Highlights
- •156 patients with FH receiving atorvastatin were followed for 12 months.
- •The presence and type of LDLR mutations influence response to lipid-lowering therapy.
- •More aggressive treatment should be practiced in FH patients with an LDLR mutation.
Abstract
Objectives
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly
by LDLR mutations. This study assessed the influence of the presence and type of LDLR mutation on lipid profile and the response to lipid-lowering therapy in Brazilian
patients with heterozygous FH.
Methods
For 14 ± 3 months, 156 patients with heterozygous FH receiving atorvastatin were followed.
Coding sequences of the LDLR gene were bidirectionally sequenced, and the type of LDLR mutations were classified according to their probable functional class.
Results
The frequencies of the types of LDLR mutations were: null-mutation (n = 40, 25.6%), defective-mutation (n = 59, 37.8%), and without an identified mutation (n = 57, 36.6%). Baseline total cholesterol (TC) and low-density lipoprotein cholesterol
(LDL-C) were higher in patients carrying a null mutation (9.9 ± 1.9 mmol/L, 7.9 ± 1.7 mmol/L),
compared to those with a defective (8.9 ± 2.2 mmol/L, 7.0 ± 2.0 mmol/L), or no mutation
(7.9 ± 1.9 mmol/L, 5.8 ± 1.9 mmol/L) (p < 0.001). After treatment, the proportion of patients attaining an LDL-C<3.4 mmol/L
was significantly different among groups: null (22.5%), defective (27.1%), and without
mutations (47.4%) (p = 0.02). The presence of LDLR mutations was independently associated with higher odds of not achieving the LDL-C
cut-off (OR 9.07, 95% CI 1.41–58.16, p = 0.02).
Conclusions
Our findings indicate that the presence and type of LDLR mutations influence lipid profile and response to lipid-lowering therapy in Brazilian
patients with heterozygous FH. Thus, more intensive care with pharmacological therapeutics
should be performed in patients who have a molecular analysis indicating the presence
of a LDLR mutation.
Keywords
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Article info
Publication history
Accepted:
December 5,
2013
Received in revised form:
December 4,
2013
Received:
August 25,
2013
Identification
Copyright
© 2014 Published by Elsevier Inc.
