Hyperlipidemias: Watala C

Watala C. · Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Poland. · Curr Pharm Des. · Pubmed #16022671 No free full text.

Abstract: Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.

Markuszewski L, Rosiak M, Golanski J, Rysz J, Spychalska M, Watala C. · Department of Interventional Cardiology, Cardiodiabetology and Cardiac Rehabilitation, Medical University of Lodz, University Hospital no. 2, Lodz, Poland. · Basic Clin Pharmacol Toxicol. · Pubmed #16635110 No free full text.

Abstract: The study was designed to assess blood platelet sensitivity to acetylsalicylic acid and its associations with dyslipidaemia and inflammation in coronary artery disease patients. Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75-150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8-15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45-50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313-728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients.