Endothelial dysfunction precedes atherosclerosis in systemic sclerosis--relevance for prevention of vascular complications

Szűcs, Gabriella; Tímár, Orsolya; Szekanecz, Zoltán; Dér, Henriett; Kerekes, György; Szamosi, Szilvia; Shoenfeld, Yehuda; Szegedi, Gyula; Soltész, Pál

doi:10.1093/rheumatology/kel426

Cited by 120 publications

(118 citation statements)

References 19 publications

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“…These surrogate markers of atherosclerosis have also been investigated in SSc. Although cIMT and carotid plaque prevalence were widely varied among different studies (9)(10)(11)(12), pooled data from meta-analyses and recent larger studies indicated that SSc patients had both a higher frequency of subclinical atherosclerosis and higher cIMT compared to HS (13,16,18). The discrepancies in the study results could be partially explained by differences in included patients and the sample sizes.…”

Section: Discussionmentioning

confidence: 98%

“…However, in the disease process of SSc, compared to RA and SLE, there is less prominent inflammation with more significant vascular dysfunction and fibrosis. Currently, although some conflicting data exist about atherosclerosis in SSc (9)(10)(11)(12)(13)(14)(15)(16)(17)(18), it is still not clear whether increased CVD in SSc is due to accelerated atherosclerosis or disease-related processes.…”

Section: Introductionmentioning

confidence: 99%

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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: 98%

Section: Introductionmentioning

confidence: 99%

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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“…Although not confirmed in all patient cohorts (46), this idea is supported by the finding that endothelial dysfunction appears also to be a trigger for atherosclerosis in SSc (47). When endothelium-dependent, flowmediated dilation was compared to endothelium-independent, nitroglycerinmediated dilation of the brachial artery in SSc patients, an impairment of endothelium-dependent vasodilatation indicated by low flow-mediated dilation in SSc could be found.…”

Section: Perivascular Alterationsmentioning

confidence: 98%

Mechanisms of vascular damage in systemic sclerosis

et al. 2009

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Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature.

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“…It is thought that the vascular involvement is the result of an immune/inflammatory response that activates and injures the vascular endothelium (1), and it is known that inflammation and endothelial dysfunction are key mechanisms in the pathogenesis of atherosclerosis (2). The vasculopathy of SSc typically affects the small arteries and capillaries, although macrovascular disease has been demonstrated by carotid ultrasonography, the ankle brachial blood pressure index, and peripheral angiography (3,4).…”

Section: Introductionmentioning

confidence: 99%

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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Endothelial dysfunction precedes atherosclerosis in systemic sclerosis--relevance for prevention of vascular complications

Cited by 120 publications

References 19 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

Mechanisms of vascular damage in systemic sclerosis

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

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