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. , MD, FESC, FAHA - - . - Slide 2 NCEP ATP III: The Metabolic Syndrome 102 cm (>40 in) >88 cm (>35 in) Men Women 110 mg/dL (6.0 mmol/L) Fasting glucose 130/85 mmHg Blood pressure HDL-C 150 mg/dL (1.7 mmol/L) TG Abdominal obesity (Waist circumference) Defining Level Risk Factor Recommends a diagnosis when 3 of these risk factors are present Adapted from NCEP, Adult Treatment Panel III, 2001. JAMA 2001:285;24862497. Slide 3 PREVALENCE OF METS IN GREECE Mets-Greece study (Athyros et al). 4056 adults. Prevalence 22.8%. Similar men and women. Increasing with age ( 4,7% 18-29y, 44,2% >60y). 62% 3 components, 28% 4, 10% all 5. 74th EAS Congress, Seville, 17-20 April 2004 ATTICA study (Panagiotakos et al). 2282 adults. Prevalence 19,8%. Men 25,2%, women 14,6%. Prevalence increased with age. Am Heart J 2004; 147: 106-12. Slide 4 The presence of the Metabolic Syndrome is associated with increased CHD, CVD and total mortality Unadjusted Kaplan-Meier hazard curves for men with and without the Metabolic Syndrome based on factor analysis. Median follow-up was 11.6 (9.1-13.7) years. Relative risks were determined by age-adjusted Cox proportional hazards regression analysis. Lakka HM et al, J Am Med Assoc 2002;288:2709-2716 Slide 5 2004 PPS Odds Ratio95% CIP Value Metabolic syndrome2.011.53-2.64 Declining HDL-C in the Population >12,000 respondents to a biennial population survey in the Pawtucket Heart Health Program Between 1981 and 1993, 0.08 mmol/L (3.1 mg/dL) decline Adjusted for other risk factor changes Reprinted from Ann Epidemiol, Vol. 8, Derby CA et al., 84-91, copyright 1998, with permission from Elsevier. HDL-C (mmol/L) 1.5 1.4 1.3 1.2 1.1 0.0 1.3 1.2 1.1 1.0 0.0 1.3 1.2 1.1 1.0 0.0 1.3 1.2 1.1 1.0 0.0 MenWomen 1.5 1.4 1.3 1.2 1.1 0.0 1.5 1.4 1.3 1.2 1.1 0.0 Nonsmokers Smokers Nonsmokers Smokers Alcohol No Alcohol Alcohol BMI Definitions and classification of office blood pressure levels (mmHg) CategorySystolicDiastolic Optimal< 120And< 80 Normal120-129And/or80-84 High normal130-139And/or85-89 Grade 1 hypertension 140-159And/or90-99 Grade 2 hypertension 160-179And/or100-109 Grade 3 hypertension > = 180And/or> = 110 Isolated systolic hypertension >= 140and< 90 Slide 29 BP Goals all be treated toSlide 30 Slide 31 Life style changes Salt A reduction to 5 g per day can decrease systolic blood pressure about 1 to 2 mm Hg in normotensive individuals and 4 to 5 mm Hg in hypertensive patients, he said. Wt loss Losing about 5 kg can reduce systolic blood pressure by as much as 4 mm Hg, aerobic endurance training can reduce systolic blood pressure 7 mm Hg Slide 32 When to start drug Rx Consider BP level and correlate with overall risk: cardiovascular risk factors overt cardiovascular disease asymptomatic organ damage diabetes chronic kidney disease. Slide 33 Slide 34 Asymptomatic Target Organ Damage (TOD) Pulse pressure ( in the elderly) >= 60 mmHg Electrocardiograhic LVH( Sokolow-Lyon index > 3.5 mV; RaVL > 1.` mV; Cornell voltage duration product> 244 mV* ms), or Echocardiographic LVH [ LVM index: men > 115 g/m2; women > 95 g/m2 (BSA)]a Carotid wall thickening (IMT > 0.9 mm) or plaque Carotid- femoral PWV > 10 m/s Ankle- brachial index < 0.9 CKD with Egfr 30-60 ml/min/1.73 m2 (BSA) Microalbuminuria (30-300 mg/24 h), or albumin- creatinine ratio(30-300 mg/g; 3.4-34 mg/mmol) (preferentially on morning spot urine) Slide 35 Slide 36 Combination Rx For patients at high risk for cardiovascular events or those with a markedly high baseline blood pressure In those at low or moderate risk for cardiovascular events or with mildly elevated blood pressure, a single starting agent is preferred. For a high-risk individual, you can't play around with one drug after another, trying to control blood pressure Slide 37 Drugs to be preferred in specific conditions Slide 38 Compelling and possible contra-indications to the use of antihypertensive drugs Slide 39 Effects of lipid-lowering therapy on CHD events in statin trials 25 20 15 10 5 0 Patients with CHD event (%) 90110130150170190210 S=statin treated P=placebo treated *Extrapolated to 5 years 4S-P CARE-P LIPID-P 4S-S WOSCOPS-S -P AFCAPS-P -S LIPID-S CARE-S Primary Prevention Simvastatin Pravastatin Lovastatin Modified from Kastelein JJP. Atherosclerosis. 1999;143(Suppl 1): S17-S21. HPS-S -P Atorvastatin ASCOT-S * -P * Secondary Prevention LDL-C (mg/dL) Slide 40 Metabolic syndrome was based on the updated NCEP ATP III definition, 1 and was defined as 3 of the following prior to open-label run-in: Waist circumference: Men 40 inches (102 cm); Women 35 inches (88 cm)* Waist circumference: Men 40 inches (102 cm); Women 35 inches (88 cm)* Triglycerides 150 mg/dL ( 1.7 mmol/L) Triglycerides 150 mg/dL ( 1.7 mmol/L) HDL-C: MenSlide 41 Time to First Major Cardiovascular Event in Patients with Metabolic Syndrome (MetS) Time (years) Metabolic Syndrome Subgroup Cumulative incidence of major cardiovascular events* *Coronary heart disease death, nonfatal nonprocedure- related myocardial infarction, resuscitated cardiac arrest, fatal or nonfatal stroke Deedwania P et al. Lancet. 2006;368:919-928. Metabolic syndrome, no diabetes Atorvastatin 10 mg (n=2191) Atorvastatin 80 mg (n=2162) HR = 0.70 (95% CI: 0.57, 0.84) P=.0002 All metabolic syndrome Atorvastatin 10 mg (n=2820) Atorvastatin 80 mg (n=2764) HR = 0.71 (95% CI: 0.61, 0.84) P Smoking Cessation Increases HDL-C Level In study by Moffatt, smokers had HDL-C levels 1520% lower than nonsmokers (P < 0.05). 1 PROCAM showed less of an effect of smoking on HDL-C (7% lower than nonsmokers). 2 HDL-C levels returned to normal within 3060 days after smoking cessation. 1 In eight women who smoked > 1 packs per day for 5 years, HDL-C levels increased from 51 to 64 mg/dL after quitting for 60 days. 1 1. Moffatt RJ. Atherosclerosis 1988;74:8589 2. Cullen P et al. Eur Heart J 1998;19:16321641 Slide 55 Weight and HDL-C Inverse correlation between body weight and HDL-C is consistently observed in both men and women. For every 3 kg of weight loss, HDL-C levels increase 1 mg/dL. Dattilo AM, Kris-Etherton PM. Am J Clin Nutr 1992;56:320328 Slide 56 Caloric Restriction Acutely Lowers HDL-C Level Trials of very-low-calorie diets show that HDL-C levels decrease by 212 mg/dL during acute caloric restriction. After 12 wks, HDL-C returned to pretreatment range, and this trend was still apparent after 1 year. Therefore, benefits of weight-loss programs should not be assessed during acute caloric restriction. Rssner S et al. Atherosclerosis 1987;64:125130 Slide 57 Alcohol Increases HDL-C Level Alcohol increases HDL-C level in a dose-dependent manner. Half bottle of wine per day (39 g alcohol) for 6 weeks significantly increased mean HDL-C level by 7 mg/dL in 12 healthy subjects. 1 Wine intake did not significantly affect Total-C, Total-TG, or LDL-C. 1 One beer per day (13.5 g alcohol) for 6 weeks significantly increased mean HDL-C level by 2 mg/dL in 20 healthy subjects. 2 Beer intake did not significantly affect LDL-C, VLDL-C, TG, or apolipoproteins. 1. Thornton J et al. Lancet 1983;ii:819822 2. McConnell MV et al. Am J Cardiol 1997;80:12261228 Slide 58 Slide 59 Slide 60 HDL-C Response to Pharmacological Intervention Slide 61 ACCORD Study Design Overall ACCORD Glycemia Trial: 10,251 participants Lipid Trial: 5,518 in Lipid Trial 2765 randomized to fenofibrate 2753 randomized to placebo Primary Outcome: First occurrence of a major cardiovascular event (nonfatal MI, nonfatal stroke, cardiovascular death) 87% power to detect a 20% reduction in event rate, assuming placebo rate of 2.4%/yr and 5.6 yrs follow-up in participants without events. Slide 62 ACCORD Lipid Trial Eligibility Stable Type 2 Diabetes >3 months HbA1c 7.5% to 11% High risk of CVD events = clinical or subclinical disease or 2+ risk factors Age (limited to