Cardiovascular Assessment in

Metabolic syndrome &

Diabetes Patient:

What Guideline Says?

Bambang Irawan Cardiometabolic Conference 2011

The Metabolic Syndrome

Abdominal

Obesity

"Metabolic Syndrome" is a cluster of

metabolic abnormalities associated with

high cardiovascular and diabetes risk.

Cardiometabolic risk (ie, risk of development of type 2 diabetes and

cardiovascular disease) is increased by a number of interrelated factors. These

factors include a patient's abnormal lipid metabolism, age, genetics, hypertension,

inflammation hypercoagulation, insulin resistance, overweight/ obesity, sex, and

smoking. ApoB indicates apolipoprotein B; BP, blood pressure; CVD,

cardiovascular disease; HDL, high-density lipoprotein cholesterol; LDL, low-

density lipoprotein cholesterol.

CHD is increased in subjects with increased

waistline and increased TG

3.6

4

2.5

Odds ratio for CAD

3.5

3 2.5

2

1.5

1.1 1

?2

1

0.5 <2

0

Waist girth (cm)

Relative odds (95% CI) of finding CAD, as defined by stenosis >50% in a major coronary vessel measured by angiography among patients classified on basis of waist circumference and fasting TG levels in the Quebec Cardiovascular Study

Lemieux I et al, Circulation.2000;102:179-184

mportant features of ATP

Focus on Multiple Risk Factors Modification of Lipid and

Lipoprotein Classification

Diabetes: CHD eventequivalent

Framingham projections of 10- year CHD risk

■ Identify certain patients with

multiple risk factors for more

intensive treatment

Multiple metabolic risk factors(metabolic syndrome)

Complete lipoprotein profile

preferred

Fasting total cholesterol, LDL- C, HDL-C, triglycerides

LDL- C <100 mg/dl— optimalHDL- C <40 mg/dl

Categorical risk factorRaised from <35 mg/dl

Lower triglyceride classification cut

points

(e.g. > 150 mg/dl in the M.S.)

Generally more attention given tomoderate elevations

National Cholesterol Education Program Adult Treatment Panel III

Any three or more ofthe following:

Central Obesity: Waist CircumferenceMales, 102 cmFemales, 88 cm

Elevated Triglyceride Concentration

150 mg/dL (1.7 mmol/L)Low HDL-C Level

Males, 40 mg/dL (1.03 mmol/L)Females, 50 mg/dL (1.29 mmol/L)

Hypertension130/85 mm Hg or Taking medication

Fasting Plasma Glucose Level110 mg/dL (6.1 mmol/L)

World ealth Organization

Impaired fasting glucose, impairedglucose tolerance, type

2 diabetes, or lowered insulin sensitivity plus any two ofthe

following:

Waist-Hip RatioMales, 0.9Females, 0.85 orBody mass index 30

DyslipidemiaTriglyceride concentration 150 mg/dL (1.7 mmol/L) orHDL-C level

— males, 35 mg/dL (0.9 mmol/L or— females, 39 mg/dL (1.0 mmol/L)

HypertensionBlood pressure 140/90 mm Hg orTreatment with medication

MicroalbumininuriaAlbumin excretion 20 g/min orAlbumin-creatinine ratio 30 mg/g

American eart Association/National

Heart, Lung, and Blood Institute

Any three or more ofthe following:

Elevated Waist Circumference

Males, 102 cmFemales, 88 cm

Elevated Triglyceride Concentration150 mg/dL (1.7 mmol/L) orReceiving drug therapy

Low HDL-C LevelMales, 40 mg/dL (1.03 mmol/L)Females, 50 mg/dL (1.29 mmol/L) orReceiving drug treatment

HypertensionSystolic blood pressure 130 mm Hg orDiastolic blood pressure 85 mm Hg orDrug treatment in patient withhistory of hypertension

Fasting Plasma Glucose Level100 mg/dL (5.6 mmol/L)

nternational Diabetes Foundation

Central obesity (as measured by ethnic-specific waist

circumference) plus any two ofthe following: Elevated Triglyceride Concentration

150 mg/dL (1.7 mmol/dL) orTreatment

Low HDL-C LevelMales, 40 mg/dL (1.03 mmol/L)Females, 50 mg/dL (1.29 mmol/L) orTreatment

HypertensionBlood pressure 130/85 mm Hg orMedication

Fasting Plasma Glucose Level100 mg/dL (5.6 mmol/L) orPreviously diagnosed type 2 diabetes mellitus

American Association of Clinical Endocrinologists

The greater the number ofcomponents an individual has, the more likely that individual is to

have metabolic syndrome. Components ofmetabolic syndrome include:

Impaired Glucose Metabolism120 min post–glucose challenge, 140-200 mg/dL or Fasting, 110-125 mg/dL impaired fasting glucose and/or impaired glucose

tolerance but not diabetesmellitus

DyslipidemiaTriclyceride concentration 150 mg/dLHDL-C level — Men, 40 mg/dL — Women, 50 mg/dL

Blood Pressure: 135/85 mm HgOther

Abnormal uric acid metabolismElevated prothrombotic factorsEndothelial dysfunction

Factors Associated With Metabolic SyndromeDiagnosis of cardiovascular disease, hypertension, polycystic ovarian

syndrome, nonalcoholic fatty liverdisease, or acanthosis nigricans

Family history of type 2 diabetes mellitus, hypertension, or cardiovascular disease

History of gestational diabetes or glucose intoleranceNon-Caucasian ethnicitySedentary lifestyleBody mass index 25.0 (or waist circumference 40 inches in men, 35 inches

in women)Age 40 Years

Cardiovascular Assessment

New features of ATP

Table I.3–1. New Features of ATP III

NCEP

Focus on Multiple Risk Factors

Raises persons with diabetes without CHD (most of whom display multiple risk factors) to the risk level of CHD risk equivalent

Uses Framingham projections of 10-year absolute CHD risk (i.e., the percent probability of having a CHD event in 10 years) to identify certain patients with multiple (2+) risk factors for more intensive treatment

Identifies persons with multiple metabolic risk factors (metabolic syndrome) as candidates for intensified therapeutic lifestyle changes

New features of ATP Modifications of Lipid and Lipoprotein Classification

Identifies LDL cholesterol <100 mg/dL as optimal Raises categorical low HDL cholesterol from <35 mg/dL to

<40 mg/dL because the latter is a better measure of a depressed HDL

Support for Implementation Recommends lipoprotein analysis (total cholesterol, LDL

Lowers the triglyceride classification cutpoints to give more attention to moderate elevations

cholesterol, HDL cholesterol, and triglycerides) as the preferred initial test, rather than screening for total cholesterol and HDL alone

Encourages use of plant stanols/sterols and viscous (soluble)

Presents strategies for promoting adherence to therapeutic

fiber as therapeutic dietary options to enhance lowering of

lifestyle changes and drug therapies

LDL cholesterol

Recommends treatment beyond LDL lowering for persons with triglycerides ≥200 mg/dL

Target classification Table II.2–4. ATP III Classification of Total Cholesterol and LDL

Cholesterol

Total Cholesterol (mg/dL) LDL Cholesterol (mg/dL) <100 Optimal

<200 Desirable 100–129 Near optimal/above optimal 200–239 Borderline High 130–159 Borderline High ≥240 High 160–189 High

≥190 Very High

Table II.3–1. Classification of Serum Triglycerides

Triglyceride Category ATP II Levels ATP III Levels

Normal triglycerides <200 mg/dL <150 mg/dL Borderline-high triglycerides 200–399 mg/dL 150–199 mg/dL High triglycerides 400–1000 mg/dL 200–499 mg/dL Very high triglycerides >1000 mg/dL ≥500 mg/dL

AHA-NHLBI-ADA

AHA-NHLBI-ADA

Management of metabolic risk factor ■ Although therapeutic lifestyle modification is first-

line therapy for the metabolic syndrome and thus deserves

initial attention, drug therapy may be necessary in many

patients to achieve recommended goals.

■ Risk assessment in patients with metabolic syndrome is

critical for setting goals of therapy.

AHA-NHLBI-ADA

Risk Assessment — metabolic syndrome

Atherogenic dyslipidemiaElevated blood pressureInsulin resistance & hypreglycemiaProthrombotic state:

Elevation of fibrinogens, PAI-1, and possibly othercoagulation factors.

Proinflammatory state:Elevated cytokinesElevated in acute phase reactants (CRP,

fibrinogen)

AHA-NHLBI-ADA nvestigation algorithm for patients with CAD & DM

ESC-EASD

CA D

CAD unknown

ECG,

echocardiography,

exercise test

NormalFollow up

CAD known

ECG,

echocardiography,

exercise test,

Positive finding,

Cardiology consultation

DM unknown

OGTT

Blood lipids & glucose

NormalFollow up

A b n o r m a l

Cardiology consultation

Ischaemia treatment:

N o n - i n v a s i v e o r

i n v a s i v e

Newly detected

DM or IGT.

Metabolic syndrome.

Diabetology consultation

DM known

Screening

Nephropathy,

Diabetology consultation

Main diagnosis

DM + CAD

Main diagnosis

CAD + DM

& DM

NICE

1.9. Cardiovascular Risk Estimation:

NICE Clinal Guideline 66 - Type 2 diabetes

1.9.1. Consider a person to be at high premature cardiovascular

risk for his or her age unless he or she:

is not overweight, tailoring this with an assessment of body-weight-associated risk according to ethnic group

is normotensive (< 140/80 mmHg in the absence ofantihypertensive therapy)

does not have microalbuminuriadoes not smokedoes not have a high-risk lipid profilehas no history of cardiovascular disease andhas no family history of cardiovascular

disease.

Cardiovascular Risk Protection:

DF Recommendation of standard care

CV1. Assess cardiovascular risk at diagnosis and at least annually thereafter:

current or previous cardiovascular disease (CVD)age and BMI (abdominal adiposity)conventional cardiovascular (CV) risk factors including smoking and

serumlipids, and family history of premature CVD

other features of the metabolic syndrome and renal damage (including low

HDL cholesterol, high triglycerides, raised albumin excretion rate)

atrial fibrillation (for stroke).

Do not use risk equations developed for non-diabetic populations. The UKPDS

risk engine may be used for assessment and communication of risk.

IDF

2.Ensure optimal management through lifestyle measures (seeLifestyle management), and measures directed at good blood glucose

and blood pressure control (see Glucose control, Bloodpressure

control).

3.Arrange smoking cessation advice in smokers contemplativeof reducing or stopping tobacco consumption.

4.Provide aspirin 75-100 mg daily (unless aspirin intolerant orblood pressure uncontrolled) in people with evidence of CVD or

at high risk.

CV5. Provide active management of the blood lipid profile:

a statin at standard dose for all >40 yr old (or all with declared CVD)a statin at standard dose for all >20 yr old with microalbuminuria or

assessedas being at particularly high risk

in addition to statin, fenofi brate where serum triglycerides are >2.3 mmol/l(>200 mg/dl), once LDL cholesterol is as optimally controlled as possible

consideration of other lipid-lowering drugs (ezetimibe, sustained releasenicotinic acid, concentrated omega 3 fatty acids) in those failing to reach lipid

lowering targets or intolerant of conventional drugs.

Reassess at all routine clinical contacts to review achievement of lipid targets:

LDL cholesterol <2.5 mmol/l (<95 mg/dl), triglyceride <2.3 mmol/l (<200

mg/dl), and HDL cholesterol >1.0 mmol/l (>39 mg/dl).

CV6. Refer early for further investigation and

consideration of revascularization those with

problematic or symptomatic peripheral arterial disease,

those with problems from coronary artery disease, and

those with evidence of carotid disease.

Gu idelines Increasingly Acknowledge the Importance of Comprehensive Lipid Management

All Patients 2004 ATP III NECP: Fibrates or nicotinic acid may have an adjunctive role in the

All Patients

2005 IDF: Providing active management of the blood lipid profile (....) in addition to a

statin, fenofibrate where serum TG >2.3 mmol/L (>200 mg/dL), once LDL is optimally controlled as possible.2

treatment of patients with high TG/low HDL-C, especially in combination w i t h s t a t i n s . 1

Type 2 Diabetes

2007 ESC: HDL-C <40 mg/dL (1.0 mmol/L) and TG >150 mg/dL (1.7 mmol/L) indicate increased risk of CVD. Fibrates cannot be recommended as 1st line treatments in T2D but may be considered in those with persistently low HDL-C. Fibrates may be considered in those with severely elevated TG, primarily to prevent complications, such as pancreatitis.3

Type 2 Diabetes 2007 ESC/EASD: In diabetic patients with elevated TG >2 mmol/L (177 mg/dL)

remaining after having reached LDL-C target with statins (...) combination therapy with fibrates or nicotinic acid may be considered.4

1.Grundy SM et al. Circulation 2004,110:227-39 3. Eur Heart J 2007,28:2375-2414 2.http://www.idf.org/home/index.cfmnode=1457 4. Eur Heart J 2007,28:1401-1402

mmol/L) in men and >50 mg/dL in women are desirable. LDL-C targeted statin therapy remains the first line strategy.1

-Combination therapy with a statin and a fibrate or statin and niacin may be efficacious for treatment of all three lipid fractions. The risk of rhabdomyolysis is higher with higher doses of statins and with renal

Guidelines Increasingly Acknowledge the Importance of Comprehensive Lipid Management

2008 T

levels <150 mg/dL (1 7 mmol/L) and HDL C >40 mg/dL (1 0

: G

insufficiency, and seems to be

lower when statins are combined with

2008

Type 2 Diabetes NICE:- Prescribe a fibrate (fenofibrate as first line) if TG remains above 4.5 mmol/L (400 mg/dL) despite attention to other causes (LDL-C).2

-If cardiovascular risk is high, as usual in T2DM, consider adding a fibrate to a statin therapy if

fenofibrate then gemfibrozil.1

-Severe hypertrygliceridemia needs immediate therapy with lifestyle and pharmacologic therapies (fibrates or niacin) to reduce risk of pancreatitis.1

TG in the range of 2.3- 4.5 mmol/L (200-400

Type 2 Diabetes

ADA

1.Diab Care 2008,31(Suppl.1):S12-S542.http://www.nice.org.uk/guidance/index