Oscillatory shear stress induces hemostatic imbalance in healthy men.

INTRODUCTION: In vitro and animal model studies have demonstrated that oscillatory shear can trigger vascular hemostasis and remodeling. However, the roles of hemodynamic forces in vascular human biology are not well understood. This study aimed to determine the effects of increasing oscillatory shear stress (OSS) on coagulation/fibrinolysis factors and matrix metalloproteinase-9 activity in healthy subjects. MATERIALS AND METHODS: Ten healthy males (35 ±â€¯7 years) underwent a 30-minute dominant forearm cuff occlusion (75 mm Hg) to exacerbate OSS in the brachial artery. Blood flow was quantified (Doppler ultrasound), and plasma samples were obtained from both arms at rest and during the last 30 s of cuff occlusion on the dominant arm. A proximal cuff (40 mm Hg, close to axilla) was also occluded to facilitate venous blood biomarker trapping. RESULTS: The retrograde shear rate and oscillatory shear index were increased and the mean shear rate, mean blood velocity, and mean blood flow were decreased in the cuffed arm (p < 0.05 vs. baseline and non-cuffed arm). Cuff occlusion induced increases in platelet microparticle release (p = 0.05 vs. baseline), prothrombin time (p < 0.05 vs. baseline and non-cuffed arm), tissue plasminogen activator (p < 0.01 vs. baseline and non-cuffed arm), plasminogen activator inhibitor-1 (p < 0.02 vs. baseline and non-cuffed arm), and matrix metalloproteinase-9 activity (p = 0.01 vs. baseline). No significant changes were found in the non-cuffed arm throughout the protocol. CONCLUSIONS: Exacerbation of OSS induced in vivo disturbances in platelet microparticle release, coagulation-fibrinolysis, and matrix metalloproteinase-9 activity in healthy individuals. These are potential mechanisms involved in OSS-mediated endothelial dysfunction.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. OBJECTIVE: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. RESULTS: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (p sex < 0.01). CONCLUSIONS: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome / Diferenças na Proteína C Reativa Ultrassensível associado ao gênero em Indivíduos com Fatores de Risco da Síndrome Metabólica

Abstract Background: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. Objective: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. Results: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (psex < 0.01). Conclusions: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Resumo Fundamento: A síndrome metabólica (SM) está associada a um maior risco de mortalidade por todas as causas. A proteína C reativa ultrassensível (PCRus) é um marcador prototípico de inflamação que está geralmente aumentado na SM. Mulheres com doenças relacionadas à SM apresentam níveis mais elevados de PCRus quando comparadas com homens com doenças relacionadas à SM, sugerindo diferenças associados ao gênero nos marcadores inflamatórios. No entanto, não é claro se os níveis séricos de PCRus já estão aumentados em homens e/ou mulheres com fatores de risco da SM, sem doenças pré-estabelecidas ou sob tratamento farmacológico. Objetivo: Determinar o impacto do número de fatores de risco da SM sobre os níveis séricos de PCRus em mulheres e homens. Métodos: Cento e dezoito pacientes (70 homens e 48 mulheres; 36±1 anos) foram divididos em quatro grupos de acordo com o número de fatores de risco da SM: grupo saudável (CT; sem fatores de risco), SM ≤ 2, SM = 3 e SM ≥ 4. Após 12 horas de jejum, amostras de sangue foram coletadas para determinação de variáveis bioquímicas e níveis de PCRus, analisada pelo método imunoturbidimétrico. Resultados: Os grupos com fatores de risco da SM apresentaram níveis séricos mais elevados de PCRus quando comparados com o grupo CT (p < 0,02). Não foram observadas diferenças nos níveis de PCRus entre os grupos com fatores de risco da SM (p > 0,05). O melhor modelo de regressão linear para explicar a associação entre fatores de risco da SM com níveis de PCRus foram a circunferência da cintura e os níveis de HDL-colesterol (r = 0,40, p < 0,01). Mulheres com fatores de risco da SM apresentaram valores mais elevados de PCRus quando comparadas com homens (psexo < 0,01). Conclusões: Apesar da ausência de doenças pré-estabelecidas e tratamento farmacológico, os indivíduos com fatores de risco da SM já apresentaram aumento nos níveis de PCRus, que foram significativamente mais elevados nas mulheres do que nos homens em condições semelhantes.