Transcript Cardiometabolic Syndrome

Cardiometabolic Syndrome
Nabil Sulaiman
Dr. Dhafir A. Mahmood
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
o Abdominal obesity prevalence
o Targeting Cardiometabolic Risk factors
o Multiple Risk Factor management
o A Critical Look at the Metabolic Syndrome
Clustering of Components
o Hypertension: BP. > 140/90
o 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 DM
FPG > 110 mg/dL (6.1mmol/L)
2hr.PG >200 mg/dL (11.1mmol/L)
o Microalbuninuria (WHO)
Global cardiometabolic risk*
* working definition
Gelfand EV et al, 2006; Vasudevan AR et al, 2005
International Diabetes Federation (IDF)
Consensus Definition 2005
The new IDF definition focuses on abdominal
obesity rather than insulin resistance
Why a New Definition of the MeS:
IDF Objectives
Needs
o 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
Fat Topography In
Type 2 Diabetic Subjects
Intramuscular
Subcutaneous
Intrahepatic
Intraabdominal
FFA*
TNF-alpha*
Leptin*
IL-6 (CRP)*
Tissue Factor*
PAI-1*
Angiotensinogen*
Abdominal obesity and increased risk of
cardiovascular events
Adjusted relative risk
The HOPE study
Waist
circumference (cm):
1.4
Tertile 1
Men
<95
Women
<87
Tertile 2
Tertile 3
95–103
>103
87–98
>98
1.29
1
0.8
1.27
1.17
1.2
1
1.16
1
CVD death
1.35
1.14
1
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
24
Relative risk
20
16
12
8
4
0
<71
71–75.9
76–81
81.1–86
86.1–91 91.1–96.3
Waist circumference (cm)
Carey VJ et al, 1997
>96.3
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
3.0
Relative risk
2.5
p for trend = 0.007
2.06
2.0
1.5
2.31
2.44
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)
CHD: coronary heart disease; BMI: body mass index
Rexrode KM et al, 1998
Diabetes in the new millennium
Interdisciplinary problem
Diabetes
Diabetes in the new millennium
Interdisciplinary problem
OBESITY
Diabetes in the new millennium
Interdisciplinary problem
DIAB
ESITY
Targeting
Cardiometabolic Risk
Central obesity: a driving force for
cardiovascular disease & diabetes
Front
Back
“Balzac” by Rodin
Insulin Resistance: Associated
Conditions
Linked Metabolic Abnormalities:
o Impaired glucose handling/insulin resistance
o Atherogenic dyslipidemia
o Endothelial dysfunction
o Prothrombotic state
o Hemodynamic changes
o Proinflammatory state
o Excess ovarian testosterone production
o Sleep-disordered breathing
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)
Multiple Risk Factor Management
o Obesity
o Glucose Intolerance
o Insulin Resistance
o Lipid Disorders
o Hypertension
o Goals: Minimize Risk of Type 2 Diabetes
and Cardiovascular Disease
Glucose Abnormalities:
o 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:
o IDF:
– BP >130/85 or on Rx for previously
diagnosed hypertension
Dyslipidemia:
o IDF:
– Triglycerides - >150mg/dL (1.7 mmol /L)
– HDL - <40 mg/dL (men), <50 mg/dL
(women)
Public Health Approach
Screening/Public Health Approach
o Public Education
o Screening for at risk individuals:
– Blood Sugar/ HbA1c
– Lipids
– Blood pressure
– Tobacco use
– Body habitus
– Family history
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 diabetes
o Goals:
Brisk walking - 30 min./day
10% reduction in body wt.
Smoking Cessation / Avoidance:
o A risk factor for development in children and
adults
o Both passive and active exposure harmful
o 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 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
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 diabetesrelated 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:
o Insulin Sensitizers:
– Biguanides – metformin
– Glitazones, Gltazars
– Can be used in combination
o Insulin Secretagogues:
– Sulfonylurea - glipizide, glyburide,
glimeparide, glibenclamide
– Meglitinides - repaglanide, netiglamide
BP Control - How Important?
o Goal: BP.<130/80
o 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
o Precedes literature on Metabolic Syndrome
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.
Substantial residual cardiovascular risk in
statin-treated patients
The MRC/BHF Heart Protection Study
% patients
30
Placebo
Statin
20
Risk reduction=24%
(p<0.0001)
19.8% of statin-treated
patients had a major
cardiovascular event
by 5 years
10
0
0
1
2
3
4
5
6
Year of follow-up
Heart Protection Study Collaborative Group, 2002
Medications:
o Hypertension:
– ACE inhibitors, ARBs
– Others - thiazides, calcium channel
blockers, beta blockers, alpha blockers
– Central acting Alfa agonist: Moxolidin
o Dylipidemia:
– Statins, Fibrates, Niacin
o Platelet inhibitors:
– ASA, clopidogrel
Individual metabolic abnormalities among
Qatari population according to gender
(Musallam et al 08)
Men (n = 405)
Variable
ATP III
n(%)
n(%)
Women (n=412)
p-Value
Abdominal obesity 227(56.0)
Hypertension
Diabetes
143(35.3)
77(19.0)
308(74.8)
156(37.9)
<0.001
0.448
107(26.0)
0.017
Hypertriglyceridemia
113(27.9)
83(20.1)
Low HDL
121(29.4)
0.055
95(23.5)
0.009
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
Country
Year
Sample
Prevalence (%)
Arab Americans
2003
542
23
Oman
2001
1419
21
Jordan
2002
1121
36
Saudi Arabia
2004
2250
20.8
Palestine
1998
Qatar
2007
817
27.6
Turkey
2004
1637
33.4*
?
10368
33.7
Iran
* Crude rates
17*
Mussallam et al. Int J Food Safety and PH 2008
A Critical Look at the Metabolic 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
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’.”
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.
Insulin Resistance: Associated
Conditions
Determinants and dynamics of the CVD
Epidemic in the developing Countries
Data from South Asian Immigrant studies
o Excess, early, and extensive CHD in persons of South Asian
origin
o 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”
Determinants and dynamics of the CVD
Epidemic in the developing Countries
Other 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)
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
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
Central obesity: a driving force for
cardiovascular disease & diabetes
Front
Back
“Balzac” by Rodin
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).
Insulin Resistance: Associated
Conditions
Prevalence (%)
Prevalence of the Metabolic Syndrome
Among US Adults NHANES 1988-1994
45
40
35
30
25
20
15
10
5
0
Men
Women
20-29
30-39
40-49
50-59
60-69
> 70
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
o 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.
International Diabetes Federation
(IDF) Consensus Definition 2005
The new IDF definition focuses on abdominal
obesity rather than insulin resistance
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 pressure
Systolic : > 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
Stop
smoking
Oral hypoglycaemics
ACEI &/or A2 receptor
blockers
Diet,
Exercise,
Lifestyle
change
Insulin
Statins &
Fibrates
Aspirin
CB1 Receptor
Blocker
Antihypertensives
Recommendations for treatment
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.
Management of the Metabolic Syndrome
o Appropriate & aggressive therapy is essential
for reducing patient risk of cardiovascular disease
o Lifestyle measures should be the first action
o 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
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
Contact Information
Nabil Sulaiman
[email protected]