Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Peled, Nir; Shitrit, David; Fox, Benjamin D.; Shlomi, D.; Amital, Anat; Daniele, Bruno; Kramer, Mordechai R.

doi:10.3899/jrheum.081088

Cited by 62 publications

(59 citation statements)

References 46 publications

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“…In our study, the strongest association with subclinical atherosclerosis in SSc was observed with PAH (OR 4). This finding is important because it indicates that microvascular disease in SSc, like PAH with robust data about association with endothelial dysfunction (44,45), may have implications in macrovascular disease and atherosclerosis in SSc.…”

Section: Discussionmentioning

confidence: 76%

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices

Özen

İnanç

Ünal

et al. 2016

Arthritis Care & Research

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ObjectiveTo determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis.MethodsA total of 110 SSc patients (102 females and 8 males, mean ± SD age 50.5 ± 11.9 years), 110 age‐ and sex‐matched RA patients, and 51 HS without CV disease were examined with ultrasonography (US). Carotid intima‐media thickness (cIMT) >0.90 mm and/or carotid plaques were used as the gold standard for subclinical atherosclerosis (US+). Systematic Coronary Risk Evaluation (SCORE), QRisk II, and 2013 American College of Cardiology (ACC)/American Heart Association (AHA) CV risk indices were calculated.ResultsTwenty‐one (19.1%) SSc patients, 24 (21.8%) RA patients, and 3 (5.9%) HS had subclinical atherosclerosis (SSc versus RA: P = 0.62, SSc versus HS: P = 0.029). cIMT in SSc was higher compared to HS (0.68 ± 0.15 mm versus 0.61 ± 0.10 mm; P = 0.008) but similar to RA patients (0.66 ± 0.14 mm; P = 0.82). Subclinical atherosclerosis in SSc was associated with age (odds ratio [OR] 1.07, P = 0.013), elevated erythrocyte sedimentation rate (OR 3.4, P = 0.045), and pulmonary arterial hypertension (OR 4.27, P = 0.012). Concerning CV risk indices, of the 21 US+ SSc patients only 0, 3 (14.2%), and 6 (28.6%) were classified as high CV risk according to SCORE, QRisk II, and ACC/AHA risk indices, respectively.ConclusionSubclinical atherosclerosis in SSc patients is more frequent than in HS, but is as frequent as in RA patients in which accelerated atherosclerosis is clearly defined. CV risk indices for the general population are considerably insufficient to detect SSc patients with atherosclerosis.

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Section: Discussionmentioning

confidence: 76%

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices

Özen

İnanç

Ünal

et al. 2016

Arthritis Care & Research

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“…Timar et al (11) found that augmentation index and PWV were both elevated in 40 patients with SSc and 35 controls. However, several other studies have been unable to demonstrate a significant difference in arterial stiffness between patients with SSc and controls (41,42). Several studies have found an impaired CFR in patients with rheumatic disease who had no evidence of CVD (43,44); very often, the CFR was reduced but still remained above pathologic values, therefore confirming that the prevalence of microvascular in- volvement is high and more common than large-vessel disease (45).…”

Section: Discussionmentioning

confidence: 80%

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Turiel¹,

Gianturco²,

Ricci³

et al. 2013

Arthritis Care & Research

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Objective. An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients. Methods. The study involved 20 patients (2 men and 18 women with a mean ؎ SD age of 52.96 ؎ 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age-and sex-matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels. Results. All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (␤) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower (P ‫؍‬ 0.0033) and plasma ADMA levels were higher (P < 0.0001) than in healthy controls. Conclusion. SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.

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“…Our findings indicate a relationship between an impaired peripheral endothelial function and the presence and degree of PH in this subset of patients. This relationship has been described in idiopathic pulmonary arterial hypertension, 24 in PH associated with congenital heart disease 25 and in connective tissue diseases, such as scleroderma, 26 but has never before been reported in HFpEF. The presence of PED may be associated with impaired pulmonary endothelial function and could account for the precapillary component of the PH that has been described in these patients.…”

Section: Peripheral Endothelial Dysfunctionmentioning

confidence: 99%

Pulmonary Hypertension Is Related to Peripheral Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction

Farrero

Blanco

Batlle

et al. 2014

Circ: Heart Failure

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Background-Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF.; Methods and Results-Flow-mediated dilation of the brachial artery, matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C-terminal propeptide of type I procollagen were determined in 28 patients with . There was a significant inverse correlation between flow-mediated dilation and pulmonary vascular resistance in patients with HFpEF and PH (r=−0.679; P=0.002). Patients with HFpEF showed higher matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide of type I procollagen values also had higher mean pulmonary artery pressure (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary vascular resistance (r=0.626; P=0.004). Conclusions-In patients with HFpEF, there is a significant correlation between PED and pulmonary vascular resistance.Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify patients with HFpEF at risk of developing PH. (Circ Heart Fail. 2014;7:791-798.)

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Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Abstract: Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Cited by 62 publications

References 46 publications

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Pulmonary Hypertension Is Related to Peripheral Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction

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