Cardiometabolic Syndrome Nabil Sulaiman

Dr. Dhafir A. Mahmood

Cardiometabolic Syndrome

Nabil SulaimanHOD Family and Community Medicine,

Sharjah University and University of Melbourne

Dr. Dhafir A. MahmoodConsultant Endocrinologist

Al- Qassimi & Al-Kuwait HospitalSharjah

Cardiometabolic Syndrome II

Aimso Abdominal obesity prevalence

o Targeting Cardiometabolic Risk factors

o Multiple Risk Factor management

o A Critical Look at the Metabolic Syndrome

Clustering of Components

o Hypertension: BP. > 140/90o Dyslipidemia: TG > 150 mg/dL ( 1.7 mmol/L )

HDL- C < 35 mg/dL (0.9 mmol/L)o Obesity (central): BMI > 30 kg/M2

Waist girth > 94 cm (37 inch)Waist/Hip ratio > 0.9

o Impaired Glucose Handling: IR, IGT or DMFPG > 110 mg/dL (6.1mmol/L)2hr.PG >200 mg/dL

(11.1mmol/L) o Microalbuninuria (WHO)

Global cardiometabolic risk*

Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition

The new IDF definition focuses on abdominal obesity rather than insulin

resistance

International Diabetes Federation (IDF) Consensus Definition 2005

Why a New Definition of the MeS:IDF Objectives

Needso To identify individuals at high

risk of developing cardiovascular disease (and diabetes)

o To be useful for clinicians

o To be useful for international comparisons

Fat Topography In Type 2 Diabetic Subjects

Intramuscular

Intrahepatic

Subcutaneous

Intra-abdominal

FFA*TNF-alpha*Leptin*IL-6 (CRP)*Tissue Factor*PAI-1*

Angiotensinogen*

Abdominal obesity and increased risk of cardiovascular events

Dagenais GR et al, 2005

Ad

juste

d r

ela

tive r

isk

1 1 1

1.17 1.16 1.14

1.29 1.27

1.35

0.8

1

1.2

1.4

CVD death MI All-cause deaths

Tertile 1

Tertile 2Tertile 3

Men Women<95

95–103>103

<87

87–98>98

Waistcircumference (cm):

The HOPE study

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

Abdominal obesity increases the risk of developing type 2

diabetes

<71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3

24

20

16

12

8

4

0

Rela

tive r

isk

Waist circumference (cm)

Carey VJ et al, 1997

Abdominal obesity is linked to an increased risk of coronary heart

diseaseWaist 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

0.0

0.5

1.0

1.5

2.0

2.5

3.0

<69.8 69.8<74.2 74.2<79.2 79.2<86.3 86.3<139.7

1.27

2.06 2.31

2.44p for trend = 0.007

Rela

tive r

isk

Quintiles of waist circumference (cm)

Rexrode KM et al, 1998

CHD: coronary heart disease; BMI: body mass index

Diabetes in the new millennium

Interdisciplinary problem

Diabetes

Diabetes in the new millennium

Interdisciplinary problem

OBESITY

Diabetes in the new millennium

Interdisciplinary problem

DIAB

ESITY

Targeting

Cardiometabolic Risk

Central obesity: a driving force for cardiovascular disease & diabetes

“Balzac” by RodinFront

Back

Insulin Resistance: Associated Conditions

Linked Metabolic Abnormalities:

o Impaired glucose handling/insulin

resistanceo Atherogenic dyslipidemiao Endothelial dysfunctiono Prothrombotic stateo Hemodynamic changeso Proinflammatory stateo Excess ovarian testosterone productiono Sleep-disordered breathing

Resulting Clinical Conditions:

o Type 2 diabetes

o Essential hypertension

o Polycystic ovary syndrome (PCOS)

o Nonalcoholic fatty liver disease

o Sleep apnea

o Cardiovascular Disease (MI, PVD,

Stroke)

o Cancer (Breast, Prostate, Colorectal,

Liver)

Multiple Risk Factor Management

o Obesity

o Glucose Intolerance

o Insulin Resistance

o Lipid Disorders

o Hypertension

o Goals: Goals: Minimize Risk of Type 2 Minimize Risk of Type 2 Diabetes and Cardiovascular Diabetes and Cardiovascular DiseaseDisease

Glucose Abnormalities:Glucose Abnormalities:

o IDF:IDF:– FPG >100 mg/dL (5.6 mmol. L) or

previously diagnosed type 2 diabetes

– (ADA: FBS >100 mg/dL [ 5.6 mmol/L ])

Hypertension:Hypertension:

o IDF:IDF:– BP >130/85 or on Rx for previously

diagnosed hypertensionhypertension

Dyslipidemia:Dyslipidemia:o IDF:IDF:

– Triglycerides - >150mg/dL (1.7 mmol /L)

– HDL - <40 mg/dL (men), <50 mg/dL (women)

Public Health Approach

Screening/Public Health Approach

o Public Educationo Screening for at risk

individuals:– Blood Sugar/ HbA1c– Lipids– Blood pressure– Tobacco use– Body habitus– Family history

Life-Style Modification: Is it Important?

o Exercise– Improves CV fitness, weight control,

sensitivity to insulin, reduces incidence of diabetes

o Weight loss– Improves lipids, insulin sensitivity, BP

levels, reduces incidence of diabeteso Goals: Goals: Brisk walking - 30 min./dayBrisk walking - 30 min./day 10% reduction in body wt.10% reduction in body wt.

Smoking Cessation / Avoidance:

o A risk factor for development in children and adults

o Both passive and active exposure harmfulo A major risk factor for:

– insulin resistance and metabolic syndrome– macrovascular disease (PVD, MI, Stroke)– microvascular complications of diabetes– pulmonary disease, etc.

Diabetes Control - How Important?

Goals: o FBS - premeal <110, o postmeal <180. o HbA1c <7%o For every 1% rise in Hb A1c there is an 18% rise

in risk of cardiovascular events & a 28% increase in peripheral arterial disease

o Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD

Lifestyle modification

• Diet• Exercise• Weight loss• Smoking

cessation

If a 1% reduction in HbA1c is achieved, you could

expect a reduction in risk of:

• 21% for any diabetes-related endpoint

• 37% for microvascular complications

• 14% for myocardial infarction

However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis

Stratton IM et al. BMJ 2000; 321: 405–412.

Overcome Insulin Resistance/ Overcome Insulin Resistance/ Diabetes:Diabetes:

o Insulin Sensitizers:– Biguanides – metformin– Glitazones, Gltazars – Can be used in combination

o Insulin Secretagogues:– Sulfonylurea - glipizide, glyburide,

glimeparide, glibenclamide– Meglitinides - repaglanide, netiglamide

BBP Control - How Important?

o Goal: BP.<130/80o MRFIT and Framingham Heart Studies:

– Conclusively proved the increased risk of CVD with long-term sustained hypertension

– Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40.

– 40% reduction in stroke with control of HTNo Precedes literature on Metabolic Syndrome

Lipid Control - How Important?

o Goals: HDL >40 mg% (>1.1 mmol /l)

LDL <100 mg/dL (<3.0 mmol /l)

TG <150 mg% (<1.7 mmol /l)

oMultiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.

Substantial residual cardiovascular risk in statin-

treated patients

Placebo Statin

Year of follow-up

% p

ati

en

ts

0 1 2 3 4 5 6

10

20

30

0

Risk reduction=24%(p<0.0001)

The MRC/BHF Heart Protection Study

Heart Protection Study Collaborative Group, 2002

19.8% of statin-treatedpatients had a majorcardiovascular event by 5 years

Medications:

o Hypertension:– ACE inhibitors, ARBs– Others - thiazides, calcium channel

blockers, beta blockers, alpha blockers

– Central acting Alfa agonist: Moxolidino Dylipidemia:

– Statins, Fibrates, Niacino Platelet inhibitors:

– ASA, clopidogrel

Individual metabolic abnormalities among Qatari population according

to gender (Musallam et al 08)

Men (n = 405) Women (n=412)

Variable n(%) n(%) p-ValueATP III

Abdominal obesity 227(56.0) 308(74.8) <0.001

Hypertension143(35.3) 156(37.9) 0.448

Diabetes 77(19.0) 107(26.0) 0.017

Hypertriglyceridemia 113(27.9) 83(20.1) 0.009

Low HDL 95(23.5) 121(29.4) 0.055

Individual metabolic abnormalities among Qatari population according

to gender

Men (n = 405) Women (n = 412)Variablen(%) n(%) p-Value

None88(21.7) 74(18.0) –

One 103(25.4) 100(24.3) 0.033

Two 125(30.9) 111(26.9) –

Three or more89(22.0) 127(30.8) –

No of components of ATP III

Prevalence of MeS in different Countries

Country Year SamplePrevalence

(%)

Arab Americans 2003 542 23

Oman 2001 1419 21

Jordan 2002 1121 36

Saudi Arabia 2004 2250 20.8

Palestine 1998 17*

Qatar 2007 817 27.6

Turkey 2004 1637 33.4*

Iran ? 10368 33.7

* Crude rates Mussallam et al. Int J Food Safety and PH 2008

A Critical Look at the Metabolic Syndrome

Is it a Syndrome?*Is it a Syndrome?*o “…too much clinically important

information is missing to warrant its designations as a syndrome.”

o Unclear pathogenesis, Insulin resistance is not a consistent finding in some definitions.

o CVD risks has not shown to be greater than the sum of it’s individual components.

*ADA

A Critical Look at the Metabolic Syndrome

Research

o “Until much needed research is

completed, clinicians should evaluate

and treat all CVD risk factors without

regard to whether a patient meets the

criteria for diagnosis of the ‘metabolic

syndrome’.”

A Critical Look at the Metabolic Syndrome

Lifestyle

o The advice remains to treat individual

risk factors when present & to prescribe

therapeutic lifestyle changes & weight

management for obese patients with

multiple risk factors.

Insulin Resistance: Associated Conditions

Determinants and dynamics of the CVD Epidemic in the developing

Countries Data from South Asian Immigrant studieso Excess, early, and extensive CHD in persons of South

Asian origino The excess mortality has not been fully explained by

the major conventional risk factors.o Diabetes mellitus and impaired glucose tolerance

highly prevalent. (Reddy KS, circ 1998).o Central obesity, ↑triglycerides, ↓HDL with or without

glucose intolerance, characterize a phenotype.o Genetic factors predispose to ↑lipoprotein(a) levels,

the central obesity/glucose intolerance/dyslipidemia complex collectively labeled as the “metabolic syndrome”

Determinants and dynamics of the CVD Epidemic in the developing

CountriesOther Possible factors o Relationship between early life characteristics and

susceptibility to NCD in adult hood ( Barker’s hypothesis) (Baker DJP,BMJ,1993)

– Low birth weight associated with increased CVD– Poor infant growth and CVD relation

o Genetic–environment interactions (Enas EA, Clin. Cardiol. 1995; 18: 131–5)

- Amplification of expression of risk to some environmental changes esp. South Asian population)

- Thrifty gene (e.g. in South Asians)

CVD epidemic in developing &developed countries. Are they

same?o Urban populations have higher levels of CVD risk factors related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes)

o Tobacco consumption is more widely prevalent in rural population

o The social gradient will reverse as the epidemics mature.

o The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-curative care.

o The scarce societal resources to the treatment of these disorders dangerously depletes the resources available for the ‘unfinished agenda’ of infectious and nutritional disorders that almost exclusively afflict the poor

Burden of CVD in Pakistan

o Coronary heart disease o Mortality statistics o Specific mortality data ideal for making

comparisons with other countries are not available

o Inadequate and inappropriate death certification, and multiple concurrent causes of death

Central obesity: a driving force for cardiovascular disease & diabetes

“Balzac” by RodinFront

Back

Why people physically inactive?

o Lack of awareness regarding the physical activity for health fitness and prevention of diseases

o Social values and traditions regarding physical exercise (women, restriction).

o Non-availability public places suitable for physical activity (walking and cycling path, gymnasium).

o Modernization of life that reduce physical activity (sedentary life, TV, Computers, tel, cars).

Insulin Resistance: Associated Conditions

Prevalence of the Metabolic Syndrome Among US Adults

NHANES 1988-1994

Pre

vale

nce (

%)

05

1015202530354045

20-29 30-39

40-49 50-59 60-69 > 70

MenWomen

Age (years)Ford E et al. JAMA. 2002(287):356.1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+)NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women

Prevention of CVDo There is an urgent need to establish appropriate

research studies, increase awareness of the CVD burden, and develop preventive strategies.

o Prevention and treatment strategies that have been proven to be effective in developed countries should be adapted for developing countries.

o Prevention is the best option as an approach to reduce CVD burden.

o Do we know enough to prevent this CVD Epidemic in the first place.

The new IDF definition focuses on abdominal obesity rather than insulin

resistance

International Diabetes Federation (IDF) Consensus

Definition 2005

International Diabetes Federation (IDF) Consensus Definition 2005

Central ObesityWaist circumference – ethnicity specific* – for Europids: Male > 94 cm Female > 80 cm

plus any two of the following:

Raised triglycerides > 150 mg/dL (1.7 mmol/L)or specific treatment for this lipid abnormality

Reduced HDL cholesterol

< 40 mg/dL (1.03 mmol/L) in males< 50 mg/dL (1.29 mmol/L) in femalesor specific treatment for this lipid abnormality

Raised blood pressure

Systolic : > 130 mmHg orDiastolic: > 85 mmHg orTreatment of previously diagnosed hypertension

Raised fasting plasma glucose

Fasting plasma glucose > 100 mg/dL (5.6 mmol/L) or Previously diagnosed type 2 diabetesIf above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not necessary to define presence of the syndrome.

Treatment of Metabolic Syndrome: 2005

AspirinDiet, Exercise, Lifestyle change

Stop smoking

CB1 Receptor Blocker

Oral hypoglycaemics

Antihypertensives

Statins & Fibrates

Insulin

ACEI &/or A2 receptor blockers

Primary management for the Metabolic Syndrome is healthy lifestyle promotion. This includes:

oModerate calorie restriction (to achieve a 5-10% loss of body weight in the first year)

oModerate increases in physical activity

oChange dietary composition to reduce saturated fat and total intake, increase fibre and, if appropriate, reduce salt intake.

Recommendations for treatment

o Appropriate & aggressive therapy is essentialfor reducing patient risk of cardiovascular disease

o Lifestyle measures should be the first actiono Pharmacotherapy should have beneficial effects

on

– Glucose intolerance/diabetes– Obesity– Hypertension– Dyslipidaemia

o Ideally, treatment should address all of the components of the syndrome and not the individual components

Management of the Metabolic Syndrome

Summary: new IDF definition for the Metabolic Syndrome

The new IDF definition addresses both clinical and research needs: •Provides a simple entry point for primary care physicians to diagnose the Metabolic Syndrome•Providing an accessible, diagnostic tool suitable for worldwide use, taking into account ethnic differences•Establishing a comprehensive ‘platinum standard’ list of additional criteria that should be included in epidemiological studies and other research into the Metabolic Syndrome

Contact Information

Nabil Sulaimannsulaiman@sharjah.ac.ae