The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons
Open accessAbstract
Objective The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. Methods Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. Results The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01). Conclusions Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively.
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Low SHBG levels contribute to long term consequences of METS; associations between low SHBG and higher risk of coronary and peripheral artery disease have been found, independent of other cardiovascular risk factors.
“Furthermore, low SHBG levels also contribute to long term consequences of METS. Associations between low SHBG and higher risk of coronary and peripheral artery disease have been found, independent of other cardiovascular risk factors [137, 138].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [137]
The Results (SHBG; page not provided) report that low SHBG was associated with PAD in older men after adjustment for multiple confounders, including metabolic syndrome. The association was not significant in women or after further adjustment for testosterone and estradiol. The paper does not establish a low-SHBG association with coronary artery disease, and its Limitations section says the cross-sectional study cannot determine whether SHBG contributes causally to PAD. (LLM, conf=0.88)
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- [1]Lloyd-Jones D Adams RJ Brown TM American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation 2010 121 948 954 Erratum in: Circulation 2010; 121:e259. 20177011
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- Authors
- Maggio, M., Cattabiani, C., Lauretani, F., Artoni, A., Bandinelli, S., Schiavi, G., Vignali, A., Volpi, R., Ceresini, G., Lippi, G., Aloe, R., De Vita, F., Giallauria, F., McDermott, M. M., Ferrucci, L., & Ceda, G. P.
- Affiliations
- University of Parma (IT)
- Ospedale di Parma (IT)
- Azienda Sanitaria di Firenze (IT)
- University of Naples Federico II (IT)
- Northwestern University (US)
- National Institutes of Health (US)
- Corresponding author
- Maggio, M.
- ORCID
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 225
- Issue
- 2
- Pages
- 469-474
- ISSN
- 0021-9150 (ISSN-L)
- PMC
- PMC4050374
- OpenAlex
- W1985179766
- Cited by
- 24
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 4
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Italian Ministry of Health (ICS 110.1/RS97.71)
- US National Institute on Aging (N01-AG-916413, N01-AG-821336)
- Intramural Research Program of the US National Institute on Aging (263 MD 9164 13, 263 MD 821336)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- peripheral arterial disease, sex hormones, sex hormone-binding globulin, testosterone, estradiol, older adults, ankle-brachial index, sex differences, metabolic syndrome, InCHIANTI cohort
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Cross-Sectional Studies, Estradiol, Female, Humans, Italy, Male, Risk Factors, Sex Factors, Sex Hormone-Binding Globulin, Testosterone, Biomarkers, Down-Regulation, Up-Regulation, Comorbidity, Chi-Square Distribution, Logistic Models, Ankle Brachial Index, Peripheral Arterial Disease
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