Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial.

Patients with primary hyperparathyroidism are at increased risk for high blood pressure, vascular stiffening, and left ventricular hypertrophy, but previous studies have failed to demonstrate the direct associations with circulating parathyroid hormone (PTH) levels. The authors investigated cross-sectional relationships between PTH and 24-hour pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index in patients with primary hyperparathyroidism who were treatment-naive with cinacalcet, renin-angiotensin-aldosterone-system inhibitors, and thiazide or loop diuretics. In 76 patients, mean±SD of pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index values were 9.3±1.8 m/s, 116.6±17.0 mm Hg, and 92.8±23.0 g/m². In multivariate linear regression analyses with adjustment for potentially confounding parameters, PTH was independently associated with nocturnal systolic blood pressure (adjusted ß coefficient=.284, P=.040), mean 24-hour pulse wave velocity (ß=.199, P=.001), and left ventricular mass index (ß=.252, P=.025). PTH may promote vascular and cardiac remodeling in primary hyperparathyroidism. Interventional trials are needed to test the antihypertensive and cardioprotective effects of PTH-inhibitory treatment strategies.

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.

OBJECTIVES: 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 67 ±â€Š10 years, 78% women). Median PTH was 99 (interquartile range: 82-124) pg/ml and mean calcium was 2.63 ±â€Š0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson's r = 0.241, P < 0.01) and DBP (r = 0.328, 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 ß-coefficient = 0.289, P < 0.01; DBP: ß = 0.399, 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.

Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients.

Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2 ±â€Š10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ±â€Š12.8/77.1 ±â€Š9.2 mmHg and with a median of 2 (IQR: 1-3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3 ±â€Š42.0 milliseconds for males and 434.7 ±â€Š38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ±â€Š9.8 and 10.0 ±â€Š3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ±â€Š42.4 milliseconds; ß-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38-12.22 bpm]; ß-coefficient = -0.133; P = 0.01).In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.