Allostatic load and cardiovascular outcomes in males with prostate cancer

Nickolas Stabellini; Jennifer Cullen; Marcio S Bittencourt; Justin X Moore; Lifen Cao; Neal L Weintraub; Ryan A Harris; Xiaoling Wang; Biplab Datta; Steven S Coughlin; Jorge Garcia; John Shanahan; Nelson Hamerschlak; Kristin Waite; Nathanael R Fillmore; Martha Terris; Alberto J Montero; Jill S Barnholtz-Sloan; Avirup Guha

doi:10.1093/jncics/pkad005

Allostatic load and cardiovascular outcomes in males with prostate cancer

JNCI Cancer Spectr. 2023 Mar 1;7(2):pkad005. doi: 10.1093/jncics/pkad005.

Authors

Nickolas Stabellini^{1

2

3

4}, Jennifer Cullen^{4

5}, Marcio S Bittencourt⁶, Justin X Moore⁷, Lifen Cao², Neal L Weintraub^{8

9}, Ryan A Harris^{10

11}, Xiaoling Wang¹², Biplab Datta^{13

14}, Steven S Coughlin^{13

14}, Jorge Garcia², John Shanahan¹⁵, Nelson Hamerschlak¹⁶, Kristin Waite¹⁷, Nathanael R Fillmore^{18

19}, Martha Terris^{20

21}, Alberto J Montero², Jill S Barnholtz-Sloan^{17

22}, Avirup Guha^{23

24

25}

Affiliations

¹ Graduate Education Office, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
² Department of Hematology-Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA.
³ Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
⁴ Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁵ Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
⁶ Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Cancer Prevention, Control, & Population Health Program, Department of Medicine, Medical College of Georgia at Augusta University, GA, USA.
⁸ Department of Medicine, Cardiology Division, Medical College of Georgia at Augusta University, Augusta, GA, USA.
⁹ Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA.
¹⁰ Department of Medicine, Georgia Prevention Institute, Augusta University, Augusta, GA, USA.
¹¹ Sport and Exercise Science Research Institute, Ulster University, Jordanstown, Northern Ireland, UK.
¹² Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
¹³ Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA, USA.
¹⁴ Institute of Public and Preventive Health, Augusta University, Augusta, GA, USA.
¹⁵ Cancer Informatics, Seidman Cancer Center at University Hospitals of Cleveland, Cleveland, OH, USA.
¹⁶ Oncohematology Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
¹⁷ Trans-Divisional Research Program (TDRP), Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁸ Cooperative Studies Program (CSP) Informatics Center, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.
¹⁹ Harvard Medical School, Boston, MA, USA.
²⁰ Urology Section, Department of Surgery, Veterans Affairs Medical Centers, Augusta, GA, USA.
²¹ Division of Urologic Surgery, Department of Surgery, Medical College of Georgia, Augusta, GA, USA.
²² Center for Biomedical Informatics and Information Technology (CBIIT), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²³ Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
²⁴ Cardio-Oncology Program, Ohio State University, OH, USA.
²⁵ Cardio-Oncology Program, Department of Medicine, Cardiology Division, Medical College of Georgia, Augusta University, Augusta, GA, USA.

Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death in men with prostate cancer (PC). Accumulated stress plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL).

Methods: The initial cohort included males aged 18 years and older diagnosed with PC (2005-2019). AL was modeled as an ordinal variable (0-11). Fine-Gray competing risk regressions measured the impact of precancer diagnosis AL and postdiagnosis AL in 2-year major cardiac events (MACE). The effect of AL changes over time on MACE development was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after PC diagnosis).

Results: We included 5261 PC patients of which 6.6% had a 2-year MACE. For every 1-point increase in AL before and within 60 days after PC diagnosis, the risk of MACE increased 25% (adjusted hazard ratio [aHR] =1.25, 95% confidence interval [CI] = 1.18 to 1.33) and 27% (aHR = 1.27, 95% CI = 1.20 to 1.35), respectively. Using AL as a time-varying exposure, the risk of MACE increased 19% (aHR = 1.19, 95% CI = 1.11 to 1.27), 22% (aHR = 1.22, 95% CI = 1.14 to 1.33), 28% (aHR = 1.28, 95% CI = 1.23 to 1.33), and 31% (aHR = 1.31, 95% CI = 1.27 to 1.35) for every 1-point increase in AL before, 2 months after, 6 months after, and 1 year after PC diagnosis, respectively.

Conclusion: AL and its changes over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Allostasis*
Cardiovascular Diseases*
Humans
Male
Prostatic Neoplasms*

Abstract

Publication types

MeSH terms

Grants and funding