Pfetsch Vanessa, Sanin Veronika, Jaensch Andrea, Dallmeier Dhayana, Mons Ute, Brenner Hermann, Koenig Wolfgang, Rothenbacher Dietrich
Deutsches Herzzentrum München, Technische Universität München, Lazarettstr. 36, 80636, Munich, Germany.
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
Cardiovasc Drugs Ther. 2017 Apr;31(2):167-177. doi: 10.1007/s10557-017-6718-1.
sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders.
Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates.
The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02-2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32-27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03-2.13)) and short-term FU (HR 3.06 (95% CI 1.29-7.24)).
Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.
可溶性肿瘤生长抑制因子2（sST2）是白细胞介素-1家族成员，被认为在心脏重塑和炎症信号传导中起作用。我们评估了稳定型冠心病（CHD）患者中sST2与多种心血管结局及全因死亡率之间的关联，同时控制了大量潜在混杂因素。
对1081例患者队列在基线时测定血浆sST2浓度（酶联免疫吸附测定法，Critical Diagnostics公司）。采用Cox比例风险模型确定sST2在调整协变量后对心血管疾病（CVD）联合终点、心血管死亡和全因死亡率的预后价值。
sST2水平中位数为28.9 ng/mL（四分位间距23.8，35.1）（基线时平均年龄58.9岁，男性占84.6%）。sST2浓度与炎症标志物及新出现的危险因素呈正相关，如胱抑素C、N末端脑钠肽前体（NT-proBNP）、高敏（hs）肌钙蛋白T和I、中段心房利钠肽原（MR-proANP）以及生长分化因子15（GDF-15）。在短期和长期（分别为4.5年和12.3年）随访后，将sST2浓度最高四分位数（Q4）与最低四分位数（Q1）进行比较时，未发现与非致命和致命CVD事件联合终点有统计学显著关联。在长期随访中，即使在包括临床风险变量的多变量调整后，sST2与CVD死亡率存在关联（风险比1.65；95%置信区间1.02 - 2.86），但在完全调整模型中无此关联，而相比之下，在短期随访后仍具有高度显著性（风险比5.97（95%置信区间1.32 - 27.06））。此外，在包括临床变量和基于胱抑素C的估计肾小球滤过率、NT-proBNP、hsCRP和hs-TnI的完全调整模型中，在长期随访（风险比1.48（95%置信区间1.03 - 2.13））和短期随访（风险比3.06（95%置信区间1.29 - 7.24））期间，将Q4与Q1比较时，sST2浓度仍与全因死亡率密切相关。
稳定型CHD患者中sST2浓度升高可能独立预测致命CVD事件和全因死亡率的短期及长期风险，但不能预测非致命CVD事件。
