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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.

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Purpose Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined. Materials and methods Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer. Measurements were performed at the site of radiation treatment and at a contralateral control, non-radiated site. Cutaneous vascular conductance (CVC) was calculated by normalizing for mean arterial pressure. Results and Conculsions In part 1, patients received an average radiation dose of 2104 ± 236 cGy. A significantly lower peak ACh-mediated endothelium-dependent vasodilation was observed within the radiated microvasculature when compared to non-radiated (radiated: 532 ± 167%, non-radiated 1029 ± 263%; P = 0.02). In part 2, the average radiation dose received was 2251 ± 196 cGy. Iontophoresis of SNP elicited a similar peak endothelium-independent vasodilator response in radiated and non-radiated tissue (radiated: 179 ± 58%, non-radiated: 310 ± 158; P = 0.2). The time to 50% of the peak response for ACh and SNP was similar between radiated and non-radiated microvasculature (P < 0.05). These data provide evidence of early endothelium-dependent microvascular dysfunction in cancer patients currently receiving chest radiation and provide the scientific premise for future work evaluating coronary endothelial function and vasomotor reactivity using more detailed and invasive procedures.