Aktuelle Ernährungsmedizin 2020; 45(03): 228
DOI: 10.1055/s-0040-1710236
Abstracts
Prävention, Lebensstil

High circulating levels of adrenomedullin are associated with metabolic syndrome, insulin resistance and low cardiorespiratory fitness in BRCA1 and BRCA2 mutation carriers

J Lammert
1   Frauenklinik am Universitätsklinikum rechts der Isar der Technischen Universität München, München, Germany
,
S Grill
1   Frauenklinik am Universitätsklinikum rechts der Isar der Technischen Universität München, München, Germany
,
M Yahiaoui-Doktor
2   Institut für Medizinische Informatik, Statistik und Epidemiologie, Universität Leipzig, Leipzig, Germany
,
M Basrai
3   Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Germany
,
J Struck
4   Sphingotec GmbH, Hennigsdorf, Germany
,
O Hartmann
4   Sphingotec GmbH, Hennigsdorf, Germany
,
SC Bischoff
3   Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Germany
,
M Halle
5   Zentrum für Prävention und Sportmedizin am Universitätsklinikum rechts der Isar der Technischen Universität München, München, Germany
,
M Kiechle
1   Frauenklinik am Universitätsklinikum rechts der Isar der Technischen Universität München, München, Germany
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    Background Risk factors for cardiovascular disease (CVD) and breast cancer overlap substantially. Identification of the underlying mechanisms associated with this co-occurrence is of great public health importance. Adrenomedullin (AM) is a widely expressed peptide with vasodilator and natriuretic properties. Previous studies showed a link between high AM levels and worse prognosis in patients with myocardial infarction and heart failure, indicating a crucial role in the pathophysiology of CVD. Elevated AM levels are associated with arterial hypertension, obesity and smoking. Moreover, 80 % of breast cancers express AM, and the degree of expression is associated with tumour progression.

    Objective Recent studies revealed that BRCA mutation carriers are potentially at higher cardiovascular risk. The value of AM in BRCA mutation carriers is unknown. The aim of this study was to examine plasma AM levels in BRCA mutation carriers and to assess their link to modifiable risk factors.

    Methods AM concentrations were measured in 292 BRCA1/2 mutation carriers from the LIBRE study, by an immunoassay (sphingotest bio‐ADM). Subjects were classified into high versus low AM levels based on the median plasma AM level in the entire cohort (13.7 pg/mL). Univariate logistic regression models were used to estimate the odds ratio (OR) of having elevated AM levels by metabolic syndrome (MetS, according to the joint interim statement criteria), cardiorespiratory fitness (CRF, measured by VO2peak during cycle ergometry), body mass index (BMI), insulin resistance (HOMA-IR ≥2.5), smoking and previous diagnosis of breast cancer.

    Results Of all women (median age: 43 years), 58 % had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was 3 years (range: 0-32 years). Women presenting with MetS had > 21 times higher odds of elevated AM levels (OR = 21.9, p <  0.001). Elevated AM levels were associated with lower VO2peak (OR = 0.88, p <  0.001), higher BMI (OR = 1.27, p <  0.001) and a HOMA-IR of ≥ 2.5 (OR = 3.94, p <  0.001). AM levels were higher in women who have ever smoked (OR = 1.77, p = 0.02), and AM levels increased with the number of pack-years (OR = 1.04, p = 0.01). AM levels were not associated with previous diagnosis of breast cancer (p = 0.3).

    Conclusions This is the first study in BRCA mutation carriers that has linked circulating AM levels to MetS, IR and CRF. The long-term clinical implications of these findings are yet to be determined.


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    Publication History

    Article published online:
    16 June 2020

    © Georg Thieme Verlag KG
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