Effects of oral paricalcitol therapy on arterial stiffness and osteopontin in hypertensive patients with chronic kidney disease and secondary hyperparathyroidism.

BACKGROUND: Arterial stiffness is linked to the progression of atherosclerosis, while activation of vitamin D receptor exerts favorable cardiovascular effects in patients with renal insufficiency. In this study, we investigated the effects of oral treatment with paricalcitol, a potent vitamin D receptor activator, on arterial stiffness and osteopontin, a marker of atherosclerosis, in hypertensive patients with chronic kidney disease (CKD) and secondary hyperparathyroidism. METHODS: We followed up 29 treated hypertensive patients (mean age: 74.1 years, 19 men, office blood pressure = 132/85 mmHg) with CKD stages 3-5 (mean glomerular filtration rate [GFR] = 19.4 ml/min/1.73 m2) who were on therapy with oral paricalcitol for 1 year. The control group consisted of 10 age-, sex-, and GFR-matched hypertensive patients with secondary hyperparathyroidism. RESULTS: After 1 year of treatment with paricalcitol compared to baseline, there was no statistical difference in levels of GFR, office blood pressure, and osteopontin (p = NS for all), while carotid-femoral PWV was reduced from 11.8 ± 2.6 m/s to 11.2 ± 2.4 m/s (p < 0.05). The control group exhibited no significant changes in carotid-femoral PWV (p = NS). CONCLUSIONS: Treatment with oral paricalcitol in hypertensive subjects suffering from CKD stages 3-5 and secondary hyperparathyroidism is accompanied by amelioration of arterial stiffness as reflected by the reduction of carotid-femoral PWV.

GLP-1 receptor agonists and cardiovascular outcome trials: An update.

Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system.

ADMA, C-reactive protein, and albuminuria in untreated essential hypertension: a cross-sectional study.

BACKGROUND: Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded. PREDICTORS: ADMA and high-sensitivity C-reactive protein (hs-CRP) levels. OUTCOME VARIABLE: Albuminuria assessed using albumin-creatinine ratio (ACR). MEASUREMENTS: Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples. RESULTS: 64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R(2) = 0.674; P < 0.001). LIMITATIONS: Cross-sectional study. CONCLUSIONS: In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.