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.