METABOLIC SYNDROME

Dr. Md.Toufiqur Rahman

MBBS, FCPS, MD, FACC, FESC, FRCPE, FSCAI, FAPSC, FAPSIC, FAHA, FCCP, FRCPG

Associate Professor of Cardiology

National Institute of Cardiovascular Diseases(NICVD),Sher-e-Bangla Nagar, Dhaka-1207

Consultant, Medinova, Malibagh branch

Honorary Consultant, Apollo Hospitals, Dhaka and STS Life Care Centre, Dhanmondi

drtoufiq19711@yahoo.com

Introduction Integration of CM risk factors Targeting obesity Management of hypertension Management of dyslipidemia Antiplatelet therapy Management of microalbuminuria CB1 blockade Conclusion

METABOLIC SYNDROME

METABOLIC SYNDROME

Heart disease and stroke are the most

common life-threatening consequences of diabetes mellitus, with mortality rates up to two to four times higher for persons with diabetes vs. those without.

JAMA.2002;288:2709-2716

INTRODUCTION

Type-2 diabetes is associated with clustering of multiple cardiometabolic risk factors such as

Obesity, Hypertension, Dyslipidaemia, Microalbuminuria, Prothombotic state. Proinflammatory state

METABOLIC SYNDROME (MS)

Cluster of cardiovascular risk factors occurring in association with insulin resistance and obesity.

Obesity, insulin resistance/hyperglycemia and dyslipidemias (high TG and low HDL) are common components in all definitions of MS.

In patients with the metabolic syndrome, relative risk for ASCVD ranges form 1.5 to 3.0

Once diabetes develops, cardiovascular risk increases even more.

ASCVD risk in MS is greater than the sum of its measured risk factors and the risk rises geometrically instead of linearly (Grundy 2006).

INTEGRATION OF MULTIPLE CARDIOMETABOLIC RISK FACTORS

TARGETING OBESITY

TARGETING OBESITY

• Measures of obesity- body mass index (BMI) as a measure of overall obesity and waist circumference (WC) as a measure of abdominal obesity.

• WHO 1999 - BMI > 30 kg/m2 or Waist-to-hip ratio>0.9 (male) or >0.85 (female)

Waist circumference NCEP ATP III - ≥102 cm (male), ≥88 cm

(female) IDF 2005 (South Asian) - ≥90 cm (male), ≥80 cm (female)

THERAPEUTIC GOALS AND RECOMMENDATIONS WEIGHT MANAGEMENT

Goals: Reduce body weight by 7% to 10%

during year 1 of therapy. BMI - 18.5-24.9 kg/m2 Waist circumference: <90 cm in male <80 cm in female

RECOMMENDATIONS -- WEIGHT MANAGEMENT

Balance of physical activity, caloric intake, and formal behavior-modification programs.

Decrease caloric intake by 500 to 1000 calories per day for over weight or obese or metabolic syndrome.

Lake of Physical Activity

How much active we are?

THERAPEUTIC GOALS AND RECOMMENDATIONSPHYSICAL INACTIVITY Goals Regular moderate-intensity physical

activity; at least 30 min of continuous or intermittent (and preferably 60 min) 5 d/wk, but preferably daily

RecommendationsFor general public (without any risk factors)

> 30 mins brisk walking at least 5 days of the week, preferably daily.

Those with obesity or metabolic syndrome sixty minutes or more of continuous or intermittent aerobic activity, preferably done every day, will promote weight loss or weight-loss maintenance

RECOMMENDATIONS Preference is given to 60 minutes of moderate

intensity brisk walking to be supplemented by other activities including :

multiple short (10- to 15-minute) bouts of activity (walking breaks at work, gardening, or household work),

using simple exercise equipment (e.g., treadmills),

jogging, swimming,

biking, golfing, team sports, and engaging in resistance training

avoiding common sedentary activities in leisure time (television watching and computer games)

Lack of vegetables& fruits

Excess alcohol/soft drinks

Excess salty sugary fatty food

Recipe for Unhealthy Diet

THERAPEUTIC GOALS AND RECOMMENDATIONS -- DIET Goals: Ample intake of fresh fruits and vegetables, Low salt intake Reduced intakes of saturated fats, trans fats and

cholesterol Recommendations: At least 5 portions of fresh fruits and vegetables

per day (one large apple, guava or tomato or 2 teaspoonful cooked vegetables is equal to one portion)

Whole grains and fish intake should be encouraged

Fiber intake (20-35g/d) including 2g/d plant stanol /sterols and > 10g/d viscous fiber

Encourage omega-3 fatty acid in the form of fish or in capsule form (1g/d)

RECOMMENDATIONS -DIET (CONT’D):

Saturated fat ,<7% of total calories; Reduce trans fat; Dietary cholesterol < 200 mg daily; Total fat 25–35% of total calories; Most dietary fat should be unsaturated; Carbohydrates- 50-60 % of total calories Proteins 15 % of total calories Simple sugars should be limited. Moderation of alcohol intake; overweight

patients should avoid alcohol.

HYPERTENSION

Blood pressure should be measured at every routine diabetes visit.

Goals: Patient of diabetes

should be treated to a SBP <130 mmHG and DBP <80 mmHG.

HYPERTENSION

SBP 130-139 mmHG & DBP 80-89 mmHG :

Lifestyle and behavioral therapy for a maximum of 3 months. If target are not achieved treat

with pharmacological agent.

SBP≥140 mmHG & DBP ≥90 mmHG: Start with drug therapy in addition to lifestyle and behavioral therapy.

HYPERTENSION

Multiple drug therapy (Two or more agents at proper doses) is required to achieve blood pressure target.

All patient with diabetes and hypertension should be treated with a regimen that includes either an ACE inhibitor or an ARB.

If ACEi, ARBs or diuretics is used, monitor renal function and serum potassium level.

MANAGEMENT OF DIABETIC DYSLIPIDEMIA

THE CHANGING LANDSCAPE OF CARDIOMETABOLIC RISK

Past burden : High LDL Coming burden :

Dyslipidaemia ( low HDL, high TG & small, dense LDL)

HDL WITH NEW DIMENTIONS

Numerous prospective epidemiological studies have shown a strong inverse relationship between HDL cholesterol (HDL-C) levels and coronary heart disease (CHD).

Many controlled clinical trials demonstrate that treating patients with low HDL-C with lipid modifying therapies, can reduce major coronary events.

Even in patients treated to aggressive LDL-C goals, coronary events still occur, and low HDL-C is a major risk factor in this group.

CURRENT APPROACHES TO PATIENTS WITH LOW HDL-C

Therapeutic lifestyle changes: Smoking cessation Aerobic exercise Weight reduction Diet Pharmacological therapy: Increases HDL by- Statins ---5-10% Fibrates ---- 5-20% Niacin ------ 15-30% Pioglitazone ----5-15%

P.J. Barter, Editorial, Arterioscler Thromb Vasc Biol. 2005;25:1305-1306

NEW APPROACHES TO THERAPEUTIC TARGETING OF HDL New Approaches are based on current

understanding of M/A of HDL.

An important concept is that simply raising HDL-C levels may not necessarily be the optimal target for the development of new therapies targeted toward HDL.

Function of HDL is more important than its concentration and that therapies that improve HDL “function,” even if they do not increase HDL-C levels, may have important antiatherogenic and vascular protective effects.

THE TARGET AREAS FOR THERAPY

Apolipoprotein A-I–Directed Therapies -Recombinant Apo A-I Milano and synthetic HDL-C -Apo A-I mimetic peptide

Therapies Directed to Promotion of Macrophage Cholesterol Efflux and RCT

-Increase expression of ABCAI receptor

Therapies Intended to Alter HDL and ApoA-I Metabolism to Raise Their Levels in Plasma

-CETP inhibitors : Torcetrapib, JTT-705

LOWERING TG Goal: Lower TG to<150mg/dl Lifestyle interventions: Weight loss Increased physical activity Restricted intake of saturated fat Increased monounsaturated fat Reduction of carbohydrate

intake Reduction of alcohol

consumption.

LOWERING TG

Improved glycaemic control

Fibric acid derivatives (gemfibrozil, fenofibrate)

Niacin

High dose statins (in those who also have high LDL cholesterol)

ANTIPLATELET AGENT

Aspirin therapy (75-162mg/day) is recommended in all patients with 10 years risk of CHD ≥10%,CHD patients, and coronary risk equivalents including diabetes.

MANAGEMENT OF MICROALBUMINURIA

Screening: Annually in all type-2 diabetic

patients starting at diagnosis and during pregnancy.

Treatment: In the treatment of both micro

and macroalbuminuria, either ACEi or ARBs should be used except during

pregnancy.

ATTACKING MULTIPLE RISK FACTORS BY SINGLE AGENT – RIMONABANT (CB1 BLOCKER)

Central blockade(hypothalamus)

Decreased food intake (decrease weight)

Peripheral blockade(adipose tissue)

Decreased abdominal fat (waist circumference) Adiponectin Triglycerides High-density lipoprotein Small, dense low-density lipprotein C-reactive protein Insulin resistance

THANK YOUdrtoufiq19711@yahoo.com

Asia Pacific Congress of Hypertension, 2014, February

Cebu city, Phillipines

Seminar on Management of Hypertension, Gulshan, Dhaka