Cardiology Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China.
Laboratory Department, Jilin Provincial Hospital of Integrated TCM and Western Medicine, Jilin, China.
Int J Cardiol. 2023 Nov 1;390:131233. doi: 10.1016/j.ijcard.2023.131233. Epub 2023 Jul 31.
The relationship between circulating osteoprotegerin (OPG) levels and the risk of cardiovascular diseases (CVDs) has been the subject of conflicting results in previous observational and experimental studies. To assess the causal effect of genetically predicted OPG levels on the risk of a wide range of CVDs, we used the Mendelian randomization design.
We initially extracted information of genetic variants on OPG levels and their corresponding effect values from the summary data based on the European ancestry genome-wide association study. Subsequently, we performed two-sample Mendelian randomization analyses to assess the causal effect of genetically predicted OPG levels on CVDs by using inverse variance weighting (IVW), MR-Egger, weighted median, and MR-PRESSO methods. We also conducted sensitivity analyzes as well as complementary analyses with a more relaxed threshold for the exposure genetic instrumental variable (P < 5 × 10) to test the robustness of our results.
Our results indicated that genetically predicted OPG levels causally reduce the risk of atrial fibrillation (IVW OR = 0.84; 95% CI = 0.72-0.98; P = 0.0241), myocardial infarction(IVW OR = 0.89; 95% CI = 0.80-0.98; P = 0.0173) and coronary heart disease (IVW: OR = 0.90; 95% CI = 0.82-0.99; P = 0.0286). Further complementary analyses also confirmed the above results remain robust and we also identified a potential causal association of OPG levels with a reduced risk of hypertensive diseases(IVW OR = 0.94;95% CI = 0.88-1.00; P = 0.0394).
This study provides compelling evidence for a causal relationship between genetically predicted OPG levels and risk reduction of coronary heart disease, myocardial infarction, and atrial fibrillation, indicating that OPG could potentially serve as a cardiovascular risk marker in clinical practice.
循环骨保护素（OPG）水平与心血管疾病（CVDs）风险之间的关系一直是先前观察性和实验性研究中存在争议的问题。为了评估遗传预测的 OPG 水平对广泛 CVDs 风险的因果效应，我们使用了孟德尔随机化设计。
我们最初从基于欧洲血统全基因组关联研究的汇总数据中提取了 OPG 水平的遗传变异及其相应的效应值信息。随后，我们通过使用逆方差加权（IVW）、MR-Egger、加权中位数和 MR-PRESSO 方法进行两样本孟德尔随机化分析，以评估遗传预测的 OPG 水平对 CVDs 的因果效应。我们还进行了敏感性分析以及更宽松的暴露遗传工具变量阈值（P < 5 × 10）的补充分析，以检验我们结果的稳健性。
我们的结果表明，遗传预测的 OPG 水平可导致心房颤动（IVW OR = 0.84；95%CI = 0.72-0.98；P = 0.0241）、心肌梗死（IVW OR = 0.89；95%CI = 0.80-0.98；P = 0.0173）和冠心病（IVW：OR = 0.90；95%CI = 0.82-0.99；P = 0.0286）的风险降低。进一步的补充分析也证实了上述结果仍然稳健，我们还发现 OPG 水平与降低高血压疾病风险之间存在潜在的因果关系（IVW OR = 0.94；95%CI = 0.88-1.00；P = 0.0394）。
本研究为遗传预测的 OPG 水平与冠心病、心肌梗死和心房颤动风险降低之间的因果关系提供了有力证据，表明 OPG 可能在临床实践中作为心血管风险标志物。
