a National Institute for Health Research Bristol, Biomedical Research Centre , University Hospitals Bristol NHS Foundation Trust and University of Bristol , Bristol , UK.
b Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School , University of Bristol , Bristol , UK.
Scand Cardiovasc J. 2019 Jun;53(3):125-132. doi: 10.1080/14017431.2019.1612087. Epub 2019 May 9.
Evidence from case-control studies as well as meta-analyses of these study designs suggest elevated lipoprotein(a) [Lp(a)] to be associated with an increased risk of venous thromboembolism (VTE). Prospective evidence on the association is limited, uncertain, and could be attributed to regression dilution bias. We aimed to assess the prospective association of Lp(a) with risk of VTE and correct for regression dilution. We related plasma Lp(a) concentrations to the incidence of VTE in 2,180 men of the Kuopio Ischemic Heart Disease cohort study. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and repeat measurements of Lp(a) at 4 and 11 years from baseline, were used to correct for within-person variability. After a median follow-up of 24.9 years, 110 validated VTE cases were recorded. The regression dilution ratio of log Lp(a) adjusted for age was 0.85 (95% CI: 0.82-0.89). In analyses adjusted for several established risk factors and potential confounders, the HR (95% CI) for VTE per 1 SD (equivalent to 3.56-fold) higher baseline log Lp(a) was 1.06 (0.87-1.30). In pooled analysis of five population-based cohort studies (including the current study) comprising 66,583 participants and 1314 VTE cases, the fully-adjusted corresponding HR for VTE was 1.00 (95% CI: 0.94-1.07), with no evidence of heterogeneity between studies. Primary analysis as well as pooled evidence from previous studies suggest circulating Lp(a) is not prospectively associated with future VTE risk, indicating that evidence of associations demonstrated in case-control designs may be driven by biases such as selection bias.
来自病例对照研究以及这些研究设计的荟萃分析的证据表明，脂蛋白(a) [Lp(a)]升高与静脉血栓栓塞症（VTE）风险增加相关。关于这种关联的前瞻性证据有限、不确定，并且可能归因于回归稀释偏差。我们旨在评估 Lp(a) 与 VTE 风险的前瞻性关联，并纠正回归稀释。我们将血浆 Lp(a)浓度与库奥皮奥缺血性心脏病队列研究的 2180 名男性的 VTE 发生率相关联。评估风险比 (HR)（95%置信区间 [CI]），并使用基线时的 4 年和 11 年的 Lp(a)重复测量值来纠正个体内变异性。在中位随访 24.9 年后，记录了 110 例经证实的 VTE 病例。对数 Lp(a)调整年龄后的回归稀释比为 0.85（95%CI：0.82-0.89）。在调整了几个既定风险因素和潜在混杂因素的分析中，VTE 每 1 SD（相当于 3.56 倍）更高的基线对数 Lp(a)的 HR（95%CI）为 1.06（0.87-1.30）。在包括当前研究在内的五项基于人群的队列研究（共 66,583 名参与者和 1,314 例 VTE 病例）的汇总分析中，VTE 的完全调整后相应 HR 为 1.00（95%CI：0.94-1.07），各研究之间无异质性证据。主要分析以及来自先前研究的汇总证据表明，循环 Lp(a)与未来 VTE 风险无前瞻性关联，表明在病例对照设计中显示的关联证据可能受到选择偏差等偏倚的驱动。
