甘油三酯和残余胆固醇与主动脉瓣狭窄风险的关联：哥本哈根普通人群研究中的孟德尔随机化研究
Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study.
作者信息
Kaltoft Morten, Langsted Anne, Nordestgaard Børge G
机构信息
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, DK-2730 Herlev, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark.
出版信息
Eur Heart J. 2020 Jun 21;41(24):2288-2299. doi: 10.1093/eurheartj/ehaa172.
AIMS
We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis.
METHODS AND RESULTS
We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides <1 mmol/L (<89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87-1.19] for individuals with triglycerides of 1.0-1.9 mmol/L (89-176 mg/dL), 1.22 (1.02-1.46) for 2.0-2.9 mmol/L (177-265 mg/dL), 1.40 (1.11-1.77) for 3.0-3.9 mmol/L (266-353 mg/dL), 1.29 (0.88-1.90) for 4.0-4.9 mmol/L (354-442 mg/dL), and 1.52 (1.02-2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides <2.0 mmol/L (77 mg/dL), 6.5% at 2.0-4.9 mmol/L (177-442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for <0.5 mmol/L (19 mg/dL), 5.6% for 0.5-1.4 mmol/L (19-57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13-16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20-1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17-18, 1.41 (1.31-1.52; +25%; +22%) for allele score 19-20, and 1.51 (1.22-1.86; +51%; +44%) for individuals with allele score 21-23.
CONCLUSION
Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.
目的
我们检验了如下假设，即血浆甘油三酯和残留胆固醇水平升高在观察性研究和基因层面均与主动脉瓣狭窄风险增加相关。
方法与结果
我们纳入了哥本哈根普通人群研究中的108559名个体。测定了血浆甘油三酯、残留胆固醇（总胆固醇减去低密度脂蛋白和高密度脂蛋白胆固醇）以及导致这些水平升高或降低的16种基因变异。1593名个体发生了新发主动脉瓣狭窄。在观察性研究中，与甘油三酯<1 mmol/L（<89 mg/dL）的个体相比，甘油三酯为1.0 - 1.9 mmol/L（89 - 176 mg/dL）的个体发生主动脉瓣狭窄的多因素调整风险比为1.02 [95%置信区间（CI）0.87 - 1.19]，甘油三酯为2.0 - 2.9 mmol/L（177 - 265 mg/dL）的个体为1.22（1.02 - 1.46），甘油三酯为3.0 - 3.9 mmol/L（266 - 353 mg/dL）的个体为1.40（1.11 - 1.77），甘油三酯为4.0 - 4.9 mmol/L（354 - 442 mg/dL）的个体为1.29（0.88 - 1.90），甘油三酯≥5 mmol/L（≥443 mg/dL）的个体为1.52（1.02 - 2.27）。到85岁时，血浆甘油三酯<2.0 mmol/L（77 mg/dL）的个体中主动脉瓣狭窄的累积发病率为5.1%，甘油三酯为2.0 - 4.9 mmol/L（177 - 442 mg/dL）的个体为6.5%，血浆甘油三酯≥5.0 mmol/L（443 mg/dL）的个体为8.2%。残留胆固醇类别的相应数值为，<0.5 mmol/L（19 mg/dL）时为4.8%，0.5 - 1.4 mmol/L（19 - 57 mg/dL）时为5.6%，≥1.5 mmol/L（58 mg/dL）时为7.4%。在基因层面，与等位基因分数为13 - 16的个体相比，等位基因分数为17 - 18的个体发生主动脉瓣狭窄的优势比为1.30（95% CI 1.20 - 1.42；甘油三酯增加12%；残留胆固醇增加11%），等位基因分数为19 - 20的个体为1.41（1.31 - 1.52；增加25%；增加22%），等位基因分数为21 - 23的个体为1.51（1.22 - 1.86；增加51%；增加44%）。
结论
较高的甘油三酯和残留胆固醇在观察性研究和基因层面均与主动脉瓣狭窄风险增加相关。
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