Cardiometabolic Syndrome Nabil Sulaiman Dr. Dhafir A. Mahmood
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Transcript of Cardiometabolic Syndrome Nabil Sulaiman Dr. Dhafir A. Mahmood
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Cardiometabolic Syndrome Nabil Sulaiman
Dr. Dhafir A. Mahmood
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Cardiometabolic Syndrome
Nabil SulaimanHOD Family and Community Medicine,
Sharjah University and University of Melbourne
Dr. Dhafir A. MahmoodConsultant Endocrinologist
Al- Qassimi & Al-Kuwait HospitalSharjah
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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
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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)
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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 focuses 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
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
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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
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
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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
Rela
tive r
isk
Waist circumference (cm)
Carey VJ et al, 1997
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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
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Diabetes in the new millennium
Interdisciplinary problem
Diabetes
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Diabetes in the new millennium
Interdisciplinary problem
OBESITY
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Diabetes in the new millennium
Interdisciplinary problem
DIAB
ESITY
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Targeting
Cardiometabolic 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 Abnormalities:
o Impaired glucose handling/insulin
resistanceo Atherogenic dyslipidemiao Endothelial dysfunctiono Prothrombotic stateo Hemodynamic changeso Proinflammatory stateo Excess ovarian testosterone productiono Sleep-disordered breathing
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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)
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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
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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 ])
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Hypertension:Hypertension:
o IDF:IDF:– BP >130/85 or on Rx for previously
diagnosed hypertensionhypertension
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Dyslipidemia:Dyslipidemia:o IDF:IDF:
– Triglycerides - >150mg/dL (1.7 mmol /L)
– HDL - <40 mg/dL (men), <50 mg/dL (women)
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Public Health Approach
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Screening/Public Health Approach
o Public Educationo 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?
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.
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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.
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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
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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/ 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
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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
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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.
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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
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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
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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
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
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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
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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
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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
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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’.”
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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.
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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 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”
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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)
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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
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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
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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?
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).
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Insulin Resistance: Associated Conditions
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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
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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.
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The new IDF definition focuses 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 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.
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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:
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
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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
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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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