Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease
2015 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 8, e001853- p.Article in journal (Refereed) Published
Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, Pless than0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.
Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2015. Vol. 4, no 8, e001853- p.
adiponectin; atherosclerosis; carotid intima-media thickness; genetics; Mendelian randomization
IdentifiersURN: urn:nbn:se:liu:diva-123165DOI: 10.1161/JAHA.115.001853ISI: 000364150900006PubMedID: 26276317OAI: oai:DiVA.org:liu-123165DiVA: diva2:877379
Funding Agencies|European Commission [QLG1-CT-2002-00896]; Swedish Heart-Lung Foundation; Swedish Research Council [8691, 0593]; Knut and Alice Wallenberg Foundation; Foundation for Strategic Research; Stockholm County Council ; Karolinska Institutet; Stockholm County Council; European Union Framework Programme 7 for the Innovative Medicine Initiative [IMI/115006]; Academy of Finland ; British Heart Foundation [RG2008/08, RG2008/014]; Italian Ministry of Health (Ricerca Corrente); Uppsala University; Uppsala University Hospital; Swedish Research Council for Infrastructures; Swedish Heart-Lung Foundation [20120600, 20130399]; Tore Nilsson foundation; Gamla Tjanarinnor foundation; Thurings foundation; Stiftelsen for Gamla Tjanarinnor; Ake Wiberg foundation; Tore Nilssons foundation; Magnus Bergvall Foundation; Foundation for Old Servants; Ministry of Education and Culture in Finland; Vasterbotten County Council; Swedish Heart and Lung Foundation; National Excellence Program [TAMOP 4.2.4.A/1-11-1-2012-0001]; European Union; European Social Fund; UK Medical Research Council [K013351]; Economic and Social Research Council; Academy of Finland; University College London Genetics Institute2015-12-072015-12-042016-01-19