Chronic Beta-blockade Research Articles

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days

BackgroundThere is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. MethodsThe present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. ResultsA total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). ConclusionsContinuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Prognostic value of diastolic wall strain in patients with chronic heart failure with reduced ejection fraction.

Left ventricular (LV) diastolic dysfunction plays a crucial role in heart failure with reduced ejection fraction (HFrEF). LV stiffness is a main component of diastolic function, but its role and prognostic value in HFrEF patients remains unclear. This study aimed to determine whether diastolic wall strain (DWS) as a noninvasive and simple marker of LV stiffness can predict the prognosis of HFrEF patients who were administrated chronic beta blockade enough. We enrolled 75 HFrEF patients who were administrated chronic beta blockade. We evaluated the echocardiographic parameters and plasma brain natriuretic peptide (BNP) before the induction of beta blockade and also obtained pulmonary artery wedge pressure (PAWP) from the right heart catheterization. DWS was obtained from standard M-mode echocardiography as follows: DWS=[(LV posterior wall thickness (LVPWT) at end-systole-LVPWT at end-diastole)/LVPWT] at end-systole. DWS did not correlate with other echocardiographic parameters and PAWP. We defined primary outcome as HF hospitalizationor cardiovascular death and followed for 7years. The incidence rate was higher in low DWS than high DWS patients (p=0.04). Other echocardiographic parameters could not be significant predictors of HFrEF outcome under the condition of enough beta blocker therapy. In multivariate analysis, DWS was the independent contributor to the event-free time. Impaired LV stiffness evaluated with DWS was associated with worse outcome and DWS might be an independent prognostic factor in HFrEF patients with chronic beta blockade.

Abstract 11763: Impact of Beta Blockade on Prognosis in Patients With Chronic Severe Degenerative Mitral Regurgitation

Background: The impact of chronic beta blockade (BB) on cardiac events (CE) in patients (pts) with chronic severe mitral regurgitation (MR) has not been studied by randomized trials but is inferred as beneficial from observational data. However a recent randomized preclinical study demonstrated increased mortality with BB in MR. Methods: We retrospectively analyzed 45 consecutive study-eligible pts (age 49±12 yrs, 69% male) with isolated chronic severe non-ischemic MR without concomitant coronary disease, followed through 19 yrs, to assess impact of chronic BB use at entry on CE (death or indications for valve surgery). At entry, all pts were non-hypertensive (HTN) and free of surgical indications; 9 pts chronically received BB at entry (of whom 7 continued receiving BB throughout the study period). CE rate differences were assessed by Kaplan-Meier log rank comparison; 6 pts on non-selective BBs were analyzed separately on an exploratory basis. Cox model analysis was used to adjust for variations in other baseline covariates (age, gender, etiology, other cardiac drugs). Results: During follow-up, CE included: sudden death (1), heart failure (8), a-fib (6), left ventricular (LV) dimensions (IDs)>4.5cm (11), LV ejection fraction (EF)<60% (6), right ventricular (RV) EF<35% (2), combination CE (7). CE risk was 2-fold higher among pts receiving BB (Avg annual risk [AAR]= 15.28%) vs. those not receiving BB (AAR= 33.04%) (p<.05) (Figure). A > 3-fold relative CE risk was observed when pts on selective BB were excluded (AAR: BB vs no BB = 56.18% vs. 15.28%, p=.01). BB effects remained statistically significant (p<.05) when analyses were adjusted for other baseline covariates. Conclusions: Contrary to earlier observational data, in our series BB appears to increase CE risk in pts without HTN. Further research including larger numbers of MR pts, preferably via randomized design, is needed to clarify the discrepancy between the different findings among existing studies.

Abstract 13770: DWS as an Index of Myocardial Stiffness and a Predictor of Heart Failure Outcome in Patients with Chronic Beta-blockade Therapy

Background: Diastolic dysfunction determines symptoms and prognosis in patients with left ventricular (LV) dysfunction. Diastolic wall strain (DWS) is associated with poor outcomes in heart failure with preserved ejection fraction. However, the utility of DWS is still unknown in heart failure with reduced ejection fraction (HFrEF). Our aim is to determine whether DWS is predictive of the outcome in HFrEF. Methods: We studied 54 HFrEF patients (LVEF<50%) and followed DWS as an index of myocardial stiffness for 6 months after the induction of beta blockade (Bisoprolol 2.5-10 mg / day). DWS was determined in the LV M-mode echocardiogram using the following equation: DWS = {(LV posterior wall thickness at end-systole - LV posterior wall thickness at end-diastole) / LV posterior wall thickness at end-systole}. We followed for 7years after the induction of beta-blockade. Results: DWS increased after the induction of beta-blockade (0.32±0.11 vs 0.25±0.12,p<0.05). DcT, EF and E’ also increased after the induction of beta-blockade. HR at rest and log BNP decreased following beta blockade. Patients with DWS ≤ median (0.25) before the induction of beta-blockade had higher rate of HF hospitalization than those with DWS >median during 7 years (Log-rank p =0.025). DcT, EF, E’, HR at rest and log BNP before the induction of beta blockade were not significant predictors of HF outcome (Log-rank p=0.263, 0.504, 0.0796, 0.289 and 0.877) respectively. Conclusions: Induction of beta-blockade provided an improvement in DWS. DWS might be useful as an index of myocardial stiffness to predict the outcomes in HFrEF patients with chronic beta-blockade therapy.

A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study

PurposeClonidine may help prevent cardiac complications in patients undergoing non-cardiac surgery and receiving chronic beta-blocker therapy. We conducted a multicentre pilot randomized trial to estimate recruitment rates for a full-scale trial and to assess the safety and tolerability of combining clonidine with chronic beta-blockade.MethodsPatients who were at elevated perioperative cardiac risk, receiving chronic beta-blockade, and scheduled for major non-cardiac surgery were recruited in a blinded (participants, clinicians, outcome assessors) placebo-controlled randomized trial at three Canadian hospitals. Participants were randomized to clonidine (0.2 mg oral tablet one hour before surgery, plus 0.2 mg·day−1 transdermal patch placed one hour before surgery and removed four days after surgery or hospital discharge, whichever came first) or matching placebo. Feasibility was evaluated based on recruitment rates, with each centre being required to recruit 50 participants within 12-18 months. Additionally, we reviewed study drug withdrawals and safety outcomes, including clinically significant hypotension or bradycardia.ResultsEighty-two of the 168 participants were randomized to receive clonidine and 86 to receive placebo. The average time to recruit 50 participants at each centre was 14.3 months. Six patients (7%) withdrew from clonidine, while four (5%) withdrew from placebo. Based on qualitative review, there were no major safety concerns related to clonidine. There was a moderate overall rate of cardiac morbidity, with 18 participants (11%) suffering postoperative myocardial infarction.ConclusionThis pilot randomized trial confirmed the feasibility, safety, and tolerability of a full-scale trial of oral and transdermal clonidine for reducing the risk of cardiac complications during non-cardiac surgery. This trial was registered at www.clinicaltrials.gov: NCT00335582.Electronic supplementary materialThe online version of this article (doi:10.1007/s12630-014-0226-6) contains supplementary material, which is available to authorized users.

Reconsidering the Use of Propranolol in the Treatment of Cosmetic Infantile Hemangiomas

Reconsidering the Use of Propranolol in the Treatment of Cosmetic Infantile Hemangiomas

P10 Randomised Placebo Controlled Trial to Evaluate Chronic Dosing Effects of Propranolol in Steroid Treated Persistent Asthmatics

Introduction and ObjectivesBeta-blockers are associated with acute bronchospasm in asthmatics. However preliminary unblinded studies have shown potential therapeutic benefits with chronic beta-blockade on airway hyper-responsiveness (AHR) in steroid naïveasthmatics. We...

Risk to and resilience of the coronary heart disease patient during surgery

Three topics are at the forefront of the investigation and treatment of patients with coronary artery disease (CAD) undergoing major noncardiac surgery: prophylactic perioperative beta-blockade (PPBB), prophylactic statins and prophylactic preoperative coronary revascularization (PCR). The purpose of the review is to summarize the investigational efforts in each one of these fields and to provide a subjective evaluation as to their impact on perioperative patient care. The data on PPBB are still controversial. Most recent studies are observational with contradicting results on whether PPBB improves perioperative survival and whether chronic beta-blockade is better than beta-blockers added acutely postoperatively. The data on statins are still evolving and the main question remains whether the proven long-term pleiotrophic, plaque-stabilizing effects of statins translate into measurable improvements in hard outcome in the acute, perioperative setting. The data on PCR are also incomplete. The study that previously reported lack of any perioperative benefit to PCR now provides data that in selected patients PCR may nevertheless improve outcome. These topics demonstrate how difficult it is to prove a significant change in outcome in high-risk CAD patients by prophylactic preoperative measures and that there is no alternative to clinical judgment and individualized patient care.

Incremental value and safety of oral ivabradine for heart rate reduction in computed tomography coronary angiography

BackgroundHeart rate (HR) reduction is essential to achieve optimal image quality and diagnostic accuracy with computed tomography coronary angiography (CTCA). Administration of ivabradine could be an attractive alternative to beta-blockade to reduce HR. MethodsOne-hundred-twenty-three patients referred for CTCA were prospectively enrolled. Patients were divided in two groups depending on the absence or presence of chronic beta-blockade treatment. Within the two groups patients were randomized to either no additional premedication or oral ivabradine for 5days prior to CTCA. In presence of chronic beta-blockade therapy it was shifted to atenolol 50mg twice a day for 5days prior to CTCA. HR and blood pressure were assessed at admission (T0), immediately before CTCA (T1) and during CTCA (T2). The target HR was <65bpm. ResultsIvabradine significantly reduced HR during CTCA. Mean relative HR reduction was 15% for controls, 12% for chronic beta-blockade, 19% for ivabradine and 24% for both chronic beta-blockade and ivabradine at T2 (p for trend <0.001). The rate of patients who reached the target HR at T2 was 83% in controls, 71% with chronic beta-blockade, 97% with ivabradine and 97% with both (p for trend <0.05). The percentage of patients that needed additional IV beta-blockade at T1 decreased from 69% to 40% with ivabradine and 30% with both (p for trend <0.05). ConclusionsIvabradine is safe and effective in increasing the rate of patients at target HR and in reducing the need for additional IV beta-blockade in patients referred for CTCA.

Attenuation of Adenosine-Induced Myocardial Perfusion Heterogeneity by Atenolol and Other Cardioselective β-Adrenoceptor Blockers: A Crossover Myocardial Perfusion Imaging Study

Little is known about the effect of chronic beta-blockade on adenosine actions. We sought to investigate the effect of oral beta-blockers on the presence, extent, and severity of myocardial perfusion abnormality induced by adenosine in patients with coronary artery disease. In this crossover study, 45 male patients with coronary artery disease on beta-blocker therapy with atenolol, bisoprolol, or metoprolol underwent adenosine myocardial perfusion imaging both on and off beta-blockade in a random order on separate days. Myocardial perfusion was assessed both qualitatively and quantitatively. Hemodynamic response, image analysis, and sensitivity for the detection of coronary stenosis (>or=50% luminal diameter reduction on x-ray coronary angiography) were compared between the on and off beta-blocker studies. Rate pressure product both at baseline and at peak adenosine infusion decreased by 23% +/- 15% and 21% +/- 18%, respectively, after beta-blockade (P < 0.001 for all). The median (interquartile range) summed difference score, a measure of defect reversibility, and quantitative defect size were both significantly lower after beta-blockade (median, 7.0 [interquartile range, 2.0-9.5] vs. median, 5.0 [interquartile range, 0-8.0], P = 0.002; and quantitative defect size, 18% [interquartile range, 9%-34%] vs. quantitative defect size, 6% [interquartile range, 0%-19%], P < 0.001, respectively). The overall sensitivity for the detection of coronary stenosis decreased from 0.76 (95% confidence interval, 0.65-0.88) to 0.58 (95% confidence interval, 0.45-0.71) after beta-blockade (P = 0.03). beta-blockade causes a small but significant reduction in the extent and severity of perfusion abnormality by adenosine. This may reduce the diagnostic sensitivity of adenosine myocardial perfusion imaging for the detection of flow-limiting coronary stenosis.

The experts debate: Perioperative beta-blockade for noncardiac surgery—proven safe or not?

Guidelines on perioperative management of patients undergoing noncardiac surgery recommend the use of prophylactic perioperative beta-blockers in high-risk patients who are not already taking them, and their continuance in patients on chronic beta-blockade prior to surgery. These recommendations were challenged recently by results of the Perioperative Ischemic Evaluation (POISE), a large randomized trial of extended-release metoprolol succinate started immediately before noncardiac surgery in patients at high risk for atherosclerotic disease. While metoprolol significantly reduced myocardial infarctions relative to placebo in POISE, it also was associated with significant excesses of both stroke and mortality. The merits and limitations of POISE and its applicability in light of other trials of perioperative beta-blockade are debated here by two experts in the field-Dr. Don Poldermans and Dr. P. J. Devereaux (co-principal investigator of POISE).

Cardiovascular problems in noncardiac surgery

Perioperative cardiac complications remain a major area of concern as our surgical population increases in volume, age and frequency of comorbidity. A variety of strategies can be used to optimize patients and potentially reduce the incidence of these serious complications. Recent literature suggests a trend towards less invasive testing for detection and quantification of coronary artery disease and greater interest in pharmacologic 'cardioprotection' using beta-blockers, statins and other agents targeting heart rate control and other mechanisms (e.g. reducing inflammatory responses). The recent Perioperative Ischemic Evaluation study has substantially altered this approach at least towards widespread application to lower/intermediate risk cohorts. Considerable attention has been focused on ensuring optimal standardized perioperative management of patients with a recent percutaneous coronary intervention, particularly those with an intracoronary stent. Widespread surveillance of postoperative troponin release and increasing recognition of the prognostic potential of elevated preoperative brain natriuretic peptides point towards changing strategies for long-term risk stratification. The complexity of a particular patient's physiologic responses to a wide variety of surgical procedures, which are undergoing constant technological refinement generally associated with lesser degrees of invasivity and stress make calculation of patients' perioperative risk very challenging. At the present time, adequate information is available for the clinician to screen patients with high-risk preoperative predictors, delay elective surgery for patients with recent intracoronary stents and continue chronic beta-blockade in appropriate patients. New large-scale database and subanalyses of major trials (e.g. Perioperative Ischemic Evaluation and Coronary Artery Revascularization Prophylaxis) should provide additional information to minimize perioperative cardiac risk.

The influence of beta-blockade on the hemodynamic effects of levosimendan in elderly (>= 70 years) patients with acutely decompensated systolic heart failure

The purpose of this study was to evaluate the influence of chronic beta-blockade on the hemodynamic parameters in elderly (>or= 70 years) patients with acutely decompensated systolic heart failure treated with levosimendan. Eighteen patients with acutely decompensated systolic heart failure (8 on chronic beta-blockade) were included in this study. Inclusion criteria were symptoms and signs of acute heart failure in the presence of: a) left ventricular ejection fraction < 0.35; b) cardiac index < 2.5 l/min/m2, c) pulmonary capillary wedge pressure > 15 mmHg; and d) systolic blood pressure between 90 and 110 mmHg. After completion of baseline hemodynamic measurements, a levosimendan intravenous infusion was started (initial loading dose given as an infusion of 24 microg/kg over 10 minutes, followed by a continuous infusion of 0.1 microg/kg/min for 24 hours). At the end of levosimendan infusion hemodynamic measurements were repeated. Demographic characteristics as well as baseline systolic and diastolic blood pressure were not significantly different between patients not receiving beta-blockers (Group A) and those under beta-blockade (Group B), whereas heart rate was significantly lower in the latter. Treatment with levosimendan was associated with an increase in the cardiac index and a decrease in wedge pressure in both groups (Group A: 43.8% and 33%; p < 0.001 vs. baseline; Group B: 17.72% and 17.5%, p < 0.001 vs. baseline, respectively). Peripheral and pulmonary resistance significantly decreased in both groups (31% vs. 15%, p < 0.001 and 44.5% vs. 25%, p < 0.001, respectively). Thus, the beneficial hemodynamic effects of levosimendan are maintained in elderly patients with acute decompensated systolic heart failure treated with beta-blockers.

Withdrawal phenomena after chronic beta-blockade. Causes and therapeutic consequences

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Tonic β-Adrenergic Drive Provokes Proinflammatory and Proapoptotic Changes in Aging Mouse Heart

Tonic activation of adrenergic drive has been found to be associated with aging, and its further activation is also seen in aging patients with major surgery or congestive heart failure. Nevertheless, its potential effect on the aging heart remains enigmatic. In the present study, at baseline, significant inflammatory and apoptotic changes were found in the aging mouse (20 months old), as evidenced by increases in inducible nitric oxide synthase (iNOS) expression, myocardial apoptosis in the heart, and C-reactive protein (CRP) release in the circulation. These phenotypic changes in aging animals can be induced in young animals (3 months old) by chronic beta-adrenergic receptor (AR) stimulation with isoproterenol (ISO), and they can be markedly reduced in aging animals by chronic beta-blockade with propranolol. Compared with young animals, chronic beta-AR stimulation with ISO in aging animals induced larger increases in iNOS expression, nitrotyrosine formation in the heart, and nitric oxide (NO) production and CRP release in the circulation; it also accelerated myocardial apoptosis and resulted in an enlarged infarct size when animals were subjected to myocardial ischemia and reperfusion (MI/R). However, the pretreatment of 1400W (N-(3-(aminomethyl) benzyl)acetamidine)-a specific iNOS inhibitor-significantly reduced iNOS-mediated nitrative stress associated with a marked decrease in myocardial apoptosis and infarct size in aging mice. These results demonstrate that tonic activation of the beta-adrenergic system associated with aging induces proinflammatory and proapoptotic changes in the heart and that additional beta-AR stimulation results in an exaggerated nitrative stress, mediated by iNOS, that is associated with more severe myocardial injury in aging mice.

Effect of chronic β-blockade on QT interval in patients with liver cirrhosis

QT interval prolongation is frequent in cirrhosis, predicts a poor prognosis and may trigger severe ventricular arrhythmias. Our aim was to evaluate the effect of chronic beta-blockade on QT prolongation. Clinical and laboratory evaluation, ECG and hepatic vein pressure gradient (HVPG) measurement were performed in 30 cirrhotic patients before and 1-3 months after prophylactic nadolol. QT was corrected for heart rate by the cirrhosis-specific formula and other formulas. QT(cirrhosis) was prolonged in 10 patients (33%); HVPG was increased in all cases. QT(cirrhosis) was correlated with the Child-Pugh score (r=0.40; p=0.027). Nadolol shortened QT interval only with the Bazett formula (p=0.01), remaining unchanged with the other formulas. The QT interval shortened only if prolonged at baseline (from 473.3+/-5.5 to 458.4+/-6.5 ms; p=0.007), while it lengthened when normal (from 429.8+/-3.1 to 439.3+/-2.9 ms; p=0.01). QTc changes were directly related to the baseline value (p<0.001). HVPG decreased from 19.4+/-0.8 to 15.6+/-1.3 mmHg (p=0.004). The HVPG changes did not correlate with QTc changes. Chronic beta-blockade shortens the QT interval only in patients with prolonged baseline values, and this is likely due to a direct cardiac effect.

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Section 3: Prevention of Ventricular Remodeling, Cardiac Dysfunction, and Heart Failure

Spontaneous diastolic contractions and phosphorylation of the cardiac ryanodine receptor at serine-2808 in congestive heart failure in rat

The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contractile waves due to propagating SR Ca2+ release in trabeculae from rats with CHF. Here, we studied the influence of RyR destabilization by FK506 and isoproterenol on twitch force (Ftw) and SL fluctuations in right ventricular (RV) trabeculae. We measured phosphorylation of RyRS2808 in rats with myocardial infarction (MI) with or without beta-blockade and in rats during isoproterenol stimulation in order to assess the role of RyRS2808 phosphorylation in SL fluctuations in failing hearts. Five groups of male Lewis Brown-Norway rats were studied 3 months after MI: i) Sham; ii) MI with CHF (cMI); iii) MI without CHF; iv) metoprolol-treated MI, with and without CHF. The root mean square (RMSSL) of SL fluctuations in RV trabeculae was calculated. RMSSL increased strongly both following a short train of stimuli at 2.5 Hz and following catecholamine activation in trabeculae from MI with CHF, resulting in a decrease in Ftw in proportion to RMSSL. RyRS2808 phosphorylation was increased significantly in the left ventricle (LV; approximately 58%, P<0.05) but not in the RV (n.s.) in MI rats with CHF. FK506 tripled high frequency stimulation-induced RMSSL in nonfailing trabecula but did not further enhance RMSSL in failing trabecula. Isoproterenol increased RMSSL in nonfailing trabeculae only modestly despite a substantial increase in RyRS2808 phosphorylation in the RV (approximately 60%, P<0.05). Isoproterenol induced SL fluctuation without an increase in RV-RyRS2808 phosphorylation in failing trabeculae. Chronic beta-blockade decreased high frequency and catecholamine stimulation-induced RMSSL while RyRS2808 phosphorylation in the RV was indistinguishable from that in cMI. Acute RyRS2808 phosphorylation by itself does not cause spontaneous contractile waves owing to RyR2 destabilization. Spontaneous contractile waves in CHF are not caused by RyRS2808 phosphorylation alone, suggesting that factors other than RyRS2808 phosphorylation affect RyR function.

Vagal heart rate responses to chronic beta‐blockade in human heart failure relate to cardiac norepinephrine spillover

We have documented a pre-junctional beta-2 adrenoceptor mediated reduction in cardiac norepinephrine spillover (CNES) in heart failure patients receiving chronic beta-blockade. Our present objective was to ascertain the consequence of this decrease for vagal heart rate (HR) regulation by determining CNES, arterial baroreflex sensitivity for HR (BRS) and arterial baroreflex modulation of muscle sympathetic nerve activity (MSNA) before and upon 4 months of beta-blockade with either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm (age: 55+/-2 [mean+/-S.E.]; ejection fraction: 20+/-2%), beta-blockade increased BRS from 4.8+/-0.9 to 7.9+/-1.3 ms/mm Hg (P<0.005) but had no effect on arterial baroreflex modulation of MSNA. Changes in CNES and BRS were inversely related (r=-0.52; n=16, P<0.05). Chronic beta-blockade in heart failure augments reflex vagal control of HR at an efferent site of interaction involving blockade of cardiac sympathetic pre-junctional beta-2 adrenoceptors that facilitate NE release.

β-Blockade and increased dyslipidemia in patients bearing Glu27 variant of β2 adrenergic receptor gene

In this study, the effects of polymorphisms of the beta(2) and beta(3) adrenergic receptor genes on the occurrence of dyslipidemia and diabetes mellitus in hypertensive patients treated with beta-blockers (atenolol or metoprolol) were evaluated. Patients who gave written informed consent were asked to return for blood sampling for estimation of serum glucose, total cholesterol, HDL, triglycerides and for genotype determination. Genotyping analysis was performed by PCR-RFLP assay. In patients bearing beta(2)AR Glu27 or the beta(3)AR Arg64 variant there was a larger occurrence of hypertriglyceridemia, alone or in combination with elevated cholesterol levels. Furthermore, the beta(2)AR Glu27 variant significantly associates with hypetriglyceridemia in a cumulative fashion. The risk to develop this side effect after beta-blockade was four-fold higher in patients homozygous for the beta(2)AR Glu27 variant as compared to beta(2)AR27Gln allele. This result allows the identification of patients at high risk to develop metabolic complications to chronic beta-blockade treatment.