Rationale: PCSK9 has been shown to affect cardiovascular system beyond its involvement in lipid metabolism. Recent studies raised the hypothesis that elevated PCSK9 may represent a novel risk factor for cardiovascular events.
Working hypothesis: Our hypothesis is that elevated levels of PCSK9 may increase the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with non-alcoholic fatty liver disease (NAFLD).
Main objectives: Primary endpoint will be to investigate the association between PCSK9 levels and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during follow-up. Secondary endpoints will be the identification of factors affecting circulating levels of PCSK9, to correlate PCSK9 to non-invasive markers liver fibrosis and steatosis and to investigate the association between adherence to Mediterranean Diet and PCSK9. Furthermore, in a subgroup of patients with biopsy-proven NASH, the association between PCSK9 and histological features will be investigated.
Experimental design: We will perform a prospective observational cohort study including 950 patients with ultrasonography evidence of liver steatosis. At baseline a blood sample will be collected for all patients to measure PCSK9 levels. After enrollment, patients will be followed for 1 year to see the occurrence of MACCE.
