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 FFA* TNF-alpha* Leptin* IL-6 (CRP)* Tissue Factor* PAI-1* Angiotensinogen*

Intrahepatic Intraabdominal

Abdominal obesity and increased risk of cardiovascular events

The HOPE study
Tertile 1 Waist circumference (cm): Men <95 95103 >103 Women <87 8798 >98

Adjusted relative risk

1.4
1.29

Tertile 2 Tertile 3

1.35

1.27 1.16 1 1 1.14

1.2
1

1.17

0.8

CVD death

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 20
Relative risk

16
12 8 4 0
<71 7175.9 7681 81.186 86.191 91.196.3 >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
2.5
Relative risk p for trend = 0.007

2.31 2.06

2.44

2.0 1.5 1.0 0.5 0.0 <69.8 69.8<74.2 1.27

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 Balzac by Rodin

Back

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?

Goals:

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

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: 405412.

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
30
Placebo Statin

% patients

20

Risk reduction=24%
(p<0.0001)

10

19.8% of statin-treated patients had a major cardiovascular event by 5 years

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) Variable n(%) ATP III Abdominal obesity Hypertension Diabetes n(%)

Women (n=412) p-Value

227(56.0) 143(35.3) 77(19.0)

308(74.8) 156(37.9) 107(26.0)

<0.001 0.448 0.017

Hypertriglyceridemia
Low HDL

113(27.9)
95(23.5)

83(20.1)
121(29.4)

0.009
0.055

Individual metabolic abnormalities among Qatari population according to gender No of components of ATP III Men (n = 405) Variable n(%) n(%) None 88(21.7) Women (n=412)

p-Value
74(18.0)

One
Two

103(25.4)
125(30.9)

100(24.3)
111(26.9)

0.033

Three or more

89(22.0)

127(30.8)

Prevalence of MeS in different Countries

Country Arab Americans Oman Jordan Saudi Arabia Palestine Qatar Turkey Year 2003 2001 2002 2004 1998 2007 2004 817 1637 Sample 542 1419 1121 2250 Prevalence (%) 23 21 36 20.8 17* 27.6 33.4*

Iran
* Crude rates

10368

33.7

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 its 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

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

Data from South Asian Immigrant studies

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 ( Barkers hypothesis) (Baker DJP,BMJ,1993) Low birth weight associated with increased CVD Poor infant growth and CVD relation

Geneticenvironment interactions
(Enas EA, Clin. Cardiol. 1995; 18: 1315)

- 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 Balzac by Rodin

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 1988-1994

45 40 35 30 25 20 15 10 5 0

Prevalence (%)

Men Women

20-29

30-39

40-49

50-59

60-69

> 70

Ford E et al. JAMA. 2002(287):356.

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 Reduced HDL cholesterol > 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality < 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 Systolic : > 130 mmHg or Diastolic: > 85 mmHg or Treatment of previously diagnosed hypertension 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.

Raised blood pressure

Raised fasting plasma glucose

Treatment of Metabolic Syndrome: 2005

Stop smoking Oral hypoglycaemics ACEI &/or A2 receptor blockers Diet, Exercise, Lifestyle change

Aspirin

Insulin

Statins & Fibrates

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