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Effect of nebivolol beneficial on lipid profile and glycemic control in comparison with Atenolol in patients with type 2 DM with concomitant hypertension.
Majid, A, Javed, A, Hussain, M, Faisal, Z, Elahi, A, Akhtar, L
Pakistan journal of pharmaceutical sciences. 2021;(5(Supplementary)):1891-1895
Abstract
Blood pressure control in hypertensive patients with metabolic abnormalities is challenging because many antihypertensive drugs adversely affect metabolism. Nebivolol a 3rd generation vasodilatory β-blocker offer neutral or beneficial effects on insulin sensitivity and lipid metabolism. The purpose of this study was to evaluate the effect of nebivolol and atenolol on glycemic control and lipid profile in type 2 diabetes patients with concomitant hypertension. We conducted a 12 weeks double blind randomized clinical trial at Sheik Zayed Hospital Rahim Yar Khan. Patients were randomly divided in to two groups. Patients in group were given tablet nebivolol 5-10mg while patients in group B were given tablet Atenolol 25-50mg/daily for a period of 12 weeks. Pre and post data were analyzed by SPSS 20. After 12 weeks, Both drugs lowered blood pressure significantly i.e. nebivolol (SBP from152±12 to130±14 with p=0.004, DBP from 95±12 to78±8.5 with p=0.002) Atenolol (SBP from148±16.5 to 128±15.5 with p=0.006, DBP from 90±10.5 to 82±12 with p=0.003).Similarly both Nebivolol and Atenolol did not any significant effect on glycemic control and lipid profile at 12 week with in groups. However when comparison was done between two groups, Nebivolol significantly reduced blood sugar (p=0.001), HbA1c (p=0.0032), total Cholesterol (p=0.002), triglycerides (p=0.012), LDL-Cholesterol (p=0.007) and HDL-Cholesterol (p=0.001) as compared to atenolol. In comparison with atenolol, Nebivolol has a beneficial effect on glycemic control and serum lipid profile.
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Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.
Van Driest, SL, Sleeper, LA, Gelb, BD, Morris, SA, Dietz, HC, Forbus, GA, Goldmuntz, E, Hoskoppal, A, James, J, Lee, TM, et al
The Journal of pediatrics. 2020;:213-220.e5
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OBJECTIVE To test whether variants in ADRB1 and CYP2C9 genes identify subgroups of individuals with differential response to treatment for Marfan syndrome through analysis of data from a large, randomized trial. STUDY DESIGN In a subset of 250 white, non-Hispanic participants with Marfan syndrome in a prior randomized trial of atenolol vs losartan, the common variants rs1801252 and rs1801253 in ADRB1 and rs1799853 and rs1057910 in CYP2C9 were analyzed. The primary outcome was baseline-adjusted annual rate of change in the maximum aortic root diameter z-score over 3 years, assessed using mixed effects models. RESULTS Among 122 atenolol-assigned participants, the 70 with rs1801253 CC genotype had greater rate of improvement in aortic root z-score compared with 52 participants with CG or GG genotypes (Time × Genotype interaction P = .005, mean annual z-score change ± SE -0.20 ± 0.03 vs -0.09 ± 0.03). Among participants with the CC genotype in both treatment arms, those assigned to atenolol had greater rate of improvement compared with the 71 of the 121 assigned to losartan (interaction P = .002; -0.20 ± 0.02 vs -0.07 ± 0.02; P < .001). There were no differences in atenolol response by rs1801252 genotype or in losartan response by CYP2C9 metabolizer status. CONCLUSIONS In this exploratory study, ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome. If these findings are confirmed in future studies, ADRB1 genotyping has the potential to guide therapy by identifying those who are likely to have greater therapeutic response to atenolol than losartan.
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On-treatment HDL cholesterol predicts incident atrial fibrillation in hypertensive patients with left ventricular hypertrophy.
Okin, PM, Hille, DA, Wachtell, K, Kjeldsen, SE, Julius, S, Devereux, RB
Blood pressure. 2020;(5):319-326
Abstract
Purpose: Hypertensive patients are at increased risk of atrial fibrillation (AF). Although low baseline high density lipoprotein (HDL) cholesterol has been associated with a higher risk of AF, this has not been verified in recent population-based studies. Whether changing levels of HDL over time are more strongly related to the risk of new AF in hypertensive patients has not been examined.Material and methods: Incident AF was examined in relation to baseline and on-treatment HDL levels in 8267 hypertensive patients with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. HDL levels at baseline and each year of testing were categorised into quartiles according to baseline HDL levels.Results: During 4.7 ± 1.10 years of follow-up, 645 patients (7.8%) developed new AF. In univariate Cox analyses, compared with the highest quartile of HDL levels (>1.78 mmol/l), patients with on-treatment HDL in the lowest quartile (≤ 1.21 mmol/l) had a 53% greater risk of new AF. Patients with on-treatment HDL in the second and third quartiles had intermediate increased risks of AF. Baseline HDL in the lowest quartile was not a significant predictor of new AF (hazard ratio (HR): 1.14, 95% confidence interval (CI): 0.90-1.43). In multivariable Cox analyses adjusting for multiple baseline and time-varying covariates, the lowest quartile of on-treatment HDL remained associated with a nearly 54% increased risk of new AF (HR: 1.54, 95% CI: 1.16-2.05) whereas a baseline HDL≤ ⩽1.21 mmol/l was not predictive of new AF (HR: 1.01, 95% CI: 0.78-1.31).Conclusion: Lower on-treatment HDL is strongly associated with risk of new AF. These findings suggest that serial assessment of HDL can estimate AF risk better than baseline HDL in hypertensive patients with left ventricular hypertrophy. Future studies may investigate whether therapies that increase HDL can lower risk of developing AF.Clinical Trials Registration: http://clinicaltrials.gov/ct/show/NCT00338260?order=1.
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Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome.
Handisides, JC, Hollenbeck-Pringle, D, Uzark, K, Trachtenberg, FL, Pemberton, VL, Atz, TW, Bradley, TJ, Cappella, E, De Nobele, S, Groh, GK, et al
The Journal of pediatrics. 2019;:250-255.e1
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OBJECTIVE To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. STUDY DESIGN The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. RESULTS Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. CONCLUSIONS Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.
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Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies.
Solayman, MH, Langaee, TY, Gong, Y, Shahin, MH, Turner, ST, Chapman, AB, Gums, JG, Boerwinkle, E, Beitelshees, AL, El-Hamamsy, M, et al
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2019;:93-98
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β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.
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The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct.
Joseph, P, Pais, P, Dans, AL, Bosch, J, Xavier, D, Lopez-Jaramillo, P, Yusoff, K, Santoso, A, Talukder, S, Gamra, H, et al
American heart journal. 2018;:72-79
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BACKGROUND It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.
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A randomized, double blind pilot study to assess the effects of losartan vs. atenolol on the biophysical properties of the aorta in patients with Marfan and Loeys-Dietz syndromes.
Sandor, GG, Alghamdi, MH, Raffin, LA, Potts, MT, Williams, LD, Potts, JE, Kiess, M, van Breemen, C
International journal of cardiology. 2015;:470-5
Abstract
BACKGROUND Patients with Marfan (MFS) and Loeys-Dietz (LDS) syndromes have been shown to have abnormal aortic biophysical properties. The purpose of this study was to compare the effects of 12-months of therapy with atenolol or losartan on vascular function in young patients with MFS and LDS. METHODS Seventeen patients with MFS or LDS were recruited and randomized to treatment with atenolol, 25-50mg, or losartan, 25mg daily. Prior to treatment and following therapy, echocardiography for left ventricular size, function and aortic root size was performed. Pulse wave velocity (PWV), input (Zi, ZiF) and characteristic (Zc, ZcF) impedances, arterial stiffness (Ep and β-index), total arterial compliance (TAC), mean (Wm) and total (Wt) hydraulic power, efficiency, power cost per unit of forward flow (Wt/CI) and brachial artery flow-mediated dilation (FMD) were measured. RESULTS The atenolol group consisted of 9 females (17.6years) and the losartan group 7 males and 1 female (17.0years). Their height, weight, BSA, BMI, systolic and diastolic blood pressures were similar. Baseline to 12-month changes for atenolol and losartan were PWV (20% vs -14%), Zi (-2% vs -27%), Zc (-20% vs -27%), Ep (1%, vs -13%), β-index (10% vs 14%), FMD (11% vs 20%), TAC (3% vs 42%), Wm (-24% vs 15%), Wt (-24% vs 17%), and Wt/CI (3% vs 21%). There was a trend for losartan to decrease PWV and stiffness indexes while atenolol decreased power and power/unit flow. CONCLUSION This pilot study suggests that atenolol and losartan may have different mechanisms of action on vascular function. A larger clinical trial is needed to confirm these effects.Clinical trials registration NCT00593710 (ClinicalTrials.gov).
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Long-term antihypertensive treatment fails to improve E/e' despite regression of left ventricular mass: an Anglo-Scandinavian cardiac outcomes trial substudy.
Barron, AJ, Hughes, AD, Sharp, A, Baksi, AJ, Surendran, P, Jabbour, RJ, Stanton, A, Poulter, N, Fitzgerald, D, Sever, P, et al
Hypertension (Dallas, Tex. : 1979). 2014;(2):252-8
Abstract
Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the short term, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine±perindopril-based or an atenolol±bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (≈1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5-116.8; atenolol: 122.9-117.5; P<0.001 for both). Conversely, tissue Doppler diastolic indices did not change in the amlodipine±perindopril-based regimen (E/e', 7.5-7.6 cm/s; P=not significant), but deteriorated in the atenolol±bendroflumethiazide-based regimen (E/e', 8.0-8.5 cm/s; P<0.01). Despite regression of left ventricular hypertrophy, there was no associated improvement in diastolic function. In fact, long-term treatment with atenolol±bendroflumethiazide resulted in a progressive deterioration in E/e'. This may be a factor contributing to the previously described worse clinical outcome in patients treated with atenolol±bendroflumethiazide compared with amlodipine±perindopril.
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Anti-sympathetic action enhances statin's pleiotropic effects: the combined effect of rosuvastatin and atenolol on endothelial function.
Takase, B, Hattori, H, Tanaka, Y, Nagata, M, Ishihara, M
International angiology : a journal of the International Union of Angiology. 2014;(1):27-34
Abstract
AIM: Assessment of flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery by a new device (UNEXEF18G) has been reported to be excellent for evaluating endothelial function, and sympathetic overdrive can accelerate the atherosclerotic process. The purpose of this study was to investigate and confirm whether anti-sympathetic beta-blocking action can enhance the pleiotropic effects of statins. METHODS FMD and NMD were measured using the UNEXEF18G before and after 4-week treatment of rosuvastatin (5 mg/day) with or without atenolol (25 mg/day) in 44 hypercholesterolemic patients (70±8 years old, LDL-C >140 mg/dL) with hypertension. Patients were randomly allocated to two treatment arms: rosuvastatin alone (R-group, N.=22) and rosuvastatin with atenolol (RA-group, N.=22). RESULTS Baseline FMD was not different between the two treatment arms, and both groups showed improvement in FMD (R-group, 3.48±1.9% to 4.65±2.41%, P<0.05; RA-group, 3.42±1.48% to 5.46±1.79%, P<0.05), while there were no differences in NMD. The effects on lipid profiles were identical in the two groups. In addition, FMD improvement was greater in the RA-group than in the R-group (Δchange 2.15±1.29% vs. 1.16±1.15%, P<0.05). CONCLUSION Beta-blockade enhances the pleiotropic effects of statins on endothelial function. The mechanism should be confirmed by further studies.
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Effect of long-term antihypertensive treatment on white-coat hypertension.
Mancia, G, Facchetti, R, Parati, G, Zanchetti, A
Hypertension (Dallas, Tex. : 1979). 2014;(6):1388-98
Abstract
Limited evidence is available on the extent and frequency by which antihypertensive treatment lowers office blood pressure (BP) in white-coat hypertension (WCH). Data are even more scanty and discrepant on the corresponding effect on ambulatory BP (ABP). In the hypertensive patients of the European Lacidipine Study on Atherosclerosis (ELSA), office and ABP were measured before treatment and at 6-month (office BP) or 12-month (ABP) intervals during the 4-year administration of calcium channel blocker-based or β-blocker-based treatment. The two groups were pooled and data were analyzed separately in patients with both office and ABP elevation (n=1670; sustained hypertension) or WCH (n=251; office BP elevation only). In sustained hypertension, office and 24-hour mean systolic BP were both markedly reduced through the treatment period, the mean change being -20.0±12.5 and -10.1±11.0 mm Hg, respectively (P<0.0001 for both). In striking contrast, in WCH the office BP reduction was almost as marked as in sustained hypertension (-19.1±11.2 mm Hg; P<0.0001), whereas 24-hour systolic BP values showed no fall or a slight progressive significant increase, its mean change during treatment being 1.6±8.6 mm Hg (P=0.007). Lowering of office BP occurred at a lower treatment intensity in WCH than in sustained hypertension. Similar findings were obtained for diastolic BP. In WCH, antihypertensive treatment should not be expected to have a lowering effect on ABP, even when office BP undergoes a concomitant marked and persistent reduction. The consequence of this contrasting effect on the incidence of hypertension-related outcomes remains to be established.