15-keto-13-14-dihydroprostaglandin-f2alpha and Cardiovascular-Diseases

An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2 α (PGF(2α)). Prostaglandin F2 α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF(2α) concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF(2α) formation, by measuring urinary 15-keto-dihydro-PGF(2α), and mortality risk in a community setting.. Urinary 15-keto-dihydro-PGF(2α) was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF(2α) was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF(2α): 1.18; 95% CI:1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF(2α) was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF(2α): 1.11; 95% CI: 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF(2α) concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).. This is the first study to show that the inflammatory mediator PGF(2α) was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF(2α) in fatal cardiovascular disease.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Dinoprost; Humans; Longitudinal Studies; Male; Neoplasms; Risk Factors; Sweden

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

Topics: Adiposity; Adolescent; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Dairy Products; Dietary Fats; Dinoprost; Fatty Acids; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Linear Models; Male; Obesity; Oxidative Stress; Phospholipids; Risk Factors

Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2alpha, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2alpha), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2alpha compared to all lower quartiles and decreased levels of PGF2alpha compared to all lower quartiles at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, alpha-tocopherol and beta-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Diet; Dinoprost; Follow-Up Studies; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Isoprostanes; Longitudinal Studies; Male; Middle Aged; Oxidative Stress; Radioimmunoassay; Selenium; Serum Amyloid A Protein; Sweden