Nazarzadeh Milad, Copland Emma, Smith Byrne Karl, Canoy Dexter, Bidel Zeinab, Woodward Mark, Yang Qianqian, McKay James, Mälarstig Anders, Hedman Åsa K, Chalmers John, Teo Koon K, Pepine Carl J, Davis Barry R, Kjeldsen Sverre E, Sundström Johan, Rahimi Kazem
Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom.
Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom; National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
JACC CardioOncol. 2025 Aug;7(5):609-623. doi: 10.1016/j.jaccao.2025.03.005. Epub 2025 May 13.
Pharmacologic blood pressure (BP) lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensive agents and the risk for cancer. However, evidence from randomized controlled trials (RCTs) regarding the effect of long-term pharmacologic BP lowering on the risk for new-onset cancer is limited, with most knowledge derived from observational studies.
The aim of this study was to assess whether long-term BP lowering affects the risk for new-onset cancer, cause-specific cancer death, and selected site-specific cancers.
Individual-level data from 42 RCTs were pooled using a one-stage individual participant data meta-analysis. The primary outcome was incident cancer of all types, and secondary outcomes were cause-specific cancer death and selected site-specific cancers. Prespecified subgroup analyses were conducted to assess the heterogeneity of the BP-lowering effect by baseline variables and over follow-up time. Cox proportional hazards regression, stratified by trial, was used for the statistical analysis. For site-specific cancers, analyses were complemented with Mendelian randomization, using naturally randomized genetic variants associated with BP lowering to mimic the design of a long-term RCT.
Data from 314,016 randomly allocated participants without known cancer at baseline were analyzed. Over a median follow-up of 4 years (Q1-Q3: 3-5 years), 17,954 participants (5.7%) developed cancer, and 4,878 (1.5%) died of cancer. In the individual participant data meta-analysis, no associations were found between reductions in systolic or diastolic BP and cancer risk (HR per 5 mm Hg reduction in systolic BP: 1.03 [95% CI: 0.99-1.06]; HR per 3 mm Hg reduction in diastolic BP: 1.03 [95% CI: 0.98-1.07]). No changes in relative risk for incident cancer were observed over follow-up time, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on cause-specific cancer death was found. For site-specific cancers, no evidence of an effect was observed, except a possible link with lung cancer risk (HR for systolic BP reduction: 1.17; 99.5% CI: 1.02-1.32). Mendelian randomization studies showed no association between systolic or diastolic BP reduction and site-specific cancers, including overall lung cancer and its subtypes.
Randomized data analysis provided no evidence to indicate that pharmacologic BP lowering has a substantial impact, either increasing or decreasing, on the risk for incident cancer, cause-specific cancer death, or selected site-specific cancers.
药物降压通常是一种终身治疗方法，临床医生和患者可能都担心长期使用抗高血压药物及其致癌风险。然而，关于长期药物降压对新发癌症风险影响的随机对照试验（RCT）证据有限，大多数认知来自观察性研究。
本研究旨在评估长期降压是否会影响新发癌症风险、特定病因癌症死亡风险以及特定部位癌症风险。
采用单阶段个体参与者数据荟萃分析汇总了42项随机对照试验的个体水平数据。主要结局是所有类型的新发癌症，次要结局是特定病因癌症死亡和特定部位癌症。进行了预先设定的亚组分析，以评估通过基线变量和随访时间的降压效果异质性。采用按试验分层的Cox比例风险回归进行统计分析。对于特定部位癌症，分析通过孟德尔随机化进行补充，使用与降压相关的自然随机遗传变异来模拟长期随机对照试验的设计。
分析了来自314,016名基线时无已知癌症的随机分配参与者的数据。在中位随访4年（第一四分位数 - 第三四分位数：3 - 5年）期间，17,954名参与者（5.7%）患癌症，4,878名（1.5%）死于癌症。在个体参与者数据荟萃分析中，未发现收缩压或舒张压降低与癌症风险之间存在关联（收缩压每降低5 mmHg的风险比：1.03 [95%置信区间：0.99 - 1.06]；舒张压每降低3 mmHg的风险比：1.03 [95%置信区间：0.98 - 1.07]）。随访期间未观察到新发癌症相对风险的变化，也没有证据表明基线亚组间治疗效果存在异质性。未发现对特定病因癌症死亡有影响。对于特定部位癌症，未观察到有影响的证据，除了可能与肺癌风险存在关联（收缩压降低的风险比：1.17；99.5%置信区间：1.02 - 1.32）。孟德尔随机化研究表明，收缩压或舒张压降低与特定部位癌症之间无关联，包括总体肺癌及其亚型。
随机数据分析没有证据表明药物降压对新发癌症风险、特定病因癌症死亡风险或特定部位癌症风险有实质性影响，无论是增加还是降低。
