Search

Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

Acute kidney injury (AKI) with progression to oliguric or anuric acute renal failure (ARF) is often related to use of well-known nephrotoxic agents including medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs), and certain classes of antibiotics. Hyperosmolar IV contrast is also a well-known nephrotoxic agent. Severe sepsis with subsequent hypotension, marked hyperglycemia, and those with difficulty accessing water or with poor oral intake can also present with acute kidney injury related to kidney hypoperfusion, dehydration, and volume depletion. In this case report, we discover and discuss the possible effects of regular and daily occupational exposure of jet fuel (a mixture of hydrocarbons) on renal function. Jet fuel is an underdescribed and not well-known nephrotoxic agent; however, its direct toxicity on kidney function appears to be reversible with removal of exposure and aggressive fluid hydration.

Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study objective was to determine the risk factors and relationship between large artery stiffness and carotid intimal thickness in African Americans with type II diabetes. Methods: 125 patients with diabetes were recruited from medical clinics. Medical information was obtained via interview and electronic medical record review. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Carotid Intimal Medial Thickness (CIMT) was obtained using B-mode ultrasound image analysis of the common carotid artery. Statistical analysis was done using SPSS version 23. Results: Mean age 60±8 years, 64% female. 82% hypertension, dyslipidemia 83%, diabetes duration 10.2±7.6 years, Mean HbA1C= 8.1±2.2%. Mean CIMT=0.68±0.15, PWV= 8.6±2.9. There was no significant association between PWV and CIMT. CIMT positively correlated with gender (r=0.302, p=0.001), smoking (r=0.278, p=0.002), creatinine (r=0.260, p=0.006), triglycerides (r=0.279, p=0.002), pooled cohort score (r=0.353, p=0.001), and negatively with HDL (r= -0.196, p=0.031). PWV positively correlated with creatinine (r=0.300, p=0.001), duration of diabetes (r=0.195, p=0.037) and age (β=0.359, p Conclusion: Our findings indicate that PWV and CIMT differ in risk factor profile in African Americans with type II diabetes mellitus. Further studies are needed to clarify mediating factors. Disclosure A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. A. Bakillah: None. J. Lazar: None.

Previous studies have shown that HDL isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of nitrated apolipoprotein AI (NT-apoAI). The significance of NT-apoAI in the pathogenesis of vascular diabetic complications is not well understood. We aimed to evaluate the relationship between plasma NT-apoAI and vascular function in African-Americans diabetic patients. 125 patients with type 2 diabetes were enrolled over a 6 months period. Levels of plasma NT-apoAI was quantified by enzyme-linked immunosorbent assays (ELISA). Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound image analysis. Patients population was divided in two groups (well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71). Mean age 60±8 years; 64% female; 80% had hypertension; 90% had dyslipidemia and 15% had CKD. Mean HbA1c levels were 8.1±2.2% and duration of diabetes was 10.29±3.79 years. NT-apoAI was negatively correlated with levels of apoAI and VRI in well-controlled patients but not in poorly-controlled patients (r= -0.298, p=0.025 and r= -0.265, p=0.042; respectively). Multi-regression analysis revealed that NT-apoAI was independently associated with VRI, but neither with PWV nor CIMT, after adjustment for independent variables such as age, gender, weight, hypertension, stroke, smoking, duration of diabetes, dyslipidemia, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.001, p= 0.025; r2= 0.325 for the model). NT-apoAI, independently of other clinical variables, can predict microvascular dysfunction particularly in well-controlled diabetic patients. NT-apoAI could be used as marker to identify diabetic patients at risk of developing early vascular complications. Disclosure A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.

Background: LDL plays a key role in development and progression of atherosclerosis. Elevated LDL amplifies the atherosclerotic process but the significance of modified LDL in pathogenesis of vascular complications is unclear. We aimed to assess plasma modified LDL levels and their relationship with vascular function in African American diabetic patients. Methods: 125 patients with type-2 diabetes were enrolled. Levels of glycated LDL (g-LDL), carbamylated LDL (c-LDL), nitrated LDL (n-LDL) and oxidized LDL (ox-LDL) were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assesses changes in digital temperature before and after release of arterial cuff occlusion. Carotid-femoral pulse wave velocity (PWV) assessed arterial stiffness using applanation tonometry. B-mode ultrasound image analysis assessed Carotid intima-media thickness (CIMT). Patient population was divided into well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71. Results: Age 60±8 years; 64% Female, 80% Hypertension, 90% Dyslipidemia and 15% CKD. HbA1c level 8.1±2.2%, diabetes duration 10.29±3.79 years. Mean plasma g-LDL, c-LDL, n-LDL and ox-LDL were 1.56±0.64 mg/dL, 0.85±0.11 mg/dL, 2.33±0.39 ng/mL, and 61.93±9.25 ng/mL. Ox-LDL was positively correlated with CIMT in well-controlled patients (r= 0.45, p=0.001), but not in poorly-controlled (r= 0.12, p=0.30). Multi-regression analysis revealed ox-LDL was independently associated with CIMT, but neither with PWV nor VRI after adjustment for variables such as age, gender, weight, smoking, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.003, p= 0.012; r2= 0.38). Conclusion: Ox-LDL offered better predictive value for CIMT in well-controlled patients than other forms of modified LDL. These data favor ox-LDL as potential marker to identify diabetic patients at risk of developing atherosclerotic vascular complications. Disclosure A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.

High-density lipoprotein (HDL) is cardioprotective because of its anti-atherogenic properties. Nevertheless, our goal to optimize HDL cholesterol (HDL-C) levels have had little effects on the atherothrombotic burden and suggests a closer look be taken at HDL function and dysfunction. HDL is a group of complex macromolecules composed of a lipid- and proteome that work in synergy to execute its anti-inflammatory, anti-atherogenic, and anti-thrombotic effects. However, throughout its life-span in circulation, HDL undergoes significant modification. Carbamylation, a non-enzymatic and irreversible post-translational modification of protein, is one effector of HDL which has growing evidence that it plays a crucial role in the development and progression of atherosclerotic cardiovascular disease (ASCVD), particularly in chronic kidney disease (CKD). We summarize HDL's function, susceptibility to modification, and discuss HDL carbamylation and its effect in cardiovascular disease.

Background: Patients with chronic kidney disease (CKD) have a high prevalence of sleep disorders. The association between sleep duration and self-reported CKD was examined in a population of Americans who participated in a national survey over a 3-year period. Study Design: A cross-sectional study using survey data from the National Health Interview Survey (NHIS) from the year 2004-2006 was carried out. A retrospective examination of data from a community-based survey of 128,486 noninstitutionalized US civilian residents over the age of 18 years was conducted. Self-reported CKD was defined as having ‘weak or failing kidneys'. The sleep duration was defined by a self-reported estimate of habitual sleep duration. Results: The prevalence of participants self-reporting kidney disease was higher in those with short (≤6 h per night) and long (≥8 h per night) sleep durations when compared to those sleeping 7 h per night. Self-reported information about sleep, demographic information, and information on comorbidities were assessed using standardized validated questionnaires which reported no kidney disease. A multivariate logistic regression analysis showed increased odds of self-reported kidney disease in study participants with both short and long sleep durations compared to healthy sleepers (sleeping >7-8 h per night). Observational data do not permit examination of causality, although possible confounders in observations of interest can be adjusted. Conclusion: Among Americans surveyed in the NHIS (2004-2006), those with short or long sleep duration had higher odds of reporting that they had CKD. i 2014 S. Karger AG, Basel

Human F11 receptor (F11R) is an important cell adhesion molecule implicated in inflammatory thrombosis. F11R is associated with the presence and severity of cardiovascular disease. Endothelial dysfunction in diabetes has been attributed to lack of bioavailability of nitric oxide (NO), another key

The effect of race/ethnicity on the risk of obesity associated with short or long sleep durations is largely unknown. This study assessed whether the sleep-obesity link differentially affects black and whites.Analysis was based on data obtained from 29,818 adult American respondents from the 2005 National Health Interview Survey, a cross-sectional household interview survey.Multivariate-adjusted odds ratios for obesity associated with short sleep (≤6 h) among blacks and whites were 1.98 (95% CI: 1.69-2.30) and 1.20 (95% CI: 1.10-1.31), respectively, and with long sleep (≥9 h) for blacks and whites were 1.48 (95% CI: 1.14-1.93) and 0.77 (95% CI: 0.67-0.89), respectively (all p0.001).Race/ethnicity may have significantly influenced the likelihood of reporting obesity associated with short and long sleep durations. Relative to white respondents, an excess of 78% of black respondents showed increased obesity odds associated with short sleep. Black long sleepers also showed increased odds for obesity, but white long sleepers may be at a reduced obesity risk.

Summary Background and objectives CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. Design, setting, participants, & measurements This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged $55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4–8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m2) as follows: normal/ increased ($90; n=8027), mild reduction (60–89; n=17,778), and moderate/severe reduction (,60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. Results After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P,0.001). In participants with an eGFR ,60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. ConclusionsCKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidoneinpreventingcardiovascularevents,mortality,orESRDduring9-yearfollow-up.Becausedataon proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Studies showed conflicting results for the association of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) with glycemic parameters and risk of type 2 diabetes. Whether plasma levels of PCSK9 could directly influence vascular function is still unclear. The present study aims to

Ceftazidime-avibactam (CAZ-AVI) is a novel cephalosporin beta lactamase inhibitor combination that has shown activity against carbapenem-resistant Enterobactericeae. Data are limited on its utilization in the treatment of carbapenem-resistant Klebsiella pneumoniae osteomyelitis in solid organ transplant patients. We describe a case report on the use of CAZ-AVI in the treatment of vertebral osteomyelitis in a renal transplant recipient.

Evidence from well-defined cohort studies has shown that short sleep, through sleep fragmentation caused by obstructive sleep apnea (OSA) or behavioral sleep curtailment because of lifestyle choices, is associated with increased incidence of diabetes. In this report, we review epidemiologic and clinical data suggesting that OSA is involved in the pathogenesis of altered glucose metabolism. Evidence suggesting increased risk of developing diabetes resulting from curtailed sleep duration is also considered. Proposed mechanisms explaining associations between short sleep and diabetes are examined and clinical management of OSA among patients with diabetes is discussed.

End-stage renal disease (ESRD) is a growing public health concern and non-adherence to treatment has been associated with poorer health outcomes in this population. Depression, likely to be the most common psychopathology in such patients, is associated with increased morbidity and mortality. We compared psychological measures and self-reported medication adherence of 94 kidney transplant recipients to those of 65 patients receiving hemodialysis in a major medical center in Brooklyn, New York. Compared to the transplant group, the hemodialysis cohort was significantly more depressed as determined by the Beck Depression Inventory score. They also had a significantly lower adherence to medication as reported on the Medication Therapy Adherence Scale. Using hierarchical multiple regression analysis, the variance in depression was the only statistically significant predictor of medication adherence beyond gender and mode of treatment, accounting for an additional 12% of the variance. Our study strongly suggests that a depressive affect is an important contributor to low medication adherence in patients with ESRD on hemodialysis or kidney transplant recipients.

One-third of women worrying about breast cancer report impaired ability to function daily. It is unclear whether women who worry about breast cancer would experience more sleep problems than those who do not. Data were obtained from a cross-sectional study of black and white women to investigate the association between breast cancer worry and insomnia complaints. Several questionnaires were administered during face-to-face interviews to elicit health and sociodemographic data. The present analyses focused on black and white women (n = 1,038; age range = 50-70 years) with no cancer antecedents or history. Overall, 62% of the women worried about breast cancer, and 49% reported insomnia complaints. Logistic regression analyses, adjusting for effects of age, ethnicity, family history, and perceived risk of developing breast cancer, yielded an odds ratio for insomnia complaints of 1.52 (95% CI: 1.15-2.02, p.001) among women reporting breast cancer worry. More than one half of the women worrying about breast cancer were likely to report insomnia complaints, notwithstanding the fact that those women did not have a history of cancer. Although fewer black women reported breast cancer worry and insomnia complaints, they were as affected as white women by the impact of worry on mood and daily activities.

Background and objectives: There is growing identification of the need to seriously study the psychiatric presentations of end-stage renal disease patients treated with hemodialysis. This study reports on the course of depression and anxiety diagnoses and their impact on quality of life and health status. Design, setting, participants, & measurements: The 16-mo course of psychiatric diagnoses in 50 end-stage renal disease patients treated with hemodialysis was measured by structured clinical interview. Results: Three different pathways were identified: one subset of patients not having a psychiatric diagnosis at either baseline or 16-mo follow-up (68% for depression, 51% for anxiety), one group having an intermittent course (21% for depression, 34% for anxiety), and one group having a persistent course (11% for depression, 15% for anxiety), with diagnoses at both time 1 and time 2. For depression, the people with the persistent course showed marked decreases in quality of life and self-reported health status compared with the nondepressed and intermittently depressed cohorts. The most powerful predictor of depression at time 2 is degree of depressive affect at time 1(P < 0.05). Conclusions: Patients at risk for short- and long-term complications of depression can be potentially identified by high levels of depressive affect even at a single time point. As nearly 20% of the sample had chronic depression or anxiety, identifying a psychiatric diagnosis in hemodialysis patients and then offering treatment are important because, in the absence of intervention, psychiatric disorders are likely to persist in a substantial proportion of patients.

Few minority patients with sleep apnea have been evaluated or treated. This study ascertained adherence rate to referrals for sleep apnea evaluation by primary care physicians in a community-based sample of black patients; it also examined baseline characteristics likely to influence adherence rates.A retrospective chart audit was conducted at a hospital-based sleep clinic. Scrutiny was limited to male and female patients between the ages of 20 and 80 years. Data obtained for this analysis included baseline characteristics from a detailed sleep history and/or screening questionnaires and polysomnographic parameters.Of the 421 patients referred by their private care physicians, 38% (n=160) adhered to the recommendation for a sleep consultation, but all who showed up for their appointment underwent polysomnographic studies. Logistic regression analyses showed that obesity and daytime sleepiness were the most important factors predicting adherence, with multivariate-adjusted odds ratios of 2.69 [95% CI: 1.54-4.71, p0.001] and 6.98 [95% CI: 3.86-12.64, p0.001], respectively. Of the patients who underwent a polysomnographic sleep evaluation, 91% received a sleep apnea diagnosis and were treated.Black patients may be underutilizing available sleep services, but direct comparisons with other ethnic groups could not be made because of insufficient archival data. While the present study does not identify specific barriers to accessing services for sleep problems, it indicates that blacks who are obese and/or are experiencing daytime sleepiness are likely to adhere to recommendations of their physician. Targeted culturally congruent educational interventions to increase awareness of sleep apnea in black communities might help to increase adherence rate.

Although obstructive sleep apnea and cardiovascular disease have common risk factors, epidemiologic studies show that sleep apnea increases risks for cardiovascular disease independently of individuals' demographic characteristics (i.e., age, sex, and race) or risk markers (i.e., smoking, alcohol, obesity, diabetes, dyslipidemia, atrial fibrillation, and hypertension). Individuals with severe sleep apnea are at increased risk for coronary artery disease, congestive heart failure, and stroke. The underlying mechanisms explaining associations between obstructive sleep apnea and cardiovascular disease are not entirely delineated. Several intermediary mechanisms might be involved including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress. Other abnormalities such as disorders in coagulation factors, endothelial damage, platelet activation, and increased inflammatory mediators might also play a role in the pathogenesis of cardiovascular disease. Linkage between obstructive sleep apnea and cardiovascular disease is corroborated by evidence that treatment of sleep apnea with continuous positive airway pressure reduces systolic blood pressure, improves left ventricular systolic function, and diminishes platelet activation. Several systematic studies are necessary to explicate complex associations between sleep apnea and cardiovascular disease, which may be compounded by the involvement of diseases comprising the metabolic syndrome (i.e., central obesity, hypertension, diabetes, and dyslipidemia). Large-scale, population-based studies testing causal models linking among sleep apnea, cardiovascular morbidity, and metabolic syndrome are needed. Citation: Jean-Louis G; Zizi F; Clark LT; Brown CD; McFarlane SI. Obstructive sleep apnea and cardiovascular disease: role of the metabolic syndrome and its components. J Clin Sleep Med 2008;4(3):261–272.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that disproportionately affects blacks. While clinical and epidemiologic data indicate intraethnic differences in several medical diseases, little is known about whether OSA symptoms differ within the black ethnic group. We estimated the rate of OSA symptoms in a community-based sample of Caribbean-born black men and women. We also ascertained which sociodemographic and/or medical factors were associated with OSA risk. A total of 554 patients (mean age = 48.17 +/- 16.75 years) participated in the study; 55% were women. Data were collected in four primary-care clinics in Brooklyn, NY. A health educator explained the purpose of the study to interested patients and assisted consenting participants in completing questionnaires, which required 15 min to complete. Participants reporting habitual snoring, excessive daytime sleepiness, and sleep fragmentation were considered at high OSA risk. The rate of OSA symptoms was: snoring (45%), excessive daytime sleepiness (33%), and difficulty maintaining sleep (34%). Many reported falling asleep while watching television (47%) or while driving (14%). Based on logistic regression analysis, a history of heart disease was the most important predictor of the likelihood of expressing OSA symptoms, with a corresponding multivariate-adjusted odds ratio of 11 (95% confidence interval = 3.03-40.63). Findings suggest the need to investigate whether Caribbean-born blacks are at greater risk for developing OSA than African Americans and whites. Caribbean-born blacks with a history of heart disease should be a prime target for interventions that promote adequate screening and timely OSA diagnosis.

Depression is well established as a prevalent mental health problem for people with ESRD and is associated with morbidity and mortality. However, depression in this population remains difficult to assess and is undertreated. Current estimates suggest a 20 to 30% prevalence of depression that meets diagnostic criteria in this population. The extent of other psychopathology in patients with ESRD is largely unknown. The aim of this study was to expand the research on psychiatric complications of ESRD and examine the prevalence of a broad range of psychopathology in an urban hemodialysis center and their impact on quality of life. With the use of a clinician-administered semistructured interview in this randomly selected sample of 70 predominately black patients, >70% were found to have a psychiatric diagnosis. Twenty-nine percent had a current depressive disorder: 20% had major depression, and 9% had a diagnosis of dysthymia or depression not otherwise specified. Twenty-seven percent had a current major anxiety disorder. A current substance abuse diagnosis was found in 19%, and 10% had a psychotic disorder. The mean Beck Depression Inventory score was 12.1 +/- 9.8. Only 13% reported being in current treatment by a mental health provider, and only 5% reported being prescribed psychiatric medication by their physician. A total of 7.1% had compound depression or depression coexistent with another psychiatric disorder. The construct of depression was also disentangled from the somatic effects of poor medical health by demonstrating a unique relationship between depressive affect and depression diagnosis, independent of health status. This study also suggests the utility of cognitive variables as a meaningful way of understanding the differences between patients who have ESRD with clinical depression or other diagnoses and those who have no psychiatric comorbidity. The findings of both concurrent and isolated anxiety suggest that the prevalence of psychopathology in patients with ESRD might be higher than previously expected, and the disorders may need to be treated independently. In addition, the data suggest that cognitive behavioral therapeutic techniques may be especially advantageous in this population of patients who are treated with many medications.

Background. Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations.Methods. Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively.Results. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p=0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p=0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation.Conclusions. Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease.

The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterolor = 160 andor = 300 mg/dl and triglycerides400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.

Background: Acute coronary syndrome is the leading cause of morbidity and mortality regardless of race or gender. Although multicenter trials have provided information on gender differences and racial disparities in access to healthcare and application of treatment guidelines, very few data are available that assess gender differences in clinical characteristics, treatment trajectory and the severity of coronary artery obstruction in predominantly African-descent populations. Methods: Using the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE) qualitative initiative, a retrospective chart review was conducted in 198 consecutive patients admitted to the SUNY Downstate University Hospital with the diagnosis of acute coronary syndrome from September 1 2003 to August 31 2004. Sociodemographics, clinical characteristics and treatment patterns for men and women were a...

Erythropoietin was administered to five anemic azotemic diabetic subjects for 1 year to assess the effect of increasing red cell mass on clinical well-being and the course of renal functional decline. None of the subjects manifested worsened hypertension or cerebrovascular or cardiovascular complications despite an increase in mean hematocrit from a baseline mean of 29.6% to a mean of 39.5%. The serum creatinine concentration after 1 year of treatment with erythropoietin was 3.7 mg/dL, which was unchanged from the baseline value of 3.5 mg/dL. Plasma viscosity remained constant as red cell mass increased. Although the viscosity of whole blood rose as the hematocrit increased, it was within the range of normal blood viscosity for an equivalent hematocrit. The favorable impact of erythropoietin treatment on three diabetic subjects who had macular edema and anemia is described. One hypothesis to explain the benefit of a raised hematocrit on both diabetic nephropathy and retinopathy is that the metabolic, hormonal, and hemodynamic components of the diabetic syndrome, in concert, produce tissue and cellular hypoxia that is ameliorated in part by the greater oxygen-transporting capacity of a raised red cell mass. The pseudohypoxia of diabetes may be implicated in the pathogenesis of diabetic neuropathy, retinopathy, muscular dysfunction, and nephropathy.

Background/Aims The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. Methods Participants in the ALLHAT were studied. Those randomized to doxazosin, older than 74 years, and those with a history of coronary heart disease were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by estimated glomerular filtration rate categories, and stratification by race (black vs non-black). The primary outcome was a composite of fatal coronary heart disease, nonfatal myocardial infarction, coronary revascularization, and hospitalized angina. Results There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and sex and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P = .02). In addition, net reclassification improvement was not significant for any subgroup based on race and sex, ranging from −5.5% to 4.4%. Conclusion The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.

Cardiovascular disease is the major cause of mortality in renal transplant recipients. Plasma levels of low-density lipoprotein cholesterol (LDL-C) are often elevated following renal transplantation, and the immunosuppressant cyclosporin A has been implicated as a predisposing factor for posttransplantation hyperlipidemia. Lipoprotein(a) [Lp(a)] is an LDL-like lipoprotein particle; elevated levels of Lp(a) provide an independent and significant risk factor for cardiovascular disease. Plasma concentrations of Lp(a) vary greatly among individuals, and the mechanisms that govern changes in their levels in transplant patients are unknown. The effect(s) of cyclosporin A on Lp(a) was studied in two groups of renal transplantation patients. In group I plasma lipoproteins including Lp(a) were measured before and after successful renal transplantation; this group received both prednisone and cyclosporin A for immunosuppression. Group II patients were studied after renal transplantation and received prednisone alone for immunosuppression. Following surgery, group I patients demonstrated increased plasma concentrations of LDL-C (mean +/- SEM range, 111 +/- 6 to 142 +/- 17 mg/dL; P < .005). In contrast, plasma Lp(a) levels for this group were markedly decreased after renal transplantation (median, 34.3 to 19.7 mg/dL). Patients not treated with cyclosporin A (group II) exhibited mean LDL-C and median Lp(a) levels (118 +/- 42 and 33.1 mg/dL, respectively) that were remarkably similar to those observed before renal transplantation (group I). These data confirm that hyperlipidemia following renal transplantation is associated with cyclosporin A therapy and show that this drug has opposing effects on plasma Lp(a) and LDL-C accumulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular diseases are the leading cause of death among adults in developed countries. An increase in prevalent cardiovascular risk factors (e.g., obesity, hypertension and diabetes) has led to a concerted effort to raise awareness of the need to use evidence-based strategies to help patients at risk of developing cardiovascular disease and to reduce their likelihood of suffering a stroke. Sleep apnea has emerged as an important risk factor for the development of cardiovascular disease. Epidemiologic and clinical evidence has prompted the American Heart Association to issue a scientific statement describing the need to recognize sleep apnea as an important target for therapy in reducing cardiovascular disease risks. This article examines evidence supporting associations of sleep apnea with cardiovascular disease and considers evidence suggesting cardiovascular risk reductions through sleep apnea treatment. Perspectives on emerging therapeutic approaches and promising areas of clinical and experimental research are also discussed.

Background: Anxiety and insomnia are associated with cardiovascular (CV) symptoms. We assessed whether the relation between anxiety and CV symptoms is modulated by insomnia. Methods: Independently living women (n = 1,440; mean age = 59.36 ± 6.53 years) were recruited by cluster sampling technique. We obtained data on demographic characteristics, health beliefs, access to health care, CV symptoms, sleep, stress and anxiety levels. Results: Overall, 56% of the sample reported insomnia; 46% reported CV symptoms, and 54% were highly anxious. There was a greater likelihood for highly anxious women and those experiencing insomnia to report CV symptoms (rs = 0.31* and rs = 0.32*, respectively). In logistic regression analysis, the adjusted odds ratios for reporting CV symptoms were 1.39 for patients with insomnia and 2.79 for those with anxiety. With control for insomnia, we observed a 3-fold reduction in the magnitude of the association between anxiety and CV symptoms (rp = 0.09*). Stepwise adjustments for sociodemographic factors, CV risk markers, and factors anchoring health beliefs and access to health care showed lesser impact on the relationships. With simultaneous control for those covariates, the correlation was rp = 0.13*; * p < 0.01. Conclusion: The association of CV symptoms with anxiety is partly accounted for by insomnia.

Although obstructive sleep apnea and cardiovascular disease have common risk factors, epidemiologic studies show that sleep apnea increases risks for cardiovascular disease independently of individuals' demographic characteristics (i.e., age, sex, and race) or risk markers (i.e., smoking, alcohol, obesity, diabetes, dyslipidemia, atrial fibrillation, and hypertension). Individuals with severe sleep apnea are at increased risk for coronary artery disease, congestive heart failure, and stroke. The underlying mechanisms explaining associations between obstructive sleep apnea and cardiovascular disease are not entirely delineated. Several intermediary mechanisms might be involved including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress. Other abnormalities such as disorders in coagulation factors, endothelial damage, platelet activation, and increased inflammatory mediators might also play a role in the pathogenesis of cardiovascular disease. Linkage between obstructive sleep apnea and cardiovascular disease is corroborated by evidence that treatment of sleep apnea with continuous positive airway pressure reduces systolic blood pressure, improves left ventricular systolic function, and diminishes platelet activation. Several systematic studies are necessary to explicate complex associations between sleep apnea and cardiovascular disease, which may be compounded by the involvement of diseases comprising the metabolic syndrome (i.e., central obesity, hypertension, diabetes, and dyslipidemia). Large-scale, population-based studies testing causal models linking among sleep apnea, cardiovascular morbidity, and metabolic syndrome are needed.

Epidemiologic studies have shown the importance of habitual sleep duration as an index of health and mortality risks. However, little has been done to ascertain ethnic differences in sleep duration in a national sample. This study compares sleep duration in a sample of black and white participants in the National Health Interview Survey (NHIS).Data were collected from 29,818 Americans (age range 18-85 years) who participated in the 2005 NHIS. The NHIS is a cross-sectional household interview survey that uses a multistage area probability design, thus permitting representative sampling of U.S. households. During face-to-face interviews conducted by trained interviewers from the U.S. Census Bureau, respondents provided demographic data and information about physician-diagnosed chronic conditions, estimated habitual sleep duration and functional capacity, and rated their mood.Fisher's exact test results indicated that blacks were less likely than whites to report sleeping 7 hours (23% vs. 30%; chi2 = 94, p0.0001). Blacks were more likely to experience both short sleep (or = 5 hours) (12% vs. 8%, chi2 = 44, p0.0001) and long sleep (or = 9 hours) (11% vs. 9%, chi2 = 23, p0.0001). Logistic regression analysis, adjusting for differences in sociodemographic factors, depression, functional capacity and medical illnesses, demonstrated that black ethnicity was a significant predictor of extreme sleep duration (Wald = 46, p0.0001; OR = 1.35, 95% CI: 1.24-1.47).Independent of several sociodemographic and medical factors, blacks had more prevalent short and long sleep durations, suggesting greater variation in habitual sleep time. Therefore, blacks might be at increased risks of developing medical conditions associated with short and long sleep.

A 76-year-old woman hemodialysis patient was hospitalized for community-acquired pneumonia complicating chronic obstructive pulmonary disease. End-stage renal disease secondary to hypertension had been diagnosed at the age of 64 for which the patient was initiated on maintenance hemodialysis. Then, she received a deceased donor kidney transplant at the age of 68 that succumbed to chronic rejection 4 years later when she was restarted on hemodialysis. Hemodialysis was performed via a right subclavian vein double lumen catheter for 2 months when a right brachio-axillary graft was inserted. Severe venous congestion, swelling, and nipple tenderness of her right breast noted on admission had been increasing for 6 weeks before hospital admission. No arm swelling was evident. Initial management of the patient's pneumonia and chronic obstructive pulmonary disease consisted of intravenous ceftriaxone and albuterol inhaler to which intravenous oxacillin (1 g q 6 hr) was added for presumed right mastitis. Radiological work-up for masses and malignancies was negative. An angiogram of the right upper extremity detected stenosis of the dialysis access graft at its anastomosis with the axillary vein. Angioplasty of the stenosis was performed without incident or evidence of central vein stenosis. Rapid resolution over 10 days of the unilateral breast congestion followed without complication.

Association of reduced red blood cell deformability and diabetic nephropathy.BackgroundImpaired red blood cell deformability may play a key role in the pathogenesis of chronic vascular complications of diabetes mellitus and progression of renal failure. The present study was conducted to test whether impaired red blood cell deformability is indeed associated with development of diabetic nephropathy.MethodsWe studied 57 adult type 2 diabetic patients divided into three groups according to serum creatinine concentration. Group I comprised 28 diabetic patients with normal renal function (serum creatinine concentration

Recent clinical trials have confirmed the value of intervention on major risk factors, particularly hypertension and hyperlipidemia, in preventing the progression and clinical sequelae of atherosclerosis. Less is known about the prevalence and impact of atherosclerosis risk factors in minorities. A review of recent literature reporting the prevalence of established and new predictors of atherosclerotic events in minority populations and the inclusion of minorities in clinical trials is presented. The prevalence of risk factors differs considerably in minority populations. The role of "premature" coronary death and the level of some risk factors, particularly obesity and blood pressure in African descendants and high triglycerides, low high-density lipoproteins, and diabetes in some Hispanics, is higher than in whites. With few exceptions, however, minorities have not been included in clinical trials in sufficient numbers to determine whether significant differences in the benefit of risk factor intervention exists. Prevalence of key risk factors differs among minority groups. Risk factor intervention should be pursued in minority groups but with the understanding that clinical trials have not ruled out the possibility of qualitative or quantitative differences in response rates among different groups.

Coincidental with the pandemic growth of diabetes as the prime cause of end-stage renal disease (ESRD), blindness attributable to diabetic retinopathy has become a major concern for all those involved in the care of diabetic ESRD patients. Vision loss is linked to progression of proliferative retinopathy and macular edema.Extracted from a study of azotemic anemic pre-ESRD patients treated with erythropoietin, a cohort of five diabetic subjects was reassessed in terms of stability of renal function, changes in blood rheology, and course of diabetic eye disease.All subjects reported subjective improvement in well-being, including enhanced effort tolerance following an increase in hematocrit from a baseline level of to 29.6 +/- 2.0% to a level of 39.5 +/- 2.4% after one year of treatment with erythropoietin (P =0.0005). Neither hypertension nor deterioration of renal function was noted in any subject. Three patients with macular edema evinced substantive improvement-based stable vision and documented resolution noted in flourescein angiography.Erythropoietin treatment of anemic azotemic diabetic patients is well tolerated. In a small observational retrospective study of three patients with macular edema, retention of vision and resolution of exudates was noted.

Hypertension is a serious health problem in Western society, in particular for the African-American population. Although previous studies have suggested that the angiotensinogen (AGT) gene locus is involved in human essential hypertension, the molecular mechanisms involved in hypertension in African-Americans remain unknown. We show that an A/G polymorphism at −217 in the promoter of the AGT gene plays a significant role in hypertension in African-Americans. The frequency of the −217A allele was increased significantly in African-American hypertensive subjects compared with normotensive controls. We also show that the nucleotide sequence of this region of the AGT gene promoter bound strongly to CAAT/enhancer-binding protein (C/EBP) family transcription factors when nucleoside A was present at −217. In addition, we show that reporter constructs containing the human AGT gene promoter with nucleoside A at −217 had increased basal transcriptional activity upon transient transfection in HepG2 cells compared with reporter constructs with nucleoside G at −217. Finally, we show that interleukin-6 treatment in the presence or absence of overexpressed C/EBPβ increased the promoter activities of reporter constructs containing nucleoside A at −217 compared with reporter constructs containing nucleoside G at −217. Because the AGT gene is expressed primarily in liver and adipose tissue, and C/EBP family transcription factors play an important role in gene expression in these tissues, we propose that increased transcriptional activity of the −217A allele of the human AGT gene is associated with hypertension in African-Americans.

Impaired RBC-deformability (RBC-df) is noted in diabetes and may play a role in the pathogenesis of microvasculopathy and nephropathy. We now report the effects of EPO alone and combined EPO and AG (Alteon, Ramsey, NJ) treatment for one year on RBCdf in pre-dialysis patients with renal insufficiency (PDPs) and patients with end stage renal diseases (ESRD) on maintenance hemodialysis (DPs).

Perturbation in blood rheology are thought to contribute to the genesis of progressive micro- and macrovascular complications in diabetes mellitus [1]. Specifically, hyper-viscosity of whole blood and plasma, and reduced RBC deformability (RBC-df), have been linked to the pathogenesis and progression of overt nephropathy in diabetic persons [2],[3]. In a previous study [4] we reported a highly significant correlation between RBC-df impairment and the loss of renal function in diabetic subjects.

Anemia is a common complication of acute and chronic renal failure and prior to the onset of ESRD, it is a usual clinical feature of renal insufficiency. Correction of the anemia associated with renal disease by erythropoietin (EPO) treatment, has proven to be a major contribution to the general medical care of patients with renal failure. Aside from clinically significant improvement in hematocrit, EPO treatment has resulted in significant improvement in physical working capacity, appetite, physical well-being [1], cognitive performance [2], and sexual function [3].

Lack of adherence to recommended treatment for obstructive sleep apnea remains an ongoing public health challenge. Despite evidence that continuous positive airway pressure (CPAP) is effective and improves overall quality of life, adherence with the use of CPAP in certain racial/ethnic groups, especially blacks, is suboptimal. Evidence indicates that the incidence and prevalence of obstructive sleep apnea are higher among blacks, relative to whites, and blacks are less likely to adhere to recommended treatment compared with other racial/ethnic groups. Using a two-arm randomized controlled design, this study will evaluate the effectiveness of a culturally and linguistically tailored telephone-delivered intervention to promote adherence to physician-recommended sleep apnea assessment and treatment among blacks with metabolic syndrome, versus an attention-control arm. The intervention is designed to foster adherence to recommended sleep apnea care using the stages-of-change model. The intervention will be delivered entirely over the telephone. Participants in the intervention arm will receive 10 phone calls to address challenges and barriers to recommended care. Outcomes will be assessed at baseline, and at 6- and 12-months post-randomization. This tailored behavioral intervention will improve adherence to sleep apnea assessment and treatment among blacks with metabolic syndrome. We expect to demonstrate that this intervention modality is feasible in terms of time and cost and can be replicated in populations with similar racial/ethnic backgrounds. The study is registered at clinicaltrials.gov NCT01946659 (February 2013)

Pharmocologic treatment of the hyperlipidemia associated with the nephrotic syndrome with lovastatin has been previously shown to be safe and effective. However, there is no information on the effect of lovastatin treatment on plasma lipoprotein(a) [Lp(a)] levels in patients with the nephrotic syndrome. We administered lovastatin (40 to 80 mg/day) to 20 adult patients with unremitting nephrotic syndrome for 8 weeks to assess its effect on plasma Lp(a) and other plasma lipid concentrations. Apoprotein(a) (apo(a)) phenotype was determined in all patients. Patients were grouped according to their plasma Lp(a) levels. Those with elevated plasma Lp(a) (> or = 30 mg/dL) were placed in group I and those with normal Lp(a) levels (< 30 mg/dL) were placed in group II. Mean total cholesterol and LDL cholesterol were similarly and significantly reduced in groups I and II (-35.9% and -43.3%, P < 0.0005, P < 0.0005 group I, and -31.0% and -42.0%, P < 0.02, P < 0.03 group II, respectively). The median reduction in plasma Lp(a) was -32% (P < 0.003) in nephrotic patients in group I, whereas the median decline in plasma Lp(a) levels in nephrotic patients in group II was only -8.0% (P = 0.052). The overall frequency of the high molecular weight (M(r)) apo(a) phenotype S4 was 70% in nephrotic patients. There was no correlation between plasma Lp(a) and apo(a) phenotype. Treatment with lovastatin results in a favorable response in terms of total and low-density lipoprotein cholesterol lowering in patients with the nephrotic syndrome; however, plasma Lp(a) levels are uniformly and significantly reduced only in nephrotic patients with elevated baseline plasma Lp(a) concentrations. There was no correlation between plasma Lp(a) concentration and other lipid and biochemical parameters.

Exercise training has been associated with decreases in total cholesterol and increases in high-density lipoprotein (HDL) cholesterol. The effect of the intensity of the exercise on alterations in cholesterol and lipoprotein fractions has not been defined and is the subject of this study. We divided 49 healthy men (aged 44 +/- 8 years) into four groups and evaluated them before and after 12 weeks of cycle ergometer exercise training at (1) an intensity of 65% of maximal achieved heart rate, (2) 75% maximal heart rate, (3) 85% maximal heart rate, and (4) a 12-week nonexercise control period. Pre- and post-training evaluations included maximal ergometer exercise ECG examinations with measurement of maximal minute oxygen consumption and serum total cholesterol, HDL cholesterol, and triglyceride levels. Low-density (LDL) and very low-density lipoprotein (VLDL) cholesterol levels were calculated. Dietary histories were obtained before and after the training period, and body weight and percentage of body fat were measured. Post-training oxygen uptake was significantly increased (training effect) in the groups exercising to 65%, 75%, and 85% maximal heart rate. Results of within-group analysis showed significant increases in the HDL cholesterol fractions in the 75% and 85% groups but not in the 65% group or the control group. Significant decreases in calculated LDL fractions occurred only in the 75% exercise-trained group with maximal heart rate. Aerobic exercise training favorably alters plasma lipoprotein profiles. A minimum training intensity equal to 75% maximal heart rate is required to the increase HDL cholesterol level.

Background: The prevalence of reduced glomerular filtration rate (GFR) in older hypertensive patients and the relationship between level of GFR and cardiovascular disease (CVD) and its risk factors are not well known. Methods: We evaluated baseline renal function in 40514 hypertensive patients 55 years or older who were enrolled in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). We used the simplified Modification of Diet in Renal Disease study equation to estimate GFR and examined the prevalence of CVD in patients with different levels of GFR. Results: Fifty-seven percent of patients had mild (60-89 mL/min per 1.73 m 2 ), 17.2% had moderate (30-59 mL/ min per 1.73 m 2 ), and 0.6% had severe (29 mL/min per 1.73 m 2 ) reductions in GFR. Compared with patients with normal or mildly reduced GFR, patients with moderate or severe reductions in GFR were more likely to have had a prior myocardial infarction or stroke (19.2% and 23.4% vs 28.7% and 26.9%, respectively), have ischemic changes on electrocardiography (ECG) (16.0% and 18.9% vs 24.6% and 34.1%, respectively), and have left ventricular hypertrophy on ECG (ECG-LVH) (3.9% and 4.2% vs 6.0% and 11.2%, respectively). A decrease in GFR of 10 mL/min per 1.73 m 2 was independently associated with a 6% higher risk for CVD and 14% higher risk for ECG-LVH. The increase in risk was marked at a GFR of approximately 60 to 70 mL/min per 1.73 m 2 . Conclusions: The prevalence of reduced GFR is high in older hypertensive patients. Patients with moderate or severe reduction in GFR are more likely to have a history of CVD and ECG-LVH. Even modest reductions in GFR are independently associated with a higher prevalence of CVD and ECG-LVH. Arch Intern Med. 2004;164:969-976