Importance There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT. Objective To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP. Design, Setting, and Participants This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more). Main Outcomes and Measures The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT. Results Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia). Conclusion and Relevance CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.

中文翻译：

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接受造血细胞移植的多发性骨髓瘤患者的克隆造血和心血管疾病。

重要性 对于癌症患者，包括接受造血细胞移植 (HCT) 的多发性骨髓瘤 (MM) 患者，不确定潜能克隆造血 (CHIP) 与心血管疾病 (CVD) 之间关系的信息很少。 HCT 后发生 CVD 的风险。目的 研究 MM 患者 CHIP 与 CVD 之间的关联，并描述 CHIP 患者 CVD 风险的修正因素。设计、设置和参与者 这是一项回顾性队列研究，对象为 2010 年至 2016 年间在加利福尼亚州杜阿尔特市希望之城综合癌症中心接受 HCT 的 MM 患者，并在 HCT 前冷冻保存了动员外周血干细胞 (PBSC) 产品并可用于 CHIP 分析。研究小组进行了靶向组 DNA 测序，以检测 CHIP 的存在（变异等位基因频率为 2% 或更高）。主要结果和措施 主要终点是 HCT 后 5 年累积发生率和新发 CVD（心力衰竭、冠状动脉疾病或中风）的风险。结果 在 1036 名连续接受第一次自体 HCT 的 MM 患者（580 名男性 [56%]；中位年龄 60.0 岁）中，201 名患者至少有 1 个 CHIP 变异（19.4%），35 名患者有 2 个或更多变异（3.4 %）。与未患有 CHIP 的患者相比，患有 CHIP 的患者 5 年 CVD 发病率显着较高（21.1% vs 8.4%；P < .001）；具有 2 种或更多变异的患者的 5 年发病率为 25.6%。在多变量模型中，CHIP 与 CVD 风险增加相关（风险比 [HR]，2.72；95% CI，1.70-4.39），以及包括心力衰竭在内的个人结果（HR，4.02；95% CI）。 CI，2.32-6.98）、冠状动脉疾病（HR，2.22；95% CI，1.06-4.63）和中风（HR，3.02；95% CI，1.07-8.52）。同时患有 CHIP 且既往患有高血压或血脂异常的患者，其 CVD 风险分别增加近 7 倍和 4 倍（参考：无 CHIP、无高血压或血脂异常）。结论和相关性 CHIP 与接受 HCT 的 MM 患者的 CVD 风险显着且独立相关，并且可以作为该队列中 CVD 的一种新的生物学上合理的生物标志物。患有 MM 且同时具有 CHIP 和心血管危险因素的患者发生 CVD 的风险极高。需要进行更多研究来确定心血管预防措施是否可以降低 CHIP 相关的 CVD 风险。