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Cardiometabolic Syndrome Dr. Nabil Sulaiman HOD Family and Community Medicine, Sharjah University and University of Melbourne & Dr Dhafir A. Mahmood Consultant Endocrinologist Al- Qassimi & Al-Kuwait Hospital Sharjah. Agenda. History & Definition

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slide1
Cardiometabolic Syndrome

Dr. Nabil Sulaiman

HOD Family and Community Medicine, Sharjah University and University of Melbourne

&

Dr Dhafir A. Mahmood

Consultant Endocrinologist

Al- Qassimi & Al-Kuwait Hospital

Sharjah

agenda
Agenda
  • History & Definition
  • Clustering component of Metabolic Syndrome
  • Cardiovascular disease worldwide
  • Global cardiometabolic risks
  • Abdominal obesity prevalence ( National & International )
  • Intra Abdominal Adiposity & associated risks
  • Targeting Cardiometabolic Risk factors
  • Multiple Risk Factor management
  • A Critical Look at the Metabolic Syndrome
metabolic syndrome history
Metabolic Syndrome (History)
  • 1923 - Kylin first to describe the clustering of hypertension, hyperglycemia, hyperuricemia
  • 1936 - Himsworth first reported Insulin insensitivity in diabetics
  • 1965 - Yalow and Berson developed insulin assay and correlated insulin levels & glucose lowering effects in resistant and non-resistant individuals
metabolic syndrome history cont
Metabolic Syndrome History (cont.)
  • 1988 - Reaven in his Banting lecture at the ADA meeting coined the term Syndrome X and brought into focus the clustering of features of Metabolic Syndrome
  • Reaven now prefers the name, Insulin-Resistance Syndrome - feels insulin resistance is the common denominator for Metabolic Syndrome
  • Literature now extensive
other names used
Other Names Used:
  • Syndrome X
  • Cardiometabolic Syndrome
  • Cardiovascular Dysmetabolic Syndrome
  • Insulin-Resistance Syndrome
  • Metabolic Syndrome
  • Beer Belly Syndrome
  • Reaven’s Syndrome
  • etc.
clustering of components
Clustering of Components:
  • Hypertension: BP. > 140/90
  • Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L )

HDL- C < 35 mg/ dL (0.9 mmol/L)

  • Obesity (central): BMI > 30 kg/M2

Waist girth > 94 cm (37 inch)

Waist/Hip ratio > 0.9

  • Impaired Glucose Handling: IR , IGT or DM

FPG > 110 mg/dL (6.1mmol/L)

2hr.PG >200 mg/dL(11.1mmol/L)

  • Microalbuninuria (WHO)
necessary criteria to make diagnosis
Necessary Criteria to Make Diagnosis
  • WHO:

Impaired G handling + 2 other criteria.

    • Also requires microalbuminuria - Albumen/ creatinine ratio >30 mg/gm creatinine
  • IDF:
    • Require central obesity plus two of the other abnormalities
  • NCEP/ATP III:
    • Require three or more of the five criteria
what is cardiometabolic risk
What is cardiometabolic risk?*
  • Global cardiometabolic risk represents the overall risk of developing type 2 diabetes and/or cardiovascular disease (including MI and stroke), which is due to a cluster of modifiable risk factors/markers
  • These include classical risk factors such as smoking, high LDL, hypertension, elevated blood glucose and emerging risk factors closely related to abdominal obesity (especially intra-abdominal adiposity), such as insulin resistance, low HDL, high triglycerides and inflammatory markers
  • Cardiometabolic risk is based on the concept of risk continuum

MI: myocardial infarction; LDL: low-density lipoprotein;

HDL: high-density lipoprotein

* working definition

global cardiometabolic risk
Global cardiometabolic risk*

Gelfand EV et al, 2006; Vasudevan AR et al, 2005

* working definition

despite therapeutic advances cv disease remains the leading cause of death usa

Male

Female

35

30

25

20

15

10

5

0

Despite therapeutic advances, CV disease remains the leading cause of death (USA)

Data for 2002

No. of deaths(left axis)

Number of deaths (thousands)

% All deaths (male + female)

% of all deaths(right axis)

National Center for Health Statistics, 2004

substantial residual cardiovascular risk in statin treated patients
Substantial residual cardiovascular risk in statin-treated patients

The MRC/BHF Heart Protection Study

30

Placebo

Statin

20

Risk reduction=24%

(p<0.0001)

19.8% of statin-treatedpatients had a majorcardiovascular event

by 5 years

% patients

10

0

0

1

2

3

4

5

6

Year of follow-up

Heart Protection Study Collaborative Group, 2002

abdominal obesity has reached epidemic proportions worldwide
Abdominal obesity has reached epidemic proportions worldwide

Prevalence of abdominal obesity by region

1. Ford ES et al, 2003; 2 Haftenberger M et al, 2002; 3. Kim MH et al 2004; 4. Cameron AJ et al, 2003; 5. Puoane T et al, 2002

targeting cardiometaboilc risk defining cardiometabolic risk
Targeting Cardiometaboilc RiskDefining cardiometabolic Risk
  • What is Abdominal Obesity ?
  • Can be defined by Waist Circumference;
slide14

Fat Topography In Type 2 Diabetic Subjects

FFA*

TNF-alpha*

Leptin*

IL-6 (CRP)*

Tissue Factor*

PAI-1*

Angiotensinogen*

Intramuscular

Subcutaneous

Intrahepatic

Intra-

abdominal

abdominal obesity is linked to multiple cardiometabolic risk factors
Abdominal obesity is linked to multiple cardiometabolic risk factors

Patients with abdominal obesity often present with one or more additional cardiovascular risk factors (NCEP ATP III criteria)

HDL: high-density lipoprotein; BP: blood pressure

National Cholesterol Education Panel/Adult Treatment Panel III, 2002

targeting cardiometaboilc risk defining cardiometabolic risk1
Targeting Cardiometaboilc RiskDefining cardiometabolic Risk

86% At least 1 additional CM risk factor

24% 2 or more additional CM risk factors

abdominal obesity and increased risk of cardiovascular events
Abdominal obesity and increased risk of cardiovascular events

The HOPE study

Men

Women

Tertile 1

<95

<87

Waistcircumference (cm):

Tertile 2

95–103

87–98

Tertile 3

>103

>98

1.4

1.35

1.29

1.27

1.17

1.2

1.16

1.14

Adjusted relative risk

1

1

1

1

0.8

CVD death

MI

All-cause deaths

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

Dagenais GR et al, 2005

abdominal obesity increases the risk of developing type 2 diabetes
Abdominal obesity increases the risk of developing type 2 diabetes

24

20

16

12

Relative risk

8

4

0

<71

71–75.9

76–81

81.1–86

86.1–91

91.1–96.3

>96.3

Waist circumference (cm)

Carey VJ et al, 1997

abdominal obesity is linked to an increased risk of coronary heart disease

3.0

2.44

p for trend = 0.007

2.31

2.5

2.06

2.0

Relative risk

1.5

1.27

1.0

0.5

0.0

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

Quintiles of waist circumference (cm)

Abdominal obesity is linked to an increased risk of coronary heart disease

Waist 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

CHD: coronary heart disease; BMI: body mass index

Rexrode KM et al, 1998

slide23
Targeting

Cardiometabolic Risk

linked metabolic abnormalities
Linked Metabolic Abnormalities:
  • Impaired glucose handling/ insulin resistance
  • Atherogenic dyslipidemia
  • Endothelial dysfunction
  • Prothrombotic state
  • Hemodynamic changes
  • Proinflammatory state
  • Excess ovarian testosterone production
  • Sleep-disordered breathing
resulting clinical conditions
Resulting Clinical Conditions:
  • Type 2 diabetes
  • Essential hypertension
  • Polycystic ovary syndrome (PCOS)
  • Nonalcoholic fatty liver disease
  • Sleep apnea
  • Cardiovascular Disease (MI, PVD, Stroke)
  • Cancer (Breast, Prostate, Colorectal, Liver)
multiple risk factor management
Multiple Risk Factor Management
  • Obesity
  • Glucose Intolerance
  • Insulin Resistance
  • Lipid Disorders
  • Hypertension
  • Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease
glucose abnormalities
Glucose Abnormalities:
  • IDF:
    • FPG >100 mg/dL (5.6 mmol. L) or previously diagnosed type 2 diabetes
  • WHO:
    • Presence of diabetes, IGT, IFG, insulin resistance
  • ATP III:
    • FBS >110 mg/dL, <126 mg/dL (6.1-7.1 mmol/L )
    • (ADA: FBS >100 mg/dL [ 5.6 mmol/L ])
hypertension
Hypertension:
  • IDF:
    • BP >130/85 or on Rx for previously diagnosed hypertension
  • WHO:
    • BP >140/90
  • NCEP ATP III:
    • BP >130/80
dyslipidemia
Dyslipidemia:
  • IDF:
    • Triglycerides - >150mg/dL (1.7 mmol /L)
    • HDL - <40 mg/dL (men), <50 mg/dL (women)
  • WHO:
    • Triglycerides - >150 mg/dL (1.7 mmol/L)
    • HDL - <35 mg/dL (men), >39 mg/dL) women
  • ATP III:
    • Same as IDF
screening public health approach
Screening/Public Health Approach
  • Public Education
  • Screening for at risk individuals:
    • Blood Sugar/ HbA1c
    • Lipids
    • Blood pressure
    • Tobacco use
    • Body habitus
    • Family history
life style modification is it important
Life-Style Modification: Is it Important?
  • Exercise
    • Improves CV fitness, weight control, sensitivity to insulin, reduces incidence of diabetes
  • Weight loss
    • Improves lipids, insulin sensitivity, BP levels, reduces incidence of diabetes
  • Goals:

Brisk walking - 30 min./day

10% reduction in body wt.

smoking cessation avoidance
Smoking Cessation / Avoidance:
  • A risk factor for development in children and adults
  • Both passive and active exposure harmful
  • A majorrisk factorfor:
    • insulin resistance and metabolic syndrome
    • macrovascular disease (PVD, MI, Stroke)
    • microvascular complications of diabetes
    • pulmonary disease, etc.
diabetes control how important
Diabetes Control - How Important?
  • For every 1% rise in Hb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease
  • Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD
  • Goals:
  • FBS - premeal <110,
  • postmeal<180.
  • HbA1c <7%
overcome insulin resistance diabetes
Overcome Insulin Resistance/ Diabetes:
  • Insulin Sensitizers:
    • Biguanides - metformin
    • PPAR α, γ & δ agonists – Glitazones, Gltazars

Rosiglitazon, Pioglitazon

    • Can be used in combination
  • Insulin Secretagogues:
    • Sulfonylurea - glipizide, glyburide, glimeparide, glibenclamide
    • Meglitinides - repaglanide, netiglamide
bp control how important
BP Control - How Important?
  • 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 HTN
  • Precedes literature on Metabolic Syndrome
  • Goal:BP.<130/80
lipid control how important
Lipid Control - How Important?
  • Multiple major studies show 24 - 37% reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.
  • Goals:LDL <100 mg/dL (<3.0 mmol /l)

(high risk <70 mg/dL- <2.6 mmol/L)

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

HDL >40 mg% (>1.1 mmol /l)

medications
Medications:
  • Hypertension:
    • ACE inhibitors, ARBs
    • Others - thiazides, calcium channel blockers, beta blockers, alpha blockers
    • Central acting Alfa agonist : Moxolidin
  • Dylipidemia:
    • Statins, Fibrates, Niacin
  • Platelet inhibitors:
    • ASA, clopidogrel
a critical look at the metabolic syndrome
A Critical Look at the Metabolic Syndrome

Is it a Syndrome?*

  • “…too much clinically important information is missing to warrant its designations as a syndrome.”
  • Unclear pathogenesis, Insulin resistance may not underlie all factors, & is not a consistent finding in some definitions.
  • CVD risks associated with metabolic syndrome has not shown to be greater than the sum of it’s individual components.

*ADA & EASD

a critical look at the metabolic syndrome1
A Critical Look at the Metabolic Syndrome
  • “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 ‘metabolicsyndrome’.”
  • The advice remains to treat individual risk factors when present & to prescribe therapeutic lifestyle changes & weight management for obese patients with multiple risk factors.
individual metabolic abnormalities among qatari population according to gender musallam et al 08
Individual metabolic abnormalities among Qatari population according to gender (Musallam et al 08)

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

Variable n(%) n(%) p-Value

ATP III

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

Hypertension 143(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
Individual metabolic abnormalities among Qatari population according to gender

No of components of ATP III

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

Variable n(%) n(%) p-Value

None 88(21.7) 74(18.0) –

One 103(25.4) 100(24.3) 0.033

Two 125(30.9) 111(26.9) –

Three or more 89(22.0) 127(30.8) –

slide42
Multivariate logistic regression analysis of factors associated with Metabolic Syndrome according to (ATP III criteria)

Odds ratio95% CIp-Value

Age 1.07 1.05–1.09 <0.001

Female gender 1.86 1.30–2.67 0.001

Body Mass Index 1.05 1.02–1.07 <0.001

Fam his of DM 1.66 1.12–2.44 0.011

Smoking 3.27 1.63–6.55 0.001

prevalence of mes in different countries
Prevalence of MeS in different Countries

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

prevalence of mes in different countries1
Prevalence of MeS in different Countries

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

determinants and dynamics of the cvd epidemic in the developing countries
Determinants and dynamics of the CVD Epidemic in the developing Countries

Data from South Asian Immigrant studies

  • Excess, early, and extensive CHD in persons of South Asian origin
  • The excess mortality has not been fully explained by the major conventional risk factors.
  • Diabetes mellitus and impaired glucose tolerance highly prevalent. (Reddy KS, circ 1998).
  • Central obesity, ↑triglycerides, ↓HDL with or without glucose intolerance, characterize a phenotype.
  • 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 countries1
Determinants and dynamics of the CVD epidemic in the developing countries

Other Possible factors

  • 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
  • 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
CVD epidemic in developing &developed countries. Are they same?
  • Urban populations have higher levels of CVD risk factors related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes)
  • Tobacco consumption is more widely prevalent in rural population
  • The social gradient will reverse as the epidemics mature.
  • The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-curative care.
  • 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
Burden of CVD in Pakistan

Coronary heart disease

Mortality statistics

  • Specific mortality data ideal for making comparisons with other countries are not available
  • Inadequate and inappropriate death certification, and multiple concurrent causes of death
slide53

Central obesity: a driving force for

cardiovascular disease & diabetes

“Balzac” by Rodin

Front

Back

developing a new definition of the metabolic syndrome idf objectives
Developing A New Definition of the Metabolic Syndrome: IDF Objectives

Needs:

  • To identify individuals at high risk of developing cardiovascular disease (and diabetes)
  • To be useful for clinicians
  • To be useful for international comparisons
slide55

International Diabetes Federation (IDF) Consensus Definition 2005

The new IDF definition focusses on abdominal obesity rather than insulin resistance

why people physically inactive
Why people physically inactive?
  • Lack of awareness regarding the of physical activity for health fitness and prevention of diseases
  • Social values and traditions regarding physical exercise (women, restriction).
  • Non-availability public places suitable for physical activity (walking and cycling path, gymnasium).
  • Modernization of life that reduce physical activity (sedentary life, TV, Computers, tel, cars).
slide58

45

Men

40

Women

35

30

25

Prevalence (%)

20

15

10

5

0

20-29

30-39

40-49

50-59

60-69

> 70

Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994

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 cvd
Prevention of CVD
  • There is an urgent need to establish appropriate research studies, increase awareness of the CVD burden, and develop preventive strategies.
  • Prevention and treatment strategies that have been proven to be effective in developed countries should be adapted for developing countries.
  • Prevention is the best option as an approach to reduce CVD burden.
  • Do we know enough to prevent this CVD Epidemic in the first place.
slide61

International Diabetes Federation (IDF) Consensus Definition 2005

The new IDF definition focusses on abdominal obesity rather than insulin resistance

slide63

Stop smoking

Oral hypoglycaemics

ACEI &/or A2 receptor blockers

Diet, Exercise, Lifestyle change

Aspirin

Insulin

CB1 Receptor Blocker

Statins & Fibrates

Antihypertensives

Treatment of Metabolic Syndrome: 2005

slide64

Recommendations for treatment

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

  • moderate calorie restriction (to achieve a 5-10% loss of body weight in the first year)
  • moderate increases in physical activity
  • change dietary composition to reduce saturated fat and total intake, increase fibre and, if appropriate, reduce salt intake.
slide65

Management of the Metabolic Syndrome

  • Appropriate & aggressive therapy is essentialfor reducing patient risk of cardiovascular disease
  • Lifestyle measures should be the first action
  • Pharmacotherapy should have beneficial effects on
    • Glucose intolerance/diabetes
    • Obesity
    • Hypertension
    • Dyslipidaemia
  • Ideally, treatment should address all of the components of the syndrome and not the individual components
slide66

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
lifestyle modification
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.