Cardiometabolic Syndrome (2)
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Cardiometabolic Syndrome
Nabil SulaimanHOD Family and Community Medicine, Sharjah
University and University of Melbourne
&Dr Dhafir A. Mahmood
Consultant EndocrinologistAl- Qassimi & Al-Kuwait Hospital
Sharjah
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Cardiometabolic Syndrome II
Aims
• Abdominal obesity prevalence
• Targeting Cardiometabolic Risk factors
• Multiple Risk Factor management
• A Critical Look at the Metabolic Syndrome
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Clustering of ComponentsClustering 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)
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Global cardiometabolic risk*
Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition
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The new IDF definition focusses on abdominal obesity
rather than insulin resistance
International Diabetes Federation (IDF) Consensus Definition 2005
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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
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Fat Topography In Type 2 Diabetic Subjects
Intramuscular
Intrahepatic
Subcutaneous
Intra-abdominal
FFA*TNF-alpha*Leptin*IL-6 (CRP)*Tissue Factor*PAI-1*
Angiotensinogen*
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Abdominal obesity and increased risk of cardiovascular events
Dagenais GR et al, 2005
Ad
just
ed r
elat
ive
risk
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
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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
Rel
ativ
e ri
sk
Waist circumference (cm)
Carey VJ et al, 1997
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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
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
Rel
ativ
e ri
sk
Quintiles of waist circumference (cm)
Rexrode KM et al, 1998
CHD: coronary heart disease; BMI: body mass index
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Diabetes in the new millenniumInterdisciplinary problem
Diabetes
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Diabetes in the new millenniumInterdisciplinary problem
OBESITY
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Diabetes in the new millenniumInterdisciplinary problem
DIAB
ESITY
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TargetingTargeting
Cardiometabolic RiskCardiometabolic Risk
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Central obesity: a driving force for cardiovascular disease & diabetes
“Balzac” by RodinFront
Back
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Insulin Resistance: Associated Conditions
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Linked Metabolic AbnormalitiesLinked Metabolic Abnormalities::
• Impaired glucose handling/ insulin resistance
• Atherogenic dyslipidemia
• Endothelial dysfunction
• Prothrombotic state
• Hemodynamic changes
• Proinflammatory state
• Excess ovarian testosterone production
• Sleep-disordered breathing
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Resulting Clinical ConditionsResulting 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)
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Multiple Risk Factor ManagementMultiple Risk Factor Management
• Obesity
• Glucose Intolerance
• Insulin Resistance
• Lipid Disorders
• Hypertension
• Goals: Goals: Minimize Risk of Type 2 Minimize Risk of Type 2 Diabetes and Cardiovascular DiseaseDiabetes and Cardiovascular Disease
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Glucose AbnormalitiesGlucose Abnormalities::
• 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 ])
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HypertensionHypertension::
• IDF:IDF:– BP >130/85 or on Rx for previously
diagnosed hypertensionhypertension
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DyslipidemiaDyslipidemia::
• IDF:IDF:– Triglycerides - >150mg/dL (1.7 mmol /L)– HDL - <40 mg/dL (men), <50 mg/dL
(women)
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Public Health ApproachPublic Health Approach
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Screening/Public Health ApproachScreening/Public Health Approach
• Public Education
• Screening for at risk individuals:– Blood Sugar/ HbA1c– Lipids– Blood pressure– Tobacco use– Body habitus– Family history
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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: Goals: Brisk walking - 30 min./dayBrisk walking - 30 min./day 10% reduction in body wt.10% reduction in body wt.
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Smoking Cessation / AvoidanceSmoking Cessation / Avoidance::
• A risk factor for development in children and adults
• Both passive and active exposure harmful
• A major risk factor for:– insulin resistance and metabolic syndrome– macrovascular disease (PVD, MI, Stroke)– microvascular complications of diabetes– pulmonary disease, etc.
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Diabetes Control - How ImportantDiabetes Control - How Important??
GoalsGoals:
• FBS - premeal <110, FBS - premeal <110,
• postmealpostmeal <180. <180.
• HbA1c <7%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
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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.
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Overcome Insulin Resistance/ DiabetesOvercome Insulin Resistance/ Diabetes::
• Insulin Sensitizers:– Biguanides – metformin– Glitazones, Gltazars – Can be used in combination
• Insulin Secretagogues:– Sulfonylurea - glipizide, glyburide,
glimeparide, glibenclamide– Meglitinides - repaglanide, netiglamide
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BP Control - How ImportantBP Control - How Important??
• Goal: BP.BP.<130/80<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
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Lipid Control - How ImportantLipid Control - How Important??
• Goals:Goals: HDL >40 mg% (>1.1 mmol /l) HDL >40 mg% (>1.1 mmol /l)
LDL LDL <100 mg/dL (<3.0 mmol /l)<100 mg/dL (<3.0 mmol /l)
TG <150 mg% (<1.7 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.
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Substantial residual cardiovascular Substantial residual cardiovascular risk in statin-treated patientsrisk in statin-treated patients
Placebo Statin
Year of follow-up
% p
atie
nts
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
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MedicationsMedications::
• 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
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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
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
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Individual metabolic abnormalities among Qatari population according to gender
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) –
No of components of ATP III
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Prevalence of MeS in different Countries
CountryYear SamplePrevalence (%)
Arab Americans200354223
Oman2001141921
Jordan2002112136
Saudi Arabia2004225020.8
Palestine199817*
Qatar200781727.6
Turkey2004163733.4*
Iran?1036833.7
* Crude rates Mussallam et al. Int J Food Safety and PH 2008
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A Critical Look at the Metabolic SyndromeA Critical Look at the Metabolic Syndrome
Is it a 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
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A Critical Look at the Metabolic SyndromeA 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 ‘metabolic syndrome’.”
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A Critical Look at the Metabolic SyndromeA 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.
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Insulin Resistance: Associated Conditions
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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”
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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)
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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
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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
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Central obesity: a driving force for cardiovascular disease & diabetes
“Balzac” by RodinFront
Back
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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).
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Insulin Resistance: Associated Conditions
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Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994
Pre
vale
nc
e (
%)
P
reva
len
ce
(%
)
05
10
15
2025
3035
40
45
20-29 30-39 40-49 50-59 60-69 > 70
MenMenWomenWomen
Age (years)Age (years)Ford E et al. JAMA. 2002(287):356.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
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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.
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The new IDF definition focusses on
abdominal obesity rather than insulin
resistance
International Diabetes Federation (IDF) Consensus Definition 2005
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International Diabetes Federation (IDF) Consensus Definition 2005
Central Obesity
Waist 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 females
or specific treatment for this lipid abnormality
Raised blood pressureSystolic : > 130 mmHg or
Diastolic: > 85 mmHg or
Treatment of previously diagnosed hypertension
Raised fasting plasma glucose
Fasting plasma glucose > 100 mg/dL (5.6 mmol/L) or
Previously diagnosed type 2 diabetes
If above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not necessary to define presence of the syndrome.
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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
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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.
Recommendations for treatment
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• 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
Management of the Metabolic Syndrome
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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
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