0
selected
-
1.
Low cholesterol efflux capacity and abnormal lipoprotein particles in youth with type 1 diabetes: a case control study.
Gourgari, E, Playford, MP, Campia, U, Dey, AK, Cogen, F, Gubb-Weiser, S, Mete, M, Desale, S, Sampson, M, Taylor, A, et al
Cardiovascular diabetology. 2018;(1):158
Abstract
BACKGROUND Patients with type 1 diabetes (T1DM) have increased mortality from cardiovascular disease (CVD). Risk factors for CVD include an elevation of LDL (LDLp) and small HDL (sHDLp) particles, and a decrease in reverse cholesterol transport i.e. HDL-cholesterol efflux capacity (CEC). Our objective was to compare lipoprotein particles and CEC between T1DM and healthy controls (HC) and to explore the associations between NMR lipid particles and cholesterol efflux. METHODS 78 patients with T1DM and 59 HC underwent fasting lipoprotein profile testing by NMR and measurements of CEC by cell-based method. The associations between NMR lipid particles with CEC were analyzed using multivariable linear regression models. RESULTS Youth with T1DM had higher total LDLp 724 [(563-985) vs 622 (476-794) nmol/L (P = 0.011)] (Maahs et al. in Circulation 130(17):1532-58, 2014; Shah et al. in Pediatr Diabetes 16(5):367-74, 2015), sHDLp [11.20 (5.7-15.3) vs 7.0 (3.2-13.1) μmol/L (P = 0.021)], and lower medium HDLp [11.20 (8.5-14.5) vs 12.3 (9-19.4), (P = 0.049)] and lower CEC (0.98 ± 0.11% vs 1.05 ± 0.15%, P = 0.003) compared to HC. Moreover, CEC correlated with sHDLp (β = - 0.28, P = 0.045) and large HDLp (β = 0.46, P < 0.001) independent of age, sex, ethnicity, BMIz, HbA1c, hsCRP and total HDLp in the diabetic cohort. CONCLUSIONS Youth with T1DM demonstrated a more atherogenic profile including higher sHDL and LDLp and lower CEC. Future efforts should focus on considering adding lipoprotein particles and CEC in CVD risk stratification of youth with T1DM. Trial registration Clinical Trials Registration Number NCT02275091.
-
2.
Efficacy and safety of a novel oral inducer of apolipoprotein a-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial.
Nicholls, SJ, Gordon, A, Johansson, J, Wolski, K, Ballantyne, CM, Kastelein, JJ, Taylor, A, Borgman, M, Nissen, SE
Journal of the American College of Cardiology. 2011;(9):1111-9
Abstract
OBJECTIVES The purpose of this study was to investigate the safety, tolerability, and efficacy of RVX-208, the first oral agent designed to enhance apolipoprotein (apo) A-I synthesis. BACKGROUND No agent that selectively induces synthesis of apoA-I has reached an advanced stage of clinical development. METHODS A total of 299 statin-treated patients with coronary artery disease were treated with placebo or with RVX-208 at a dose of 50, 100, or 150 mg twice daily for 12 weeks. Changes in lipid-related biomarkers, in addition to safety and tolerability, of RVX-208 were investigated. RESULTS For each dose of RVX-208, individual pairwise comparisons of apoA-I changes with placebo, the primary end point, did not achieve statistical significance. However, treatment with RVX-208 was associated with a dose-dependent increase in apoA-I levels by up to 5.6% (p = 0.035 for trend). Administration of RVX-208 resulted in significant increases in levels of high-density lipoprotein cholesterol (HDL-C) ranging from 3.2% to 8.3% (p = 0.02), and large HDL particles increased by 11.1% to 21.1% (p = 0.003). ApoA-I levels increased rapidly from 8 to 12 weeks, suggesting that peak pharmacological effect has not been achieved by the end of the 12-week study. Transient and reversible elevations in liver transaminases >3 times the upper limit of normal were observed in 18 patients treated with RVX-208, with no associated increase in bilirubin levels. CONCLUSIONS Administration of RVX-208 for 12 weeks was associated with increases in apoA-I, HDL-C, and concentration of large HDL particles, consistent with facilitation of cholesterol mobilization. Maximal increases in apoA-I may require longer exposure. An increase in liver enzymes was observed with active treatment. (Clinical Trial for Dose Finding and Safety of RVX000222 in Subjects With Stable Coronary Artery Disease; NCT01058018).
-
3.
Comparison of indirect methods of measuring intra-abdominal pressure in children.
Davis, PJ, Koottayi, S, Taylor, A, Butt, WW
Intensive care medicine. 2005;(3):471-5
Abstract
OBJECTIVE To determine the most accurate indirect method of measuring intra-abdominal pressure (IAP) in children. DESIGN AND SETTING Single-centre, prospective, clinical study in a 23-bed specialist paediatric intensive care unit in Australia. PATIENTS AND PARTICIPANTS 20 children admitted to paediatric intensive care with a peritoneal dialysis catheter in situ following congenital cardiac surgery. INTERVENTIONS IAP was measured directly via the peritoneal dialysis catheter and by intragastric manometry via an indwelling nasogastric tube, and by intravesical manometry via an indwelling transurethral urinary catheter, using volumes of 0, 1, 3 and 5 ml/kg body weight of sterile saline instilled into the bladder. MEASUREMENTS AND RESULTS Across the range of IAPs of 1-8 mmHg the Bland-Altman method for assessing agreement between two methods of clinical measurement showed bladder pressure measured via the urinary catheter with 1 ml/kg body weight of saline instilled to be the most accurate indirect measurement technique, tending to give pressures between 0.07 and 1.23 mmHg higher than the direct measurement (95% CI for bias). Measuring bladder pressure with either no saline instilled or more saline per kilogram body weight instilled was less accurate over the same range of pressures, as was measuring the gastric pressure. CONCLUSIONS The most accurate indirect method of measuring IAP in children over the normal range of IAPs involves measuring bladder pressure via a transurethral urinary catheter with 1 ml/kg body weight of sterile saline instilled into the bladder.
-
4.
Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors.
White, WB, Kent, J, Taylor, A, Verburg, KM, Lefkowith, JB, Whelton, A
Hypertension (Dallas, Tex. : 1979). 2002;(4):929-34
Abstract
Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.