Background. Metabolic syndrome T2DM CARDIOVASCULAR DISEASE. Major Unmet Clinical Need. Novel Risk Factors. Classical Risk Factors LDL-C.

Transcription

1 The effect of metabolic syndrome for left ventricular geometry, arterial stiffness and carotid intima-media thickness in Korean general population Result from Atherosclerosis RIsk of Rural Area in Korea General population (ARIRANG) study Kyounghoon Lee 1, Jang-Young Kim 1, Kyung-Hoon Choe 1, Sang Baek Koh 2, Jong Ku Park 2 Department of Internal Medicine, department of cardiology 1, Preventive Medicine and Institute of Occupational Medicine 2, Yonsei University, Wonju College of Medicine

2 Background Major Unmet Clinical Need LDL-C Classical Risk Factors BP Smoking Novel Risk Factors Metabolic syndrome HDL-C TNF IL-6 Insulin Abdominal Obesity Glu PAI-1 TG T2DM CARDIOVASCULAR DISEASE

3 Background Metabolic syndrome increases all-cause and vascular mortality: the Hong Kong Cardiovascular Risk Factor Study Table 2. Adjusted hazard ratios (and 95% confidence intervals) for all-cause and vascular disease mortality associated with the metabolic syndrome *P-value < Adjusted for age, gender (where appropriate), education, job activity, leisure-time activity frequency, smoking, use of alcohol. Thomas GN et al. Clin Endocrinol (Oxf) 2007 ;66:

4 Background Metabolic Syndrome and Ischemic Stroke Risk Northern Manhattan Study Figure 2. A comparison of vascular risk ratios for metabolic syndrome and each of its components. Boden-Albala B et al. Stroke. 2008;39:30-35.

5 Background Table IV. Target organ damage and cardiovascular complications in non-diabetic hypertensive patients in relation to the number of criteria of metabolic syndrome: ERIC-HTA study GFR, glomerular filtration rate. a Includes myocardial infarction, angina, heart failure, stroke and intermittent claudication. **p corresponding to linear association (chi-square trend) Table V. Odds ratio of the prevalence of target organ damage and cardiovascular disease in nondiabetic hypertensive patients with metabolic syndrome: ERIC-HTA study The reference group is the group of patients without metabolic syndrome. The adjusted odds ratios (Adj OR) are presented with their 95% confidence intervals. GFR, glomerular filtration rate. a Adjusted for age, sex, smoking, body mass index, cholesterol, systolic blood pressure and diastolic blood pressure. b Adjusted for the previous parameters and for left ventricle hypertrophy and altered kidney function. Blood Pressure. 2007; 16: 20 27

6 Background A comparison of the NCEP-ATPIII, IDF and AHA/NHLBI metabolic syndrome definitions with relation to early carotid atherosclerosis in subjects with hypercholesterolemia or at risk of CVD: Evidence for sex-specific differences Fig. 1. Association of IDF, NCEP-ATPIII and AHA/NHLBI metabolic syndrome with carotid atherosclerosis in (a) males, and (b) females. IMT median and plaque analysed using logistic regression analyses. All models include age, smoking status and LDL cholesterol. Results displayed as OR (95% CIs). *p 0.05, p Skilton MR et al. Atherosclerosis 2007 ;190:

7 Background A Cross-Sectional Study of the Effects of Type 2 Diabetes and Other Cardiovascular Risk Factors on Structure and Function of Nonstenotic Arteries of the Lower Limb Figure 1 Plot of SFA IMT (A), PA IMT (B), and SFA PWCV (C) against the number of factors of the metabolic syndrome present in a subject. The selected factors included hypertension, type 2 diabetes, increased WHR (men >1; women >0.85) (24), and hypertriglyceridemia ( 2.1 mmol/l) in association with decreased HDL cholesterol (<1.1 mmol/l) (25). Plot represents mean ± SD n (47) (44) (32) (20) (13) n (47) (44) (32) (20) (13) n (47) (44) (32) (20) (13) Metabolic syndrome components O Neal DN et al. Diabetes Care 2003;26:

8 Arterial Stiffness and Cardiovascular Outcome Table 1 Outcome studies of pulse wave velocity PWV, pusle wave velocity; CV, cardiovascular; ESRD, end-stage renal disease; CHD, coronary heart disease; CI, confidence interval; N/A, not available. Zoungas S et al. Clin Exp Pharmacol Physiol ;34(7):

9 Background The impact of metabolic syndrome and its components on pulse wave velocity Table 4. Multiple regression analysis of PWVs with age, gender and categorical risk factors BP, blood pressure; PWV, pulse wave velocity; ba, brachial-ankle; hf, heartfemoral; SE, standard error Kim YK. Korean J Med 2005;68:

10 The impact of metabolic syndrome and its components on pulse wave velocity Figure 1. Heart-femoral pulse wave velocity (hfpwv) and brachial-ankle pulse wave velocity (bapwv) according to the number of the components of metabolic syndrome (MS). Values are presented as mean±sd. The p value indicates p for the difference adjusted for age and gender among the groups. Figure 2. Heart-femoral pulse wave velocity (hfpwv) and brachial-ankle pulse wave velocity (bapwv) by the metabolic syndrome (MS) status. Values are presented as mean±sd. The p value indicates p for the difference adjusted for age, gender and blood pressure between the groups. Kim YK. Korean J Med 2005;68:

11 Brachial-ankle Pulse Wave Velocity in Koreans with the Metabolic Syndrome Fig. 1. Plot of bapwv According to the Number of Components of the Metabolic Syndrome Choi KM et al. (J Kor Diabetes Assoc 2004;28:36 44.

12 Objective few data of metabolic syndrome and subclinical surrogate measures such as echocardiographic LV geometry, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) for Korean general population especially by prospective cohort study Objective to identify and quantify relationships between the metabolic syndrome and subclinical surrogate measures echocardiographic LV geometry pulse wave velocity (PWV) carotid intima-media thickness (IMT)

13 Methods : Infra-Structure of Cohort

14 Methods : Survey Biochemical and Clinical data Disease History Socio-economic assessment Regular Follow-up and Lab. Assay Secure genetic resources. Serum -Plasma -DNA extraction

15 Methods : Echocardiography commercially available machine (Vivid 7 GE- Vingmed, Horten, Norway) with a 3.5-MHz transducer (GE-Vingmed, Horten, Norway) data analysis : Echopac system (GE-Vingmed, Horten, Norway). the American Society of Echocardiography guidelines Automatic wave form analyzer (PP-1000, hanbyul meditech Co, Korea)

16 Method (Study population) The Korean genomic regional cohort (KGRC) ongoing epidemiologic study senior population (40 < age 70 years) 3,508 Korean adult subjects 1,437 men (mean age; 56.9 ± 7.9) 2,071 women (mean age; 55.8 ± 8.1) Period From October to April

17 Method (Study population) 평창 768 명 원주 751 명 금산 1002 명 나주 987 명

18 ATP III: The Metabolic Syndrome Diagnosis is established when 3 of these risk fact ors are present Risk Factor ATP III IDF AHA/NHLBI Abdominal obesity (Waist Cir) Men Women 90 cm 80 cm necessity 90 cm 80 cm 90 cm 80 cm TG 150 mg/dl 150 mg/dl 150 mg/dl HDL-C Men Women <40 mg/dl <50 mg/dl <40 mg/dl <50 mg/dl <40 mg/dl <50 mg/dl Blood pressure 130/ 85 mm Hg 130/ 85 mm Hg 130/ 85 mm Hg Fasting glucose 110 mg/dl 100 mg/dl 100 mg/dl Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation And Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285: Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation 2005;112: The metabolic syndrome a new worldwide definition. Lancet 2005;366:

19 Results : Study Population Period : 1차 차 Korean Rural 4 Areas Age : Total N=3508 Wonju N=751 Mean age : 56.3±8.0 Male : 56.3% (n=1437) Echocardiogram N= 531 Mean age : 55.7±8.4 Male : 42.7% (n=227) Metabolic syndrome N=232 (43.7%) No metabolic syndrome N=299 (56.3%)

20 Result Baseline Characteristics Total (N = 531) Normal (N = 299) Metabloic syndrome (N = 232) P value Age (years) 55.7± ± ± Height (cm) 158.3± ± ± Weight (kg) 63.3± ± ± BMI (kg/m 2 ) 24.3± ± ± SBP (mmhg) 131.2± ± ± DBP (mmhg) 82.2± ± ± Hb (g/dl) 14.1± ± ± T.chol. (mg/dl) 206.2± ± ± TG (mg/dl) 169.8± ± ± HDL (mg/dl) 47.0± ± ± LDL (mg/dl) 11.7± ± ± BUN (mg/dl) 15.3± ± ± Cr (mg/dl) 0.94± ± ± hscrp (mg/dl) 2.2± ± ± Fasting insulin 8.9± ± ± Fasting Glc (mg/dl) 94.3± ± ±

21 Normal (N = 299) Result Baseline Characteristics Metabloic syndrome (N = 232) P value CVA (%) MI (%) CHF (%) HTN (%) <0.001 Hypercholeste rolemia (%) DM (%) <0.001

22 Result Echocardiographic Indeces Normal (N = 299) Metabloic syndrome (N = 232) P value LVIDd (mm/m 2 ) 31.6± ± LVIDs (mm/m 2 ) 20.8± ± LVM/BSA (g/m 2 ) 73.9± ± RWT 0.27± ± EF (%) 62.7± ± E (m/s) 0.72± ± A (m/s) 0.97± ± E (m/s) 0.12± ± E/E ratio 9.55± ±3.45 <0.001 LVH

23 Result Mean Echocardiographic Iindeces According to Number of Metabolic Syndrome Number on metabolic syndrome None Any 1 Any 2 All 3 P value LVIDd (mm/m 2 ) 32.7± ± ± ± LVIDs (mm/m 2 ) 21.2± ± ± ± LVM/BSA (g/m 2 ) 72.07± ± ± ± RWT 0.274± ± ± ± EF (%) 64.0± ± ± ± E/E ratio 9.05± ± ± ± IMT Avg 0.58± ± ± ± hfpwv 8.12± ± ± ± hrpwv 7.43± ± ± ± fapwv 10.08± ± ± ± hfpwv : heart to femoral pulse wave velocity hrpwv : heart to radial pulse wave velocity fapwv : femoral to ankle pulse wave velocity by ANOVA

24 Result Adjusted Mean Echocardiographic Iindeces According to Number of Metabolic Syndrome by ANCOVA LVIDd Total ±4.1 ±2.4 ±4.9 p=0.003 p=0.044 p=0.006 Men Women (mm) ± ±3.8 ± ±3.4 ±3.5 ± ±3.5 ±3.7 ± None Any 1 Any 2 All 3 Number of Metabolic Syndrome

25 Result Adjusted Mean Echocardiographic Iindeces According to Number of Metabolic Syndrome RWT Total by ANCOVA p=0.039 Men p=0.512 Women p= ±0.06 ±0.06 ±0.07 ±0.06 ±0.07±0.06 ±0.07 ±0.08±0.06 ± ±0.08 ± None Any 1 Any 2 All 3 Number of Metabolic Syndrome

26 Result Adjusted Mean Echocardiographic Iindeces According to Number of Metabolic Syndrome LVM/BSA (g/m 2 ) Total p=0.020 p=0.288 p=0.020 Men by ANCOVA Women ±26.1 ±22.4 ± ±15.5±8.8 ±17.9 ±21.1 ±21.6±18.2 ±20.4 ±22.4± None Any 1 Any 2 All 3 Number of Metabolic Syndrome

27 Result Adjusted carotid IMT According to Number of Metabolic Syndrome by ANCOVA IMT (mm) Total p=0.001 p=0.168 p=0.211 Men Women ± ± ±0.20 ±0.11 ±0.14±0.07 ±0.15 ±0.16±0.12 ±0.15 ±0.15±0.14 None Any 1 Any 2 All 3 Number of Metabolic Syndrome

28 Result Adjusted aortic PWV According to Number of Metabolic Syndrome by ANCOVA hrpwv (m/sec) Total 7.4 ±0.9 p=0.026 p=0.494 p=0.003 Men Women ±1.02±0.72 ±1.2 ±1.21±1.05 ±1.2 ±1.14±1.19 ±1.3 ±1.32 ±1.23 None Any 1 Any 2 All 3 Number of Metabolic Syndrome

29 Conclusions degree of metabolic syndrome clustering was strongly related to Total LV mass index LVIDd, RWT Carotid IMT hr PWV Men LVIDd Women LV mass index LVIDd hr PWV

30 Study Limitation Cross-sectional population-based study No proper study of disease history depended on history taking This is a ongoing study.

31 Future Direction Coronary Heart Disease Surrogates for atherosclerosis (IMT, PWV, AI, FMD) & LV mass index Component of metabolic syndrome non-traditioanl marker of atherosclerosis (fibrinogen, uric acid, non-hdl chol., microalbuminuria)

32