Milad Nazarzadeh DPhil , Emma Copland MSc , Karl Smith Byrne DPhil , Dexter Canoy MD , Zeinab Bidel MSc , Mark Woodward PhD , Qianqian Yang MSc , James McKay PhD , Anders Mälarstig PhD , Åsa K. Hedman PhD , John Chalmers MD , Koon K. Teo MD , Carl J. Pepine MD , Barry R. Davis MD , Sverre E. Kjeldsen MD , Johan Sundström MD , Kazem Rahimi DM , Blood Pressure Lowering Treatment Trialists’ Collaboration
{"title":"Blood Pressure Lowering and Risk of Cancer","authors":"Milad Nazarzadeh DPhil , Emma Copland MSc , Karl Smith Byrne DPhil , Dexter Canoy MD , Zeinab Bidel MSc , Mark Woodward PhD , Qianqian Yang MSc , James McKay PhD , Anders Mälarstig PhD , Åsa K. Hedman PhD , John Chalmers MD , Koon K. Teo MD , Carl J. Pepine MD , Barry R. Davis MD , Sverre E. Kjeldsen MD , Johan Sundström MD , Kazem Rahimi DM , Blood Pressure Lowering Treatment Trialists’ Collaboration","doi":"10.1016/j.jaccao.2025.03.005","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 5","pages":"Pages 609-623"},"PeriodicalIF":12.8000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jacc: Cardiooncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666087325001310","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
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.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
期刊介绍:
JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge.
The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention.
Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.