INTRODUCCIÓN: REVISIÓN CRITICA DEL PROBLEMA

CAPÍTULO IV
have moreover been shown to reverse the atherosclerotic process in mice 243 . In a
recent study of 2571 non-diabetic patients, Lindsey et al. showed by computed
tomography that calcification in the coronary arteries is inversely related to plasma
sRAGE levels, so that sRAGE may be considered a protective factor against
atherosclerosis 284 . Similar results were obtained by Falcone et al. in 328 non-
diabetic patients, in whom low sRAGE plasma levels were associated with
coronary artery disease 283 . There are, however, other reports of a direct positive
correlation between sRAGE levels and arterial coronary disease, one of which
shows that in type-2 diabetic patients lower levels of sRAGE correlate with fewer
angiographically documented coronary events 289 . With respect to these
discrepancies it should be borne in mind that not all sRAGEs play a similar
pathophysiological role in cardiovascular disease. The N-truncated form, for
example, lacks the V-domain which is critical for binding of AGE and is thus
unable to perform the decoy function of other types of soluble RAGE. Similarly, a
study of 130 type-1 diabetic patients showed that esRAGE (the endogenous
secretory form with the V-domain), but not sRAGE, levels were inversely
correlated with carotid atherosclerosis (indicated from carotid intima-media
thickness) 279 . Lu et al., moreover, have recently demonstrated an inverse
association between esRAGE and arterial coronary disease in both non-diabetic
and type-2 diabetic patients in 1320 subjects 286 . Yan et al 290 have shown that in
non-diabetic patients there is an inverse correlation between sRAGE, esRAGE
and coronary artery disease, whereas in patients with diabetes mellitus an inverse
correlation is only maintained between esRAGE and coronary damage, and a
positive correlation appears between sRAGE and coronary disease. None of these
studies, however, were carried out in patients with HF.
To date, the only study to analyse sRAGE in patients with HF is that by Koyama et
al. 175 This prospective study of 160 patients with HF of different aetiologies
followed up for 872 days, concluded that sRAGE serum levels are related to a
worse prognosis of HF and to a more severe clinical condition. The study was able
to determine a 1220 pg/mL cut-off point for sRAGE which was predictive with high
sensitivity and specificity for the occurrence of a cardiac event in the short-middle
term. These authors did not, however, take into account differences in sRAGE
levels in the aetiology of HF. In the current study, we have not only confirmed the
120