Plasma Osteoprotegerin Levels in the General Population: Relation to Indices of Left Ventricular Structure and Function

Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system. Myocardial expression and circulating levels of osteoprotegerin are increased in heart failure. The relationship between osteoprotegerin levels in the general population and indices of left ventricular structure and function is unknown. Plasma osteoprotegerin levels and cardiac MRI indices of left ventricular structure and function were available in 2715 subjects (median age: 44 years; 45% male) enrolled in the Dallas Heart Study. The associations between osteoprotegerin concentration and indices of left ventricular structure and function were assessed by linear regression analysis, adjusting for possible confounders. By gender-specific linear regression analysis, higher osteoprotegerin levels were significantly associated with higher left ventricular mass, left ventricular wall thickness, left ventricular concentricity index, and lower left ventricular ejection fraction (P<0.001 for all). After adjustment for age, race, fat-free mass, fat mass, hypertension, diabetes, coronary artery disease, estimated glomerular filtration rate, hypercholesterolemia, smoking status, hormone replacement therapy, coronary artery calcium score >10, and presence of aortic plaque, osteoprotegerin remained significantly associated with each of these left ventricular indices among male subjects (P<0.05 for each). Among female subjects, higher osteoprotegerin was independently associated with higher left ventricular end-systolic volume and lower ejection fraction (P<0.0001 for each) but not with indices of left ventricular hypertrophy. These findings are compatible with the theory that osteoprotegerin may play a pathophysiological role in the development of left ventricular hypertrophy and systolic dysfunction.

[1]  Brian J. Bennett,et al.  Osteoprotegerin Inactivation Accelerates Advanced Atherosclerotic Lesion Progression and Calcification in Older ApoE−/− Mice , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[2]  F. Ohsuzu,et al.  Left ventricular hypertrophy in mice with a cardiac-specific overexpression of interleukin-1. , 2006, American journal of physiology. Heart and circulatory physiology.

[3]  S. Khalifé,et al.  Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population , 2006, Clinical endocrinology.

[4]  A. Khera,et al.  Relationship Between C-Reactive Protein and Subclinical Atherosclerosis: The Dallas Heart Study , 2005, Circulation.

[5]  I. Jaussent,et al.  Plasma osteoprotegerin is associated with mortality in hemodialysis patients. , 2005, Journal of the American Society of Nephrology : JASN.

[6]  H. Parving,et al.  Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. , 2006, European Journal of Endocrinology.

[7]  S. Sankaralingam,et al.  Changes in RANKL/OPG/RANK gene expression in peripheral mononuclear cells following treatment with estrogen or raloxifene , 2005, Steroids.

[8]  K. Choi,et al.  Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity , 2005, Clinical endocrinology.

[9]  M. Drazner,et al.  Left Ventricular Hypertrophy Is More Prevalent in Blacks Than Whites in the General Population: The Dallas Heart Study , 2005, Hypertension.

[10]  G. Christensen,et al.  Dysregulated Osteoprotegerin/RANK Ligand/RANK Axis in Clinical and Experimental Heart Failure , 2005, Circulation.

[11]  R. E. Noble.  Depression in women. , 2005, Metabolism: clinical and experimental.

[12]  J. Woo,et al.  Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients. , 2005, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  W. Leslie,et al.  Serum Osteoprotegerin Is Increased in Crohn's Disease: a Population‐Based Case Control Study , 2005, Inflammatory bowel diseases.

[14]  Hyun Ah Choi,et al.  The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone , 2005, Clinical endocrinology.

[15]  Won-Young Lee,et al.  Circulating osteoprotegerin levels are associated with age, waist-to-hip ratio, serum total cholesterol, and low-density lipoprotein cholesterol levels in healthy Korean women. , 2005, Metabolism: clinical and experimental.

[16]  S. Del Prato,et al.  Low-Grade Inflammation and Microalbuminuria in Hypertension , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[17]  P. Collin‐Osdoby.  Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin , 2004, Circulation research.

[18]  M. Nieminen,et al.  Prognostic significance of left ventricular mass change during treatment of hypertension. , 2004, JAMA.

[19]  L. Demer,et al.  Skeleton key to vascular disease. , 2004, Journal of the American College of Cardiology.

[20]  K. Dickstein,et al.  Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. , 2004, Journal of the American College of Cardiology.

[21]  J. Woo,et al.  Inflammation, residual kidney function, and cardiac hypertrophy are interrelated and combine adversely to enhance mortality and cardiovascular death risk of peritoneal dialysis patients. , 2004, Journal of the American Society of Nephrology : JASN.

[22]  Ronald M Peshock,et al.  The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. , 2004, The American journal of cardiology.

[23]  W. Poewe,et al.  Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease , 2004, Circulation.

[24]  A. Bitto,et al.  Effects of the Phytoestrogen Genistein on the Circulating Soluble Receptor Activator of Nuclear Factor ␬b Ligand-osteoprotegerin System in Early Postmenopausal Women , 2022 .

[25]  B. Howard,et al.  Relation of left ventricular hypertrophy to inflammation and albuminuria in adults with type 2 diabetes: the strong heart study. , 2003, Diabetes care.

[26]  David L. Lacey,et al.  Osteoclast differentiation and activation , 2003, Nature.

[27]  L. Hofbauer,et al.  Increased osteoprotegerin serum levels in men with coronary artery disease. , 2003, The Journal of clinical endocrinology and metabolism.

[28]  T. Imaizumi,et al.  Roles of Intercellular Adhesion Molecule-1 in Hypertensive Cardiac Remodeling , 2003, Hypertension.

[29]  Y. Ikari,et al.  Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease , 2002, Circulation.

[30]  S. Cummings,et al.  Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. , 2001, The Journal of clinical endocrinology and metabolism.

[31]  G Shimamoto,et al.  Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density , 1997, Cell.

[32]  J. Michel,et al.  Inflammatory cells and myocardial fibrosis: spatial and temporal distribution in renovascular hypertensive rats. , 1996, Cardiovascular research.

[33]  J. Michel,et al.  Colocalization of myocardial fibrosis and inflammatory cells in rats. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[34]  S. Yusuf,et al.  Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. , 1992, The New England journal of medicine.

[35]  K. Weber,et al.  Pathological Hypertrophy and Cardiac Interstitium: Fibrosis and Renin‐Angiotensin‐Aldosterone System , 1991, Circulation.

[36]  D E Manyari,et al.  Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. , 1990, The New England journal of medicine.