Journal of Cardiac Failure
Volume 17, Issue 9 , Pages 703-709, September 2011

Comparative Long Term Effects of Nebivolol and Carvedilol in Hypertensive Heart Failure Patients

• Giuseppe Marazzi, MD, PhD,
• Maurizio Volterrani, MDGiuseppe Caminiti, MDLuigi Iaia, MDRosalba Massaro, MDCristiana Vitale, MD, PhDBarbara Sposato, MD
• Giuseppe Mercuro, MDGiuseppe Rosano, MD, PhD

Received 14 May 2010; received in revised form 1 May 2011; accepted 3 May 2011. published online 17 June 2011.

Abstract

Beta-blockers improve left ventricular (LV) systolic function and prognosis in patients with chronic heart failure (CHF), but their different pleiotropic properties may influence their cardiovascular effects. This open-label study compared the effects of long-term treatment with nebivolol versus carvedilol on LV ejection fraction (LVEF), in hypertensive CHF patients. Secondary end points were to assess the effect of the 2 beta-blockers on exercise capacity and clinical outcome.

Methods and Results

A total of 160 hypertensive CHF patients, with LVEF <40% and in New York Heart Association (NYHA) functional class I, II, or III, were randomly assigned to receive nebivolol or carvedilol for 24 months. At baseline and at the end of treatment, all patients underwent clinical evaluation, echocardiography, and 6-minute walking test. The target doses were 10 mg/d for nebivolol and 50 mg/d for carvedilol. Compared with baseline values, LVEF increased by a similar extent in the carvedilol (C) and nebivolol (N) groups (C from 36.1% (SD 1.5%) to 40.9% (SD 1.9%), P < .001; N from 34.1% (SD 1.8%) to 38.5% (SF 2.2%), P < .001). Heart rate and NYHA functional class decreased significantly in both groups, and the 6-minute walking distance increased (C from 420 m (SD 104 m) to 490 m (SD 115 m), P < .001; N from 421 m (SD 118 m) to 487 m (SD 138 m), P < .001). During 24 months, 21 carvedilol recipients (26%) and 18 nebivolol recipients (22%) had cardiac events, including 3 and 4 deaths, respectively.

Conclusion

In the long term, nebivolol and carvedilol appear to be similarly effective in the treatment of hypertensive patients with CHF.

Vasc Health Risk Manag. 2012;8:151-60. Epub 2012 Mar 13.

Nebivolol: impact on cardiac and endothelial function and clinical utility.

Toblli JE, DiGennaro F, Giani JF, Dominici FP.

Source

Hospital Aleman, Universidad de Buenos Aires, Buenos Aires, Argentina. jorgetoblli@fibertel.com.ar

Abstract

Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/ nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care. Thus, nebivolol is an effective and well tolerated agent with benefits above those of traditional β-blockers due to its influence on nitric oxide release, which give it singular hemodynamic effects, cardioprotective activity, and a good tolerability profile. This paper reviews the pharmacology structure and properties of nebivolol, focusing on endothelial dysfunction, clinical utility, comparative efficacy, side effects, and quality of life in general with respect to the other antihypertensive agents.

Both morning and evening dosing of nebivolol reduces trough mean blood pressure surge in hypertensive patients

Journal of the American Society of Hypertension
Volume 6, Issue 1 , Pages 66-72, January 2012

Maria Czarina Acelajado, MD,Roberto Pisoni, MDTanja Dudenbostel, MDSuzanne Oparil, MDDavid A. Calhoun, MD Stephen P. Glasser, MD

Abstract

The morning blood pressure surge (MBPS) has been shown to be an independent predictor of cardiovascular events. There is insufficient evidence on the effect of nebivolol, a vasodilating β1-receptor blocker, on the MBPS when given in the morning or the evening. This is a prospective, randomized, double-blind, crossover study designed to test morning vs. evening dosing of nebivolol in nondiabetic, hypertensive patients. Patients received nebivolol 5 mg/day (force-titrated to 10 mg/day after 1 week) in the morning or evening and corresponding placebos. Patients underwent ambulatory BP monitoring at baseline and after each treatment phase. Forty-two patients were randomized, of whom 38 completed both study periods. Both morning and evening dosed nebivolol significantly lowered daytime, nighttime, and 24-hour BP after 3 weeks of treatment. Evening (but not morning) dosing significantly reduced prewaking systolic BP from baseline (8.64 ± 26.46 mm Hg, P = .048). Nebivolol given in the morning or the evening significantly reduces 24-hour BP parameters. Evening dosed nebivolol may confer some advantage over morning dosing in reducing prewaking systolic BP.

Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies.

Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies. AuthorsOmboni S, et al. Show all Journal J Hypertens. 2012 Jul;30(7):1468-1477. Affiliation aItalian Institute of Telemedicine, Varese bDepartment of Internal Medicine. Ospedale L. Sacco, University of Milan, Milan, Italy cCardiology and Arterial Hypertension, CHU de Grenoble, Grenoble, France dDivision of Cardiology, II Faculty of Medicine, University of Rome 'La Sapienza' and IRCCS Neuromed, Pozzilli, Isernia eCentro di Fisiologia Clinica e Ipertensione Università di Milano and Istituto Auxologico Italiano, Milan, Italy. Abstract OBJECTIVE: To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS: After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS: In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS: Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake. PMID 22573127 [PubMed - as supplied by publisher] Full text: Lippincott Williams & Wilkins s. AuthorsOmboni S, et al. Show all Journal J Hypertens. 2012 Jul;30(7):1468-1477. Affiliation aItalian Institute of Telemedicine, Varese bDepartment of Internal Medicine. Ospedale L. Sacco, University of Milan, Milan, Italy cCardiology and Arterial Hypertension, CHU de Grenoble, Grenoble, France dDivision of Cardiology, II Faculty of Medicine, University of Rome 'La Sapienza' and IRCCS Neuromed, Pozzilli, Isernia eCentro di Fisiologia Clinica e Ipertensione Università di Milano and Istituto Auxologico Italiano, Milan, Italy. Abstract OBJECTIVE: To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS: After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS: In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS: Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake. PMID 22573127 [PubMed - as supplied by publisher] Full text: Lippincott Williams & Wilkins

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Effects of lipid-lowering treatment on platelet reactivity and platelet-leukocyte aggregation in diabetic patients without and with chronic kidney dis

Nephrol Dial Transplant. 2012 Jun 13.

Effects of lipid-lowering treatment on platelet reactivity and platelet-leukocyte aggregation in diabetic patients without and with chronic kidney disease: a randomized trial.

Almquist T, Jacobson SH, Lins PE, Farndale RW, Hjemdahl P.

Source

1Department Medicine Solna, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital/Solna, Stockholm SE-171 76, Sweden.

Abstract

BackgroundDiabetes mellitus (DM) is associated with hyperreactive platelets and increased platelet-leukocyte aggregation (PLA), but the impact of concomitant chronic kidney disease (CKD) has been much less studied. Lipid-lowering treatment (LLT) may have favorable effects on platelet activation and inflammation. The objective of this mechanistic study was to investigate the impact of CKD on platelet function and inflammatory parameters in patients with DM and the effects of LLT.MethodsAfter a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S + E) were compared in a randomized, double-blind, cross-over study on platelet reactivity, PLA formation and inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1.73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75 mL/min (DM-only) were included.ResultsPLAs were elevated at baseline in DM-CKD compared with DM-only (P = 0.04). S + E reduced PLAs among total leukocytes and neutrophils in DM-CKD patients (P = 0.01 for both) but not in the DM-only group. Platelet reactivity did not differ between patient groups or with LLT. Plasma levels of sCD40L (P < 0.001), elastase (P < 0.01) and von Willebrand factor (VWF) (P < 0.001) were elevated in DM-CKD compared with DM-only. S + E reduced sCD40L in DM-CKD patients (P = 0.01), but LLT did not influence VWF or elastase.ConclusionsDM patients with CKD stages 3-4 had increased PLA and inflammatory activity compared with DM patients with normal GFR. Simvastatin + ezetimbe decreased PLAs and plasma sCD40L in DM patients with concomitant CKD.Clinical Trial registrationhttp://www.clinicaltrials.gov. Identifier NCT01035320.

Statins in Heart Failure: The Paradox Between Large Randomized Clinical Trials and Real Life

Statins in Heart Failure: The Paradox Between Large Randomized Clinical Trials and Real Life
by Paloma Gastelurrutia, Josep Lupón, Marta de Antonio, Agustin Urrutia, Crisanto Díez, Ramón Coll, Salvador Altimir, Antoni Bayes-Genis on Jun 7, 2012 12:03 PM
Abstract: Objective: To assess the relationship between statins and prognosis in ischemic and nonischemic patients with heart failure (HF) in a real-life cohort followed up for a long period. Patients and Methods: This prospective study included 960 patients with HF with preserved or depressed left ventricular ejection fraction (LVEF), irrespective of HF etiology, who were referred to the HF clinic of a university hospital between August 1, 2001, and December 31, 2008. The patients were followed up for a maximum of 9.1 years (median, 3.7 years), and survival in ischemic and nonischemic patients was determined. Results: Median age was 69 years, and median LVEF was 31%. Of the 960 patients, 532 (55.4%) had ischemic HF etiology, and most received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (846; 88.1%) and β-blockers (776; 80.8%). Patients with HF of ischemic origin were more often treated with statins (P<.001). During follow-up, 440 patients (45.8%) died. Statin therapy was associated with significantly improved survival (hazard ratio, 0.45 [95% confidence interval, 0.37-0.54]; P<.001). After adjustment for HF prognostic factors (age, sex, cholesterol level, New York Heart Association class, HF etiology, LVEF, body mass index, HF duration, atrial fibrillation, implantable cardioverter-defibrillator therapy, and medicines), statins remained significantly associated with lower mortality risk in both ischemic (P=.007) and nonischemic (P=.002) patients. Conclusion: In contrast to results of large randomized trials, statins were independently and significantly associated with lower mortality risk in our real-life HF cohort, including patients with nonischemic HF etiology.

Olmesartan Linked to Severe GI Problems That Mimic Celiac Disease

Olmesartan Linked to Severe GI Problems That Mimic Celiac Disease

ROCHESTER, Minn -- June 21, 2012 -- Researchers have discovered an association between olmesartan and severe gastrointestinal (GI) issues such as nausea, vomiting, diarrhoea, weight loss, and electrolyte abnormalities.

From 2008 to 2011, physicians from the Mayo Clinic, Rochester, Minnesota, treated 22 patients with symptoms similar to celiac disease, including intestinal inflammation and abnormalities. Patients came from 17 states, and some had been diagnosed with celiac disease. They had chronic diarrhoea and weight loss (median weight loss was 17.70 kg [39 lbs] and 1 patient lost 56.71 kg [125 lbs]).

Fourteen of the 22 patients were hospitalised because of the severity of their symptoms. When given a blood test, however, these patients didn’t come back with results typical of celiac disease. They also didn’t respond to treatments such as gluten-free diets.

After examining their medications, Joseph Murray, MD, Mayo Clinic, pulled several of the patients off olmesartan. Surprisingly, their symptoms dramatically improved.

Eventually, all 22 were taken off the drug, and all showed improvement. Eighteen of the 22 patients had intestinal biopsies after stopping the medication and showed improvement.

“We thought these cases were celiac disease initially because their biopsies showed features very like celiac disease, such as inflammation,” said Dr. Murray. “What made them different was they didn’t have the antibodies in their blood that are typical for celiac disease.”

“It’s really an awareness issue,” he said. “We want doctors to be aware of this issue, so if they see a patient who is having this type of syndrome, they can think about medications as a possible association. “What needs to be known next is the science to understand why there is such an association.”

SOURCE: Mayo Clinic

Effects of atorvastatin and rosuvastatin on renal function: A meta-analysis

Source: Int J Cardiology

Effects of atorvastatin and rosuvastatin on renal function: A meta-analysis; Savarese G, Musella F, Volpe M, Paneni F, Perrone-Filardi P; International Journal of Cardiology (May 2012)

BACKGROUND: Atorvastatin (A) and rosuvastatin (R) are highly effective and widely used statins. However, conflicting results have been reported regarding their renal effects. The aim of the present study was to compare the effects of A and R on glomerular filtration rate (GFR) and new onset proteinuria in patients at high cardiovascular risk. METHODS: Randomized trials about A or R treatments reporting clinical end-points were included in the meta-analysis. Influence of both treatments on GFR and new onset proteinuria was assessed. RESULTS: 23 trials enrolling 29,147 participants were included. A significant reduction in GFR was detected in placebo-treated compared to statin-treated patients (standard mean difference [SMD]: 0.056, 95% confidence interval [CI]:0.028 to 0.083, p<0.01). In particular, a significant reduction in GFR was detected in placebo as compared to either R-treated (SMD: 0.052, CI: 0.022 to 0.081, p=0.001) or A-treated patients (SMD: 0.084, CI: 0.008 to 0.161, p=0.031). No significant difference in GFR was detected in 5 head-to-head studies comparing A to R (SMD: 0.043, CI: -0.041 to 0.126, p=0.319). In 9 studies comparing A to R, R treatment significantly increased the risk of proteinuria when compared to A (odds ratio [OR]: 0.656, CI: 0.440 to 0.977, p=0.038, heterogeneity p=0.026), but this effect was no longer significant when studies using highest therapeutic doses of R (40mg/daily) were excluded from analysis, abolishing significant heterogeneity (OR: 1.505, CI: 0.827 to 2.739, p=0.181). CONCLUSIONS: A and R show similar reno-protective effects in patients at high cardiovascular risk, with comparable rates of new onset proteinuria when commonly used doses are considered.

Daily aspirin has five times higher risk of bleeding than first thought

13 June, 2012

Taking aspirin daily is linked to an increased risk of major bleeding much higher than previous research suggests, a large new study shows.

The study found aspirin was associated with a 55% increased risk of gastrointestinal bleeding and a 54% increased risk of intracranial bleeding after comparing almost 190,000 people taking low-dose aspirin to the same number of controls during a median follow-up rate of 5.7 years.

“Aspirin use was significantly associated with an increased risk of major bleeding,” the Italian researchers reported in JAMA.

The incidence of serious bleeds was five times higher in this real-world setting compared to previous randomised prospective clinical trials, they said.

The researchers also found that diabetes was the only subgroup not associated with a greater risk of bleeding, carrying a 36 percent increased risk of serious bleeds irrespective of aspirin use.

“Our study shows for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of individuals with diabetes,” they wrote.

The accelerated platelet turnover in diabetes could explain the reduced incidence of adverse effects related to aspirin, the authors suggested, as well as its limited efficacy in preventing major cardiovascular events.

In an accompanying editorial, Professor Jolanta Siller-Matula from the University of Vienna said the study “underscores that the potential risk of bleeding should be carefully considered in decision making”.

“There is only a thin line between efficacy and safety and the reduction in ischemic events comes at the cost of increased major bleedings,” she said.

JAMA, June 2012. doi:10.1001/jama.2012.5034/ doi:10.1001/jama.2012.6152

Comparison of Alternate-day Atorvastatin Treatment to Daily Treatment in Maintaining LDL-cholesterol Targets in Patients With Variable Coronary Risk Profile

Comparison of Alternate-day Atorvastatin Treatment to Daily Treatment in Maintaining LDL-cholesterol Targets in Patients With Variable Coronary Risk Profile; Pattanaik S, Malhotra S, Sharma YP, Pandhi P; Journal of Cardiovascular Pharmacology 59 (5), 479-84 (May 2012)
ABSTRACT:: 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity of atorvastatin lasts upto 20-30 hours. This study aimed at comparing the maintenance of National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) goal by the alternate-day therapy to daily treatment. This randomized, open-label trial included 300 patients of dyslipidemia or coronary artery disease on stable doses of atorvastatin. These patients met their respective NCEP-ATPIII cholesterol goals and were randomized to receive the same doses of atorvastatin every day (QD) or every other day (QOD) in a 1:1 ratio for 12 weeks. The efficacy criteria were (1) proportion of patients maintaining the low-density lipoprotein-cholesterol (LDL-C) goal, (2) comparison of changes in the total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride levels from baseline. The proportions of patients maintaining their LDL-C goals in QD and QOD groups at 6 weeks were 83.9% (60.3-97.5) versus 70.9% (59.3-82.5) (P<0.01) and at 12 weeks were 84.6% (70.9-98.3) versus 73.8% (63.8-83.8) (P<0.05). Per-protocol analysis showed 95.5% (80.0-111.0) versus 79.1% (66.2-92.0) (P<0.001) patients at 6 weeks and 91.9% (82.0-106.8) versus 77.4% (64.8-90) (P<0.05) patients at 12 weeks had maintained their LDL-C goals in the QD and QOD groups. A significant increase was observed in the levels of total cholesterol, LDL-C, and triglyceride at 6 and 12 weeks compared with baseline values in the QOD group. Alternate-day treatment of atorvastatin was inferior to daily treatment in maintaining the NCEP-ATPIII goal.

10 Signs of Alzheimer's

	Memory loss that disrupts daily life
	One of the most common signs of Alzheimer's is memory loss, especially forgetting recently learned information. Others include forgetting important dates or events; asking for the same information over and over; increasingly needing to rely on memory aides (e.g., reminder notes or electronic devices) or family members for things they used to handle on their own. What's a typical age-related change? Sometimes forgetting names or appointments, but remembering them later.

	Challenges in planning or solving problems
	Some people may experience changes in their ability to develop and follow a plan or work with numbers. They may have trouble following a familiar recipe or keeping track of monthly bills. They may have difficulty concentrating and take much longer to do things than they did before. What's a typical age-related change? Making occasional errors when balancing a checkbook.

	Difficulty completing familiar tasks at home, at work or at leisure
	People with Alzheimer's often find it hard to complete daily tasks. Sometimes, people may have trouble driving to a familiar location, managing a budget at work or remembering the rules of a favorite game. What's a typical age-related change? Occasionally needing help to use the settings on a microwave or to record a television show.

	Confusion with time or place
	People with Alzheimer's can lose track of dates, seasons and the passage of time. They may have trouble understanding something if it is not happening immediately. Sometimes they may forget where they are or how they got there. What's a typical age-related change? Getting confused about the day of the week but figuring it out later.

	Trouble understanding visual images and spatial relationships
	For some people, having vision problems is a sign of Alzheimer's. They may have difficulty reading, judging distance and determining color or contrast, which may cause problems with driving. What's a typical age-related change? Vision changes related to cataracts.

	New problems with words in speaking or writing
	People with Alzheimer's may have trouble following or joining a conversation. They may stop in the middle of a conversation and have no idea how to continue or they may repeat themselves. They may struggle with vocabulary, have problems finding the right word or call things by the wrong name (e.g., calling a "watch" a "hand-clock"). What's a typical age-related change? Sometimes having trouble finding the right word.

	Misplacing things and losing the ability to retrace steps
	A person with Alzheimer's disease may put things in unusual places. They may lose things and be unable to go back over their steps to find them again. Sometimes, they may accuse others of stealing. This may occur more frequently over time. What's a typical age-related change? Misplacing things from time to time and retracing steps to find them.

	Decreased or poor judgment
	People with Alzheimer's may experience changes in judgment or decision-making. For example, they may use poor judgment when dealing with money, giving large amounts to telemarketers. They may pay less attention to grooming or keeping themselves clean. What's a typical age-related change? Making a bad decision once in a while.

	Withdrawal from work or social activities
	A person with Alzheimer's may start to remove themselves from hobbies, social activities, work projects or sports. They may have trouble keeping up with a favorite sports team or remembering how to complete a favorite hobby. They may also avoid being social because of the changes they have experienced. What's a typical age-related change? Sometimes feeling weary of work, family and social obligations.

Patients with hypertension also suffered hidden heart disease caused by high blood pressure even though they displayed no symptoms

ScienceDaily (June 8, 2012) — A Wayne State University School of Medicine study has found that an overwhelming majority of African-American patients with hypertension also suffered hidden heart disease caused by high blood pressure even though they displayed no symptoms.
The study -- "Subclinical Hypertensive Heart Disease in African-American Patients with Elevated Blood Pressure in an Inner-City Emergency Department" -- was conducted by Phillip Levy, M.D., M.P.H., associate professor of Emergency Medicine, and was recently published online in Annals of Emergency Medicine.
Nine of every 10 patients tested suffered hidden heart damage caused by high blood pressure, the study found. While slightly more than 93 percent of 161 patients in the study had a history of hypertension, 90.7 percent tested positive for hidden hypertensive heart disease. None of them knew their high blood pressure was affecting their hearts and did not show any symptomatic signs of heart disease.
"These results present a tremendous opportunity to screen for heart disease before it becomes symptomatic, especially in a population with high rates of hypertension," Levy said. "If we can detect incipient heart disease early, we have a better shot at treating it before it turns into a full-blown health emergency. Our study is also a strong reminder that emergency patients with chronic disease -- in this case, hypertension -- are generally a high-risk group."
The patients were enrolled in the study after appearing at the emergency room of Detroit Receiving Hospital. They did not come to the hospital for heart disease symptoms. Once enrolled in the study, they underwent echocardiograms, which revealed the hypertensive heart disease. Of the total 161 patients, 93.8 percent were inner-city African-Americans; 51.6 percent were male. The mean age of the patients enrolled was 49.8 years.
Most of the patients (93.8 percent) had a history of high blood pressure and were aware that they had the condition, but only 68.3 percent were receiving treatment.
Of those found to have hidden heart disease, the majority were diagnosed with diastolic dysfunction, defined as the heart's inability to adequately pump blood. Levy said the echocardiograms found the presence of subclinical hypertensive heart disease "ubiquitous."
He noted that hypertension is commonplace in the United States, and affects more than 76 million adults. The prevalence of the condition is higher in African-Americans, who are at "tremendous risk" for pressure-related consequences of hypertension, especially the premature onset of damage to and impairment of heart function.
According to the U.S. Centers for Disease Control and Prevention, 228.3 in every 100,000 Michigan residents 35 and older died of hypertension-related causes in 2009. In African-Americans, the rate was 381.9 deaths for every 100,000, and in whites it was 211. All Michigan rates were higher than national statistics. In rates of hypertension hospitalizations of Michigan residents 65 and older who are Medicare beneficiaries, African-Americans had higher rates (14 hospitalizations per 1,000 Medicare beneficiaries) than whites (3.6 per 1,000). Again, both rates were higher than national numbers.
Since subclinical heart disease is unlikely to be detected in such hypertensive patients until the damage manifests in visibly recognized symptoms, the early identification of the condition "has emerged as an important aspect of secondary cardiovascular disease prevention," Levy said.
Emergency room physicians may underestimate the prevalence of hidden hypertensive heart disease in inner-city African-Americans, who are considered an especially high-risk group and who rely on emergency rooms for treatment because of lack of access to primary care physicians.
"Emergency physicians are uniquely positioned to lessen the overall impact of chronic high blood pressure in at-risk communities," Levy said. "Blood pressure readings are taken for every patient in the ER. By not just taking in new information but also acting on it, we can substantively contribute to much-needed secondary disease prevention efforts."
In 2010, the CDC reported the financial burden of hypertension in the U.S. was $76.6 billion in health care, medication and missed days of work.
Recognizing the likelihood of previously unrecognized subclinical hypertensive heart disease prevalence in African-Americans holds therapeutic promise that could reduce the adverse outcomes, Levy said. Blacks progress from hidden to symptomatic stages of left-ventricular dysfunction more rapidly than other population groups, and the mean age of blacks admitted to hospitals with heart failure is much lower than that of whites (63.6 years versus 75.2 years).
"While we must recognize the risk that exists for these patients, we should not expect emergency departments to perform the further studies needed to identify subclinical end-organ damage," Levy said. "Emergency departments should focus on identification of poorly controlled hypertension -- whether or not it was the primary reason for the emergency visit -- and hospital systems, especially those where high disease prevalence exists, should have some coordinated mechanism where patients can be referred for follow-up. Moreover, at that follow-up, a mechanism should exist to perform effective intervention, including risk stratification, even if patients lack insurance."
The study was funded by the Blue Cross Blue Shield of Michigan Foundation.

Comer pescado a diario reduce el riesgo de cáncer de hígado

Comer pescado a diario reduce el riesgo de cáncer de hígado Ciencia y Salud Los científicos dividieron en cinco grupos a los participantes, a los que dieron diferentes raciones de pescado rico en ácidos grasos, especialmente los de la familia del omega 3 como el eicosapentaenoico y el docosahexaenoico/ Una de las investigadoras niponas encargadas del estudio, Norie Sawada, detalló que los ácidos grasos del pescado previenen la inflamación del hígado Comer a diario un pescado rico en ácidos grasos, como el besugo, el salmón o el jurel, reduce el riesgo de padecer cáncer de hígado, según un estudio realizado por el Centro japonés de Cáncer sobre 90.000 personas durante 11 años. Para presentar los resultados, los investigadores hicieron un seguimiento a 90.000 hombres y mujeres de nueve provincias de Japón y de edades comprendidas entre los 45 y los 74 años, a los que les suministraron ocho clases diversas de este tipo de pescado en su dieta, informó hoy el diario Yomiuri y reprodujo EFE. Los científicos dividieron en cinco grupos a los participantes, a los que dieron diferentes raciones de pescado rico en ácidos grasos, especialmente los de la familia del omega 3 como el eicosapentaenoico (EPA) y el docosahexaenoico (DHA). Los investigadores compararon los análisis médicos periódicos de los participantes con los de otras personas a las que se había diagnosticado de cáncer de hígado, para poder cotejar sus resultados. El estudio revela que los participantes que comieron un pescado de tamaño medio a diario tenían un 36 por ciento menos de posibilidades de desarrollar cáncer de hígado en comparación con el grupo que ingirió tan sólo un pescado a la semana. Una de las investigadoras niponas encargadas del estudio, Norie Sawada, detalló que los ácidos grasos del pescado previenen la inflamación del hígado con lo que reducen el riesgo de padecer este tipo de cáncer, según las declaraciones recogidas por la cadena NHK.

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Pioglitazone (Actos, Takeda) is associated with an increased risk of incident bladder cancer among those with type 2 diabetes

Adapted from Medscape Medical News—a professional news service of WebMD
Montreal, QC - Pioglitazone (Actos, Takeda) is associated with an increased risk of incident bladder cancer among those with type 2 diabetes, according to the results of a nested case-control study published online yesterday in the British Medical Journal [1]. The risk doubled in patients treated with pioglitazone for two years or more.

"The safety of pioglitazone, an oral antidiabetic agent in the thiazolidinedione class, is controversial," write Dr Laurent Azoulay (Jewish General Hospital, Montreal, QC) and colleagues. "Although pioglitazone is effective at reducing glycated hemoglobin . . . and may decrease the risk of cardiovascular events, it has also been associated with weight gain and an increased risk of congestive heart failure. Although available data are limited, there is now some evidence suggesting that pioglitazone may be associated with an increased risk of bladder cancer."

In August 2011, the US Food and Drug Administration updated the label to warn against starting pioglitazone in patients who have active bladder cancer and to use caution if starting pioglitazone in patients with a prior history of the cancer. The European Medicines Agency issued similar warnings.

Using data from the General Practice Research Database, including more than 600 general practices in the UK, investigators of the present study identified 115 727 people with type 2 diabetes who were newly treated with oral hypoglycemic agents between January 1, 1988, and December 31, 2009. Incident cases of bladder cancer during follow-up were each matched to up to 20 control patients.

During an average of 4.6 years of follow-up, 470 patients were diagnosed with bladder cancer (89.4 per 100 000 person-years). Of these, 376 cases of bladder cancer diagnosed beyond one year of follow-up were matched with 6699 controls.

Exposure to pioglitazone was associated with an increased rate of bladder cancer (rate ratio [RR] 1.83, 95% CI 1.10-3.05). The rate of bladder cancer increased with dosage and duration of use, and was highest in patients treated with pioglitazone for more than 24 months (RR 1.99, 95% CI 1.14-3.45; p=0.05 for trend) and in those with a cumulative dosage exceeding 28 000 mg (RR 2.54, 95% CI 1.05-6.14; p=0.03 for trend).

These findings remained consistent in several sensitivity analyses. Absolute risks for bladder cancer associated with pioglitazone were low, at up to 137 extra cases per 100 000 person-years (95% CI 4-271). In contrast, use of rosiglitazone was not associated with an increased risk of bladder cancer.

"[T]he results of this study provide evidence that pioglitazone is associated with an increased risk of bladder cancer, whereas no increased risk was observed with the thiazolidinedione rosiglitazone," the study authors write. "The increased risk associated with pioglitazone became apparent after use for at least 24 months and [in those] receiving cumulative dosages greater than 28 000 mg. Such associations may have been underestimated in the previous observational studies that included prevalent users."

In an accompanying editorial [2], Drs Dominique Hillaire-Buys and Jean-Luc Faillie (Centre Hospitalier Regional Universitaire de Montpellier, France) suggest that the risks of treatment with pioglitazone seem to outweigh the benefits.

"Taking into account Azoulay and colleagues' current findings and given the consistency of these results, the relative strength of the association, the dose-response effect, the known pharmacodynamic characteristics of pioglitazone, and evidence of a significant association in a meta-analysis of randomized trials, it can confidently be assumed that pioglitazone increases the risk of bladder cancer," they write. "It also seems that this association could have been predicted earlier. Worldwide, exposure to pioglitazone is estimated to be more than 20 million patient-years. Considering that the benefit of pioglitazone in reducing cardiovascular events is questionable, prescribers who are ultimately responsible for therapeutic choices can legitimately question whether the benefit-risk ratio of pioglitazone is still acceptable for their patients with diabetes."

This study was supported by the Canadian Institutes of Health Research and Canadian Foundation for Innovation. One of the study authors served as a consultant for Novo Nordisk and Sanofi-Aventis and received research funding from Novo Nordisk. Hillaire-Buys and Faillie disclosed no relevant financial relationships.
The complete contents of Medscape Medical News, a professional news service of WebMD, can be found at www.medscape.com, a website for medical professionals.
Sources
Azoulay L, Yin H, Filion KB, et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. BMJ 2012; DOI: 10.1136/bmj.e3645. Available at: http://www.bmj.com/.
Hillaire-Buys D, Faillie J-L. Pioglitazone and the risk of bladder cancer. BMJ 2012; DOI: 10.1136/bmj.e3500. Available at: http://www.bmj.com/.

Related links
New pioglitazone label highlights bladder-cancer risk
[Lipid/Metabolic > Lipid/Metabolic; Aug 05, 2011]
EMA updates on pioglitazone and varenicline
[Clinical cardiology > Clinical cardiology; Jul 21, 2011]
FDA: Use of pioglitazone over one year may increase risk of bladder cancer
[Lipid/Metabolic > Lipid/Metabolic; Jun 15, 2011]
Review of data suggests risk of bladder cancer with pioglitazone
[Lipid/Metabolic > Lipid/Metabolic; May 18, 2011]

AHA/ASA Statement Calls Stroke a Cardiac Risk Equivalent

May 30, 2012 — Ischemic stroke patients should be included among those deemed to be at high risk for further atherosclerotic coronary events, concludes a new scientific statement from the American Heart Association (AHA) and American Stroke Association (ASA).

"This is an important message," Daniel T. Lackland, DrPH, from the Medical University of South Carolina in Charleston, and co-chair of the statement writing group, noted in an interview with Medscape Medical News.

"We've typically recognized that if a patient has heart disease or another condition you often treat them differently, maybe more aggressively," he explained. "But it's been unclear what you do with someone who has had a stroke. Do you treat them differently? This has been a big question for a really long time."

"This is a very strong writing team that got together and looked at the evidence and determined that indeed stroke should be recognized as a cardiac risk equivalent and that stroke should be considered in risk models. Until now, this was never clearly stated," Dr. Lackland said.

The American Academy of Neurology (AAN) has affirmed the value of the guideline as an educational tool for neurologists. The statement is published online May 24 in Stroke.

"Rotten in the Basement, Rotten in the Attic"

Reached for comment on the statement, Philip B. Gorelick, MD, MPH, medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan, congratulated the authors for their "comprehensive review and conclusions on 2 key questions." Should stroke patients be included among those at high absolute risk for subsequent cardiovascular disease (CVD), specifically coronary heart disease (CHD), and is stroke a relevant outcome in the cluster recommended for use in risk prediction instruments?

"From an intuitive standpoint, the answer to both questions should be yes," said Dr. Gorelick, who was not part of the writing group. "The old bedside teaching adage, 'rotten in the basement, rotten in the attic,' has been passed down to generations of medical students and residents for years," he added. "That is, if you have atherosclerosis of the coronary or peripheral arteries, you will more than likely have it in the cerebral arteries and vice versa."

In the 36-page statement, the writing team cites several reasons to consider stroke patients, particularly patients with atherosclerotic stroke, among the groups of patients at high absolute risk for CHD and CVD.

"First, evidence suggests that patients with ischemic stroke are at high absolute risk of fatal or nonfatal myocardial infarction or sudden death, approximating the ≥20% absolute risk over 10 years that has been used in some guidelines to define coronary risk equivalents," they write.

"Second, inclusion of atherosclerotic stroke would be consistent with the reasons for inclusion of diabetes mellitus, peripheral vascular disease, chronic kidney disease, and other atherosclerotic disorders despite an absence of uniformity of evidence of elevated risks across all populations or patients. Third, the large-vessel atherosclerotic subtype of ischemic stroke shares pathophysiological mechanisms with these other disorders."

The writing group notes that including stroke as a high-risk condition expands by roughly 10% the number of patients considered to be at high risk.

They also note that because of the heterogeneity of stroke, it remains unclear whether other stroke subtypes, including hemorrhagic and nonatherosclerotic ischemic stroke subtypes, should be considered to present the same high levels of risk. The group concludes that further research is needed on this issue.

Dr. Gorelick points out, "With better blood and neuroimaging biomarkers, in the future we may be able to better sort out gaps in our knowledge about germane nonatherosclerotic stroke subtype questions in relation to risk equivalency and CVD prediction."

Add Stroke to Risk Algorithms

For the purposes of primary prevention, the writing group concludes that ischemic stroke should be included among CVD outcomes in absolute risk assessment algorithms.

They say including stroke with myocardial infarction and sudden death among the outcome cluster of CV events in risk prediction instruments is "appropriate because of the impact of stroke on morbidity and mortality, the similarity of many approaches to prevention of stroke and these other forms of vascular disease, and the importance of stroke relative to coronary disease in some subpopulations."

They also note that non-US guidelines often include stroke patients among others at high cardiovascular risk and include stroke as a relevant outcome along with cardiac end points.

"As a take-away message," said Dr. Gorelick, "it is recommended that clinicians continue to follow current risk factor management guidelines for stroke until new risk prediction models are developed, validated and recommended for use. The work by Lackland et al heightens the visibility of stroke and may eventually lead to raising the prevention and treatment bar," he added.

Dr. Lackland has disclosed no relevant financial relationships. A complete list of disclosures for the writing group is listed with the original article. Dr. Gorelick has no disclosed no relevant financial relationships.

Stroke. Published online May 24, 2012. Abstract

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