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2.
J Rheumatol ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770503

RESUMO

OBJECTIVE: Monotherapy is an option as first-line therapy for pulmonary arterial hypertension (PAH). However, combination therapy is a beneficial alternative. Our objective was to evaluate the efficacy of monotherapy versus combination therapy in patients with systemic sclerosis (SSc)-associated PAH. METHODS: All patients with SSc-associated PAH from the Spanish Scleroderma Registry (RESCLE) were reviewed. Patients were split into 3 groups: monotherapy versus sequential combination versus upfront combination therapy. The primary endpoint was death from any cause at 1, 3, and 5 years from PAH diagnosis. RESULTS: Seventy-six patients (4.2%) out of 1817 had SSc-related PAH. Thirty-four patients (45%) were receiving monotherapy [endothelin receptor antagonist (n = 22; 29%) or phosphodiesterase-5 inhibitors (n = 12; 16%)], 25 (33%) sequential combination, and 17 (22%) upfront combination therapy. A lower forced vital capacity/DLCO in the sequential combination group was reported (2.9 ± 1.1 vs 1.8 ± 0.4 vs 2.3 ± 0.8; p = 0.085) and also a higher mean pulmonary arterial pressure in combination groups (37.2 ± 8.7 mmHg vs 40.8 ± 8.8 vs 46 ± 15.9; p = 0.026) at baseline. Treatment regimen (p = 0.017) and functional class (p = 0.007) were found to be independent predictors of mortality. Sequential combination therapy was found to be an independent protective factor (HR 0.11, 95% CI 0.03-0.51; p = 0.004), while upfront combination therapy showed a trend (HR 0.68, 95% CI 0.23-1.97; p = 0.476). Survival from PAH diagnosis among monotherapy, sequential, and upfront combination groups was 78% versus 95.8% versus 94.1% at 1 year, 40.7% versus 81.5% versus 51.8% at 3 years, and 31.6% versus 56.5% versus 34.5% at 5 years (p = 0.007), respectively. Side effects were not significantly different among groups. CONCLUSION: Combination sequential therapy improved survival in our cohort.

3.
Medicina (Kaunas) ; 55(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795629

RESUMO

Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine the association of different components of physical fitness with body composition in women with SLE with mild disease activity. Materials and Methods: This cross-sectional study included 77 women with SLE (43.2 ± 13.8 years old) and clinical stability during the previous 6 months. Body composition (including body mass index (BMI), fat mass index (FMI), waist circumference, waist-to-height ratio and waist-to-hip ratio) was assessed using a stadiometer, an anthropometric tape, and a bioimpedance device. Physical fitness included cardiorespiratory fitness (Siconolfi step test and 6 min walk test), muscular strength (handgrip strength test as upper body measure and 30 s chair stand as lower body measure), and flexibility (back-scratch test). Participants with a fitness level equal or above the median of the study sample were categorized as "fit" and those below the median were categorized as "unfit". Linear regression assessed the association of physical fitness with body composition parameters. Results: Cardiorespiratory fitness and upper body muscular strength were negatively associated with BMI, FMI, waist circumference, and waist-to-height ratio (all, p < 0.05). Lower body muscular strength and flexibility were negatively related to FMI, waist circumference, waist-to-height ratio, and waist-to-hip ratio (all, p < 0.05). These relationships were still significant after controlling for age, disease duration, accrual damage, and SLE activity. Overall, fit patients presented significantly lower values in all body composition parameters compared to unfit patients (all, p < 0.05). Conclusions: The main findings of the present study suggest that physical fitness is inversely associated with body composition in women with SLE. Given the cross-sectional nature of this study, future clinical trials should study the causal pathways underlying these relationships.


Assuntos
Composição Corporal , Aptidão Cardiorrespiratória/fisiologia , Força da Mão/fisiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Circunferência da Cintura , Razão Cintura-Estatura , Relação Cintura-Quadril , Teste de Caminhada
4.
J Clin Med ; 7(12)2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30477218

RESUMO

This study assessed the effect of 12-week aerobic exercise on arterial stiffness (primary outcome), inflammation, oxidative stress, and cardiorespiratory fitness (secondary outcomes) in women with systemic lupus erythematosus (SLE). In a non-randomized clinical trial, 58 women with SLE were assigned to either aerobic exercise (n = 26) or usual care (n = 32). The intervention comprised 12 weeks of aerobic exercise (2 sessions × 75 min/week) between 40⁻75% of the individual's heart rate reserve. At baseline and at week 12, arterial stiffness was assessed through pulse wave velocity (PWV), inflammatory (i.e., high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TFN-α], and inteleukin 6 [IL-6]) and oxidative stress (i.e., myeloperoxidase [MPO]) markers were obtained from blood samples, and cardiorespiratory fitness was assessed (Bruce test). There were no between-group differences in the changes in arterial stiffness (median PWV difference -0.034, 95% CI -0.42 to 0.36 m/s; p = 0.860) or hsCRP, TNF-α, IL-6, and MPO (all p > 0.05) at week 12. In comparison to the control group, the exercise group significantly increased cardiorespiratory fitness (median difference 2.26 minutes, 95% CI 0.98 to 3.55; p = 0.001). These results suggest that 12 weeks of progressive treadmill aerobic exercise increases cardiorespiratory fitness without exacerbating arterial stiffness, inflammation, or oxidative stress in women with SLE.

6.
Clin Exp Rheumatol ; 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30183606

RESUMO

OBJECTIVES: Blood pressure (BP) physiologically declines more than 10% at night. Subjects who do not experience this drop are classified as non-dippers. They have a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non-dipper pattern have been associated in the general population. Patients with systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency, a non-dipper pattern and CVD. We aimed to evaluate a possible relationship between vitamin D deficiency and non-dipper pattern in patients with SLE. METHODS: Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided into dippers and non-dippers. 25-hydroxyvitamin D (25(OH)D) levels were compared between both groups. A multivariate analysis was used to determine which variables were independently associated with non-dipper pattern. RESULTS: 62% of patients were non-dippers. They had lower levels of 25(OH)D than dippers (19.4±8.9 vs. 25.9±10.1 ng/ml, p=0.005). Patients with lower 25(OH)D levels were more likely to be non-dippers (OR 3.7, 95%CI 1.2-11.4; p=0.025). The nocturnal decline of mean BP correlated with levels of 25(OH)D (r=0.227, p=0.047). Night-time systolic, diastolic and mean BP inversely correlated with the levels of 25(OH)D (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but only night- time systolic BP remained significant after adjustment for age and body mass index (r=-0.228, p=0.049). 25(OH)D levels and the use of mycophenolate were found to be independently associated with non-dipper pattern in SLE patients. CONCLUSIONS: Vitamin D deficiency may contribute to the development of a non-dipper pattern in patients with SLE.

9.
Clin Rheumatol ; 37(4): 999-1009, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29214548

RESUMO

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.


Assuntos
Artralgia/etiologia , Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Avaliação de Sintomas
10.
Angiology ; 69(8): 672-676, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29232972

RESUMO

Resting heart rate (RHR) is associated with arterial stiffness, inflammation, and cardiovascular (CV) and all-cause mortality in the general population and in patients at high CV risk. We assessed the association of RHR with arterial stiffness and low-grade inflammation (LGI) in a cross-sectional study that included 101 women with systemic lupus erythematosus (SLE) without a history of CV disease or arrhythmia or who were under treatment that may cause bradycardia. Pulse wave velocity (PWV; a measure of arterial stiffness), RHR, and markers of LGI (ie, C-reactive protein, fibrinogen, erythrocyte sedimentation rate, insulin, and homeostatic model assessment index) were measured. The patients with the highest RHR (quartile 4; mean RHR = 87.2 bpm) had a PWV 0.61 m/s (95% confidence interval [CI]: 0.08-1.14; P = .024) greater than patients with the lowest RHR (quartile 1; RHR = 63.0 bpm), independent of age, systolic blood pressure, disease activity, smoking, and being physically inactive. Similarly, patients with the highest RHR (quartile 4) showed a significantly less favorable clustered LGI index than patients in quartile 1 ( b = .58; 95% CI: 0.212-0.948; P = .002). Higher RHR is associated with greater arterial stiffness and LGI in women with SLE. Further research to determine the prognostic value of RHR in this population is warranted.

11.
Semin Arthritis Rheum ; 47(6): 849-857, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29246416

RESUMO

OBJECTIVE: To assess the prevalence and causes of hepatobiliary involvement (HBI) in systemic sclerosis (SSc), to investigate the clinical characteristics and prognosis of SSc patients with HBI (SSc-HBI) and without HBI (SSc-non-HBI), and to compare both groups according to the cutaneous SSc subsets. METHODS: In all, 1572 SSc patients were collected in the RESCLE registry up to January 2015, and all hepatobiliary disturbances were recorded. We investigated the HBI-related characteristics and survival from the entire SSc cohort and according to the following cutaneous subsets: diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc). RESULTS: Out of 1572, 118 (7.5%) patients had HBI. Primary biliary cholangitis (PBC) was largely the main cause (n = 67, 4.3%), followed by autoimmune hepatitis (n = 19, 1.2%), and anti-mitochondrial negative PBC (n = 6, 0.4%). Other causes of HBI were as follows: secondary liver diseases (n = 11, 0.7%), SSc-related HBI (n = 7, 0.4%), nodular regenerative hyperplasia (n = 3, 0.2%), liver cirrhosis (n = 3, 0.2%), and HBI of unknown origin (n = 2, 0.1%). In multivariate analysis, HBI was independently associated to lesser risk of dcSSc (5.1% vs. 24.4%), and higher frequency of calcinosis (26% vs. 18%), left ventricular diastolic dysfunction (46% vs. 27%), sicca syndrome (51% vs. 29%), and anti-centromere antibodies (ACA, 73% vs. 44%). According to the cutaneous subsets, HBI was associated (1) in lcSSc, to longer time from SSc onset to diagnosis (10.8 ± 12.5 vs. 7.2 ± 9.3 years), sicca syndrome (54% vs. 33%), and ACA (80% vs. 56%); (2) in ssSSc, to sicca syndrome (44% vs. 19%), and (3) in dcSSc, no associations were found. HBI was the cause of death in 2.3% patients but the cumulative survival according to the presence or absence of HBI showed no differences. CONCLUSIONS: HBI prevalence in SSc is 7.5% and dcSSc is the least involved subset. PBC is the main cause of HBI. Patients with SSc-HBI exhibited specific clinical and immunologic profile. Survival is similar for SSc patients with HBI.


Assuntos
Colangite/etiologia , Hepatite Autoimune/etiologia , Escleroderma Sistêmico/complicações , Adulto , Idoso , Colangite/mortalidade , Feminino , Hepatite Autoimune/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Escleroderma Sistêmico/mortalidade , Síndrome de Sjogren/complicações , Síndrome de Sjogren/mortalidade , Espanha , Taxa de Sobrevida
12.
Clin Exp Rheumatol ; 35 Suppl 106(4): 89-97, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28980905

RESUMO

OBJECTIVES: The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in Ssc patients, and contradictory results have often been show among those studies that have been performed. METHODS: A prospective study was conducted with the Spanish RESCLE register to analyse the influence of gender on survival of SSc patients. RESULTS: In total, 1506 SSc patients (1341 women, 165 men) were recruited from 21 centres. Older age at onset (OR 1.02), shorter time from onset to diagnosis (OR 0.96), smoking (OR 2.57), interstitial lung disease (ILD) (OR 1.58), less predisposition to sicca syndrome and to antinuclear antibody positivity (OR 0.29 and 0.43, respectively), and higher compliance with the ACR 1980 criteria (OR 1.79) were independently associated with the male sex. During follow-up, 30.4% of men versus 14.6% of women died (p<0.001). Survival at 10 years from the onset of symptoms was 75.3% for men and 92.9% for women (p<0.001), and the difference remained after selecting only SSc-related deaths (85.6% vs. 96.1%, p<0.001). The mortality predictive factors were diffuse SSc (OR 2.26), ILD (OR 1.82), digital ulcers (OR 1.38), tendon friction rubs (OR 1.74), male sex (OR 1.53), increased age at onset (OR 1.13) and isolated PH (considering only deaths from diagnosis), both in the overall (OR 3.63) and female cohorts (OR 3.97). The same risk factors were observed in the male cohort, except for isolated PH and ILD. CONCLUSIONS: The present study confirms the existence of epidemiological, clinical, laboratory and prognostic gender differences in systemic sclerosis patients.


Assuntos
Escleroderma Sistêmico/mortalidade , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Caracteres Sexuais
13.
Clin Exp Rheumatol ; 35 Suppl 106(4): 98-105, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28980912

RESUMO

OBJECTIVES: To assess the clinical manifestations and prognosis of Spanish patients with systemic sclerosis (SSc) according to their immunological profile. METHODS: From the Spanish Scleroderma Study Group or RESCLE (Registro de ESCLErodermia as Spanish nomenclature) Registry we selected those patients in which anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA) antibodies had been determined, and a single positivity for each SSc specific antibody was detected. Demographic, clinical, laboratory, and survival data were compared according to the serologic status of these antibodies. RESULTS: Overall, 209 SSc patients were included. In 128 (61%) patients ACA was the only positive antibody, 46 (22%) were only positive for ATA, and 35 (17%) for ARA. Of note, the three groups were mutually exclusive. In univariate analysis, patients with ACA presented more frequently limited cutaneous SSc (lcSSc) (p<0.001), whereas diffuse cutaneous SSc (dcSSc) was the most frequent subtype in patients with ATA (54%) and ARA (62%) (both p<0.001). Positive patients for ARA showed the highest prevalence of joint involvement (p<0.001) and those from ATA group had a higher prevalence of interstitial lung disease (ILD) (p<0.001). Scleroderma renal crisis was more frequent in the ARA group (p<0.001). In multivariate analysis, ACA were associated with female gender and were protective for dcSSc and ILD. ATA were found to be protective for lcSSc and they were independently associated with interstitial reticular pattern. ARA positivity was independently associated with dcSSc. We did not find differences in mortality between the three groups. CONCLUSIONS: In Spanish SSc patients, the presence of SSc specific antibodies conferred a distinctive clinical profile.


Assuntos
Autoanticorpos/análise , Escleroderma Sistêmico/imunologia , Adulto , Idoso , Centrômero/imunologia , Estudos de Coortes , DNA Topoisomerases Tipo I/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Polimerase III/imunologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/mortalidade
16.
Autoimmun Rev ; 16(8): 796-802, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28564618

RESUMO

OBJECTIVES: According to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated. METHODS: The characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression. RESULTS: 1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria (p=0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1-47.2). CONCLUSIONS: The classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment.


Assuntos
Escleroderma Sistêmico/diagnóstico , Adulto , Anticorpos Antinucleares/imunologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Prognóstico , Doença de Raynaud/epidemiologia , Doença de Raynaud/imunologia , Sistema de Registros , Fatores de Risco , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/imunologia , Espanha/epidemiologia , Adulto Jovem
17.
Clin Exp Rheumatol ; 35 Suppl 106(4): 40-47, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28229826

RESUMO

OBJECTIVES: To determine the changes in the pattern of death of patients with systemic sclerosis (SSc) throughout 20 years. METHODS: Data were collected from the Spanish Scleroderma Registry (RESCLE), retrospective multicentre database from 1990 to 2009. SSc-related and SSc-non related causes of death were assessed. RESULTS: 987 patients were recruited. Overall standardised mortality ratio (SMR) was 2.34 (2.24-2.44). SSc-related causes of death were responsible of 72% of all deaths of those patients diagnosed within 1990-99 vs. 48% within 2000-09 (p=0.006). Relative pulmonary death rate was stable over time (68.1% within 1990-99 vs. 63.9% within 2000-09, p=0.815). Relative renal death rate was decreasing over time (17% within 1990-99 vs. 5.5% within 2000-09, p=0.175). Heart distribution tripled its ratio (12.8% within 1990-99 vs. 30.6% within 2000-09, p=0.058). CONCLUSIONS: SSc-related causes of death were decreasing over time and, among them, pulmonary involvement was the leading cause of death in both decades. The ratio of renal causes decreased since 1990 at the time that the ratio of cardiac causes increased.


Assuntos
Sistema de Registros , Escleroderma Sistêmico/mortalidade , Adulto , Idoso , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Fatores de Tempo
20.
PLoS One ; 11(4): e0152291, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27064990

RESUMO

INTRODUCTION AND OBJECTIVES: The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. MATERIAL AND METHODS: 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett's formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. RESULTS: Clinical basal characteristics were similar in both groups. QTc interval was 415 ± 21.4 milliseconds in all patients, and 407 ± 19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. CONCLUSION: QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events.


Assuntos
Espessura Intima-Media Carotídea , Síndrome do QT Longo/etiologia , Lúpus Eritematoso Sistêmico/complicações , Rigidez Vascular , Adulto , Estudos de Casos e Controles , Estudos Transversais , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Onda de Pulso , Fatores de Risco
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