Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis?

BACKGROUND: Psoriasis is an immune mediated inflammatory skin disease associated with systemic inflammation resulting in increased risk for associated cardiovascular co-morbidities. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook to study the platelet activation markers in psoriasis, as compared to controls and to identify its association with disease severity in psoriasis. METHODS: Sixty-two patients with psoriasis and 62 age and gender matched healthy controls were enrolled in this cross-sectional study. The severity of the disease was assessed using the psoriasis area severity index (PASI) scoring. The platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] were estimated by an automated haematological laser optical analyzer. Plasma soluble P-selectin and platelet derived microparticle (PDMP) concentrations, serum high sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentrations were estimated in all study participants. Platelet aggregation was assessed using adenosine diphosphate (ADP) as aggregating agent. RESULTS: We observed that there was significantly higher platelet indices (MPV and PDW) in patients with psoriasis, when compared to controls. Plasma soluble P-selectin concentrations, PDMP and platelet aggregation were significantly elevated in patients with psoriasis, as compared to controls. We also found significantly higher concentrations of hs-CRP and IL-6 in patients with psoriasis, as compared to controls. Platelet activation and systemic inflammation markers correlated positively with PASI, except PDW. We also observed significant positive correlation between platelet activation and systemic inflammation in psoriasis. CONCLUSION: Significant platelet activation and systemic inflammation were observed in patients with psoriasis, especially when associated with severe disease. The increased platelet activation might be the missing link between the persistent inflammation and the development of atherosclerotic plaque leading onto cardiovascular co-morbidities seen associated with psoriasis.

Platelet activation in chronic urticaria and its correlation with disease severity.

Chronic urticaria (CU) is characterized by the occurrence of wheals lasting for more than 6 weeks. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook a cross-sectional study among 45 patients with CU and 45 age- and gender-matched healthy controls. The severity of the disease was assessed using the urticaria severity score. The autologous plasma skin test (APST) was done in all cases of CU. The platelet count and indices were estimated by an automated haematological laser optical analyzer. Platelet aggregation and soluble P-selectin levels were estimated in all study participants. It was observed that there was a significantly higher mean platelet volume (MPV) and platelet distribution width (PDW) in patients with CU when compared to controls. Platelet aggregation and soluble P-selectin levels were significantly higher in patients with CU, as compared to controls. Urticaria severity score correlated positively with platelet aggregability and soluble P-selectin levels. APST-positive patients had significantly higher platelet aggregation and higher soluble P-selectin levels, when compared to the APST-negative patients, indicating more platelet activation in the autoimmune group. There is significant platelet activation in patients with CU, especially in those with autoreactivity.

Synergy of iron, high sensitivity C-reactive protein and ceruloplasmin with oxidative stress in non-diabetic normo-tensive South Indian obese men.

BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis of obesity and its related complications. Previous studies have suggested a potential link between obesity and altered iron metabolism. The present study was designed to evaluate iron, C-reactive protein, ceruloplasmin and oxidative stress and their association, if any, in non-diabetic normo-tensive South Indian obese men. METHODS: 30 obese men and 30 age-matched males with normal body weight were recruited in the study. Serum iron, copper, ceruloplasmin, high sensitivity C-reactive protein (hs-CRP), malondialdehyde, protein carbonyl, total oxidant status and total antioxidant status were estimated in all the subjects. RESULTS: Serum iron, ceruloplasmin, high sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), protein carbonyl and total oxidant status were significantly increased and total antioxidant status was significantly reduced in obese men, compared to controls. Linear regression analysis shows highly significant positive association of iron with hs-CRP. CONCLUSION: The data from the present study concludes that oxidative stress parameters, hs-CRP, iron and ceruloplasmin were significantly elevated in obese Indian men, suggesting they are more prone to develop cardiovascular disease, than age-matched men with normal body weight.

Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria.

BACKGROUND: Recent studies implicate the role of immune-inflammatory responses in chronic spontaneous urticaria (CSU). Although it is well known that platelets release inflammatory mediators and reactive oxygen species upon activation, their role in CSU is poorly characterized. The present study was designed to evaluate platelet oxidative stress [platelet malondialdehyde (MDA), platelet superoxide dismutase (SOD), platelet glutathione peroxidase (GPx)] and systemic inflammatory markers [plasma Interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP)] in patients with CSU and their association with disease severity. METHODS: Forty-five patients with CSU and 45 age- and gender-matched healthy controls were included in the study. Severity grading was completed according to the urticaria severity score (USS). Autologous plasma skin test (APST) was done in all patients with CSU. Platelet MDA, SOD and GPx and inflammatory markers plasma IL-6 and hs-CRP were assayed in all study participants. RESULTS: In patients with CSU, platelet SOD and GPx were significantly lowered, while platelet MDA levels were significantly elevated in comparison to healthy controls. Both IL-6 and hs-CRP were significantly elevated in patients with CSU and correlated with platelet oxidative stress parameters (p<0.05). Platelet MDA, SOD and GPx and inflammatory markers (plasma IL-6 and hs-CRP) showed a significant correlation with USS in patients with CSU. CONCLUSIONS: Our results indicate significant systemic inflammation and platelet oxidative stress in patients with CSU.

Relationship of raised serum total and protein bound sialic acid levels with hyperinsulinemia and indices of insulin sensitivity and insulin resistance in non-diabetic normotensive obese subjects.

AIMS: Obesity is known to be associated with cardiovascular disease and interaction between inflammation and insulin resistance is reported to enhance the cardiovascular risk in these subjects. The present study was designed to assess indices of insulin sensitivity, insulin resistance and sialic acid levels and their association in non-diabetic normotensives obese subjects. MATERIALS AND METHODS: The present study was conducted in 30 obese male subjects and results were compared with 30 subjects with normal body weight. Insulin, total sialic acid and protein bound sialic acid were estimated in all the subjects. Insulin resistance was calculated by using Homeostatic Model Assessment-insulin resistance formula. Insulin sensitivity was assessed by quantitative insulin check index and insulin sensitivity index. RESULTS: Insulin resistance, serum total and protein bound sialic acid levels were significantly increased in obese cases as compared to non-obese controls. Total sialic acid showed significant positive correlation with HOMA-IR (p<0.01), BMI (p<0.01), waist and hip circumference (p<0.01) and negative correlation with QUICKI (p<0.01) and insulin sensitivity index (p=0.018). There was no significant correlation between protein bound sialic acid and indices of insulin resistance and insulin sensitivity. CONCLUSION: Sialic acid levels are elevated in obese subjects and its association with insulin resistance and reduced insulin sensitivity may enhance the cardiovascular risk in these subjects.