Transcript Cardiometabolic Syndrome Nabil Sulaiman HOD Family and Community Medicine, Sharjah University and University of Melbourne & Dr Dhafir A.

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
Targeting Cardiometabolic Risk factors
Multiple Risk Factor management
A Critical Look at the Metabolic Syndrome
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*
* working definition
Gelfand EV et al, 2006; Vasudevan AR et al, 2005
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
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
Subcutaneous
Intrahepatic
Intraabdominal
FFA*
TNF-alpha*
Leptin*
IL-6 (CRP)*
Tissue Factor*
PAI-1*
Angiotensinogen*
Abdominal obesity and increased risk of
cardiovascular events
The HOPE study
Adjusted relative risk
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
>96.3
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
3.0
Relative risk
2.5
p for trend = 0.007
2.31
2.44
2.06
2.0
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)
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:
• 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:
• 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
• Obesity
• Glucose Intolerance
• Insulin Resistance
• Lipid Disorders
• Hypertension
• Goals: Minimize Risk of Type 2
Diabetes and Cardiovascular Disease
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:
•
IDF:
– BP >130/85 or on Rx for previously
diagnosed hypertension
Dyslipidemia:
•
IDF:
– Triglycerides - >150mg/dL (1.7 mmol /L)
– HDL - <40 mg/dL (men), <50 mg/dL
(women)
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?
•
•
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:
•
•
•
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 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
•
•
•
•
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:
•
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?
•
•
•
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?
• 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
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:
•
•
•
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(%)
ATP III
n(%)
p-Value
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
No of components of ATP III
Men (n = 405)
Variable n(%)
n(%)
Women (n=412)
p-Value
None
88(21.7)
74(18.0) –
One
103(25.4)
100(24.3)
Two
125(30.9)
111(26.9) –
Three or more
89(22.0)
127(30.8) –
0.033
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*
Iran
?
10368
33.7
* Crude rates
17*
Mussallam et al. Int J Food Safety and PH 2008
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 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 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
Front
Back
“Balzac” by Rodin
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 (%)
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
Ford E et al. JAMA. 2002(287):356.
40-49
50-59
60-69
> 70
Age (years)
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.
International Diabetes Federation
(IDF) Consensus Definition 2005
The new IDF definition focusses 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
Insulin
Statins &
Fibrates
ACEI &/or A2 receptor
blockers
Diet,
Exercise,
Lifestyle
change
Aspirin
CB1 Receptor
Blocker
Antihypertensives
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.
Management of the Metabolic Syndrome
• Appropriate & aggressive therapy is essential
for 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
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