Comparative Study

. 2015 Aug 14;4(8):e001853.

doi: 10.1161/JAHA.115.001853.

Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

Jonas Persson¹, Rona J Strawbridge², Olga McLeod², Karl Gertow², Angela Silveira², Damiano Baldassarre³, Natalie Van Zuydam⁴, Sonia Shah⁵, Cristiano Fava⁶, Stefan Gustafsson⁷, Fabrizio Veglia⁸, Bengt Sennblad⁹, Malin Larsson¹⁰, Maria Sabater-Lleal², Karin Leander¹¹, Bruna Gigante¹², Adam Tabak¹³, Mika Kivimaki¹⁴, Jussi Kauhanen¹⁵, Rainer Rauramaa¹⁶, Andries J Smit¹⁷, Elmo Mannarino¹⁸, Philippe Giral¹⁹, Steve E Humphries²⁰, Elena Tremoli³, Ulf de Faire¹¹, Lars Lind²¹, Erik Ingelsson⁷, Bo Hedblad²², Olle Melander²², Meena Kumari²³, Aroon Hingorani²³, Andrew D Morris⁴, Colin N A Palmer⁴, Pia Lundman¹, John Öhrvik², Stefan Söderberg²⁴, Anders Hamsten²; IMPROVE Study Group

Collaborators, Affiliations

Collaborators

IMPROVE Study Group:
Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Anders Hamsten, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino

Affiliations

¹ Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden (J.P., B.G., P.L.).
² Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., O.M.L., K.G., A.S., B.S., M.S.L., J., A.H.).
³ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy (D.B., E.T.) Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).
⁴ Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, United Kingdom (N.V.Z., A.D.M., C.A.P.).
⁵ University College London Genetics Institute, University College London, London, United Kingdom (S.S.) Diamantina Institute and Queensland Brain Institute, University of Queensland, Australia (S.S.).
⁶ Division of Internal Medicine C, Department of Medicine, Hospital "Policlinico G.B Rossi", University of Verona, Italy (C.F.) Clinical Research Center, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden (C.F., B.H., O.M.).
⁷ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (S.G., E.I.).
⁸ Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).
⁹ Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., O.M.L., K.G., A.S., B.S., M.S.L., J., A.H.) Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden (B.S.).
¹⁰ IFM Bioinformatics, Linköping University, Linköping, Sweden (M.L.).
¹¹ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (K.L., B.G., U.F.).
¹² Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden (J.P., B.G., P.L.) Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (K.L., B.G., U.F.).
¹³ Department of Epidemiology and Public Health, University College London, London, United Kingdom (A.T., M.K.) 1st Department of Medicine, Semmelweis University Faculty of Medicine, Semmelweis University, Budapest, Hungary (A.T.).
¹⁴ Department of Epidemiology and Public Health, University College London, London, United Kingdom (A.T., M.K.).
¹⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland (J.K.).
¹⁶ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland (R.R.) Department of Clinical Physiology and Nuclear Medicine, University Hospital of Kuopio, Kuopio, Finland (R.R.).
¹⁷ Department of Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
¹⁸ Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Italy (E.M.).
¹⁹ Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France (P.G.).
²⁰ Centre for Cardiovascular Genetics, University College London, London, United Kingdom (S.E.H.).
²¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden (L.L.).
²² Clinical Research Center, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden (C.F., B.H., O.M.).
²³ Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, United Kingdom (M.K., A.H.).
²⁴ Division of Medicine, Department of Public Health and Clinical Medicine, University of Umeå, Sweden (S.).

PMID: 26276317
PMCID: PMC4599454
DOI: 10.1161/JAHA.115.001853

Comparative Study

Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

Jonas Persson et al. J Am Heart Assoc. 2015.

. 2015 Aug 14;4(8):e001853.

doi: 10.1161/JAHA.115.001853.

Authors

Collaborators

IMPROVE Study Group:
Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Anders Hamsten, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino

Affiliations

¹ Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden (J.P., B.G., P.L.).
² Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., O.M.L., K.G., A.S., B.S., M.S.L., J., A.H.).
³ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy (D.B., E.T.) Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).
⁴ Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, United Kingdom (N.V.Z., A.D.M., C.A.P.).
⁵ University College London Genetics Institute, University College London, London, United Kingdom (S.S.) Diamantina Institute and Queensland Brain Institute, University of Queensland, Australia (S.S.).
⁶ Division of Internal Medicine C, Department of Medicine, Hospital "Policlinico G.B Rossi", University of Verona, Italy (C.F.) Clinical Research Center, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden (C.F., B.H., O.M.).
⁷ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (S.G., E.I.).
⁸ Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).
⁹ Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., O.M.L., K.G., A.S., B.S., M.S.L., J., A.H.) Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden (B.S.).
¹⁰ IFM Bioinformatics, Linköping University, Linköping, Sweden (M.L.).
¹¹ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (K.L., B.G., U.F.).
¹² Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden (J.P., B.G., P.L.) Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (K.L., B.G., U.F.).
¹³ Department of Epidemiology and Public Health, University College London, London, United Kingdom (A.T., M.K.) 1st Department of Medicine, Semmelweis University Faculty of Medicine, Semmelweis University, Budapest, Hungary (A.T.).
¹⁴ Department of Epidemiology and Public Health, University College London, London, United Kingdom (A.T., M.K.).
¹⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland (J.K.).
¹⁶ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland (R.R.) Department of Clinical Physiology and Nuclear Medicine, University Hospital of Kuopio, Kuopio, Finland (R.R.).
¹⁷ Department of Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
¹⁸ Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Italy (E.M.).
¹⁹ Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France (P.G.).
²⁰ Centre for Cardiovascular Genetics, University College London, London, United Kingdom (S.E.H.).
²¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden (L.L.).
²² Clinical Research Center, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden (C.F., B.H., O.M.).
²³ Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, United Kingdom (M.K., A.H.).
²⁴ Division of Medicine, Department of Public Health and Clinical Medicine, University of Umeå, Sweden (S.).

PMID: 26276317
PMCID: PMC4599454
DOI: 10.1161/JAHA.115.001853

Abstract

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 concentration was 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 (β=-0.018, P<0.001) in men but not in women (β=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β=-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% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β=-0.0008, P=0.004) but not in women (β=-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.

Keywords: Mendelian randomization; adiponectin; atherosclerosis; carotid intima‐media thickness; genetics.

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Figures

**Figure 1**
Lower plasma adiponectin concentrations were observed in northern recruitment centers.

**Figure 2**
The allelic score in relation to log Bif-IMT_mean (blue bars) and plasma adiponectin (green line) in men. Bif-IMT indicates bifurcation intima-media thickness.

**Figure 3**
Kaplan–Meier plot of freedom from coronary events in men classified according to the allelic score.

See this image and copyright information in PMC

References

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Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

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Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

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