Case of "slow" stroke from carotid artery occlusion treated by delayed but cautious endovascular intervention.

In a challenging case of carotid occlusion with slowly evolving stroke, we used brain imaging to facilitate endovascular revascularization resulting in the relief of the patient's symptoms. Patients with carotid occlusion and continued neurological worsening or fluctuations present enormous treatment challenges. These patients may present "slow" strokes with subacute infarcts that present significant challenges and risks during attempts at revascularization of the occluded artery. We present such a case in which we used multimodal imaging techniques, including MR-perfusion, to facilitate endovascular revascularization. Our approach of delayed but cautious intra-arterial thrombolytic therapy, guided by brain imaging, and followed by stent placement across the residual stenosis, enabled revascularization of the occluded artery without overt in-hospital complications.

Calcification of a collagen-liposome complex

The purpose of the study was to evaluate in vitro calcification potential among liposomes composed of phospholipids with variations in fatty acid chains and polar head groups. The liposome was also modified by utilizing mixed phospholipids, incorporation of different types of protein to the liposome, or complexing with various collagen preparations. The samples were then incubated in a metastable calcium phosphate solution for the proposed time period. Calcium and phosphate uptake were measured. Resulting precipitates were processed for x-ray diffraction and electron microscopy. Acidic phospholipid, Dioleoylphosphatidic acid and mixed phospholipids, Dioleoylphosphatidic acid/Dipalmitoylphosphatidylethanolamine liposomes calcified at a faster rate and to a greater degree than other phospholipids tested. The incorporation of polylysine, fibronectin, bone protein, or the complexing with collagen decreased the rate and amount of calcification. Electron microscopy demonstrated the similarity of the calcified collagen-liposome complex to the natural calcification matrix. These preparations may be used as a model to study the role of membrane lipids and collagen-phospholipid during the process of calcification.^ The in vivo study was designed to determine whether the potential existed for the promotion of bone healing by the synthetic liposome-collagen complex. The implant materials were modified to provide decreased antigenicity, biocompatability while maintaining their bone conduction properties. The samples were placed subcutaneously and/or subperiosteally and/or in 8 mm calvarium defects of adult rats. Histological and immunological studies demonstrated that the implant itself retained minimal antigenicity and did not inhibit bone formation. However, modification of the implant may contain the bone induction property and be utilized to stimulate bony healing. ^

The angiotensin-converting enzyme insertion/deletion polymorphism and its associations with carotid artery wall thickness and coronary heart disease: The atherosclerosis risk in communities study

Coronary heart disease (CHD) is the leading cause of death in the United States. Recently, renin-angiotensin system (RAS) was found associated with atherosclerosis formation, with angiotensin II inducing vascular smooth muscle cell growth and migration, platelet activation and aggregation, and stimulation of plasminogen activator inhibitor-1. Angiotensin II is converted from angiotensin I by angiotensin I-converting enzyme (ACE) and this enzyme is mainly genetically determined. The ACE gene has been assigned to chromosome 17q23 and an insertion/deletion (I/D)polymorphism has been characterized by the presence/absence of a 287 bp fragment in intron 16 of the gene. The two alleles form three genotypes, namely, DD, ID and II and the DD genotype has been linked to higher plasma ACE levels and cell ACE activity.^ In this study, the association between the ACE I/D polymorphism and carotid artery wall thickness measured by B-mode ultrasound was investigated in a biracial sample, and the association between the gene and incident CHD was investigated in whites and if the gene-CHD association in whites, if any, was due to the gene effect on atherosclerosis. The study participants are from the prospective Atherosclerosis Risk in Communities (ARIC) Study, including adults aged 45 to 65 years. The present dissertation used a matched case-control design for studying the associations of the ACE gene with carotid artery atherosclerosis and an unmatched case-control design for the association of the gene with CHD. A significant recessive effect of the D allele on carotid artery thickness was found in blacks (OR = 3.06, 95% C.I: 1.11-8.47, DD vs. ID and II) adjusting for age, gender, cigarette smoking, LDL-cholesterol and diabetes. No similar associations were found in whites. The ACE I/D polymorphism is significantly associated with coronary heart disease in whites, and while stratifying data by carotid artery wall thickness, the significant associations were only observed in thin-walled subgroups. Assuming a recessive effect of the D allele, odds ratio was 2.84 (95% C.I:1.17-6.90, DD vs. ID and II) and it was 2.30 (95% C.I:1.22-4.35, DD vs. ID vs. II) assuming a codominant effect of the D allele. No significant associations were observed while comparing thick-walled CHD cases with thin-walled controls. Following conclusions could be drawn: (1) The ACE I/D polymorphism is unlikely to confer appreciable increase in the risk of carotid atherosclerosis in US whites, but may increases the risk of carotid atherosclerosis in blacks. (2) ACE I/D polymorphism is a genetic risk factor for incident CHD in US whites and this effect is separate from the chronic process of atherosclerosis development. Finally, the associations observed here are not causal, since the I/D polymorphism is in an intron, where no ACE proteins are encoded. ^

Are functional and genetic components of platelets linked to coronary artery disease: A case-control study

Coronary artery disease (CAD) is a multifactorial disease process involving behavioral, inflammatory, clinical, thrombotic, and genetic components. Previous epidemiologic studies focused on identifying behavioral and demographic risk factors of CAD, but none focused on platelets. Current platelet literature lacks the known effects of platelet function and platelet receptor polymorphisms on CAD. This case-control analysis addressed these issues by analyzing data collected for a previous study. Cases were individuals who had undergone CABG and thus had been diagnosed with CAD, while the controls were volunteers presumed to be CAD free. The platelet function variables analyzed included fibrinogen Von Willebrand Factor activity (VWF), shear-induced platelet aggregation (SIPA), sCD40L, and mean platelet volume; and the platelet polymorphisms studied included PIA, α2 807, Ko, Kozak, and VNTR. Univariate analysis found fibrinogen, VWF, SIPA, and PIA to be independent risk factors of CAD. Logistic regression was used to build a predictive model for CAD using the platelet function and platelet polymorphism data adjusted for age, sex, race, and current smoking status. A model containing only platelet polymorphisms and their respective receptor densities, found polymorphisms within GPIbα to be associated with CAD, yielding an 86% (95% C.I. 0.97–3.55) increased risk with the presence of at least 1 polymorphism in Ko, Kozak, or VNTR. Another model included both platelet function and platelet polymorphism data. Fibrinogen, the receptor density of GPIbα, and the polymorphism in GPIa-IIa (α2 807) were all associated with CAD with odds ratios of 1.10, 1.04, and 2.30 for fibrinogen (10mg/dl increase), GPIbα receptors (1 MFI increase), and GPIa-IIa, respectively. In addition, risk estimates and 99% confidence intervals adjusted for race were calculated to determine if the presence of a platelet receptor polymorphism was associated with CAD. The results were as follows: PIA (1.64, 0.74–3.65); α2 807 (1.35, 0.77–2.37); Ko (1.71, 0.70–4.16); Kozak (1.17, 0.54–2.52); and VNTR (1.24, 0.52–2.91). Although not statistically significant, all platelet polymorphisms were associated with an increased risk for CAD. These exploratory findings indicate that platelets do appear to have a role in atherosclerosis and that anti-platelet drugs targeting GPI-IIa and GPIbα may be better treatment candidates for individuals with CAD. ^

Prospective gated 64 slice computed tomography in assessment of coronary artery disease: A single center experience and relationship of body mass index to outcomes

Coronary artery disease (CAD) is the most common cause of morbidity and mortality in the United States. While Coronary Angiography (CA) is the gold standard test to investigate coronary artery disease, Prospective gated-64 Slice Computed Tomography (Prosp-64CT) is a new non-invasive technology that uses the 64Slice computed tomography (64CT) with electrocardiographic gating to investigate coronary artery disease. The aim of the current study was to investigate the role of Body Mass Index (BMI) as a factor affecting occurrence of CA after a Prosp-64CT, as well as the quality of the Prosp-64CT. Demographic and clinical characteristics of the study population were described. A secondary analysis of data on patients who underwent a Prosp-64CT for evaluation of coronary artery disease was performed. Seventy seven patients who underwent Prosp-64CT for evaluation for coronary artery disease were included. Fifteen patients were excluded because they had missing data regarding BMI, quality of the Prosp-64CT or CA. Thus, a total of 62 patients were included in the final analysis. The mean age was 56.2 years. The mean BMI was 31.3 kg/m 2. Eight (13%) patients underwent a CA within one month of Prosp-64CT. Eight (13%) patients had a poor quality Prosp-64CT. There was significant association of higher BMI as a factor for occurrence of CA post Prosp-64CT (P<0.05). There was a trend, but no statistical significance was observed for the association of being obese and occurrence of CA (P=0.06). BMI, as well as obesity, were not found to be significantly associated with poor quality of Prosp-64CT (P=0.19 and P=0.76, respectively). In conclusion, BMI was significantly associated with occurrence of CA within one month of Prosp-64CT. Thus, in patients with a higher BMI, diagnostic investigation with both tests could be avoided; rather, only a CA could be performed. However, the relationship of BMI to quality of Prosp-64CT needs to be further investigated since the sample size of the current study was small.^

A case-comparison study of weight fluctuations during young adulthood and coronary artery disease during middle age

The hypothesis that large fluctuations in weight during young adulthood are associated with the degree of coronary artery disease was investigated by comparing patterns of weight change of patients with angiographically defined diseased or normal arteries. Participants (n = 823) were selected from men and women aged 40-74 years who had undergone angiography at North Carolina Baptist Hospital during 1987-88. Weight history from age 20 to 40 was assessed with a mailed questionnaire. Per cent prevalence of "yo-yo dieting" adjusted for age, race, and coronary disease risk factors in patients who had 0, 1, 2, 3, or more than 3 diseased arteries was 8.6, 8.8, 3.7, 5.6 and 7.1 per cent respectively (p = 0.313). These results do not support the research hypothesis. However, since the results may have been confound by neuroticism, they should not be interpreted as strong evidence against this hypothesis. ^

The role of serotonin in depression and clotting in the coronary artery disease population

Background: The mechanisms underlying the relationship between depression and acute coronary syndrome (ACS) remain unclear. Platelet serotonin has been associated with both depression and coronary artery disease in stable outpatients. Understanding the association between depression and platelet serotonin, during ACS, may explain some of the acute cardiovascular events seen in some individuals with depression. ^ Objectives: This study was designed to evaluate whether levels of platelet serotonin, during ACS, differ between individuals who screen positive for depression and individuals who screen negative for depression and to determine if a dose-response relationship exists between depressive symptoms and platelet serotonin levels. ^ Methods: In this cross-sectional study, data was collected on 51 patients hospitalized for ACS. Multiple linear regression models were used to determine if a relationship exists between depression and platelet serotonin levels. ^ Results: Of the 51 ACS patients, 24 screened positive for depression and 27 screened negative for depression. Platelet serotonin levels were not significantly different between the depressed group (942.10 ± 461.3) and the non-depressed group (1192.41 ± 764.3) (p= .293 and β= -4.093) and a dose-response relationship between depressive symptoms and platelet serotonin levels was not found (p= .250 and β= -.254). ^ Discussion: In this study, a relationship between depression and platelet serotonin levels was not found. Future research should focus on gaining a better understanding of the variables that may influence platelet serotonin levels in the ACS population. ^