Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the sarcoplasmic reticulum (SR) Ca(2+)-uptake and the expression of phospholamban (PLB) and Ca(2+)-ATPase (CAA) in left ventricular (LV) and right ventricular (RV) myocardium of 6 normal (NL) dogs and 6 dogs with chronic heart failure (HF). In addition, gene expression of PLB and CAA was also examined in LV myocardium of NL and HF dogs. HF (LV ejection fraction 23+/-2%) was produced by multiple sequential intracoronary microembolizations. Oxalate-dependent Ca(2+)-uptake was measured in isolated membrane vesicles. Using specific dog myocardial monoclonal antibody, the expression of CAA, PLB and calsequestrin (CSQ) were measured in sodium dodecyl sulfate extract prepared from LV and RV tissue. Steady-state mRNA levels were determined by Northern hybridization using specific cDNA clones of PLB, CAA, CSQ, and glyceraldehyde-3-phosphate dehydrogenase (GADPH), a house keeping gene. SR Ca(2+)-uptake of NL and HF dogs increased with increasing Ca(2+)concentrations and reached a plateau at 3 microm in both LV and RV. Total capacity (134+/-9 v 224+/-10 nmol(45)Ca/mg protein/10 min, P<0.05) and maximal velocity (15+/-2 v 2 nmol(45)Ca/mg protein/min, P<0.05) of the SR to sequester Ca(2+)was significantly lower in LV myocardium of HF dogs compared to NL, whereas the Hill coefficient and the affinity of the Ca(2+)-pump for Ca(2+)were unchanged. LV tissue levels of the PLB and CAA, normalized to noncollagen protein or to CSQ and the PLB and CAA mRNA levels, normalized to CSQ or GADPH mRNA, were also significantly lower in HF dogs compared to NL. In RV myocardial tissue, no significant differences in total capacity of SR to sequester Ca(2+), maximal velocity of SR Ca(2+)-uptake, the affinity and Hill Coefficient of the Ca(2+)-pump for Ca(2+), or tissue levels of PLB and CAA were observed between NL dogs compared to HF dogs. We conclude that SR Ca(2+)-uptake and SR PLB and CAA protein and gene expression levels are reduced in LV myocardium of dogs with chronic HF. These abnormalities can lead to Ca(2+)-overload and subsequent global LV dysfunction.
 ...
PMID:Reduced sarcoplasmic reticulum Ca(2+)-uptake and expression of phospholamban in left ventricular myocardium of dogs with heart failure. 1040 55

This is a secondary analysis of data from a cross-sectional study to evaluate the diagnostic efficiency of cystatin C as a marker of the glomerular filtration rate in the elderly. Thirty patients (15 male, 15 female, mean age 75.4 +/- 7.1 years) attending a geriatric ward were enrolled. Exclusion criteria were previously diagnosed renal disease, dementia and heart failure (NYHA III or IV). Cystatin C in serum was determined by a particle-enhanced turbidimetric assay. Inulin clearance was assessed using a single-shot method. Also, Cockcroft-Gault formula was calculated. Twelve patients had a reduced glomerular filtration rate (<70 ml/min/ 1.73 m2). The mean values were 88.4 micromol/l (+/- 27.7) for serum creatinine, 1.57 mg/l (+/- 0.34) for cystatin C and 88.7 ml/min/1.73 m2 (+/- 34.6) for inulin clearance. Maximum efficiency was 0.73 for serum creatinine (cut-off limit 82 micromol/l), 0.67 for cystatin C (cut-off limit 1.63 mg/l) and 0.8 for Cockcroft and Gault estimation (cut-off limit 54 ml/min/1.73 m2). A receiver operating characteristics (ROC) analysis did not show any differences between the various methods. Therefore, cystatin C in serum may not improve the diagnostic efficiency in detecting a reduced glomerular filtration rate in the elderly. Furthermore, normal ranges for serum creatinine in the elderly might need to be adjusted.
 ...
PMID:Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced glomerular filtration rate in the elderly. 1252 Dec 32

Cardiac sarcoplasmic reticulum (SR) sequesters Ca(2+) and plays a crucial role in the regulation of intracellular Ca(2+). Its functional properties are central to the excitation-contraction cycle of cardiac muscle. In this study, we hypothesized that alterations in SR function occur during the development of left ventricular (LV) hypertrophy. LV hypertrophy was produced in Lewis rats by the one-kidney, one-clip (1K1C) procedure. LV tissues were obtained from 1K1C rats 1 week (mild, N=7), 4 weeks (moderate, N=7), and 8 weeks (severe, N=7) post-surgery and from the corresponding age-matched, sham-operated controls (N=7 at each stage). In all of these rats, the ratio of LV weight (g) to body weight (kg) was determined and considered as an index for LV hypertrophy. In addition, the ratio of lung weight (g) to body weight (kg) was determined and considered as an index for pulmonary congestion and heart failure. In each LV specimen, SR Ca(2+)-uptake and tissue Ca(2+)-ATPase (CAA) level were determined. In 1K1C rats, LV hypertrophy increased by 21, 40, and 90% at 1, 4, and 8 weeks post-surgery, respectively, compared to the age-matched, sham-operated rats, whereas pulmonary congestion did not occur at 1 and 4 weeks but increased significantly by about 21% at 8 weeks. Further, both SR Ca(2+)-uptake and immunodetectable CAA level did not change at 1 week, increased (54%) to the same extent at 4 weeks, and decreased (42%) by approximately the same extent at 8 weeks in 1K1C rats compared to the age-matched, sham-operated rats. In summary, as LV hypertrophy evolved, Ca(2+)-uptake and CAA expression did not change in the early, increased in the moderate, and then declined in the later stages of hypertrophy development. The increase in Ca(2+)-uptake and CAA expression suggests, at the cellular level, a compensatory response to LV hypertrophy, while the decline at later stages indicates the transition to heart failure.
 ...
PMID:Assessment of sarcoplasmic reticulum Ca2+-uptake during the development of left ventricular hypertrophy. 1262 24

Previous studies indicate that serum cystatin C predicts incident heart failure in older adults. Children with chronic kidney disease (CKD) develop left ventricular (LV) diastolic dysfunction, often the initial abnormality of cardiac function. We hypothesized that cystatin C might predict LV diastolic dysfunction in children with CKD. Fifty-seven subjects, aged 6-21 years, with stage 2-4 CKD underwent echocardiography. Diastole was assessed from transmitral Doppler [maximum early (E wave) and late (A wave) diastolic flow velocities (E/A ratio)] and from tissue Doppler [septal mitral annular peak velocities (E')]. LV filling pressures were determined, using a ratio of E/E'. Fourteen (25%) patients had low E' and 15 (26%) had high E/E'. Children with abnormal E' or E/E' had significantly higher cystatin C levels than children with normal indices (P<0.05). Neither serum creatinine nor measured glomerular filtration rate (GFR) significantly correlated with E' or E/E'. Stepwise multiple regression analysis showed that cystatin C (beta=-0.825, P=0.023) and left ventricular mass (LVM) index (beta=0.099, P=0.006) independently predicted E'; LVM index independently predicted E/E' (beta=0.0173, P=0.01). We conclude that, in contrast to measured GFR or serum creatinine level, elevated serum cystatin C might be associated with diastolic dysfunction in children with CKD.
 ...
PMID:Serum cystatin C and left ventricular diastolic dysfunction in children with chronic kidney disease. 1672 86

Heart failure and chronic kidney disease share a number of risk factors and pathophysiological pathways. Renal insufficiency is common in patients with chronic heart failure (CHF). The aim of the study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL) could represent a novel, sensitive marker of kidney function in adult patients with chronic heart failure and normal serum creatinine. The study was performed on 150 patients with chronic heart failure due to coronary artery disease. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, eGFR. In multiple regression analysis predictors of serum NGAL were NYHA class, cystatin C, and eGFR. Taking into consideration the fact that the recent DOQI states that individuals with a reduced GFR is at greater risk for cardiovascular disease and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.
 ...
PMID:Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in patients with chronic heart failure and coronary artery disease. 1928 80

Blood cystatin C has increasingly been used as an endogenous marker for estimating glomerular filtration rate (GFR) and evaluating prognosis in patients with acute or chronic heart failure. The goal of the study was to investigate the impact of heart failure on the determination of renal function based on cystatin C or creatinine in nonacute cardiac patients. A total of 880 consecutive and clinically stable patients with heart disease were prospectively evaluated. Serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) showed a stronger correlation with cystatin C (r = 0.60, p <0.001) compared with creatinine (r = 0.46, p <0.001). Multivariate analysis identified estimated GFR according to the MDRD Study formula (p <0.001), serum NT-pro-BNP (p <0.001), use of immunosuppressive agents (p <0.001), and allopurinol treatment (p <0.001) as the strongest independent predictors of serum cystatin C. Parallel measurement of creatinine clearance using timed urine collection in a subgroup of 160 patients showed that estimated GFR according to cystatin C was almost identical to measured creatinine clearance independent of NT-proBNP. Conversely, creatinine-based calculation using the MDRD Study formula underestimated GFR in patients from the low (12 to 238 pg/ml) and medium (241 to 990 pg/ml) NT-pro-BNP tertiles. In conclusion, in patients without severe heart failure, indicated by low serum NT-pro-BNP, estimation of GFR using creatinine-based formulas underestimated renal function. The known prognostic impact of cystatin C in cardiac patients might result from a strong correlation with NT-pro-BNP, as well as its superior ability to predict renal function in patients with and without heart failure.
 ...
PMID:Role of N-terminal pro-brain natriuretic peptide and cystatin C to estimate renal function in patients with and without heart failure. 1936 1

Increased systemic myeloperoxidase (MPO) has been associated with both the presence and severity of heart failure (HF). This study tested the hypothesis that increased systemic MPO in apparently healthy elderly subjects may predict increased risk of developing HF. Systemic MPO was measured in all available samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS). After excluding subjects without available blood samples or with a history of prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were included. A total of 569 subjects developed incident HF during 7.2 +/- 2.3 years of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher risk of developing incident HF after adjusting for MI, age, gender, systolic blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus, and any subclinical cardiovascular disease (hazard ratio 1.34, 95% confidence interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after censoring subjects with incident MI before incident HF, even when adjusted for C-reactive protein and cystatin C (hazard ratio 1.46, 95% confidence interval 1.08 to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation between increased MPO and HF risk was stronger in subjects without traditional cardiovascular risk factors (<or=75 years old, systolic blood pressure <or=136 mm Hg, no subclinical cardiovascular disease, and no diabetes mellitus). In conclusion, an independent association between increased MPO and the development of HF in apparently healthy elderly subjects was observed, particularly beyond MI and traditional cardiac risk factors.
 ...
PMID:Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure. 1940 70

The aims of this study were to compare the prognostic value of cystatin C over creatinine and the Modification of Diet in Renal Disease (MDRD) equation and to evaluate whether it provides complementary information to cardiac biomarkers in the risk stratification of an unselected cohort of patients with acute heart failure. Consecutive hospitalized patients with established diagnoses of acute heart failure were prospectively studied. Blood samples were collected on hospital arrival to determine cystatin C, cardiac troponin T, and N-terminal-pro-brain natriuretic peptide. Clinical follow-up was obtained, and the occurrence of mortality and/or heart failure readmission was registered. One hundred thirty-eight patients (median age 74 years, interquartile range 67 to 80; 54% men) were studied. During a median follow-up period of 261 days (interquartile range 161 to 449), 60 patients (43.5%) presented with adverse events. After multivariate adjustment, cystatin C, N-terminal-pro-brain natriuretic peptide, cardiac troponin T, New York Heart Association functional class III or IV, and diabetes mellitus were identified as independent predictors of mortality and/or heart failure readmission. In contrast to creatinine and the MDRD equation, the highest cystatin C tertile (>1.50 mg/L) was a significant independent risk factor for adverse events (hazard ratio 3.08, 95% confidence interval 1.54 to 6.14, p = 0.004). A multimarker approach combining cardiac troponin T, N-terminal-pro-brain natriuretic peptide, and cystatin C improved risk stratification further, showing that patients with 2 (hazard ratio 2.37, 95% confidence interval 1.10 to 5.71) or 3 (hazard ratio 3.64, 95% confidence interval 1.55 to 8.56) elevated biomarkers had a higher risk for adverse events than patients with no elevated biomarkers (p for trend = 0.015). In conclusion, in this unselected cohort, cystatin C was a stronger predictor of adverse events than conventional measures of kidney function. In addition, cystatin C offered complementary prognostic information to cardiac biomarkers and could help clinicians perform more accurate risk stratification of patients with acute heart failure.
 ...
PMID:Complementary prognostic value of cystatin C, N-terminal pro-B-type natriuretic Peptide and cardiac troponin T in patients with acute heart failure. 1953 88

Cystatin C is a novel marker of renal function that has been found to predict adverse cardiovascular outcomes in ambulatory patients. The aim of this study was to investigate whether this biomarker predicts the length of hospitalization and adverse outcomes in patients hospitalized for heart failure. Two hundred forty consecutive patients aged > or =25 admitted to Johns Hopkins Hospital with exacerbations of heart failure were prospectively enrolled. Cystatin C levels were measured on admission. Patients were followed for 1 year. The primary outcome measure was the length of hospitalization. Secondary outcomes included all-cause mortality and readmission for heart failure. Cystatin C showed no significant association with the length of hospitalization. Patients in the highest quartile (quartile 4) of cystatin C level were at increased risk for death (hazard ratio 2.07 for quartile 4 vs quartiles 1 to 3, p = 0.01) and death or rehospitalization (hazard ratio 1.61 for quartile 4 vs quartiles 1 to 3, p = 0.01). The association between cystatin C and the combined end point of death or rehospitalization during 1-year follow-up remained significant after adjusting for age, race, gender, co-morbidities, and creatinine. Cystatin C was more predictive of these end points than creatinine, and the combination of cystatin C and creatinine was more predictive than either variable alone. In conclusion, cystatin C may be useful in addition to creatinine for predicting outcomes after admission for acute heart failure exacerbations.
 ...
PMID:Usefulness of cystatin C and prognosis following admission for acute heart failure. 1961 73

The pathophysiology of heart failure is complex, and the list of biomarkers representing distinct pathophysiologic pathways is growing rapidly. This article focuses on some promising newer biomarkers that have contributed to a better understanding of pathophysiologic mechanisms involved in heart failure but for which less data are currently available: osteoprotegerin, galectin-3, cystatin C, chromogranin A, and the adipokines adiponectin, leptin, and resistin. Despite the intriguing early information from these newer markers, none is ready for routine clinical use. Much additional study is needed to determine how these biomarkers will fit into diagnostic and treatment algorithms for patients who have heart failure.
 ...
PMID:Newer biomarkers in heart failure. 1963 Nov 81


1 2 3 4 5 6 7 8 Next >>