Atherosclerosis: a necessary fellow of aging?

Almost three decades of research in B –mode ultrasound of carotid arteries, carried out by using carotid artery intima media thickness (C-IMT) as a surrogate marker of carotid and even coronary atherosclerosis, has provided undisputable evidences that aging is one of the most complex factors associated to atherosclerosis in humans. Complexity derives by the fact that this worldwide recognised atherosclerosis risk factor affects atherogenesis with two different but indistinguishable processes. The first is an arterial wall change, which occurs physiologically with aging even in absence of recognised vascular risk factors (VRFs), resulting in a slow, continuous and apparently symmetrical increase of carotid IMT. The second acts above and beyond this intrinsic process. Carotid IMT, in fact, increases with aging also in response to a variety of metabolic VRFs, such as hypertension, hyperglycemia and dyslipidemia, which are strongly associated with age. A number of epidemiological and intervention studies carried out by using C-IMT as primary surrogate endpoint of generalized atherosclerosis clearly demonstrated that, controlling these metabolic VRFs with life-style changes and pharmacological approaches, it is possible not only to inhibit carotid IMT progression but even to induce a significant regression of pre-existing atherosclerosis, often paralleled by a reduction of vascular events. In addition, the finding that even normolipidemic subjects may benefit from pharmacological treatments (i.e. statins) in terms of both reduction of vascular events and atherosclerosis progression suggests that even the intrinsic effect of age may be, in some way, controlled. The comprehension of the effect of age on carotid atherosclerosis considering also possible interaction with VRFs requires very large studies. A very large prospective, multicenter, longitudinal, long-term, observational study (The IMPROVE study), carried out in a large European population (n=3711), is currently ongoing. Although the main objective of this study was to investigate the capacity of carotid IMT and its progression to predict future vascular events, the analysis of baseline data has also provided interesting results about the age and age-VRFs interaction as determinant of cross-sectional carotid IMT.