Co-administration of resveratrol and lipoic acid, or their synthetic combination, enhances neuroprotection in a rat model of ischemia/reperfusion.

The present study demonstrates the benefits of combinatorial antioxidant therapy in the treatment of ischemic stroke. Male Sprague-Dawley rats were anaesthetised and the middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion. Pretreatment with resveratrol 30 minutes prior to MCA occlusion resulted in a significant, dose-dependent decrease in infarct volume (p<0.05) compared to vehicle-treated animals. Neuroprotection was also observed when resveratrol (2 × 10(-3) mg/kg; iv) was administered within 60 minutes following the return of blood flow (reperfusion). Pretreatment with non-neuroprotective doses of resveratrol (2 × 10(-6) mg/kg) and lipoic acid (LA; 0.005 mg/kg) in combination produced significant neuroprotection as well. This neuroprotection was also observed when resveratrol and LA were administered 15 minutes following the onset of MCA occlusion. Subsequently, we synthetically combined resveratrol and LA in both a 1 ∶ 3 (UPEI-200) and 1 ∶ 1 (UPEI-201) ratio, and screened these new chemical entities in both permanent and transient ischemia models. UPEI-200 was ineffective, while UPEI-201 demonstrated significant, dose-dependent neuroprotection. These results demonstrate that combining subthreshold doses of resveratrol and LA prior to ischemia-reperfusion can provide significant neuroprotection likely resulting from concurrent effects on multiple pathways. The additional protection observed in the novel compound UPEI 201 may present opportunities for addressing ischemia-induced damage in patients presenting with transient ischemic episodes.

UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion.

Edaravone, an electron spin trapper with radical scavenging activity, has been shown to be effective in reducing infarct volume in humans following ischemic stroke. However, concerns of edaravone-induced renal toxicity have limited its clinical adoption. Previous work has demonstrated that edaravone produced significant neuroprotection when injected prior to a period of ischemia and/or reperfusion. The current investigation was designed to determine if a newly synthesized co-drug consisting of lipoic acid and edaravone, named UPEI-300, could produce neuroprotection in in vitro and/or an in vivo rodent model of stroke. UPEI-300 produced dose-dependent neuroprotection in vitro and was subsequently tested in vivo. Male rats were anaesthetized and the middle cerebral artery was occluded for 30 min followed by 5.5 h of reperfusion (ischemia/reperfusion; I/R). Pre-administration of UPEI-300 dose-dependently decreased infarct volume. Significant neuroprotection was also observed when UPEI-300 (1.0 mg/kg) was injected during the 30 min period of ischemia as well as up to 60 min following the start of reperfusion. These results indicate that a co-drug consisting of edaravone and lipoic acid is a potent neuroprotectant, and clinically, the use of such a novel co-drug following an ischemic stroke might maintain neuroprotection while potentially decreasing edaravone associated renal toxicity.

Nebivolol monotherapy in younger adults (younger than 55 years) with hypertension: a randomized, placebo-controlled trial.

Nebivolol, a vasodilatory ß1-blocker, may be well suited for the hemodynamics of the younger hypertensive patient. In this 8-week trial, 18- to 54-year-olds with a diastolic blood pressure (DBP) of 95 mm Hg to 109 mm Hg who completed a 4-week placebo-only phase were randomized to receive nebivolol (5 mg/d, titrated to 10-20 mg/d based on achievement of blood pressure <140/90 mm Hg [n=427]) or placebo (n=214). Primary and secondary efficacy parameters were changes in trough seated DBP and systolic blood pressure (SBP), respectively. Safety parameters included adverse events (AEs). The baseline mean age was 45.3 years; SBP/DBP, 154/100 mm Hg; and heart rate, 78 beats per minute. Completion rates were 91.3% (nebivolol) and 88.3% (placebo). At endpoint, there was a significant effect of nebivolol over placebo for DBP (-11.8 mm Hg vs -5.5 mm Hg, P<.001) and SBP (-13.7 mm Hg vs -5.5 mm Hg, P<.001). Total AE rates were 34.7% (nebivolol) and 32.2% (placebo). Nebivolol monotherapy is efficacious and well tolerated in adults younger than 55 years of age with increased DBP.

Changes in biomarkers and 24 hours blood pressure in hypertensive African Americans with the metabolic syndrome: comparison of amlodipine/olmesartan versus hydrochlorothiazide/losartan.

We evaluated the efficacy of amlodipine and olmesartan (A/O; Azor) versus losartan and hydrochlorothiazide (L/H; Hyzaar), on changes in serum and urine biomarkers of inflammation and oxidation, neutrophil reactive oxygen species generation, and changes in systolic blood pressure (BP), diastolic BP, and heart rate as measured with 24 hours ambulatory BP monitoring in a high-risk, hypertensive African-American population with the metabolic syndrome. Sixty-six African-American subjects with Stage 1 and 2 hypertension and characteristics of the metabolic syndrome were treated in open-label, active comparator fashion for 20 weeks. After 14 weeks of therapy, treatment with A/O had a significant effect on reducing the production of reactive oxygen series, plasminogen activator inhibitor-1, F2 isoprostane, myeloperoxidase, and homeostasis model assessment for insulin resistance while L/H treatment only significantly lowered levels of plasminogen activator inhibitor-1 and homeostasis model assessment for insulin resistance. Treatment with A/O showed a trend of a more immediate and sustained systolic and diastolic BP-lowering, as well as night time BP reduction. In addition to a trend toward lower blood pressure, treatment with A/O in comparison with L/H has superior efficacy in reducing reactive oxygen species generation and production of inflammatory and oxidative biomarkers in a hypertensive African-American population with features of the metabolic syndrome.

Changes in Central Aortic Pressure, Endothelial Function and Biomarkers in Hypertensive African-Americans with the Cardiometabolic Syndrome: Comparison of Amlodipine/Olmesartan versus Hydrochlorothiazide/Losartan.

Sixty-six self-identified African-American subjects with stage 1 and 2 hypertension and characteristics of the cardiometabolic syndrome were treated with amlodipine/olmesartan (A/O) versus losartan/hydrochlorothiazide (L/H) for 20 weeks in an open-label, active comparator fashion. Subjects not meeting a blood pressure (BP) value of <125/75 mm Hg on either regimen at week 14 were placed on additional or alternative therapy. After 20 weeks of therapy, systolic BP was reduced by 34.6 ± 4.2 mm Hg in the A/O group and by 27.0 ± 4.1 mm Hg in the L/H group (p = 0.012 A/O vs. L/H). Diastolic BP was reduced by 16.9 ± 2.0 mm Hg in the A/O group and by 12.3 ± 2.0 mm Hg in the L/H group (p = 0.022 A/O vs. L/H). There was a substantial increase in endothelial function of 44 and 103% in the L/H and A/O groups, respectively (p < 0.005 A/O vs. L/H). Central aorta augmentation pressure was significantly reduced by 42% with the A/O treatment, and a smaller, significant reduction of 28% was observed with the L/H treatment (p = 0.034 A/O vs. L/H). There was a reduction in sIL-6 levels of 20 and 33%, a reduction in serum leptin levels of 22 and 40%, and an increase in serum adiponectin of 19 and 46% in the L/H and A/O groups, respectively (p < 0.005 A/O vs. L/H for each biomarker). Treatment with A/O after 14 weeks reduced pulse wave velocity by 22% (p = 0.011 time comparison), whereas L/H treatment had no significant effect. Our findings suggest that, in addition to effective BP reduction, A/O differentially regulates markers of inflammation and obesity, thereby potentially providing greater vascular protection.

Vascular effects of nebivolol added to hydrochlorothiazide in African Americans with hypertension and echocardiographic evidence of diastolic dysfunction: the NASAA study.

BACKGROUND: African Americans have greater risk of cardiovascular events than comparator populations of white European origin. A potential reason for this is reduced nitric oxide bioavailability in African Americans, resulting in increased prevalence of factors that contribute to ventricular dysfunction. We investigated the effects of nebivolol with the diuretic hydrochlorothiazide (HCTZ) in hypertensive African Americans with echocardiographic evidence of diastolic dysfunction. METHODS: A total of 42 African American patients were assigned to nebivolol and HCTZ in an open-label fashion for a 24-week period. Changes in blood pressure (BP), echocardiographic parameters, and success in attaining target BP were determined. As an indirect determinant of endothelial function, serum total nitric oxide (NOx) levels and asymmetric dimethyl arginine (ADMA) levels were performed at baseline and after the treatment period. RESULTS: The systolic BP decreased from 150 ± 13 to 136 ± 16 mm Hg (P < .005). Diastolic BP decreased from 94 ± 13 to 84 ± 9 mm Hg (P = .008). Of the patients that completed the study, 77% achieved a combined target BP of systolic BP <140 mm Hg and a diastolic BP <90 mm Hg. Serum NOx increased by 41% and 39% in patients that were treated with 10 mg and 20 mg daily nebivolol, respectively. The ADMA levels decreased by 44% following treatment. The change in systolic BP was strongly correlated to the change in ADMA (r = .54; P = .024). Furthermore, in comparison to a group of age-matched patients controlled with diuretic therapy only, the ADMA levels were significantly lower in the nebivolol posttreatment group (controlled BP with diuretic: 0.32 ± 0.07µmol/L; nebivolol posttreatment: 0.24 ± 0.06 µmol/L; P < .05). CONCLUSION: Reduced BP with nebivolol in hypertensive African Americans and echocardiographic evidence of diastolic dysfunction correlates with improved endothelial function. Furthermore, improvement in endothelial function and increased nitric oxide bioavailability suggests a potential mechanism of efficacy of nebivolol in these patients.

Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model.

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1-50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5-10 mg/kg) and INV-161 (1-10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.

UPEI-100, a conjugate of lipoic acid and apocynin, mediates neuroprotection in a rat model of ischemia/reperfusion.

Previous work in our laboratory has provided evidence that preadministration of apocynin and lipoic acid at subthreshold levels for neuroprotection enhanced the neuroprotective capacity when injected in combination. Therefore, the present investigation was designed to determine whether a co-drug consisting of lipoic acid and apocynin functional groups bound by a covalent bond, named UPEI-100, is capable of similar efficacy using a rodent model of stroke. Male rats were anesthetized with Inactin (100 mg/kg iv), and the middle cerebral artery was occluded for 6 h or allowed to reperfuse for 5.5 h following a 30-min occlusion (ischemia/reperfusion, I/R). Preadministration of UPEI-100 dose-dependently decreased infarct volume in the I/R model (P < 0.05), but not in the middle cerebral artery occlusion model of stroke. Using the optimal dose, we then injected UPEI-100 during the stroke or at several time points during reperfusion, and significant neuroprotection was observed when UPEI-100 was administered up to 90 min following the start of reperfusion (P < 0.05). A time course for this neuroprotective effect showed that UPEI-100 resulted in a decrease in infarct volume following 2 h of reperfusion compared with vehicle. The time course of this neuroprotective effect was also used to study several mediators along the antioxidant pathway and showed that UPEI-100 increased the level of mitochondrial superoxide dismutase and oxidized glutathione and decreased a marker of lipid peroxidation due to oxidative stress (HNE-His adduct formation). Taken together, the data suggest that UPEI-100 may utilize similar pathways to those observed for the two parent compounds; however, it may also act through a different mechanism of action.

The impact of lipoic acid on endothelial function and proteinuria in quinapril-treated diabetic patients with stage I hypertension: results from the QUALITY study.

BACKGROUND: We sought to determine whether a combination of angiotensin-converting enzyme inhibitors (ACEIs) and the nutraceutical α-lipoic acid (ALA) regulates blood pressure, endothelial function, and proteinuria in diabetic patients with Stage I hypertension. METHODS: A total of 40 diabetic patients with Stage I hypertension were treated in a crossover double-blinded manner. Patients were administered quinapril ([QUI] 40 mg/d) for 8 weeks or QUI + ALA (600 mg/d) for 8 weeks. Measurements included blood pressure, 24-hour collection of urinary albumin, and endothelial-dependent flow-mediated dilation (FMD). RESULTS: There was a change of metabolic parameters in both study groups after 8 weeks of therapy. In comparison to baseline, the 24-hour urinary albumin significantly decreased by 30% in the QUI group (P = .018, time comparison) and 53% in QUI + ALA group (P < .005, time and group comparison). Also, when compared with baseline, FMD significantly increased by 58% in QUI group (P < .005, time comparison) and by 116% in QUI + ALA group (P < .005, time and group comparison). Systolic and diastolic blood pressure reduced significantly by 10% with QUI treatment. There was no further blood pressure reduction when patients were administered both QUI and ALA. CONCLUSIONS: In diabetic patients with hypertension, QUI reduces blood pressure, proteinuria, and improves endothelial function. Moreover, this effect is strongly potentiated with a combination of QUI and ALA. These results may attenuate the progression of vascular pathophysiology seen in patients with a combination of diabetes and hypertension.

Lifestyle risk factors and cardiovascular disease in cubans and cuban americans.

Cardiovascular disease is the leading cause of mortality in Cuba. Lifestyle risk factors for coronary heart disease (CHD) in Cubans have not been compared to risk factors in Cuban Americans. Articles spanning the last 20 years were reviewed. The data on Cuban Americans are largely based on the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-1984, while more recent data on epidemiological trends in Cuba are available. The prevalence of obesity and type 2 diabetes mellitus remains greater in Cuban Americans than in Cubans. However, dietary preferences, low physical activity, and tobacco use are contributing to the rising rates of obesity, type 2 diabetes mellitus, and CHD in Cuba, putting Cubans at increased cardiovascular risk. Comprehensive national strategies for cardiovascular prevention that address these modifiable lifestyle risk factors are necessary to address the increasing threat to public health in Cuba.

Apocynin may limit total cell death following cerebral ischemia and reperfusion by enhancing apoptosis.

The present study was designed to determine a dose-response relationship between apocynin and infarct volume as well as to provide a possible molecular mechanism mediating this effect. We tested the hypothesis that apocynin protects against cell death following stroke and reperfusion injury. Apocynin was administered 30 min prior to, or immediately following removal of sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the sutures, the MCA was allowed to undergo 5.5h of reperfusion. Pretreatment with apocynin 30 min prior to occlusion resulted in a dose-dependent reduction in infarct volume by ∼50 %. Analysis of tissue from the ischemic cortex of apocynin-treated rats showed an increase in the level of glutathione (GSH), protein adducts (HNE-His), hydrogen peroxide (H(2)O(2)) and DNA fragmentation (apoptotic cell death) was also observed. This suggests that apocynin may increase antioxidant defense systems (GSH) to limit the degree of ischemia-induced cellular stress. In addition, this moderate cell stress results in more apoptotic vs necrotic cell death, and thus may limit the spreading depression and total cell death that occurs following ischemia/reperfusion. These effects may serve as a potential novel mechanism of action contributing to the apocynin-induced neuroprotection observed.

The effect of amlodipine besylate, losartan potassium, olmesartan medoxomil, and other antihypertensives on central aortic blood pressure and biomarkers of vascular function.

Biomarkers are being increasingly used in the study of cardiovascular disease because they provide readily quantifiable surrogate endpoints and allow accurate assessment of the effects of therapy on particular pathological processes. However, in order to be useful, biomarkers must be relevant, predictable, accurate, and reproducible. There is compelling evidence from large-scale clinical trials that inhibitors of the renin-angiotensin system [angiotensin-converting enzyme inhibitors and angiotensin type II receptor blockers (ARBs)] and calcium channel blockers (CCBs) may have beneficial effects beyond blood pressure control in the treatment of hypertension. Biomarkers are expected to provide further insight into these beneficial effects and allow for quantitative assessment. This review summarizes the published clinical evidence on the effects of various antihypertensive drugs, particularly ARBs (e.g. losartan and olmesartan medoxomil) and CCBs (e.g. amlodipine), alone and in combination with other agents (e.g. hydrochlorothiazide), on central aortic pressure and the biomarkers high-sensitivity C-reactive protein (hsCRP), adiponectin, cystatin C, homeostasis model assessment of insulin resistance (HOMA-IR), procollagen, tumor necrosis factor-α, and interleukin-6. Of these biomarkers, the benefits of antihypertensive therapy on hsCRP, adiponectin, and HOMA-IR reflect a potential for quantifiable long-term vascular benefits.

Protected carotid artery stenting in patients at high risk for carotid endarterectomy.

OBJECTIVES: To compare the 30-day, six-month, and one-year outcomes of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in male veterans, and to identify any predictors of adverse outcomes. CAS has been shown to be non-inferior to CEA in patients at high-risk for CEA. The outcome of CAS compared to low-risk CEA is less clear. METHODS: Retrospective analysis of 96 consecutive patients who underwent CAS (N = 31) or CEA (N = 65). The cumulative 30-day, six-month, and one-year incidence of ipsilateral transient ischemic attack (TIA) or stroke, restenosis or reocclusion, need for target vessel revascularization, non-fatal myocardial infarction (MI), and death were compared. RESULTS: All patients in the CAS group were at high risk for CEA. Among the CEA group, 50 (76.9%) were at high risk and the remaining 15 (23.1%) were considered to be at low risk. The cumulative incidence of adverse outcomes with CAS and CEA, respectively, at 30 days (3.2% vs 9.2%, P = ns), six months (3.2 vs 18.5%, P = 0.047), and one year (9.7% vs 18.5%, P = ns) favored CAS. This difference was primarily due to adverse events in the high-risk CEA patients. There was no significant difference in outcome between the CAS and low-risk CEA groups. The independent significant predictors for adverse outcomes within six months were the group (P = 0.047) and number of risk factors (P = 0.01). Interestingly, the use of angiotensin-converting enzyme inhibitors (ACE-I) predicted adverse outcomes within one year (P = 0.01). CONCLUSION: CAS may be superior to high-risk CEA with better six-month outcomes. The outcomes with CAS were not significantly different compared to low-risk CEA, suggesting that CAS may be non-inferior to low-risk CEA.

Cellular mechanisms by which lipoic acid confers protection during the early stages of cerebral ischemia: a possible role for calcium.

Lipoic acid (LA) is a naturally occurring compound and dietary supplement with powerful antioxidant properties. Although LA is neuroprotective in models of stroke, little is known about the cellular mechanisms by which it confers protection during the early stages of ischemia. Here, using a rat model of permanent middle cerebral artery occlusion (MCAO), we demonstrated that administration of LA 30 min prior to stroke, reduces infarct volume in a dose dependent manner. Whole-cell patch clamp techniques in rat brain slices were used to determine if LA causes any electrophysiological alterations in either healthy neurons or neurons exposed to oxygen and glucose deprivation (OGD). In healthy neurons, LA (0.005 mg/ml and 0.05 mg/ml) did not significantly change resting membrane potential, threshold or frequency of action potentials or synaptic transmission, as determined by amplitude of excitatory post synaptic currents (EPSCs). Similarly, in neurons exposed to OGD, LA did not alter the time course to loss of EPSCs. However, there was a significant delay the onset of anoxic depolarization as well as in the time course of the depolarization. Next, intracellular calcium (Ca(2+)) levels were monitored in isolated neurons using fura-2. Pretreatment with 0.005 mg/ml and 0.05 mg/ml LA for 30 min and 6 h did not significantly alter resting Ca(2+) levels or Ca(2+) response to glutamate (250 µM). However, pretreatment with 0.5 mg/ml LA for 6 h significantly increased resting Ca(2+) levels and significantly decreased the Ca(2+) response to glutamate. In summary, these findings suggest that LA does not affect neuronal physiology under normal conditions, but can protect cells from an ischemic event.

Lipoic acid protects against reperfusion injury in the early stages of cerebral ischemia.

Lipoic acid (LA) is a known antioxidant currently used as a therapy in patients with vascular and metabolic disorders. We tested the hypothesis that lipoic acid is protective against the cell death observed following stroke. Lipoic acid was administered 30minutes prior to, or immediately following removal of sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the sutures, the MCA territory was allowed to undergo 5.5hrs of reperfusion. This ischemia/reperfusion (I/R) resulted in a focal infarct restricted to the prefrontal cortex (24±3mm(3)). Pretreatment with LA 30minutes prior to occlusion resulted in a dose-dependent reduction in infarct volume. This reduction in infarct volume was not observed when the LA was administered immediately prior to reperfusion (30minutes post-occlusion). To investigate a potential hemodynamic mechanism for this LA-induced neuroprotection, blood pressure, heart rate and baroreceptor reflex sensitivity (BRS) were measured. Intravenous administration of LA did not result in any significant changes in any of these parameters compared to saline-treated rats. Similarly, there was no significant contribution of systemic nitric oxide or alteration in cerebral perfusion measured following pretreatment with lipoic acid or during the course of occlusion and reperfusion compared with saline-treated rats. Western blot analysis of tissue from the ischemic cortex showed an increase in protein expression of superoxide dismutase (SOD2), but not SOD1, in LA pretreated rats. This suggests a potential mechanism of action contributing to the LA-induced neuroprotection observed. Furthermore, the data in the present investigation suggest the potential use of LA pretreatment as a neuroprotectant in stroke patients.

Raising HDL cholesterol in women.

High-density lipoprotein cholesterol (HDL-C) concentration is essential in the determination of coronary heart disease (CHD) risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.

A global perspective on blood pressure treatment and control in a referred cohort of hypertensive patients.

Hypertensive patients with cardiovascular (CV) comorbidities are at increased risk, and cardiologists' care should put particular emphasis on controlling blood pressure. Data on blood pressure treatment and control and drug utilization on a global scale, however, are scarce. Aiming to resolve this lack of information, the authors analyzed the data of International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients With Hypertension (i-SEARCH) to gain further insights into national and regional blood pressure control and antihypertensive pharmacotherapy prescribed in cardiology practice. A total of 22,282 patients with hypertension from 26 countries were enrolled in 2005/2006. A total of 18,652 patients were treated (mean age, 63.0±11.4 years; 52.2% male; mean body mass index, 28.9 kg/m2). Mean systolic blood pressure was 148.2±19.8 mm Hg and diastolic blood pressure was 86.7±11.6 mm Hg. Blood pressure was controlled in 8.3% of diabetic and 25.3% of nondiabetic patients (21.2% overall), with particularly good control rates in North and Latin America (28.0% and 30.6%, respectively). A total of 31.2% of patients were treated with 1, 39.7% with 2, and 29.1% with ≥3 drugs. ß-blockers were being used most frequently (47.9%), in both monotherapy and combination therapy despite low numbers of patients with respective compelling indications for their use. The present data illustrate the potential for an improvement of blood pressure treatment and control in daily cardiology practice.

Effects of labetalol on hemodynamic parameters and soluble biomarkers of inflammation in acute coronary syndrome in patients with active cocaine use.

Cocaine use is associated with increased cardiovascular mortality and can promote acute coronary syndrome (ACS). Use of beta-blockers is controversial in patients who use cocaine, and the safety and efficacy of these medications in ACS in patients actively using cocaine is unknown. We enrolled 90 patients with ACS and positive urine drug screen for cocaine. Patients received standard ACS therapy plus either labetalol (n = 60) or diltiazem (n = 30). Blood pressure and heart rate were measured at baseline and 48 hours. Levels of serum CD40 ligand, interleukin (IL)-6, and choline at baseline and 48 hours were determined. There were no baseline differences in hemodynamics or serum levels of inflammatory markers between the labetalol and diltiazem groups. Both groups experienced a significant and equivalent decrease in BP and HR at 48 hours compared with baseline. At 48 hours of treatment, there were significant decreases of 17% in CD40 ligand (P < .005) and 16% in IL-6 (P < .005) but no change in choline in the diltiazem group. Furthermore, in the labetalol group, there were significant differences of 30% in CD40 ligand (P < .005 time and group comparison), 22% in IL-6 (P < .005 time and group comparison), and 18% in choline (P < .005 time and group comparison). There were no adverse events during hospitalization in any patients who received labetalol. In conclusion, labetalol appears to be safe in cocaine-associated ACS. Furthermore, labetalol provides a beneficial hemodynamic response and, in comparison to diltiazem, potentiates an anti-inflammatory vascular response in this setting.

Benefits of yoga for African American heart failure patients.

BACKGROUND: The number of African American (AA) patients living with heart failure (HF) has been increasing, especially among the economically disadvantaged. Yoga therapy has been found to improve physical and psychological parameters among healthy individuals, but its effect in patients with HF remains unknown. The purpose of this study was to examine the effects of yoga therapy on cardiovascular endurance (VO2peak), flexibility, quality of life (QoL), and inflammatory markers on medically stable HF patients. METHODS: Forty patients (38 AA, 1 Asian, and 1 Caucasian) with systolic or diastolic HF were randomized to the yoga group (YG, n = 21) or the control group (CG, n = 19). All patients were asked to follow a home walk program. Premeasurement and postmeasurement included a treadmill stress test to peak exertion, flexibility, interleukin-6 (IL-6), C-reactive protein (CRP), and extracellular superoxide dismutase (EC-SOD). QoL was assessed by the Minnesota Living with Heart Failure Questionnaire (MLwHFQ). RESULTS: The statistical analyses (assessed by ANOVA and t-tests) were significant for favorable changes in the YG, compared with those in the CG, for flexibility (P = 0.012), treadmill time (P = 0.002), VO2peak (P = 0.003), and the biomarkers (IL-6, P = 0.004; CRP, P = 0.016; and EC-SOD, P = 0.012). Within the YG, pretest to posttest scores for the total (P = 0.02) and physical subscales (P < 0.001) of the MLwHFQ were improved. CONCLUSIONS: Yoga therapy offered additional benefits to the standard medical care of predominantly AA HF patients by improving cardiovascular endurance, QoL, inflammatory markers, and flexibility.