Metabolic Syndrome, a map of the cardiovascular damage

The metabolic syndrome (MS) is a cluster of metabolic abnormalities with abdominal obesity (increased waist circumference) at its centre. Although all forms of obesity have a negative impact on human health, metabolic syndrome describes a set of particularly adverse biochemical changes accompanying (abdominal) obesity.

These biochemical changes explain the increase in diabetes and cardiovascular disease (heart attack, stroke, heart failure) seen with MS, less clearly seen in those forms of obesity which minimally interfere with metabolism. Recent guidelines therefore identified the metabolic syndrome as a risk factor for cardiovascular disease deserving increased clinical attention. MS is most often identified by having three or more out of five possible abnormalities (components) which form the metabolic syndrome cluster.

These five abnormalities in the cluster are:

1. increased waist circumference (abdominal obesity),
2. elevated triglycerides (a fat component in the blood),
3. low HDL-cholesterol ("good" cholesterol),
4. a slightly increased blood glucose level (impaired fasting glycemia: the blood sugar level is not as high as in diabetes but is elevated above normal), and
5. high blood pressure.

At present few data are available with regard to MS prevalence in Europe and its early links with early cardiac and vascular damage. Our research from the Asklepios Study indicates that in (young) middle-aged subjects (35-55 year old) MS is frequently present (9-16% of subjects depending on the definition used) and that its presence coincides with a wide range of adverse cardiovascular changes. More specifically we found a strong association between presence of MS and inflammation (a well documented marker of risk for future heart attacks and stroke), thickening and stiffening of the heart (potentially predisposing to heart failure) and more pronounced atherosclerosis (calcification and narrowing of the arteries). Importantly these effects were graded, every additional MS component present translated into a gradually higher likelihood of finding cardiovascular damage. Whilst subjects with one or two metabolic abnormalities do not have a metabolic syndrome (three or more components are necessary by definition), they do have a higher risk than an individual without any metabolic abnormalities. Metabolic syndrome is not only an all/none diagnosis (present in 9-16% of the population) as every additional component of the MS yielded an increase in cardiovascular abnormalities. The implications of the present findings should therefore also be relevant for much larger segment of the population (more than 50%) having at least one MS component. Furthermore our data suggest that although men in this age group have the MS more frequently, that women seem more prone to its adverse consequences. Efforts should be focused on awareness of abdominal obesity as a risk factor for developing heart disease, and on wide ranging preventive strategies to avert its (potentially epidemic) consequences.

The Asklepios Study is a cross-sectional and longitudinal population study focusing on the interplay between aging, cardiovascular haemodynamics and inflammation in (preclinical) cardiovascular disease. The 2524 participants (1301 female) are a representative cohort of apparently healthy 35-55 year-old subjects (median age 46 years) randomly sampled from the twinned Belgian communities of Erpe-Mere and Nieuwerkerken (Belgium). The study is the result of a close cooperation between the regional primary care physicians in Erpe-Mere and Nieuwerkerken (ASKLEPIOS association of primary care physicians) and the University of Ghent. A novel aspect of the study is non-invasive biomechanical assessment of cardiac function, arterial function and their interaction (ventriculo-vascular function) through combination of modeling, fundamental hydraulic measurements and system identification techniques. A second novel aspect is the determination of peripheral blood leukocyte telomere length as a possible marker for biological aging. These novel aspects represent fresh attempts at broadening our understanding of "blood pressure" and "aging". Baseline examinations were performed during a consecutive two-year period, which ended in October 2004. During follow-up, the baseline examinations will be repeated and the occurence of cardiovascular events will be monitored. The primary aim is to build a combined dataset that will act as a tool to answer a cluster of questions about ageing, haemodynamics and emergence of cardiovascular disease. The study will reassess current risk factors (such as blood pressure) and provide a long-term base for detection of novel genetic and non-genetic risk factors and for more performant risk stratification modalities. Within these broader goals, a constant will be to strive toward more fundamental mechanistic-haemodynamic insights into the cardiovascular disease processes.