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SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization.

ABSTRACT: SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients.In high-risk Caucasians undergoing cardiac catheterization, we tested the association between rs4149056/625T>C and rs2306283/492A>G with low-density lipoprotein cholesterol (LDL-c) over 3 years (n = 1402) and death/MI over 6 years (n = 2994), accounting for statin use or type during follow-up.Carriers of the rs4149056 C allele had 6.2 ± 1.7 mg/dl higher LDL-c per C allele (p < 0.001) but were not at higher risk for death/MI (p = 0.9). We found no associations between rs2306283 and LDL-c or death/MI (p > 0.6).Functional SLCO1B1 variants are not associated with death/MI in patients commonly treated with statins, despite higher LDL-c in carriers of the rs4149056 C allele.

SUBMITTER: Li JH

PROVIDER: S-EPMC4719145 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization.

Li Josephine H JH Suchindran Sunil S Shah Svati H SH Kraus William E WE Ginsburg Geoffrey S GS Voora Deepak D

Pharmacogenomics 20150101 5

<h4>Aim</h4>SLCO1B1 variants are associated with intermediate outcomes that may increase risk of death/myocardial infarction (MI) in statin-treated patients.<h4>Patients & methods</h4>In high-risk Caucasians undergoing cardiac catheterization, we tested the association between rs4149056/625T>C and rs2306283/492A>G with low-density lipoprotein cholesterol (LDL-c) over 3 years (n = 1402) and death/MI over 6 years (n = 2994), accounting for statin use or type during follow-up.<h4>Results</h4>Carrie ...[more]

PMID: 25916517

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Project description:Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ?190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

Dataset Information

SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization.

Publications

SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization.

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