Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the \uaaEplerenone in Primary Hyperparathyroidism \uba (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e', diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal probrain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted \u3b2-coefficient = 0.201, P = 0.035) and e' (\u3b2 = 0.188, P = 0.042), respectively. OC (\u3b2 = 0.192, P = 0.039) and BALP (\u3b2 = 0.198, P = 0.030) were each independently related with e'. CTX showed no correlations with LVEF or e'. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies

Is there a difference in rhythm outcome between patients undergoing first line versus second line paroxysmal atrial fibrillation ablation?

BackgroundCatheter ablation of atrial fibrillation (AF) is an established second line therapy for patients with symptomatic paroxysmal AF (PAF) and may be considered as a first line therapy in selected patients who are highly symptomatic, considering patient choice, benefit, and risk, according to recent guidelines. Our study investigated whether a first line vs. second line ablation approach may result in improved sinus rhythm maintenance after ablation.MethodsA total of 153 patients undergoing pulmonary vein isolation for PAF were included in the study (age 55±12 years, 29% female). Seventy-nine patients underwent first line AF ablation and 74 patients underwent second line AF ablation after failed antiarrhythmic drug therapy. There was no significant difference in baseline characteristics such as age, history of AF, left atrial size or LVEF between groups. Success was defined as atrial tachyarrhythmia free survival during a 12-month follow-up by means of serial ECG Holter monitoring.ResultsThere was no significant difference in cumulative arrhythmia-free survival between those patients who received AF ablation as a first or second line therapy. Single procedure success was 78% in the first line group vs. 81% in the second line group; multiple procedure success was 90 vs. 91%, (n.s.). Complication rate was 1.3% vs. 1.4% (n.s.).ConclusionSuccess of AF ablation did not differ between patients who receive ablation as first vs. second line therapy. Based on these data, a trial of AAD therapy before AF ablation may be justified in most patients with symptomatic PAF eligible for rhythm control

Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: The eplerenone in primary hyperparathyroidism trial

18siObjectives: The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to-renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients. Methods: Cross-sectional data of the single-center ‘‘Eplerenone in Primary Hyperparathyroidism’’ trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included. Results: Full data were available in 136 patients (mean age 6710 years, 78% women). Median PTH was 99 (interquartile range: 82–124) pg/ml and mean calcium was 2.630.15mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson’s r¼0.241, P<0.01) and DBP (r¼0.328, P<0.01). In multivariate regression analyses, with adjustment for age, sex, PTH, FGF-23, traditional cardiovascular risk factors, antihypertensive medication and parameters of calcium metabolism ARR remained significantly and directly related with nocturnal BP (SBP: adjusted b-coefficient¼0.289, P<0.01; DBP: b¼0.399, P<0.01). The relationship between ARR and nocturnal SBP was exclusively present in patients with PTH levels above the median of 99 pg/ml. Conclusion: ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT.J Hypertens ARR FGF 2016reservedmixedVerheyen, Nicolas; Fahrleitner-Pammer, Astrid; Pieske, Burkert; Meinitzer, Andreas; Belyavskiy, Evgeny; Wetzel, Julia; Gaksch, Martin; Grübler, Martin R.; Catena, Cristiana; Sechi, Leonardo A.; Van Ballegooijen, Adriana J.; Brandenburg, Vincent M.; Scharnagl, Hubert; Perl, Sabine; Brussee, Helmut; März, Winfried; Pilz, Stefan; Tomaschitz, AndreasVerheyen, Nicolas; Fahrleitner Pammer, Astrid; Pieske, Burkert; Meinitzer, Andreas; Belyavskiy, Evgeny; Wetzel, Julia; Gaksch, Martin; Grübler, Martin R.; Catena, Cristiana; Sechi, Leonardo Alberto; Van Ballegooijen, Adriana J.; Brandenburg, Vincent M.; Scharnagl, Hubert; Perl, Sabine; Brussee, Helmut; März, Winfried; Pilz, Stefan; Tomaschitz, Andrea

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial

AbstractBackground: Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and parameters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro-inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters. Methods: Cross-sectional baseline data from the "Eplerenone in Primary Hyperparathyroidism” trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e′. Results: Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e′ as respective dependent variables, and C-reactive protein and tryptophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was independently associated with CRP (adjusted β-coefficient=0.193, p=0.030) and QUIN (β=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (β=0.315, p<0.001), kynurenine (β=0.256, p=0.005) and QUIN (β=0.213, p=0.044). E/e′ was related with kynurenine (β=0.221, p=0.022) and QUIN (β=0.292, p=0.006). Tryptophan was not associated with any of the remodeling parameters. [Correction added after online publication (22 April 2017: The sentence "Among 136 subjects with pHPT (79% females), 100 (73%) had left ventricular hypertrophy.” was corrected to "Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%.”] Conclusions: Cardiac remodeling is common in pHPT and is associated with low-grade inflammation and activation of the tryptophan-kynurenine pathway. The potential role of kynurenine and QUIN as cardiovascular risk factors may be further investigated in future studies

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: The EPATH trial

Background: Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and para- meters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro- inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters. Methods: Cross-sectional baseline data from the \u201cEplerenone in Primary Hyperparathyroidism\u201d trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryp- tophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e\u2032. Results: Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e\u2032 as respec- tive dependent variables, and C-reactive protein and tryp- tophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was indepen- dently associated with CRP (adjusted \u3b2-coefficient = 0.193, p = 0.030) and QUIN (\u3b2 = 0.270, p = 0.007), but not kynure- nine. LAVI was related with CRP (\u3b2 = 0.315, p < 0.001), kynurenine (\u3b2 = 0.256, p = 0.005) and QUIN (\u3b2 = 0.213, p = 0.044). E/e\u2032 was related with kynurenine (\u3b2 = 0.221, p = 0.022) and QUIN (\u3b2 = 0.292, p = 0.006). Tryptophan was not associated with any of the remodeling parameters

Correlations between parathyroid hormone/calcium and markers of bone turnover in univariate and multivariate analyses.

<p>Correlations between parathyroid hormone/calcium and markers of bone turnover in univariate and multivariate analyses.</p

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

<div><p>Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the “Eplerenone in Primary Hyperparathyroidism” (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e’, diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e’ (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e’. CTX showed no correlations with LVEF or e’. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.</p></div

Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry

<div><p>Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2–6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested.</p></div

Correlations between markers of bone turnover and echocardiographic parameters of left ventricular function in univariate and multivariate analyses.

<p>Correlations between markers of bone turnover and echocardiographic parameters of left ventricular function in univariate and multivariate analyses.</p