Early and Supernormal Vascular Aging

Abstract

Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<−5.7 years), normal (Δ-age −5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly ( P <0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 [95% CI, 0.41–0.85]), whereas early vascular aging had higher risk (hazard ratio, 2.70 [95% CI, 1.55–4.70]) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.

The probabilistic model of Alzheimer disease: the amyloid hypothesis revised

“…Similarly to the interaction of PSEN1 with the APOE ɛ3 Christchurch mutation, the effect of APOE ε4/ε4 homozygosity may be modulated by both non-APOE genetic variants associated with AD and environmental exposures (see below). A similar phenomenon is known in the field of vascular diseases, in which individuals featuring supernormal vascular ageing (SUPERNOVA) have been described who do not show age-dependent increased arterial stiffness in spite of a heavy cardiovascular risk factor burden 135,136 . Epigenetic mechanisms have been invoked to explain the SUPERNOVA phenomenon.…”

Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)

“…Early vascular aging (EVA) and supernormal vascular aging are two extreme vascular ageing phenotypes. EVA or arterial stiffness is a concept mentioned in the literature for the first time in 2008 [ 148 ] and includes premature changes in the structure and function of the arteries due to the action of cardiovascular risk factors, environmental factors, genetic predisposition or fetal programming [ 149 , 150 ]. On the other hand, supernormal vascular aging is defined as abnormally low arterial stiffness [ 151 ].…”

“…Between these two entities, EVA and SUPERNOVA are patients with healthy vascular aging interpreted as low blood pressure and pulse wave velocity over 50 years old [ 155 ]. Bruno et al [ 148 ] demonstrated that estimation of the age difference between the vascular and chronological one might be a useful clinical tool for identifying patients with SUPERNOVA phenotype. Individuals with a vascular age at least 6 years younger than their chronological age are associated with a 40% lower risk of cardiovascular events compared to subjects with a normal vascular age despite the prevalence of cardiovascular risk factors.…”

Hol van a normális és a kóros vérnyomás közötti határ, és mi a terápiás cél a cardiovascularis és a renalis betegségekben?

“…), amelyek szervezetünk érrendszerében -a micro-és a macrovascularis struktúrában egyaránt -végbemennek, hozzák létre a szöveti károsodásokat, majd a betegségeket [32]. Hypertoniában, illetve általában a systolés vérnyomás tekintetében a korral együtt járó növekedés rendszerint párhuzamos az atherosclerosis okozta folyamattal, illetve az ezt mérő artériás merevség (stiffness) folyamatos növekedésével [33]. Mindez megbízhatóan mérhető a CAC-pontrendszer alapján is [34].…”