The metabolic syndrome is associated with increased risk of a variety of disease outcomes including diabetes, cardiovascular disease, fatty liver and non-alcoholic steatohepatosis, polycystic ovary syndrome, gallstones, asthma, sleep apnoea and some malignant diseases. The biggest impact the metabolic syndrome has on health is the increased incidence of atheromatous vascular disease.

(A) Cardiovascular disease

Until the last few years there had been few studies of mortality or morbidity associated with the metabolic syndrome although the individual components of hypertension, dyslipidaemia and glucose intolerance were all known to be associated with increased atheromatous vascular disease. Recently published studies have used different criteria for the metabolic syndrome and followed subjects for varied lengths of time. Thus the magnitude of risk associated with the metabolic syndrome varies across the studies.

In a study of Japanese men without cardiovascular disease at baseline followed for 7 years, the subsequent development of cardiovascular disease was correlated with the number of features of the metabolic syndrome at baseline. Those men with 3 or more features at baseline had more than 12 times the risk of developing cardiovascular disease than those with none.(1) Other studies have shown a relative risk of developing cardiovascular disease for those with 3 or more features compared to those with 2 or less of 1.3 to 1.7.(2-4) For individuals with diabetes the relative risk is higher with 5 times increased risk of cardiovascular disease for those with the metabolic syndrome and diabetes compared to those with diabetes without the metabolic syndrome.(5)

All cause mortality is increased by 20-80% in individuals with the metabolic syndrome with mortality from cardiovascular disease increased by 60-280% and death from coronary heart disease increased by 70-330%.(6-8)The presence of the metabolic syndrome confers an increased risk of death from coronary heart disease in women compared to men.(9)

(B) Peripheral arterial disease

The relationship between insulin resistance, type 2 diabetes and the metabolic syndrome and peripheral arterial disease has been less extensively studied than the relationship with coronary artery disease.

Smoking is probably the most important risk factor for the development of peripheral vascular disease. More than 90% of patients attending surgical clinics with peripheral vascular disease have smoked at some point in their life.(10) Risk increases with number of cigarettes smoked per day.(11) Although smoking is the strongest predictor for the development of peripheral vascular disease, the presence of the metabolic syndrome can also predict the development of peripheral vascular disease. In a prospective study of 1 559 men and women aged 55-74 years at baseline and followed for 15 years, 24% of those with the metabolic syndrome developed peripheral arterial disease, defined as an ankle to brachial pressure ratio of less than 0.9 compared to 15% of those without the metabolic syndrome.(12)

(C) Non alcoholic steatohepatitis NASH is an important condition strongly associated with metabolic syndrome that was previously thought to be relatively harmless. This is a complex condition and it is beyond the scope of this review to consider the subject matter in detail. The reader is referred to more detailed reviews such as Angulo et al.(13) NASH is a poorly understood condition. Insulin resistance and increased non esterified fatty acid supply to the liver is associated with increased intrahepatic production of free fatty acids from glucose not taken up by peripheral adipocytes and myocytes. Excess hepatic fatty acids are not oxidised and are converted to diacyl- and triacylglycerols and stored in the hepatocyte cytoplasm, leading to steatosis. NASH is not a harmless condition and contributes to liver fibrosis and potentially to cirrhosis in a proportion of patients.(14)

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2. Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly DS, Haffner SM, et al. 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 Jul 29;108(4):414-9.
3. Girman CJ, Rhodes T, Mercuri M, Pyorala K, Kjekshus J, Pedersen TR, et al. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 2004 Jan 15;93(2):136-41.
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9. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, et al. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2005 Feb;28(2):385-90.
10. Fowkes FGR. Epidemiology of peripheral arterial disease. London: Springer Verlag; 1991.
11. Bowlin SJ, Medalie JH, Flocke SA, Zyzanski SJ, Goldbourt U. Epidemiology of intermittent claudication in middle-aged men. Am J Epidemiol 1994 Sep 1;140(5):418-30.
12. Wild S, Smith F, Lee A, Fowkes G. Ankle-brachial pressure index and metabolic syndrome are independent predictors of cardiovascular disease mortality in the Edinburgh Artery Study cohort. Circulation 2004 Feb 24;109(7):E133-E134.
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