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Relationship Between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis

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Relationship Between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis Acta Cardiol Sin 2017;33:514-522 Original Article doi: 10.6515/ACS20170220A Pulmonary Arterial Hypertension Relationship between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis Burabha Pussadhamma,1 Wannipa Suwannakrua,1 Panorkwan Toparkngarm,1 Chaiyasith Wongvipaporn,1 Chingching Foocharoen2 and Ratanavadee Nanagara2 Background: Pulmonary hypertension (PH) is an important lethal manifestation of systemic sclerosis (SSc). Evidence of an association between peripheral and pulmonary arterial vasculopathy in SSc has been demonstrated. We hypothesized that peripheral arterial stiffness could predict PH in SSc. Methods: We performed a cross-sectional study among patients with SSc who underwent Cardio-Ankle Vascular Index (CAVI, VaSera VS-1000; Fukuda Denshi, Tokyo, Japan) and transthoracic echocardiography (TTE) examination to evaluate peripheral arterial stiffness and PH, respectively. The correlation between CAVI score and PH hemodynamics [right ventricular systolic pressure (RVSP) and tricuspid regurgitation velocity (TRV)] was studied. Results: A total of 145 patients underwent both CAVI and TTE evaluation. The mean (standard deviation, SD) patient age was 51.5 (12.3) years; female patients constituted 72% of the subjects. Diffuse SSc occurred in 75% of the cases. The mean (SD) CAVI score was 7.6 (0.9), and the mean (SD) RVSP was 29.9 (11.2) mmHg. Correlation coefficient (r) between CAVI score and RVSP in overall, limited, and diffuse SSc were 0.107 (p = 0.200), 0.040 (p = 0.815), and 0.194 (p = 0.043), respectively. CAVI scores were borderline or abnormal (³ 8) in 30.3% of subjects. PH was classified intermediate or high probability (TRVmax ³ 2.9 m/s) in 19.3% of the subjects. Among the overall population, the odds ratios (95% CI) of CAVI score ³ 8forTRVmax³ 2.9 m/s in univariate and multivariate analysis were 1.23 (0.46-3.21, p = 0.678), and 0.54 (0.10-2.84, p = 0.471), respectively. Conclusions: Peripheral arterial stiffness, as measured by CAVI, has a correlation trend with the level of pulmonary arterial pressure assessed by TTE, specifically in the diffuse SSc subgroup. Key Words: Cardio-Ankle Vascular Index · Peripheral arterial stiffness · Pulmonary hypertension · Systemic sclerosis INTRODUCTION tive tissue disease with potentially serious consequ- ences, and pulmonary arterial hypertension (PAH) is one Systemic sclerosis (SSc) is an autoimmune connec- of its major manifestations.1 A study undertaken by Songsak et al. (2007) found PAH in 36.4% of patients with SSc in Northeast Thailand.2 Received: October 21, 2015 Accepted: February 20, 2017 Systemic sclerosis-related pulmonary arterial hyper- 1 Division of Cardiology and Queen Sirikit Heart Center of the tension (SSc-PAH) is a condition with a poor prognosis 2 Northeast; Division of Allergy-Immunology-Rheumatology, Srinagarind 3 Hospital, Department of Medicine, Faculty of Medicine, Khon Kaen and high mortality. However, early diagnosis and treat- University, Khon Kaen 40002, Thailand. ment can improve hemodynamics and reduce the risk of Corresponding author: Dr. Burabha Pussadhamma, Division of progression.4 Nevertheless, asymptomatic or mildly Cardiology, Department of Medicine, Faculty of Medicine, Khon Kaen 5 University, Khon Kaen 40002, Thailand. Tel: 66-43-363-664, 6689- symptomatic patients may go unrecognized. Hence, 6179959; Fax: 66-43-203-058; E-mail: [email protected] screening for SSc-PAH is warranted. Acta Cardiol Sin 2017;33:514-522 514 Peripheral Arterial Stiffness in Systemic Sclerosis Transthoracic echocardiography (TTE) has been re- Committee in human research. commended as a standard tool for pulmonary hyperten- sion (PH) screening by evaluating right ventricular sys- Study population tolic pressure (RVSP) and tricuspid regurgitation maxi- Patients with SSc who had undergone TTE evalua- mal velocity (TRVmax).6,7 A good correlation between tion were recruited from the SSc clinic. All patients were right ventricular to right atrial pressure gradient mea- over 18 years of age and a diagnosis of SSc had been sured by TTE and pulmonary artery systolic pressure made based on criteria established by the American Col- (PASP) measured by cardiac catheterization has been lege of Rheumatology.15 The SSc was classified as either demonstrated.8 Buttherearesomeobstaclesintheuse the limited or the diffuse type according to LeRoy, et of TTE, e.g. the inadequacy of equipment, shortage of al.16 Patients were excluded if: 1) they had limb defects skilled-operators, unavoidable inter- and intra-observer making CAVI measurement impracticable; 2) the arterial variability, and discrepancies of screening algorithm pulse of the extremities could not be measured by among guidelines.5-7 All of these limit the routine use of Doppler ultrasonography; and 3) they exhibited condi- TTE for screening. tions causing overestimation of CAVI measurement in- Pulmonary endothelial dysfunction leading to pul- cluding; end-stage renal disease with or without hemo- monary vasculopathy is one of the main pathobiologic dialysis, metabolic syndrome, obesity with BMI > 30, di- mechanisms of PH in SSc.9 Reichenberger et al.10 found abetics mellitus, obstructive sleep apnea, or were cur- a high level of endothelin (ET), a marker of vasocon- rent smokers. All patients provided written informed striction and vascular damage, in bronchoalveolar la- consent. vage fluid from patients with SSc, while Kadono et al.11 and Vancheeswaran et al.12 also found an increased Transthoracic echocardiography level of plasma ET in patients with SSc. Peled et al.13 The TTE (AlokaProSound F75 or AlokaProSound a10 found a trend towards increased peripheral arterial stiff- sonographic system; Hitachi-Aloka Medical, Ltd, Tokyo, ness among 10 SSc-PAH patients. And a report based on Japan) was performed by two cardiologists. Left ven- 33 Thai patients with SSc revealed a significant correla- tricular systolic function was represented by left ven- tion between peripheral arterial stiffness and PASP.14 tricular ejection fraction (LVEF, Teichholz method). Left Therefore, it is possible that there is an association be- ventricular diastolic function was represented by E ve- tween pulmonary and peripheral arterial vasculopathy locity, deceleration time, A velocity, and E’ velocity, re- in SSc, and detection of peripheral arterial vasculopathy spectively.17 RVSP was calculated from TRVmax using a might indicate the likelihood of PH among patients with modified Bernoulli equation; RVSP = 4 ´ TRVmax2 +right SSc. atrial pressure (RAP), with the mean RAP estimated to The purpose of our study was to evaluate the corre- be 3, 8, or 15 mmHg, according to the inferior vena cava lation between peripheral arterial stiffness as measured dimension and its collapsibility.18 by Cardio-Ankle Vascular Index (CAVI) and PH as mea- sured by TTE in a SSc population larger than in the previ- Cardio-Ankle Vascular Index ous study in Thailand. This would allow us to assess The CAVI automated vascular device (VaSera VS- whether or not CAVI had the potential to predict the 1000; Fukuda Denshi, Tokyo, Japan) was used to evalu- presence of PH among patients with SSc. ate the peripheral arterial stiffness. The subjects lay on their backs for five minutes, then arterial cuffs were ap- plied on their arm and leg on the same side. An electro- MATERIALS AND METHODS cardiogram electrode was placed on the arm and the microphone on the sternum to obtain the phonocardio- A cross-sectional analytic study was conducted be- graphy measurement. The machine automatically calcu- tween April, 2012 and April, 2013 at Srinagarind hospi- lated the CAVI score according to a formula using the tal, Khon Kaen University, in Khon Kaen, Thailand. The distance from the aortic valve to the ankle artery and study was approved by the Khon Kaen University Ethics the time that the pulse wave took to travel from the 515 Acta Cardiol Sin 2017;33:514-522 Burabha Pussadhamma et al. aortic valve to the brachium, i.e., CAVI = a {(2r/DP) ´ odds ratio (OR) and 95% confidence intervals (CI). Stata 2 19 ln(Ps/Pd)PWV }+b. In this formula, a and b are con- version 10.0 (Stata Corp., College Station, Texas, USA) stants, r is blood density, Ps and Pd are systolic and dia- was used for the analysis. All statistical tests were two- stolic blood pressure, respectively, DPisPs-Pd,andPWV tailed and a p value < 0.05 was considered statistically is the pulse wave velocity between heart and ankle. This significant. formula was derived from Bramwell-Hill’s equation and the stiffness parameter. The CAVI measurement was performed on both sides of the body using the same RESULTS method and the average used as the CAVI score. CAVI is the blood pressure-independent parameter,20 and ves- One hundred and forty-five patients were enrolled sels with lower compliance have higher arterial pressure (104 female; 72%, 109 diffuse SSc; 75%). The mean ± and higher blood flow velocity distally, resulting in a standard deviation (SD) for age was 51.5 ± 12 years. higher CAVI.17 According to the manufacturer’s judg- Over half of the patients (57%) were asymptomatic ment criteria, a CAVI < 8.0 is considered normal, a CAVI [World Health Organization functional class (WHO FC) I] ³ 9.0 raised a suspicion of atherosclerosis, whereas a and about one-third (39%) were mildly symptomatic CAVI ³ 8 but < 9 is considered borderline.21 (WHO FC II). The means ± SDs for RVSP, TRVmax, LVEF, The clinical evaluation and CAVI measurement were and CAVI score were 29.9 mmHg ± 11.2, 2.51 m/s ± done either on the same day as the TTE evaluation or 0.48, 66.9% ± 7.6, and 7.60 ± 0.91, respectively (Table less than six months apart in patients whose functional 1). Subjects with diffuse SSc had statistically significant class was stable. The CAVI was performed by a single re- higher mean Rodnan scores than subjects with limited search assistant. One hundred thirty-one out of 145 TTE SSc (12.28 versus 5.1; p = < 0.001), higher prevalence of procedures (90%) were performed by one cardiologist, digital pitting scars (28.4% versus 5.6%; p = 0.009), with the remainder by another.
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