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
Cardiometabolic Syndrome II
Aims
• Abdominal obesity prevalence
• Targeting Cardiometabolic Risk factors
• Multiple Risk Factor management
• A Critical Look at the Metabolic Syndrome
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)
Global cardiometabolic risk*
Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition
The new IDF definition focusses on abdominal obesity
rather than insulin resistance
International Diabetes Federation (IDF) Consensus Definition 2005
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
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
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
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
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
Diabetes in the new millenniumInterdisciplinary problem
Diabetes
Diabetes in the new millenniumInterdisciplinary problem
OBESITY
Diabetes in the new millenniumInterdisciplinary problem
DIAB
ESITY
TargetingTargeting
Cardiometabolic RiskCardiometabolic Risk
Central obesity: a driving force for cardiovascular disease & diabetes
“Balzac” by RodinFront
Back
Insulin Resistance: Associated Conditions
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
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)
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
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 ])
HypertensionHypertension::
• IDF:IDF:– BP >130/85 or on Rx for previously
diagnosed hypertensionhypertension
DyslipidemiaDyslipidemia::
• IDF:IDF:– Triglycerides - >150mg/dL (1.7 mmol /L)– HDL - <40 mg/dL (men), <50 mg/dL
(women)
Public Health ApproachPublic Health Approach
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
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.
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.
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
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/ 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
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
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.
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
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
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
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
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
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
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’.”
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.
Insulin Resistance: Associated Conditions
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
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?• 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
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
Central obesity: a driving force for cardiovascular disease & diabetes
“Balzac” by RodinFront
Back
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).
Insulin Resistance: Associated Conditions
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
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.
The new IDF definition focusses on
abdominal obesity rather than insulin
resistance
International Diabetes Federation (IDF) Consensus Definition 2005
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.
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:
• 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
• 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
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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