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Biomedical subjects

Sanjay Rajagopalan

Publications and source records attributed to Sanjay Rajagopalan.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral arterial disease in patients with end-stage renal disease: observations from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Patients with end-stage renal disease are at high risk for cardiovascular morbidity and mortality. The aims of the present study were to describe the prevalence of peripheral arterial disease (PAD) and its effects on prognosis and health-related quality of life (HRQOL) in an international cohort of patients on hemodialysis. METHODS AND RESULTS: Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, international, observational study of hemodialysis patients (n=29,873), were analyzed. Associations between baseline clinical variables and PAD were evaluated by logistic regression analysis. Cox regression models were used to test the association between PAD and risk for all-cause mortality, cardiac mortality, and hospitalization. PAD was diagnosed in 7411 patients (25.3%) with significant geographic variation. Traditional cardiovascular risk factors including age, male sex, diabetes, hypertension, and smoking were identified, together with the duration of hemodialysis, as significant correlates of PAD. Diagnosis of PAD was associated with increased all-cause mortality (hazard ratio [HR]=1.36; P<0.0001), cardiac mortality (HR=1.43; P<0.0001), all-cause hospitalization (HR=1.19; P<0.0001), and hospitalization for a major adverse cardiovascular event (HR=2.05; P<0.0001). HRQOL questionnaires revealed physical health scores that were significantly lower in PAD compared with non-PAD patients (P<0.0001). CONCLUSIONS: PAD is common in hemodialysis patients and is associated with increased risk of cardiovascular mortality, morbidity, and hospitalization and reduced HRQOL.

Aged↗
PubMed2006

Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study).

Although the determinants of cardiovascular calcium have been well described in dialysis patients, the prevalence and predictors in predialysis chronic kidney disease (CKD) are less known. One hundred six patients with CKD from the Renal Research Institute-CKD Study underwent multidetector computed tomography for the assessment of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve. Cardiovascular risk factors and renal function-related parameters (glomerular filtration rate, glomerular filtration rate slope, serum creatinine, serum urea nitrogen, hemoglobin, albumin, calcium, phosphate, and parathyroid hormone) were included in multivariate regression models to predict cardiovascular calcium. Prevalences of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve were 69%, 46%, 39%, and 16%, respectively. On multivariate analysis, coronary artery calcium score was predicted by age (p < 0.0001), gender (p = 0.0001), diabetes (p = 0.024), and history of coronary artery disease (p = 0.016), but not by renal function related parameters. Similarly, renal function related parameters were not predictive of aortic or valvular calcium. In conclusion, predialysis CKD is associated with a high prevalence of cardiovascular calcium. The extent of cardiovascular calcium in patients with predialysis CKD is related to some of the traditional risk factors for atherosclerosis but not to indexes of abnormal renal function or progression in renal dysfunction.

Adult↗
PubMed2006

Detection of healed myocardial infarction with multidetector-row computed tomography and comparison with cardiac magnetic resonance delayed hyperenhancement.

Decreased myocardial attenuation on contrast-enhanced multidetector computed tomography (MDCT) images can be observed in subjects with myocardial infarctions (MIs). It was hypothesized that myocardial hypoattenuation in MDCT can accurately detect the presence of a healed MI as determined by cardiac magnetic resonance delayed hyperenhancement (CMR-DH). Coronary MDCT and CMR-DH were performed in 42 subjects. Pre- and postcontrast MDCT images were analyzed for the presence of myocardial hypoattenuation, and volumes of MIs were quantified on MDCT and CMR-DH images in a blinded manner. The sensitivity, specificity, and negative and positive predictive values of postcontrast MDCT for the detection of MI were 91%, 81%, 83%, and 90%, respectively. MI sizes by postcontrast MDCT and by CMR-DH were strongly correlated (r=0.87, p<0.0001), although MDCT systematically underestimated MI volume (2.7+/-2.5 vs 25.9+/-19.9 ml, p<0.0001). MI size by MDCT was correlated negatively with the left ventricular ejection fraction (r=-0.62, p=0.03) and positively with left ventricular volumes (r=0.68 to 0.72, p<0.01). In 71% of subjects with MIs by CMR-DH, corresponding areas of hypoattenuation were noted also in precontrast MDCT. In conclusion, healed MIs can be detected as areas of myocardial hypoattenuation on MDCT images with high diagnostic accuracy, although their sizes are largely underestimated compared with CMR-DH. The presence of precontrast hypoattenuation suggests that mechanisms independent of reduced contrast delivery contribute to this finding.

Adolescent↗
PubMed2006

The utility of magnetic resonance imaging in cardiac tissue regeneration trials.

The past decade has seen the emergence of paradigm shifts in concepts involving cardiovascular tissue regeneration, including the idea that adult stem cells originate in hematopoietic or bone marrow cells, the belief that even adult organs, such as the heart and nervous system, are capable of post-mitotic regeneration, and the concept of inherent plasticity in cells that have undergone limited lineage differentiation. There has consequently been a flurry of proposed regenerative strategies, and safety and limited efficacy data from both animal and limited human trials have been presented. The drive to push these advances from the bench to the bedside has created a unique environment where the therapeutic agents, delivery approaches, and methods of measuring efficacy (often imaging technology) are evolving practically in parallel. The encouraging results of recent cell-therapy trials should therefore be assessed cautiously and in consonance with an understanding of the advantages and limitations of delivery strategies and end points. Arguably, the use of imaging technologies to evaluate surrogate end points might help overcome the difficulty posed by large sample sizes required for hard end point trials in cardiovascular therapeutics. Cardiac magnetic resonance imaging is one of the most sensitive techniques available to assess spatial and temporal changes following local or systemic therapies, and the availability of a bevy of complementary techniques enables interrogation of physiology, morphology, and metabolism in one setting. We contend that cardiac magnetic resonance imaging is ideally suited to assess response to myocardial regeneration therapy and can be exploited to yield valuable insights into the mechanism of action of myocardial regeneration therapies.

Adenosine Triphosphate↗
PubMed2006

Technology insight: Clinical role of magnetic resonance angiography in the diagnosis and management of renal artery stenosis.

Noninvasive modalities, including duplex ultrasonography, renal scintigraphy, CT angiography and magnetic resonance angiography (MRA), may usefully contribute to diagnosis and treatment planning in patients with suspected renal artery stenosis. Important technical developments have increased the accuracy and feasibility of MRA for the detection of renal artery stenosis. A number of different MRA techniques can be applied to the study of renal arteries, but contrast-enhanced MRA represents the most valuable approach; several studies corroborate the high diagnostic accuracy of this technique, especially for the detection of atherosclerotic renal artery stenosis. A combined MRA protocol, which might include angiographic information provided by contrast-enhanced technique in addition to renal flow information derived from phase-contrast imaging, could help in classifying patients appropriately. Limitations of renal MRA include low accuracy in the evaluation of renal fibromuscular dysplasia and in the assessment of patients who undergo stenting of the renal arteries. This review describes the MRA techniques applied to the study of renal artery stenosis, including the technical features of current approaches and forthcoming developments. An overview of the clinical role of MRA, in conjunction with the other diagnostic modalities, in the identification and management of patients with renal artery stenosis, is also presented.

Algorithms↗
PubMed2006

Angiotensin receptor blockade improves vascular compliance in healthy normotensive elderly individuals: results from a randomized double-blind placebo-controlled trial.

The renin-angiotensin system (RAS) may play a role in vascular aging. The authors hypothesized that blockade of the angiotensin II type 1 receptor with an angiotensin receptor blocker in healthy elderly subjects improves vascular compliance and endothelial function. Thirty-five healthy elderly subjects were randomized to valsartan or placebo in a double-blind crossover study after baseline testing for pulse wave velocity, aortic augmentation index, and brachial artery flow-mediated dilation. Angiotensin II type 1 receptor blockade with valsartan improved vascular compliance but not flow-mediated dilation. Changes in pulse wave velocity with valsartan were correlated with change in central systolic blood pressure and pulse pressure and remained associated on multivariate analysis. Change in pulse wave velocity after adjusting for degree of blood pressure change, age, and sex remained correlated with assignment to the angiotensin receptor blocker but not placebo. These data suggest that angiotensin II type 1 receptor blockade improves aging-related vascular compliance without alterations in flow-mediated dilation. Mechanisms regulating compliance and endothelial function are complex and may not necessarily converge in aging.

Aged↗
PubMed2006

Vascular calcification in patients with chronic kidney disease.

Chronic kidney disease (CKD) represents an extremely common condition, and cardiovascular diseases are frequently reported in this patient population. Traditional risk factors are not accurate prognostic predictors in CKD patients, and new potential markers to predict the cardiovascular involvement in uremic patients need to be identified. Vascular calcification (VC) represents a hallmark of the atherosclerotic process in CKD. This review summarizes the processes responsible for VC (particularly focusing on the mechanisms operative in the presence of renal dysfunction), discusses the utility of computer tomography modalities in the detection of VC in patients with CKD, and reports the potential role of VC as pathophysiological link between kidney disease and cardiovascular events.

Atherosclerosis↗
PubMed2006

Aldosterone receptor antagonists for heart failure: current status, future indications.

Many patients with heart failure should receive an aldosterone receptor antagonist, ie, either spironolactone (Aldactone) or the newer agent eplerenone (Inspra)--in addition to an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) or both, and a beta-blocker. We review the evidence and indications.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

Air Pollutants↗
PubMed2005

Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level.

OBJECTIVES: This study sought to determine the effect of aggressive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low-density lipoprotein (LDL) concentrations. BACKGROUND: The effects of statins may well go beyond lipid lowering, and these pleiotropic effects may be of benefit in the treatment of heart failure. METHODS: Fifteen patients with NICM on standard maximized heart failure medication were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV) or matching placebo for a 12-week treatment period with a minimum of an 8-week washout period. The following surrogate markers were evaluated: N-terminal-pro brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha, circulating levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate variability. RESULTS: After ATV therapy, there was a significant decrease in LDL concentration from 110 +/- 27 mg/dl to 55 +/- 18 mg/dl (p < 0.05). There were no differences between ATV and placebo with regard to the surrogate markers measured. CONCLUSIONS: Based on these findings, it seems that the administration of high-dose statins to a heart failure population with modest LDL levels and no other indication for statin therapy was neither beneficial nor detrimental as determined by surrogate marker measures. Further studies are needed to determine whether there is an appropriate patient population and optimal dose (LDL concentration) for the treatment of systolic heart failure with statin therapy.

C-Reactive Protein↗
PubMed2005

Intrasubject variability of radial artery flow-mediated dilatation in healthy subjects and implications for use in prospective clinical trials.

Flow-mediated dilation (FMD) in the brachial artery is a widely used end point in clinical trials despite large within-subject variability and a small dynamic range. Recent studies suggest that the radial artery may be more advantageous for investigating FMD because of an enhanced vasodilator response. This study therefore assessed the validity and repeatability of radial artery FMD (FMD-R) to evaluate its suitability for the noninvasive evaluation of endothelial function. Thirty-three healthy subjects were recruited over a period of 11 months. Intra- and inter-reader reproducibilities were measured with high-resolution ultrasound at 4 time points: twice 1 morning (1 to 3 hours apart) and twice again within 7 days (range 4 to 9 days between visits). Conduit endothelial-dependent and -independent vasomotion were assessed by responses to reactive hyperemia and nitroglycerin, respectively. FMD-R measurements demonstrated significant intra- and interday variabilities (intraclass correlation coefficients [ICCs] 0.38 and 0.23, p = 0.04 and 0.12, respectively). Bland-Altman plots confirmed the test-retest variation in FMD-R. In contrast, radial artery diameter measurements (intra- and inter-reader) demonstrated a high degree of repeatability (interstudy ICC >0.8, p <0.0001). The number of subjects needed to detect a treatment difference of 2% in FMD-R with a p value of 0.05 and a power of 0.80 would be 118 in a crossover design and 234 in a parallel design for assessing group changes. In conclusion, these findings show that FMD-R is highly variable within subjects, even in a healthy population, after adjusting for multiple technical factors and implies biologic variation in radial artery tone.

Adult↗
PubMed2005

Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb.

PURPOSE: We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide-co-glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue. METHODS: C57BL/6J mice (n = 20/group) underwent unilateral hind limb ischemia surgery and were randomized to groups of no scaffold implantation (0-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 microg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and alpha-smooth muscle actin. In vitro release kinetics of VEGF from PLG was also measured. RESULTS: PLG-VEGF resulted in improved lower extremity perfusion vs. controls as measured by LDPI% at 7, 14, 21, and 28 days (p < 0.05). PLG-VEGF was associated with significantly greater percentage of vessels staining for CD31 and alpha-smooth muscle actin compared to the Empty-PLG or 0-Implant (p < 0.05 for both). CONCLUSIONS: The PLG-VEGF scaffolds resulted in sustained VEGF delivery, improved tissue perfusion, greater capillary density, and more mature vasculature compared to the controls. The sustained-release PLG polymer vehicle is a promising delivery system for therapeutic neovascularization applications.

Actins↗
PubMed2005

Variation in outcomes after percutaneous coronary intervention in the United States and predictors of periprocedural mortality.

The objective of this study was to characterize variation in mortality rates across hospitals performing percutaneous coronary intervention (PCI) in the United States. For this purpose, data (n = 735,022) from the Nationwide Inpatient Sample from 1996 to 2001 were analyzed. The primary outcome for the analysis was postprocedural in-hospital mortality. Mortality rates were calculated by race, gender, geographic region, comorbid status and hospital volume. There were significant variations in mortality across gender groups, comorbid status, regions and by hospital volume status. Independent predictors of mortality in this large cohort were older age, female gender, lower income and lower hospital volume. The data suggests targets for quality improvement initiatives for patients undergoing PCI particularly in the elderly, females, lower income patients and low volume hospitals. Even in the contemporary era of adjunctive pharmacological therapies and ubiquitous use of stents, hospital volume remains a significant independent predictor of in-hospital mortality.

Age Factors↗
PubMed2005

Development of a multicenter peripheral arterial interventional database: the PVD-QI2.

BACKGROUND: The number of peripheral vascular intervention (PVI) procedures performed is steadily increasing in the United States. PVD-QI 2 is a prospective, multicenter observational study designed to improve the quality of care for patients undergoing PVI and to better understand the effectiveness and appropriateness of PVI in improving outcomes of peripheral arterial disease. The registry aims to elucidate which comorbid conditions and procedure-related variables are associated with beneficial or adverse outcomes after vascular interventions. METHODS: Five centers are currently prospectively collecting data on consecutive PVIs performed at their institutions and will include patients with both claudication and critical limb ischemia. A common data collection form and a standard set of definitions were developed during several planning meetings. Information on patient demographics, clinical history, comorbid conditions, treatment approaches, and in hospital outcomes are being collected. Patients will be followed up at 30 days, 6 months, and 1 year after each procedure to identify recurrent vascular events, medication use, lifestyle modifications (regular exercise, dietary modification), self-reported walking scores, and mortality. Data validity will be assured through review of data form accuracy by a trained nurse, by automatic database diagnostic routines, and by site visits that include review of angiography suite logs and randomly selected charts. CONCLUSIONS: The development of a quality-controlled PVI registry requires the commitment and collaboration of clinician-investigators and hospital systems devoted to understanding factors that contribute to quality outcomes. Central to achievement of this goal is the creation of a careful diagnostic and data quality assessment system. This registry will provide important clinical insights into patient demographic and clinical characteristics, procedural characteristics, and current practice patterns that foster or impede achievement of long-term quality-based clinical outcomes for patients with peripheral arterial disease.

Databases, Factual↗
PubMed2005

Statin therapy is associated with improved cardiovascular outcomes and levels of inflammatory markers in patients with heart failure.

BACKGROUND: We wished to determine whether the addition of statins affect cardiovascular events and markers of inflammation in patients with heart failure. METHODS AND RESULTS: A total of 446 patients with heart failure and ejection fraction < or =35% were followed in a prospective, nonrandomized fashion and were classified according to treatment with a statin. We determined all-cause mortality, cardiovascular morbidity, and serum markers of inflammation over a 24-month period. Statin therapy in patients with heart failure was associated with decreased all-cause mortality at 2 years compared with those not on statin therapy (15% versus 33%, P < .005) as well as hospitalizations for heart failure (22% versus 38%, P = .001) and nonfatal myocardial infarction (11% versus 15%, P < .001). In addition, statin therapy was associated with a decrease in serum levels of C-reactive protein (1.12 +/- 0.13 versus 1.47 +/- 0.11 mg/dL, P = .001), interleukin-6 (13.3 +/- 0.8 versus 17.3 +/- 1.4 ng/dL, P = .001), and tumor necrosis factor-alpha receptor II (24.3 +/- 1.0 versus 34.5 +/- 3.0 ng/dL, P = .001). CONCLUSION: The use of statin therapy in this nonrandomized trial was associated with a significant reduction in all-cause mortality and cardiac morbidity. In addition, the improvement in levels of several serum inflammatory markers with statin therapy suggests in part possible mechanisms by which these agents may exert their benefits.

Adult↗
PubMed2005

Vascular calcification in patients with renal failure: culprit or innocent bystander?

The mortality from cardiovascular events in CKD and dialysis patients is substantially higher than in the general population. VC is ubiquitous and progresses rapidly in this patient population. Although there has been progress in the understanding of the pathogenesis and correlates of VC, much work needs to be done in this area. The role of calcium and, probably, phosphate (obligatory participants) is unquestionable, but the understanding of the paracrine and molecular determinants of VC in renal failure is continuously evolving. VC is probably a dynamic process resulting from the imbalance between molecules that promote and those that inhibit VC. The understanding of latter area has recently evolved with identification of new signaling pathways with molecules such as osteoprotegerin, fetuin-A, and MPG. From a clinical perspective, new modalities such as EBCT and MDCT allow noninvasive detection and quantification of VC. VC may represent a potential useful index for prognostic stratification and treatment planning in patients who have renal failure. At present, however, the data on the prognostic value of VC are available only in populations of patients who have normal renal function. Large-scale, prospective, observational studies should be designed to identify the determinants of VC and to define the prognostic role of calcium scoring in cohorts of patients who have predialysis CKD and with ESRD.

Atherosclerosis↗