Metabolic syn and CVD { Dr : dehestani Imam reza hospital
Global Distribution of CVDs as Causes of Death, WHO 2011
Worldwide Mortality from Ischemic Heart Disease and Cerebrovascular Disease 2011 Ischemic Heart Disease Cerebrovascular Disease
Metabolic Syndrome (History) 1923 - Kylin first to describe the clustering of hypertension, hyperglycemia, hyperuricemia 1936 - Himsworth first reported Insulin insensitivity in diabetics 1965 - Yalow and Berson developed insulin assay and correlated insulin levels & glucose lowering effects in resistant and nonresistant individuals
1988 - Reaven in his Banting lecture at the ADA meeting coined the term Syndrome X and brought into focus the clustering of features of Metabolic Syndrome Reaven now prefers the name, Insulin- Resistance Syndrome - feels insulin resistance is the common denominator for Metabolic Syndrome Literature now extensive
Other Names Used: Syndrome X Cardiometabolic Syndrome Cardiovascular Dysmetabolic Syndrome Insulin-Resistance Syndrome Metabolic Syndrome Beer Belly Syndrome Reaven s Syndrome etc.
ميزان شيوع در ايران و جهان سندرم کل ي شيوع گرفته صورت بررسي چند اساس بر متابوليك در جمعيت ايراني حدود %33 و در زنان به طور معنيداري بيشتر از مردان است )%40(. بررسيها نشان ميدهد که شيوع سندرم متابوليك در ايران به مراتب بيش از آمريكا و اروپا )%25( و بسياري از کشورهاي ديگر آسيايي است %41 به سال پنجاه باالي سنين در آن شيوع بهطوريکه ميرسد.
Clustering of Components: Hypertension: BP. > 140/90 Dyslipidemia: TG > 150 mg/ dl ( 1.7 mmol/l ) HDL- C < 35 mg/ dl (0.9 mmol/l) Obesity (central): BMI > 30 kg/m2 Waist girth > 94 cm (37 inch) Waist/Hip ratio > 0.9 Impaired Glucose Handling: IR, IGT or DM FPG > 110 mg/dl (6.1mmol/L) 2hr.PG >200 mg/dl(11.1mmol/l) Microalbuninuria (WHO)
The metabolic syndrome, a cluster of glucose intolerance and hyperinsulinemia accompanied by hyper triglyceridemia, low HDL levels, hypofibrinolysis, hypertension, microalbuminuria, a predominance of small dense LDL particles, and central obesity
Although several formal definitions of the metabolic syndrome have been proposed, the definition adopted by the National Cholesterol Education Program Adult Treatment Panel requires at least three of the followingfive criteria: (1) waist circumference larger than 102 cm in men and 88 cm in women; (2) serum triglyceride levels of at least 150 mg/dl; (3) HDL cholesterol less than 40 mg/dl in men and less than 50 mg/dl in women; (4) blood pressure of at least 130/85 mm Hg; and (5) serum glucose concentration of at least 110 mg/dl. Using these criteria, metabolic syndrome has a prevalence of almost 25% (affecting almost 50 million persons) in the United States alone
the definition of metabolic syndrome varies among various national guidelines and statements. Some of these criteria require measurement of insulin resistance whereas others, including the Adult Treatment Panel III criteria, use variables readily available from a standard clinical evaluation various risk factors in the definition of metabolic syndrome. Moreover, controversy continues regarding insulin resistance as a unifying pathophysiologic pathway that accounts for all of the features of the so-called metabolic syndrome
Insulin resistance and diabetes rank among the major cardiovascular risk factors; the presence of diabetes confers an equivalent risk to aging 15 years, an impact comparable with if not greater than that of smoking
Almost 35 million people in the United States have some degree of abnormal glucose tolerance, a condition along with obesity that markedly increases the risk for type 2 diabetes and premature athero thrombosis
Patients with diabetes have twofold to eightfold higher rates of future cardiovascular events as compared with age- and ethnically matched nondiabetic subjects, and 75% of all deaths in diabetic patients result from coronary heart disease. Compared with unaffected persons, diabetic patients have a greater atherosclerotic burden in the major arteries, as well as of microvascular disease
Not surprisingly, diabetic patients have substantially increased rates of atherosclerotic complications in the settings of primary prevention and after coronary interventional procedures. Insulin resistance alone confers an elevated risk of congestive heart failure and probably explains the association of obesity with this common vascular complication. Moreover, the risk of cardiovascular disease starts to increase long before the onset of clinical diabetes.
Although hyperglycemia is associated with microvascular disease,insulin resistance itself promotes atherosclerosis even before it produces frank diabetes, and available data corroborate the role insulin resistance as an independent risk factor for atherothrombosis. This finding has prompted recommendations for increased surveillance for the metabolic syndrome, a cluster of glucose intolerance and hyperinsulinemia accompanied by hypertriglyceridemia, low HDL levels, hypofibrinolysis, hypertension, microalbuminuria, a predominance of small dense LDL particles, and central obesity
the metabolic syndrome have elevated vascular event rates. In the Kuopio Ischaemic Heart Disease Risk Factor Study, patients with metabolic syndrome showed markedly increased rates of coronary, cardiovascular, and all-cause mortality. Other analyses focus on abnormalities of fasting glucose and reach similar conclusions the metabolic syndrome have elevated vascular event rates.
Global cardiometabolic risk* working definition Gelfand EV et al, 2006; Vasudevan AR et al, 2005
Fat Topography In Type 2 Diabetic Subjects Intramuscular Subcutaneous Intrahepatic Intraabdominal FFA* TNF-alpha* Leptin* IL-6 (CRP)* Tissue Factor* PAI-1* Angiotensinogen*
Patients with abdominal obesity often present with one or more additional cardiovascular risk factors (NCEP ATP III criteria) Abdominal obesity is linked to multiple cardiometabolic risk factors Cardiovascular risk factor Parameters Increased waist circumference Men 102 cm (40 in) Women 88 cm (35 in) Elevated LDL- Cholesterol Elevated triglycerides > 2.6 mmol/l (> 70 mg/d ) 1.7 mmol/l ( 150 mg/dl) Low HDL- Cholesterol Men <1.03 mmol/l (<40 mg/dl) Women <1.30 mmol/l (<50 mg/dl) Hypertension BP 130/80 mm Hg Elevated fasting glucose 6.1 mmol/l ( 110 mg/dl)
Adjusted relative risk Abdominal obesity and increased risk of cardiovascular events The HOPE study 1.4 Waist circumference (cm): 1.29 Tertile 1 Tertile 2 Tertile 3 Men <95 95 103 >103 1.27 Women <87 87 98 >98 1.35 1.2 1.17 1.16 1.14 1 1 1 1 0.8 CVD death MI All-cause deaths Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-c; CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index; DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol Dagenais GR et al, 2005
Relative risk Abdominal obesity increases the risk of developing type 2 diabetes 24 20 16 12 8 4 0 <71 71 75.9 76 81 81.1 86 86.1 91 91.1 96.3 >96.3 Waist circumference (cm) Carey VJ et al, 1997
Relative risk Abdominal obesity is linked to an increased risk of coronary heart disease Waist circumference has been shown to be independently associated with increased age-adjusted risk of CHD, even after adjusting for BMI and other cardiovascular risk factors 3.0 2.5 2.0 p for trend = 0.007 2.06 2.31 2.44 1.5 1.0 0.5 0.0 1.27 <69.8 69.8 <74.2 74.2 <79.2 79.2 <86.3 86.3 <139.7 Quintiles of waist circumference (cm) CHD: coronary heart disease; BMI: body mass index Rexrode KM et al, 1998
Intra-abdominal adiposity is a major contributor to increased cardiometabolic risk IAA = high risk fat Associated with inflammatory markers (C-reactive protein) Dyslipidaemia Free fatty acids Insulin resistance Increased cardiometabolic risk Secretion of adipokines ( adiponectin) Inflammation IAA: intra-abdominal adiposity
Abdominal obesity: a major underlying cause of acute myocardial infarction PAR (%) a 60 40 20 Cardiometabolic risk factors in the INTERHEART Study 49 20 Abdominal obesity predicts the risk of CVD beyond BMI 18 10 0 Abnormal Abdominal Hypertension Diabetes lipids obesity a Proportion of MI in the total population attributable to a specific risk factor; CVD: cardiovascular disease; BMI: body mass index; PAR: population attributable risk; MI: myocardial infarction
mg/dl mg/dl Intra-abdominal adiposity and dyslipidaemia Triglycerides HDL-cholesterol 310 60 248 186 124 45 62 0 30 Lean Low High Lean Low High Visceral fat (obese subjects) Visceral fat (obese subjects) HDL: high-density lipoprotein Pouliot MC et al, 1992
Persons with predominantly subcutaneous fat, in the gynoid or pear distribution, have less cardiovascular risk for a given body mass index than those with the centripetal android or apple pattern associated with visceral adiposity. Some obese persons do not develop insulin resistance or other cardiovascular risk factors related to the metabolic syndrome. This observation has given rise to the concept of the fit fat. For this reason, body mass index itself may not predict incremental cardiovascular risk as well as do biomarkers of systemic inflammation
The most recent definition of metabolic syndrome from the National Heart, Lung and Blood Institute (NHLBI) includes a pro inflammatory state. Thus inflammatory biomarkers such as hscrp may help further stratify clinical risk and improve the prognostic value of metabolic syndrome. For example, data from the Women s Health Study have indicated that an hscrp level greater than 3 mg/liter adds important prognostic information about cardiovascular risk at all levels of the metabolic syndrome, whereas those with levels less than 1 mg/literare at substantially lower risk86
Odds of CVD Stratified by CRP Levels in U.S. Persons (Malik and Wong et al., Diabetes Care 2005; 28: 690-3) O d d s R a t i o 6 5 4 3 2 1 0 * * *** *** ** High CRP No disease Metabolic Syndrome Diabetes Low CRP *p<.05, **p<.01, **** p<.0001 compared to no disease, low CRP CRP categories: >3 mg/l (High) and <3 mg/l (Low) age, gender, and risk-factor adjusted logistic regression (n=6497)
Because traditional risk algorithms and metabolic syndrome definitions do not capture inflammation explicitly, integrating features of the metabolic syndrome may explain part of the usefulness of hscrp in adding to cardiovascular risk prediction to traditional instruments such as the Framingham algorithm. Obesity and intra abdominal fat, which require imaging studies for rigorous definition account for part, but not all, of hscrp s ability to refine cardiovascular risk prediction
metabolic syndrome