INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Vol. 27, no. 4, 645-651 (2014)
LETTER TO THE EDITOR
SUBCLINICAL CAROTID ATHEROSCLEROSIS IN ELDERLY PATIENTS WITH PRIMARY SJOGREN SYNDROME: A DUPLEX DOPPLER SONOGRAPHIC STUDY E.M. ZARDI, G. SAMBATARO, F. BASTA, D.P.E. MARGIOTTA and A.M.V AFELTRA
Department ofClinical Medicine and Rheumatology, University "Campus Bio-Medico" ofRome, Italy Received June 13, 2014 - AcceptedAugust 28, 2014 A growing body of evidence presents a link between chronic inflammatory rheumatic diseases and atherosclerosis. Toevaluate subclinical carotid atherosclerosis in an elderly group of patients with primary Sjogren syndrome compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors, we enrolled 18 patients with Primary Sjogren Syndrome (mean age 65±5.93 SD) and 18 mild Ostheoarthritic patients (mean age 66±5.94 SD) from the outpatient department of Rheumatology, University "Campus Bio-Medico, Rome, Italy, matched for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler sonographic study of carotids was performed in order to evaluate intimamedia thickness (IMT), stiffness and haemodynamic parameters [resistivity and pulsatility indices (RI and PI, respectively)]. No significant difference was found between primary Sjogren syndrome and control patients in IMT, stiffness and haemodynamic parameters. The lack of significant difference in subclinical atherosclerosis between elderly primary Sjogren syndrome and control matched patients, indicates that traditional cardiovascular risk factors, immunologic alterations and chronic inflammation do not influence the progression of vascular damage in the carotid circulation of patients with median disease duration of 6.5 years. lacrimal and salivary glands, belongs to the group of connective tissue diseases but little knowledge exists about whether it is associated with an increased prevalence of atherosclerosis. To date, pSS has been studied less than other connective tissue diseases in order to assess its cardiovascular risk. In a previous study, precocious intima-media thickness was found in young patients with pSS (l0), without significant difference in cardiovascular death rate between patients and the general population (11), however, no studies exist on carotid atherosclerosis in elderly patients. The aim ofthis study was to evaluate intima-media thickness (IMT), stiffness and some haemodynamic
For several years, assessment ofatherosclerosis in connective tissue diseases has been gaining interest in rheumatology research, due to the growing evidence of a link between chronic inflammatory rheumatic diseases and atherosclerosis (1-8). Indeed, the pathophysiology of atherosclerosis in connective tissue diseases is multifactorial, regarding chronic inflammation, immunologic alterations, prevalence of traditional cardiovascular risk factors and corticosteroid use, all of which may favor an increased vascular stiffness and intimamedia thickness (9). Primary Sjogren syndrome (PSS), characterized by inflammation of exocrine glands, especially
Key words: atherosclerosis, connective tissue disease, Sjogren syndrome, ultrasonography Mailing address: Enrico Maria Zardi, MD, PhD, Universita "Campus Bio-Medico" Via Alvaro del Portillo, 200 00128 Roma, Italy Tel.: +39 06225411214 Fax: +39 0622541456 e-mail: [email protected]
0394-6320 (2014)
645
Copyright © by BIOLIFE, s.a.s, This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties
DISCLOSURE: ALLAUTIIORS REPORT NO CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.
646
E.M. ZARDI ET AL.
parameters [resistivity and pulsatility indices (RI and PI, respectively)] in carotid circulation of an elderly group of patients with pSS compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors. MATERIALS AND METHODS Over a period of six months, 23 patients with pSS (mean age 65±5.93 SD) and 27 age- and gender-matched controls with no history of autoimmune diseases were enrolled in the Rheumatology Department of "Campus Bio-Medico" University of Rome. Of the total patients, 5 were excluded from the final analysis due to lack of compliance with the inclusion criteria of the study (3 for having rheumatoid arthritis and 2 for being too young). Among the control group, 9 patients were excluded from the study (2 for the presence of rectal cancer, 5 for infection of the urinary tract and 2 for being too young). The control group was composed of osteoarthritic patients, referring to our Department for a control, with a very mild disease in the absence of simultaneous inflammatory disease. Anthropometric measurements were taken in both pSS patients and controls. BMI was calculated according to the following formula: BMI= weight in kilograms I height in meters'. Blood pressure was measured in all pSS and control patients three times in 30 min. HOMA IR was calculated with the formula [Insulin (~U/mL) x Glycemia (mmollL)] 122,5. Low Density Lipoprotein (LDL) was measured on plasma with Dimension Vista™ system (made by Siemens, code K3131). This study was approved by the ethics committee of Campus Bio-Medico University, and was carried out in accordance with the ethical standards laid down in the last version of the 1964 Declaration of Helsinki. Written informed consent was obtained from each patient prior to performing any study-specific procedures. Duplex Doppler sonographic examination Duplex Doppler sonography of common and internal carotid was performed on both sides of the neck, with the patient in the supine decubitus position, during quiet respiration. The study was conducted by the same operator, who was unaware of the patient's diagnosis and his clinical data, using a high resolution ultrasonographic machine LOGIQ E9 general electric GE healthcare (Little Chalfont, United Kingdom) equipped with a linear 6-15 MHz transducer. In all PSS and control patients the vessels were insonated in perpendicular orientation by a lateral-longitudinal projection, optimizing the B mode
settings of gain, depth, focal zone and making a mild focal compression to improve the quality of wall carotid images. Measurements were made in on-line mode, paying attention to correctly scan the interface lumenintima where it was regular and parallel to adventitia; in this area an electronic caliper was used to calculate the distance between the two echogenic lines that mark the interfaces of the carotid wall. Carotid IMT was defined as the distance between the interface of the complex "media-adventitia" and the interface of the complex "lumen-intima"; values of IMT greater than 1.5 mm defined the presence of atherosclerotic plaques (12) and were excluded by the statistical calculation. The three regions of interest, on the near and the far carotid wall were: i) the distal portion of common carotid (1 em before the carotid bulb); ii) the carotid bulb; iii) the first portion of the internal carotid (1 em past the carotid bulb). For the data analysis, the mean value of three measurements obtained from the right and left sides was used. Doppler sonographic parameters of the common and internal carotid, left and right sides, were obtained after placing the sample volume of the ultrasound beam in the middle of the artery, with an angle of insonation of 60° between the ultrasound beam and longitudinal axis of the carotid segment. Then, RI and PI were automatically calculated, by the ultrasound machine, according to the following formulas: RI=(sV-dV)/sV PI=(sV-dV)/mV where sV =peak systolic velocity; dV =end diastolic velocity and mV=mean velocity. The mean value of three measurements from the right and left sides was used for statistical evaluation. Due to the close interrelationship with the endothelial function, stiffness parameters were also investigated (13). In accordance with others (14), stiffness parameters were assessed evaluating the diameter changes of the common carotid during an entire cardiac cycle. After using a minimum pressure on the vessel, both common carotids were scanned more than 2 em proximal to the carotid bifurcation, at a plaque-free site, in M-Mode sonographic approach; the maximum and the minimum diameter at systole (sDIA) and diastole (dDIA), detected by a synchronous ECG, were measured by means of a caliper as the distance between the trailing edge of the anterior wall and the leading edge of the posterior wall. Stiffness parameters [common carotid vascular strain (VS), vascular distensibility (VD), vascular stiffness
Int. J. Immunopathol. Pharmacol.
(VSt) and pressure-strain elastic modulus (PSEM)] were calculated applying the following equations: VS= (sDia - dDia)/dDia, VD= [2(sDIA-dDIA)/dDIA]/ (sBP-dBP) , VSf= [(sBP- dBP)]/ (sDIA- dDIA)/dDIA, PSEM= k(sBP-dBP)NS where sBP is the systolic blood pressure; dBP the diastolic blood pressure; and k the conversion factor from mmHgto Pa (k = 7xlO-3). All data are expressed as mean value of three right and left carotid measurements for each subject. Statistical analysis Statistical analysis
was performed
by suitable
647
software (Prism 6.0, Inc., San Diego, California, USA). Comparisons of continuous variables among groups were performed by Mann-Whitney U test. The categorical variables were analysed by Fisher F test. Two-sided p values 130/85mmHg) * Renal failure * Hepatic failure * Diabetes * Bleeding desorders * Sedentary life * BMI** WC (em) ** HC (em) ** Insulin (microIU/ml) ** Glycemia (mmol/l) ** Homa-IR ** LDL (mg/dl) ** HDL (mg/dl) ** Total cholesterol (mg/dl) ** Tryglicerides (mg/dl) ** Omocysteine (umol/L, normal value 0.99 >0.99 0.43 0.43 0.99 >0.99 >0.99 >0.99 >0.99 >0.99 0.12 0.45 0.54 0.61 0.40 0.82 0.72 0.92 0.81 0.78 0.92
Vol. 27, no. 4, 645-651 (2014)
LETTER TO THE EDITOR
SUBCLINICAL CAROTID ATHEROSCLEROSIS IN ELDERLY PATIENTS WITH PRIMARY SJOGREN SYNDROME: A DUPLEX DOPPLER SONOGRAPHIC STUDY E.M. ZARDI, G. SAMBATARO, F. BASTA, D.P.E. MARGIOTTA and A.M.V AFELTRA
Department ofClinical Medicine and Rheumatology, University "Campus Bio-Medico" ofRome, Italy Received June 13, 2014 - AcceptedAugust 28, 2014 A growing body of evidence presents a link between chronic inflammatory rheumatic diseases and atherosclerosis. Toevaluate subclinical carotid atherosclerosis in an elderly group of patients with primary Sjogren syndrome compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors, we enrolled 18 patients with Primary Sjogren Syndrome (mean age 65±5.93 SD) and 18 mild Ostheoarthritic patients (mean age 66±5.94 SD) from the outpatient department of Rheumatology, University "Campus Bio-Medico, Rome, Italy, matched for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler sonographic study of carotids was performed in order to evaluate intimamedia thickness (IMT), stiffness and haemodynamic parameters [resistivity and pulsatility indices (RI and PI, respectively)]. No significant difference was found between primary Sjogren syndrome and control patients in IMT, stiffness and haemodynamic parameters. The lack of significant difference in subclinical atherosclerosis between elderly primary Sjogren syndrome and control matched patients, indicates that traditional cardiovascular risk factors, immunologic alterations and chronic inflammation do not influence the progression of vascular damage in the carotid circulation of patients with median disease duration of 6.5 years. lacrimal and salivary glands, belongs to the group of connective tissue diseases but little knowledge exists about whether it is associated with an increased prevalence of atherosclerosis. To date, pSS has been studied less than other connective tissue diseases in order to assess its cardiovascular risk. In a previous study, precocious intima-media thickness was found in young patients with pSS (l0), without significant difference in cardiovascular death rate between patients and the general population (11), however, no studies exist on carotid atherosclerosis in elderly patients. The aim ofthis study was to evaluate intima-media thickness (IMT), stiffness and some haemodynamic
For several years, assessment ofatherosclerosis in connective tissue diseases has been gaining interest in rheumatology research, due to the growing evidence of a link between chronic inflammatory rheumatic diseases and atherosclerosis (1-8). Indeed, the pathophysiology of atherosclerosis in connective tissue diseases is multifactorial, regarding chronic inflammation, immunologic alterations, prevalence of traditional cardiovascular risk factors and corticosteroid use, all of which may favor an increased vascular stiffness and intimamedia thickness (9). Primary Sjogren syndrome (PSS), characterized by inflammation of exocrine glands, especially
Key words: atherosclerosis, connective tissue disease, Sjogren syndrome, ultrasonography Mailing address: Enrico Maria Zardi, MD, PhD, Universita "Campus Bio-Medico" Via Alvaro del Portillo, 200 00128 Roma, Italy Tel.: +39 06225411214 Fax: +39 0622541456 e-mail: [email protected]
0394-6320 (2014)
645
Copyright © by BIOLIFE, s.a.s, This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties
DISCLOSURE: ALLAUTIIORS REPORT NO CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.
646
E.M. ZARDI ET AL.
parameters [resistivity and pulsatility indices (RI and PI, respectively)] in carotid circulation of an elderly group of patients with pSS compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors. MATERIALS AND METHODS Over a period of six months, 23 patients with pSS (mean age 65±5.93 SD) and 27 age- and gender-matched controls with no history of autoimmune diseases were enrolled in the Rheumatology Department of "Campus Bio-Medico" University of Rome. Of the total patients, 5 were excluded from the final analysis due to lack of compliance with the inclusion criteria of the study (3 for having rheumatoid arthritis and 2 for being too young). Among the control group, 9 patients were excluded from the study (2 for the presence of rectal cancer, 5 for infection of the urinary tract and 2 for being too young). The control group was composed of osteoarthritic patients, referring to our Department for a control, with a very mild disease in the absence of simultaneous inflammatory disease. Anthropometric measurements were taken in both pSS patients and controls. BMI was calculated according to the following formula: BMI= weight in kilograms I height in meters'. Blood pressure was measured in all pSS and control patients three times in 30 min. HOMA IR was calculated with the formula [Insulin (~U/mL) x Glycemia (mmollL)] 122,5. Low Density Lipoprotein (LDL) was measured on plasma with Dimension Vista™ system (made by Siemens, code K3131). This study was approved by the ethics committee of Campus Bio-Medico University, and was carried out in accordance with the ethical standards laid down in the last version of the 1964 Declaration of Helsinki. Written informed consent was obtained from each patient prior to performing any study-specific procedures. Duplex Doppler sonographic examination Duplex Doppler sonography of common and internal carotid was performed on both sides of the neck, with the patient in the supine decubitus position, during quiet respiration. The study was conducted by the same operator, who was unaware of the patient's diagnosis and his clinical data, using a high resolution ultrasonographic machine LOGIQ E9 general electric GE healthcare (Little Chalfont, United Kingdom) equipped with a linear 6-15 MHz transducer. In all PSS and control patients the vessels were insonated in perpendicular orientation by a lateral-longitudinal projection, optimizing the B mode
settings of gain, depth, focal zone and making a mild focal compression to improve the quality of wall carotid images. Measurements were made in on-line mode, paying attention to correctly scan the interface lumenintima where it was regular and parallel to adventitia; in this area an electronic caliper was used to calculate the distance between the two echogenic lines that mark the interfaces of the carotid wall. Carotid IMT was defined as the distance between the interface of the complex "media-adventitia" and the interface of the complex "lumen-intima"; values of IMT greater than 1.5 mm defined the presence of atherosclerotic plaques (12) and were excluded by the statistical calculation. The three regions of interest, on the near and the far carotid wall were: i) the distal portion of common carotid (1 em before the carotid bulb); ii) the carotid bulb; iii) the first portion of the internal carotid (1 em past the carotid bulb). For the data analysis, the mean value of three measurements obtained from the right and left sides was used. Doppler sonographic parameters of the common and internal carotid, left and right sides, were obtained after placing the sample volume of the ultrasound beam in the middle of the artery, with an angle of insonation of 60° between the ultrasound beam and longitudinal axis of the carotid segment. Then, RI and PI were automatically calculated, by the ultrasound machine, according to the following formulas: RI=(sV-dV)/sV PI=(sV-dV)/mV where sV =peak systolic velocity; dV =end diastolic velocity and mV=mean velocity. The mean value of three measurements from the right and left sides was used for statistical evaluation. Due to the close interrelationship with the endothelial function, stiffness parameters were also investigated (13). In accordance with others (14), stiffness parameters were assessed evaluating the diameter changes of the common carotid during an entire cardiac cycle. After using a minimum pressure on the vessel, both common carotids were scanned more than 2 em proximal to the carotid bifurcation, at a plaque-free site, in M-Mode sonographic approach; the maximum and the minimum diameter at systole (sDIA) and diastole (dDIA), detected by a synchronous ECG, were measured by means of a caliper as the distance between the trailing edge of the anterior wall and the leading edge of the posterior wall. Stiffness parameters [common carotid vascular strain (VS), vascular distensibility (VD), vascular stiffness
Int. J. Immunopathol. Pharmacol.
(VSt) and pressure-strain elastic modulus (PSEM)] were calculated applying the following equations: VS= (sDia - dDia)/dDia, VD= [2(sDIA-dDIA)/dDIA]/ (sBP-dBP) , VSf= [(sBP- dBP)]/ (sDIA- dDIA)/dDIA, PSEM= k(sBP-dBP)NS where sBP is the systolic blood pressure; dBP the diastolic blood pressure; and k the conversion factor from mmHgto Pa (k = 7xlO-3). All data are expressed as mean value of three right and left carotid measurements for each subject. Statistical analysis Statistical analysis
was performed
by suitable
647
software (Prism 6.0, Inc., San Diego, California, USA). Comparisons of continuous variables among groups were performed by Mann-Whitney U test. The categorical variables were analysed by Fisher F test. Two-sided p values 130/85mmHg) * Renal failure * Hepatic failure * Diabetes * Bleeding desorders * Sedentary life * BMI** WC (em) ** HC (em) ** Insulin (microIU/ml) ** Glycemia (mmol/l) ** Homa-IR ** LDL (mg/dl) ** HDL (mg/dl) ** Total cholesterol (mg/dl) ** Tryglicerides (mg/dl) ** Omocysteine (umol/L, normal value 0.99 >0.99 0.43 0.43 0.99 >0.99 >0.99 >0.99 >0.99 >0.99 0.12 0.45 0.54 0.61 0.40 0.82 0.72 0.92 0.81 0.78 0.92
