Dietary fatty acids, hemostasis, and cardiovascular disease risk

The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.     

Mortality Rates and Predictors of Mortality Among Late-Middle-Aged and Older Substance Abuse Patients

This study describes mortality rates and predictors of mortality among late-middle-aged and older (55+) substance abuse inpatients ( n = 21, 139) in Department of Veterans Affairs (VA) Medical Centers in the 4 years after an index episode of care. A total of 24% of the patients died; this mortality rate was 2.64 times higher than expected. Predictors of earlier mortality included older age and nonmarried status, alcohol psychosis and organic brain disorder diagnoses, and several medical diagnoses, including neoplasms, liver cirrhosis, respiratory, endocrine and metabolic, and blood system disorders. Three proxy indicators of illness severity also predicted mortality: more prior inpatient and outpatient medical care and an index episode in an extended care unit. In contrast, more prior outpatient mental health care and remitted status predicted lower mortality. These diagnostic and treatment indicators can be used to identify patients at heightened risk for premature mortality. Moreover, they show that intensive mental health aftercare and remission of substance abuse may delay mortality, even among older patients who have longstanding substance abuse problems.     

Echocardiographic demonstration of important abnormalities of the mitral valve in congenitally corrected transposition.

Whereas abnormalities of the morphological tricuspid valve are common in the setting of discordant atrioventricular connections, there are only a few postmortem reports of abnormalities of the mitral valve in this condition. This report describes two patients with discordant atrioventricular connections, in whom important abnormalities of the mitral valve were found during life by cross sectional echocardiography.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Immunology: High fecundity rates following in- vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin

This study was undertaken to explore whether intervention withheparin and aspirin (H/A) in selected patients undergoing in-vitrofertilization (TVF) and embryo transfer could improve fecundityrates. Specifically, it explored the possibility that womendiagnosed with organic pelvic disease who demonstrated antiphospholipidantibodies (APA) could benefit from H/A administration in asimilar manner to that used in patients with recurrent pregnancyloss. We used an enzyme–linked immunosorbent assay forsix different phospholipids to identify patients who expressedAPA before they underwent IVF/embryo transfer. This study wasconfined to the first IVF/embryo transfer cycle that followedassessment of APA status and accordingly, the number of IVF/embryotransfer cycles corresponds with the number of patients treated.APA seropositive patients were treated with aspirin, 81 mg orallyq.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1 ofcontrolled ovarian stimulation. The endpoint for success wasa live birth or an ultrasound confirming fetal cardiac activity(a viable pregnancy). The prevalence of APA in patients diagnosedwith organic pelvic disease (53%) was much higher than in thosewithout female pathology (14%). The administration of H/A toAPA seropositive patients significantly (P < 0.05) improvedthe viable pregnancy rate (49%) compared to the untreated APAseropositive group (16%). The viable pregnancy rate for APAseropositive women treated with H/A was also significantly (P< 0.001) higher than for untreated APA seronegative patients(27%). We conclude that all women undergoing IVF/embryo transfershould be tested for APA prior to initiating ovarian stimulation,and those with APA seropositivity should be treated with H/A.