Faculty Bibliography

Beta blockers used for the treatment of hypertension may be associated with increased risk for new-onset diabetes mellitus (DM). A search of Medline, PubMed, and EMBASE was conducted for randomized controlled trials of patients taking beta blockers as first-line therapy for hypertension with data on new-onset DM and follow-up for > or =1 year. Twelve studies evaluating 94,492 patients fulfilled the inclusion criteria. Beta-blocker therapy resulted in a 22% increased risk for new-onset DM (relative risk 1.22, 95% confidence interval [CI] 1.12 to 1.33) compared with nondiuretic antihypertensive agents. A higher baseline fasting glucose level (odds ratio [OR] 1.01, 95% CI 1.00 to 1.02, p = 0.004) and greater systolic (OR 1.05, 95% CI 1.05 to 1.08, p = 0.001) and diastolic (OR 1.06, 95% CI 1.01 to 1.10, p = 0.011) blood pressure differences between the 2 treatment modalities were significant univariate predictors of new-onset DM. Multivariate meta-regression analysis showed that a higher baseline body mass index (OR 1.17, 95% CI 1.01 to 1.33, p = 0.034) was a significant predictor of new-onset DM. The risk for DM was greater with atenolol, in the elderly, and in studies in which beta blockers were less efficacious antihypertensive agents and increased exponentially with increased duration on beta blockers. For the secondary end points, beta blockers resulted in a 15% increased risk for stroke, with no benefit for the end point of death or myocardial infarction. In conclusion, beta blockers are associated with an increased risk for new-onset DM, with no benefit for the end point of death or myocardial infarction and with a 15% increased risk for stroke compared with other agents. This risk was greater in patients with higher baseline body mass indexes and higher baseline fasting glucose levels and in studies in which beta blockers were less efficacious antihypertensive agents compared with other treatments

PURPOSE: An obesity paradox, a 'paradoxical' decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known. METHODS: A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66+/-9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m2 (thin), 20 to 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: With patients of normal weight (BMI 20 to<25 kg/m2) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P<.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P<.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (-17.5+/-21.9 mm Hg/-9.8+/-12.4 mm Hg vs -20.7+/-23.1 mm Hg /-10.6+/-12.5 mm Hg, P<.001). CONCLUSION: In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention

OBJECTIVES: The purpose of this study was to evaluate the role of diastolic dysfunction as measured by left atrial (LA) size in patients undergoing stress echocardiography (SE). BACKGROUND: Left atrial size is a surrogate marker of diastolic function. However, its prognostic value in patients referred for SE is not well defined. METHODS: We evaluated 2,705 patients (60 +/- 13 years, 47% men) undergoing SE (56% dobutamine). Patients with significant mitral valve disease (mitral stenosis or > or = moderate mitral regurgitation) were excluded. Enlarged LA was defined as a LA size indexed to body surface area > or =2.4 cm/m2. Follow-up (mean 2.7 +/- 1.0 years) for nonfatal myocardial infarction or cardiac death (n = 122) was obtained. RESULTS: A dilated LA was able to further risk-stratify both the normal and abnormal SE groups. In the presence of a dilated LA, an abnormal SE portends a worse prognosis compared with patients with normal LA size. Cox proportional modeling showed that a dilated LA added incremental value over traditional risk factors, stress electrocardiographic, rest echocardiographic, and SE variables for the prediction of hard events (global chi-square increased from 90.4 to 113.1 to 176.1 to 184.4 to 190.5; p < 0.05 all groups). Left atrial size was a significant predictor of events independent of left ventricular systolic dysfunction and ischemia (relative risk = 1.84, 95% confidence interval 1.19 to 2.85; p = 0.006). CONCLUSIONS: In patients referred for stress echocardiography, LA size provides independent and incremental value over standard risk factors including left ventricular systolic dysfunction and ischemia. Left atrial size is a powerful prognosticator and should be routinely used in the prognostic interpretation of stress echocardiography

BACKGROUND: The prognostic value of stress echocardiography (SE) for the diagnosis and risk stratification of coronary artery disease in octogenarians is not well defined. METHODS: Follow-up of 5 years (mean 2.9 +/- 1.0 years) for confirmed nonfatal myocardial infarction (n = 17) and cardiac death (n = 37) was obtained in 335 patients, age > or =80 years (mean age 84 +/- 3 years, 44% male), undergoing SE (33% treadmill, 67% dobutamine). Left ventricular (LV) regional wall motion was assessed by a consensus of two echocardiographers and scored as per standard five-point scale, 16-segment model of wall motion analysis. Ischemic LV wall segment was defined as deterioration in the thickening and excursion during stress (increase in wall-motion score index (WMSI) > or =1). RESULTS: By univariate analysis, inducible ischemia (chi-square = 38.4, P < 0.001), left ventricular ejection fraction (chi-square = 41.2, P < 0.001), a history of previous myocardial infarction (chi-square = 22.3, P < 0.01), hypertension (chi-square = 33, P < 0.01), and age (chi-square = 27.7, P < 0.01) were significant predictors of future cardiac events. WMSI, an index of inducible ischemia, provided incremental prognostic information when forced into a multivariable model where clinical and rest echocardiography variables were entered first. WMSI effectively stratified octogenarians into low- and high-risk groups (annualized event rates of 1.2 versus 5.8%/year, P < 0.001). CONCLUSIONS: Stress echocardiography yields incremental prognostic information in octogenarians and effectively stratifies them into low- and high-risk groups. Precise therapeutic decision making in very elderly patients should incorporate combined clinical and stress echocardiography data

For more than 3 decades, beta-blockers have been widely used in the treatment of hypertension and are still recommended as first-line agents by national and international guidelines. Recent meta-analyses indicate that, in patients with uncomplicated hypertension, compared with other antihypertensive agents, first-line therapy with beta-blockers was associated with an increased risk of stroke, especially in the elderly cohort with no benefit for the end points of all-cause mortality, cardiovascular morbidity, and mortality. In this review, we critically analyze the evidence supporting the use of beta-blockers in patients with hypertension and evaluate evidence for its role in other indications. The review of the currently available literature shows that in patients with uncomplicated hypertension, there is a paucity of data or absence of evidence to support use of beta-blockers as monotherapy or as first-line agents. Given the increased risk of stroke, their 'pseudo-antihypertensive' efficacy (failure to lower central aortic pressure), lack of effect on regression of target end organ effects like left ventricular hypertrophy and endothelial dysfunction, and numerous adverse effects, the risk benefit ratio for beta-blockers is not acceptable for this indication. However, beta-blockers remain very efficacious agents for the treatment of heart failure, certain types of arrhythmia, hypertropic obstructive cardiomyopathy, and in patients with prior myocardial infarction

The purpose of this study was to evaluate the role of stress echocardiography in the risk stratification and prognosis of patients with left ventricular (LV) hypertrophy. One thousand two patients (mean age 62 +/- 13 years, 35% men) with LV hypertrophy (defined by LV mass index >115 g/m(2) for men and >95 g/m(2) for women) were evaluated. LV mass was calculated using the linear dimension method, as recommended by the American Society of Echocardiography. The calculation of relative wall thickness was performed using the formula (2 x posterior wall thickness)/LV internal diameter. Concentric and eccentric LV hypertrophy were defined as relative wall thicknesses > or =0.42 and <0.42 cm, respectively. Follow-up (2.6 +/- 1.1 years) for confirmed myocardial infarction and cardiac death (n = 71) was obtained. Four hundred seventy-three patients (47%) had concentric hypertrophy, and 529 patients (53%) had eccentric hypertrophy. In patients with either concentric or eccentric LV hypertrophy, stress echocardiography was able to effectively risk-stratify normal versus abnormal subgroups (event rate 1.1% vs 4.9% per year, p <0.0001), whereas stress electrocardiography was unable to do so. In the cohort with normal stress echocardiographic results, patients with concentric LV hypertrophy had an event rate 5 times higher than those with eccentric LV hypertrophy (event rate 1.7% vs 0.3% per year, p = 0.007). In conclusion, stress echocardiography effectively risk-stratifies patients with LV hypertrophy compared with stress electrocardiography. Normal stress echocardiographic results in patients with concentric LV hypertrophy indicate a worse prognosis than in patients with eccentric LV hypertrophy, probably reflecting decreased sensitivity in this cohort. However, abnormal stress echocardiographic results portend a worse prognosis in patients with either concentric or eccentric LV hypertrophy

It has been suggested that Asians may respond differently to antithrombotic therapy, but contemporary management and outcomes of non-ST-segment elevation (NSTE) acute coronary syndromes (ACSs) in Asian patients have not been well characterized. Using data from the CRUSADE initiative, we compared baseline characteristics, treatment patterns, and in-hospital outcomes between 1,071 Asian and 72,513 non-Asian white patients hospitalized with NSTE ACS. Asian patients were more likely to have hypertension, diabetes, and renal insufficiency compared with non-Asian whites. Body mass index was lower in Asian patients (24.9 vs 27.8 kg/m(2), p <0.0001). Use of acute medical therapies, cardiac catheterization, and percutaneous or surgical revascularization did not significantly differ between Asian and white groups after adjustment for patient and hospital characteristics. In-hospital mortality (5.0% vs 4.4%, adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 0.88 to 1.73) and reinfarction rates (2.0% vs 2.3%. adjusted OR 0.94, 95% CI 0.65 to 1.38) were also similar. In contrast, rates of major bleeding (13.4% vs 9.4%, p <0.0001) and red blood cell transfusion (9.6% vs 6.6%, p = 0.0005) were significantly higher in the Asian population and this higher bleeding risk persisted after adjustment for bleeding risk factors and body mass index; adjusted ORs were 1.32 (95% CI 1.08 to 1.62) and 1.32 (95% CI 1.01 to 1.72), respectively. In conclusion, despite similar treatment, Asian patients with NSTE ACS have significantly higher bleeding risk even after adjustment for risk factors and body mass index. Further investigation is needed to explore the potential for ethnic variability in antithrombotic susceptibility

BACKGROUND: Compliance with treatment is a sine qua non for successful treatment of chronic conditions like hypertension. Fixed-dose combinations are designed to simplify the medication regimen and potentially improve compliance. However the data on comparison of fixed-dose combination with free-drug regimen to improve patient's medication compliance is limited. METHODS: We conducted a MEDLINE search of studies using the words fixed-dose combinations, compliance and/or adherence. The inclusion criteria were studies which involved fixed-dose combination versus free-drug components of the regimen given separately. Only studies which reported patient's compliance were included. RESULTS: Of the 68 studies on fixed-dose combinations, only 9 studies fulfilled the inclusion criteria. Two studies were in patients with tuberculosis, 4 in the hypertensive population, 1 in patients with human immunodeficiency virus (HIV) disease and 2 in the diabetic population. A total of 11,925 patients on fixed-dose combination were compared against 8317 patients on free-drug component regimen. Fixed-dose combination resulted in a 26% decrease in the risk of non-compliance compared with free-drug component regimen (pooled relative risk [RR] 0.74; 95% confidence interval [CI], 0.69-0.80; P <.0001). There was no evidence of heterogeneity in this analysis (chi(2)=14.49, df=8; P=.07). A subgroup analysis of the 4 studies on hypertension showed that fixed-dose combination (pooled RR 0.76; 95% CI, 0.71-0.81; P <.0001) decreased the risk of medication non-compliance by 24% compared with free-drug combination regimen. CONCLUSIONS: Fixed-dose combination decreases the risk of medication non-compliance and should be considered in patients with chronic conditions like hypertension for improving medication compliance which can translate into better clinical outcomes

PURPOSE: Patients with type 2 diabetes are commonly overweight, which can contribute to poor cardiovascular outcomes. beta-blockers may promote weight gain, or hamper weight loss, and are a concern in high-risk patients. The current analysis of the Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial evaluates the effects of carvedilol and metoprolol tartrate on weight gain in patients with type 2 diabetes and hypertension. METHODS: This prespecified secondary analysis of the GEMINI study (n=1106) evaluated change in body weight after 5 months. RESULTS: Mean (+/-SE) baseline weights were 97.5 (+/-20.1) kg for carvedilol and 96.6 (+/-20.1) kg for metoprolol tartrate. Treatment difference (c vs m) in mean (+/-SE) weight change from baseline was -1.02 (+/-0.21) kg (95% confidence interval [CI], -1.43 to -0.60; P <.001). Patients taking metoprolol had a significant mean (+/-SE) weight gain of 1.19 (+/-0.16) kg (P <.001); patients taking carvedilol did not (0.17 [+/-0.19] kg; P =.36). Metoprolol tartrate-treated patients with body mass index (BMI) >30 kg/m2 had a statistically significant greater weight gain than comparable carvedilol-treated patients. Treatment differences (c vs m) in the obese (BMI >30 kg/m2) and morbidly obese groups (BMI >40 kg/m2) were -0.90 kg (95% CI, -1.5 to -0.3; P =.002) and -1.84 kg (95% CI, -2.9 to -0.8; P =.001), respectively. Pairwise correlation analyses revealed no significant associations between weight change and change in HbA1c, HOMA-IR, or blood pressure. CONCLUSIONS: Metoprolol tartrate was associated with increased weight gain compared to carvedilol; weight gain was most pronounced in subjects with hypertension and diabetes who were not taking insulin therapy