Description: BACKGROUND Renal sympathetic denervation (RSD) represents an effective treatment option for patients with resistant arterial hypertension (HT). Extracellular matrix (ECM) turnover and deposition are essential processes in HT-related cardiovascular remodeling, fibrosis, and cardiac hypertrophy and contribute to hypertensive heart disease. OBJECTIVES The primary aim of the present study was to examine the effect of RSD on increased collagen turnover as reflected by serum levels of amino-terminal pro-peptides (PINP, PIIINP) and a carboxyl-terminal pro-peptide (PICP), specific biomarkers for cardiac ECM turnover and cardiovascular fibrosis. METHODS A total of 100 consecutive patients (mean age: 65.9±10.1 years) undergoing RSD were included in this study. A therapeutic response was defined as an office systolic blood pressure (SBP) reduction of 〉10mm Hg 6 months after RSD. Venous serum samples for measurement of PICP, PINP, and PIIINP were collected prior to and 6 months after RSD. RESULTS A significant reduction in the office SBP of 24.3mm Hg (SBP baseline: 166.9±14.3mm Hg ( P 〈 0.001) was documented 6 months after RSD. At this time point, the serum levels of PICP, PINP, and PIIINP ( P 〈 0.01) were significantly decreased compared to baseline values in patients with an increased collagen turnover, showing significant differences comparing BP responders and nonresponders. CONCLUSION In addition to the effective blood pressure reduction in response to RSD, this study demonstrates a positive effect of RSD on biomarkers reflecting cardiovascular ECM turnover and deposition. These results suggest a beneficial effect of RSD on cardiovascular fibrosis, hypertensive heart disease, and end-organ damage in high-risk patients.

Description: Background Pregnancy and tuberculosis treatment or prophylaxis can affect efavirenz pharmacokinetics, maternal human immunodeficiency virus type 1 (HIV-1) treatment outcomes, and mother-to-child transmission (MTCT) risk. Methods We evaluated a prospective cohort of pregnant, HIV-infected women with and without tuberculosis in Soweto, South Africa. Pharmacokinetic sampling was performed at gestation week 37 and during the postpartum period . Efavirenz trough concentrations (C min ) were predicted using population pharmacokinetic models. HIV-viral load was measured at delivery for mothers and at 6 weeks of age for infants. Results Ninety-seven women participated; 44 had tuberculosis. Median efavirenz C min during pregnancy was 1.35 µg/mL (interquartile range [IQR], 0.90–2.07 µg/mL; 27% had an efavirenz C min of 〈 1 µg/mL), compared with a median postpartum value of 2.00 µg/mL (IQR, 1.40–3.59 µg/mL; 13% had an efavirenz C min of 〈 1 µg/mL). A total of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz C min of 〈1 µg/mL. Rifampin did not reduce the efavirenz C min . Isoniazid (for prophylaxis or treatment), though, reduced the rate of efavirenz clearance. At delivery, median durations of ART were 13 weeks (IQR, 9–18 weeks) and 21 weeks (IQR, 13–64 weeks) for women with and those without tuberculosis, respectively; 55% and 83%, respectively, had a viral load of 〈20 copies/mL ( P = .021). There was 1 case of MTCT. Conclusions Pregnancy increased the risk of low efavirenz concentrations, but MTCT was rare. A detectable HIV-viral load at delivery was more common among pregnant women with tuberculosis, in whom ART was generally initiated later.