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Association of cardiotrophin-1 with left ventricular systolic properties in asymptomatic hypertensive patients

Ravassa, Susanaa,*; Beloqui, Oscarb,*; Varo, Nereac; Barba, Joaquínd; López, Begoñaa; Beaumont, Javiera; Zalba, Guillermoa; Díez, Javiera,d; González, Arantxaa

doi: 10.1097/HJH.0b013e32835ca903

Objectives: Cardiotrophin-1 (CT-1) induces hypertrophic growth and contractile dysfunction in cardiomyocytes. This cross-sectional study was aimed to analyze CT-1 associations with echocardiographically assessed left ventricular systolic properties taking into account the influence of left ventricular growth [i.e. left ventricular hypertrophy (LVH) and inappropriate left ventricular mass (iLVM)] in asymptomatic hypertensive patients.

Methods: Serum CT-1 was measured by ELISA in 278 asymptomatic hypertensive patients with a left ventricular ejection fraction more than 50% and in 25 age and sex-matched normotensive patients.

Results: Serum CT-1 was increased in hypertensive patients as compared to normotensive patients. CT-1 was directly correlated with parameters of left ventricular mass (LVM) and inversely correlated with parameters assessing myocardial systolic function and left ventricular chamber contractility in hypertensive patients, these associations being independent of a number of potential confounding factors. Interestingly, the associations of CT-1 with myocardial systolic function were independent of LVM even in patients with LVH or iLVM. In addition, there was a significant increment of serum CT-1 in hypertensive patients with LVH or iLVM, especially in those in whom LVH or iLVM were accompanied by impaired myocardial systolic function, as compared to the remaining hypertensive patients and normotensive patients. Plasma amino-terminal pro-brain natriuretic peptide was not correlated with any of the assessed left ventricular systolic parameters in either group of patients.

Conclusion: These findings suggest that serum CT-1 is associated with myocardial systolic dysfunction in asymptomatic hypertensive patients, independently of LVM, even in those patients with pathologic left ventricular growth.

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aDivision of Cardiovascular Sciences, Centre for Applied Medical Research

bDepartment of Internal Medicine, University of Navarra Clinic

cDepartment of Biochemistry, University of Navarra Clinic

dDepartment of Cardiology and Cardiac Surgery, University of Navarra Clinic. University of Navarra. Pamplona, Spain

*Susana Ravassa and Oscar Beloqui contributed equally to the writing of this article.

Correspondence to Dr Arantxa González and Professor Javier Díez, Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra. Av. Pío XII, 55 31008 Pamplona, Spain. Tel: +34 948 194700; fax: +34 948 194716; e-mails: or

Abbreviations: aLVM, appropriate left ventricular mass; cESS, circumferential end-systolic stress; CT-1, cardiotrophin-1; Ees, left ventricular end-systolic elastance; EesI, left ventricular end-systolic elastance normalized by left ventricular mass/left ventricular end-diastolic volume; HF, heart failure; iLVM, inappropriate left ventricular mass; LVEF, left ventricular ejection fraction; LVESVi, left ventricular end-systolic volume index; LVH, left ventricular hypertrophy; LVM, left ventricular mass; mESS, meridional end-systolic stress; MFS, midwall fractional shortening; NT-proBNP, N-terminal pro-brain natriuretic peptide; SHR, spontaneously hypertensive rats

Received 8 August, 2012

Revised 13 November, 2012

Accepted 15 November, 2012

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© 2013 Lippincott Williams & Wilkins, Inc.