HF may be tied to cancer incidence, mortality in those 50 years and older
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HF may be associated with cancer incidence as well as risk for cancer-related mortality, especially among individuals aged 50 to 70 years, according to new data published in JACC: CardioOncology.
“The association between HF and cancer has gained increasing attention in the last years. The coexistence of these two entities is increasingly common caused by the progressive aging of the population and the growth in risk factors predisposing to both conditions, posing a substantial clinical and economic burden,” Edoardo Bertero, MD, of the Comprehensive Heart Failure Center at University Clinic Würzburg, Germany, and colleagues wrote. “It remains unclear whether HF is associated with an excess risk of cancer and cancer-related mortality. In this context, we assessed cancer incidence and mortality in a large cohort of HF patients compared with matched control subjects.”
For the present analysis, researchers included individuals from the Puglia region of Italy aged 50 years or older with no cancer within 3 years before the study and at least 5 years of follow-up data. The 104,020 participants with HF at baseline (47% men) were matched with the same number of controls without HF, based on age, sex, drug-derived complexity index, Charlson comorbidity index and follow-up duration.
HF and cancer risk
According to the study, the incidence of cancer in patients with HF was 21.36 per 1,000 person-years (95% CI, 20.98-21.74) compared with 12.42 per 1,000 person-years among controls (95% CI, 12.14-12.72).
The risk for cancer was greater among individuals with HF at baseline compared with the control group without HF (HR = 1.76; 95% CI, 1.71-1.81).
The researchers reported that cancer-related mortality was also higher among patients with HF compared with controls (HR = 4.11; 95% CI, 3.86-4.38), and the degree varied by age:
- younger than 70 years (HR = 7.54; 95% CI, 6.33-8.98);
- 70 to 79 years (HR = 3.8; 95% CI, 3.44-4.19); and
- 80 years or older (HR = 3.1; 95% CI, 2.81-3.43).
Overall, HF was associated with elevated risk for most types of cancer, including colorectal cancer, lung cancer, lymphoma and multiple myeloma (P for all < .001). HF was not associated with female breast cancer.
Moreover, high-dose loop diuretic use was associated with elevated cancer incidence (HR = 1.11; 95% CI, 1.03-1.21) and mortality (HR = 1.35; 95% CI, 1.19-1.53) among individuals with HF.
“This study supports the notion that HF does portend an increased risk of cancer, regardless of sex and age, although the incidence rate of cancer was markedly higher in males and increased with age,” the researchers wrote. “It is notable that the findings presented here were obtained after matching HF patients and control subjects based on drug-derived complexity index and, secondarily, Charlson comorbidity index, thus at least in part controlling for the potential confounding effect of comorbidities.”
‘Little evidence’ that HF causes cancer
In a related editorial, Harry Klimis, MBBS, PhD, clinical and research fellow at the Population Health Research Institute and department of medicine at McMaster University and Hamilton Health Sciences in Ontario, Canada, and colleagues discussed how, despite large sample sizes, analyses such as this cannot definitively label HF as a cause of cancer.
“Based on this analysis of the findings of Bertero and others, there is little evidence that heart failure in and of itself causes cancer. More generally, administrative data have important strengths and limitations for cardio-oncology research. Their strength lies in the large sample sizes available and the large number of outcome events,” Klimis and colleagues wrote. “It must be recognized that large sample sizes with many outcome events do not address unmeasured confounding but as in all retrospective analyses carry a risk of bias. Therefore, large sample sizes, which decrease confidence intervals surrounding estimates, have the potential to lead to estimates that are very precisely biased. Thus, while further research into the factors underlying the association between heart failure and cancer incidence reported may be interesting, based on the present data, we cannot yet conclude that heart failure in and of itself causes cancer.”
Reference:
Perspective
Back to TopSherry-Ann Brown, MD, PhD, FACC, FAHA
There is indication that remodeling in the setting of HF may promote a pro-oncogenic environment. The reverse is also true. HF and cancer share a bidirectional risk relationship that can be modified by other factors as well (de Boer RA, et al. Cardio-Oncology. 2021;doi:10.1186/s40959-021-00110-1). The balance and the direction of this shift is particularly dependent on patient and environment characteristics. Whichever disease condition comes first still yet inevitably may help facilitate development of the other. Multiple hits of various sorts can tip the balance and shift the equilibrium in one direction or other, towards cancer or towards CVD, or both. This has led to the proposed five-tier classification system for cardio-oncology syndromes. In cardio-oncology syndromes Type III, progressive scarring and remodeling of the heart and kidney, can cause a pro-oncogenic environment. This particular study by our colleagues in Italy supports these concepts and may suggest a dose-response relationship for cardio-oncology syndromes Type III.
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