PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-8 (8)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
1.  Immune Activation and Inflammation in Patients with Cardiovascular Disease Are Associated with Higher Phenylalanine to Tyrosine Ratios: The Ludwigshafen Risk and Cardiovascular Health Study 
Journal of Amino Acids  2014;2014:783730.
Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD). Preferentially Th1-type cytokine interferon-γ stimulates neopterin production by GTP cychlohydrolase I (GCH-I) in parallel in monocyte-derived macrophages and dendritic cells. In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary cofactor of amino acid hydroxylases like phenylalanine 4-hydroxylase (PAH). Serum concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. The phenylalanine to tyrosine ratio (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme activity. Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did not differ between individuals with or without CAD (Welch's t-test: P = n.s.). Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls (P < 0.0001) and they correlated with Phe/Tyr (Spearman's rank correlation for neopterin: rs = 0.216 and hsCRP: rs = 0.122; both of P < 0.0001) concentrations. In conclusion, immune activation is associated with higher Phe/Tyr in CAD patients. Data indicates subnormal PAH activity which might be involved in the precipitation of neuropsychiatric symptoms in patients.
doi:10.1155/2014/783730
PMCID: PMC3934657  PMID: 24660059
2.  Circulating Dopamine and C-Peptide Levels in Fasting Nondiabetic Hypertensive Patients 
Diabetes Care  2012;35(8):1771-1773.
OBJECTIVE
Accumulating evidence supports a potential role for dopamine in the regulation of insulin secretion. We examined the association between circulating dopamine and C-peptide concentrations using data from the Graz Endocrine Causes of Hypertension (GECOH) study.
RESEARCH DESIGN AND METHODS
After 12 h of fasting, we measured plasma dopamine and serum C-peptide levels and established determining factors of insulin secretion in 201 nondiabetic hypertensive patients (mean age 48.1 ± 16.0 years; 61.7% women).
RESULTS
Mean dopamine and C-peptide concentration were 33.4 ± 38.6 pg/mL and 3.1 ± 2.7 ng/mL, respectively. A strong and inverse correlation was observed between dopamine and C-peptide levels (r = −0.423, P < 0.001). There was no significant relationship between C-peptide, plasma epinephrine, and norepinephrine. C-peptide levels decreased steadily and significantly from tertile 1 of dopamine (3.6 ng/mL [95% CI 2.9–4.1]) to tertile 3 (1.6 ng/mL [1.5–2.7], P < 0.001) after multivariate adjustment.
CONCLUSIONS
The inverse association between dopamine and C-peptide highlights the need to evaluate whether dopamine could be effective for modulating endocrine pancreatic function.
doi:10.2337/dc11-2384
PMCID: PMC3402263  PMID: 22699284
3.  Glomerular Filtration Rate (GFR) determination via individual kinetics of the inulin-like polyfructosan sinistrin versus creatinine-based population-derived regression formulae 
BMC Nephrology  2013;14:159.
Background
In renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae.
Methods
In 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses.
Results
Reasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m2]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods.
Conclusions
For routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73 m2] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination.
Consort
http://www.consort-statement.org/index.aspx?o=1190
doi:10.1186/1471-2369-14-159
PMCID: PMC3726368  PMID: 23876053
eGFR; MDRD; CKD-EPI; mGFR; Sinistrin; Kinetics
4.  Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study 
PLoS ONE  2013;8(5):e63560.
Background
Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD).
Methods
We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54–5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease.
Results
Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min), 2.64±1.06 µmol/L (GFR 60–90 ml/min), 2.52±1.24 µmol/L (GFR 30–60 ml/min) and 2.05±0.78 µmol/L (GFR<30 ml/min), respectively (p = 0.002). The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L) of homoarginine (HR 1.62, 95% CI 1.16–2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11–2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98–1.98, p = 0.06).
Conclusions
Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations.
doi:10.1371/journal.pone.0063560
PMCID: PMC3655120  PMID: 23691067
5.  Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial 
Background
Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.
Methods/design
Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.
The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.
Discussion
In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.
Trial registration
ISRCTN33941607
doi:10.1186/1472-6823-12-19
PMCID: PMC3515510  PMID: 22974443
Aldosterone; Mineralocorticoid receptor blocker; Hyperparathyroidism
6.  Associations of Sun Exposure with 25-Hydroxyvitamin D and Parathyroid Hormone Levels in a Cohort of Hypertensive Patients: The Graz Endocrine Causes of Hypertension (GECOH) Study 
Sunlight-induced vitamin D, synthesis in the skin is the major source of vitamin D, but data on the relationship of sun-related behaviour with vitamin D and parathyroid hormone (PTH) levels are relatively sparse. We evaluated whether habitual sun exposure is associated with 25-hydroxyvitamin D (25[OH]D) and PTH levels and whether there exist seasonal variations. We examined 111 hypertensive patients in Austria (latitude 47° N). Frequent sunbathing at home and outdoor sports were associated with higher 25(OH)D levels (P < 0.05 for both). Red or blond scalp hair as a child, memory of sunburns, preferring sunbathing, frequent stays on the beach or in open-air pools, and solarium use were associated with lower PTH levels (P < 0.05 for all). Multiple linear regression analyses including age, sex, and body mass index showed that sun exposure score was significantly associated with 25(OH)D (beta coefficient = 0.27; P = 0.004) and by trend with PTH (beta coefficient = −0.16; P = 0.09). These associations were more prominent in summer in which 25(OH)D levels were significantly higher compared to winter. Translation of these findings into recommendations for the prevention and treatment of vitamin D deficiency remains a challenge for the future.
doi:10.1155/2012/732636
PMCID: PMC3296164  PMID: 22518130
7.  Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients 
European Journal of Heart Failure  2011;13(8):852-859.
Aims
Sudden cardiac death (SCD) is a major contributor to the excess mortality of patients on maintenance dialysis. Homoarginine deficiency may lead to decreased nitric oxide availability and endothelial dysfunction. Based on this rationale we assessed whether homoarginine deficiency is a risk factor for SCD in dialysis patients.
Methods and results
This study examined the association of homoarginine with cardiovascular outcomes in 1255 diabetic haemodialysis patients from the German diabetes and dialysis study. During a median of 4 years of follow-up, hazard ratios (HR) (95% CI) for reaching the following pre-specified, adjudicated endpoints were determined: SCD, myocardial infarction, stroke, death due to heart failure, and combined cardiovascular events. There was a strong association of low homoarginine concentrations with the presence of congestive heart failure and left ventricular hypertrophy as well as increased levels of brain natriuretic peptide. Per unit decrease in homoarginine, the risk of SCD increased three-fold (HR 3.1, 95% CI 2.0–4.9), attenuating slightly in multivariate models (HR 2.4; 95% CI 1.5–3.9). Patients in the lowest homoarginine quintile experienced a more than two-fold increased risk of SCD, and more than three-fold increased risk of heart failure death than patients in the highest quintile, which accounted for the high incidence of combined cardiovascular events. Low homoarginine showed a trend towards increased risk of stroke, however, myocardial infarction was not meaningfully affected.
Conclusion
Low homoarginine is a strong risk factor for SCD and death due to heart failure in haemodialysis patients. Further studies are needed to elucidate the underlying mechanisms, offering the potential to develop new interventional strategies.
doi:10.1093/eurjhf/hfr056
PMCID: PMC3143829  PMID: 21791541
Homoarginine; Sudden cardiac death; Heart failure; Amino acids; Haemodialysis
8.  Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism 
Background
Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.
Methods and design
In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR) as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT) as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL) who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin.
Conclusion
Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.
doi:10.1186/1472-6823-9-11
PMCID: PMC2671510  PMID: 19351411

Results 1-8 (8)