Associations of Plasma Bioactive Adrenomedullin Levels with Cardiovascular Risk Factors in BRCA1/2 Mutation Carriers

Abstract

Background Cardiovascular disease (CVD) is an important cause of morbidity and mortality in breast cancer survivors. Effective screening modalities to identify CVD risk are lacking in this population. Adrenomedullin (ADM) has been suggested as a biomarker for subclinical cardiac dysfunction in the general population. Levels of ADM have been proven to be responsive to lifestyle changes that lead to improved cardiovascular health. As BRCA1/2 mutation carriers are deemed to be at an increased risk for CVD, the aim of this study was to examine plasma ADM levels in a cohort of BRCA mutation carriers and to assess their association with cardiovascular risk factors.

Methods Plasma ADM concentrations were measured in 292 female BRCA1/2 mutation carriers with and without a history of breast cancer. Subjects were classified into high versus low ADM levels based on the median ADM level in the entire cohort (13.8 pg/mL). Logistic regression models were used to estimate the odds ratios (OR) of having elevated ADM levels by several cardiovascular risk factors.

Results Of all women (median age: 43 years), 57.5% had a previous diagnosis of breast cancer. The median time between diagnosis and study entry was three years (range: 0 – 32 years). Women presenting with metabolic syndrome had 22-fold increased odds of having elevated ADM levels (p < 0.001). Elevated ADM levels were associated with lower cardiorespiratory fitness (OR = 0.88, p < 0.001) and several parameters of obesity (p < 0.001). ADM levels were higher in women who have ever smoked (OR = 1.72, p = 0.02). ADM levels were not associated with a previous diagnosis of breast cancer (p = 0.28).

Conclusions This is the first study in BRCA mutation carriers that has linked circulating ADM levels to traditional cardiovascular risk factors. The long-term clinical implications of these findings are yet to be determined.

Zusammenfassung

Hintergrund Herz-Kreislauf-Erkrankungen (HKE) sind eine wichtige Ursache für Morbidität und Mortalität bei Brustkrebsüberlebenden. Es fehlt aber an effektiven Früherkennungsuntersuchungen, welche die HKE-Risiken in dieser Population identifizieren könnten. Adrenomedullin (ADM) wurde bereits als möglicher Biomarker für subklinische Herzerkrankungen in der Allgemeinbevölkerung vorgeschlagen. Es hat sich gezeigt, dass Lebensstiländerungen, die zu einer Verbesserung der kardiovaskulären Gesundheit führen, sich in ADM-Plasmakonzentrationen widerspiegeln. Da Trägerinnen von BRCA1/2-Mutationen ein erhöhtes HKE-Risiko haben, zielt diese Studie darauf ab, die ADM-Plasmakonzentrationen in einer Gruppe von BRCA-Mutationsträgerinnen zu messen und den Zusammenhang mit HKE-Risikofaktoren zu untersuchen.

Methoden ADM-Plasmakonzentrationen wurden in 292 BRCA1/2-Mutationsträgerinnen mit oder ohne frühere Brustkrebsdiagnose gemessen. Basierend auf der medianen ADM-Konzentration der Gesamtgruppe (13,8 pg/ml) wurden die untersuchten Frauen gemäß ihrer ADM-Konzentrationen in 2 Gruppen (hohe bzw. niedrige ADM-Konzentration) eingeteilt. Logistische Regressionsmodelle wurden verwendet, um das Chancenverhältnis (OR) verschiedener kardiovaskulärer Risikofaktoren in Abhängigkeit der Höhe der ADM-Konzentration zu schätzen.

Ergebnisse Bei 57,5% der Frauen (Durchschnittsalter: 43 Jahre) wurde zuvor Brustkrebs diagnostiziert. Die mediane Zeit zwischen der Krebsdiagnose und die Aufnahme in dieser Studie betrug 3 Jahre (Spanne: 0 – 32 Jahre). Frauen mit metabolischem Syndrom hatten eine 22-fach höhere Wahrscheinlichkeit eines erhöhten ADM-Spiegels (p < 0,001). Erhöhte ADM-Spiegel waren mit niedriger kardiorespiratorischer Fitness (OR = 0,88, p < 0,001) sowie verschiedenen Übergewichtsparametern (p < 0,001) assoziiert. Der ADM-Spiegel war höher bei Frauen, die rauchten bzw. früher geraucht hatten (OR = 1,72, p = 0,02). Es gab kein Zusammenhang zwischen ADM-Konzentrationen und einer früheren Brustkrebsdiagnose (p = 0,28).

Schlussfolgerungen Dies ist die erste Studie von BRCA-Mutationsträgerinnen, welche die Verbindung zwischen ADM-Plasmakonzentrationen und traditionellen kardiovaskulären Risikofaktoren untersucht. Die langfristigen klinischen Implikationen der Befunde müssen noch ermittelt werden.

Key words

BRCA1 - BRCA2 - cardiovascular risk - breast cancer survivors

Schlüsselwörter

BRCA1 - BRCA2 - kardiovaskuläres Risiko - Brustkrebsüberlebende

Publication History

Received: 19 January 2022

Accepted after revision: 28 March 2022

Article published online:
03 June 2022

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