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PCSK9 non è un buon marcatore del rischio di aterosclerosi

PCSK9 (proprotein convertase subtilisin/hexin type 9) svolge un ruolo importante nella regolazione dell'attività dei recettori per le LDL. Se è basso, la concentrazione di LDL è elevata e viceversa quando la sua attività nel plasma è alta. La misura di PCSK9 potrebbe perciò essere un buon predittore del danno vascolare. Nel loro studio, Zhu e coll. hanno trovato una correlazione positiva tra PCSK9 e colesterolo LDL, trigliceridi e insulina e una inversa con l'indice di massa corporea, ma non sono riusciti a dimostrare un'associazione tra PCSK9, sindrome metabolica, vasodilatazione flusso-mediata e spessore medio-intimale delle carotidi, che sono indici accettati di danno vascolare subclinico. La conclusione è che la concentrazione di PCSK9 non ha valore come indice di rischio per aterosclerosi o di danno vascolare.

Association of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) With Cardiovascular Risk in Primary Prevention

Zhu YM, Anderson TJ, Sikdar K, Fung M, McQueen MJ1, Lonn EM, Verma S

Arterioscler Thromb Vasc Biol. 2015;35:2254-9

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of low-density lipoprotein metabolism. This study was conducted to evaluate the relationship between serum PCSK9 concentrations and measures of vascular health, subclinical atherosclerosis, and adverse cardiovascular events. The relationship between traditional risk factors and PCSK9 concentrations was also examined.
APPROACH AND RESULTS: The cohort consisted of 1527 middle-aged men enrolled in the Firefighters and Their Endothelium (FATE) study, who were free of vascular disease and followed up over a mean period of 7.2±1.7 years. Baseline evaluation included assessment of traditional cardiovascular risk factors and measurements of flow-mediated dilation, reactive hyperemic velocity time integral, and carotid intima-media thickness. Biochemical parameters, including serum PCSK9 concentrations, were analyzed to determine predictors of vascular measures and to evaluate the role of PCSK9 in the occurrence of adverse cardiovascular events. Multivariate linear regression analyses indicated that body mass index, insulin, low-density lipoprotein-cholesterol, and triglycerides were independent predictors of PCSK9. Further modeling revealed no correlation between PCSK9 concentration and carotid intima media thickness, flow-mediated dilation, or reactive hyperemic velocity time integral. Analyses indicated no significant association between PCSK9 concentrations and cardiovascular event occurrences.
CONCLUSIONS: Although correlated with low-density lipoprotein-cholesterol, insulin, and triglycerides, PCSK9 was not associated with measures of vascular function or structure. There was also no significant relationship between PCSK9 concentrations and cardiovascular events. Thus, although PCSK9 is an important therapeutic target to reduce circulating low-density lipoprotein-cholesterol concentrations, it is unlikely to be a biomarker of atherosclerotic risk or vascular health.

Arterioscler Thromb Vasc Biol. 2015;35:2254-9