Epidemiology of Acute Lung Injury and Acute Respiratory Distress Syndrome in children in Vietnam

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are life- threatening disorders that can result from many severe conditions and diseases. Since the American European Consensus Conference established the internationally accepted definition of ALI and ARDS, the epidemiology of pediatric ALI/ARDS has been described in some developed countries. In the developing world, however, there are very few data available regarding the burden, etiologies, management, outcome, and factors associated with outcomes of ALI/ARDS in children. ^ Therefore, we conducted this observational, clinical study to estimate the prevalence and case mortality rate of ALI/ARDS among a cohort of patients admitted to the pediatric intensive care unit (PICU) of the National Hospital of Pediatrics in Hanoi, the largest children's hospital in Vietnam. Etiologies and predisposing factors, and management strategies for pediatric ALI/ARDS were described. In addition, we determined the prevalence of HIV infection among children with ALI/ARDS in Vietnam. We also identified the causes of mortality and predictors of mortality and prolonged mechanical ventilation of children with ALI/ARDS. ^ A total of 1,051 patients consecutively admitted to the pediatric intensive care unit from January 2011 to January 2012 were screened daily for development of ALI/ARDS using the American-European Consensus Conference Guidelines. All identified patients with ALI/ARDS were followed until hospital discharge or death in the hospital. Patients' demographic and clinical data were collected. Multivariable logistic regression models were developed to identify independent predictors of mortality and other adverse outcome of ALI/ARDS. ^ Prevalence of ALI and ARDS was 9.6% (95% confidence interval, 7.8% to 11.4%) and 8.8% (95% confidence interval, 7.0% to 10.5%) of total PICU admissions, respectively. Infectious pneumonia and sepsis were the most common causes of ALI/ARDS accounting for 60.4% and 26.7% of cases, respectively. Prevalence of HIV infection among children with ALI/ARDS was 3.0%. The case fatality rate of ALI/ARDS was 63.4% (95% confidence interval, 53.8% to 72.9%). Multiple organ failure and refractory hypoxemia were the main causes of death. Independent predictors of mortality and prolonged mechanical ventilation were male gender, duration of intensive care stay prior to ALI/ARDS diagnosis, level of oxygenation defect measured by PaO2/FiO2 ratio at ALI/ARDS diagnosis, presence of non-pulmonary organ dysfunction at day one and day three after ALI/ARDS diagnosis, and presence of hospital acquired infection. ^ The results of this study demonstrated that ALI/ARDS was a common and severe condition in children in Vietnam. The level of both pulmonary and non-pulmonary organ damage influenced survival of patients with ALI/ARDS. Strategies for preventing ALI/ARDS and for clinical management of the disease are necessary to reduce the associated risks.^

THE MOLECULAR INTERACTION BETWEEN TYPE II DIABETES AND ALZHEIMER’S DISEASE THROUGH CROSS-SEEDING OF PROTEIN MISFOLDING

With the population of the world aging, the prominence of diseases such as Type II Diabetes (T2D) and Alzheimer’s disease (AD) are on the rise. In addition, patients with T2D have an increased risk of developing AD compared to age-matched individuals, and the number of AD patients with T2D is higher than among aged-matched non-AD patients. AD is a chronic and progressive dementia characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), neuronal loss, brain inflammation, and cognitive impairment. T2D involves the dysfunctional use of pancreatic insulin by the body resulting in insulin resistance, hyperglycemia, hyperinsulinemia, pancreatic beta cell (β-cell) death, and other complications. T2D and AD are considered protein misfolding disorders (PMDs). PMDs are characterized by the presence of misfolded protein aggregates, such as in T2D pancreas (islet amyloid polypeptide - IAPP) and in AD brain (amyloid– Aβ) of affected individuals. The misfolding and accumulation of these proteins follows a seeding-nucleation model where misfolded soluble oligomers act as nuclei to propagate misfolding by recruiting other native proteins. Cross-seeding occurs when oligomers composed by one protein seed the aggregation of a different protein. Our hypothesis is that the pathological interactions between T2D and AD may in part occur through cross-seeding of protein misfolding. To test this hypothesis, we examined how each respective aggregate (Aβ or IAPP) affects the disparate disease pathology through in vitro and in vivo studies. Assaying Aβ aggregates influence on T2D pathology, IAPP+/+/APPSwe+/- double transgenic (DTg) mice exhibited exacerbated T2D-like pathology as seen in elevated hyperglycemia compared to controls; in addition, IAPP levels in the pancreas are highest compared to controls. Moreover, IAPP+/+/APPSwe+/- animals demonstrate abundant plaque formation and greater plaque density in cortical and hippocampal areas in comparison to controls. Indeed, IAPP+/+/APPSwe+/- exhibit a colocalization of both misfolded proteins in cerebral plaques suggesting IAPP may directly interact with Aβ and aggravate AD pathology. In conclusion, these studies suggest that cross-seeding between IAPP and Aβ may occur, and that these protein aggregates exacerbate and accelerate disease pathology, respectively. Further mechanistic studies are necessary to determine how these two proteins interact and aggravate both pancreatic and brain pathologies.

Osteopontin (OPN) and neoplastic disease: Circulating levels and tissue distribution

OPN is a secreted phosphate containing protein which is expressed by osteoblasts and a variety of other cells in vivo. Data from in vitro studies has accumulated which relates OPN to cellular transformation. We hypothesize that OPN expression is associated with neoplastic disease in humans as suggested by cell culture models. The overall objective of the current study was to determine the tissue distribution of OPN in human malignancy and to determine whether or not a correlation exists between OPN serum levels and malignancy. At the inception of this project, no study had been made demonstrating the relevance of OPN expression with naturally occurring neoplastic disease in humans. To date, few studies have reported OPN distribution in human neoplasia and are limited by either the number of specimens analyzed or the technique used in analysis. In this dissertation study, OPN was purified from human milk and $\alpha$-OPN antiserum developed and characterized. Following antibody development, the distribution and prevalence of OPN in human oral squamous cell carcinoma and human prostate carcinoma was evaluated using immunohistochemical localization. OPN immunolocalization was found in a high percentage of oral epithelial dysplasia and oral squamous cell carcinoma in humans. One oral squamous cell carcinoma cells line, UMSCC-1, was found to express OPN mRNA using Northern blotting. OPN localized to a high percentage of primary prostate adenocarcinomas. OPN localized to 52% of androgen dependent cases and 100% of androgen independent cases. Androgen dependent cell lines such as LNCap and NbE showed minimal OPN mRNA expression while the androgen independent lines C4-2 and PC3 produced ample OPN mRNA. An OPN sandwich assay was developed and used to determine the serum level of OPN in normal males, patients with BPH (benign prostate hypertrophy), and patients with prostate carcinoma. No statistically significant difference was found in OPN serum levels among the three groups. However, a trend of increasing OPN in the serum was noted in patients with BPH and prostate cancer. ^

Clinical, microbiological, and immunological markers of gingival and periodontal disease induction and progression

The potential impact of periodontal disease, a suspected risk factor for systemic diseases, presents challenges for health promotion and disease prevention strategies. This study examined clinical, microbiological, and immunological factors in a disease model to identify potential biomarkers that may be useful in predicting the onset and severity of both inflammatory and destructive periodontal disease. This project used an historical cohort design based on data obtained from 47 adult, female nonhuman primates followed over a 6-year period for 5 unique projects where the ligature-induced model of periodontitis was utilized. Standardization of protocols for sample collection allowed for comparison over time. Bleeding and pocket depth measures were selected as the dependent variables of relevance to humans based upon the literature and historical observations. Exposure variables included supragingival plaque, attachment level, total bacteria, black-pigmented bacteria, Gram-negative and Gram-positive bacteria, total IgG and IgA in crevicular fluid, specific IgG antibody in both crevicular fluid and serum, and IgG antibody to four select pathogenic microorganisms. Three approaches were used to analyze the data from this study. The first approach tested for differences in the means of the response variables within the group and among longitudinal observations within the group at each time point. The second approach examined the relationship among the clinical, microbiological, and immunological variables using correlation coefficients and stratified analyses. Multivariable models using GEE for repeated measures were produced as a predictive description of the induction and progression of gingivitis and periodontal disease. The multivariable models for bleeding (gingivitis) include supragingival plaque, total bacteria and total IgG while the second also contains supragingival plaque, Gram-positive bacteria, and total IgG. Two multivariable models emerged for periodontal disease. One multivariable model contains plaque, total bacteria, total IgG and attachment level. The second model includes black-pigmented bacteria, total bacteria, antibody to Campylobacter rectus, and attachment level. Utilization of the nonhuman primate model to prospectively examine causal hypotheses can provide a focus for human research on the mechanisms of progression from health to gingivitis to periodontitis. Ultimately, causal theories can guide strategies to prevent disease initiation and reduce disease severity. ^

The roles of costimulatory molecules in the cooperative effects of combination epinephrine and dexamethasone on type-1/type-2 cytokine production in tetanus-toxoid specific stimulated human peripheral blood mononuclear cells

A growing number of studies show strong associations between stress and altered immune function. In vivo studies of chronic and acute stress have demonstrated that cognitive stressors are strongly correlated with high circulating levels of catecholamines (CT) and corticosteroids (CS) that are associated with changes in type-1/type-2 cytokine expression. Although individual pharmacologic doses of CS and CT can inhibit the expression of T-helper 1 (Th1, type-1 like) and promote the production of T-helper 2 (Th2, type-2 like) cytokines in antigen-specific and mitogen stimulated human leukocyte cultures in vitro, little attention has been focused on the effects of combination physiologic-stress doses of CT and CS that may be more physiologically relevant. In addition, both in-vivo and in-vitro studies suggest that the differential expression of the B7 family of costimulatory molecules CD80 and CD86 may promote the expression of type-1 or type-2 cytokines, respectively. Furthermore, corticosteroids can influence the expression of β2-adrenergic receptors in various human tissues. We therefore investigated the combined effects of physiologic-stress doses of in vitro CT and CS upon the type-1/type-2 cytokine balance and expression of B7 costimulatory molecules of human peripheral blood mononuclear cells (PBMC) as a model to study the immunomodulatory effects of physiologic stress. Results demonstrated a significant decrease in type-1 cytokine expression and a significant increase in type-2 cytokine production in our CS+CT incubated cultures when compared to either CT or CS agents alone. In addition, we demonstrated the differential expression of CD80/CD86 in favor of CD86 at the cellular and population level as determined by flow cytometry in lipopolysaccharide stimulated human Monocytes. Furthermore, we developed flow cytometry based assays to detect total β2AR in human CD4+ T-lymphocytes that demonstrated decreased expression of β2AR in mitogen stimulated CD4+ T-lymphocytes in the presence of physiologic stress levels of CS and CT as single in vitro agents, however, when both CS and CT were combined, significantly higher expression of β2AR was observed. In summary, our in vitro data suggest that both CS and CT work cooperatively to shift immunity towards type-2 responses. ^

Impact of oral contraceptives on weight, body composition, and cardiovascular disease risk factors in women age 18--30 years participating in a 15-week exercise program

Objective. To assess differences in body weight, body composition, total cholesterol, blood pressure, and blood glucose between OC users and non-users age 18-30 y before and after a 15-week cardiovascular exercise program in Houston, TX from 2003 to 2007.^ Study Design. Secondary analysis of prospective data. ^ Study Subjects. 453 Non-Hispanic white (NHW), Hispanic, and African American (AA) women age 18-30 y with no previous live birth, a history of menstruating, no use of other hormonal contraceptives or medications, no menopause or hysterectomy, and no current pregnancies.^ Measurements. Demographic data, medication use, and menstrual history were assessed via self-administered questionnaires at baseline. Anthropometric and laboratory measures were taken at baseline and 15-weeks. ^ Data Analysis. Linear regression assessed the association between OC use and study variables at baseline, and the change in study variables from baseline to 15-weeks. Logistic regression assessed the association between OC use and CVD risk. Each analysis was also stratified by race/ethnicity. ^ Results. At baseline, OC users had higher total cholesterol (p<.0005) and were above cholesterol risk cut points for CVD (OR=4.3, 95% CI=2.4-7.7) compared to non-users. At baseline, OC use was also associated with higher diastolic blood pressure (p=.018) compared to non-users, primarily in non-Hispanic whites (p=.007). OC use was associated with lower blood glucose compared to non-users in Hispanics only (p=.008). OC use was associated with absolute change in diastolic blood pressure (p=.044) and total cholesterol (p=.003). There was evidence that OC use may affect individuals differently based on race/ethnicity for certain obesity and CVD risk factors.^ Conclusions. OC users and non-users responded similarly to a 15-week cardiovascular exercise program. Exceptions included a greater change in diastolic blood pressure and total cholesterol among NHW and Hispanic OC users compared to non-users after exercise intervention. At baseline, OC use was associated with diastolic blood pressure and was most strongly associated with increased levels of total cholesterol. OC users were at greater risk of having total cholesterol above CVD risk cut points than non-users.^

Trends in anti-tuberculosis drug resistance from 2003--2007 at Pham Ngoc Thach tuberculosis and lung disease hospital, Ho Chi Minh City, Vietnam

Vietnam is one of the countries with the highest prevalence and incidence of tuberculosis (TB) in the world (1). Although Vietnam has had many successes in TB control, it still faces the challenge of drug resistant and multidrug-resistant tuberculosis (MDR-TB). MDR-TB appears to be relatively stable, but data on MDR-TB continues to be scarce and routine testing of all isolates for drug susceptibility is not performed under Vietnam's National Tuberculosis Program (6). Pham Ngoc Thach Hospital (PNT), the leading tuberculosis and lung disease hospital in Ho Chi Minh City, serves as a reference hospital and laboratory for both Ho Chi Minh City and the Southern Vietnam region. This study is an unmatched, nested case-control study consisting of a secondary analysis of a previously created dataset composed of drug susceptibility and basic demographic data from a cohort of patients diagnosed with tuberculosis at PNT from 2003 through 2007 in order to calculate the prevalence of resistance among acid-fast bacilli smear-positive patients. The susceptibility records for the years 2003-2004 were not representative of the entire population, but over the years 2005-2007 the investigator found a decrease in resistance to all primary TB drugs on which records were available, as well as MDR-TB. Overall, females showed a higher proportion of resistance to TB drugs than males, and females had a greater likelihood of presenting with MDR-TB than males (OR=1.77). Persons 35-54 had greater likelihood of having MDR-TB than younger and older age groups. Among the population with HIV data, HIV-positivity was associated with greater likelihood of MDR-TB (OR=1.70, 95% CI=0.97-3.11). This study shows that rates of TB drug resistance are high, but declining, in one of Vietnam's largest TB hospitals, and that females and HIV-positive individuals are possible high-risk groups in this population.^

The relationship of obesity and cardiovascular disease

Aim. To review published literature on the relationship of obesity and cardiovascular disease.^ Methods. To look at all the studies published on the topic from 2005.^ Results. In the studies done prior to 2011, body mass index and in particular waist to hip ratio (51.57) was found to be associated with coronary heart disease. But, this relationship was challenged by the latest Lancet 2011meta-analysis 1 which concluded that singly or in combination, body-mass index, waist circumference, and waist-to-hip ratio did not importantly improve prediction of first-onset cardiovascular disease when additional information exists on blood pressure, history of diabetes, and cholesterol measures were available. Furthermore, they also found long-term reproducibility of BMI to be superior to that of waist-to-hip ratio (or waist circumference). Interestingly, body mass index in later childhood and early adult life showed positive association with coronary heart disease later in life 2. In US female health professionals 3 increasing body mass index was found to be associated with increased coronary heart disease risk. Overall 4, physical activity was found to be independently associated with fewer risk factors, less coronary artery disease, and fewer adverse events in women. Finally, obesity was found to be associated with increased overall cardiovascular mortality and coronary heart disease mortality 5.^ Conclusions. There is insufficient data to draw guidelines regarding parameters of obesity affecting cardiovascular disease. But there is data to support that lower body mass index would lead to decreased cardiovascular disease mortality. And physical activity has a direct association with less coronary artery disease in women.^

Temporal variations of dyspnea, fatigue, and lung function in chronic lung disease

Background. Research investigating symptom management in patients with chronic obstructive pulmonary disease (COPD) largely has been undertaken assuming the homeostatic construct, without regard to potential roles of circadian rhythms. Temporal relations among dyspnea, fatigue, peak expiratory flow rate (PEFR) and objective measures of activity/rest have not been reported in COPD. ^ Objectives. The specific aims of this study were to (1) explore the 24-hour patterns of dyspnea, fatigue, and PEFR in subjects with COPD; (2) examine the relations among dyspnea, fatigue, and PEFR in COPD; and (3) examine the relations among objective measures of activity/rest and dyspnea, fatigue, and PEFR in COPD. ^ Methods. The repeated-measures design involved 10 subjects with COPD who self-assessed dyspnea and fatigue by 100 mm visual analog scales, and PEFR by peak flow meter in their home 5 times a day for 8 days. Activity/rest was measured by wrist actigraphy. Single and population mean cosinor analyses and correlations were computed for dyspnea, fatigue, and PEFR; correlations were done among these variables and activity/rest. ^ Results. Circadian rhythms were documented by single cosinor analysis in 40% of the subjects for dyspnea, 60% for fatigue, and 60% for PEFR. The population cosinor analysis of PEFR yielded a significant rhythm (p < .05). The 8-day 24-hour means of dyspnea and fatigue was moderately correlated (r = .48, p < .01). Dyspnea and PEFR, and fatigue and PEFR, were weakly correlated in a negative way (r = −.11, p < .05 and r = −.15, p < .01 respectively). Weak to moderate correlations (r = .12–.34, p < .05) were demonstrated between PEFR and mean activity level measured up to 4 hours before PEFR measurement. ^ Conclusions. The findings suggest that (1) the dyspnea and fatigue experienced by COPD patients are moderately related, (2) there is a weak to modest positive relation between PEFR and activity levels, and (3) temporal variation in lung function may not affect the dyspnea and fatigue experienced by patients with COPD. Further research, examining the relations among dyspnea, fatigue, PEFR, and activity/rest is needed. Replication of this study is suggested with a larger sample size. ^

THE ROLE OF A2B ADENOSINE RECEPTOR SIGNALING IN ADENOSINE DEPENDENT LUNG DISEASE

Chronic lung diseases and acute lung injuries are two distinctive pulmonary disorders that result in significant morbidity and mortality. Adenosine is a signaling nucleoside generated in response to injury and can serve both protective and destructive functions in tissues and cells through interaction with four G-protein coupled adenosine receptors: A1R, A2AR, A2BR, and A3R. However, the relationship between these factors is poorly understood. Recent findings suggest the A2BR has been implicated in the regulation of both chronic lung disease and acute lung injury. The work presented in this dissertation utilized the adenosine deaminase-deficient mouse model and the bleomycin-induced pulmonary injury model to determine the distinctive roles of the A2BR at different stages of the disease. Results demonstrate that the A2BR plays a protective role in attenuating vascular leakage in acute lung injuries and a detrimental role at chronic stages of the disease. In addition, tissues from patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were utilized to examine adenosine metabolism and signaling in chronic lung diseases. Results demonstrate that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of these patients. Furthermore, this study provides the first evidence that A2BR signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders. Taken together, these findings suggest that the A2BR may have a bi-phasic effect at different stages of lung disease. It is protective in acute injury, whereas pro-inflammatory and pro-fibrotic at the chronic stage. Patients with acute lung injury or chronic lung disease may both benefit from adenosine and A2BR-based therapeutics.

Osteopontin and cadherin 11 are novel mediators and drug targets for chronic lung diseases

Chronic lung diseases (CLDs) are a considerable source of morbidity and mortality and are thought to arise from dysregulation of normal wound healing processes. An aggressive, feature of many CLDs is pulmonary fibrosis (PF) and is characterized by excess deposition of extracellular matrix (ECM) proteins from myofibroblasts in airways. However, factors regulating myofibroblast biology are incompletely understood. Proteins in the cadherin family contribute epithelial to mesenchymal transition (EMT), a suggested source of myofibroblasts. Cadherin 11 (CDH11) contributes to developmental and pathologic processes that parallel those seen in PF and EMT. Utilizing Cdh11 knockout (Cdh11 -/-) mice, the goal of this study was to characterize the contribution of CDH11 in the bleomycin model of PF and assess the feasibility of treating established PF. We demonstrate CDH11 in macrophages and airway epithelial cells undergoing EMT in lungs of mice given bleomycin and patients with PF. Endpoints consistent with PF including ECM production and myofibroblast formation are reduced in CDH11-targeted mice given bleomycin. Findings suggesting mechanisms of CDH11-dependent fibrosis include the regulation of the profibrotic mediator TGF-â in alveolar macrophages and CDH11-mediated EMT. The results of this study propose CDH11 as a novel drug target for PF. In addition, another CLD, chronic obstructive pulmonary disease (COPD), is characterized by airway inflammation and destruction. Adenosine, a nucleoside signaling molecule generated in response to cell stress is upregulated in patients with COPD and is suggested to contribute to its pathogenesis. An established model of adenosine-mediated lung injury exhibiting features of COPD is the Ada -/- mouse. Previous studies in our lab suggest features of the Ada -/- phenotype may be secondary to adenosine-dependent expression of osteopontin (OPN). OPN is a protein implicated in a variety of human pathology, but its role in COPD has not been examined. To address this, Ada/Opn -/- mice were generated and endpoints consistent with COPD were examined in parallel with Ada -/- mice. Results demonstrate OPN-mediated pulmonary neutrophilia and airway destruction in Ada -/- mice. Furthermore, patients with COPD exhibit increased OPN in airways which correlate with clinical airway obstruction. These results suggest OPN represents a novel biomarker or therapeutic target for the management of patients with COPD. The importance of findings in this thesis is highlighted by the fact that no pharmacologic interventions have been shown to interfere with disease progression or improve survival rates in patients with COPD or PF.

Occupational beryllium exposure: Reconciling federal policies, regulations and contractor implementation guides to protect worker health

Beryllium is a widely distributed, highly toxic metal. When beryllium particulates enter the body, the body's defense mechanisms are engaged. When the body's defenses cannot easily remove the particulates, then a damage and repair cycle is initiated. This cycle produces chronic beryllium disease (CBD), a progressive, fibrotic respiratory involvement which eventually suffocates exposed individuals. ^ Beryllium disease is an occupational disease, and as such it can be prevented by limiting exposures. In the 1940s journalists reported beryllium deaths at Atomic Energy Commission (AEC) facilities, the Department of Energy's (DOE) predecessor organization. These reports energized public pressure for exposure limits, and in 1949 AEC implemented a 2 μg/m3 permissible exposure limit (PEL). ^ The limits appeared to stop acute disease. In contrast, CBD has a long latency period between exposure and diagnosable disease, between one and thirty years. The lack of immediate adverse health consequences masked the seriousness of chronic disease and pragmatically removed CBD from AEC/DOE's political concern. ^ Presently the PEL for beryllium at DOE sites remains at 2 μg/m 3. This limit does not prevent CBD. This conclusion has long been known, although denied until recently. In 1999 DOE acknowledged the limit's ineffectiveness in its federal regulation governing beryllium exposure, 10 CFR 850. ^ Despite this admission, the PEL has not been reduced. The beryllium manufacturer and AEC/DOE have a history of exerting efforts to maintain and protect the status quo. Primary amongst these efforts has been creation and promotion of disinformation within peer reviewed health literature which discusses beryllium, exposures, health effects and treatment, and targeting graduate school students so that their perspective is shaped early. ^ Once indoctrinated with incorrect information, professionals tend to overlook aerosol and respiratory mechanics, immunologic and carcinogenic factors. They then apply tools and perspectives derived from the beryllium manufacturer and DOE's propaganda. Conclusions drawn are incorrect. The result is: health research and associated policy is conducted with incorrect premises. Effective disease management practices are not implemented. ^ Public health protection requires recognition of the disinformation and its implications. When disinformation is identified, then effective health policies and practices can be developed and implemented. ^

The effect of chronic arthritis and hypertension on general well-being

The purpose of the investigation is to elucidate the effect of chronic symptomatic and asymptomatic disease, i.e. arthritis and hypertension, on general well-being, and to quantify the contribution that the duration of the disorder makes to this effect. The data is drawn from the National Health and Nutrition Examination Survey (NHANES I). The results show that arthritics do not have a significant effect on GWB scores while hypertension has a significantly negative impact on GWB. The most striking difference is seen between those without knowledge of hypertension and those recently diagnosed. This difference is attributed to the labeling effect on changes in perceived wellness. ^

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. ^