t k complication li ti

Lancet 2008;371 :1612

AHA/ ASA G Guideline id li


Guidelines for the Primary Prevention of Stroke
A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The 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 Judith A. Hi Hinchey, h MD MD, MS MS, FAHA FAHA; Vi Virginia i i J J. H Howard, d PhD PhD, FAHA FAHA; Edward Ed d C. C Jauch, J h MD, MD MS 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 2011;42;517-584; 584; originally published online Dec 2 2, 2010;


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Stroke remains a major j healthcare p problem. Approximately pp y 795 000 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 survivors Stroke 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 is Stroke i a life-changing lif h i event t th that t affects ff t not t only l stroke t k patients themselves but their family members and caregivers as well.

Generally Nonmodifiable Risk Factors


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Age, y 1844 4564 45 64 6574


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Prevalence of first stroke (percent per 100 000) 0.5 2.4 7.6 11.2 I id Incidence of f first fi stroke k ( (per 1000)1 White men White women 1.0 1.6 4.2 11.3 16.5 Black Men Black women 3.5* 4.9 10.4 23.3* 24.7* 2.9 4.6 9.8 13.5 21.8

4554 5564 6574 7584


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1.4 2.9 7.7 13.5 32.1

Generally Nonmodifiable Risk Factors


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Sex (age adjusted)

Prevalence (percent per 100 000) Men: 2.9 Women: 2.3 2 for birth weight 2500 g vs 4000 g The odds of stroke were more than double for those with birth weights of 2500 g compared with those weighing 4000 g Prevalence (p (percent per p 100 000) ) Asian: 1.8 Blacks: 4.6 p 1.9 Hispanics: Whites: 2.4

Low birth weight

/ y( (age g adjusted) j ) Race/ethnicity

Generally Nonmodifiable Risk Factors


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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 Stroke


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Age adjusted d death ratio MRFIT: Stroke mortality y for 6 y years ( (n=350,977) , )
Subarachnoid hemorrhage Intracranial hemorrhage Non-hemorrhagic

6 4 2 0

160-199 200-239 < 160 Serum cholesterol (mg/dl)

240-279

>280

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

Inconsitent - weak association CHOLESTEROL


AND

STROKE

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

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

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

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Recommendations of the NCEP-ATP III


( National Cholesterol Educational Program and the Adult Treatment Panel)
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Management of factors contributing to hypertriglyceridemia


Obesity and overweight Physical inactivity Cigarette smoking Excess alcohol intake High carbohydrate diets (>60% of energy intake) Metabolic M b li syndrome d or type 2 diabetes di b

Recommendations of the NCEP-ATP III


( National Cholesterol Educational Program and the Adult Treatment Panel)
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Management of factors contributing to hypertriglyceridemia


Chronic renal failure Nephrotic syndrome Medications (corticosteroids, estrogens, retinoids and highdose-blockers) Genetic disorders (familial combined hyperlipidemia, familial hypertriglyceridemia and familial dysbetalipoproteinemia)

Recommendations of the NCEP-ATP III


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3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins): 730% reduction d


Lovastatin 2080 mg daily Pravastatin 2080 mg daily Simvastatin 20 2080 80 mg daily Fluvastatin 2080 mg daily Atorvastatin 1080 mg daily Immediate-release (crystalline) nicotinic acid 1.54.5 g daily Extended-release nicotinic acid 12 g daily Niaspan Sustained-release nicotinic acid 12 g daily Gemfibrozil 600 mg twice daily Fenofibrate 200 mg daily Clofibrate 1 1,000 000 mg twice daily

Nicotinic acid: 2050% reduction


Fibric acids: 2050% reduction


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

Pengaruh g Statin pada p stroke


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Stroke Prevention by y Aggressive gg Reduction in Cholesterol Levels(SPARCL) studi [Amarenco, 2006] adalah yang pertama, dirancang khusus untuk menyelidiki pengaruh penurunan kadar kolesterol dengan statin dalam pencegahan stroke sekunder Pada 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 relatif).

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

Statins, Fibrates and Lipids


LDL C LDL-C

STATINS

HDL-C

FIBRATES

TG

LDL-C: Low density lipoprotein cholesterol (BAD Cholesterol) 56 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, LDL no major effect on HDL and TG)

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood C Cholesterol in Adults ( (Adult Treatment Panel III). ) C Circulation. 2002;106(25):3143-421 ( ) Farnier M et al. Eur Heart J. 2005 May;26(9):897-905 Farnier et al. Am Heart J 2007; 153: 335-338 Athyros VG et al. Diabetes Care. 2002;25(7):1198-202. 57 Athyros VG et al. Diabetes Care. 2002;25(7):1198-202.

Guidelines for the Diagnosis and Management of Dyslipidemias 2008


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

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Peningkatan g kadar TG, , dosis statin y yang g lebih tinggi gg diperlukan. Untuk peningkatan moderat LDL-C pada pasien dengan peningkatan TG, niacin (Niaspan) adalah pengobatan alternatif Secara umum alternatif. 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 dengan statin.

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Medication-Specific Treatment Recommendations

TG Level < 499

RX Goal LDL-C < 70

Start and maximize

Then add or switch to

atorvastatin 40Add Niaspan 80 mg, simvastatin 1000-2000 mg 40-80 mg or daily Vytorin 20-80/10 mg** Niaspan 2000 mg, omega-3 3 fish fi h oils il 4 g or fenofibrate 200 mg g Add Niaspan, omega-3 3 fish fi h oils, il fenofibrate, or statin

> 500

LDL-C < 70 and non-HDL-C HDL C < 100

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Statins Medications atorvastatin (Lipitor) fluvastatin lovastatin pravastatin rosuvastatin*( C Crestor) ) simvastatin

Azetidinone ezetimibe

Nicotinic Acid Fibrates niacin (Niaspan) niacin/lovasta tin (Advicor)30 niacin/simvast atin i (Simcor)30 gemfibrozil fenofibrate (Lofibra, Tricor, Antara)

Lipid Effects LDL C LDL-C HDL-C TG Major M j U Use

lower 18-60% lower 17-23% lower 10-25% lower 5-20% (may raise) raise 5-15% raise 2% raise 15-35% raise 10-20% lower 7-30% lower 4-11% lower 20-50% lower 20-50% elevated v LDLC, mild to moderately elevated TG, mildly ildl l low HDL-C elevated v LDL - moderately y C elevated LDL-C, elevated TG, l HDL low HDL-C C TG G > 400 00 mg/dL

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Statins Contraindicati on - Absolute - Relative liver disease, pregnancy concomitant use of fibric acid derivatives

Azetidinone severe liver disease

Nicotinic Acid Fibrates liver disease, pregnancy gout, hyperuricemia pregnancy28 liver or severe renal disease, gallstones

Major Side Effects

myopathy, well tolerated myalgia, by abdominal most pain pain, hepatotoxicity

flushing, abdominal pain, gout, hyperglycemi a, hepatotoxicity, ulcers

dyspepsia, gallstone pain, hepatotoxicity

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

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