For example, a previous meta-analysis suggested that sodium retention, sympathetic nervous system activation, hyperinsulinemia, IR-related metabolic alterations, and greater sensitivity to angiotensin II may be involved; that higher IR is associated with higher risk of HF; and that there may be a causal relationship between IR and HF, according to the results of a Mendelian randomization study [41–43]. This evidence concerns the gene AGT and hyperinsulinism.