Increased HDL-C Values and Mortality: Revolutionizing a Historical Paradigm?

Many clinical studies and the derived guidelines and recommendations have for long included exercise programs aimed at generating improvements in patient fitness and/or cardiovascular rehabilitation, with the underlying assumption that raising HDL-C would be always beneficial. Nonetheless, it is now time to plan additional studies investigating the real interplay between HDL and physical activity in modulating the risk of death across a wide range of HDL-C concentrations. Moreover, taking the important evidence of a “J-” or even “U-”shaped association between HDL-C and mortality, doubts emerge as to whether the current guidelines that advocate boosting HDL-C values (mostly through physical activity) may need to be revised, for example by including a target range of desirable HDL-C values (e.g., between 60 and 80 mg/dL) rather than a simple indication of “equal and/or above”. Additionally, studies could better determine the potential harms of extremely high intakes of ethanol that may impact the association of HDL-C with all-cause and cancer mortality.