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Metabolic syndrome and risk factors for vascular disease

By Cristiano Antonino On Oct 26, 2022

The complex network of reciprocal neurohormonal influences on the endothelium gives rise to what is now clinically referred to as the ‘metabolic syndrome’

The metabolic syndrome is the tendency for five risk factors for vascular disease to be associated in synergy with each other:

insulin resistance
endothelial dysfunction
arterial hypertension
dyslipidaemia
visceral obesity.

By reciprocal synergy, we mean precisely the bringing into play of all those mechanisms whose cross-relationships we have tried to explain: arterial hypertension is an agent capable of mechanically damaging the endothelium; the latter loses the capacity to adapt the capillary microcirculation in the tissues, entering into a state of inflammation, platelet hyperaggregation and dysregulation of oxidative metabolism, which trigger the loss of sensitivity to insulin.

The hyperinsulinism induced in this way then activates counter-insulin hormones, thus fuelling the state of chronic arterial hypertension and at the same time shifting energy metabolism in favour of an increased demand for glucose along with the storage of fats in the adipose tissue and subendothelial layers of the vessels, ultimately worsening endothelial dysfunction.

In reality, the vicious circles triggered by these five pathological conditions are much more complex and ramified, firstly because the enzymatic cascades responsible are in turn regulated by intrinsic molecular events that modulate their amplitude and direction, and secondly because the predisposing conditions themselves are inconstant from subject to subject, so that the associations between pathogenetic mechanisms can intertwine to varying degrees; it is therefore not necessary for a patient to present all five pathological conditions from the outset for the consequent vascular damage to develop and, even more important in therapeutic terms, sometimes the correction of one of the five positively influences the control of the other four.

Rather than linear cause-and-effect mechanisms, metabolic syndrome introduces a modern view of pathology generated by ‘clouds’ of reciprocal interactions

On a strictly clinical level, it should be noted that, while arterial hypertension and visceral obesity are easy to detect objectively (a sphygmomanometer, a dressmaker’s tape measure and a scale, as well as a minimum ‘clinical eye’ are sufficient), the assessment of the other three factors requires a certain level of laboratory and instrumental instrumentation.

In particular, direct and indirect indices on the functional state of the endothelium are still difficult to obtain, partly because the alterations may more or less selectively affect certain vascular districts that cannot be easily investigated, and partly because the homeostatic mechanisms that tend to oppose degenerative phenomena do not allow early detection of initial dysfunctional phenomena before the signs of vasculopathy that are already underway (atherosclerosis, organ decompensation, ischaemia, haemorrhage, etc.) have emerged.

A very interesting field in this regard is the study of circulating inflammatory cytokines, a very complex epiphenomenon of the regulatory activity of tissue inflammatory processes carried out by the endothelium, but so far no unambiguous and standardised indices have emerged that can predict the risk of vascular pathology.