Effect Of Β-blocker Use Research Articles

Effects of the Use of Beta-Blockers on Chronic Obstructive Pulmonary Disease Associated with Cardiovascular Comorbities: Systematic Review and Meta-analysis.

Cardiovascular comorbidity is common in individuals with chronic obstructive pulmonary disease (COPD). This factor interferes with pharmacological treatment. The use of β-blockers has been proposed for their known cardioprotective effects. However, due to their adverse reactions, and the risk of causing bronchospasm, there is reluctance to use them. To summarize existing evidence on the effects of β-blocker use in COPD associated with cardiovascular comorbidities in relation to disease severity, exacerbation, and mortality outcomes. EMBASE, Medline, Lilacs, Cochrane Library, and Science Direct databases were used. Observational studies that evaluated the effects of β-blockers on individuals with COPD and cardiovascular comorbidities, and related disease severity, exacerbations, or mortality outcomes were included. Studies that did not present important information about the sample and pharmacological treatment were excluded. Twenty studies were included. Relevance to patient care and clinical practice: The use of β-blockers in individuals with COPD and cardiovascular disease caused positive effects on mortality and exacerbations outcomes, compared with the results of individuals who did not use them. The severity of the disease caused a slight change in forced expiratory volume in 1 second. The odds ratio for mortality was 0.50 (95% confidence interval [CI], 0.39 to 0.63; p<0.00001), and for exacerbations, 0.76 (95% CI, 0.62 to 0.92; p=0.005), being favorable to the group that used β-blockers. Further studies are needed to study the effect of using a specific β-blocker in COPD associated with a specific cardiovascular comorbidity.

Protective effects of β-blocker use on bone loss in older men with dementia in the health ABC study

Protective effects of β-blocker use on bone loss in older men with dementia in the health ABC study

The Possible Effect of β-Blocker Use on the Circulating MMP-2/TIMP-2 System in Patients with Chronic Kidney Disease on Conservative Treatment.

Background: The purpose of the study was to determine whether the use of β-adrenoceptor antagonists (β-blockers) can affect metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in patients with chronic kidney disease (CKD) on conservative treatment. Methods: The circulating MMP-2/TIMP-2 system, proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the marker of oxidative stress-Cu/Zn superoxide dismutase (Cu/Zn SOD)-were measured in 23 CKD patients treated with β-blockers [β-blockers (+)] and in 27 CKD patients not receiving the above medication [β-blockers (-)]. Results: The levels of MMP-2, TIMP-2, and IL-6 were significantly lower in the β-blockers (+) than in the β-blockers (-) group, whereas Cu/Zn SOD concentrations were not affected by β-blocker use. There was a strong, independent association between MMP-2 and TIMP-2 in both analyzed patient groups. In the β-blockers (+) group, MMP-2 levels were indirectly related to the signs of inflammation, whereas in the β-blockers (-) group, the alterations in the MMP-2/TIMP-2 system were associated with the oxidative stress marker and CKD etiology. Conclusions: This study is the first to suggest that the use of β-blockers was associated with the reduction in IL-6 and the MMP-2/TIMP-2 system in CKD, providing a pharmacological rationale for the use of β-blockers to reduce inflammation and abnormal vascular remodeling in CKD.

Effect of β-Blocker Use on Long-Term Mortality in Takotsubo Cardiomyopathy: A Systematic Review and Meta-Analysis

Effect of β-Blocker Use on Long-Term Mortality in Takotsubo Cardiomyopathy: A Systematic Review and Meta-Analysis

Pharmacogenomic Effects of β-Blocker Use on Femoral Neck Bone Mineral Density.

ContextRecent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.ObjectiveTo investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study.MethodsWe used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD.ResultsOne variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings.ConclusionThis analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.

Evaluating Central Aortic Blood Pressures in a Tertiary South Indian Hospital

Abstract Background Of late, central aortic blood pressure (CABP) has emerged as a better parameter than peripheral blood pressure (BP) in the diagnosis of cardiovascular events. Advent of new technologies has facilitated the calculation of CABP from machine-derived peripheral BP. In this study, the author determined the differences between peripheral BP measured manually or by machine and machine-derived CABP and examined whether this difference is stable even after categorizing the sample pool based on sex, hypertension, diabetes status, and β-blocker use. Materials and Methods A total of 83 patients (both male and female) who attended the cardiology outpatient department were enrolled in the study. BP was recorded both manually and using Mobil-O-Graph pulse wave analyzer (ARC Solver) in the patient's sitting posture. The author compared the derived central, manual, and device-measured BP among the patient samples and assessed whether sex, hypertension, diabetes, and β-blocker use influence these differences. Results Among the study population, 28 were females and 55 were males; patients’ mean age was 59.97 ± 12.15 years. The mean peripheral systolic BP (SBP) and diastolic BP (DBP) measured manually were127.55 ± 20.15 and 79.73 ± 9.57 mm Hg, respectively. Similar measurements recorded by the device were 129.68 ± 19.93 and 78.92 ± 13.48, respectively. The derived mean central aortic SBP and DBP was 117.69 ± 17.78 and 80.15 ± 13.71, respectively. Statistically significant difference in the manual and central aortic SBP (9.85 ± 11.16; p < 0.0001) was observed. This difference was significant irrespective of sex, hypertension, diabetes status, and β-blocker use. Similarly, difference between machine-derived peripheral SBP and central aortic SBP was statistically significant (p < 0.0001). However, the difference in manual and central aortic DBP was nonsignificant (p = 0.6976). Interestingly, a small (−1.34 ± 2.28) but statistically significant difference (p < 0.0001) between machine-derived peripheral DBP and central aortic DBP was observed. Further analysis to find out effect of β-blocker use on CABP revealed that the central aortic SBP is slightly, but statistically significantly, lower in β-blocker users (117.7 ± 17.71; p < 0.0001) than that of β-blocker nonusers (118.9 ± 18.37; p< 0.0001). Conclusion Central aortic systolic pressure is statistically significantly lower than the manually recorded peripheral SBP irrespective of sex, hypertension, diabetes status, and β-blocker use. A small but significant difference was observed between machine-derived peripheral DBP and central aortic DBP. Patients using β-blockers were observed to have marginally lower CABP values than those who are not using them.

β-Blocker use and reduced disease progression in patients with thick melanoma: 8 years of follow-up.

Previous observational studies have reported the protective effect of β-blockers on the progression of different types of cancers. In 2011, we published a prospective study, including patients with histologically confirmed malignant melanoma in stage II-IIIA. In total, 25% of them reported previous use of β-blockers that were administered at any time for any other diseases. After a median follow-up of 2.5 years, 34% of the patients in the untreated group showed disease progression. In contrast, only 3% of the patients in the treated group showed progression. We report the findings obtained in the same cohort after a longer period of β-blocker therapy and follow-up (8 years). We prospectively reviewed data of the patients enrolled in the original prospective study. Disease progression was assessed by evaluating the presence of lymphatic, in-transit or visceral metastases. Deaths by any cause and deaths because of melanoma were recorded. A multivariate Cox proportional hazards model was used to evaluate the effect of β-blocker use on disease-free survival and overall survival, adjusting for significant confounders. After a median follow-up of 8 years and a median duration of β-blocker use of 7.6 years, 45% of the patients in the untreated group and 30% of the patients in the treated group showed disease progression. Notably, in the untreated group 35% patients died from melanoma and only 17% patients died from melanoma in the treated group. Results of this hospital-based prospective cohort study with a median follow-up of 8 years confirmed our previous results that the use of β-blockers significantly reduced the risk of recurrence and mortality in melanoma patients.

β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies.

A number of epidemiologic studies have attempted to link the use of β blockers to mortality in cancer patients, but their findings have been inconclusive. A meta-analysis was carried out to derive a more precise estimation. Relevant studies were identified by searching PubMed and EMBASE to May 2015. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. Twenty cohort studies and four case-control studies involving 76 538 participants were included. The overall results showed that patients who used β blockers after diagnosis had an HR of 0.89 (95% CI 0.81-0.98) for all-cause mortality compared with nonusers. Those who used β blockers after diagnosis (vs. nonusers) had an HR of 0.89 (95% CI 0.79-0.99) for cancer-specific mortality. Prediagnostic use of β blockers showed no beneficial effect on all-cause mortality or cancer-specific mortality. Stratifying by cancer type, only breast cancer patients who used β blockers after diagnosis had a prolonged overall survival. A linear but nonsignificant trend was found between postdiagnostic β-blocker use and mortality of cancer patients. In conclusion, the average effect of β-blocker use after diagnosis but not before diagnosis is beneficial for the survival of cancer patients.

Effect of β-blockers on cardiac and pulmonary events and death in older adults with cardiovascular disease and chronic obstructive pulmonary disease.

In older adults with multiple conditions, medications may not impart the same benefits seen in patients who are younger or without multimorbidity. Furthermore, medications given for one condition may adversely affect other outcomes. β-Blocker use with coexisting cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) is such a situation. To determine the effect of β-blocker use on cardiac and pulmonary outcomes and mortality in older adults with coexisting COPD and CVD. The study included 1062 participants who were members of the 2004-2007 Medicare Current Beneficiary Survey cohorts, a nationally representative sample of Medicare beneficiaries. Study criteria included age over 65 years plus coexisting CVD and COPD/asthma. Follow-up occurred through 2009. We determined the association between β-blocker use and the outcomes with propensity score-adjusted and covariate-adjusted Cox proportional hazards. The 3 outcomes were major cardiac events, pulmonary events, and all-cause mortality. Half of the participants used β-blockers. During follow-up, 179 participants experienced a major cardiac event; 389 participants experienced a major pulmonary event; and 255 participants died. Each participant could have experienced any ≥1 of these events. The hazard ratio for β-blocker use was 1.18 [95% confidence interval (CI), 0.85-1.62] for cardiac events, 0.91 (95% CI, 0.73-1.12) for pulmonary events, and 0.87 (95% CI, 0.67-1.13) for death. In this population of older adults, β-blockers did not seem to affect occurrence of cardiac or pulmonary events or death in those with CVD and COPD.

Does Our “Flight and Fight” Response Have a Link With Cancer?

Does Our “Flight and Fight” Response Have a Link With Cancer?

Association Between Use of β-Blockers and Prostate Cancer–Specific Survival: A Cohort Study of 3561 Prostate Cancer Patients with High-Risk or Metastatic Disease

BackgroundWe recently reported reduced prostate cancer (PCa)–specific mortality for β-blocker users among patients receiving androgen-deprivation therapy in a health survey cohort including 655 PCa patients. Information on clinical characteristics was limited. ObjectiveTo assess the association between β-blockers and PCa-specific mortality in a cohort of 3561 prostate cancer patients with high-risk or metastatic disease, and to address potential confounding from the use of statins or acetylsalicylic acid (ASA). Design, setting, and participantsClinical information from all men reported to the Cancer Registry of Norway with a PCa diagnosis between 2004 and 2009 (n=24 571) was coupled with information on filled prescriptions between 2004 and 2011 from the Norwegian Prescription Database. Exclusion criteria were low- or intermediate-risk disease; planned radiotherapy or radical prostatectomy; initiation of β-blocker, ASA, or statin use after diagnosis where applicable; missing information on baseline Gleason score, prostate-specific antigen level, T stage or performance status; and missing follow-up. Outcome measurements and statistical analysisCox proportional hazards modelling and competing risk regression modelling were used to analyse the effects of β-blocker use on all-cause and PCa-specific mortality, respectively. Differences between β-blocker users and nonusers regarding baseline clinical characteristics were assessed by the Wilcoxon-Mann-Whitney U test, Pearson chi-square test, and Student t test. Results and limitationsMedian follow-up was 39 mo. β-Blocker use was associated with reduced PCa mortality (adjusted subhazard ratio: 0.79; 95% confidence interval [CI], 0.68–0.91; p value: 0.001). The observed reduction in PCa mortality was independent of the use of statins or ASA. We observed no association with all-cause mortality (adjusted hazard ratio: 0.92; 95% CI, 0.83–1.02). The main limitations of the study were the observational study design and short follow-up. Conclusionsβ-Blocker use was associated with reduced PCa-specific mortality in patients with high-risk or metastatic disease at the time of diagnosis. Our findings need validation from further observational studies.

Effect of β-blocker use on outcomes after discharge in patients who underwent cardiac surgery

Beta-blockers improve outcomes in patients with heart failure or a history of myocardial infarction, but it remains uncertain whether they are beneficial after the perioperative period in cardiac surgery patients without these conditions. This study was designed to examine whether discharge use of beta-blockers was associated with outcomes after hospitalization in patients who had undergone nontransplant cardiac surgery. We analyzed outcomes in a prospective cohort of 3102 patients discharged alive after cardiac surgery (2547 of whom had undergone coronary artery bypass grafting surgery) between September 2002 and August 2005. Beta-blockers were prescribed for 2580 (83%) patients at hospital discharge. Over a mean follow-up of 75 months (standard deviation, 20 months), 10% (259/2580) of patients discharged with beta-blockers and 19% (97/522) not prescribed beta-blockers at the time of hospital discharge died (hazard ratio of 0.65 [95% confidence interval, 0.49-0.87] after adjustment for covariates). One-year mortality was also lower in those discharged with beta-blockers: 2.2% (57/2580) in beta-blocker users versus 7.2% (38/522) in nonusers (adjusted odds ratio, 0.54 [95% confidence interval, 0.30-0.97]). The association between beta-blocker use and lower mortality was consistent across all examined subgroups, including patients without prior myocardial infarction or without heart failure (all P < .01). Patients discharged with beta-blockers after cardiac surgery exhibit a substantially lower mortality rate during long-term follow-up, even among those without a history of myocardial infarction or heart failure.

The Effect of β-Blocker Use on Cyclosporine Level in Cardiac Transplant Recipients

Beta-blockers are frequently used after cardiac transplantation for blood pressure control. There is no well-known interaction between beta-blockers and cyclosporine A (CsA). However, recent reports have suggested that carvedilol, but not metoprolol, modulates P-glycoprotein (P-gp), a membrane protein that regulates CsA absorption. We evaluated the effects of carvedilol and metoprolol on CsA level when initiated in cardiac transplant recipients. Using our cardiac transplant database, we identified patients who were started on either carvedilol or metoprolol for blood pressure control. We then compared their CsA doses and levels before and within 2 weeks after the initiation of beta-blocker therapy. We found 20 patients taking metoprolol and 12 patients taking carvedilol. With initiation of metoprolol, CsA level decreased in 12 patients and increased in 8 patients. The mean CsA level before and after metoprolol initiation was 236 ng/ml and 253 ng/ml, respectively (p = 0.50). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was not significantly adjusted (from a mean of 293 mg/day to a mean of 294 mg/day; p = 0.92). In the Carvedilol Group, CsA level increased in 10 of 12 patients. The mean CsA level before the initiation of carvedilol was 257 ng/ml. The mean CsA level after carvedilol initiation was 380 ng/ml (p = 0.009). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was reduced by 10%, from a mean of 319 mg/day to a mean of 288 mg/day (p = 0.004). Carvedilol, but not metoprolol, was associated with a significant increase in CsA levels after initiation in cardiac transplant recipients. Although carvedilol and CsA do not interact at the level of cytochrome P450 system, it appears that carvedilol influences CsA levels through its effects on P-gp. An average reduction of 10% is necessary on the CsA dose upon initiation of carvedilol, and close follow-up of the level is essential.

Clinical Relevance of Pharmacokinetic Differences Between Beta Blockers

Fundamental differences in the pharmacodynamic and pharmacokinetic profiles of β-adrenergic blocking agents must be considered in optimizing their efficacy and determining the appropriate selection of these drugs in different patients. Beta blockers are contraindicated in patients with asthma and should be used cautiously in heart failure. Clinically important distinctions are related to whether a β blocker is β 1-selective or nonselective. Most adverse effects of β-blocker use are related to interference with β 2-mediated functions including bronchodilation, vasodilation, and mobilization of free fatty acids. To achieve the potential benefits of β 1 blockade (decreased heart rate, blood pressure, cardiac workload, and excitability), a low plasma concentration of a β 1-selective drug is required. Adverse effects of β blockers can be further decreased by selecting a sustained-release β 1-selective drug. Beta blockers are further differentiated on the basis of lipophilicity or hydrophilicity. Lipophilic β blockers cross the blood-brain barrier, whereas hydrophilic agents do not enter the central nervous system. Some lipophilic agents (metroprolol, timolol, and propanolol) have been shown to decrease mortality in coronary heart disease, particularly sudden cardiac death.