The role of Clusterin in attenuation of inflammation and reverse cholesterol transfer makes this molecule a potential candidate as a marker for cancer, cardiovascular disease, diabetes mellitus, and metabolic syndrome. In elderly subjects cardiovascular diseases represent the primary cause of death and different clinical studies have shown a positive correlation of these diseases with changes in the lipid pattern. This work aimed at evaluating the relationship between circulating clusterin and the biochemical parameters that characterize the lipid profile of a Sardinian population divided into five age groups including centenarians; the high frequency in Sardinia of these long-lived individuals gave us the opportunity to extend the range of the age groups to be analyzed to older ages and to better evaluate the changes in the lipid balance during ageing and its relationship with clusterin concentration in plasma. Our results showed that Clusterin concentration values of the youngest group were more similar with the centenarian's group compared to the other age groups, and a positive correlation arises with LDL. Furthermore given the high prevalence of cardiovascular diseases in the population examined and the association of Clusterin with these pathologies we evaluated Clusterin concentration variation in two groups with or without cardiovascular diseases. In presence of cardiovascular disease, Clusterin is significantly related to the most atherogenic components of lipid profile (total cholesterol and LDL), especially in women, suggesting its potential role in modulating cardiovascular metabolic risk factors.