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. 2022 Jul 5;80(1):22-32.
doi: 10.1016/j.jacc.2022.04.042.

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study

Roberta Florido  1 , Natalie R Daya  2 , Chiadi E Ndumele  3 , Silvia Koton  4 , Stuart D Russell  5 , Anna Prizment  6 , Roger S Blumenthal  3 , Kunihiro Matsushita  7 , Yejin Mok  2 , Ashley S Felix  8 , Josef Coresh  2 , Corinne E Joshu  9 , Elizabeth A Platz  9 , Elizabeth Selvin  2
Affiliations

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study

Roberta Florido et al. J Am Coll Cardiol. .

Abstract

Background: More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking.

Objectives: The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study.

Methods: We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD.

Results: Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk.

Conclusions: Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.

Keywords: cancer; cardio-oncology; cardiovascular disease; epidemiology; heart failure; prevention.

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Conflict of interest statement

Funding Support and Author Disclosures The ARIC study has been supported with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health (NIH), and the Department of Health and Human Services under contract numbers 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, and 75N92022D00005. Studies on cancer in the ARIC study are also supported by the National Cancer Institute (grant U01CA164975). This research was additionally supported by a Cancer Center Support Grant from the National Cancer Institute (grant P30 CA006973). Ms Daya was supported by NIH/NHLBI grant T32HL007024. Dr Selvin was supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases grants K24 HL152440 and R01 DK089174. Dr Ndumele was supported by NIH/NHLBI grant R01 HL146907 and American Heart Association grant 20SFRN35120152. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.
Association of Cancer Survivorship with Cardiovascular Disease, by Cancer Type Caption: Forest plot demonstrating the association of cancer and cancer subtypes with incident CVD, after adjustment for demographic variables and shared risk factors between cancer and CVD (Model 2). a) Model 2: Adjusted for baseline age, sex, race-center, educational level, drinking status, and time-varying smoking status and cigarette pack-years, NSAID use (including aspirin), and time-varying, body mass index, LDL-cholesterol, HDL-cholesterol, triglycerides, use of lipid lowering medications, hypertension, diabetes mellitus and eGFR. b) N = total number of participants included in the analyses, including cancer survivors and persons without cancer.
Central Illustration.
Central Illustration.. Cardiovascular Disease Risk in Cancer Survivors and Proposed Pathways Linking Cancer and Cardiovascular Disease.
Cancer related pathways underlying the associations of cancer with CVD include but are not limited to common biologic predisposition; inflammation, oxidative stress, a pro-thrombotic state promoted by the cancer itself; and cardiotoxic effects of various cancer therapies. Non-cancer related pathways include lifestyle factors such as diet and physical activity, and other shared risk factors between cancer and CVD such as smoking, obesity and diabetes.
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