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Cardiometabolic Syndrome 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. Cardiometabolic Syndrome II Aims. Abdominal obesity prevalence

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slide1
Cardiometabolic Syndrome

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

cardiometabolic syndrome ii aims
Cardiometabolic Syndrome IIAims
  • Abdominal obesity prevalence
  • Targeting Cardiometabolic Risk factors
  • Multiple Risk Factor management
  • A Critical Look at the Metabolic Syndrome
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)
global cardiometabolic risk
Global cardiometabolic risk*

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

* working definition

slide5

International Diabetes Federation (IDF) Consensus Definition 2005

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

why a new definition of the mes idf objectives
Why a New Definition of the MeS: 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
slide7

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 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

slide14
Targeting

Cardiometabolic Risk

slide15

Central obesity: a driving force for

cardiovascular disease & diabetes

“Balzac” by Rodin

Front

Back

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
    • (ADA: FBS >100 mg/dL [ 5.6 mmol/L ])
hypertension
Hypertension:
  • IDF:
    • BP >130/85 or on Rx for previously diagnosed hypertension
dyslipidemia
Dyslipidemia:
  • IDF:
    • Triglycerides - >150mg/dL (1.7 mmol /L)
    • HDL - <40 mg/dL (men), <50 mg/dL (women)
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?

Goals:

  • FBS - premeal <110,
  • postmeal<180.
  • HbA1c <7%
  • 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
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.

overcome insulin resistance diabetes
Overcome Insulin Resistance/ Diabetes:
  • Insulin Sensitizers:
    • Biguanides – metformin
    • Glitazones, Gltazars
    • Can be used in combination
  • Insulin Secretagogues:
    • Sulfonylurea - glipizide, glyburide, glimeparide, glibenclamide
    • Meglitinides - repaglanide, netiglamide
bp control how important
BP Control - How Important?
  • Goal:BP.<130/80
  • 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
lipid control how important
Lipid Control - How Important?
  • Goals:HDL >40 mg% (>1.1 mmol /l)

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

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

  • Multiple 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
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

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
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) –

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

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

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 is not a consistent finding in some definitions.
  • CVD risks has not shown to be greater than the sum of it’s individual components.

*ADA

a critical look at the metabolic syndrome1
A Critical Look at the Metabolic Syndrome

Research

  • “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’.”
a critical look at the metabolic syndrome2
A Critical Look at the Metabolic Syndrome

Lifestyle

  • The advice remains to treat individual risk factors when present & to prescribe therapeutic lifestyle changes & weight management for obese patients with multiple risk factors.
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
slide50

Central obesity: a driving force for

cardiovascular disease & diabetes

“Balzac” by Rodin

Front

Back

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).
slide53

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.
slide56

International Diabetes Federation (IDF) Consensus Definition 2005

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

slide58

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

slide59

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.
slide60

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
slide61

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