Massive thoracic aortic aneurysm.
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Aortic Aneurysm, Thoracic↗
Biomedical subjects
F Leyva
Publications and source records attributed to F Leyva.
New insights into the progression of aortic stenosis: implications for secondary prevention.
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Aortic Valve Stenosis↗
Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease.
BACKGROUND: In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease. METHODS AND RESULTS: Healthy individuals (n=10, aged 41.6+/-3. 0 years, mean+/-SEM) and patients with angiographically proven coronary heart disease (n=13, aged 65.5+/-2.4 years) underwent an intravenous glucose tolerance test with simultaneous measurement of right forearm blood flow at 28 time points, using mercury-in-silastic venous occlusion plethysmography. In controls, forearm blood flow increased to a mean of 31.7% above baseline values at 7 min and remained above baseline up to 180 min after intravenous glucose. In contrast, patients with coronary heart disease exhibited an opposite response, with forearm blood flow decreasing to a mean of -16.2% below baseline values at 7 min and -25.8% at 180 min. Marked group differences emerged in net changes from baseline in forearm blood flow throughout the intravenous glucose tolerance test, expressed as incremental areas under the forearm blood flow profiles (controls: +351.3+/-121.7; coronary heart disease patients: -244.3+/-72.4 min ml(-1). 100 ml(-1), P=0. 001). CONCLUSIONS: We have demonstrated for the first time that in healthy individuals forearm blood flow increases after an intravenous bolus of glucose, and that paradoxically, this response is reduced below baseline forearm blood flow in patients with coronary heart disease. Further studies are needed to determine whether plethysmographic measurement of forearm blood flow after an intravenous bolus of glucose could provide a clinically useful non-invasive test for the diagnosis of occult coronary heart disease.
Adult↗
C-Reactive protein, serum amyloid A protein, and coronary events.
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Adult↗
Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure.
BACKGROUND: Chronic heart failure is one of a number of disorders associated with the development of a wasting syndrome. The precise mechanisms of this remain unknown, but previous studies have suggested a role for immune and neurohormonal factors. METHODS: We aimed to investigate in detail the differences in body composition (dual X-ray absorptiometry) and the relationship to candidate biochemical factors of the immune, neurohormonal and metabolic systems in 15 healthy controls, 36 stable non-cachectic and 18 cachectic patients with chronic heart failure. RESULTS: Non-cachectic patients showed reduced leg lean tissue (-9.1%, P<0.01) compared to controls. Cachectic patients had significantly reduced lean (-21.0% vs controls, -19.9% vs non-cachectics), fat (-33.0% vs controls, -37. 0% vs non-cachectics) and bone tissue (-17.5% vs controls, -15.9% vs non-cachectics) (all P<0.0001). Cachectic patients showed a significantly increased cortisol/dehydroepiandrosterone ratio (+203% vs controls, P<0.0001; +89% vs non-cachectics, P=0.0011) and increased cytokine levels (TNF-alpha, soluble TNF-receptor 1, interleukin-6). The levels of catabolic hormones and cytokines correlated significantly with reduced muscle and fat tissue content and reduced bone mass. CONCLUSION: Peripheral loss of muscle tissue is a general finding in chronic heart failure. The wasting in cardiac cachexia affects all tissue compartments and is significantly related to neurohormonal and immunological abnormalities.
Adult↗
Loss of the normal coupling between the anaerobic threshold and insulin sensitivity in chronic heart failure.
OBJECTIVE: To explore whether the anaerobic threshold, a measure of the balance between aerobic and anaerobic cellular metabolism, is related to whole body insulin sensitivity in healthy individuals and in patients with chronic heart failure, which involves is an imbalance of aerobic and anaerobic metabolism. DESIGN: Case-control study. SETTING: A teaching hospital department specialising in heart failure. PATIENTS: 20 healthy individuals (mean (SEM) age 55.2 (2.7) years) and 36 patients with chronic heart failure (59.1 (2.0) years, New York Heart Association class I-IV, anaerobic threshold 11.8 (0. 7) ml/kg/min, left ventricular ejection fraction 26 (2)%). INTERVENTIONS: An intravenous glucose tolerance test for assessment of insulin sensitivity (minimal model analysis) and a maximum treadmill exercise test for assessment of the anaerobic threshold, derived from measurement of oxygen consumption and carbon dioxide output. MAIN OUTCOME MEASURES: Relation between insulin sensitivity and the anaerobic threshold in patients with chronic heart failure. RESULTS: While anaerobic threshold was positively correlated with insulin sensitivity in healthy controls (r = 0.72, p < 0.001), no such relation was observed in patients with chronic heart failure. In stepwise multiple linear regression analyses of variables in healthy individuals, insulin sensitivity emerged as the only predictor of anaerobic threshold (standardised coefficient = 0.72, p < 0.001), while fasting insulin, incremental insulin area, and total body fat (dual photon x ray absorptiometry) failed to enter into final models (joint R = 0.52, p < 0.001). CONCLUSIONS: In healthy individuals, whole body insulin sensitivity is related, or "coupled, " to the anaerobic threshold. The absence of such metabolic coupling in patients with chronic heart failure provides further evidence of disturbed cellular metabolism in patients with this condition.
Aged↗
The glycolytic pathway to coronary heart disease: a hypothesis.
Coronary heart disease (CHD) is pathogenetically linked to numerous metabolic disturbances. These are inextricably interrelated, constituting identifiable clusters or syndromes of cardiovascular risk. Prominent among these is the insulin resistance syndrome, whose components, including hyperuricemia, have all been linked to CHD pathogenesis. Many mechanisms have been put forward to account for the emergence of this syndrome, but none offer a satisfactory explanation for the involvement of hyperuricemia. Possible explanations relate to the observation of glycolytic disturbances in insulin-resistant and hyperuricemic states. This might be expected from the fact that uric acid production is linked to glycolysis and that glycolysis is controlled by insulin. Phosphoribosylpyrophosphate (PPRP) is an important metabolite in this respect. Its availability depends on ribose-5-phosphate (R-5-P), the production of which is governed by glycolytic flux. Diversion of glycolytic intermediates toward R-5-P, PPRP, and uric acid will follow if there is diminished activity of glyceraldehyde-3-phosphate dehydrogenase (GA3PDH), which is regulated by insulin. Serum triglyceride concentrations may also increase, as might be expected from accumulation of glycerol-3-phosphate. Thus, intrinsic defects in GA3PDH and a loss of its responsiveness to insulin, by causing accumulation of glycolytic intermediates, may explain the association between insulin resistance, hyperuricemia, and hypertriglyceridemia. This scenario raises the possibility that disturbances of a single glycolytic enzyme may be pivotal in the modulation of metabolic risk factors for CHD.
Animals↗
Uric acid in chronic heart failure: a measure of the anaerobic threshold.
The anaerobic threshold (AT) is a measure of the balance between aerobic and anaerobic cellular metabolism. Hyperuricemia occurs in conditions that involve an imbalance between cellular oxygen consumption and carbon dioxide production, such as chronic heart failure (CHF). We therefore hypothesized that in CHF, serum uric acid might be related to the AT. Patients with CHF (n=40, aged 58.7+/-1.9 years; New York Heart Association Class I-IV; maximal oxygen consumption [MVO2], 18.7+/-01.1 mL/kg/min; left ventricular ejection fraction, 26%+/-2%) and 10 age-matched healthy controls underwent measurement of the serum uric acid level at rest and assessment of the AT. This was derived from MVO2 and the regression slope relating minute ventilation to carbon dioxide output (VE - VCO2) during a maximal treadmill exercise test. Compared with the healthy controls, patients with CHF had a lower AT (11.8+/-0.7 v 16.9+/-1.1 mL/kg/min, P < .001) and a higher serum uric acid concentration (493.8+/-22.4 v 308.7+/-21.5 micromol/L, P < .001). In univariate analyses of the CHF group, the AT correlated with serum uric acid (r=-.56, P < .001; AT=19.93 - (0.016 x uric acid), R2=.31, P < .001) and plasma creatinine (r=-.43, P < .01), but not with the diuretic dose. In stepwise regression analyses of the CHF group, serum uric acid emerged as a predictor of the AT (standardized coefficient=-.56, P < .001), whereas the diuretic dose and plasma creatinine failed to enter into the final models (multiple R2=.31, P < .001). In conclusion, in CHF there is an inverse relationship between the AT and the resting serum uric acid concentration. This is consistent with the known links between uric acid production and the imbalance in aerobic/anaerobic metabolism that occur in CHF. These findings provide the basis for using the simple measurement of the serum uric acid level as a surrogate measure of the AT.
Anaerobiosis↗
Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study (HDDRISC-1).
OBJECTIVES: To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men. DESIGN: Cohort study with baseline characterisation, clinical follow-up, and identification of predictors of coronary artery disease and diabetes. SETTING: University hospital metabolic day ward. SUBJECTS: Participants in a company health programme (n=742). MAIN OUTCOME MEASURES: Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT). RESULTS: Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake. CONCLUSIONS: Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol consumption was associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.
Adult↗
Hyperleptinaemia in chronic heart failure. Relationships with insulin.
BACKGROUND: Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels. METHODS: Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels. RESULTS: Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001). CONCLUSIONS: Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.
Adipose Tissue↗
Uric acid in chronic heart failure: a marker of chronic inflammation.
BACKGROUND: Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. METHODS AND RESULTS: Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P<0.001), E-selectin and sTNFR2 (both P<0.05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0.74), interleukin-6 (r=0.66), sTNFR2 (r=0.63), TNFa (r=0.60) (all P<0.001), and ICAM-1 (r=0.41, P<0.01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. CONCLUSIONS: Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.
Cardiomyopathy, Dilated↗
Factors of the metabolic syndrome: baseline interrelationships in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). Heart Disease and Diabetes Risk Indicators in a Screened Cohort.
Syndromes of risk factor disturbance may contribute to the development of coronary heart disease and non-insulin-dependent diabetes mellitus, but their definition and quantification remain problematic. Using factor analysis, constellations of risk factor variables that could indicate distinct syndromes of metabolic disturbance were explored in the baseline data of the first follow-up cohort of 742 men from the Heart Disease and Diabetes Risk Indicators in a Screened Cohort (HDDRISC) study. The primary analysis considered 16 intercorrelated variables measured in more than 90% of cohort participants. A missing-values estimation routine was used to ensure inclusion of all participants in the analysis. Subanalyses were undertaken, including a repeat of the primary analysis on the 522 individuals who had received measurement of HDL cholesterol, an oblique rather than orthogonal factor rotation procedure performed on primary and HDL subset analyses, a repeat of these two primary and HDL subset analyses using only those participants with complete measurements, and a repeat of these six analyses including only the seven variables conventionally associated with the metabolic syndrome. The principal factor that emerged in all analyses undertaken comprised oral glucose tolerance test insulin and glucose response, serum uric acid, and body mass index. Fasting serum triglyceride concentration was included in this factor in 11 of the 12 analyses undertaken, fasting plasma insulin in 8, fasting plasma glucose in 5, and mean arterial pressure in 3. HDL cholesterol factored in isolation from insulin in all analyses undertaken. These findings provide strong support for a core metabolic cluster, which is unlikely to include blood pressure and does not include HDL. The factor scores relating to this cluster will provide a means of assessing its quantitative importance in prospective analysis of the development of CHD and diabetes in this cohort.
Adult↗
Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.
In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the variables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor dominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusion, interindividual variations in plasma leptin concentrations are strongly related to the principal components of the insulin resistance syndrome. Further studies are needed to determine whether the insulin-leptin axis plays a coordinating role in this syndrome and whether plasma leptin concentrations could provide an additional measure of cardiovascular risk.
Blood Pressure↗
Physiological hyperinsulinemia is not associated with alterations in venous plasma levels of endothelin-1 in healthy individuals.
Elevations in circulating levels of both endothelin-1 (ET-1) and insulin are found in coronary heart disease and chronic heart failure. Although several studies have shown that insulin can stimulate ET-1 release from endothelial cell cultures, in vivo studies have yielded equivocal results. We sought to determine whether endogenous insulin at physiological concentrations leads to alterations in venous plasma ET-1 levels in healthy subjects. In addition, we investigated the effects of physiological and supraphysiological doses of insulin on the release of ET-1 from human umbilical vein endothelial cells (HUVECs) in vitro. In the in vitro experiment, ET-1 and insulin levels were measured during an intravenous glucose tolerance test (IVGTT) in 10 healthy subjects. In the in vitro experiment, HUVECs were incubated in the absence of serum and with different concentrations of insulin (25 pmol/L to 1 mumol/L) for 4 hours before measurement of secreted ET-1. The in vivo study showed no significant alterations in venous plasma ET-1 levels during IVGTTs (maximum plasma insulin, 616.9 +/- 147.0 pmol/L [mean +/- SEM]). In the in vitro experiment, increases in ET-1 release were observed under serum-free conditions at 100 pmol/L (physiological) and 1 mumol/L (supraphysiological) insulin (ET-1, 22.4% and 46.4% higher than control cultures, respectively, both P < .05). Our results show that insulin at physiological concentrations does not alter plasma ET-1 levels in healthy individuals, but does stimulate its secretion from vascular endothelial cells in vitro. This may have implications for the study of elevated ET-1 in hyperinsulinemic states.
Blood Glucose↗
Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure.
OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral muscular changes influence the progression of heart failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and myocardial muscle. METHODS: We investigated insulin sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic evidence of coronary artery disease without CHF and 20 healthy control subjects-and assessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensitivity was estimated by minimal modeling analysis of the glucose and insulin and profiles during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS: Compared with control subjects, patients with CHF had similar mean fasting glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p < 0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independently. Rest norepinephrine and epinephrine levels, left ventricular ejection fraction and heart failure etiology were not related to insulin sensitivity. Patients with coronary artery disease but no CHF had an intermediate mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Advanced heart failure (in terms of reduced peak VO2) is related to increased insulin resistance, but this is not directly mediated through ventricular dysfunction or increased catecholamine levels.
Blood Glucose↗
Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.
BACKGROUND: Elevated serum uric acid concentrations have been observed in clinical conditions associated with hypoxia. Since chronic heart failure is a state of impaired oxidative metabolism, we sought to determine whether serum uric acid concentrations correlate with measures of functional capacity and disease severity. METHODS: Fifty nine patients with a diagnosis of chronic heart failure due to coronary heart disease (n = 34) or idiopathic dilated cardiomyopathy (n = 25) and 20 healthy controls underwent assessment of functional capacity. Maximal oxygen uptake (MVO2) and regression slope relating to minute ventilation to carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise test. Metabolic assessment consisted of measuring serum uric acid and fasting lipids, and insulin sensitivity, obtained by minimal modelling analysis of glucose and insulin responses during an intravenous glucose tolerance test. Clustering of indices of functional disease capacity and metabolic factors was explored using factor analysis and multivariate regression analysis. RESULTS: Compared to 20 healthy controls, patients with chronic heart failure had a 52% lower MVO2 (P < 0.001), 56.8% higher serum uric acid concentrations (P < 0.001) as well as a 60.5% lower insulin sensitivity (P < 0.001). Salient univariate correlations in the chronic heart failure group included serum uric acid concentrations with exercise time during the exercise test (r = -0.53), MVO2 (r = -0.50) (both P < 0.001), VE-VCO2 slope (r = 0.45), and NYHA functional class (r = 0.36) (both P < 0.01). In factor analysis of the chronic heart failure group, serum uric acid formed part of a principal cluster of metabolic variables which included MVO2 and VE-VCO2 slope. In multivariate regression analysis, serum uric acid concentrations emerged as a significant predictor of MVO2, exercise time (both P < 0.001,) VE-VCO2 slope and NYHA functional class (both P < 0.02), independent of diuretic dose, age, body mass index, serum creatinine, alcohol intake, plasma insulin levels, and insulin sensitivity index. CONCLUSIONS: There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.
Aged↗
Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure.
OBJECTIVE: To determine whether lower limb blood flow is related to serum uric acid concentrations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN: Lower limb blood flow was measured at rest and after maximum exercise followed by a five minute period of ischaemia (maximum blood flow) using strain gauge venous occlusion plethysmography. All patients underwent a metabolic assessment, which included an intravenous glucose tolerance test (IVGTT)-to obtain an index of insulin sensitivity- and measurement of serum uric acid. SETTING: University and hospital departments specialising in cardiology and metabolic medicine. SUBJECTS: 22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively. Patients in the upper tertile of serum uric acid had lower maximum blood flow than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P = 0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P < 0.001), but not with resting blood flow. In stepwise regression analysis, uric acid emerged as the only predictor of maximum blood flow (standardised coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong inverse relation between serum uric acid concentrations and maximum leg blood flow in patients with chronic heart failure. Further studies are needed to determine whether serum uric acid can be used as an index of vascular function in cardiovascular diseases.
Biomarkers↗
In vitro and in vivo effects of penicillin and clindamycin on expression of group A beta-hemolytic streptococcal capsule.
Encapsulation of group A beta-hemolytic streptococci (GABHS) is an important virulence factor. The changes that occur in the frequency of encapsulation of GABHS during pharyngotonsillitis, in 20 patients treated with penicillin and 20 treated with clindamycin, were investigated. The effects of subinhibitory concentrations of these agents were also evaluated in vitro. At day 4, 8 of 10 (80%) GABHS isolates recovered from children treated with penicillin were encapsulated, compared with 1 of 5 (20%) of those from children treated with clindamycin (P < 0.05). Two days following 10 days of therapy, GABHS was eliminated from 13 of the 20 (65%) children treated with penicillin and from all treated with clindamycin (P < 0.05). At that time, six of the seven GABHS isolates recovered in patients treated with penicillin were encapsulated. GABHS were not detected after 4 days of therapy in those treated with clindamycin. Incubation of GABHS isolates with one-half of the MIC of clindamycin reduced the frequency of encapsulation, compared with that after incubation with one-half of the MIC of penicillin (12.5 versus 67.5%). These data illustrate the superiority of clindamycin over penicillin in reducing the expression of a capsule by GABHS.
Bacterial Capsules↗