Gaetano Crepaldi
Department of Medical and Surgical sciences, University of Padova, Italy

In 1965, Pietro Avogaro and I described a new syndrome characterised by an association of metabolic abnormalities, specifically hyperlipidaemia, obesity, and diabetes. Interestingly, we also pointed out the quite frequent presence of hypertension in association with these metabolic abnormalities, as well as the high risk of coronary artery disease (CAD) in carriers of this cluster of metabolic abnormalities. Over the last 35 years, the definition of this pluriMetabolic Syndrome has evolved from the original description, with the addition of a more detailed definition of the typical lipoprotein abnormalities by Reaven who called it Syndrome X. Then Williams and colleagues in Salt Lake City described the clustering of hypertension, high triglycerides and VLDL, low HDL-cholesterol, obesity, and type 2 diabetes defining the syndrome as Familial Dyslipidaemic Hypertension. More recently, Kaplan defined the presence of a Deadly Quartet as the concurrent association of upper body obesity, glucose intolerance, hypertriglyceridaemia, and hypertension. The latest definition of the Metabolic Syndrome was given more recently by ATP III who defined it as the concurrent presence of three or more of the following abnormalities: abdominal obesity, glucose intolerance or diabetes, hypertriglyceridaemia, low HDL-cholesterol, hypertension.

Therefore, any patient with Metabolic Syndrome is for numerous reasons at very high risk of atherosclerosis. Many emerging risk factors not routinely measured are found to be abnormal in patients with the Metabolic Syndrome:

• insulin resistance,
• small, dense LDL,
• endothelial dysfunction,
• abnormal sympathetic nervous activity,
• prothrombotic markers-plasminogen activator inhibitor 1 (PAI-1), fibrinogen,
• proinflammatory markers such as C-Reactive Protein (CRP); Vascular Cell Adhesion Molecule (VCAM).

This emphasises the value of recognising Metabolic Syndrome in assessing CAD risk.
The effect of some components of the Mediterranean diet on these risk factors – and specifically on LDL density but also on endothelial dysfunction and the expression of proinflammatory markers such as CRP and VCAM – have been proven.
In particular, the Mediterranean diet, low in saturated fats and rich in antioxidants, may have beneficial effects both on the oxidizability of LDL particles and on thrombogenesis, apart from the effect on LDL-cholesterol levels per se. The Seven Country study clearly showed that the dietary intake of flavonoids, a large group of polyphenolic antioxidants, in the various countries in the Study was inversely associated with mortality from CAD and explained about 25% of the variance in CAD rates in the 16 cohorts assessed. In the same study, a multivariate analysis showed that saturated fat intake and flavonoids, independently of antioxidant vitamins, together explained about 65% of the variance in CAD rates. The Mediterranean diet is rich in flavonoids from a variety of sources (wine, vegetables, fruits, olive oil, etc).

In conclusion, the data accumulated over the past 40 years have contributed to defining the pluriMetabolic Syndrome as a complex clustering of many risk factors for cardiovascular disease. Recent data on the striking prevalence of Metabolic Syndrome make this disease the leading threat to cardiovascular health in our society. To deal with such a multifaceted disease, the ideal therapy calls for a multifactorial approach, such as that provided by the Mediterranean diet, which improves or even corrects some of the main metabolic abnormalities present in Metabolic Syndrome: small, dense LDL, low HDL-cholesterol, hypertriglyceridaemia, endothelial dysfunction, but also blood pressure and intra-abdominal obesity.