Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry

Background Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. Methods Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-C-F) and the Martin/Hopkins (LDL-C-M/H) equations as well as after correcting LDL-C-M/H for Lp(a) levels [LDL-C-Lp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. Results This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-C-F and LDL-C-M/H levels were similar [235 +/- 70 mg/dL (6.1 +/- 1.8 mmol/L) vs 235 +/- 69 mg/dL (6.1 +/- 1.8 mmol/L), respectively; P = NS], while LDL-C-Lp(a)corM/H levels were non-significantly lower than LDL-C-F [211 +/- 61 mg/dL (5.5 +/- 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-C-F [150 +/- 71 mg/dL (3.9 +/- 1.8 mmol/L)] and LDL-C-M/H levels [151 +/- 70 mg/dL (6.1 +/- 1.8 mmol/L); P = 0.746] were similar, whereas LDL-C-Lp(a)corM/H levels were significantly lower than LDL-C-F [121 +/- 62 mg/dL (3.1 +/- 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-C-M/H (2.5%) and especially LDL-C-Lp(a)corM/H methods (10.7%) were significantly different than LDL-C-F (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-C-F was lower compared with LDL-C-M/H and LDL-C-Lp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). Conclusion LDL-C-Lp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-C-Lp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.