One of the known consequences of systemic cancer treatments includes increasing the risk of subsequent cardiovascular disease and therefore lowering long-term survival. On the other hand, there is substantial data on the positive impact of improving muscle strength and cardiovascular fitness to improve cancer-specific and all-cause mortality.
Here is a review of two publications that directly deal with both issues. They are entitled “Association of Muscle Strength and Cardiorespiratory Fitness with All-Cause and Cancer-Specific Mortality” and “Risk of Cardiovascular Disease in Cancer Survivors after Systemic Treatment”. This review will highlight their aims, methods, results, and implications in the context of cancer survivorship and long-term health risks.
Introduction and Objectives
Both studies contribute critically to understanding long-term health outcomes in cancer patients but approach the issue from distinct angles. The first report, a systematic review and meta-analysis by Bettariga et al., focuses on how physical fitness — specifically muscle strength and cardiorespiratory fitness (CRF) — correlates with all-cause and cancer-specific mortality in people already diagnosed with cancer. The second, by Mulder et al., is a large population-based cohort study that investigates the long-term cardiovascular disease (CVD) risks among cancer survivors treated with systemic therapies compared to matched cancer-free individuals.
Together, these reports address complementary aspects of post-cancer health: one emphasizes the protective value of fitness, while the other warns about treatment-associated cardiotoxicities and thrombotic risks.
Methods
Bettariga et al. conducted a systematic review and meta-analysis of 42 prospective cohort studies covering over 46,000 patients with various cancer types and stages. They included studies that assessed muscle strength (mainly handgrip) and CRF (often by cardiopulmonary exercise testing or 6-minute walk tests) and analyzed mortality outcomes. Their methods adhered to PRISMA guidelines, with robust quality assessments using the Newcastle-Ottawa Scale.
Conversely, Mulder et al. used Denmark’s high-quality national registries to build a cohort of 91,407 cancer survivors who had completed systemic treatment and remained cancer-free for at least three years. These survivors were matched to 457,035 cancer-free controls for age, sex, and calendar year. They were then followed for up to five years to capture incidence of multiple cardiovascular endpoints, including heart failure, venous thromboembolism (VTE), stroke, and kidney failure.
The contrasting methodological strengths are notable: Bettariga’s meta-analysis synthesizes many heterogeneous studies to extract robust, generalizable estimates for fitness and mortality; Mulder’s design minimizes confounding by using precise registry data and a carefully matched comparator cohort.
Key Findings
1. Protective Role of Fitness (Bettariga et al.)
The meta-analysis strongly supports that better fitness is linked with better survival. Specifically:
- High muscle strength or CRF is associated with a 31–46% reduction in all-cause mortality.
- Unit increases in muscle strength or CRF yield incremental survival benefits — each unit increase in CRF reduces cancer-specific mortality by 18%.
- These protective associations are consistent across most cancer types, including advanced stages and lung/digestive cancers.
This underscores the direct benefit of maintaining or improving strength and aerobic capacity during and after cancer treatment.
2. Elevated CVD Risks Post-Treatment (Mulder et al.)
Mulder et al. found that even years after systemic treatment, survivors face elevated risks of several cardiovascular conditions:
- Heart failure/cardiomyopathy risk was 8% higher overall, with even greater risk in survivors of hematologic and prostate cancers.
- VTE risk was 50% higher, consistent across nearly all cancer types.
- Inflammatory heart diseases (pericarditis, myocarditis, endocarditis) and kidney failure also showed modest increases.
- Interestingly, the risk of ischemic heart disease and stroke was not generally elevated except in certain groups (e.g., lung cancer survivors for ischemic heart disease, platinum compound recipients for stroke).
- Hormonal therapy did not increase CVD risks, while chemotherapy and some targeted therapies clearly did, especially anthracyclines and plant alkaloids.
This quantifies the legacy cardiovascular burden of systemic cancer treatments, showing that even when cancer is in remission, prior therapies continue to influence survivor health.
Comparison: Different Perspectives on Fitness and CVD
These studies converge on a key message: physical health and treatment toxicity both shape survivorship outcomes, but from opposite directions.
- Bettariga et al. advocate for proactive fitness monitoring and intervention, suggesting that increasing strength and CRF may mitigate the risk of premature death — likely through direct effects on tumor biology, immune function, and resilience to treatment side effects.
- Mulder et al. highlight the persistent risks posed by systemic therapies, which can damage cardiovascular structures or provoke thrombotic states long after active treatment ends.
Together, they imply a two-pronged survivorship strategy:
- Build and maintain fitness to reduce all-cause and cancer-specific mortality.
- Closely monitor and manage cardiovascular risks, particularly for survivors exposed to cardiotoxic or thrombogenic drugs.
Implications for Research and Practice
For clinicians and policy makers, these results urge integrated care:
- Exercise oncology programs should be standard — not only to counteract deconditioning but also as a survival-enhancing intervention.
- Cardio-oncology services must extend beyond the active treatment phase, with risk stratification based on the cancer type, stage, and specific agents used.
- Personalized surveillance could focus on high-risk groups — e.g., hematologic cancer survivors for heart failure, lung cancer survivors for ischemic disease, and nearly all survivors for VTE prevention.
For researchers, Bettariga et al. point out data gaps — e.g., limited evidence for fitness associations in less common cancers or childhood survivors. Mulder et al. reveal how treatment-specific data (e.g., breakdown by agent class) can refine risk predictions.
Both highlight the need for longitudinal trials: How much can tailored fitness interventions offset treatment-related CVD risks? What is the optimal timing and intensity of rehabilitation?
Limitations
Each study has caveats:
- Bettariga et al.’s meta-analysis pools observational data, which cannot prove causality; residual confounding remains possible.
- Mulder et al. cannot exclude the impact of undiagnosed recurrence or unmeasured lifestyle factors affecting cardiovascular outcomes.
Nevertheless, both employ robust, large-scale methods that lend high credibility to their findings.
Conclusion
In sum, these two complementary studies deliver a clear message: improving physical fitness is not only safe but likely life-extending for cancer survivors, while vigilant cardiovascular monitoring remains essential due to enduring treatment-related risks. Integrating these insights offers the best chance of optimizing both longevity and quality of life in a growing global population of cancer survivors.
References
Bettariga F, et al. Br J Sports Med 2025;59:722–732. doi:10.1136/bjsports-2024-108671
Mulder et al JACC CardioOcology, Vol. 7, No. 4, June 2025: 360-378
