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Syndrome X & Cardiac Effects Do You Know Everything You Should?

Syndrome X & Cardiac Effects Do You Know Everything You Should?. Julia Garrison RN, MSN, CCRN, PCCN. Code 266 Proceedings Book pg. 641. Statistics. 24% of the adult population have Metabolic Syndrome X (Met Syn X) and the prevalence reaches 50-60% over age 50 years. Statistics.

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Syndrome X & Cardiac Effects Do You Know Everything You Should?

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  1. Syndrome X & Cardiac EffectsDo You Know Everything You Should? Julia Garrison RN, MSN, CCRN, PCCN Code 266 Proceedings Book pg. 641

  2. Statistics 24% of the adult population have Metabolic Syndrome X (Met Syn X) and the prevalence reaches 50-60% over age 50 years.

  3. Statistics Soon metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population.

  4. JAMA 287:356, 2002

  5. Statistics 50% of hypertensive pts and 10% of those with normal blood pressure having evidence of hyperinsulinemia.

  6. Statistics In Framingham, the metabolic syndrome alone predicted approximately 25% of all new onset CVD.

  7. Prediction The epidemic of insulin resistance syndrome will prevent our ability to improve rates of CVD, which currently accounts for half of deaths among men and one-third of deaths among women.

  8. Risk Factors • For Women • Android Appearance Alopecia Hirsutism Central obesity • History Amenorrhea Infertility Gestational diabetes Birth of baby > 9 lbs • For Men & Women • Physical Assessment Acanthosis Nigricans Skin Tags

  9. Are you one of the “Lucky” ones? • PCOS (Polycystic Ovary Syndrome) • The most common endocrinopathy of women, • present in 4-7% of women • Younger persons with CHD • Metabolic syndrome is particularly likely • to be present • Not Diabetic? • Approximately one in five nondiabetic persons • will develop the metabolic syndrome over the • next 5 years

  10. Why Do We Care? Insulin resistance will lead to type 2 diabetes and subsequent CHD

  11. Does This Person Sound Familiar? E.C. - a 53 year old postmenopausal female -referred for tx of hypertension, with a family hx of T2D, hypertension, and CHD. She has felt well, postmenopausal symptoms had responded to hormone replacemnt tx. BP was “too high” during routine physical exam. BMI 23.7kg/m2, BP145/95. Lab results revealed a normal blood count and urinalysis, with glucose 102, triglycerides 238, LDL 147, HDL 40

  12. How do we define it? • The syndrome was first identified in 1988 • ICD –9 diagnostic code 277.7

  13. Major Characteristics of Met Syn X • insulin resistance/ glucose intolerance • abdominal obesity • elevated blood pressure • lipid abnormalities (elevated levels of triglycerides and low levels of high density lipoprotein HDL) • Proinflammatory state • prothrombotic state  

  14. Cardio protection Tonic vasoconstriction Abnormal vascular reactivity Vascular flow reserve Pro-apoptotic state Hyperinsulinemia Sodium retention Platelet Hyperaggregability Metabolic Syndrome Effects of Insulin Resistance Atherosclerosis ROS generation Oxidative stress Anti-fibrinolytic state Chronic Pro-Inflammatory State Pro-thrombotic State

  15. Diagnostic Criteria

  16. ATP III Clinical Manifestations - Abdominal Obesity Men >102 cm (>40in) Women >88 cm (>35in) - Triglycerides > 150 mg/dl - HDL Cholesterol Men < 40 mg/dl Women < 50 mg/dl - Blood Pressure >130/>85 mmHg - Fasting Glucose >110 mg/dl JAMA 285:2486, 2001.

  17. WHO Clinical Criteria Insulin Resistance, identified by 1 of the following: • Type II diabetes • Impaired fasting glucose • Impaired glucose tolerance • Or for those with normal fasting glucose levels(<110mg/dl), glucose uptake below the lowest quartile for background population under investigation under hyperinsulinemic, euglycemic conditions Plus any 2 of the following: • Antihypertensive medication &/or high blood pressure (>140 mmHg systolic or >90 mmHg diastolic) • Plasma triglycerides >150 mg/dl • HDL cholesterol <35 mg/dl in men or <39 mg/dl in women • BMI >30kg/m2 &/or waist:hip ratio>0.9 in men,>0.85 in women • Urinary albumin excretion rate >20mcg/min or albumin:creatinine ratio >30mg/g

  18. AACE Clinical Criteria - Overweight/obesity BMI >25kg/m2 - Elevated Triglycerides >150 mg/dl (1.69mmol/L) - Low HDL Cholesterol Men < 40 mg/dl (1.04 mmol/L) Women < 50 mg/dl (1.29 mmol/L) - Elevated Blood Pressure > 130/85 mmHg - 2 hr post glucose challenge > 140 mg/dl - Fasting Glucose Between 110 and 126 mg/dl - Other risk factors - Family history of type 2 diabetes, hypertension, or CVD - Polycystic ovary syndrome - Sedentary lifestyle - Advancing age - Ethic groups having high risk for type 2 diabetes or CVD

  19. Other Useful Measures • Triglyceride-to-HDL Cholesterol Ratio • Small LDL particles • Impaired glucose tolerance (IGT) • Variation in coagulation factors • plasminogen activator inhibitor (PAI-1) • fibrinogen

  20. CRP • There is a correlation between C-reactive protein (CRP) level and the number of syndrome components. • CVD and CRP • Waist circumference and CRP

  21. Circulation 107:391, 2003

  22. Additional Tools to Help Make the Diagnosis • Insulin resistance score (HOMA-IR) • fasting plasma glucoses (mmol/L) X fasting serum insulin (mIU/ml) / 22.5. • Obtain lipid levels when most appropriate

  23. Screening Questions • Do you have difficulty losing weight despite exercising regularly? • Do you have a close relative who has had heart disease, high blood pressure, T2D, polycystic ovarian syndrome, infertility problems, or obesity? • Do you experience frequent cravings for sugars or other • high carbohydrate foods? 4. Do you often feel tired after a meal? 5. Do you eat meals that consist of pasta, rice, potatoes, and corn more than 2-3 times per week? 6. Do you awaken at night 2 or more times to urinate? • Have you either gained or lost more than 5 lbs in the • last 3 months? • For women: Do you feel that you have more facial hair • than other women in your family, racial, and/or ethnic group?

  24. The Metabolic Syndrome and Its Relationship to Type 2 Diabetes and Cardiovascular Disease Excess Energy Intake Over Expenditure Genetic Predispostion Truncal Obesity Muscular Inactivity Acquired or Genetic Insulin Resistance Metabolic Syndrome Unbalanced Diet Hypertension Acquired or Genetic Beta Cell Defect Cardiovascular Disease Type 2 Diabetes

  25. Pathophysiology 3 potential etiologic categories: 1-obesity and disorders of adipose tissue 2-insulin resistance 3-constellation of independent factors the mediate specific components of the syndrome.

  26. Insulin Properties: • Vasodilation • Anti-inflammatory • Sodium retention

  27. Insulin Resistance Aging is the most important environmental factor in causing insulin resistance. Physical fitness is as powerful as obesity in predicting insulin sensitivity 

  28. Hyperinsulinemia Results in: • Increased CHD risk • Reactive hypoglycemia • High triglycerides • Low HDL • Hypercholesteremia • Hypertension • Hypofibrinolysis • Polycystic ovaries

  29. PCOS • The most common endocrinopathy among young women • Affects 6-10% of women of childbearing age • Accounts for 50-60% of female infertility • 82% of women with T2D have polycystic ovaries.

  30. Why fat? • The Real Question Is: Where Are The Famines?

  31. Adipose Tissue • An important source of hormones, the best known of which is Leptin. • Decrease in Insulin Sensitivity • Increased hepatic triglyceride production and higher free fatty acid FFA level. • Elevated Angiotensin II levels

  32. Adipose Tissue - proinflammatory cytokines (C-reactive protein) • Adipose tissue also plays a central role in insulin resistance because it synthesizes and secretes: - tumor necrosis factor - plasminogen activator inhibitor-1 (PAI-1) - interleukin-6 - nonesterified fatty acids (NEFA) - Adiponectin - Cortisol

  33. Leptin • Leptin increases sympathetic activity and may increase sodium reabsorption and heart rate. • When insufficient levels, there is a marked increase in tissue fat, increased triglycerides, • Insulin increases Leptin production

  34. Inflammation • Result of excessive caloric intake

  35. Organ Involvement - Renal • Uric acid clearance is also correlated with insulin sensitivity. • RAS – cross talk between angiotensin II and insulin signaling contributes to the pathophysiology

  36. Organ Involvement - Lung • Abnormal lung function and sleep apnea may be related to diabetes • 2hr insulin levels show a progressive rise with increased frequency of sleep apnea.

  37. Organ Involvement - Liver • The liver is the major organ involved in lipid and glucose homeostasis. • Similar to alcoholic liver disease, there is a spectrum of abnormalities, progressing to nonalcoholic steatohepatits (NASH)

  38. Dyslipidemias HDL LDL Triglycerides HDL & LDL VLDL

  39. Cardiovascular System • Hypertension • Somatostatin • Sodium retention and angiotensin II • Hypertension and lipid metabolism • Increased vascular resistance • abnormal vascular smooth muscle function

  40. Other Important Modifiers • Physical inactivity promotes the development of obesity and modifies muscle insulin sensitivity. • Aging is commonly accompanied by a loss of muscle mass and by an increase in body fat particularly accumulation of fat in the abdomen, both changes can increase insulin resistance.

  41. Management of the Metabolic Syndrome • Consists primarily of 2 strategies: • modification or reversal of the root causes, including weight reduction and increased physical activity • direct treatment of the metabolic risk factors, including atherogenic dyslipidemia, elevated blood pressure, the prothrombotic state, and underlying insulin resistance.

  42. Intervention • Opportunity for early intervention is present when insulin levels are elevated in association with the other components of the metabolic syndrome • Optimal to screen for all components of metabolic syndrome when obtaining a fasting insulin level.

  43. Two Main Treatment Goals 1 – reduce the contribution of underlying causes such as obesity and physical inactivity. 2 – treat the patient for lipid and nonlipid risk factors.

  44. The ABCDE’s for Treatment for Metabolic Syndrome X • Antiplatelet • BP (Hypertension) Control – Which are best? • Cholesterol Control • Diet • Exercise

  45. Tx of Pro-Inflammatory State • Growing interest in development of drugs to dampen the pro-inflammatory state. • Several lipid - lowering drugs will reduce CRP levels, which could reflect an anti-inflammatory action.

  46. Tx of Pro-Thrombotic state • No drugs are available that target PAI-I and fibrinogen. • An alternative approach to the pro-thrombotic state is antiplatelet therapy. • ACE inhibitors have been found to improve the fibrinolytic profile of the MSX by reducing plasma PAI-1 levels.

  47. BP (Hypertension) Control – Which are Best? • Blood pressure lowering agents do not necessarily affect comorbidities • Vasoactive qualities need to be considered

  48. RAS and Intervention with ARBs and ACE Inhibitors Angiotensinogen Renin Angiotensin I ACEAngiotensin Converting InhibitorsEnzyme (ACE) Angiotensin II Angiotensin Receptor Blockers AT1 Receptor AT2 Receptor Vasoconstriction Vasodilation Sympathetic Activation Inhibition of Cell Growth Cell Proliferation Apoptosis Aldosterone Release Renal Sodium Resorption Atherosclerosis, hypertension

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