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우은석 한
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1 이화여자대학교목동병원 뇌졸중센터 김용재 Metabolic Syndrome, Diabetes and Stroke 23 차대한당뇨병학회춘계학술대회

2 What is Stroke? Epidemiologic Evidence Diabetes and Stroke Suspicion Management Strategies 2

3 A stroke is a focal neurologic deficit caused by a disruption of the cerebral circulation (occlusion or rupture) Stroke is a clinical Syndrome Cerebrovascular Disease (CVD) 뇌졸중 ( 腦卒中 ) 뇌혈관질환 CerebroVascular Attack (CVA) 중풍 ( 中風 )

4 허혈뇌졸중 Ischemic stroke ( 뇌경색 infarction) 일과성허혈발작 (Transient Ischemic Attack; TIA) 혈전뇌경색 Atherothrombotic 색전뇌경색 Embolic 열공뇌경색 Lacunar 출혈뇌졸중 Hemorrhagic stroke ( 뇌출혈 hemorrhage) 뇌내출혈 Intracerebral H 거미막밑출혈 Subarachnoid H 경막밑출혈 Subdural H 경막밖출혈 Epidural H

5 Atherosclerosis Intra / Extra-cranial A. Stenosis Artery-to-Artery Embolism

6 Lacunar Syndromes Pure motor hemiparesis Pure sensory stroke Sensorimotor Stroke Ataxic hemiparesis Dysarthria-clumsy hand syndrome

7 Cardiogenic Embolism High- Risk Mechanical prosthetic valve Mitral stenosis c AF AF ( x lone AF) Lt atrial thrombus SSS Recent MI ( < 4 weeks ) Lt ventricular thrombus Dilated cardiomyopathy Akinetic LV segment Atrial myxoma Infective endocarditis Medium- Risk Mitral valve prolapse Mitral annulus calcification Mitral stenosis s AF Lt atrial turbulence Atrial septal aneurysm Patent foramen ovale Atrial flutter Lone AF Bioprosthetic valve CHF MI ( > 4 weeks )

8 Other determined etiology Non-atherosclerotic vasculopathies hematologic disorder hypercoagulable state Undetermined etiology a. Two or more causes medium risk cardiac source + another possible cause AF + 50% ipsilateral stenosis lacunar syndrome + 50% ipsilateral stenosis b. Negative evaluation c. Incomplete evaluation

9 Total (n=10,861) LAA SVO CE SOE SUE Age 64.5 ± ± ± ± ± ±13.1 Male 56.4% 59.2% 55.7% 51.5% 55.9% 55.3% Hypertension 65.9% 64.5% 70.9% 50.7% 29.3% 62.5% DM 27.1% 37.9% 34.0% 20.2% 10.3% 32.8% CE Source 16.8% 7.5% 4.1% 100% 6.9% 21.3% Smoking 20.4% 41.7% 42.5% 30.5% 27.6% 33.9% Hyperlipidemia 19.0% 21.8% 22.1% 14.1% 15.5% 20.2% Previous Stroke 34.2% 29.6% 19.3% 23.8% 17.2% 유경호등, 대한신경과학회, 2006

10 Iusulin Resistance & Stroke Epidemiologic research Shinozaki K, Naritomi H, Shimizu T, et al. Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke. Stroke 1996; 27: Gertler MM, Leetma HE, Koutrouby RJ, Johnson ED. The assessment of insulin, glucose and lipids in ischemic thrombotic cerebrovascular disease. Stroke 1975; 6: Lindberg O, Tilvis RS, Strandberg TE, et al. Elevated fasting plasma insulin in a general aged population: an innocent companion of cardiovascular diseases. J Am Geriatr Soc 1997; 45: Lindahl B, Dinesen B, Eliasson M, Roder M, Hallmans G, Stegmayr Lindahl B, Dinesen B, Eliasson M, Roder M, Hallmans G, Stegmayr B. High proinsulin levels precede first-ever stroke in a nondiabetic population. Stroke. 2000; 31:

11 Wannamethee SG, Perry IJ, Shaper AG. Nonfasting serum glucose and insulin concentrations and the risk of stroke. Stroke 1999; 30: Pyorala M, Miettinen H, Laakso M, Pyorala K. Hyperinsulinemia and the risk of stroke in healthy middleaged men. The 22 year follow-up results of the Helsinki Policemen Study. Stroke 1998; 29: Kuusisto J, Mykkanen L, Pyorala K, Laakso M. Non-insulindependent diabetes and its metabolic control are important predictors of stroke in elderly subjects. Stroke 1994; 25: Lakka H-M, Lakka TA, Tuomilehto J, Sivenius J, Salonen JT. Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men. Arch Intern Med 2000; 160: Folsom AR, Rasmussen ML, Chambless LE, et al. Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. Diabetes Care 1999; 22:

14 Kernan WN, Viscoli CM, Inzucchi SE, et al. Insulin resistance among patients with ischemic stroke and TIA (presented at 27 th ISC, 2002) nondiabetic patients with a recent TIA or ischemic stroke, 50% had significant insulin resistance, especially those who are young and obese

15 Kernan et al. Neurology

16 MS and IMT KOREAN METABOLIC SYNDROME STUDY 0.9 Maximal IMT & MS 1.2 Max-IMT according to associated MS p< MS(-) MS(+)

17 The clustered metabolic risk factors among patient with ischemic stroke (presented at 2003 KSA annual meeting) Men & women over 45 years of age who were admitted to EWHA Univ. Mokdong hospital from September 2002 to January 2003 for TIA or ischemic stroke 273 recent TIA or ischemic stroke 156 eligible patients 46 TIA, 110 ischemic stroke patients The average time to assessment; 70 days(range 20 to 191)

18 Age-adjusted prevalence of metabolic syndrome(atp III with >90/80cm) BMI>25 STROKE NHANES 0 Men Women

19 Relationship between metabolic syndrome and risk factor OR 95% CI Abdominal obesity BMI(>25kg/m 2 ) Blood pressure Fasting glucose HDL-cholesterol TG

20 Should consider even mildly elevated blood pressure, blood sugar, TG, and overweight as vascular risk factors Obesity is significant stroke risk factors when it occurs as part of the cluster of metabolic syndrome

21 Lesson from NOMAS Bernadette M et al. Stroke risk and the metabolic syndrome: Findings from the Northern Manhattan Study(NOMAS) (presented at 55 th AAN annual meeting) NOMAS, a 4-year prospective study of 3,298 (mean age 69)community residents At baseline more than 42% met the ATP III criteria Patients with metabolic syndrome were 1.5 times more likely develop stroke Women with metabolic syndrome were 2.1 times more likely to develop stroke

23 23

24 Stroke is different in type 2 diabetes Clinical Diabetes No Diabetes Ischemic : hemorrhagic Approx. 10:1 Approx. 5:1 Stroke risk < 55 years Higher Lower RR for male /female Female > male Female < male Infratentorial infarcts More common Less common Lacunar infarction More common Less common Infarction volume No difference Adapted from Sander D. et al. Br J Diabetes Vasc Dis

25 ischaemic strokes and increased proportion of lacunar strokes that may be clinically silent 25

26 a worse prognosis, with a twofold increase in the likelihood of subsequent strokes Hankey GJ et al. Stroke 1998 significantly greater permanent neurological and functional disability and longer hospital stay Megherbi SE et al. Stroke 2003 Risk of stroke-related dementia Luchsinger JA et al. Am J Epidemiol

27 Sex-specific differences highest risk for stroke attributable to diabetes in younger persons and particularly women 4.66 in men, 8.18 in women Adapted from Mulnier HEet al Diabetologia 2006; 49 27

28 for women, diabetes should be considered a cardiovascular disease risk equivalent for fatal stroke Hu G et al. Stroke 2005; 36 28

29 Kaplan-Meier curves for stroke in patients with type 2 diabetes mellitus, with and without previous cardiovascular disease (CVD), by sex Giorda, C. B. et al. Stroke 2007;38:

30 DAI study Age and previous stroke are the main predictors of stroke in diabetes. The combined role of Hba1c, microvascular complications, low HDL cholesterol, and treatment with insulin plus oral agents highlights the importance of diabetic history and clinical background in the development of stroke. 30

31 31

32 Vulnerable Plaque 32

33 Stroke 80-90% ischemia, 20%-30% are due to large artery disease. Old Atherosclerotic plaque formation was a slow, ongoing process to narrowing/occlusion New Arterial narrowing/occlusion develop rapidly after the plaque rupture Vulnerability of atheromatous plaque 33

34 Differences in carotid atherosclerosis plaques may be particularly prone to rupture and dispersal during recanalising interventions in diabetes Moreno PR et al. Am Coll Cardiol 2004; 44 34

35 High-resolution multicontrast MRI, diabetes represented a significant predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis Takaya, N. et al. Stroke 2006;37: Takaya, N. et al. Stroke 2006;37:

36 Different definitions of the metabolic syndrome and non-embolic ischemic stroke in Korean

37 Background Most studies were based on the standardised definitions of the World Health Organization (WHO), and the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III New definitions such as that of the National Heart, Lung and Blood Institute and the American Heart Association (NHLBI/AHA) and especially that proposed by the International Diabetes Federation (IDF) have raised concerns as to the whether they can identify high risk population for CVD

38 The IDF defined MeS according to central obesity (waist circumference > 90cm for South Asian men or >80cm for South Asian women)

39 The prevalence of MS by the revised NCEP (25.7% of men and 31.9% of women) was higher than that according to the IDF (14.2% of men and 26.6% of women). The IDF criteria failed to identify 44.9% of men and 16.6% of women identified as having MS according to the revised NCEP criteria.

40 However, the association between MeS and stroke may depend on the definition used to diagnose MeS. We performed this study to (1) investigate the prevalence of MeS in ischemic stroke patients according to the revised NCEP and IDF criteria, (2) assess the agreement between the revised NCEP and IDF criteria in defining MeS, and (3) identify the characteristics of subjects with MeS who satisfy the revised NCEP but not the IDF criteria.

41 Methods Consecutively hospitalized 1 st acute ischemic non-embolic stroke patient Preliminary Data NCEP ATP III 478/1048=45.6% IDF 167/1048=15.9%

42 More Than the Sum of Its Components? can we predict which individuals are at increased risk for stroke based on information about the metabolic syndrome? MS defined by all 6 criteria except for the ACE definition predicts incident stroke in elderly subjects Is the metabolic syndrome by itself a risk factor for stroke? However, IGT alone is as strong a predictor of stroke as the MS according to the WHO, NCEP, and updated NCEP criteria. Wang J. et al. Stroke 2008;39 42

43 Impact of Hypertension 43

44 Approach to Manage patients with Ischemic Stroke Management of Acute Phase - Improve cerebral circulation 혈전용해제 (thrombolytics) - minimize 2ndary neuronal damage 신경세포보호제 (neuroprotectants) - Prevention of thrombus extension 항혈전제 (Antithrombotics) - Prevention of complication : Pneumonia, UTI etc Physical Therapy & Rehabilitation Prevention of 2 nd Stroke Prevention of 1 st stroke 항혈전제 (anti-thrombotics) 항고혈압제 (anti-hypertensives) 지질저하제 (lipid lowering agents) 혈당저하제 (hypoglycemics) 경동맥내막절제술, 스텐트

45 뇌졸중진료지침 (2009) Less well-documented or potentially modifiable risk factors 45

46 당뇨병을동반한뇌졸중환자에서소혈관합병증 ( 근거수준 Ia, 권고수준 A) 및대혈관합병증 ( 근거수준 IIa, 권고수준 B) 의예방을위해혈당을가능한한정상수준으로조절하도록추천된다. HbA1c 의목표수치가 7% 미만이되도록혈당을조절하는것이바람직하다. ( 근거수준 IIb, 권고수준 B) 근거수준과권고수준은 US Agency for Health Care Policy and Research 46

47 허혈뇌졸중의경우, 고지질혈증은반드시교정되어야하며, 죽상경화성동맥질환에의한허혈뇌졸중이나관상동맥질환을동반한허혈뇌졸중환자의고지질혈증치료기준은 NCEP ATP III의기준을따른다. 생활방식의변경, 식이요법, 약물등이고려될수있으며, 약물의경우에는스타틴약제의사용이추천된다. ( 근거수준 Ia, 권고수준 A) 관상동맥질환을동반하거나증후성죽상경화성허혈뇌졸중환자의콜레스테롤교정목표는저밀도콜레스테롤을기준으로하여 100mg/dL 이하이다. ( 근거수준 Ia, 권고수준 A) 다발성의위험질환을동반한고위험군환자들의경우, 더욱적극적인치료를고려해볼수있다. ( 근거수준 Ia, 권고수준 A) 47

48 STOP STROKE ABS in your car ABS for our patients A for Antithrombotics B for BP control S for Statin

(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])

$(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])$ Cardiovascular Disease in Metabolic Syndrome 김상현 보라매병원내과 서울대학교의과대학내과학교실 Contents Metabolic syndrome and Cardiovascular system CVD Mortality Coronary artery disease Heart failure Atrial fibrillation Management