Carotid intima-media thickness better differentiates between groups of stroke patients and persons without cerebrovascular disease than other conventional and novel risk factors

When measured by ultrasound, the morphological markers of carotid atherosclerosis such as intima-media thickness (IMT) and cross-sectional plaque area have been associated with the risk of ischaemic stroke. We set out to determine whether the morphological parameters of the carotid arteries made it possible to better differentiate between groups of older atherothrombotic stroke patients and persons without cerebrovascular disease than conventional and novel risk factors of stroke. Of the total number of 623 persons examined, 54 stroke patients (mean age 63.3 years) and 74 controls without cerebrovascular disease (mean age 66.3 years) fulfilled the inclusion criteria for this investigation and were enrolled in the case-control study. After adjustment for age, gender and education level, the strongest associations were found between stroke and carotid IMT [odds ratio (OR) = 10.6; 95% confidence interval (CI): 4.3–26.9] and plaque area (OR = 5.4; 95%CI: 2.3–13.1). Other risk factors showed weaker associations with stroke occurrence. Of the clinical risk factors, a significant association was found between stroke and coronary heart disease (OR = 3.5; 95%CI: 1.2–10.2), hypertension (OR = 3.2; 95%CI: 1.5–7.2) and smoking (OR = 2.7; 95%CI: 1.1–6.4). From the laboratory-derived risk factors a significant association was found between stroke and triglyceride levels (OR = 4.4; 95%CI: 1.9–10.0), and an inverse correlation was observed between stroke occurrence and HDL-cholesterol level (OR = 0.4; 95%CI: 0.2–0.8). The carotid IMT and plaque area, measured with the use of ultrasonography, showed a better correlation with stroke occurrence than currently recognised clinical and biochemical risk factors. The intima-media thickness and plaque area of the carotid arteries could be useful parameters in the development of strategies to identify patients at high risk of atherothrombotic ischaemic stroke

Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study)

Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10−7), large VLDL cholesterol (odds ratio 2.36, P < 10−10), total triglycerides (odds ratio 1.88, P < 10−6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10−5), glucose disposal rate (odds ratio 0.44, P < 10−9), large HDL cholesterol (odds ratio 0.39, P < 10−9) and glomerular filtration rate (odds ratio 0.19, P < 10−10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models—our exploratory approach provides independent support for this relationship in human patients with diabetes

Mitochondrial functioning abnormalities observed in blood platelets of chronic smoke-exposed guinea pigs &ndash; a pilot study

Adam J Białas,1 Karolina Siewiera,2 Cezary Watała,2 Anna Rybicka,3 Bartłomiej Grobelski,3 Leon Kośmider,4,5 Jolanta Kurek,6 Joanna Miłkowska-Dymanowska,1 Wojciech J Piotrowski,1 Paweł G&oacute;rski1 1Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Department of Hemostasis and Hemostatic Disorders, Medical University of Lodz, Lodz, Poland; 3The animal house, Pharmaceutical Faculty, Medical University of Lodz, Lodz, Poland; 4Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA; 5Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, VA, USA; 6Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland Background: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions. Materials and methods: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions&reg; exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2&times;70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry. Results: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O2/[s &middot; 1&times;108 platelets]); bootstrap-boosted P1&alpha;=0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O2/[s &middot; mg of protein]); bootstrap-boosted P1&alpha;=0.049. Conclusion: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples. Keywords: mitochondria, electron leak, proton leak, electron transport chain, ETC, chronic obstructive pulmonary disease, COPD, animal mode