Anticancer Therapy-Related Increases in Arterial Stiffness: A Systematic Review and Meta-Analysis

J Am Heart Assoc. 2020 Jul 21;9(14):e015598. doi: 10.1161/JAHA.119.015598. Epub 2020 Jul 10.

Abstract

Background Cardio-oncology is a clinical discipline focused primarily on the early detection of anticancer therapy-related cardiomyopathy. However, there is growing evidence that the direct adverse consequences extend beyond the myocardium to affect the vasculature, but this evidence remains limited. In addition, there remains a paucity of clinically based strategies for monitoring vascular toxicity in these patients. Importantly, arterial stiffness is increasingly recognized as a surrogate end point for cardiovascular disease and may be an important vascular outcome to consider. Therefore, the aim of this systematic review and meta-analysis was to summarize evidence of increased arterial stiffening with anticancer therapy and evaluate the effect of treatment modifiers. Methods and Results A total of 19 longitudinal and cross-sectional studies that evaluated arterial stiffness both during and following anticancer therapy were identified using multiple databases. Two separate analyses were performed: baseline to follow-up (12 studies) and control versus patient groups (10 studies). Subgroup analysis evaluated whether stiffness differed as a function of treatment type and follow-up time. Standard mean differences and mean differences were calculated using random effect models. Significant increases in arterial stiffness were identified from baseline to follow-up (standard mean difference, 0.890; 95% CI, 0.448-1.332; P<0.0001; mean difference, 1.505; 95% CI, 0.789-2.221; P≤0.0001) and in patient versus control groups (standard mean difference, 0.860; 95% CI, 0.402-1.318; P=0.0002; mean difference, 1.437; 95% CI, 0.426-2.448; P=0.0052). Subgroup analysis indicated differences in arterial stiffness between anthracycline-based and non-anthracycline-based therapies (standard mean difference, 0.20; 95% CI, 0.001-0.41; P=0.048), but not follow-up time. Conclusions Significant arterial stiffening occurs following anticancer therapy. Our findings support the use of arterial stiffness as part of a targeted vascular imaging strategy for the identification of early cardiovascular injury during treatment and for the detection of long-term cardiovascular injury into survivorship.

Keywords: arterial stiffness; cancer therapy; cardiotoxicity; pulse wave velocity; vascular toxicity.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anthracyclines / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Arteries / drug effects*
  • Cross-Sectional Studies
  • Humans
  • Longitudinal Studies
  • Vascular Diseases / chemically induced*
  • Vascular Stiffness*

Substances

  • Anthracyclines
  • Antineoplastic Agents