Research from JAMA — Platelet Activation in Obese Women — Role of Inflammation and Oxidant Stress — ContextObesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities.ObjectiveTo investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women.Design, Setting, and ParticipantsCross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F2α (8-iso PGF2α) and 11-dehydrothromboxane B2 (11-dehyhdro-TxB2) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity.InterventionDuring a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d.Main Outcome MeasuresPlasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF2α (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB2 (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction.ResultsWomen with android obesity had higher levels of 8-iso PGF2α (median [interquartile range {IQR}] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB2 (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P<.001). Both 8-iso PGF2αand 11-dehyhdro-TxB2 were higher in women with android obesity than women with gynoid obesity (P<.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF2α excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P<.05), 8-iso PGF2α (median change, 32%; P = .04) and 11-dehydro-TxB2 (median change, 54%; P = .005).ConclusionsAndroid obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.

Background: Light–dark alternation has always been the strongest external circadian “zeitgeber” for humans. Due to its growing technological preference, our society is quickly transforming toward a progressive “eveningness” (E), with consequences on personal circadian preference (chronotype), depending on gender as well. The aim of this study was to review the available evidence of possible relationships between chronotype and gender, with relevance on disturbances that could negatively impact general health, including daily life aspects. Methods: Electronic searches of the published literature were performed in the databases MEDLINE and Web of Science, by using the Medical Subject Heading (MeSH), when available, or other specific keywords. Results: Results were grouped into four general areas, i.e. (a) “General and Cardiovascular Issues”, (b) “Psychological and Psychopathological Issues”, (c) “Sleep and Sleep-Related Issues” and (d) “School and School-Related Issues”. (a) E is associated with unhealthy and dietary habits, smoking and alcohol drinking (in younger subjects) and, in adults, with diabetes and metabolic syndrome; (b) E is associated with impulsivity and anger, depression, anxiety disorders and nightmares (especially in women), risk taking behavior, use of alcohol, coffee and stimulants, psychopathology and personality traits; (c) E has been associated, especially in young subjects, with later bedtime and wake-up time, irregular sleep–wake schedule, subjective poor sleep, school performance and motivation, health-related quality of life; (d) E was associated with lowest mood and lower overall grade point average (especially for women). Conclusions: Eveningness may impact general health, either physical or mental, sleep, school results and achievements, especially in younger age and in women. The role of family support is crucial, and parents should be deeply informed that abuse of technological devices during night hours may lead to the immature adjustment function of children’s endogenous circadian pacemakers.

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2 α-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2 α-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2 α-III were significantly higher in patients with COPD (median, 84 pmol / mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol / mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = − 0.38, p = 0.019). Aspirin treatment failed to decrease urinary levels of iPF2 α-III (102 ± 8 versus 99.2 ± 7.3 pmol / mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 ± 74 versus 95 ± 10 pmol / mmol creatinine) (p < 0.0001). Elevated levels of iPF2 α-III (median, 125 pmol / mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol / mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2 α-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.

Background Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function. Methods and Results We examined 64 patients with large-vessel peripheral arterial disease and 64 age- and sex-matched control subjects. TXA ₂ biosynthesis was investigated in relation to cardiovascular risk factors by repeated measurements of the urinary excretion of its major enzymatic metabolite, 11-dehydro-TXB ₂ , by radioimmunoassay. Urinary 11-dehydro-TXB ₂ was significantly ( P =.0001) higher in patients with peripheral arterial disease (57±26 ng/h) than in control subjects (26±7 ng/h). Seventy percent of patients had metabolite excretion >2 SD above the normal mean. However, 11-dehydro-TXB ₂ excretion was enhanced only in association with cardiovascular risk factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB ₂ excretion. During a median follow-up of 48 months, 8 patients experienced major vascular events. These patients had significantly ( P =.001) higher 11-dehydro-TXB ₂ excretion at baseline than patients who remained event free. Conclusions The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo. Rather, the rate of TXA ₂ biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function. Enhanced TXA ₂ biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease.