Β-blockers In Hypertension Research Articles

Blood-brain barrier permeable β-blockers linked to lower risk of Alzheimer's disease in hypertension.

Alzheimer's disease is a neurodegenerative disorder in which the pathological accumulation of amyloid-β and tau begins years before symptom onset. Emerging evidence suggests that β-blockers (β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing CSF flow. Our objective was to determine whether β-blocker treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer's disease compared to less permeable β-blockers. Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. People with indications for β-blocker use other than hypertension (e.g. heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics and socioeconomic variables. Death was modelled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment. In a cohort of 69 081 (median age = 64.4 years, 64.8% female) people treated with β-blockers for hypertension, highly blood-brain barrier-permeable β-blockers were associated with reduced risk of Alzheimer's disease versus low permeability β-blockers (-0.45%, P < 0.036). This effect was specific to Alzheimer's diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low blood-brain barrier-permeable patients also detected a decreased Alzheimer's risk (-0.92%, P < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (-0.57%, P < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment. Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood-brain barrier permeable β-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer's disease by promoting waste brain metabolite clearance.

Beta-Adrenergic Blockers’ Supportive and Adverse Role in Hypertension: A Review of Three Generations

ABSTRACT Hypertension causes significant mortality and morbidity around the world. The β-adrenergic blockers are one of the most commonly prescribed hypertension medications. Several β-adrenergic blockers with different pharmacological qualities have been developed, which may be grouped into three generations based on the differences in pharmacological properties. In this narrative review, we addressed evidence-based literature about the role of various types of β-blockers and related adverse drug reactions (ADRs) in hypertension. PubMed, Scopus, Google Scholar, and MEDLINE are used for articles search. The title was examined first, followed by the abstract, and then the entire study. We concluded that the first-generation β-blockers are non-selective and used as antihypertensive however, not recommended for diabetic, asthmatic, and chronic obstructive pulmonary disease patients. The second-generation β-blockers are β1 receptor-selective which are the effective pharmacological option for the treatment of hypertension, with a lower risk of adverse effects associated with antagonism of β2-receptor. Third-generation β-blockers showed improved effects on patients as compared to the previous two generations. This class of β-blockers (labetalol, carvedilol, and nebivolol) has vasodilatory abilities and has an extra beneficial influence with fewer ADRs. However, the effectiveness and benefit of β-blockers as first‐line therapy for hypertension is still controversial. As a result, further accurate screenings, as well as large randomized control clinical trials (RCTs), are needed to investigate the role of all β-blockers in hypertension. Keywords: Hypertension; Beta-Adrenergic Blockers; Blood Pressure; Literature Review.

β1-Blockers Lower Norepinephrine Release by Inhibiting Presynaptic, Facilitating β1-Adrenoceptors in Normotensive and Hypertensive Rats.

Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here the author tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET), presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol) reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551) and β1+2AR (nadolol) antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood–brain barrier, reduced norepinephrine overflow after adrenalectomy (AdrX), AdrX + ganglion blockade, losartan, or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1 receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as myocardial infarction.

Role of Elevated Heart Rate in the Development of Cardiovascular Disease in Hypertension

That elevated heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in healthy people as well as in patients with cardiac diseases is supported by numerous epidemiological association studies.1–4 Increased HR has been recognized as a negative prognostic factor independent of many other clinical parameters that can influence the HR, including physical activity scores, left ventricular function, or use of β-blockers. Thus, HR appears to satisfy all epidemiological criteria for being considered as a true risk factor, and its predictive value for cardiovascular disease appeared to be as strong as that of most important cardiovascular risk factors. This is particularly true for the results obtained in hypertensive patients. Elevated HR is a common feature among hypertensive individuals.1 Among the young hypertensive subjects participating in the HARVEST study, >15% had a baseline resting HR ≥85 bpm and 27% had a HR ≥80 bpm.5 According to the Tensiopulse study, which evaluated 38 145 patients cared for by 2000 general practitioners all across Italy, >30% of the hypertensive patients had a resting HR ≥80 bpm.6 In a large French population, untreated hypertensive subjects had approximately a 6-bpm faster HR than normotensive individuals.7 Elevated HR is frequently associated with high blood pressure (BP) and metabolic disturbances and increases the risk of new onset hypertension and diabetes.1 Many experimental data obtained both in animals and in human beings support the importance of HR as a true risk factor for atherosclerosis and cardiovascular disease, providing convincing evidence for this pathogenetic mechanism.1–3 The pathogenetic connection between HR and cardiovascular disease has been discussed in several reports1–3,8,9 and is beyond the scope of this review. ### High HR as a Precursor of Hypertension, Obesity, and Diabetes Numerous studies have demonstrated that tachycardia is frequently associated with hypertension in …

β-Adrenergic Antagonists in Hypertension: A Review of the Evidence

To evaluate the effects of beta-adrenergic antagonist therapy on cardiovascular and cerebrovascular outcomes in the treatment of hypertension. Literature searches were conducted using MEDLINE (1966-August 2009), International Pharmaceutical Abstracts (1970-August 2009), and Cochrane Database of Systematic Reviews (until third quarter 2009) to locate clinical trials and meta-analyses comparing beta-blocker therapy with placebo or other antihypertensive agents in patients with hypertension. Bibliographies from relevant research and review articles were reviewed for additional references. All English-language articles identified from the data sources were reviewed. Articles describing original research with cardiovascular or cerebrovascular outcomes and/or death as either primary or secondary endpoints were included. Articles describing the use of beta-blocker therapy for conditions other than hypertension were not included. Five placebo-controlled studies and 10 active-controlled studies were reviewed. In addition, 11 meta-analyses were evaluated. Placebo-controlled trials of beta-blockers in hypertension provide evidence of reduced risk for stroke, cardiovascular events, and heart failure. Only 2 studies comparing beta-blockers with other antihypertensives found significant benefit with beta-blockers. However, the majority of meta-analyses comparing beta-blockers with other antihypertensive agents show increased risk for stroke with beta-blockers, and some data suggest increased risk for cardiovascular events and all-cause mortality. The majority of data results from studies of atenolol, and many studies employed combination antihypertensive therapies, which often included thiazide diuretics. Overall, data supporting beta-blockers as preferred therapy in hypertension are inadequate. Although most negative cardiovascular and cerebrovascular outcomes of beta-blockers were associated with atenolol therapy, data supporting other beta-blockers in hypertension are lacking.

β‐Blockers in Hypertension: Truths and Half‐Truths

β‐Blockers in Hypertension: Truths and Half‐Truths

1- and 2-Adrenergic Receptor Gene Variation, -Blocker Use and Risk of Myocardial Infarction and Stroke

The benefits of β-blocker therapy may depend on underlying genetic susceptibility. We investigated the interaction of common variation in β1 and β2 adrenergic receptor (AR) genes with β-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case–control study. Participants were treated pharmacologically for hypertension, aged 30–79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. We observed an interaction of β-blocker use with β1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, β-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26–5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73–1.07). Another variant, rs#2429511, interacted with β-blocker use on both MI and ischemic stroke risks. β-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03–1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51–0.94). β-blocker use did not interact with β2-AR gene variation on the risks of MI and ischemic stroke. These results, which require replication, suggest genetic variants in the β1-AR gene may determine whether to use β-blockers in hypertension for the primary prevention of cardiovascular disease.

Another Look at β-Blockers for Hypertension

A recent meta-analysis suggested that β-blockers were less effective than other antihypertensive drugs in preventing stroke. This finding led the researchers to conclude that β-blockers should not be first-line drugs for patients with uncomplicated hypertension (Journal Watch Dec 9 2005). Now, two other researchers have conducted a meta-analysis of …

Changes in the usage of antihypertensive drugs: implications and prospects

In their paper [1], Cheung and colleagues describe changes in antihypertensive drug usage over 8 years at a university hospital in Hong Kong. The quantitative analysis of usage frequency is supplemented by estimates of the percentage of patients with blood pressure at target levels. Their findings prompt a number of questions, about patterns of drug usage in different populations worldwide, the possible influences on these patterns and how these might change over the next few years. Of course, such detailed information is not available everywhere, so some comparisons are likely to remain speculative. In this particular case there are apparently no specific Hong Kong or Chinese national guidelines which are applicable, unlike the USA or Europe [2–4]: it would indeed be very interesting to establish how far such guidelines do actually modify prescribing practice in countries where they are supposed to be applicable. Regardless of that, Cheung's paper can serve as a focus for several current issues of interest and debate.

β-blockers in hypertension: is carvedilol different?

Most studies assessing the effects of β-blockers were carried out with traditional, β 1-selective β-blockers, such as metoprolol and atenolol. Pathophysiologic and pharmacologic studies have documented that not all β-blockers are created equal. In particular, the pharmacologic and clinical profiles of the newer, vasodilating β-blockers, such as carvedilol, have been shown to differ from those of the traditional β-blockers. These differences, although relevant in the younger patient with hypertension, are particularly important in elderly patients in whom traditional β-blockers may not be as effective or as well tolerated as the newer vasodilating agents.

β-blockers in hypertension—the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.

The diet-induced proinflammatory state:: A cause of chronic pain and other degenerative diseases?

Background: It is the rare physician who includes diet therapy and nutritional supplements in patient care. Perhaps this is because chiropractic and medical schools devote very few classroom hours to nutrition. It is also possible that physicians are under the misconception that a detailed biochemical understanding of each individual disease is required before nutritional interventions can be used. Objective: The purpose of this article is two-fold: (1) to demonstrate that chronic pain and other degenerative conditions encountered in clinical practice have similar biochemical etiologies, such as a diet-induced proinflammatory state, and (2) to outline a basic nutritional program that can be used by all practitioners. Data Sources: The data were accumulated over a period of years by reviewing contemporary articles and books and subsequently by retrieving relevant articles. Articles were also selected through MEDLINE and manual library searches. Results: The typical American diet is deficient in fruits and vegetables and contains excessive amounts of meat, refined grain products, and dessert foods. Such a diet can have numerous adverse biochemical effects, all of which create a proinflammatory state and predispose the body to degenerative diseases. It appears that an inadequate intake of fruits and vegetables can result in a suboptimal intake of antioxidants and phytochemicals and an imbalanced intake of essential fatty acids. Through different mechanisms, each nutritional alteration can promote inflammation and disease. Conclusion: We can no longer view different diseases as distinct biochemical entities. Nearly all degenerative diseases have the same underlying biochemical etiology, that is, a diet-induced proinflammatory state. Although specific diseases may require specific treatments, such as adjustments for hypomobile joints, β-blockers for hypertension, and chemotherapy for cancer, the treatment program must also include nutritional protocols to reduce the proinflammatory state.

β-Blockers for Hypertension in Pregnant Diabetic Women

β-Blockers for Hypertension in Pregnant Diabetic Women

Looking for an Alternative to β-Blockers in Hypertension?

Looking for an Alternative to β-Blockers in Hypertension?

Combined use of prazosin and beta-blockers in hypertension.

Combined use of prazosin and beta-blockers in a hypertension clinic over a 3-year period was surveyed by means of a computerized record system. Of the 1,250 patients in the clinic, 171 (14%) had been treated with this combination for periods averaging 17 months. Prazosin was administered with a beta 1-selective beta-blocker in 94 cases and with a beta 1 + beta 2-blocker in 100 cases; 23 patients had received treatment with both combinations. Diuretics were given in 86% of cases and other antihypertensive drugs in 19%. The population treated had a high incidence of severe hypertension, with initial diastolic pressure greater than 120 mm Hg in 38% and between 100 and 120 mm Hg in 50%. The percentage of patients with diastolic pressure less than 100 mm Hg was 12% initially and 79% at the end of the treatment period. Side effects necessitated withdrawal of therapy in 35 cases. These were referable in 19 cases to prazosin and in 16 to beta-blockers. Prazosin was found to be more effective in lowering blood pressure in combination with beta 1-blockers than with beta 1 + beta 2-blockers, although there were fewer severe side effects with beta 1-blockers.

Mechanism of action of β-blockers in hypertension

Mechanism of action of β-blockers in hypertension