Welsh Paul, Welsh Claire, Celis-Morales Carlos A, Brown Rosemary, Ho Frederick K, Ferguson Lyn D, Mark Patrick B, Lewsey James, Gray Stuart R, Lyall Donald M, Gill Jason M R, Pell Jill P, de Lemos James A, Willeit Peter, Sattar Naveed
Institute of Cardiovascular and Medical Sciences, University of Glasgow, BHF Glasgow Cardiovascular Research Centre, 126 University Place, Glasgow G12 8TA, UK.
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Eur J Prev Cardiol. 2022 Feb 9;28(18):1991-2000. doi: 10.1093/eurjpc/zwaa063.
To investigate the population attributable fraction due to elevated lipoprotein (a) (Lp(a)) and the utility of measuring Lp(a) in cardiovascular disease (CVD) risk prediction.
In 413 734 participants from UK Biobank, associations of serum Lp(a) with composite fatal/non-fatal CVD (n = 10 066 events), fatal CVD (n = 3247), coronary heart disease (CHD; n = 18 292), peripheral vascular disease (PVD; n = 2716), and aortic stenosis (n = 901) were compared using Cox models. Median Lp(a) was 19.7 nmol/L (interquartile interval 7.6-75.3 nmol/L). About 20.8% had Lp(a) values >100 nmol/L; 9.2% had values >175 nmol/L. After adjustment for classical risk factors, 1 SD increment in log Lp(a) was associated with a hazard ratio for fatal/non-fatal CVD of 1.12 [95% confidence interval (CI) 1.10-1.15]. Similar associations were observed with fatal CVD, CHD, PVD, and aortic stenosis. Adding Lp(a) to a prediction model containing traditional CVD risk factors in a primary prevention group improved the C-index by +0.0017 (95% CI 0.0008-0.0026). In the whole cohort, Lp(a) above 100 nmol/L was associated with a population attributable fraction (PAF) of 5.8% (95% CI 4.9-6.7%), and for Lp(a) above 175 nmol/L the PAF was 3.0% (2.4-3.6%). Assuming causality and an achieved Lp(a) reduction of 80%, an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above 175 nmol/L may reduce CVD risk by 20.0% and CHD by 24.4%. Similar benefits were also modelled in the whole cohort, regardless of baseline CVD.
Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels.
研究脂蛋白(a)[Lp(a)]升高所致的人群归因分数以及测量Lp(a)在心血管疾病（CVD）风险预测中的作用。
在英国生物银行的413734名参与者中，使用Cox模型比较血清Lp(a)与复合致死性/非致死性CVD（n = 10066例事件）、致死性CVD（n = 3247）、冠心病（CHD；n = 18292）、外周血管疾病（PVD；n = 2716）和主动脉狭窄（n = 901）之间的关联。Lp(a)中位数为19.7 nmol/L（四分位间距7.6 - 75.3 nmol/L）。约20.8%的人Lp(a)值>100 nmol/L；9.2%的人Lp(a)值>175 nmol/L。在对经典危险因素进行校正后，log Lp(a)每增加1个标准差与致死性/非致死性CVD的风险比为1.12[95%置信区间（CI）1.10 - 1.15]。在致死性CVD、CHD、PVD和主动脉狭窄中观察到类似的关联。在一级预防组中，将Lp(a)添加到包含传统CVD危险因素的预测模型中，C指数提高了+0.0017（95% CI 0.0008 - 0.0026）。在整个队列中，Lp(a)高于100 nmol/L与5.8%（95% CI 4.9 - 6.7%）的人群归因分数（PAF）相关，Lp(a)高于175 nmol/L时PAF为3.0%（2.4 - 3.6%）。假设存在因果关系且Lp(a)降低80%，一项正在进行的针对CVD且Lp(a)高于175 nmol/L患者降低Lp(a)的试验可能使CVD风险降低20.0%，CHD风险降低24.4%。在整个队列中也模拟了类似的益处，无论基线CVD情况如何。
对Lp(a)升高进行人群筛查可能有助于预测CVD，并将Lp(a)降低药物（如果此类药物被证明有效）靶向应用于Lp(a)水平显著升高的人群。
