Alexander W Pastuszak1, Taylor P Kohn2, Joel Estis3, Larry I Lipshultz4. 1. Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX, USA; Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA. Electronic address: pastusza@bcm.edu. 2. Baylor College of Medicine, Houston, TX, USA. 3. Singulex, Inc, Alameda, CA, USA. 4. Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX, USA; Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
Abstract
BACKGROUND: The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers. AIM: To determine the relation between T levels and high-sensitivity CV risk biomarkers. METHODS: Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing. Patients were grouped by total T concentration and associations with the following biomarkers were determined: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-17A, N-terminal pro-B-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin. OUTCOMES: Association of CV risk markers with levels of T in men. RESULTS: The median age of the cohort was 58 years (interquartile range = 48-68), and the median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did not vary with patient age. An inverse relation between plasma T levels and CV risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-α, NTproBNP, HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1, NTproBNP, and leptin were significantly associated with a T level lower than 250 ng/dL. CLINICAL IMPLICATIONS: Men with low T levels could be at increased risk for increased CV disease as seen by increased CV risk markers. STRENGTH AND LIMITATIONS: This study was performed in a group of 10,041 men and is the first study to examine CV risk associated with circulating T levels using a large panel of 10 objective biomarkers. This study is limited by an absence of clinical data indicating whether men had pre-existing CV disease or other CV risk factors. CONCLUSION: Men with low plasma T levels exhibit increases in CV risk markers, consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. J Sex Med 2017;14:1095-1103.
BACKGROUND: The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers. AIM: To determine the relation between T levels and high-sensitivity CV risk biomarkers. METHODS: Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing. Patients were grouped by total T concentration and associations with the following biomarkers were determined: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-17A, N-terminal pro-B-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin. OUTCOMES: Association of CV risk markers with levels of T in men. RESULTS: The median age of the cohort was 58 years (interquartile range = 48-68), and the median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did not vary with patient age. An inverse relation between plasma T levels and CV risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-α, NTproBNP, HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1, NTproBNP, and leptin were significantly associated with a T level lower than 250 ng/dL. CLINICAL IMPLICATIONS: Men with low T levels could be at increased risk for increased CV disease as seen by increased CV risk markers. STRENGTH AND LIMITATIONS: This study was performed in a group of 10,041 men and is the first study to examine CV risk associated with circulating T levels using a large panel of 10 objective biomarkers. This study is limited by an absence of clinical data indicating whether men had pre-existing CV disease or other CV risk factors. CONCLUSION:Men with low plasma T levels exhibit increases in CV risk markers, consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. J Sex Med 2017;14:1095-1103.
Authors: Kay-Tee Khaw; Mitch Dowsett; Elizabeth Folkerd; Sheila Bingham; Nicholas Wareham; Robert Luben; Ailsa Welch; Nicholas Day Journal: Circulation Date: 2007-11-26 Impact factor: 29.690
Authors: Jacques Baillargeon; Randall J Urban; Yong-Fang Kuo; Kenneth J Ottenbacher; Mukaila A Raji; Fei Du; Yu-Li Lin; James S Goodwin Journal: Ann Pharmacother Date: 2014-07-02 Impact factor: 3.154
Authors: Olga M Calof; Atam B Singh; Martin L Lee; Anne M Kenny; Randall J Urban; Joyce L Tenover; Shalender Bhasin Journal: J Gerontol A Biol Sci Med Sci Date: 2005-11 Impact factor: 6.053
Authors: G Corona; G Rastrelli; E Maseroli; N Fralassi; A Sforza; G Forti; E Mannucci; M Maggi Journal: Andrology Date: 2014-07-07 Impact factor: 3.842
Authors: Giovanni Corona; Elisa Maseroli; Giulia Rastrelli; Andrea M Isidori; Alessandra Sforza; Edoardo Mannucci; Mario Maggi Journal: Expert Opin Drug Saf Date: 2014-08-19 Impact factor: 4.250
Authors: Laura A Colangelo; Pamela Ouyang; Kiang Liu; Peter Kopp; Sherita Hill Golden; Adrian S Dobs; Moyses Szklo; Dhananjay Vaidya; Mary Cushman; Susan M Gapstur Journal: Diabetes Care Date: 2009-03-16 Impact factor: 19.112
Authors: Thiago Gagliano-Jucá; M Furkan Burak; Karol M Pencina; Zhuoying Li; Robert R Edwards; Thomas G Travison; Shehzad Basaria Journal: J Clin Endocrinol Metab Date: 2018-10-01 Impact factor: 5.958
Authors: Michael Samoszuk; Abraham Morgentaler; Mark de Groot; Wouter van Solinge; Yu Li; Fiona Adair; Imo Hoefer; Saskia Haitjema Journal: Int J Impot Res Date: 2019-01-22 Impact factor: 2.896
Authors: Baris Gencer; Marco Bonomi; Maria Pia Adorni; Cesare R Sirtori; François Mach; Massimiliano Ruscica Journal: Rev Endocr Metab Disord Date: 2021-02-22 Impact factor: 6.514
Authors: Martin Aguilar; Robert A Rose; Abhijit Takawale; Stanley Nattel; Svetlana Reilly Journal: Cardiovasc Res Date: 2021-06-16 Impact factor: 10.787