Goettsch Claudia, Iwata Hiroshi, Hutcheson Joshua D, O'Donnell Christopher J, Chapurlat Roland, Cook Nancy R, Aikawa Masanori, Szulc Pawel, Aikawa Elena
From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
Arterioscler Thromb Vasc Biol. 2017 May;37(5):1005-1011. doi: 10.1161/ATVBAHA.116.308932. Epub 2017 Mar 9.
Genome-wide association studies and preclinical studies demonstrated a role of sortilin in lipid metabolism, inflammation, and vascular calcification-all cardiovascular risk factors. We evaluated the association of serum sortilin levels with the risk of major adverse cerebrovascular and cardiovascular events (MACCE) and the severity of abdominal aortic calcification (AAC).
A cohort of community-dwelling men aged ≥50 years (n=830) was assessed. At baseline, sortilin levels were measured by ELISA, and AAC was assessed on lateral spine scans obtained by dual-energy X-ray absorptiometry. Men aged ≥60 years (n=745) were followed up prospectively for the incidence of MACCE. During the median follow-up of 7.9 years, 76 MACCE occurred. The unadjusted incidence of MACCE across increasing sortilin quartiles was 8.0, 7.4, 19.8, and 20.3 per 1000 person-years. In multivariate-adjusted analysis, sortilin associated with increased risk of MACCE (hazard ratio, 1.70 per SD; 95% confidence interval, 1.30-2.20; <0.001). The third and fourth quartiles associated with 3.42-fold (95% confidence interval, 1.61-7.25; <0.005) and 3.82-fold (95% confidence interval, 1.77-8.26; <0.001) higher risk of MACCE compared with the first quartile. High sortilin also predicted MACCE independent of traditional Framingham risk factors. Higher sortilin associated with higher odds of severe AAC (score>5) after adjustment for confounders (odds ratio, 1.43 per SD; 95% confidence interval, 1.10-1.85; <0.01). The highest sortilin quartile associated with 2-fold higher odds of severe AAC (versus 3 lower quartiles combined). After adjustment for low-density lipoprotein cholesterol, the odds of severe AAC remained significant.
In older men, higher serum sortilin levels associated with higher MACCE risk and severe AAC independently of relevant confounders, including C-reactive protein and low-density lipoprotein cholesterol. This finding, however, needs to be validated in other cohorts.
全基因组关联研究和临床前研究表明，sortilin在脂质代谢、炎症和血管钙化（所有心血管危险因素）中发挥作用。我们评估了血清sortilin水平与主要不良脑血管和心血管事件（MACCE）风险以及腹主动脉钙化（AAC）严重程度之间的关联。
对一组年龄≥50岁的社区男性（n = 830）进行了评估。在基线时，通过酶联免疫吸附测定法测量sortilin水平，并通过双能X线吸收法在腰椎侧位扫描上评估AAC。对年龄≥60岁的男性（n = 745）进行前瞻性随访，以观察MACCE的发生率。在中位随访7.9年期间，发生了76例MACCE。随着sortilin四分位数增加，MACCE的未调整发病率分别为每1000人年8.0、7.4、19.8和20.3例。在多变量调整分析中，sortilin与MACCE风险增加相关（风险比，每标准差1.70；95%置信区间，1.30 - 2.20；P<0.001）。与第一四分位数相比，第三和第四四分位数与MACCE风险分别高3.42倍（95%置信区间，1.61 - 7.25；P<0.005）和3.82倍（95%置信区间，1.77 - 8.26；P<0.001）。高sortilin水平还独立于传统的弗雷明汉风险因素预测MACCE。在调整混杂因素后，较高的sortilin水平与严重AAC（评分>5）的较高几率相关（比值比，每标准差1.43；95%置信区间，1.10 - 1.85；P<0.01）。最高的sortilin四分位数与严重AAC的几率高2倍相关（相对于较低的三个四分位数总和）。在调整低密度脂蛋白胆固醇后，严重AAC的几率仍然显著。
在老年男性中，较高的血清sortilin水平与较高的MACCE风险和严重AAC相关，独立于包括C反应蛋白和低密度脂蛋白胆固醇在内的相关混杂因素。然而，这一发现需要在其他队列中进行验证。
