ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment.
ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment.
复制标题
DOI：
10.1016/j.atherosclerosis.2014.04.030
复制
发表时间：
2014-07
期刊：
影响因子：
5.3
通讯作者：
PROspective Study of Pravastatin in the Elderly at Risk Investigator
中科院分区：
文献类型：
--
作者：
Akao H;Polisecki E;Schaefer EJ;Trompet S;Robertson M;Ford I;Jukema JW;de Craen AJ;Packard C;Buckley BM;Kajinami K;PROspective Study of Pravastatin in the Elderly at Risk Investigator
我们的目标是研究特定的ATP结合盒转运体A1(ABCA1)变体rs2230806(R219K)与基线血脂、普伐他汀降低低密度脂蛋白(LDL)胆固醇、基线心脏病和心脏终点的关系。在PROSPER(普伐他汀在高危老年人中的前瞻性研究)(平均年龄75.3岁)的5,414名参与者中，对ABCA1 R219K变异进行了评估，他们被随机分配到普伐他汀40 mg/天或安慰剂，并平均随访3.2年。在这些受试者中，47.6%携带该变异，其中40.0%携带一个等位基因，7.6%同时携带两个等位基因。未发现对基线低密度脂蛋白胆固醇水平的影响，但平均高密度脂蛋白胆固醇水平根据存在的变异等位基因的数量略有增加(1.27vs1.28vs1.30 mmoL/L，p=0.024)。该变异的存在或不存在与基线时他汀类药物诱导的低密度脂蛋白降低反应或冠心病之间没有关系。然而，在试验中，与没有变异者相比，有变异者与没有变异者相比，新心血管疾病(致命性冠心病、非致命性心肌梗死或致命或非致命性中风)的总体调整后风险比为1.22(95%可信区间1.06-1.40，p=0.006)，而普伐他汀组为1.41(1.15-1.73，p=0.001)，安慰剂组为1.08(0.89-1.30，p=0.447)(交互作用0.058)。我们的数据表明，携带ABCA1R219K变异的受试者从普伐他汀治疗中获得的心脏病风险降低可能比没有该变异的受试者要少得多。
Our goals were to examine the relationships of a specific ATP-binding cassette transporter A1 (ABCA1) variant, rs2230806 (R219K), on baseline lipids, low density lipoprotein (LDL) cholesterol lowering due to pravastatin, baseline heart disease, and cardiac endpoints on trial. The ABCA1 R219K variant was assessed in 5,414 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2 years. Of these subjects 47.6 % carried the variant, with 40.0 % carryin g one allele, and 7.6 % carrying both alleles. No effects on baseline LDL cholesterol levels were noted, but mean HDL cholesterol increased modestly according to the number of variant alleles being present (1.27 vs 1.28 vs 1.30 mmol/L, p=0.024). No relationships between the presence or absence of this variant and statin induced LDL lowering response or CHD at baseline were noted. However within trial those with the variant as compared to those without the variant, the overall adjusted hazard ratio for new cardiovascular disease (fatal CHD, non-fatal myocardial infarction, or fatal or non-fatal stroke) was 1.22 (95% CI 1.06-1.40, p=0.006), w hile for those in the pravastatin group it was 1.41 (1.15-1.73, p=0.001), and for those in the placebo group it was 1.08 (0.89-1.30, p=0.447) (p for interaction 0.058). Our data indicate that subjects with the ABCA1 R219K variant may get significantly less heart disease risk reduction from pravastatin treatment than those without the variant.