A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF THE SUPPLEMENTATION WITH KIOLIC® IN PATIENTS WITH DIAGNOSIS OF METABOLIC SYNDROME TO IMPROVE ENDOTHELIAL FUNCTION AND INFLAMMATORY STATE. "KYMES"

Cardiovascular diseases (CVD) have become the main cause of death worldwide. It is estimated that 3.8 million men and 3.4 million women die every year from this cause (WHO 2006). In addition, an increase of 47 to 83 million disability-adjusted life years (DALY) between 1990 and 2020 has been projected for this disease (WHO 2006b). It is calculated that 5.3 million deaths by CVD occur in developed countries, while 8 to 9 million deaths occur in developing countries (Yusuf et al 2001; Lopez 1993). In Colombia, the death rate for CHD in 20-84 year old subjects increased from 58.5 per 100.000 in 1980 to 103.2 in 1996. Only 30% of this increase could be attributed to population aging (Lopez-Jaramillo et al 2001). From 1997 to 2001 acute myocardial infarction (AMI), stroke and diabetes mellitus type 2 (DM 2) were responsible for 213.150 deaths (19.6%). Together, these deaths exceeded those due to violent causes, which for several years were the first cause of death in this country.

The INTERHEART study (Yusuf 2004) identified the risk factors associated with AMI in 52 developed and developing countries. Smoking, hypertension, abnormal lipids, abdominal obesity (AO), diabetes and psychosocial stress were associated with ischemic disease in all regions of the world with no differences in age and gender. However, Lanas et al. (2007) reported the results of 1237 Latin American subjects from Brazil, Argentina, Chile and Colombia, included in the INTERHEART study, demonstrated that central obesity was the most important risk factor associated with AMI in this population, much more than in the entire population of the study. We have proposed that the biological response to obesity in developed countries is different than in developing countries, and that this response is modulated through epigenetic regulation (Lopez-Jaramillo et al 2008).

The consumer society has given rise to an increase in the prevalence of overweight, obesity, hypertension, diabetes mellitus type 2 (DM2) and finally metabolic syndrome (MS). Changes in the nutritional and physical habits are the main characteristics involved in the fast economic transition, where the over nutrition and the increased consumption of saturated fat and cholesterol, low intakes of polyunsaturated fat and lower physical activity are common determinants (Pi-Sunyer 2002).

The metabolic syndrome is a set of risk factors for diabetes mellitus type 2 and cardiovascular disease, characterized by the presence of resistance to insulin and compensating hyperinsulinemia, associate to alterations of carbohydrates and lipids metabolism, elevated arterial blood pressure and obesity (Pineda 2008). In 1988, Reaven observed that several risk factors (dislipidemia, hypertension, hyperglycemia) tended to be together. This set was named syndrome X (Reaven 1988). The name metabolic syndrome like a diagnostic entity with defined criteria was introduced by the WHO in 1998 (Alberti, Zimmet 1998). The metabolic syndrome prevalence varies according to some factors such as gender, age, ethnic group, but it is located between 15% to a 40%, being greater in the population of hispanic origin (Ford et al 2002). Metabolic syndrome is important in Colombia, where the population have a major sensibility to the development of an atherogenic lipid profile (Perez et al 2003), and low grade inflammation correlated to lower levels of abdominal obesity have been described (Garcia et al 2007). These factors are associated with an increase of the vascular reactivity to the angiotensin II stimulus (Rueda-Clausen et al 2007), hormone that is also produced in the visceral adiposity (17). The latter, at the endothelial level, increases the TNF production (Arenas et al 2004), a proinflammatory citokine that stimulates the hepatic production of C reactive protein (CRP), which in our population in situations such as abdominal obesity in adults (Garcia et al 2007) and children (Lopez-Jaramillo 2008b), arterial hypertension (Rueda-Clausen et al 2007), endothelial dysfunction (Garcia et al 2007b) and pregnancy induced hypertension (Teran et al 2001) is presented in higher levels than in other populations.

Recent studies have shown that obesity, insulin resistance and diabetes type 2 are proinflammatory states (Grundy et al 2004). It has been demonstrated that enlargement of adipocytes is frequently observed in obesity and in pre-diabetic individuals and in type 2 diabetics (Lundgren et al 2007). The increased adipocyte size may represent a failure in the recruitment of new adipocytes due to impaired differentiation; it has recently been shown that fat cell enlargement is an independent marker of insulin resistance (Rotter et al 2003). Cell size expansion leads to a reduction in the production of anti-inflammatory adipokines (like adiponectin) while proinflammatory cytokines (like IL-6, and PCR) are markedly increased (Rotter et al 2003).