Shared Pathways, Shared Predictions

Corresponding Author

The intertwined epidemics of cardiovascular disease (CVD) and cancer represent the preeminent global health challenges of our era, imposing an immense toll in morbidity and mortality.^1,2 Although historically approached as distinct entities, accumulating evidence suggests that these 2 conditions share overlapping risk factors and pathophysiological mechanisms.³ In this issue of JACC: CardioOncology, Henriquez Santos et al⁴ present a scoping review exploring whether cardiovascular risk scores and cardiovascular health (CVH) metrics can also predict cancer outcomes.

The scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines and included 13 prospective cohort studies comprising nearly 1 million adult participants, with median follow-up durations ranging from 8.1 to 29.6 years. These studies evaluated the predictive performance of well-established CVD scoring systems, including the Framingham risk score, Systematic Coronary Risk Evaluation score, Atherosclerotic Cardiovascular Disease Risk Estimator, and composite CVH tools such as Life’s Simple 7 (LS7) and the updated Life’s Essential 8, in relation to cancer risk.

Despite heterogeneity in study design and outcome definitions across the included studies, the review revealed a largely consistent pattern: individuals with unfavorable CVH metrics were at elevated risk for several types of cancer, most notably lung and colorectal cancers. Moreover, studies using LS7 or Life’s Essential 8 consistently demonstrated a graded inverse relationship between more favorable CVH scores and cancer incidence. For instance, some analyses indicated that each 1-point increment in the overall CVH score (eg, on a scale ranging from 0 to 7 for LS7, the higher the score, the better the CVH status) was associated with an estimated 5% to 8% reduction in cancer risk.

Importantly, tools originally developed for cardiovascular event prediction also showed utility in identifying higher cancer risk. Individuals in the highest CVD risk categories exhibited significantly increased cancer incidence, with categorical models showing risk elevations from 2.89-fold (the Systematic Coronary Risk Evaluation score) to 3.71-fold (the Atherosclerotic Cardiovascular Disease Risk Estimator) compared with those at lower risk. These findings suggest that existing CVD risk estimators might possess unexploited utility in stratifying cancer risk as well.

The review’s inclusion of both clinical variables (eg, cholesterol, blood pressure) and lifestyle factors (eg, physical activity, smoking, diet) broadened the relevance of the findings. However, the variability in how cardiovascular scores were categorized and operationalized, some as categorical tertiles or quintiles and others as continuous scores, limits direct comparisons across studies and precludes quantitative meta-analysis.

Several limitations are worth noting. First, although most studies excluded individuals with known cancer at baseline, reverse causation remains a potential concern. Subclinical malignancy may influence cardiovascular risk markers, such as unintentional weight loss and systemic inflammation, confounding observed associations.⁵ Second, certain cancers, such as breast and prostate cancer, showed less consistent relationships with cardiovascular metrics, suggesting that hormonally driven or genetically predisposed malignancies may not follow the same behavioral risk paradigms.^6,7 Furthermore, it is important to recognize the considerable heterogeneity in cancer risk both across cancer types and within subtypes.⁸ This complexity adds interpretive challenges when linking CVD scores or CVH metrics to oncologic outcomes, as different cancers may have distinct etiologic drivers and risk profiles. Third, the lack of harmonization in CVH metric definitions presents a barrier to evidence synthesis. For example, definitions of “ideal” dietary pattern or physical activity varied among studies. Fourth, it remains essential to determine whether these composite scores serve solely as proxies for established shared risk factors or whether they provide incremental predictive value for cancer by capturing a more holistic physiological state, such as systemic inflammation or metabolic resilience, that may underlie oncogenesis. Finally, residual confounding from unmeasured variables cannot be ruled out, as is typical in observational designs.

Despite these limitations, this body of evidence reinforces a critical insight: improving CVH may yield compound benefits in cancer prevention. The findings support the growing call to integrate CVH metric assessment into broader preventive strategies. In clinical practice, identifying individuals with poor CVH scores could facilitate earlier lifestyle interventions to reduce cardiovascular morbidity and mitigate cancer risk.

There is a strong rationale for interdisciplinary collaboration. Cardiologists, oncologists, epidemiologists, and public health practitioners must converge on developing integrated models of risk stratification. Such models—incorporating traditional clinical parameters, lifestyle factors, and potentially emerging biomarkers—could be used not only in research but also to inform updated clinical guidelines that reflect the dual burden of CVD and cancer. Incorporating CVH assessments into routine screening could offer a scalable, cost-effective approach to population risk management.

Future research should prioritize standardizing CVH metrics to enable pooling of data across cohorts and facilitate dose-response meta-analyses. Mechanistic studies are also needed to elucidate how shared pathways such as insulin resistance, endothelial dysfunction, and systemic inflammation might differentially contribute to oncogenesis.

In conclusion, the scoping review by Henriquez Santos et al⁴ underscores a promising frontier: the utility of cardiovascular metrics as tools for cancer risk prediction. Although definitive causal pathways and the precise incremental and independent predictive value of these metrics remain to be clarified, the existing evidence highlights the potential for shared preventive strategies. Enhancing CVH may reduce the risk for both heart disease and certain cancers. As our understanding deepens, the artificial boundary between cardiovascular and oncologic care may begin to dissolve, ushering in a more holistic approach to chronic disease prevention.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.