J.HOE1, S.L.PEK2, S.DISSANAYAKE2, J.IS.TANG2, E.Z.L.CHAN2, A.ZULKIFLI2, F.SIRAJ2, S.N.A KAMARUDDIN2, W.Y.WAN2, M.X.LIN2, S.TAVINTHARAN1
Admiralty Medical Centre1, Khoo Teck Puat Hospital2
Early, aggressive lipid lowering therapy (LLT) is required to reduce cardiovascular events in patients with Familial Hypercholesterolemia (FH). We studied the response to LLT and factors that may predict response to LLT in adult patients with heterogeneous FH in Singapore.
Prospective cohort study of 300 probands with clinical diagnosis of at least possible FH. Mutation analysis was performed for 26 lipid-related genes. Lipid panel data were obtained 0, 6 and 12 months from recruitment. LDL-C levels of >3.4 mmol/l after maximally tolerated LLT is a threshold often used by clinicians to initiate PCSK-9 inhibitors for primary prevention in FH patients. Predictors of this goal (<3.4mmo/l) achievement at 12-months were analysed.
LDLR mutations were present in 28.7% (n=86), APOB mutations in 2.3% (n=7) and other mutations in 2.0% (n=6), while 66% (n=198) were mutation negative.
Baseline LDL-C was higher in mutation positive (7.24 ± 3.13 mmol/L), compared with mutation negative probands (5.57 ± 1.49 mmol/L; p < 0.001).
Among LDLR mutations, probands with null mutations had higher baseline TC, LDL-C and a greater absolute reduction in LDL-C compared to defective mutations or mutation negative probands.
Presence of LDLR mutation and baseline LDL-C were independently associated with increased odds of not achieving LDL-C < 3.4 mmol/L at 12-months.
In FH patients, mutation positivity predicts higher cholesterol levels and poorer achievement of LDL-c goals. Genetic testing is useful in identifying patients who will need closer monitoring and intensification of LLT to better achieve LDL-c goals and potentially reduce risk of premature cardiovascular disease.