控制心血管危险因素苏大成

控制心血管危险因素：来自台 湾的经验和教训 Risk Factor Control for Cardiovascular Disease: lessons from Taiwan Ta-Chen Su, MD, PhD Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine Email: .tw Cardiovascular Disease Prevention WHO report on CVD prevention: (2003, 2006) 1. A population Strategy 2. A high-risk strategy 3. A secondary prevention strategy Clinical strategies: primary and secondary prevention 1. CVD risk factors, single or multiple or total 2. All patients with atherosclerotic CVD Wood et al. Dialogues in Cardiovascular Medicine 2009;14:83 Population Strategy (群體策略） Evidence of hypertension control in Taiwan, 1993-2002 2002-2007 follow-up study: 1. 3H and incidence of CVD 2. Trends of 3H and Metabolic syndrome The Chin-Shan Community Cardiovascular Cohort (CCCC) Study in Taiwan Early Atherosclerosis Study in Young Adult 2002台灣地區三高（高血壓、高 血糖、高血脂）調查 Evidence for Improved Control of Hypertension in Taiwan: 1993-2002 2002 Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) Su et al, J Hypertens 2008; 26;600-608. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) 2002 TwSHHH is the second nationwide survey, which was designed to assess the prevalence, awareness, treatment, and control of hyperglycemia, hyperlipidemia, and hypertension during 2002 Applied a multi-stage, stratified, and random sampling during 2002 with a total of 7566 participants from 1,648 Neighborhoods (鄰) of 68 precincts/ townships (鄉鎮市區) in Taiwan. Su et al. J Hypertens 2008;26:600- 6. Figure 1-1 Prevalence of Hypertension in the Taiwanese Populations, NAHSIT vs. TwSHHH Figure 1-2 Prevalence of Hypertension in the Taiwanese Populations, NAHSIT vs. TwSHHH Figure 1-3 Prevalence of Hypertension in the Taiwanese Populations, NAHSIT vs. TwSHHH Age group Male Figure 1-4 Prevalence of Hypertension in the Taiwanese Populations, NAHSIT vs. TwSHHH Age group Female Figure 1-5 Prevalence of Hypertension in the Taiwanese Populations, NAHSIT vs. TwSHHH Body mass index, Kg/m2 BMI Table 3 Trends in Hypertension Awareness, Treatment, and Control in the Adult Population during Two Nationwide Surveys in Taiwan P 6 month Exam: Biannual follow-up of physical examinations, electrocardiogram, glucose, lipid profile, urine, echocardiogram, and carotid duplex End-points: newly onset of DM, Hypertension, and CVD morbidity and mortality Lee et al. J Clin Epidemiol 2000 Su et al. Stroke 2001; Chien et al. Stroke 2002 Chien et al. Diabetologia 2009; Clin Chem 2008. The Chin-Shan Community Cardiovascular Cohort (CCCC) Study in Taiwan Chin-Shan: a sub-urban community 40 kilometers outside the metropolitan Taipei in northern Taiwan Area: 49.21 square kilometers Population: 18,728 (men: 9907, women: 8821) in 1990. =35 years old: 4349 Inclusion: 3,602 residents, (82.8% response rate) Men: 1703 (47.3%), Women: 1899 (52.7%) Chin-Shan Taipei Risk factorsHazard riskLower 95% CI Upper 95% CIP value Age (+1year)1.061.041.070.5 to 0.20.2-0.90.9 No. of events/participants 52/17959/17756/7863/179 Rate/1000 person-years 56.865.163.269.0 Model 1a1(reference)1.43(0.98-2.08)1.64(1.11- 2.41) 1.65(1.13- 2.41) 0.007 1.14(1.02-1.27) Model 2b1(reference)1.49(1.02-2.19)1.68(1.13- 2.48) 1.70(1.16- 2.49) 0.005 1.13(1.01-1.27) Model 3c1(reference)1.55(1.04-2.31)1.81(1.21- 2.69) 1.81(1.22- 2.68) 0.002 1.16(1.03-1.30) Women (n=853) Range(kg/m2) -0.50.5 to 0.30.3-1.11.1 No. of events/participants 76/21363/21360/21383/214 Rate/1000 person-years 69.7 Model 1a1(reference)1.00(0.72-1.41)0.85(0.60-1.20)1.25(0.91-1.72) 0.26 1.10(1.02-1.19) Model 2b1(reference)1.01(0.72-1.42).85(0.60-1.201.25(0.91-1.73) 0.25 1.10(1.02-1.19) Model 3c1(reference)1.04(0.73-1.47)(0.88(0.62-1.26)1.27(0.91-1.76) 0.24 1.10(1.01-1.19) Model 4d1(reference)1.10(0.77-1.57)0.94(0.65-1.36)1.46(1.04-2.06) 0.058 1.12(1.03-1.22) a Adjusted for age, BMI and DBP at baseline. b Adjusted for variables in model 1 as well as occupation, smoking, alcohol consumption and exercise at baseline. c Adjusted for variables in variables in model 2 and LDL and TG. d Adjusted for variables in model 3 and menopausal status. Chen et al. J Hypertens 2009;27:1370 Table Hazard ratio(95% confidence interval) of incident hypertension during follow-up period in relation to BMI change (2 years: 19901993 F/U at 2000) 兒童時期與現在心血管因子的變化與 年輕成年人心血管危險因子及早期動 脈硬化的風險 Changes of CVD Risk Factors between Childhood and Adulthood, and the Risk of Early Atherosclerosis in Young Adult 128,413 students with twice of positive urine screening Excluded 24,561 with unreliable BP 96 with unknown urine screening 9227 with HTN94529 with no HTN 5753 with address59855 with address 1251 in Taipei area17448 in Taipei area 303/1336 received CV examination Response rate = 22.7 % 487/3850 received examination Response rate = 12.6 % Only via MailVia Telephone and Mail 3474 with no address34674 with no address 平均12.5歲的青少年有兩次以上有尿液 異常者，約九年後邀請回台大醫院接受心 血管及血液檢查（頸動脈內中皮厚度） 2006-2008年 Taipei Area 總共有791位 接受追蹤 Table 2-1 CVD Risk Factors Stratified by BMI 273.12 (1.079.10)*5.58 (2.7011.54) Childhood Adulthood 1 2 O.R. BMI 270.85 (0.282.56)3.33 (1.656.74) Childhood Adulthood 3 4 5 6 1 1.17 0.85 1.12 2.99 3.33 + + + Change of BMI and Risk of Thicker Carotid IMT in Young Adult IMT 75th percentile 結 論 青少年肥胖與血壓與年輕成年時早期動脈 硬化有關 青少年時期肥胖與心血管危險因子皆會影 響其年輕成年時之肥胖與心血管危險因子 A high-risk strategy (Familial Hypercholesterolemia) A secondary prevention strategy (PCI for AMI Patients) Genetic Study of Familial Hypercholesterolemia in Taiwan 家族性高膽固醇血症 Methods Cascade screening for FH FHChip (a resequencing microarray) for index case MLPA (Multiplex ligation-dependent probe amplification) for those without findings Tsais Family 54 444 172 43 367 30 182 211 52 79 15 129 59 50 62 49 192 36 58 106 53 210 205 43 139 用藥中 51 425 82 67 328 44 163 85 44 99 27 226 74 74 118 54 243 125 51 158 28 144 80 44 75 27 152 45 51 75 25 205 99 53 132 28 171 86 54 98 27 367 140 38 301 49 236 281 41 139 Age TCHO TG HDL LDL LDLRexon02 Dup LDLRexon03 Dup LDLRexon04 Dup LDLRexon05 Dup LDLRexon06 Dup 20 539 81 43 362 25 167 92 53 96 Pans Family 50 272 108 72 178 24 141 51 43 64 Age TCHO TG HDL LDL LDLRexon03 GR at 268 D69D,N LDLRexon07 GR at 986 C308C,Y Table 3 Lipids levels and cardiovascular characteristics in single mutation and complex mutations of heterozygous familial hypercholesterolemia Complex mutations n=23 Single mutations n=161 p-value CHO, mg/dl432.13100.60294.7866.30.0001 TG, mg/dl 140.57153.77110.3057.820.3599 HDL, mg/dl54.2614.8057.4920.940.4770 LDL, mg/dl333.7491.70204.9864.35.0001 Age, years43.3518.3742.4217.010.8088 Male, %69.57 40.990.0099 BMI, kg/m2 21.732.60 22.774.070.1069 Waist, cm 74.9110.2975.3411.660.8694 HTN, % 26.0916.770.2596 SBP, mmHg113.2515.78113.2616.820.9978 DBP, mmHg68.4112.2170.6910.710.3510 DM, %8.703.110.2127 Sug AC, mg/dl97.9128.7892.4317.520.3928 Smoke, %26.0911.180.0887 Alcohol, %8.709.941.0000 CAD, %34.783.73.0001 Xanthoma, %43.481.24.0001 ApoE4, % 8.7013.660.7443 ApoA5, %13.0411.800.9597 Complex mutations include compound heterozygote, Single allele double mutations, and large chromosome mutations Conclusions Most FH are heterozygote and higher rate of complex mutations (compound heterozygote or single allele double, or large chromosome) were found in this study. MLPA have some important role in patients with severe hypercholesterolemia and tendon xanthoma but without point mutations found. Most patients have good response to combination therapy with statins and Ezetamibe. Treating FH: High-risk patients approach 治療家族性高膽固醇血症即是高危險群策略的 例子 Long-term outcomes of elective PCI either with or without prior fibrinolysis vs. primary PCI in patients with AMI Methods We retrospectively collected data from detailed chart review for patients with AMI through 1994 to 2000 in National Taiwan University Hospital (NTUH). Patients with first time diagnosis of AMI and received PCI with or without TT within 28 days were registered and matched for the mortality at 2006. Primary endpoints included mortality of all-cause, cardiovascular disease (CVD, ICD-9 code 390-459), and coronary heart disease (CHD, ICD-9 code 410-414) was compared in different reperfusion strategies. Cox proportional regression analyses were applied to estimate the hazards ratio of different reperfusion strategies and other prognostic factors. Table 1 Baseline Characteristics of the Patients According to Register Strategy Primary PTCA n=202 PTCA n=336 TT+PTCA n=181 TT n=162 MRO n=445 p-value p-value Follow-up Yr7.532.608.133.048.873.107.284.094.244.31 .0001.0001 Yr (Min-Max) 7.95(0.0011.57)8.48(0.0412.98)9.28(0.0012.99)8.41(0.0012.97)2.51(0.0012.97) (Q1-Q3) 7.95(7.299.00)8.48(7.2610.25)9.28(7.8311.19) 8.41(3.7010.75)2.51(0.107.85) Age 58.4912.7861.5111.7858.7710.9161.3912.9769.8211.66 .00010.0071 Male82.67%80.06%83.43%88.89% 66.97% .00010.1082 HTN45.54%52.68%46.41%44.44% 59.10%0.0010.2199 DM 21.29%23.51%19.89%22.22% 33.03% 0.00060.8058 CAD 11.39%9.82%8.29%11.11% 22.47% .00010.7449 Statin 20.30%12.50%15.47%5.56% 5.62% .00010.0006 Smoke 65.35%61.31%63.13%63.58% 47.75% .00010.8221 Smoking 55.45%52.38%56.98%57.41% 38.29% .00010.6571 Killip I 67.82%71.13%71.67%62.96% 41.99% .0001.0001 II 18.32%15.48%17.22%22.84% 13.09% III 3.47%11.90%5.56% 4.94% 23.70% IV 10.40%1.49%5.56%9.26% 21.22% MI Ant 52.97%56.25%61.88%54.32% 58.12% 0.42450.3263 Inf 47.03%43.75%38.12%45.68% 41.88% Q MI67.82%58.33% 74.59%68.52%58.43%0.00060.0019 Cath 17 days 40.48% 26.52%0.0067 814 days 41.96% 51.93% 1528 days 17.56%21.55% All-cause Mortality CVD Mortality CHD Mortality Cath day after AMIAllTT+PCIPCI 17 days vs. 1528 days0.06630.21500.3631 814 days vs. 1528 days 0.03440.09500.0550 17 days vs. 814 days0.84220.57750.4074 All-cause Mortality 接受TT+PCI 或 Elective PCI 者， 在兩星期接受 PCI治 療者，預後較好。 Table 3 Cox Proportional Hazard Regression Models for the Predictors of Primary Outcomes Hazards Ratio (95% CI) Variables All causeCVD CHD Age 70 2.58 (1.91-3.47).00011.91 (1.29-2.83)0.00132.14 (1.28-3.58)0.0038 55Age 70 1.42 (1.06-1.92)0.02091.24 (0.84-1.84)0.28121.64 (0.99-2.73)0.0559 Gender 0.96 (0.78-1.19)0.71681.05 (0.79-1.39)0.76011.29 (0.90-1.83)0.1653 Killip IV3.90 (3.08-4.95).00014.81 (3.54-6.54).00016.12 (4.23-8.87).0001 Killip III2.21 (1.76-2.79).00012.3 (1.66-3.17).00012.88 (1.94-4.27).0001 Killip II1.19 (0.93-1.53)0.17351.18 (0.83-1.69)0.35981.38 (0.89-2.15)0.1507 DM 1.67 (1.39-2.00).00011.33 (1.03-1.71)0.03021.23 (0.90-1.68)0.1912 Hypertension1.03 (0.86-1.22)0.75221.07 (0.85-1.36)0.56110.93 (0.70-1.23)0.6091 CAD Hx1.31 (1.06-1.62)0.01381.48 (1.12-1.96)0.00591.63 (1.17-2.26)0.0037 Smoking 0.91 (0.75-1.09)0.30400.75 (0.58-0.96)0.02280.74 (0.55-1.01)0.0543 Primary PTCA0.33 (0.24-0.45).00010.28 (0.18-0.44).00010.32 (0.19-0.53).0001 Delayed PTCA 0.34 (0.27-0.43).00010.22 (0.15-0.32).00010.20 (0.13-0.33).0001 TT + Delayed PTCA 0.30 (0.21-0.41).00010.31 (0.20-0.47).00010.30 (0.17-0.51).0001 TT 0.59 (0.45-0.78)0.00020.68 (0.48-0.97)0.03440.61 (0.39-0.95)0.0279 Q MI 1.07 (0.90-1.27)0.47171.24 (0.97-1.58)0.08301.49 (1.10-2.02)0.0093 Note: MRO as reference group; TT, thrombolytic therapy, mainly tissue-type plasminogen activator Late Open Never Too Late Long-term beneficial effect of late reperfusion for AMI with PCI in some randomized trials (Horie, Circulation 1998), in stable survivors of AMI (Zeymer, Circulation 2003), and ACS with prior CABG in a national registry (Held, EHJ 2007) Meta-analysis showed better outcome for delayed PCI (JACC 2008), Routine PCI after Fibrinolysis (NEJM 2009 June) Mechanism: patent IRA, improved LV function, prevent LV dilation and beneficial LV remodeling NCEP ATP III Guideline for ACS Patients NCEP ATP III Guideline建議 所有因急性冠心病而住院的 病人都應積極使用Statin治療 Circulation. 2004;110:227-239 2007 ACC/AHA guideline for STEMI - Lipid Management JACC 2008; 51:21047 STEMI 病人最好能將其低密度膽固醇降低至 70 mg/dL 2007 ACC/AHA guideline for UA/NSTEMI - Lipid Management JACC 2007;50:652726 2007 ACC/AHA guideline建議, 針對 UA/NSTEMI的病人,不管 其LDL-C的baseline為何,均應 給予Statin積極治療, 治療目標 為LDL-C 100mg/dl, 理想的 治療目標為LDL-C70mg/dl 結 論 急性心肌梗塞病人應積極介入治療，若未 能馬上接受(Primary PCI)，也能在28天內 （最好在一至二星期內）給與經皮冠狀動 脈血管介入性治療，長期追蹤其預後是相 當好。 急性心肌梗塞病人，無論哪一種治療，若 能給與Statins，其預後會較好。 Conclusions 總結 群體策略：國家衛生政策及行政 臨床策略：經由醫師及衛生相關專業團隊共同努力 高危險群策略：高膽固醇、高血壓、高血糖、肥胖 、代謝症候群、吸煙 續發性預防策略：積極教育及治療冠心病病患、腦 中風病患 我們需要的策略是好的群體策略而非個人策略 Treating sick population is more important than treating sick individuals. 要預防心血管疾病，高危險群介入治療是不夠的， 必須群體策略與高危險群策略兼顧。 政府、醫師、藥廠、保險團體一起合作 Acknowledgements Yuan-Teh Lee, MD, PhD Ming-Fong Chen, MD, PhD Chiau-Suong Liau, MD, PhD Kuo-Liong Chien, MD, PhD Fung-Chang Sung, MPH, PhD Jung-Der Wang, MD, DSc Chien-Jen Chen, MPH, DSc Chang-Chuan Chan, MPH, DSc Jiann-Shing Jeng, MD, PhD Pao-Ling Torng,