One Brave Idea and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.G.T., S.G., M.H., C.A.M., R.C.D.).
Department of Medicine (S.G., M.H., C.A.M., R.C.D.), Harvard Medical School, Boston, MA.
Circ Cardiovasc Qual Outcomes. 2022 Jun;15(6):e008007. doi: 10.1161/CIRCOUTCOMES.121.008007. Epub 2022 Apr 28.
Researchers routinely evaluate novel biomarkers for incorporation into clinical risk models, weighing tradeoffs between cost, availability, and ease of deployment. For risk assessment in population health initiatives, ideal inputs would be those already available for most patients. We hypothesized that common hematologic markers (eg, hematocrit), available in an outpatient complete blood count without differential, would be useful to develop risk models for cardiovascular events.
We developed Cox proportional hazards models for predicting heart attack, ischemic stroke, heart failure hospitalization, revascularization, and all-cause mortality. For predictors, we used 10 hematologic indices (eg, hematocrit) from routine laboratory measurements, collected March 2016 to May 2017 along with demographic data and diagnostic codes. As outcomes, we used neural network-based automated event adjudication of 1 028 294 discharge summaries. We trained models on 23 238 patients from one hospital in Boston and evaluated them on 29 671 patients from a second one. We assessed calibration using Brier score and discrimination using Harrell's concordance index. In addition, to determine the utility of high-dimensional interactions, we compared our proportional hazards models to random survival forest models.
Event rates in our cohort ranged from 0.0067 to 0.075 per person-year. Models using only hematology indices had concordance index ranging from 0.60 to 0.80 on an external validation set and showed the best discrimination when predicting heart failure (0.80 [95% CI, 0.79-0.82]) and all-cause mortality (0.78 [0.77-0.80]). Compared with models trained only on demographic data and diagnostic codes, models that also used hematology indices had better discrimination and calibration. The concordance index of the resulting models ranged from 0.75 to 0.85 and the improvement in concordance index ranged up to 0.072. Random survival forests had minimal improvement over proportional hazards models.
We conclude that low-cost, ubiquitous inputs, if biologically informative, can provide population-level readouts of risk.
研究人员通常会评估新的生物标志物,以将其纳入临床风险模型,在成本、可用性和易于部署之间进行权衡。对于人群健康计划中的风险评估,理想的输入应该是大多数患者已经拥有的信息。我们假设,在门诊全血细胞计数中无需进行差异分析的常见血液学标志物(例如,红细胞压积),对于开发心血管事件风险模型将是有用的。
我们为预测心脏病发作、缺血性中风、心力衰竭住院、血运重建和全因死亡率开发了 Cox 比例风险模型。对于预测因子,我们使用了 2016 年 3 月至 2017 年 5 月期间常规实验室测量中 10 种血液学指标(例如,红细胞压积),以及人口统计学数据和诊断代码。作为结果,我们使用基于神经网络的自动事件裁决,对 1028294 份出院记录进行了分析。我们在波士顿的一家医院的 23238 名患者中进行了模型训练,并在另一家医院的 29671 名患者中进行了模型评估。我们使用 Brier 评分评估校准情况,使用 Harrell 的一致性指数评估区分度。此外,为了确定高维交互的实用性,我们将比例风险模型与随机生存森林模型进行了比较。
我们的队列中事件发生率范围为 0.0067 至 0.075 人/年。仅使用血液学指标的模型在外部验证集中的一致性指数范围为 0.60 至 0.80,并且在预测心力衰竭(0.80 [95%CI,0.79-0.82])和全因死亡率(0.78 [0.77-0.80])方面显示出最佳的区分度。与仅基于人口统计学数据和诊断代码训练的模型相比,还使用血液学指标的模型具有更好的区分度和校准度。最终模型的一致性指数范围为 0.75 至 0.85,一致性指数的提高幅度高达 0.072。随机生存森林对比例风险模型的改善很小。
我们得出的结论是,如果低成本、无处不在的输入具有生物学信息,则可以提供人群风险的读数。