Atherosclerosis 237 (2014) 618e622
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients Antonio Bellasi a, b, Paolo Raggi c, *, Rosario Rossi d, Vincenzo Rochira d, Chiara Stentarelli d, Stefano Zona d, Antonella Lattanzi d, Federica Carli d, Cristina Mussini d, Giovanni Guaraldi d a
Nephrology and Dialysis Unit, Azienda Ospedaliera S. Anna, Como, Italy Department of Health Sciences, University of Milan, Italy Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada d Metabolic Clinic, Infectious and Tropical Diseases Unit, Department of Medicine, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 11 May 2014 Received in revised form 30 September 2014 Accepted 9 October 2014 Available online 18 October 2014
Aim. Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. Methods. Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. Results. Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08e2.79; p ¼ 0.021). Bootstrap and sensitivity analyses confirmed these findings. Conclusions. Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Intact PTH Atherosclerosis HIV
1. Introduction Accelerated cardiovascular (CV) aging is a common feature of HIV-infected subjects and it is linked to disability and increased mortality [1,2]. Though prevalent, traditional CV risk factors may not completely account for the risk of major CV events in these patients [2]. Among others chronic inflammation, toxicity of antiretroviral therapies, or immune system impairment have been implicated as potential HIV-specific risk factors predisposing to CV senescence [1e3].
* Corresponding author. Mazankowski Alberta Heart Institute, University of Alberta. 4A7.050, 8440 e 112 Street, Edmonton, AB T6G 2B7, Canada. E-mail address: [email protected] (P. Raggi). http://dx.doi.org/10.1016/j.atherosclerosis.2014.10.017 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
Bone mineral abnormalities have been clearly associated with an unfavorable CV outcome in the general population as well as high-risk individuals such as those with chronic kidney disease (CKD) [4], chronic heart failure or ischemic heart disease [5]. Though the biological mechanisms are far from having been elucidated, increased serum levels of intact parathyroid hormones (iPTH), phosphorous, calcium as well as vitamin D deficiency have been linked with increased cardiac mass [6e8], abnormal myocardial perfusion [9], proteinuria [10], accelerated renal function decline [11], evidence of subclinical atherosclerosis [12], endothelial dysfunction [13,14] and poor survival [4,14,15]. To date, the association between serological markers of bone mineral metabolism and vascular disease in HIV patients has not been investigated. This is a relevant question since a few antiretroviral therapies may perturb bone mineral metabolism [3,16,17]. In a large cohort of HIV-infected subjects we tested the association between
A. Bellasi et al. / Atherosclerosis 237 (2014) 618e622
carotid intima media thickness (cIMT) as a marker of subclinical atherosclerosis and a predictor of adverse CV outcomes in the general population [18], and iPTH as a marker of bone mineral metabolism. In fact, the secretion of iPTH is regulated by numerous minerals and hormones and it can be considered the final product of a complex cascade of events involved in bone remodeling and mineral metabolism. 2. Materials and methods We studied 470 consecutive HIV-infected patients receiving highly active antiretroviral therapy (HAART) referred to the HIV Metabolic Clinic of the University of Modena and Reggio Emilia, Italy between 2010 and 2013. Demographic and clinical data were systematically recorded by infectious disease specialists working in the outpatient clinic using an electronic medical record linked to a database. History of cardiovascular disease was defined as a history of myocardial infarction, stroke, coronary artery by-pass surgery, angioplasty, and peripheral arterial disease. Diabetes mellitus was defined as a self-reported medical condition or by a fasting glucose equal to or greater than 126 mg/dl or the use of hypoglycemic drugs. Hypertension was defined as a self reported medical condition or the use of antihypertensive drugs or a measured blood pressure higher than 140/90 mmHg. The glomerular filtration rate (eGFR) was estimated via the abbreviated MDRD equation (http:// mdrd.com/) and chronic kidney disease (CKD) was defined as the composite of eGFR
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients Antonio Bellasi a, b, Paolo Raggi c, *, Rosario Rossi d, Vincenzo Rochira d, Chiara Stentarelli d, Stefano Zona d, Antonella Lattanzi d, Federica Carli d, Cristina Mussini d, Giovanni Guaraldi d a
Nephrology and Dialysis Unit, Azienda Ospedaliera S. Anna, Como, Italy Department of Health Sciences, University of Milan, Italy Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada d Metabolic Clinic, Infectious and Tropical Diseases Unit, Department of Medicine, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 11 May 2014 Received in revised form 30 September 2014 Accepted 9 October 2014 Available online 18 October 2014
Aim. Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. Methods. Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. Results. Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08e2.79; p ¼ 0.021). Bootstrap and sensitivity analyses confirmed these findings. Conclusions. Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Intact PTH Atherosclerosis HIV
1. Introduction Accelerated cardiovascular (CV) aging is a common feature of HIV-infected subjects and it is linked to disability and increased mortality [1,2]. Though prevalent, traditional CV risk factors may not completely account for the risk of major CV events in these patients [2]. Among others chronic inflammation, toxicity of antiretroviral therapies, or immune system impairment have been implicated as potential HIV-specific risk factors predisposing to CV senescence [1e3].
* Corresponding author. Mazankowski Alberta Heart Institute, University of Alberta. 4A7.050, 8440 e 112 Street, Edmonton, AB T6G 2B7, Canada. E-mail address: [email protected] (P. Raggi). http://dx.doi.org/10.1016/j.atherosclerosis.2014.10.017 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
Bone mineral abnormalities have been clearly associated with an unfavorable CV outcome in the general population as well as high-risk individuals such as those with chronic kidney disease (CKD) [4], chronic heart failure or ischemic heart disease [5]. Though the biological mechanisms are far from having been elucidated, increased serum levels of intact parathyroid hormones (iPTH), phosphorous, calcium as well as vitamin D deficiency have been linked with increased cardiac mass [6e8], abnormal myocardial perfusion [9], proteinuria [10], accelerated renal function decline [11], evidence of subclinical atherosclerosis [12], endothelial dysfunction [13,14] and poor survival [4,14,15]. To date, the association between serological markers of bone mineral metabolism and vascular disease in HIV patients has not been investigated. This is a relevant question since a few antiretroviral therapies may perturb bone mineral metabolism [3,16,17]. In a large cohort of HIV-infected subjects we tested the association between
A. Bellasi et al. / Atherosclerosis 237 (2014) 618e622
carotid intima media thickness (cIMT) as a marker of subclinical atherosclerosis and a predictor of adverse CV outcomes in the general population [18], and iPTH as a marker of bone mineral metabolism. In fact, the secretion of iPTH is regulated by numerous minerals and hormones and it can be considered the final product of a complex cascade of events involved in bone remodeling and mineral metabolism. 2. Materials and methods We studied 470 consecutive HIV-infected patients receiving highly active antiretroviral therapy (HAART) referred to the HIV Metabolic Clinic of the University of Modena and Reggio Emilia, Italy between 2010 and 2013. Demographic and clinical data were systematically recorded by infectious disease specialists working in the outpatient clinic using an electronic medical record linked to a database. History of cardiovascular disease was defined as a history of myocardial infarction, stroke, coronary artery by-pass surgery, angioplasty, and peripheral arterial disease. Diabetes mellitus was defined as a self-reported medical condition or by a fasting glucose equal to or greater than 126 mg/dl or the use of hypoglycemic drugs. Hypertension was defined as a self reported medical condition or the use of antihypertensive drugs or a measured blood pressure higher than 140/90 mmHg. The glomerular filtration rate (eGFR) was estimated via the abbreviated MDRD equation (http:// mdrd.com/) and chronic kidney disease (CKD) was defined as the composite of eGFR
