Poor responders to statins: a potential target for stanol esters

Individuals vary widely in their response to a given dose of 3-hydroxy-3-me thylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). In patien ts with familial hypercholesterolaemia (FH), the reduction in low-density l iproprotein (LDL) cholesterol levels achieved by simvastatin, pravastatin a nd atorvastatin ranges from 28% to 72%. Above-average responders have highe r baseline plasma levels of mevalonic acid (MVA), a marker of cholesterol s ynthesis, and exhibit a greater decrease in MVA during statin therapy than patients whose decrease in LDL cholesterol level was below average. A simil ar variability of response occurs in subjects without FH. The response is b est in those with an apo E2 allele and worst in those with an apo E4 allele , who absorb cholesterol more efficiently than those with E2 and E3 alleles and have a lower rate of cholesterol synthesis. Thus, poor responders to s tatins have a low rate of cholesterol synthesis, which is secondary to incr eased absorption, itself due to excessive dietary intake or genetic influen ces (e.g. apo E phenotype). It is tempting to speculate that this might be overcome by eating foods containing plant stanol esters, which decrease cho lesterol absorption and thereby increase cholesterol synthesis.