Adipokines are possible risk markers for aortic stenosis requiring surgery

Abstract

Objectives

Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR).

Design

In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents.

Results

Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92–1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08–1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82–1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64–0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI).

Conclusions

The adipokine leptin may promote the development of AS.

Keywords:

• Aortic stenosis
• leptin
• adiponectin
• fat mass
• risk markers
• prospective study

Acknowledgements

The authors wish to thank Maj Jerner (biomedical analyst) for the laboratory work crucial to this project. We would also like to acknowledge the Västerbotten Intervention Project (VIP), the Northern Sweden MONICA project, the Northern Sweden Health and Disease Study, the County Council of Västerbotten and Biobank Sweden. We appreciate the assistance provided by Jan Hentschel, Elin Albertsson, Paul Holmer, Veronica Hellström, Åsa Ågren, Göran Hallmans, Camilla Ring, Mattias Söderberg, Lucy Francesca Fisher, and Catrin Johansson, all of whom have been instrumental in the completion of this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data from the NSHDS surveys are not freely available according to GDPR due to the presence of individual data. However, pseudonymized data can be shared after ethical evaluation and formal request (https://www.umu.se/en/biobankresearch–unit/research/access–to–samples–anddata/access–to–nsdd/).

Additional information

Funding

The VIP and the Northern Sweden MONICA studies were funded by the county councils in Norr– and Västerbotten. This project was partially funded by the Swedish Heart and Lung Foundation (20100635, 20120631, 20140799, 20130630), the Västerbotten county council (ALF RV-967561), and Umeå University (964731).