The metabolic syndrome and visceral obesity have an increasing prevalence and incidence in the general population. The actual prevalence of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES Ⅲ, INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer. Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944 717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical significance and may have profound health benefits on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.

Epicardial fat is a relatively neglected component of the heart and could be an important risk factor of cardiac disease. The objective of our study was to assess the relationship between epicardial adipose tissue (EAT) extent, fat distribution, and coronaropathy in a group of adult victims of accidental or suspicious sudden death. In 56 cadavers, we performed 34 measurements of EAT from five computerized photographs of the heart (anterior and posterior faces, and three ventricle transversal slices) and analyzed their relationship with anthropometric markers of adiposity (BMI, waist and leg circumference, thickness of abdominal and thigh subcutaneous adipose tissue (SAT)), with the presence and staging of coronary artery disease (CAD), and with markers of myocardial hypertrophy. Simple linear regressions showed that EAT measurements are highly intercorrelated (r from 0.4 to 0.6, P < 0.001), and correlate with age, waist circumference, and heart weight, and to a lesser extent, with BMI, abdominal SAT thickness, and leg SAT thickness. Multiple regression showed that age, waist circumference, and heart weight significantly and independently correlate with EAT (P < 0.0001). No other anthropometric measurement was found independently correlated with EAT. The EAT/myocardium ratios correlated positively with age and waist circumference. Anterior and posterior areas of EAT were found significantly increased in patients with CAD and correlated positively with CAD staging (P = 0.0034, r = 0.38). Anterior EAT surface was found positively associated with CAD (P = 0.01), independently of age and other adiposity measurements. Prospective studies are needed to assess the risk of occurrence/progression of CAD that relate to EAT excess.

Epicardial white adipose tissue (eWAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Adrenomedullin (AM) is a potent vasodilatator and antioxidative peptide which has been shown to play a cytoprotective role in experimental models of acute myocardial infarction. We studied, using immunohistochemistry and qRT-PCR, the expression of AM and its receptors calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP)2 and -3 in paired biopsies of subcutaneous WAT (sWAT) and eWAT obtained from patients with coronary artery disease (CAD) or without CAD (NCAD). In eWAT obtained from NCAD or CAD patients, immunoreactivity for AM, CRLR, and RAMP2 and -3 was detected in blood vessel walls and isolated stromal cells close to adipocytes. Some of the AM positive stromal cells colocalized CD68 immunoreactivity. eWAT from CAD patients showed increased AM immunoreactivity and AM gene expression. CRLR mRNA levels were comparable in sWAT of both groups and decreased by 40-50% in eWAT, irrespectively of the coronary status. RAMP2 mRNA concentrations did not change while RAMP3 mRNA levels increased in sWAT from CAD patients. There was a positive linear relationship between eWAT 11beta-hydroxysteroid dehydrogenase type 1 mRNA (11beta-HSD-1, the enzyme that converts inactive to active glucocorticoids) and AM mRNA. In conclusion, we demonstrate that AM and its receptors are expressed in eWAT. Our data suggest that eWAT AM, which could originate from macrophages, is related to 11beta-HSD-1 expression. AM synthesis, which is increased in eWAT during chronic CAD in humans, can play a cardioprotective role.

We have shown for the first time an increased expression of sPLA2-IIA in EAT in patients with CAD. sPLA2-IIA is a phospholipase, which has been shown to be an independent risk factor for CAD. These findings suggest that EAT has a potentially pathophysiological role in CAD.