Can Managing Heart Health Improve Cancer Outcomes?

Kevin Nead, MD

Researchers are delving deeper into the intriguing link between cardiovascular disease (CVD) and cancer, looking beyond established shared risk factors. This growing field of study seeks to understand if there are direct effects between these leading killers, potentially independent of common risk factors.

“It has long been established that cardiovascular disease and cancer have a multiple shared risk factors. Smoking would be an obvious one, but also things like type II diabetes and obesity. We know that people who have 1 of those illnesses, whether it is cancer or cardiovascular disease, are often at increased risk for the other because they have risk factors that impact both,” explained Kevin Nead, MD, an assistant professor in epidemiology and radiation oncology, University of Texas MD Anderson Cancer Center, in an interview with Targeted Oncology^TM.

“Heart disease and cancer are the number 1 and 2 killers in the world, so right away, we are interested in understanding these 2 leading causes of death,” said Nicholas Leeper, MD, professor of medicine and surgery, chief of vascular medicine and director of vascular research at Stanford University, in an interview with Targeted Oncology^TM.

Driven by the immense global burden of both diseases, experts like Nead and Leeper are exploring the connection between CVD and cancer. According to Leeper, preclinical models have shown that various types of CVD can lead to increased rates of cancer progression; however, clinical studies have not clearly determined the impact of atherosclerosis on cancer risk.

“There has also been a hint that addressing your cardiovascular risk factors may not only improve your cardiac outcomes, but also lead to better oncologic outcomes. We want to understand that better and try to see if this is all about shared risk factors, or if there may be more specific biology at play,” added Leeper.

As a result, their study looked to solidify associations beyond shared risk factors and begin to define the biological mechanisms behind this potential direct link. Further, they sought to determine whether CVD is directly linked with the development of cancer.

Nicholas Leeper, MD

Methods and Design of the Retrospective Cohort Study

The study leveraged IBM MarketScan claims data from over 130 million individuals. Researchers identified 27 million individuals who were cancer-free with at least 36 months of follow-up. Once included, participants were stratified by the presence or absence of CVD.

“It is a retrospective analysis and we are looking at patients who are part of the IBM MarketScan database, which is largely a source of clinical information for people who have private insurance,” said Nead. “When they get treated or have care, there are billing codes and procedure codes, and all of that gets recorded. [We] can use that to classify people as having or not having cardiovascular disease, for example.”

Their analysis explored the cumulative risk of cancer development in both groups, further investigating the relationship by CVD type (atherosclerotic vs nonatherosclerotic) and cancer subtype.

“We classified patients initially into 2 groups that have cardiovascular disease and don't have cardiovascular disease. After that period of determination was done, we went forward in time to look for evidence of a cancer diagnosis,” Nead explained.

“We were able to further substratify and look at different types of cardiovascular disease, including atherosclerosis, in particular, and then look at association with cancer,” added Leeper.

The retrospective cohort study included patients aged 18 years or older who were enrolled in the database since 2009. Patients must have had no cancer diagnosis codes in the first 24 months of enrollment. All individuals had a 24-month run-in period from the time of cohort entry.

Among those enrolled, the mean age was 43.3 years and 55.7% were female. The median follow-up time was 33 (IQR, 20-52) months.

“The sample size and power were major advantages. We were able to look at data from more than 130 million individuals, and then narrow that down to this cohort with 27 million people who had up to 3 years of continuous data. This is a large and diverse group of patients, which overcomes several of the limitations of prior studies,” explained Leeper.

Findings and Shared Risk Factors

3d rendered illustration of heart attack and heart disease 3D illustration: © appledesign - stock.adobe.com

The study found that individuals with CVD were 13% more likely to develop cancer compared with those without CVD (HR, 1.13; 95% CI, 1.12-1.13). This finding was statistically significant, indicating a probable association between CVD and cancer risk beyond other influencing factors.

“There seems to be a clear association between cardiovascular disease and future risk of cancer. In particular, that link seems to be even more pronounced amongst those with atherosclerotic forms of cardiovascular disease,” said Leeper.

Among those with atherosclerotic CVD, there was a stronger association with cancer risk compared with those without CVD (HR, 1.20; 95% CI, 1.19-1.21). Patients with atherosclerotic CVD also had a higher risk of developing cancer compared with patients with nonatherosclerotic CVD (HR, 1.11; 95% CI, 1.11-1.12).

“When [we] look at the patients who have cardiovascular disease and we do our utmost to adjust for all of those shared risk factors that we know that patients have, we still see a strong effect of an increased risk of cancer. Even when we account for smoking, and other common comorbidities, that risk persists. Our study design would suggest that the association between CVD and cancer is at least partially independent of those shared risk factors,” Nead explained.

This finding that atherosclerotic CVD poses a greater risk for cancer development vs nonatherosclerotic CVD underscores the need for more tailored approaches in managing cardiovascular risk and its potential cancer implications. While this study identified a link between CVD and cancer risk, further research is needed to further understand the underlying mechanisms and potential interventions.

“This reinforces the potential value of modifying cardiovascular risk factors, especially if it may provide benefit outside of cardiovascular disease…Often in medicine, we need that reinforcement to encourage us to focus on preventative medicine,” added Nead.

Investigating specific CVD types and cancer subtypes could also provide additional insights for personalized risk assessment and prevention strategies.

Next Steps in Determining the Link Between CVD and Cancer

The growing evidence suggesting a causal link between CVD and cancer requires further exploration, according to both Leeper and Nead, the first of which must focus on moving beyond just the association between the two disorders.

“The next population-level study design we would like to pursue would be a prospective population-based study,” explained Nead. “In such a study, we can make sure to capture all known modifiable risk factors."

Current research has established an association between CVD and cancer; however, prospective population-based studies are now necessary to begin to define their causal relationship. These studies would follow individuals, capturing detailed information about modifiable risk factors like smoking patterns and other exposures, providing a more comprehensive picture.

Next, there must be continued evaluation seeking to identify definitive causal association and modifiable targets. According to Nead, this can be done through combining population-level studies with mechanistic research.

"When I think about next steps... 1 aspect of studying this question is that you cannot conduct a randomized trial...The next thing that we need is to establish the evidence for an effect. That is mechanistic studies, so [preclinical] models," explained Nead, outlining the importance of preclinical research with mouse models to understand the biological pathways involved.

Through determining what the modifiable biological pathways are beyond just traditional risk factors, experts can begin to develop targeted therapies that will be used to address both CVD and cancer simultaneously.

"It is moving from association to causation, and then trying to identify the molecular underpinnings of such a link...that we could make therapies that would target both at the same time," Leeper added, emphasizing the potential for developing targeted therapies that address both diseases.

Additionally, capturing more specific and informative details in trials will help experts understand this link. For example, while there is information regarding smoking in this study, more, including pack-years of smoking and other exposures, will allow additional and more precise adjustments to further help determine the correlation between CVD and cancer.

“Ideally, [we would] have granular information like pack-years, how long have you smoked, how many packs a day, what are the other exposures...," emphasized Nead.

By implementing these steps, researchers can help strengthen the evidence for a causal relationship. This ultimately will pave the way for developing therapies that provide mutual benefit for both CVD and cancer.

“Focusing on cardiovascular health in [patients with] cancer is important, because ultimately, our goal is to cure them of their cancer. When we cure them of their cancer, we want them to go off into the world as a healthy individual,” concluded Nead.

REFERENCE:

Bell CF, Lei X, Haas A, et al. Risk of Cancer After Diagnosis of Cardiovascular Disease. JACC CardioOncol. 2023;5(4):431-440. Published 2023 Apr 11. doi:10.1016/j.jaccao.2023.01.010