The Saudi Journal of Medical Insights

Background: Cancer and cardiovascular disease (CVD) are the leading causes of morbidity and mortality worldwide, with
a rapidly growing population of cancer survivors facing competing cardiovascular risks. Cancer therapy-related
cardiovascular toxicity (CTR-CVT) and shared biological pathways contribute to elevated cardiovascular risk in this
population. This systematic review synthesizes evidence on the incidence and predictors of major adverse cardiovascular
events (MACE) in patients with cancer.
Methods: A comprehensive literature search of PubMed was conducted for studies published between January 2010 and
March 2025. Eligible studies included prospective and retrospective cohort studies, population-based registry studies, and
nested case-control studies reporting incidence rates or predictors of MACE (myocardial infarction, stroke, heart failure,
cardiovascular mortality, or composite outcomes) in cancer patients. Study quality was assessed using the Newcastle-Ottawa
Scale (NOS). Due to anticipated heterogeneity, a narrative synthesis approach was employed.
Results: Twenty studies encompassing over 1.9 million cancer patients were included. Cardiovascular risk varied
substantially by cancer type, with the highest cumulative 4-year MACE incidence observed in lung cancer (26%) and
multiple myeloma.The first year following cancer diagnosis represented the highest-risk period (standardized incidence
ratios ranging from 1.45 to 6.1). Key treatment-related predictors included anthracycline chemotherapy (hazard ratio [HR]
for heart failure: 2.0–4.18), internal mammary chain irradiation (HR 1.6–2.4), and bevacizumab (19.2% developed coronary
artery disease over five years). Patient-related predictors included pre-existing CVD (HR 2.83) sociodemographic factors
(African-American race, public insurance, lower socioeconomic status), and modifiable factors including weight gain >10%
post-diagnosis (HR 1.66) and medication nonadherence (HR 1.15–1.33). Sixteen studies demonstrated low risk of bias
(NOS score 7–9), and four showed moderate risk (score 6).
Conclusions: Patients with cancer face substantially elevated and persistent cardiovascular risk, with the highest
vulnerability in the first year post-diagnosis and among those receiving specific cardiotoxic therapies. Pre-existing CVD,
sociodemographic disparities, and modifiable risk factors significantly influence outcomes. These findings support
implementation of baseline cardiovascular risk assessment, structured surveillance protocols, and multidisciplinary cardio
oncology care to optimize outcomes in this growing population.