Resiko metabolik

Cardiometabolic Risk

Learning Objectives

• Define cardiometabolic risk and assess the non-modifiable and modifiable risk factors

• Describe methods for early identification and management of the following risk factors:– Obesity– Dyslipidemia– Hypertension

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 cardiovascular diseases (CVD) and diabetes

Daly A, Power MA. Medical Nutrition Therapy. Diabetes Mellitus and Related Disorders; Medical Management of Type 2 Diabetes, 7th Edition. American Diabetes Association, 2012.

What is Cardiometabolic Risk?

• A comprehensive picture of a patient’s health and potential risk for future disease and complications

– All risks related to metabolic changes associated with CVD

– Accommodates emerging risk factors – Focuses clinical on evaluation, education,

disease prevention and treatmentKahn, 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)2289-304.

Indonesian Cardiometabolic Risk: CVD Epidemiology

• CVDs are responsible for over 17.3 million deaths/year and are the leading causes of death in the world

• Indonesian statistics:– CVD Mortality Rates: 363-443/100 000 for males

and 181-281/100 000 for females– Burden of CVD (Disability-adjusted Life Year):

3315-4228/100000 for males and 2584-3438/100000 females

WHO. Global atlas on cardiovascular disease prevention and control. 2011

Direct and Indirect Cost of CVD and Diabetes (USD)*

2008 statistics from the American Diabetes Association and American Heart Association.

*Note: These figures may not account for potential overlap

Estimated Direct Medical Costs

Estimated Indirect Costs (disability, work loss,

premature mortality)

CVD $296 billion $152 billion

Diabetes $116 billion $58 billion

TOTAL $412 billion $210 billion


Global Diabetes/CVD Risk

Overweight / Obesity Abnormal Lipid Metabolism

LDL ApoB

HDL Trigly.

Age, Race, Gender,

Family History

Inflammation HypercoagulationHypertension

SmokingPhysical InactivityUnhealthy Eating

?

GlucoseBP Lipids

Age Genetics

Insulin ResistanceInsulin

Resistance Syndrome

Risk Factors

Nonmodifiable• Age• Race/Ethnicity• Gender• Family history

Modifiable• Overweight• Abnormal lipid

metabolism• Inflammation,

hypercoagulation• Hypertension• Smoking• Physical inactivity• Unhealthy diet• Insulin resistance

Insulin Resistance

• Overweight/ Fat distribution• Age• Genetic predisposition• Activity level• Medications• Pregnancy

Factors Affecting Insulin Resistance

• 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).

Impaired Fasting Glucose & Glucose Tolerance

Proposed Metabolic Observations in the Natural History of T2DM

Atherogenesis

Euglycemia Impaired Fasting Glucose

Diabetes

Insulin Sensitivity

Insulin Secretion

• Hypertension• Dyslipidemia

MicrovascularComplications

Age (years) Type 2 Diabetes


ADA. Therapy for Diabetes Mellitus and Related Disorders. 5 th Edition, 2009.

Associated Risk Factors

Fasting Blood Glucose

Prediabetes and Diabetes Prevention

Prediabetes

• Pre-diabetes is an important risk factor for future diabetes and CVD

• Recent studies have shown that lifestyle modifications can reduce the rate of progression from pre-diabetes to diabetes

Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)

• ADA Consensus Statement:– Treat IFG and IGT with intensive

lifestyle modification

– For certain patients with both IFG & IGT and risk factor(s), consider addition of metformin

Nathan D, et al. Impaired Fasting Glucose and Impaired Glucose Tolerance: Implications for Care. Diabetes Care 2007;30:753-9.

Relative Effectiveness of Interventions in Diabetes Prevention

Cum

ulat

ive

Inci

denc

eof

Dia

bete

s (%

)

Years

40

30

20

10

00 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Placebo

Knowler WC, et al. NEJM. 2002;346:393-403.

Metformin

Lifestyle

Prevention of T2DM: Recent Randomized Trial Results

Study Subjects Intervention Relative Risk Reduction

Behavio

r

Finnish DPSUS DPP

IGT Lifestyle 58%

IGT Lifestyle 58%

Medication

US DPPSTOP- NIDDMTRIPODXENDOSDREAM

IGT Metformin 31%

IGT Acarbose 25%

Prior GDM Troglitazone 55%

IGT Orlistat 45%

IGT Rosiglitazone/Ramipril 61% NS

Screening

• Screening is conducted on those who have diabetes risks, but do not show any symptoms of DM.

• Screening seeks to capture undiagnosed DM or prediabetes so it can be managed earlier and more appropriately.

• Mass screening is not recommended considering the costs (usually abnormal results are not followed-up with an action plan).

PERKENI Guidelines. Diabetes Mellitus National Clinical Practice Guidelines. 2011

Standard Values of Random BG and FBG for Screening and Diagnosis of DM

Note: For high-risk groups which show no abnormal results, the test should be done every year. For those aged > 45 years without other risk factors, screening can be done every 3 years.

Non DM Uncertain DM DM

Random Blood Glucose Level (mg/dL)

Venous Plasma <100 100-199 ≥200

Capillary Blood <90 90-199 ≥200

Fasting Blood Glucose Level (mg/dL)

Venous Plasma <100 100-125 ≥126

Capillary Blood <90 90-99 ≥100


Diabetes Prevention

− Medical Nutritional Therapy

− Physical activity− Weight reduction

Not yet recommended

− Hypertension− Dyslipidemia− Physical

health− Body weight

control

− If overweight, reduce body

weight by 5-10%− Physical exercise

for 30 minutes, 5x/week

2-hour OGTT is the most sensitive method for early

detection and a recommended screening test procedure

High-risk population at <30-year old− Family history of DM− Cardiovascular disorder− Overweight− Sedentary life style− Known IFG or IGT− Hypertension− Elevated Triglyseride,

low HDL or both− History of Gestational

DM− History of give birth >

4000g− PCOS

Life Style Changes

Early Detection

Pharmacology Therapy

Periodic Blood

Glucose and Risk

Factor Monitoring


Management

Early Detection

High risk population at the age < 30 years old• Family history of diabetes • Cardiovascular abnormalities• Overweight • Sedentary life• History of IFG or IGT• Hypertension• Increase of TG / Decrease of HDL or Both• History of Gestational Diabetes• History of delivering infant > 4000 g• Polycystic Ovary Syndrome

OGTT is the most sensitive method for early detection

and the recommended screening tool


Prediabetes, management

• Target lifestyle changes and use adjunct pharmacologic treatment for specific priorities eg, hypertension1

• The decision to start pharmacologic treatment must be based on a risk-benefit analysis2

– Metformin and acarbose: safe & effective– Thiazolidinedione (TZD): associated risk of

congestive heart failure and fracture should be given attention.

1.Saewonder & Pramono. Prevalence, characteristics, and predictors of pre-diabetes in Indonesia. Med J Indones 2011; 20: 283-94.2. Buku Panduan Pengelolaan dan Pencegahan Prediabetes. 2010 (Guideline book on Management and Prevention of Prediabetes)

Prediabetes, management

• Dyslipidemia: Statin is recommended

• Hypertension: ACE-I or ARB is recommended, Calcium channel blocker, second choice.

• All prediabetes subjects who do not have risk of gastrointestinal bleeding, intracranial bleeding or other risk of bleeding, may be given low dose aspirin.

Buku Panduan Pengelolaan dan Pencegahan Prediabetes. 2010 (Guideline book on Management and Prevention of Prediabetes)

Overweight/Obesity

Obesity in Indonesia: Double Burden Nutrition Problems

• Despite general improvements in food availability, health and social services, hunger and malnutrition exist in some form in almost every district

• In 2003, 27.5 percent of children under five were moderately and severely underweight

Amarita, 2005

IFLS Results: Overweight Population

• Increasing prevalence among people >18 years old

• Prevalence women>men

Indonesia Family Life Survey, 1993, 1997, 2000, 2007

IFLS-1 (1993)

IFLS-2 (1997)

IFLS-3 (2000)

IFLS-4 (2007)

% Overweight

Men 20.78 - 24.86 31.14

Women 32.28 39.55 - 48.67

Results: RISKESDAS 2007 & 2010 Overweight Population

• Over 3 years, the obesity prevalence increased in all children’s age groups, with the largest increase in the 15-18 year old female group

RISKESDAS 2010

2007 2010% Overweight

Toddlers 12.2 14.06-12 year old females 6.4 7.76-12 year old males 9.5 10.715-18 year old females 23.8 26.915-18 year old males 13.9 16.3

>18 year olds 10.3 11.7

BMI and DM

<17.9 18 – 22.9 23 – 26.9 >27

3.7%

4.4%

7.3%9.1%

Prev

alen

ce o

f DM

(RISKESDAS 2007

BMI

Clinical Obesity Measurements

• Body mass index (BMI) – Calculated as (Weight in pounds / Height in inches2) x 703– Direct correlation with risk of adverse health outcomes

and mortality

• Waist circumference– A surrogate marker of body fat distribution– Measurement may not affect clinical management

when BMI and other cardiometabolic risk factors are already determined

BMI (kg/m2) = Weight in kilograms Height in meters2

Klein S, et al. Diabetes Care. 2007;30:1647-52.

Measuring Waist Circumference

• Locate upper hip bone and top of the right iliac crest

• Place a measuring tape in a horizontal plane around the abdomen at iliac crest

• Tape should be snug, parallel to the floor, and not compress the skin

• Measurement at end of normal expiration

High-Risk Waist CircumferenceWomen: > 80 cm

Men: > 90 cm

International Diabetes Federation. Consensus worldwide definition of the metabolic syndrome. www.idf.org

Abdominal Obesity is Associated With Increased Risk of CHD

• Waist circumference is independently associated with increased age-adjusted risk of CHD, even after adjusting for BMI and other CV risk factors.

0.00.51.0

1.5

2.02.5

3.0

1 2 3 4 5

1.27

2.082.31 2.44

P for trend = .007 (women)P for trend = .001 (men)

Rel

ativ

e R

isk

Quintiles of Waist Circumference

1.00 1.011.34 1.26

1.60

1.00

Rexrode KM, et al. JAMA. 1998;280:1843-8.Rexrode KM, et al. Int J Obes (Lond). 2001;25:1047-56.

Multiple Factors Associated With Obesity Give Rise to Increased Risk of CVD

IntravascularPathology

ClinicalEvent

CVD

Atherosclerosis

Hypercoagulability

• Coronary arteries• Carotid arteries• Cerebral arteries• Aorta• Peripheral arteries

Hypertension

Dyslipidemia

Hyperinsulinemia

Hyperglycemia

Inflammation

ImpairedFibrinolysis

Endothelial Dysfunction

Insulin Resistance

Overnutrition

PrimaryMetabolic

Disturbance

Intermediate Vascular Disease

Risk Factor

Despres JP, et al. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881-87.

Obesity Practice Guidelines: Indonesia

• Summary of recommendations:– Clinical evaluation of overweight and

obese patients

– Weight management programs and support for weight loss maintenance

• Lifestyle modification• Behavioral modification• Pharmacological Treatment• Surgery

Purnamasari D et al. Identification, Evaluation and treatment of overweight and obesity in adults: Clinical Practice Guidelines of the Obesity Clinic, Wellness Cluster Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Risk Management: Weight Loss Recommendations

• Weight loss therapy is recommended for:– BMI ≥25 kg/m2

– BMI 23-24.9 kg/m2 + 2 risk factors– High-risk waist circumference + 2 risk factors

(comorbidities)

• Weight management programs should include lifestyle modification and behavioral management


Recommendations: Lifestyle Modification

• Dietary intervention– Reduce intake by 500–1000 kcal/day from total

daily intake

• Increased physical activity– Moderate activity 30-45 mins/day, 3-5 times/week– Overweight and obese individuals: Moderate

activity 45-60 mins/day 5 times/week .


Is There One “Best” Weight Loss Diet? ADA Recommendations

• For weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year)

• Ability to adhere to a diet, rather than its composition, is the primary determinant of successful weight loss

Look AHEAD: Benefits of Weight Loss

• “Magnitude of weight loss at 1 year was strongly (P<0.0001) associated with improvements in glycemia, blood pressure, triglycerides and HDL cholesterol but not with LDL cholesterol”

• Improvement was greater with weight loss of 10-15%

• Conclusions: – Even modest weight loss of 5-10% is associated with

significant improvements in cardiometabolic risk factorsWing RR et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with Type 2 Diabetes. Diabetes Care. 34: 2011.

Risk Management: Pharmacologic Treatment

• Consider pharmacologic treatment in patients with:– BMI 25 kg/m2 with comorbidities– BMI 30

• Decide based on an individual case basis and risk/benefit assessment

• Include as part of comprehensive lifestyle intervention


Abnormal Lipid Metabolism

Dyslipidemia in Indonesia

• International Diabetes Management Practices Study (IDMPS)– Study of 674 patients with T2DM

• 53.5% had dyslipidemia– 44.5% were receiving treatment

• Demonstrated that the metabolic control of diabetes is not good enough to prevent complications

Current practice in the management of type 2 diabetes in Indonesia. Results from IDMPS. J Indon Med Assoc 2011

Abnormal Lipid Metabolism

Increased:• Triglycerides• Very-low-density

lipoprotein (VLDL)• LDL and small dense LDL• Apolipoprotein B

Decreased:• HDL• Apolipoprotein A-I

American Diabetes Association. Diabetes Care. 2007;30:S4-41.

Cholesterol management

• 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)

Major Risk Factors Affecting Lipid Goals

Cholesterol Management

LDL-C Goal

Category of Risk LDL-C Goal0-1 risk factor* < 160 mg/dL or lower

Multiple (2+) risk factors* < 130 mg/dL or lower

People with coronary heart disease or risk equivalent (e.g., diabetes)

< 100 mg/dL or lower

Known CAD and DM < 70 mg/dL or lower may be ideal

Risk Management: Abnormal Lipids

• Lifestyle Modification– Increased physical activity– Diet: reduced saturated fat, trans fat,

and cholesterol

– Weight loss, if indicated


• Pharmacologic Treatment: – Primary goal is LDL lowering

– Without overt CVD: If >40 yrs of age, statin to achieve 30-40% LDL reduction

– With overt CVD: All patients, statin to achieve 30-40% LDL reduction

– Lowering TG and raising HDL with a fibrate is associated with fewer cardiovascular events in patients with clinical CVD, low HDL, and near-normal LDL

Risk Management: Abnormal Lipids in DM


Classes of Medications for Lipid Pharmacology

• Statins: Work by increasing hepatic LDL-C removal from the blood

• Resins: 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

Classes of Medications for Lipid Pharmacology (cont’d)

• Fibrates: Activate an enzyme that speeds the breakdown of triglyceriderich lipoproteins while also increasing HDL-C

• Niacin: Reduces the livers ability to produce very low density lipoprotein (VLDL) – When given at high doses, it can also

increase HDL-C

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 after initial BG control

is achieved as hyperglycemia may alter results

Hypertension

Hypertension in Indonesia

• International Diabetes Management Practices Study (IDMPS)– Study of 674 patients with T2DM

• 47.6% had hypertension– 44.3% were receiving treatment

• The high prevalence of hypertension was likely a contributing factor in the high rate of complications found in the study

Current practice in the management of type 2 diabetes in Indonesia. Results from IDMPS. J Indon Med Assoc 2011

Hypertension: Evaluation and Screening

Persons without Diabetes:• At each regular visit or at

least once /2 years if BP <120/80 mmHg

• Measured seated after 5 min rest in office

Persons with Diabetes:

• Measured at each regular visit

• Measured seated after 5 min rest in office

• Patients with ≥130 or ≥80 mmHg should have BP confirmed on a separate day

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;109:3244-55. American Diabetes Association. Diabetes Care. 2007;30:S4-41.

Management of Hypertension

• Nonpharmacologic:– Reduce salt intake– Physical activity– Weight loss, if applicable

Management of Hypertension

• Pharmacologic: – Drug therapy indicated if BP ≥140/ ≥90 mmHg– Combination therapy often necessary– Treatment should include angiotensin

converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB)

– Thiazide diuretic may be added to reach goals– Monitor renal function and serum potassium

Summary: Cardiometabolic Risk

• Assessing a patient’s cardiometabolic risk is important in the prevention of CVD and T2DM

• Identification of risk factors such as obesity, dyslipidemia and hypertension allow for the initiation of appropriate risk management strategies– Lifestyle modification – Addition of pharmacologic agents in some clinical

scenarios

Thank you

Resiko metabolik

Health & Medicine