Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population

Benjamin C Trumble; Jacob Negrey; Stephanie V Koebele; Randall C Thompson; L Samuel Wann; Adel H Allam; Bret Beheim; M Linda Sutherland; James D Sutherland; Daniel Eid Rodriguez; David E Michalik; Chris J Rowan; Guido P Lombardi; Angela R Garcia; Daniel K Cummings; Edmond Seabright; Sarah Alami; Thomas S Kraft; Paul Hooper; Kenneth Buetow; Andrei Irimia; Margaret Gatz; Jonathan Stieglitz; Michael D Gurven; Hillard Kaplan; Gregory S Thomas; Tsimane Health and Life History Project Teams

doi:10.1093/emph/eoad039

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population

Evol Med Public Health. 2023 Nov 16;11(1):472-484. doi: 10.1093/emph/eoad039. eCollection 2023.

Authors

Benjamin C Trumble¹, Jacob Negrey¹, Stephanie V Koebele¹, Randall C Thompson², L Samuel Wann³, Adel H Allam⁴, Bret Beheim⁵, M Linda Sutherland⁶, James D Sutherland⁶, Daniel Eid Rodriguez⁷, David E Michalik^{8

9}, Chris J Rowan¹⁰, Guido P Lombardi¹¹, Angela R Garcia¹, Daniel K Cummings¹², Edmond Seabright¹³, Sarah Alami¹³, Thomas S Kraft¹⁴, Paul Hooper¹², Kenneth Buetow¹, Andrei Irimia¹⁵, Margaret Gatz¹⁵, Jonathan Stieglitz¹⁶, Michael D Gurven¹⁷, Hillard Kaplan¹², Gregory S Thomas^{6

18}; Tsimane Health and Life History Project Teams

Affiliations

¹ Arizona State University, School of Human Evolution and Social Change, Center for Evolution and Medicine, Institute of Human Origins, Tempe, AZ, USA.
² Saint Luke's Mid America Heart Institute, Department of Cardiology, Kansas City, MO, USA.
³ University of New Mexico, School of Medicine, Albuquerque, NM, USA.
⁴ Al Azhar University, School of Medicine, Cairo, Egypt.
⁵ Max Planck Institute for Evolutionary Anthropology, Department of Human Behavior, Ecology and Culture, Leipzig, Germany.
⁶ MemorialCare Health System, Fountain Valley, CA, USA.
⁷ Universidad de San Simón, Department of Medicine, Cochabamba, Bolivia.
⁸ University of California Irvine, School of Medicine, Irvine, CA, USA.
⁹ Miller Women's and Children's Hospital Long Beach, CA, USA.
¹⁰ University of Nevada, School of Medicine, NV, USA.
¹¹ Universidad Peruana Cayetano Heredia, Laboratorio de Paleopatología, Lima, Peru.
¹² Chapman University, Economic Science Institute, Orange, CA, USA.
¹³ Mohammed VI Polytechnic University, School of Collective Intelligence, Ben Guerir, Morocco.
¹⁴ University of Utah, Anthropology Department, Salt Lake City, UT, USA.
¹⁵ University of Southern California, Psychology Department, Los Angeles, CA, USA.
¹⁶ Toulouse Scool of Economics, Institute for Advanced Study Toulouse, Toulouse, France.
¹⁷ University of California Santa Barbara, Department of Anthropology, Santa Barbara, CA, USA.
¹⁸ University of California Irvine, Division of Cardiology, Orange, CA, USA.

Abstract

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores.

Methodology: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years).

Results: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007).

Conclusions and implications: Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

Keywords: cardiovascular disease; coronary artery calcium; evolutionary mismatch; testosterone.

Grants and funding

R01 AG054442/AG/NIA NIH HHS/United States