Beta-blockers and risk of all-cause mortality in non-cardiac surgery.

Myocardial ischemia is a frequent complication in patients undergoing non-cardiac surgery and beta-blockers may exert a protective effect. The main benefit of beta-blockers in perioperative cardiovascular morbidity and mortality is believed to be linked to specific effects on myocardial oxygen supply and demand. beta-blockers may exert anti-inflammatory and anti-arrhythmic effects. Randomized clinical trials which evaluated the effects of beta-blockers on all-cause mortality in patients undergoing non-cardiac surgery have yielded conflicting results. In 9 trials, 10,544 patients with non-cardiac surgery were randomized to beta-blockers (n = 5274) or placebo (n = 5270) and there were a total of 304 deaths. Patients randomized to beta-blockers group showed a 19% increased risk of all-cause mortality (odds ratio [OR] 1.19, 95% confidence interval (CI) 0.95-1.50; p = 0.135). However, trials included in the meta-analysis differed in several aspects, and a significant degree of heterogeneity (I( 2) = 46.5%) was noted. A recent analysis showed that the surgical risk category had a substantial influence on the overall estimate of the effect of beta-blockers. Compared with patients in the intermediate-high-surgical-risk category, those in the high-risk category showed a 73% reduction in the risk of total mortality with beta-blockers compared with placebo (OR 0.27, 95% CI 0.10-0.71, p = 0.016). These data suggest that perioperative beta-blockers confer a benefit which is mostly limited to patients undergoing high-risk surgery.

New-onset hyperglycemia and acute coronary syndrome: a systematic overview and meta-analysis.

BACKGROUND: Patients without a history of diabetes often develop hyperglycemia during an acute coronary syndrome (ACS). New onset of hyperglycemia (NH) is associated with higher mortality both in the short and long-term. AIM: We performed a systematic review and meta-analysis of observational studies to investigate the association between NH and mortality in patients with ACS. In-hospital, 30-day and long-term mortality were analyzed separately. METHODS: We searched MEDLINE for prospective studies of patients with ACS reporting the association between NH and mortality, using Research Methodology Filters. This was supplemented by hand searching reference lists of retrieved articles. We determined study eligibility and conducted data abstraction independently and disagreements were resolved by consensus. We pooled odds ratios (OR) from individual studies using a random effects model. RESULTS: Our search strategy identified 24 studies. The prevalence of NH varied widely 3% to 71% depending on the definition of NH used. NH significantly increased the risk of in-hospital (OR 3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies, 10673 patients), 30-day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4 studies, 101447 patients), and long-term (up to 108 months) mortality (OR 2.02, 95% CI: 1.62-2.51; p < 0.0001, I2=79.4%; 12 studies, 102099 patients). CONCLUSIONS: In patients without a prior diagnosis of diabetes who are admitted to hospital for ACS, NH increases the risk of both short and long-term mortality. These data highlight the need for further studies addressing the control of blood glucose levels in patients with ACS. SUMMARY: Patients without history of diabetes may develop new hyperglycemia (NH) on admission to hospital for AMI. We systematically reviewed the prognostic impact of NH on short- and long-term mortality in patients without prior diagnosis of diabetes who attended the hospital for ACS. We identified 24 outcome studies which met a set of pre-specified criteria. Prevalence of NH ranged from 3% to 71% according to different thresholds of blood glucose concentrations. NH significantly increased the risk of in-hospital (OR 3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies, 10673 patients), 30-day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4 studies, 101447 patients)), and long-term (up to 108 months) mortality (OR 2.02, 95% CI: 1.62-2.51; p < 0.0001, I2=79.4%; 12 studies, 102,099 patients).

Comparative assessment of angiotensin receptor blockers in different clinical settings.

Cardiovascular and renal disease can be regarded as progressing along a sort of continuum which starts with cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, etc), evolves with progression of atherosclerotic lesions and organ damage, and then becomes clinically manifest with the major clinical syndromes (myocardial infarction, stroke, heart failure, end-stage renal disease). The blood pressure control remains a fundamental mechanism for prevention of cardiovascular disease. The renin-angiotensin system is believed to play an important role along different steps of the cardiovascular disease continuum. Convincing evidence accumulated over the last decade that therapeutic intervention with angiotensin receptor blockers (ARBs) is effective to slow down or block the progression of cardiovascular disease at different steps of the continuum, with measurable clinical benefits. However, despite the shared mechanism of action, each ARB is characterized by specific pharmacological properties that may influence its clinical efficacy. Indeed, important differences among available ARBs emerged from clinical studies. Therefore, generalization of results obtained with a specific ARB to all available ARBs may be misleading. The present review provides a comparative assessment of the different ARBs in their efficacy on major clinical endpoints along the different steps of the cardiovascular disease continuum.

The voltage of R wave in lead aVL improves risk stratification in hypertensive patients without ECG left ventricular hypertrophy.

OBJECTIVES: We tested the hypothesis that the voltages of QRS on ECG improve risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. METHODS AND RESULTS: We studied 2042 initially untreated patients with hypertension (mean age 49 years, 46% women) without left ventricular hypertrophy on ECG and no history of cardiovascular disease. At entry, all patients underwent diagnostic tests, including 24-h ambulatory blood pressure monitoring and echocardiography. Among the different ECG voltages, the R wave in lead aVL showed the closest association with left ventricle (LV) mass (r = 0.31; P < 0.001), followed by the R wave in D1 (r = 0.25) and the S wave in V3 (r = 0.22). Patients were followed up for a mean of 7.7 years (range 1-22 years), and treatment was tailored individually. During follow-up, there were 188 major cardiovascular events. The relationship between LV voltage and outcome was assessed using a Cox model with adjustment for age, sex, diabetes, smoking, total cholesterol, serum creatinine, LV mass on echocardiography and average 24-h ambulatory blood pressure. A 0.1 mV higher R wave voltage in lead aVL was associated with a 9% higher risk of cardiovascular disease (95% confidence interval = 0.04-0.15%; P < 0.001). Other ECG voltages and minor repolarization changes were not related to clinical outcome. CONCLUSION: Our results show for the first time that the voltage of the R wave in lead aVL improves cardiovascular risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. Its prognostic value is independent of LV mass on echocardiography and 24-h ambulatory blood pressure.

[Ambulatory blood pressure monitoring in clinical practice]. / Il monitoraggio ambulatoriale della pressione arteriosa nella pratica clinica.

Traditionally, diagnosis and management of arterial hypertension are based on blood pressure (BP) measurements taken in the physician's office. However, 24-h noninvasive ambulatory BP monitoring is increasingly used in patients with essential hypertension. Several prospective studies provided unequivocal evidence of an independent association between ambulatory BP and risk of cardiovascular disease in the general population and hypertensive patients. Ambulatory BP is a better predictor of cardiovascular morbidity and mortality than office BP after adjustment for traditional cardiovascular risk factors such as age, sex, smoking status, baseline office BP, and use of antihypertensive drugs. The more accurate prognostic value of ambulatory BP may be related to the closer association with hypertension-related organ damage such as left ventricular mass, intima-media thickness, and microalbuminuria. The superiority of ambulatory over clinic BP in predicting clinical outcome and the most appropriate way of interpreting results of ambulatory BP monitoring will be discussed in this review.

Prognostic value of circadian blood pressure changes in relation to differing measures of day and night.

Although the prognostic value of the day-night blood pressure (BP) changes is established, the most appropriate method for defining day and night is undefined. We assessed the prognostic value of the day-night BP changes by using three definitions of day and night in 2,934 initially untreated hypertensive subjects who underwent 24-hour ambulatory BP monitoring. Over a median follow-up period of 7 years, there were 356 cardiovascular events and 176 deaths. Total cardiovascular events and all-cause mortality were similarly higher in non-dippers (night/day ratio of systolic BP >10% or >0%) than in dippers regardless of the definition of day and night. In a receiver-operated characteristic (ROC) curve analysis of the night/day ratio of systolic BP on the occurrence of events, the area under the ROC curve did not differ among the different definitions of day and night (large fixed-clock intervals, narrow fixed-clock intervals, diary) for both total cardiovascular events (0.61 [95% confidence interval (CI): 0.58 to 0.64], 0.61 [95% CI: 0.57 to 0.63], 0.62 [95% CI: 0.58 to 0.65], respectively; P = 0.20) and all-cause mortality (0.65 [95% CI: 0.61 to 0.70], 0.64 [95% CI: 0.60 to 0.69], 0.65 [95% CI: 0.61 to 0.70], respectively; P = 0.78). The prognostic value of the diurnal BP changes is comparable when using different clock-dependent or independent definitions of day and night.

Effects of barnidipine on blood pressure and left ventricular diastolic function in patients with hypertension and metabolic syndrome: A 12-week, open-label noncomparison study.

BACKGROUND: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS). OBJECTIVE: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS. METHODS: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators. RESULTS: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL (P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht(2.7); LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 (P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study. CONCLUSIONS: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.

[Beta-blockers and arterial hypertension. Evidence-based medicine or excessive perseverance?]. / Betabloccanti e ipertensione arteriosa. Evidence-based medicine o eccessivo accanimento?

For more than 30 years, beta-blockers have widely been used in the treatment of patients with myocardial infarction, angina pectoris, heart failure, certain cardiac arrhythmias and hypertension. Quite recently, however, beta-blockers have been put under trial by results of some controlled studies and meta-analyses conducted in patients with essential hypertension. In summary, beta-blockers proved not better, or even worse, than alternative treatments and only marginally better than placebo. However, some arguments of caveat must be remarked. First, most of these studies have been conducted in hypertensive subjects of old age or complicated by several concomitant risk factors. A considerable portion of hypertensive patients most frequently examined in the usual practice would have not meet inclusion criteria for the above trials. In addition, several methodological issues of meta-analyses raised concern. Results were mainly driven from two major trials (LIFE and ASCOT). Unexpectedly, recent hypertension guidelines issued by the British Hypertension Society fully endorsed these results and recommended beta-blockers as fourth-line drugs in hypertensive patients with blood pressure not adequately controlled by angiotensin-converting enzyme inhibitors, calcium channel blockers and diuretics in combination. Because most of the above trials used atenolol, several lines of evidence warn against extending limitations to beta-blockers to the entire class of these drugs. Some new-generation beta-blockers, although not yet widely tested in outcome-based studies, induce peripheral vasodilatation and do not exert the detrimental effect of atenolol on central blood pressure and arterial distensibility. The present review addresses facts and theories related to the actual concern on the role of beta-blockers in the modern management of hypertensive patients.

Validation of the A&D wrist-cuff UB-511 (UB-512) device for self-measurement of blood pressure.

OBJECTIVES: To determine the accuracy of the A&D UB-511 (UB-512) oscillometric wrist-cuff device for self-measurement of blood pressure, the only difference between the two devices being the size of storage memory. METHODS: Device evaluation was performed according to the modified British Hypertension Society protocol released in 1993. Eighty-five study participants with characteristics outlined in the British Hypertension Society protocol were recruited among those attending our out-patient clinic. The device was evaluated according to the various steps of the protocol. The non-dominant arm was used for blood pressure measurement. To maintain the wrist at cardiac level during validation, the arm was kept horizontal at the mid-sternum level and supported by a soft table. The wrist was kept extended. Sequential readings were taken for the main validation test. Outcome was classified according to the criteria of the British Hypertension Society recommendations, which are based on four strata of accuracy differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The device achieved a British Hypertension Society grade B for systolic and a grade B for diastolic blood pressure. The device tended to overestimate arm blood pressure, the mean difference (+/-1 SD) between device and observers being 4.3+/-8.7 mmHg for systolic blood pressure and 3.7+/-8.1 mmHg for diastolic blood pressure for observer 2, and 4.4+/-8.6 mmHg for systolic blood pressure and 3.8+/-7.9 mmHg for diastolic blood pressure for observer 1. In a logistic regression analysis, age was the sole predictor of an achieved difference between device and mercury column by 5 mmHg or less (hazard ratio 1.020; 95% confidence interval 1.003-1.04; P=0.024). CONCLUSIONS: These data show that the A&D UB-511 (UB-512) device satisfies the British Hypertension Society recommendations with a grade B/B. The device tends to overestimate cuff blood pressure and its accuracy increases with age.