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Sindrome metabolica e stenosi aortica

La stenosi aortica calcifica è una malattia sostenuta dall'infiltrazione di lipidi, infiammazione cronica, attivazione di osteoblasti e mineralizzazione attiva. E' stata a lungo considerata una malattia degenerativa stabile ed ora appare come una malattia con molte somiglianze con l'aterosclerosi e pertanto il suo decorso potrebbe essere modificabile. I tentativi con le statine, indubbiamente attive nell'aterosclerosi, sono stati comunque deludenti. Capoulade e coll. in questo studio prospettico dimostrano che i pazienti con stenosi aortica e sindrome metabolica mostrano una più veloce progressione della malattia valvolare ed una prognosi peggiore. Rilevano che nei pazienti con sindrome metabolica, la terapia con statine peggiora il quadro metabolico aumentando l'insulino-resistenza e la formazione di LDL piccole e dense ed è associata ad una maggior velocità di progressione della stenosi. La sindrome metabolica che sembra essere un predittore indipendente di progressione della stenosi aortica, dovrebbe essere ricercata nei portatori della valvulopatia e forse la sua correzione potrebbe influenzare positivamente l'evoluzione della stenosi valvolare. Ma di questo mancano ancora prove.

Impact of metabolic syndrome on progression of aortic stenosis: influence of age and statin therapy

Capoulade R, Clavel MA, Dumesnil JG, Chan KL, Teo KK, Tam JW, Côté N, Mathieu P, Després JP, Pibarot P

J Am Coll Cardiol 2012;60:216-223

OBJECTIVES: The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS.

BACKGROUND: Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression.

METHODS: This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography.

RESULTS: Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not.

CONCLUSIONS: MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies.

J Am Coll Cardiol 2012;60:216-223