Cardiometabolic Risk : Evaluation & Treatment in Your Patient Population

1. Cardiometabolic Risk:Evaluation & Treatment in Your Patient Population Cardiometabolic Risk Faculty of Medicine Universitas Brawijaya Malang

2. Why Focus on Cardiometabolic Risk? • A comprehensive approach to patient care; Multiple disease pathways and risk factors are considered to facilitate earlier intervention • Early assessment and targeted intervention are needed to treat and prevent all risk factors associated with CVD and diabetes

3. Cardiometabolic Risk • Gives a comprehensive picture of a patient’s health and potential risk for future disease and complications • Is inclusive of all risks related to metabolic changes associated with CVD • Accommodates emerging risk factors as useful predictive tools • Focuses clinical attention to the value of systematic evaluation, education, disease prevention and treatment • Supports an integrated approach to care Kahn, et al. The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care. 2005;28 (9)2289-2304.

4. The State of Risk • 2 out of 3 Americans are overweight or obese • More than 70 million (nearly 1 in 4) Americans have varying degrees of insulin resistance • There are an estimated 54 million (more than 1 in 6) Americans with prediabetes • Nearly 1 in 4 U.S. adults has high cholesterol • 1 in 3 American adults has high blood pressure

5. Direct and Indirect Cost of CVD and Diabetes Estimated Indirect Costs (disability, work loss, premature mortality) Estimated Direct Medical Costs *Note: these figures may not account for potential overlap. Sources: 2008 statistics from the American Diabetes Association and American Heart Association.

6. Age Genetics Insulin Resistance ? Insulin Resistance Syndrome Glucose BP  Lipids Age, Race, Gender, Family History Overweight / Obesity Abnormal Lipid Metabolism LDL  ApoB  HDL  Trigly.  Cardiometabolic Risk - Graphic Cardiometabolic Risk Global Diabetes / CVD Risk Smoking Physical Inactivity Unhealthy Eating Inflammation Hypercoagulation Hypertension

7. Cardiometabolic Risk Factors Age Race/ethnicity Gender Family history Overweight Abnormal lipid metabolism Inflammation, hypercoagulation Hypertension Smoking Physical inactivity Unhealthy diet Insulin resistance Non-modifiable Modifiable

8. Case - Mr. Martin • 47-year-old African American man, hasn’t seen doctor in years • Works as a truck driver, eats mostly fast food • Smokes 1 pack per day • At health fair found to have BP = 146/86, total cholesterol = 210 • Weight = 230 lbs; BMI = 29 kg/m² • Family history of HTN and diabetes

9. What’s Mr. Martin’s Cardiometabolic Risk? • Age 47 • Race/ethnicity African American • Gender Male • Family history HTN and diabetes • Overweight/obesity BMI = 29 • Abnormal lipid metab TC = 210 • Hypertension BP = 146/86 • Smoking 1 pack per day • Physical Inactivity Yes • Unhealthy diet Fast food diet

10. Non-ModifiableRisk Factors

11. 800,000 600,000 400,000 200,000 0 Est. New Diabetes Diagnoses by Age, 2005 Number 60+ 40-59 20-39 Age Group Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.

12. Cardiovascular Risk Factor Trends Among U.S. Adults Aged 20-74 39.2 30.8 36.0 33.6 33.1 1960-1962 28.2 29.3 1971-1975 27.2 26.3 26.4 1976-1980 1988-1994 19.0 1999-2000 14.8 17.0 14.9 5.0 4.6 3.5 3.4 1.8 High Blood Pressure High Total Cholesterol Smoking Diagnosed Diabetes Centers for Disease Control & Prevention, Division for Heart Disease and Stroke Prevention, "Addressing the Nation's Leading Killers: At A Glance 2007

13. American Indians/ Alaska Natives Non-Hispanic Blacks Hispanic/Latino Americans Non-Hispanic Whites 0 2 4 6 8 10 12 14 16 18 20 Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.

14. Insulin Resistance

15. Factors affectinginsulin resistance • Overweight/ fat distribution • Age • Genetic predisposition • Activity level • Medications • Puberty • Pregnancy

16. IFG and IGT • Impaired Fasting Glucose (IFG): a condition in which the blood glucose level is between 100 mg/dL to 125mg/dL after an 8- to 12-hour fast. • Impaired Glucose Tolerance (IGT): a condition in which the blood glucose level is between 140 and 199 mg/dL at 2 hours during an oral glucose tolerance test (OGTT).

17. Interpreting BloodGlucose Levels Healthy BG FPG < 100 mg/dL Pre-diabetes FPG 100–125 mg/dL Diabetes FPG ≥126 mg/dL

18. Criteria for testing for type 2 diabetesin asymptomatic children50 • Overweight (BMI > 85th percentile for age and sex, weight for height > 85th percentile, or weight • >120 percent of ideal for height) Plus any two of the following: • Family history • Race/ethnicity • Signs of insulin resistance or conditions associated with insulin resistance • Maternal history of diabetes or GDM

19. Criteria for testing for diabetes in asymptomatic adult individuals50 • Testing should be considered in all overweight adults (BMI ≥25 kg/m2*) and have additional risk factors: • Physical inactivity • First-degree relative with diabetes • Members of a high-risk ethnic population • Women delivering baby weighing >9 lb or were diagnosed with GDM • Hypertension (≥140/90 mmHg) Continued

20. Criteria for testing for diabetes in asymptomatic adult individuals50 • HDL cholesterol level <35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl (2.82 mmol/l) • Women with polycystic ovarian syndrome (PCOS) • IGT or IFG on previous testing • Other clinical conditions associated with insulin resistance (e.g., severe obesity and acanthosis nigricans) • History of CVD

21. Criteria for testing for diabetes in asymptomatic adult individuals50 2. In the absence of the above criteria, testing for pre-diabetes and diabetes should begin at age 45 years 3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status. *At-risk BMI may be lower in some ethnic groups.

22. Insulin Resistance and CHD Mortality Paris Prospective Study (n=943) 3 P<.01 2 CHD mortality, per 1000 1 0 29 30-50 51-72 73-114 115 Quintiles (pmol) of fasting plasma insulin Insulin Sensitive Insulin Resistant Fontbonne AM, et al. Diabetes Care. 1991;14:461-469.

23. Cardiometabolic Risk Diabetes Impaired Fasting Glucose Euglycemia Proposed Metabolic Observations in the Natural History of Type 2 Diabetes InsulinSensitivity Insulin Secretion Associated Risk Factors • Hypertension • Dyslipidemia Atherogenesis Microvascular Complications FastingBlood Glucose Type 2 Diabetes Age (years)

24. Overweight/Obesity

25. Understanding Cardiometabolic Risk: Broadening Risk Assessment and Management

26. Screening: Overweight • Measure BMI routinely at each regular check-up. • Classifications: • BMI 18.5-24.9 = normal • BMI 25-29.9 = overweight • BMI 30-39.9 = obesity • BMI ≥40 = extreme obesity Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health.

27. Measuring Waist Circumference • Large waist circumference (WC) can identify some at increased risk over BMI alone • If BMI and other cardiometabolic risk factors are assessed, currently there is insufficient evidence to: • Substitute WC for BMI • Measure WC in addition to BMI Klein, et al. Waist Circumference and Cardiometabolic Risk. Diabetes Care. 2007 0: dc07-9921v1-0.

28. Insulin Resistance Hypertension Dyslipidemia Atherosclerosis Hypercoagulability Hyperglycemia • Coronary arteries • Carotid arteries • Cerebral arteries • Aorta • Peripheral arteries Hyperinsulinemia Inflammation Impaired Fibrinolysis Endothelial Dysfunction Multiple Factors Associated With Obesity Give Rise to Increased Risk of CVD Primary Metabolic Disturbance Intermediate Vascular Disease Risk Factor Intravascular Pathology Clinical Event Overnutrition CVD CVD: Cardiovascular disease Despres JP, et al. Abdominal obesity and metabolic syndrome.Nature. 2006;444:881-887.

29. Body Weight and CVD Men Women 300 267 250 200 200 Incidence of CVD per 1,000 128 150 125 121 105 100 50 0 <100 110-129 130+ <110 110-129 130+ n=56 n=75 n=30 n=191 n=199 n=78 *Metropolitan Relative Weight percent (percentage of desirable weight) Hubert HB et al. Circulation. 1983;67:968-977

30. Risk ManagementOverweight • Lifestyle modification • Reduce caloric intake by 500-1000 kcal/day (depending on starting weight) • Target 1-2 pound/week weight loss • Increase physical activity • Healthy diet • Diabetes Prevention Program • DASH diet Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health. Diabetes Prevention Program (DPP) Diabetes Care 25:2165–2171, 2002. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, NIH Publication No. 04-5230, August 2004

31. Risk Management, cont. Overweight • Consider pharmacologic treatment • BMI 30 with no related risk factors or diseases, or • BMI 27 with related risk factors or diseases • As part of a comprehensive weight loss program incl. diet & physical activity • Consider surgery • BMI 40 or • BMI 35 with comorbid conditions Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health. Diabetes Prevention Program (DPP) Diabetes Care 25:2165–2171, 2002

32. Abnormal Lipid Metabolism

33. Total Cholesterol Goals34 • Desirable — Less than 200 mg/dL • Borderline high risk — 200–239 mg/dL • High risk — 240 mg/dL and over American Diabetes Association. Understanding Cardiometabolic Risk: Broadening Risk Assessment and Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center

34. Increased: Triglycerides VLDL LDL and small dense LDL ApoB Decreased: HDL Apo A-I Abnormal Lipid Metabolism American Diabetes Association. Diabetes Care. 2007;30:S4-41.

35. Major Risk FactorsAffecting Lipid Goals36 • Cigarette smoking • Hypertension (≥140/90 mm Hg or on antihypertensive medication) • Low HDL-C (<40 mg/dL) • Family history of early heart disease • Age (men ≥45 years; women ≥55 years)

36. Statins (also called HMG-CoA reductase inhibitors) work by increasing hepatic LDL-C removal from the blood. • Resins (also called bile acid sequestrants) bind to bile acids in the intestines and prevent their reabsorption, leading to increased hepatic LDL-C removal from the blood. • Cholesterol absorption inhibitors help lower LDL-C by reducing the amount of cholesterol absorbed in the intestines; increases LDL receptor activity.

37. Fibrates (also called fibric acid derivatives) activate an enzyme that speeds the breakdown of triglyceriderich lipoproteins while also increasing HDL-C. • Niacin (also called nicotinic acid) reduces the liver’s ability to produce VLDL. When given at high doses, it can also increase HDL-C. American Diabetes Association. Understanding Cardiometabolic risk: Broadening risk Assessment and Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center

38. Cholesterol Management • For patients >20 years of age, cholesterol should be checked every 5 years • Ordering a fasting lipid panel is preferred to gauge the patient’s total cholesterol, LDL-C, HDL-C and triglycerides • Treatment priorities

39. Cholesterol Management LDL-C-lowering

40. Cholesterol Management • Improve glucose control if diabetes is present • Weight loss if overweight • Daily exercise • Smoking cessation • Dietary modifications including low saturated fat (fat intake less than 30% of total calories and saturated fat less than 7% of total calories), low cholesterol (no more than 200 mg daily) diet • Pharmacologic treatment frequently necessary • Risk factors include hypertension; HDL < 40; family history of MI before age 55; male > 45 years old; female > 55 years old; smoking.

41. Risk of CHD by Triglyceride Level:The Framingham Heart Study 3 Women Men 2.5 n=5,127 2 1.5 Relative Risk 1 0.5 0 50 100 150 200 250 300 350 400 Triglyceride Level, mg/dL Castelli WP. Epidemiology of triglycerides: a view from Framingham American Journal of Cardiology. 1992;70:3H-9H.

42. Association Between Small, Dense LDL and Insulin Resistance 12 (n=19) 10 (n=29) 8 (n=52) Mean Steady State Plasma Glucose (mmol/L) at Identical Plasma Insulin 6 4 2 0 A Larger LDL particle pattern B Small LDL particle pattern Intermediate pattern LDL-Size Phenotype Reaven GM, et al. J Clin Invest. 1993;92:141-146.

43. Low HDL-C: Independent Predictor of CHD Risk, Even When LDL-C is Low Risk of CHD HDL-C (mg/dL) LDL-C (mg/dL) Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. American Journal of Medicine. 1977;62:707-14. .

44. Screening for Dyslipidemia Persons without Diabetes • Test at least every 5 years, starting at age 20, including adults with low-risk values Persons with Diabetes • In adults, test at least annually • Lipoproteins: measure at after initial blood glucose control is achieved as hyperglycemia may alter results Preventing Cancer, Cardiovascular Disease, and Diabetes: A Common Agenda for The American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation. 2004;109:3244-3255. American Diabetes Association. Standards of Medical Care in Diabetes 2007. Available at: http://care.diabetesjournals.org/cgi/reprint/30/suppl_1/S4

45. Healthy Lipid GoalsTargets for Patients Without DM or CVD 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); National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health. NIH Publication No. 01-3670, May 2001

46. Risk ManagementAbnormal Lipids • Lifestyle modification • Increased physical activity • Diet: reduced saturated fat, trans fat, and cholesterol • Weight loss, if indicated American Diabetes Association. Diabetes Care. 2007;30:S4-41.

47. Risk ManagementAbnormal Lipids • Pharmacologic treatment: primary goal is LDL lowering • Without overt CVD: If over 40, statin therapy recommended to achieve 30-40% LDL reduction • With overt CVD: All patients should receive statin therapy to achieve 30-40% LDL reduction • Lowering triglycerides and raising HDL with a fibrate is associated with fewer cardiovascular events in patients with clinical CVD, low HDL, and near-normal LDL American Diabetes Association. Diabetes Care. 2007;30:S4-41.

48. Hypertension

49. Persons without Diabetes BP should be measured at each regular visit or at least once every 2 years if BP <120/80 mmHg BP measured seated after 5 min rest in office Persons with Diabetes BP should be measured at each regular visit BP measured seated after 5 min rest in office Patients with ≥130 or ≥80 mmHg should have BP confirmed on a separate day Hypertension: Evaluation and Screening Preventing Cancer, Cardiovascular Disease, and Diabetes A Common Agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation. 2004;109:3244-3255. American Diabetes Association. Diabetes Care. 2007;30:S4-41.

50. Non-pharmacologic DASHdiet Dietary Approaches to Stop Hypertension High in whole grains, fruits, vegetables, and low-fat dairy Low in saturated and trans fat, cholesterol Physical Activity Weight loss, if applicable Management of Hypertension The Dash Diet. http://dashdiet.org. American Diabetes Association. Diabetes Care. 2007;30:S4-41.