Cardiology - Metabolic syndrome

by Noeleen Fallon and Shirley Ingram

Cardiovascular disease and its contributory factors is among the most significant public health problem that we have faced in recent times.

The WIN Continuing Education section is continuing to focus on this important clinical area throughout 2007, given that it impacts on all areas of the Irish health service.

Diabetes is one of the primary risk factors for the development of coronary heart disease, and the focus on diabetes management will also continue this year.

This month the Cardiology Module focuses on the metabolic syndrome and its revelation in the cardiac rehabilitation population. An outline of recent research on this subject carried out in Tallaght Hospital will also feature in the February issue.

Next month’s article will focus on coronary artery bypass surgery and the role of the ANP.

There has been continuous observation and study of metabolic risk factors during the 20th Century. In 1923 a Swedish physician, Eskil Kylin identified hypertension, elevated blood sugar and uric acid levels frequently appeared in patients at the same time. His observations were published entitled The hypertension-hyperglycaemia-hyperuricaemia syndrome.1

The Framingham study in the 1950s discovered clustering of certain risk factors such as hypertension, dyslipidaemia, increased body mass index and diabetes mellitus in both sexes occurred to a greater degree than could be anticipated by chance. From this study, the concept of risk factors developed and by their treatment, the incidence of cardiovascular disease would be reduced.1

In 1988 Reaven discussed a pathophysiological concept of metabolic factors, identified as ‘syndrome x’, that included insulin resistance, glucose intolerance, hyperinsulinaemia, hypertriglyceridaemia, reduced levels of high density lipoproteins (HDL) and hypertension.2 The clustering of these risk factors in people leads to a diagnosis of metabolic syndrome, which predisposes to cardiovascular disease.3,4

The risk of CVD and premature death is very high when a person is diagnosed with metabolic syndrome. These people have three times the risk of CVD and twice the risk of CHD death and a fivefold risk of developing diabetes if this is not already present.4,5

Definition
In 1998 the World Health Organisation defined metabolic syndrome according to certain criteria (see Table 1) to create interest and debate.6 The European Group on Insulin Resistance (EGIR) in the same year categorised metabolic syndrome as insulin resistance plus two other remaining factors. In 2001 the Third Adult Treatment Panel (ATP III) in the National Cholesterol Education Program (NCEP), USA defined the syndrome as having three or more metabolic risk factors (see Table 1).7

Definitions of metabolic syndrome
(NCEP ATP III and WHO criteria)
National Cholesterol Education Program7
At least three of the following:

Abdominal obesity:

Women waist circumference > 88cm

Men waist circumference > 102cm

Triglycerides

Ž 1.7mmol/L

HDL cholesterol:

Women 1.30mmol/L

Men 1.00mmol/L

Blood pressure

Ž 130/85mmHg

Fasting glucose

Ž 6.1mmol/L

World Health Organisation6
Insulin resistance and/or glucose intolerance (plasma glucose >7.8mmol/L) plus two of the following:

Abdominal obesity:

BMI > 30 kg/m2

Waist/hip ratio – M > 0.85; F > 0.90

Triglycerides

Ž 1.7mmol/L

HDL cholesterol:

Women 1.0mmol/L

Men 0.9mmol/L

Blood pressure

Ž 140/90mmHg

Micro albuminuria

> 20mg/min

As varying definitions lead to confusion and in order to bring various groups together and establish a practical usable guide that was workable world wide, the International Diabetic Federation (IDF) in 2004 laid down the criteria set out in Table 2. The IDF included various waist measurements according to ethnicity. The American Heart Association in 2005, followed on the previous ATP III criteria of three or more factors, but changed the BSL value to < 5.6mmol/L and BP of Ž 135/85mmHg. The AHA also concurred with European colleagues that waist circumference may require ethnic variations.

International Diabetes Federation criteria for metabolic syndrome

Central obesity:

– waist circumference

Ž 94cm Europid man

– waist circumference

Ž 80cm Europid woman

Plus at least two of the following:

Triglycerides

Ž 1.70mmol/L

HDL cholesterol:

Women 1.29mmol/L

Men 1.03mmol/L

Blood Pressure

Ž 130/85mmHg

Fasting glucose

Ž 5.6mmol/L

Prevalence
In the US, the Third National Health and Nutrition Examination Study (NHANES III) involved 9,000 patients aged more than 20 years. Using the ATP III criteria, the prevalence of metabolic syndrome was 24% in men and 23% in women. Age specific prevalence increased from 5% in the 20-30 year age group to 40% for > 60 year age group. Based on this study an estimated 50 million Americans have metabolic syndrome.8 The prevalence of metabolic syndrome on entry to the West of Scotland Coronary Prevention Study was 26%. In this study metabolic syndrome was a definite predictor of CHD and diabetes.9 Prevalence increases with age. In healthy people prevalence is 10%-15%; in people with CVD prevalence rises to 10%-40%.1

Who is at risk of metabolic syndrome?
The background factors include:

Components of metabolic syndrome
The components of metabolic syndrome include:

Insulin resistance: There is an abnormal response within the body’s tissues to insulin and insulin resistance develops. This leads to glucose intolerance, increased hepatic glucogenesis and increased production of triglycerides and very low density lipoproteins (VLDL).4 There may be a genetic predisposition but acquired factors, that is, excess body fat and physical inactivity also contribute. The common feature of central obesity leads to decreased peripheral insulin mediated glucose disposal.1,10

Obesity and free fatty acids: Overweight/obesity, particularly central adiposity, is closely associated with dyslipidaemia, hypertension, insulin resistance and diabetes. Adipose tissue has been recognised as an active metabolic organ since the discovery of free fatty acids (FFA) in the 1950s. The increased abdominal adipose tissue mass is more sensitive to FFA mobilising stimuli and delivers FFA directly to the liver.10 Adipose tissue, containing triglycerides, is broken down and causes the release of FFA into the blood stream. This process is fine-tuned in order to supply fuel for the energy needs of the body. Insulin is the principal inhibitor of the fat mobilising lipolysis. An excessive rate of mobilisation raises plasma levels of FFA. This leads to insulin resistance, decreased peripheral glucose uptake and increased hepatic glucose production, leading to hyperglycaemia.

Abdominal adipose tissue is also a source of several adipokinetic hormones and other factors that are elevated in obesity such as leptin, cortisol and adiponectin.4
Atherogenic dyslipidaemia: Small dense LDL particles, high triglycerides combined with low HDL cholesterol foster plaque development within the artery walls leading to structural changes and CVD.3

Hypertension: This is strongly associated with obesity and commonly occurs in insulin resistant people.

Prothrombotic state: This is characterised by increased plasmogINOgen activator inhibitor (PAI-1) which inhibits the generation of plasmin (enzyme that dissolves fibrin within clots). A positive relationship between PAI-1 and plasma triglycerides leads to an increased risk of CHD. Metabolic syndrome is associated with increased levels of fibrINOgen, an independent risk factor for CHD.1

Proinflammatory state: Elevation of high sensitivity C reactive protein (CRP) levels reflect acute and chronic inflammatory tissue damage. CRP synthesis is stimulated by cytokines released from macrophages, in particular interleukin-6 and tumour necrosis factor alpha. CRP inhibits the production of nitric-oxide and stimulates the production of adhesion molecules in endothelial tissue.1

Complications
There is a large body of evidence showing that all components of the metabolic syndrome alone or in combination carry a high risk of atherosclerosis with the development of CVD, CVA and PVD.4 Many patients when diagnosed with this syndrome have insulin resistance/hyperglycaemia that may forecast the development of diabetes. In addition the syndrome may predispose to other clinical conditions such as fatty liver, gallstones, polycystic ovary disease, and airway or prostatic problems.1,4

Management
The cornerstone for treatment of metabolic syndrome is a two step strategy – a combination of diet and exercise. Weight loss and physical activity in overweight and obese people are paramount.1,11 The underlying insulin resistant state must become a target for therapy. If lifestyle changes don’t lead to the desired outcome, pharmaceutical measures must be applied. The initial treatment of dyslipidaemia is statin therapy. Nicotinic acid and fibrates both lower plasma triglycerides to the same extent and raise HDL. A greater rise in HDL is demonstrated with nicotinic acid and an additional benefit reduces plasma FFA by inhibiting mobilisation. By prescribing metformin and thiazolidinediones, glucose intolerance and insulin resistance may be treated effectively. Blood pressure must be treated to target but be aware of side effects of some medications.

Noeleen Fallon and Shirley Ingram are cardiac rehabilitation co-ordinators in the Cardiac Rehabilitation Department, Adelaide and Meath Hospital, Tallaght, Dublin

Research: Study on the metabolic syndrome and its revelation in the cardiac rehabilitation population carried out in the Adelaide and Meath Hospital will feature in the February issue

References

  1. Carlson LA. Clinician's Manual on The Metabolic Syndrome Science Press London 2004
  2. Reaven GM, Banting Lecture: Role of insulin resistance inhuman disease. Diabetes 1988; 37:1595-1607
  3. Gotto A et al. Dyslipidaemia and Coronary artery disease 3rd Ed. ILIB (International Lipid Information Bureau), New York 2003
  4. Grundy SM et al. Definition of Metabolic syndrome Circulation. 2004; 109: 433-438
  5. Defusing a metabolic time bomb. WIN 2005;13(10): 43-44
  6. Alberti KG, Zimmet PZ. World Health Organisation Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation, Geneva WHO 1999
  7. The expert panel. The Third Report of the National Educational Program (NCEP) Expert panel; on Detection, evaluation and Treatment of high blood cholesterol in Adults (ATP III) Final Report. Circulation 2002;106: 3143-3421
  8. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutritional Examination Survey. JAMA 2002; 287(3): 356-359
  9. Sattar N, Gaw A, Scherbakava O. Metabolic syndrome with and without c-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003; 108: 414-419
  10. Miranda PJ et al. Metabolic syndrome: Definition, pathophysiology and mechanisms. Am Heart J 2005; 149: 33-43
  11. www.americanheart.org

 Cardiology - Metabolic syndrome

 


All rights reserved by INMO. Please don't use without permission