Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Association between dietary patterns and renal function in a cross-sectional study using baseline data from the ELSA-Brasil cohort

Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP ("traditional", "fruits and vegetables", "bakery", and "low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between "bakery" and "fruits and vegetables", and both were associated with decreased eGFR and albuminuria in both genders, compared with "traditional" and "low sugar/low fat" patterns in the general population. There was a direct association of the "bakery" pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The "fruits and vegetables" pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The "fruits and vegetables" and "bakery" DPs were associated with renal dysfunction. The only independent, direct association was between "bakery" DP and MA in men, raising concerns about DP and renal damage in men.

Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106 percent increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95 percentCI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46 percent increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16 percent reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

A mathematical framework for group analysis of von Willebrand factor multimeric composition following luminography

The objective of the present study was to establish a method for quantitative analysis of von Willebrand factor (vWF) multimeric composition using a mathematical framework based on curve fitting. Plasma vWF multimers from 15 healthy subjects and 13 patients with advanced pulmonary vascular disease were analyzed by Western immunoblotting followed by luminography. Quantitative analysis of luminographs was carried out by calculating the relative densities of low, intermediate and high molecular weight fractions using laser densitometry. For each densitometric peak (representing a given fraction of vWF multimers) a mean area value was obtained using data from all group subjects (patients and normal individuals) and plotted against the distance between the peak and IgM (950 kDa). Curves were constructed for each group using nonlinear fitting. Results indicated that highly accurate curves could be obtained for healthy controls and patients, with respective coefficients of determination (r²) of 0.9898 and 0.9778. Differences were observed between patients and normal subjects regarding curve shape, coefficients and the region of highest protein concentration. We conclude that the method provides accurate quantitative information on the composition of vWF multimers and may be useful for comparisons between groups and possibly treatments

Formas graves de leptospirose: aspectos clínicos, demográficos e ambientais / Severe forms of leptospirosis: clinical, demographic and environmental aspects

Characteristics of 1,016 patients hospitalized with leptospirosis in the Hospital Couto Maia, Salvador, BA, Brazil, between 1993 and 1997 are described. Higher pluviometric precipitation was related to an increase in the number of hospitalizations during the following month. Males corresponded to 81.1% (824/1,016) of these; mean age was 35.7+/-15.4 years. Almost 94% (778/829) of the 829 patients with information about race were black or mulatto (mixed race). For ages 18 years or above, almost 93% had not completed high school level. The mean incubation period was estimated as 6.3+/-3.9 days. Average duration of symptoms was 6.1+/-2.4 days. Hemorrhagic events corresponded to 14.3% (145/1,016). The case-fatality rate among 1,009 patients that were not transferred was 14.2% (143/1,009). Renal failure was the attributable cause of death in 76.2% (109/143). The data indicate that leptospirosis is closely related to lower socioeconomic levels, and that higher pluviometric precipitation antecedes the outbreaks.

São descritas as características de 1.016 pacientes internados com leptospirose no Hospital Couto Maia, Salvador, BA, entre 1993 e 1997. Aumento na precipitação pluviométrica mostrou relação com aumento do número de internamentos no mês subsequente. Sexo masculino correspondeu a 81,1% (824/1.016); a média da idade foi 35,7±15,4 anos. Quase 94% (778/829) dos 829 com informação sobre raça eram negros ou mulatos. Para idade igual ou superior a 18 anos, quase 93% não cursaram o segundo grau. A média do período de incubação foi estimado em 6,3±3,9 dias. A duração dos sintomas foi em média 6,1±2,4 dias. Episódios hemorrágicos corresponderam a 14,3% (145/1.016). A letalidade entre 1.009 pacientes não transferidos foi de 14,2% (143/1.009). Insuficiência renal foi a causa atribuída de morte em 76,2% (109/143). Os dados indicam que leptospirose é estreitamente relacionada com baixos níveis socioeconômicos e que aumento da precipitação pluviométrica precede surtos epidêmicos.

Associaçäo entre raça e incidência de doença renal terminal secundária a glomerulonefrite: influência do tipo histológico e da presença de hipertensäo arterial / Association between race and incidence of end-stage renal disease secondary to glomerulonephritis: influence of the histologic type and presence of arterial hypertension

OBJETIVO: Avaliar retrospectivamente a associaçäo entre raça e incidência de doença renal terminal (DRT) em pacientes com glomerulonefrites em um Hospital Universitário do estado da Bahia. METODOS: A amostra foi composta de 79 pacientes com esclerose glomerular focal (EGF), 50 com glomerulonefrite membranoproliferativa (GNMP) e 44 com outros tipos de glomerulonefrites (OTGN), acompanhados entre 1970 e 1996 por pelo menos 6 meses. NÒo foram incluídos os pacientes com glomerulonefrite aguda, formas crescenticas, lesäo mínima, doenças do colágeno e com níveis de creatinina séica maior ou igual a 4 mg/dl. Quanto à raça, os pacientes foram classificados em brancos, mulatos ou negros. Para idades superiores a 18 anos e na ausência de uso de anti-hipertensivos, definiu-se como hipertensos pacientes que tiveram mÚdias das três primeiras determinaçöes da pressäo arterial sistólica ou diastólica iguais ou superiores a 140 e 90 mmHg, respectivamente; para idades igual ou abaixo de 18 anos foram utilizados critérios recomendados pela "Task Force on Blood Pressure in Children". RESULTADOS: No grupo de normotensos, a incidência de DRT foi 72 por cento menor em mulatos e negros (risco relativo (RR)=0,28; intervalo de confiança (IC) 95 por cento=0,11-0,67). No grupo de hipertensos, a associaçäo entre raça e DRT apresentou direçäo inversa (RR=1,49; IC 95 por cento=0,68-4,34; p=0,316) à observada em normotensos. Esta variaçäo no RR de acordo com a presenç ou ausência de HA foi estatisticamente significante (p=0,01). Entre os normotensos, parte da diferença racial na incidência de DRT pode ser explicada pela distribuiçäo de tipos histológicos de glomerulonefrite entre o grupo de brancos e o grupo de negros e mulatos. CONCLUSOES: Entre os normotensos com glomerulonefrite, a incidência de DRT foi significantemente maior em brancos do que em negros ou mulatos. Contrariamente, entre os hipertensos observou-se uma tendência para um risco maior de DRT no grupo de negros e mulatos. O estudo sugere que HA e o tipo histológico de glomerulonefrite influenciam a associaçäo entre raça e DRT

Medicina Baseada em Evidências: a arte de aplicar o conhecimento científico na prática clínica / Evidence-Based Medicine: the art of applying the scientific knowledge in the clinical practice

Este artigo foi escrito com o objetivo de descrever o conceito de Medicina Baseada em Evidências (MBE) e as competências necessárias para a sua prática. MBE deve ser vista como a integraçao da experiência clínica com a capacidade de analisar e aplicar racionalmente a informaçao científica ao cuidar de pacientes. A aplicaçao de métodos e estratégias para fortalecer o alicerce científico do médico, sem desprezar os valores humanitários da profissao, deverá contribuir para a melhoria da qualidade da assistência médica que é oferecida no Brasil. As Escolas e Associaçoes Médicas podem desempenhar importantes papéis na promoçao da MBE

Diferenças raciais entre pacientes com esclerose glomerular focal e glomerulonefrite membranoproliferativa em residentes no estado da Bahia / Racial differences between patients with focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis from the State of Bahia

Objetivo. Avaliar a relaçao entre raça e tipo histológico de glomerulomefrite, levando em consideraçao idade, sexo e presença da forma hepatoesplênica da esquistossomose mansônica. Material e Métodos. Pacientes do Serviço de Nefrologia da Universidade Federal da Bahia, 80 com esclerose glomerular focal (EGF) e 50 com glomerulonefrite membranoproliferativa (GNMP) foram comparados quanto à distribuiçao dos tipos raciais (negro, mulato, branco). Pacientes com lupus eritematoso sistêmico ou qualquer outro tipo de doença auto-imune nao foram incluídos na presente análise. Comparaçoes ajustadas foram feitas através do método de Mantel-Haenszel e de um modelo de regressao logística múltipla. Resultados. Raça foi significantemente associada com o tipo histológico; a relaçao entre o número de negros ou mulatos e o número de brancos foi aproximadamente 2,4 vezes maior (odds ratio=2,43; IC 95 por cento=1,09-5,45) em pacientes com EGF do que em pacientes com GNMP. Esta associaçao entre raça e tipo histológico foi independente da idade, do sexo e da presença da forma hepatoesplênica da esquistossomose. No modelo de regressao logística múltipla, raça foi significativamente (p=0,037) associada com o tipo histológico (odds ratio=2,54; IC 95 por cento=1,06-6,06). Conclusao. A maior freqüência de negros e mulatos no grupo EGF nesta amostra de pacientes da Bahia é consistente com os achados de estudos realizados nos Estados Unidos. Os dados apoiam a posibilidade de uma relaçao entre descendência africana e susceptibilidade aumentada para EGF, independente da idade, do sexo e do diagnóstico de esquistossomose. A identificaçao dos mecanismos que determinam esta diferença racial representa uma importante questao para futuras investigaçoes.

Aumento da frequência de resistência à norfloxacina e ciprofloxacina em bactérias isoladas em uroculturas / Increase in the frequency of norfloxacin and ciprofloxacin resistance of bacteria isolated from urine culture

Objetivo. Avaliar mudanças, ao longo dos anos, na freqüência de resistência à norfloxacina e ciprofloxacina em bactérias isoladas de uroculturas. Métodos. Resultados de todas as uroculturas com crescimento bacteriano de pelo menos 10(5) unidades formadoras de colônias por mL de urina (UFCmL), realizadas no Serviço de Nefrologia da Universidade Federal da Bahia durante o período 1983-1994, foram analisadas. As bactérias incluídas na análise foram aquelas mais freqüentemente isolados: Escherichia coli (n=668), Klebsiella spp. (n=286), Staphylococcus spp. (n=186), Proteus spp. (n=135) e Enterobacter spp. (n=129). Resultados. A freqüência de bactérias resistentes à norfloxacina foi de 3,2 por cento, no período 1983-1986; 5,9 por cento, no período 1987-1990; e 9,1 por cento no período de 1991-1994 (p<0,05). Klebsiella spp. e Enterobacter spp. foram as bactérias que apresentaram maiores aumentos na freqüência de resistência à norfloxacina. Para a ciprofloxacina, constatou-se resistência em 7,4 por cento das bactérias isoladas, no período 1985-1989, e 16,5 por cento, no período 1990-1994 (p<0,05). Esse aumento na freqüência de bactérias resistentes à ciprofloxacina foi mais marcante para Enterobacter spp. e Staphylococcus spp. Conclusoes. Os resultados do presente estudo mostram um aumento gradual na freqüência de resistência à norfloxacina e ciprofloxacina entre as bactérias mais comumente isoladas em uruculturas. A influência do uso prévio de quinolonas e de peculiaridades da bactéria infectante, nesses achados, representa importante questao a ser investigada.

Por que a letalidade hospitalar do infarto agudo do miocárdio é maior nas mulheres? / Why is the in-hospital case-fatality rate of acute myocardial infarction higher in women?

OBJETIVO - Avaliar a influência da idade, da gravidade da doença e das intervençöes terapêuticas na maior letalidade hospitalar do infarto agudo do miocárdio (IAM) em mulheres. MÉTODOS - Estudo de coorte retrospectivo, envolvendo 388 pacientes com IAM (50 óbitos). Foram avaliadas, como possíveis explicaçöes para a associaçäo entre sexo e letalidade hospitalar do IAM, as variáveis: idade (menor que 60 vs menor ou igual 60 anos), duraçäo de sintomas, classe Killip, tipo de IAM (com ou sem ondas Q), comorbidades, história de acidente vascular cerebral e intervençöes terapêuticas para o IAM (ácido acetil-salicílico, betabloqueadores e agentes trombolíticos). Modelos de regressäo logística foram usados para avaliar a influência de potenciais variáveis confundidoras na associaçäo entre sexo e letalidade hospitalar do IAM. RESULTADOS - A letalidade hospitalar do IAM foi mais alta em mulheres (19,5 'por cento' vs 9,4 'por cento') do que em homens (odds ratio (OR)=2,34;IC 95 'por cento'=1,12-4,47). Embora as mulheres fossem significativamente (p menor que 0,01) mais idosas, a associaçäo entre sexo e morte reduziu-se em apenas 15 'por cento' após ajuste para idade (OR=1,99;IC 95 'por cento'=1,07-3,67). Esta associaçäo tornou-se mais fraca ao se considerar a gravidade da doença na admissäo (OR=1,84;IC 95 'por cento'=0,90-3,74) e intervençöes terapêuticas para o IAM (OR=1,50;IC=0,67-3,38). CONCLUSÄO - Diferenças de idade näo podem explicar completamente a maior letalidade do IAM em mulheres. A gravidade da doença na admissäo e diferenças de abordagen terapêutica devem desempenhar importante papel na maior letalidade hospitalar do IAM em mulheres.

Fator von Willebrand e disfunçäo endotelial pulmonar. Implicaçöes prognósticas / von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

OBJETIVO - Avaliar alteraçöes quantitativas e estruturais do fator von Willebrand (fvW) circulante em 40 pacientes com hipertensäo pulmonar pré-capilar e verificar possíveis implicaçöes prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS - A atividade antigênica plasmática do fator von Willebrand (vWF:Ag) foi analisada por imunoeletroforese. A concentraçäo de multímeros de baixo peso molecular em relaçäo...

Decreased biological activity is related to abnormal multimeric structure of von Willebrand factor in pulmonary hypertension

We evaluated the correlation between decreased biological activity and abnormalities in the multimeric structure of plasma von Willebrand factor (vWF) in 27 pulmonary hypertensive patients (median age, 21 years). The biological activity of vWF was measured by the ristocetin cofactor assay and its multimeric structure was assessed by Western immunoblotting after SDS-agarose gel electrophoresis. In spite of high antigenic activity of vWF in plasma (139 ñ 65 vs 91 ñ 27 per cent in controls, P=0.003), the biological activity expressed as a percent of the control value was decreased in pulmonary hypertensive patients (60-88 per cent activity, 95 per cent CI for the mean). High molecular weight multimers (biologically active forms) were absent in patients and there was a significant increase in the concentration of low molecular weight polymers in comparison with normals (56 ñ 12 and 35 ñ 12 per cent of total multimer density, respectively, P<0.001). Multimeric abnormalities were positively correlated with plasma vWF levels (r=0.51, P=0.0007) and negatively correlated with vWF biological activity (r=-0.54, P=0.004). Thus, decreased biological function is related to abnormalities in the multimeric structure of vWF, possibility reflecting extensive endothelial dysfunction in pulmonary hypertension.

Plasma anticoagulant system in patients with pulmonary hypertension

Adults with pulmonary hypertension and polycythemia (N=22) have low levels of plasma antithrombin III (84 ñ 18 vs 98 ñ 13½ for controls, N=35, P<0.005) and protein C (66ñ21 vs 125 ñ 30%, N 8, P<0.0002 but normal levels of total protein S. Data are reported as means ñ SD and percent normal values obtained for pooled plasma from normal healthy adults. Children with the same disorder (N = 6) also had low protein C levels (66 ñ 16 vs 85 ñ 5½, P < 0.025). Total protein S was normal for children, but free protein S was decreased (66 ñ 13 vs 91 ñ 23,, P < 0.02). Since the levels observed in these patients are above those reported for congenital deficiencies, the reduction in plasma levels of anticoagulant proteins may be the result of cronic intravascular coagulation. Furthermore, normal levels of plasminogen and fibrin degradation products suggested a localized disorder or an acquired decrease in fibronolytic activity