In a study reported in JACC: CardioOncology, Emily S. Lau, MD, of the Cardiology Division, Department of Medicine, Massachusetts General Hospital, and colleagues found that the presence of cardiovascular disease (CVD) risk factors was significantly associated with an increased risk of future cancer, although no increased risk was observed among individuals with a history of CVD events or those who developed CVD events during follow-up.1
Emily S. Lau, MD
As stated by the investigators: “[R]ecent investigations have suggested that CVD itself may lead to increased risk of cancer development, although data are conflicting…. [Some] studies support an increased risk of cancer among patients with heart failure, although this has not been true across all studies…. CVD risk factors and ideal CV health [metrics] as outlined by the American Heart Association (AHA) 2020 Impact Goal have previously been associated with cancer risk. Despite a growing body of literature examining the relationship between cancer and CVD, whether the association between CVD and cancer is due to shared risk factors or other mechanisms remains unclear.”
The study involved data from the prospective follow-up of participants in the Framingham Heart Study and PREVEND study with no history of cancer at baseline. Histology-proven cancer cases were identified through surveillance of routine examinations, health updates, hospital admissions, or from death records through December 31, 2016. Multivariate models were used to analyze potential association baseline traditional CVD risk factors, 10-year atherosclerotic CVD risk score, established CVD biomarkers (including high-sensitivity cardiac troponin and natriuretic peptide), prevalent CVD, and the AHA Life’s Simple 7 CV health score with future occurrence of cancer.
In an examination of CVD risk factors, the analysis population consisted of 20,305 participants with no baseline major CVD or atrial fibrillation. Analysis of prevalent CVD included 1,020 participants with a history of major CVD at baseline.
Association of Traditional CVD Risk Factors and Biomarkers With Cancer Risk
Among the 20,305 participants, mean patient age was 50 ± 14 years, 54% were women, 33% were former and 29% current smokers, and 4% had diabetes. Overall, 15% used antihypertensive medications, and 4% had hyperlipidemia requiring statin therapy.
Over a median follow-up of 15 years (quartile 1–3 = 13.3–15.0 years), 2,548 incident cancer cases were observed. The most common cancer types included gastrointestinal (20%), lung (11%), prostate (16%), and breast (18%) cancers.
Among traditional CVD risk factors, increasing age (hazard ratio [HR] = 2.12, P < .001, per 1 standard deviation [SD] increase), male sex (HR = 1.39, P < .001), former smoker status (HR = 1.30, P < .001), and current smoker status (HR = 1.74, P < .001) were significantly associated with an increased risk of cancer. No significant associations were observed for systolic blood pressure, hypertension treatment, diabetes, body mass index, total cholesterol/high-density lipoprotein cholesterol ratio, or statin use.
The 10-year atherosclerotic CVD risk categories are defined as low (< 5%), borderline (5%–7.5%), intermediate (7.5%–20%), and high (> 20%). Higher 10-year atherosclerotic CVD risk scores were significantly associated with an increased risk of cancer, with a hazard ratio of 1.16 per 5% increase in risk (P < .001). Compared with low risk, hazard ratios were 1.88, 2.70, and 3.71 for borderline, intermediate, and high risk (all P < .001).
Increasing natriuretic peptide concentration was associated with an increased cancer risk (P = .02 for trend), both when comparing the highest vs lowest tertiles (HR = 1.40, P = .035) and when analyzed as a continuous variable (HR = 1.26, P < .001, per 1 SD increase). No significant association was observed for high-sensitivity cardiac troponin (P = .47 for trend) when comparing highest vs lowest tertiles (P =.37) or as a continuous variable (P = .07).
Associations With Prevalent CVD, Interim CVD Events, and AHA Health Score
Among the 1,020 participants with prevalent CVD at baseline, no significant association with subsequent cancer risk was observed overall (HR = 0.96, P = .61). This lack of a significant association was similarly seen among 793 with prior myocardial infarction (HR = 1.03, P = .71) and 116 with heart failure (HR = 0.66, P = .15). Among the total of 1,454 participants who developed CVD events during follow-up, no association with cancer risk was observed overall (HR = 0.99, P =.91); likewise, no association was seen among 687 with myocardial infarction (HR = 0.99, P = .95) or 681 with heart failure (HR = 1.07, P = .59).
The AHA Life’s Simple 7 CV health score was associated with a subsequent cancer risk. Scores range from 0 to 14, with scores of 0 to 6 indicating poor, 7 to 9 average, and 10 to 14 optimal CV health. Optimal CV health was associated with an age- and sex-adjusted hazard ratio of 0.94 (P = .01) per 1-point increase in score. Compared with participants with poor CV health, those with average and optimal CV health were less likely to develop cancer (overall P < .001).
The investigators stated: “Our study shows that in two cohorts with careful longitudinal ascertainment of new cancer cases, CV risk was associated with future risk of cancer, and ideal CV health was protective against incident cancer, whereas history of CVD and development of CV events in themselves did not appear to predict cancer risk. These findings provide support for the hypothesis that shared risk factors, rather than CVD itself, contributed to the association between CVD and cancer. For example, there has been growing interest in the role of inflammation, clonal hematopoiesis, and hyperinsulinemia in both CVD and cancer development.”
They concluded: “CVD risk, as captured by traditional CVD risk factors, 10-year [atherosclerotic CVD] risk score, and natriuretic peptide concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a lower risk of future cancer. These data suggest that the association between CVD and future cancer is attributable to shared risk factors.”
DISCLOSURE: Dr. Lau was supported by a grant from the National Institutes of Health.
1. Lau ES, Paniagua SM, Liu E, et al: Cardiovascular risk factors are associated with future cancer. JACC CardioOncol 3:48-58, 2021.
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