Effects of lipids in patients with familial hypercholesterolaemia on the kinetics of the sodium-lithium countertransporter

Sodium-lithium countertransport kinetics were measured in 87 patients (50 m ale; 37 female) with heterozygous familial hypercholesterolaemia (FH) and a group of 38 age range and sex-distribution matched controls. Basic clinica l data Including basic anthropometry, blood pressure were obtained and bloo d was taken for detailed lipid biochemistry, glucose and insulin measuremen t. Patients with FH had elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations compared to controls . The activity and log transformed maximal velocity (V-max) of the sodium-l ithium countertransporter unlike the affinity (K-m) were reduced in patient s with FH compared to controls (geometric means 0.172 vs 0.217 mmol Li+/L.R BC.hr; P = 0.02; 0.237 vs 0.317 mmol Li+/L.RBC.hr; P = 0.009 respectively). In multiple regression analysis, log normalised SLC activity correlated we akly with log triglyceride (beta = 0.225; P = 0.06) and cholesterol (beta = -0.112 P = 0.06). Log V-max correlated with log triglyceride (beta = 0.307 ; P = 0.02), and high-density lipoprotein (HDL) (beta = 0.74; P = 0.03) whi lst K-m correlated with HDL (beta = 1.73; P < 0.001) and apoAl (beta = -1.7 6; P = 0.0048), LDL (beta = -0.14; P = 0.05), and creatine kinase (beta = 0 .003; P = 0.01). Cholesterol and triglyceride concentrations rather than in sulin resistance seem to be the key features affecting the environmental al terations of sodium lithium countertransporter V-max in patients with famil ial hypercholesterolaemia.