After the inclusion of all the explanatory variables correlated with PAI-1 antigen levels in a multivariable linear regression model, we found that metabolic factors with the strongest contribution in the variability of PAI-1 antigen levels in patients with T2DM plus the Metabolic Syndrome were hypertension (β = 0.18; p = 0.03), NL HDL-c (β = −0.16; p = 0.05), and NL triglycerides (β = 0.15; p = 0.05). This evidence concerns the gene SERPINE1 and Hypertension.