353,273例不同肿瘤分期的结直肠肿瘤患者长期心血管死亡率：一项基于人群的大型研究

Long-Term Cardiovascular Mortality among 353,273 Patients with Colorectal Cancer by Tumor Stages: A Large Population-Based Study

摘要: 目的：在肿瘤幸存者中，良好预后与心血管疾病死亡风险增加相关。本研究的目的是探讨不同肿瘤分期的结直肠肿瘤患者的累积死亡率和心血管疾病死亡风险。方法：我们从Surveillance, Epidemiology, and End Results (SEER)数据库中检索1975~2014年、年龄超过15岁的结直肠肿瘤幸存者。心血管疾病的累积死亡率通过竞争风险模型进行估计。我们计算了结直肠肿瘤死亡患者中心血管疾病死亡的比例。将心血管疾病的标准化死亡率(Standardized mortality ratio, SMR)与美国普通人群进行比较。结果：共纳入353,273例患者，其中早期患者147,465例(41.7%)，中期患者141,541例(40.1%)，晚期患者64,267例(18.2%)。心血管疾病是所有患者的第二位死亡原因，是早期患者的第一位死亡原因。早期患者确诊后八年心血管疾病累积死亡率高于结直肠肿瘤(12.17%比11.76%，P < 0.001)。在不同肿瘤分期患者中，心血管疾病死亡比例逐渐超过结直肠肿瘤(总体：第七年30.57%比29.73%；早期：第五年30.91%比29.90%；中期：第九年34.14%比23.73%；晚期：第十二年28.83%比17.12%)。与美国普通人群相比，结直肠肿瘤患者心血管死亡率的SMR在诊断后一年内更高(早期：SMR为1.12，95%CI为1.07~1.17；中期：SMR为1.13，95%CI为1.08~1.18；晚期：SMR为1.84，95%CI为1.72~1.96)，年轻患者心血管疾病死亡的风险更高(早期：SMR为1.23，95%CI为0.90~1.64；中期：SMR为1.38，95%CI为1.02~1.83；晚期：SMR为4.19，95%CI为2.87~5.91)。结论：虽然心血管疾病在早期结直肠肿瘤患者中累积死亡率最高，但随着时间的推移，不同肿瘤分期的心血管疾病死亡风险均大于结直肠肿瘤。

Abstract: Objective: Favorable prognoses are associated with an increased risk of death from cardiovascular disease (CVD) among cancer survivors. The objective of this study is to explore cumulative mortality and risk of death from cardiovascular disease in patients with colorectal cancer by tumor stages. Methods: We retrieved colorectal cancer survivors aged 15 years or older between 1975 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative mortality from cardiovascular disease was estimated by competitive risk models. We calculated the proportions of death from cardiovascular disease among dead patients with colorectal cancer. Standardized mortality ratios (SMRs) for cardiovascular disease were estimated compared to the general US population. Results: A total of 353,273 patients were included, with 147,465 (41.7%) in the early stage, 141,541 (40.1%) in the middle stage, and 64,267 (18.2%) in the late stage. Cardiovascular disease was the second leading cause of death in all patients and the first leading cause of death in patients with localized disease. The cumulative mortality from cardiovascular disease was higher than that from colorectal cancer eight years after diagnosis in patients with localized disease (12.17% vs. 11.76%, P < 0.001). Among patients with different tumor stages, the proportion of deaths due to cardiovascular diseases gradually exceeds those due to colorectal cancer (overall: 30.57% vs 29.73% at the seventh year; early stage: 30.91% vs 29.90% at the fifth year; middle stage: 34.14% vs 23.73% at the ninth year; advanced stage: 28.83% vs 17.12% at the twelfth year). Compared with the general U.S. population, the standardized mortality ratio (SMR) for cardiovascular mortality among colorectal cancer patients is higher within one year after diagnosis (early stage: SMR is 1.12, and 95%CI is 1.07~1.17; middle stage: SMR is 1.13, and 95%CI is 1.08~1.18; advanced stage: SMR is 1.84, and 95%CI is 1.72~1.96), with younger patients at higher risk of death from cardiovascular diseases (early stage: SMR is 1.23, and 95%CI is 0.90~1.64; middle stage: SMR is 1.38, and 95%CI is 1.02~1.83; advanced stage: SMR is 4.19, and 95%CI is 2.87~5.91). Conclusions: Although cardiovascular disease possessed the highest cumulative mortality in colorectal cancer patients with localized disease, the risks of death from cardiovascular disease were greater than that from colorectal cancer among all tumor stages with time after diagnosis.