Friday, August 31, 2007

Chronic Obstructive Pulmonary Disease (COPD

Beyond the lungs—a new view of COPD

The Lancet 2007; 370:713


Despite being the fifth leading cause of death in high-income countries, and the sixth in low-income and middle-income nations, chronic obstructive pulmonary disease (COPD) has not received the attention it deserves. It is underdiagnosed, undertreated, and underfunded and neglected by the public, pharmaceutical industry, and physicians alike when compared with other major killers, such as cardiovascular disease and stroke. This neglect is sadly due in part to the perception that COPD is a self-inflicted smokers' disease that affects only elderly people and has no effective treatment. Thankfully, these misconceptions about COPD are rapidly being challenged. As this week's issue of The Lancet—which focuses on the condition to coincide with this year's European Respiratory Society meeting in Stockholm, Sweden (Sept 15–19)—shows, COPD can affect never-smokers, be caused by factors other than cigarette smoke, and susceptibility to the disease could be established in utero.

Over 15% of COPD occurs in people who have never smoked. Although smoking is the most important risk factor for COPD in high-income and middle-income countries, in low-income nations exposure to indoor air pollution, such as the fumes from biomass fuels for cooking and heating, causes most COPD cases. The BOLD study in this week's issue, which estimates the worldwide prevalence of COPD, illustrates the importance of risk factors other than smoking. The investigators found that the prevalence of COPD among individuals aged 40 years and older who had never smoked was similar to that for those who had ever smoked and had 0–10 pack-years of cigarette smoking exposure. Several study sites had exposure to potential risk factors for COPD other than smoking, including occupational hazards—irritants, fumes, and vapours—and tuberculosis.

Second-hand smoke is another risk for people who have never smoked. As Peng Yin and colleagues show, passive smoking in workplaces and homes could be responsible for 1·9 million (95% CI 0·9–2·8 million) excess deaths from COPD among never-smokers in China. The results from Yin and colleagues' study should urgently inform tobacco-control policy in China, where, according to this week's World Report, economic arguments about the country's billion-dollar tobacco industry are currently triumphing over health concerns. However, the human and economic ramifications of smoking and passive smoking in terms of health-care costs, lost years of work and productivity, and premature deaths should be the Chinese Government's greater concern.

COPD is not just a “smokers' disease”. Nor is it solely an affliction in old age, since 5–10% of non-smoking young adults show signs of COPD. Future preventive interventions might be applicable in pregnancy or infancy. As Debra Stern and colleagues show, poor airway function shortly after birth is a risk factor for airway obstruction in early adult life—a strong predictor of COPD.

What of the view that little can be done for patients? Currently, the condition cannot be reversed by the mainstay therapies—bronchodilators and anti-inflammatories—but medications can provide patients with symptomatic relief and improve quality of life. One of the problems in the search for new drugs for COPD has been that large clinical trials have excluded patients who have comorbidities commonly associated with the condition, such as ischaemic heart disease and diabetes. Such exclusion means that the results from large trials have little relevance to real-life patients.

This lack of attention to COPD comorbidities makes the suggestion put forward by the authors of this week's Viewpoint all the more compelling. Leonardo Fabbri and Klaus Rabe argue that COPD and all its comorbidities should come under a new umbrella term—chronic systemic inflammatory syndrome—because the systemic effects of smoking contribute to several other conditions, including cardiovascular disease, some cancers, and increased blood pressure.

We support this call for a new view of the disease. The non-pulmonary conditions associated with COPD need to be recognised as part of the diagnosis rather than as separate medical conditions, especially since patients are more likely to die from these conditions than COPD. Such a shift in thinking could bring us closer to the goal that has so far been elusive—treatments that can reduce mortality associated with COPD. That this year's European Respiratory Society meeting has a session devoted to COPD comorbidities is a promising start. Only with a view of COPD that goes beyond the lungs can the research community deliver what many clinicians want and patients need—a holistic approach to the management of this disabling condition.

Angioplasties Increasing, Bypass Surgeries Decreasing

Angioplasties Increasing, Bypass Surgeries Decreasing

31 Aug 2007

Use of transluminal coronary angioplasty, or PTCA, a procedure for opening blocked arteries in patients with coronary artery disease, is now used nearly three times more often than the older and more invasive coronary artery bypass graft surgery (CABG), according to the latest News and Numbers from the Agency for Healthcare Research and Quality.

AHRQ found that:

The number of angioplasties nearly doubled from 1993 to 2005, rising steadily from 418,000 to 800,000 a year.

In contrast, heart bypass surgeries rose slowly from 344,000 to 426,000 a year between 1993 and 1997, and then declined steadily to 278,000 a year by 2005.

Although hospital stays in 2005 for angioplasty are much shorter than they were in 1993 (on average 2.7 days instead of 4.6 days), hospital charges have increased by more than 50 percent during the period, rising from $31,300 to $48,000 (adjusted for inflation).

With 1.1 million hospital stays in 2005, coronary artery disease was the third most common reason for hospitalization after childbirth and pneumonia.

It was the second leading reason for men, and the seventh for women.

Clinical Evidence Concise

This clinical content conforms to AAFP criteria for evidence-based continuing medical education

A Publication of BMJ Publishing Group

Atrial Fibrillation (Chronic)

christopher j. boos, Deidre a. lane, and Gregory y.h. lipUniversity Department of Medicine, City Hospital, Birmingham, United Kingdom

What are the effects of oral medical treatments to control heart rate in persons with chronic (longer than one week) nonvalvular atrial fibrillation?

likely to be beneficial

Beta Blockers vs. Digoxin (Beta Blockers More Effective Than Digoxin in Controlling Symptoms). One randomized controlled trial (RCT) identified by a systematic review found that digoxin reduced nocturnal heart rate compared with carvedilol in persons with chronic nonvalvular atrial fibrillation. It found no significant difference in 24-hour ventricular rate, exercise tolerance, or daytime and exercise heart rate. The systematic review, which also included weaker evidence from an RCT on a withdrawn drug and expert opinion, concluded that beta blockers should be used in preference to digoxin in persons who are not sedentary.

(Categorization based on consensus.)

Beta Blockers Plus Digoxin vs. Beta Blockers Alone (Beta Blockers Plus Digoxin More Effective Than Beta Blockers Alone). We found no systematic review or RCTs of persons with chronic nonvalvular atrial fibrillation that met BMJ Clinical Evidence inclusion criteria. A systematic review, which also included weaker evidence, an RCT on a withdrawn drug, and expert opinion supported the addition of digoxin when a beta blocker alone is ineffective. (Categorization based on consensus.)

Calcium Channel Blockers (Rate Limiting) vs. Digoxin (Calcium Channel Blockers More Effective Than Digoxin for Controlling Heart Rate). One RCT identified by a systematic review found that verapamil lowered rest and exercise heart rate more effectively than digoxin in persons with chronic nonvalvular atrial fibrillation; however, significance was not assessed. The RCT also did not assess harms. The systematic review, which also included weaker evidence and expert opinion, supported the use of rate-limiting calcium channel blockers over digoxin as initial monotherapy in most persons, with the exception of sedentary persons. (Categorization based on consensus.)

Calcium Channel Blocker (Rate Limiting) Plus Digoxin vs. Calcium Channel Blocker (Rate Limiting) Alone (Calcium Channel Blocker Plus Digoxin More Effective Than Calcium Channel Blocker Alone). One RCT identified by a systematic review found that calcium channel blockers plus digoxin decreased resting and exercise heart rate and improved maximal effort capacity compared with calcium channel blockers alone. The systematic review, which also included weaker evidence and expert opinion, supported the addition of digoxin when a calcium channel blocker alone was ineffective.

trade-off between benefits and harms

Beta Blockers vs. Rate-Limiting Calcium Channel Blockers (Selection Is Dependent on Individual Risk Factors and Coexisting Morbidities). One RCT identified by a systematic review found that, in persons taking digoxin, ventricular rates (during rest and exercise), average heart rate, and maximal heart rates were lower with a beta blocker compared with a calcium channel blocker. Minimal heart rate was similar in both groups. More adverse effects were reported with the beta blocker than with the calcium channel blocker. The systematic review, which also included weaker evidence and expert opinion, supported the use of beta blockers or calcium channel blockers.

What is the effect of different treatment strategies for persons with persistent nonvalvular atrial fibrillation?

trade-off between benefits and harms

Rhythm Control vs. Rate Control (Selection Dependent on Individual Risk Factors and Coexisting Morbidities). We found inconclusive results from RCTs comparing rhythm control versus rate control strategies. One systematic review found that rate control was associated with a better prognosis than rhythm control when the combined end point of all-cause mortality and thromboembolic events was examined, particularly in older persons. Another systematic review and one RCT found no significant difference between rhythm and rate control in thromboembolism, strokes, and major bleeding. RCTs found that rhythm control improved exercise tolerance, reduced ventricular heart rate, and achieved sinus rhythm compared with rate control; however, the difference did not reach significance in some RCTs. Two RCTs found no difference in quality of life between rhythm and rate control. Adverse effects were more common with rhythm control strategies compared with rate control strategies. Current consensus supports the use of either rhythm or rate control depending on individual risk factors and coexisting morbidities.


Atrial fibrillation is the most commonly encountered and sustained cardiac arrhythmia in clinical practice.1 It is a supraventricular tachyarrhythmia, which is characterized by the presence of uncoordinated atrial activation and deteriorating atrial mechanical function.1,2 On the surface electrocardiography, P waves are absent and are replaced by rapid fibrillatory waves that vary in size, shape, and timing, leading to an irregular ventricular response when atrioventricular conduction is intact.


Chronic atrial fibrillation is most commonly classified according to its temporal pattern.3 Faced with a first detected episode of atrial fibrillation, three recognized patterns of chronic disease may develop: (1) persistent atrial fibrillation describes an episode of sustained atrial fibrillation (usually longer than seven days) that does not convert to sinus rhythm without medical intervention, with the achievement of sinus rhythm by pharmacologic or electrical cardioversion; (2) paroxysmal atrial fibrillation refers to self-terminating episodes of atrial fibrillation, usually lasting less than 48 hours (paroxysmal and persistent atrial fibrillation may be recurrent); and (3) permanent atrial fibrillation, episodes of persistent atrial fibrillation (usually longer than one year), in which cardioversion is not attempted or is unsuccessful, with atrial fibrillation accepted as the long-term rhythm for that person. Lone atrial fibrillation is largely a diagnosis of exclusion and refers to atrial fibrillation occurring in the absence of concomitant cardiovascular disease (e.g., hypertension) or structural heart disease (normal echocardiography), with normal electrocardiography and chest radiography.2

In most cases of suspected atrial fibrillation, 12-lead electrocardiography is sufficient for diagnosis confirmation.2 Where diagnostic uncertainty remains, such as in chronic permanent atrial fibrillation, the use of 24-hour (or even seven-day) Holter monitoring or event recorder (e.g., Cardiomemo) may also be required.2 The most common presenting symptoms of chronic atrial fibrillation are palpitations, shortness of breath, fatigue, chest pain, dizziness, and stroke.1,2

Incidence and Prevalence

Atrial fibrillation carries an overall population prevalence of 0.5 to 1.0 percent and an incidence of 0.54 cases per 1,000 person-years.4,5 The prevalence of atrial fibrillation is highly age dependent and increases markedly with each advancing decade of age, from 0.5 percent at 50 to 59 years of age to almost 9 percent at 80 to 90 years of age.6 The incidence of atrial fibrillation has a male predisposition, affecting men 1.5 times more commonly than women.7 The Screening for Atrial Fibrillation in the Elderly project reported that the baseline prevalence of atrial fibrillation in persons older than 65 years was 7.2 percent, with a higher prevalence in men (7.8 percent) and persons at least 75 years of age, with an incidence of 0.69 to 1.64 percent a year, depending on screening method.8 These incidence data refer to cross-sectional study data whereby most persons would have atrial fibrillation of more than seven days duration (persistent, paroxysmal, or permanent atrial fibrillation), and not acute atrial fibrillation.


Atrial fibrillation is linked to all types of cardiac disease, including cardiothoracic surgery, as well as to a large number of noncardiac conditions such as thyroid disease, any pyrexial illness, electrolyte imbalance, cancer, and acute infections.1,2


Chronic atrial fibrillation confers an enormous and significant clinical burden. It is an independent predictor of mortality and is associated with an odds ratio for death of 1.5 for men and 1.9 for women, independent of other risk factors.9 It increases the risk of ischemic stroke and thromboembolism by an average of fivefold.10 Furthermore, the presence of chronic atrial fibrillation is linked to far more severe strokes, with greater disability and lower discharge rate to their own home.10,11 Chronic atrial fibrillation is common (3 to 6 percent of all medical admissions)2 and results in longer hospital stays. In addition, chronic atrial fibrillation increases the development of heart failure and adversely affects quality of life, including cognitive function.12

search date: June 2006
Adapted with permission from Boos CJ, Lane DA, Lip GY. Atrial fibrillation (chronic). Clin Evid Handbook June 2007:27-9.

Author disclosure: Nothing to disclose.

1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257-e354.
2. National Collaborating Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London, UK: Royal College of Physicians, 2006. Accessed June 15, 2007, at:
3. Levy S, Camm AJ, Saksena S, et al. International consensus on nomenclature and classification of atrial fibrillation; a collaborative project of the Working Group on Arrhythmias and the Working Group on Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Europace 2003;5:119-22.
4. Stewart S, Hart CL, Hole DJ, et al. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001;86:516-21.
5. Murdoch DL, O'Neill K, Jackson J, et al. Are atrial fibrillation guidelines altering management? A community based study. Scott Med J 2005;50:166-9.
6. Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998;82:2N-9N.
7. Singh SN, Tang XC, Singh BN, et al. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy. J Am Coll Cardiol 2006;48:721-30.
8. Hobbs FD, Fitzmaurice DA, Mant J, et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess 2005;9:1-74.
9. Benjamin EJ, Wolf PA, D'Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946-52.
10. Wolf PA, D'Agostino RB, Belanger AJ, et al. Probability of stroke: a risk profile from Framingham Study. Stroke 1991;22:312-8.
11. Jorgensen HS, Nakayama H, Reith J, et al. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996;27:1765-9.
12. Freestone B, Lip GYH. Epidemiology and costs of cardiac arrhythmias. In: Lip GYH, Godtfredson J, eds. Cardiac Arrhythmias: A Clinical Approach. Edinburgh, UK: Mosby, 2003:3-24.

Thursday, August 30, 2007

New guidelines for cardiac pacing and cardiac resynchronization therapy

ESC publishes new guidelines for cardiac pacing and cardiac resynchronization therapy

August 30, 2007
Michael O'Riordan

Sophia Antipolis, France - On the eve of the European Society of Cardiology (ESC) 2007 Congress, which begins Sunday in Vienna, Austria, the ESC, in partnership with the European Heart Rhythm Association, has released new guidelines for cardiac pacing and cardiac resynchronization therapy (CRT) [1].

The guidelines, now published online in the European Heart Journal, aim to provide an up-to-date specialists' view of the European field and specifically address the issue of permanent pacing in bradyarrhythmias, syncope, and other conditions like hypertrophic obstructive cardiomyopathy and the use of ventricular resynchronization as an adjunct therapy in patients with heart failure.

The new guidelines, by Dr Panos Vardas (Heraklion University Hospital, Greece) and other experts, focus on the use on the appropriate use of pacemakers with various arrhythmias, including sinus node disease, atrioventricular and intraventricular conduction disturbances, pacing disturbances related to AMI, and reflex syncope, among others, and provide recommendations for clinical indications for pacing and the choice of pacing mode.
In addition, the expert panel comments on the rationale for CRT in heart-failure patients, highlights the newest evidence, and makes recommendations according to the different clinical and technical characteristics of the single patient.

"Thanks to important developments in technology and advances in the essential knowledge that we now have concerning the physiology of the paced beat, patients with sinus-node dysfunction and atrioventricular conduction system defects can now be given high-quality therapy," Vardas, chair of the new ESC guidelines, commented in an press release. "These and other developments over the past few years have advanced electrical stimulation further into the realm of ventricular resynchronization as an adjunctive therapy for patients with drug-refractory heart failure and ventricular conduction delay."

The ESC guidelines also highlight the main objectives, structure, and function of a pacemaker clinic and provide recommendations for predischarge assessment of long-term follow-up methodology. The full document, which will soon be published as a pocket-sized version and be available as a personal digital assistant download, is available at the ESC website.


Vardas PE, Auricchio A, Blanc JJ, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy. Eur Heart J 2007; DOI:10.1093/eurheart/ehm305. Available at:

Related links:

Guidelines for cardiac pacing and cardiac resynchronization therapy.
In CRT, ventricular size responds more to biventricular than to LV-only pacing [HeartWire > Heart failure; Apr 13, 2007]
Atrial fib: No reason to avoid resynchronization therapy for heart failure [HeartWire > Heart failure; Mar 20, 2007]
CRT patient-selection criteria: Studies question QRS duration, support tissue-Doppler imaging [HeartWire > Heart failure; Dec 22, 2006]
COMPANION and DEFINITE published: CRT, ICD for HF on threshold of new era [HeartWire > Heart failure; May 19, 2004]

Statin treatment withdrawal in ischemic stroke: a controlled randomized study

Statin treatment withdrawal in ischemic stroke: a controlled randomized study.

Neurology. 2007 Aug 28;69(9):904-10.

Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Dávalos A, Castillo J.

Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.

BACKGROUND: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients.

METHODS: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126).

RESULTS: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048).

CONCLUSION: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.

Warfarin Versus Aspirin for Stroke Prevention in an Elderly Community Population With Atrial Fibrillation

Title: Warfarin Versus Aspirin for Stroke Prevention in an Elderly Community Population With Atrial Fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): A Randomised Controlled Trial

Topic: Arrhythmias

Date Posted: 8/28/2007

Author(s): Mant J, Hobbs FD, Fletcher K, et al.

Citation: Lancet. 2007;370:493-503.

Clinical Trial: Yes

Study Question: Does warfarin reduce the risk of major stroke, arterial embolism, or other intracranial hemorrhage, compared with aspirin in elderly patients with atrial fibrillation?

Methods: The authors report the results of the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a randomized, open-label trial of aspirin versus warfarin in subjects over age 75 with atrial fibrillation. Patients were excluded if they had increased risk for gastrointestinal bleeding, rheumatic heart disease, intracranial hemorrhage, blood pressure >180/110 mm Hg, or at prohibitive risk for bleeding with warfarin, in their physician’s judgment. Subjects were randomized to warfarin (target INR 2-3), or aspirin 75 mg daily, for a mean of 2.7 years’ follow-up. The primary outcome was fatal or nonfatal stroke, intracranial hemorrhage, or clinically significant arterial embolism. Secondary outcomes were major hemorrhage, other vascular events, and all-cause mortality.

Results: The authors report 973 subjects were randomized from April 2001 to November 2004, among whom there were 24 primary events in the warfarin group (21 strokes, two other intracranial hemorrhages, and one systemic embolus), and 48 events in the aspirin group (44 strokes, one other intracranial hemorrhage, and three systemic emboli), (relative risk, 0.48; 95% confidence interval, 0.28-0.80; p = 0.003). This resulted in a yearly risk for primary event of 1.8% and 3.8% in the two groups, respectively. The yearly risk of extracranial hemorrhage was 1.4% (warfarin) versus 1.6% (aspirin) (relative risk, 0.87; 0.43-1.73).

Conclusions: The authors concluded that the data support the use of warfarin in patients with atrial fibrillation over age 75, unless there are contraindications, or the patient refuses warfarin therapy.

Perspective: There is a common misconception that benefits of medical therapy are fixed, while risks associated with medical therapy vary. This fallacy has led to the belief that greater risk of bleeding with advancing age makes warfarin therapy in the elderly more risky. Forgotten is the fact that risk of thromboembolic stroke from atrial fibrillation also increases with age. This same phenomenon is seen in a number of other medical conditions. Our training to compare ‘risk versus benefits’ leads, I believe, to this error in thinking. Benefits are reported and thought of as fixed (e.g., ‘warfarin lowers risk of stroke in atrial fibrillation x%’), whereas risks of therapy are seen as relative to the patient’s condition, age, and other risk factors. This error of medical decision making is compounded by the exclusion of the elderly from clinical trials—leaving us without adequate data. Ideally, we should assess both the risk of therapy, as well as the risk of not taking therapy, on an individual basis for each patient, based on available data (a ‘risk vs. risk’ comparison, rather than ‘risk vs. benefit’). Clearly, more clinical trial data that include the elderly are crucial. And we should remember that if a treatment is effective, it is logically more effective in groups at higher risk from complications of disease, and that usually means the elderly

CPAP Machine May Help Prevent Heart Attack, Stroke in People With Obstructive Sleep Apnea

Sleep Apnea Device May Help Save Heart

CPAP Machine May Help Prevent Heart Attack, Stroke in People With Obstructive Sleep Apnea

By Miranda Hitti WebMD Medical News

Reviewed by Louise Chang, MD

Aug. 29, 2007 -- A device that treats a common sleep disorder called obstructive sleep apnea may help prevent heart attacks, strokes, and other cardiovascular problems, a new study shows.

Obstructive sleep apnea is a very serious condition in which people have trouble breathing during sleep because their airway is blocked. They may have very shallow breath or even stop breathing briefly several times per night.

A device called CPAP (continuous positive airway pressure) helps people with obstructive sleep apnea breathe more easily during sleep.

The new study comes from German doctors including Nikolaus Buchner, MD, of Germany's Ruhr University Bochum.

They already knew that CPAP may reduce heart risks in people with severe obstructive sleep apnea. Buchner's team wanted to see if that's also true for people with milder obstructive sleep apnea.

CPAP Study

Buchner and colleagues offered CPAP machines to 449 adults with mild, moderate, or severe obstructive sleep apnea. All but 85 patients accepted the devices.

The patients, who got regular checkups, were typically followed for about six years.Those who accepted CPAP were 64% less likely to have certain fatal or nonfatal cardiovascular problems -- including heart attacks and strokes -- during the study period, regardless of their age, BMI (body mass index), type 2 diabetes, cholesterol, and history of heart disease.

Buchner and colleagues note that their findings may not apply to everyone with obstructive sleep apnea.

However, the researchers write that therapy for obstructive sleep apnea "should be considered" even for mild forms of obstructive sleep apnea.

The study appears in an advance online edition of the American Journal of Respiratory and Critical Care Medicine.

SOURCES: Buchner, N. American Journal of Respiratory and Critical Care Medicine, Aug. 2, 2007; advance online edition. National Heart, Lung, and Blood Institute: "Sleep Apnea." WebMD Medical News: "Treatment for Sleep Apnea May Ease Depression."

Wednesday, August 29, 2007

Heart Palpitations Are Usually Not Dangerous, Reports The Harvard Heart Letter

29 Aug 2007

Palpitations the sensation that the heart has started to race or pound, or feels like it has skipped a beat are usually caused by a harmless hiccup in the heart's rhythm.

Sometimes, though, palpitations reflect a problem in the heart or elsewhere in the body. Sorting out worrisome palpitations from harmless ones isn't always easy, reports the September 2007 issue of the Harvard Heart Letter.

Palpitations are extremely common. Different people experience them in different ways. You might feel as though your heart is fluttering, throbbing, flip-flopping, or pounding, or that it has missed a beat. Palpitations can appear out of the blue and disappear just as suddenly. Or they might be linked with certain activities, events, or feelings. Some of the most important pieces of information that can help your doctor in pinning them down is how palpitations feel, how often they strike, and when they occur.

Some palpitations result from premature contractions of the heart's chambers or malfunctions of a heart valve. But a physical exam and electrocardiogram often don't turn up any problems, which can be frustrating to the patient.

If your palpitations aren't accompanied by dizziness or other symptoms and if you don't have a valve disorder or other structural problem with your heart, that usually means palpitations are benign.

The Harvard Heart Letter suggests that if you have unexplained palpitations, start with simple steps to help alleviate them. Cut back on caffeine, smoking, and alcohol; avoid over-the-counter decongestants, eat and drink regularly, get enough sleep, and find a way to relax if you are stressed.

In some cases, your doctor may recommend medications or a procedure to correct errant electrical signals in the heart.

Harvard Heart Letter

The Rosiglitazone Story -- Lessons from an FDA Advisory Committee Meeting

NEJM -- The Rosiglitazone Story -- Lessons from an FDA Advisory Committee Meeting

Observations about the rticlr

On July 30, 2007, the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) convened to discuss the myocardial ischemic risk associated with rosiglitazone treatment in patients with type 2 diabetes mellitus. The joint committee, which I chaired, consisted of 24 experts in cardiovascular disease, epidemiology, biostatistics, and endocrinology. After lengthy discussions, we concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas.

That conclusion was based primarily on three independently conducted meta-analyses demonstrating an increase in the relative risk of myocardial infarction, angina, or sudden death among patients taking rosiglitazone

Drugs are approved or removed from the market on the basis of evidence from randomized, controlled trials. In the FDA hearing on rosiglitazone, several meta-analyses revealed a significant increase in the risk of myocardial ischemic events among patients taking rosiglitazone. However, an interim analysis of the ongoing Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial, which was designed specifically to assess cardiovascular risk among patients receiving rosiglitazone, failed to demonstrate a similar risk.5 In addition, two large observational studies, one conducted by Tricare for the Department of Defense and one conducted by WellPoint (the largest health insurer in the United States), noted no appreciable signal of increased cardiovascular risk with either of the available thiazolidinediones. The contrasts among the levels of evidence and the results regarding the safety of rosiglitazone raised new questions about relative and absolute risks but also highlighted the weaknesses of observational studies examining events that are common and whose rates are likely to be increased only slightly by a given drug, even in a large cohort (such as that used by WellPoint, which comprised 160,000 patient records).

Coronary collateral circulation reduces mortality in chronic CAD

MedWire News - Cardiology - Coronary collateral circulation reduces mortality in chronic CAD

MedWire News: Patients with chronic stable coronary artery disease (CAD) who have well-functioning coronary collateral circulation are up to a quarter less likely to die than those without a collateral supply, say Swiss researchers.

The researchers conclude in the journal Circulation: "A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply."

Tuesday, August 28, 2007

Retinal vessel diameter may predict CHD death

MedWire News - Cardiology - Retinal vessel diameter may predict CHD death

MedWire News: Retinal vessel diameter is associated with the risk for death from coronary heart disease (CHD) in middle-aged people, reports an international team of researchers.

"Our findings, if confirmed in other populations, suggest that retinal vessel diameter could be a prognostic marker of death from cardiovascular events in middle-aged persons," the authors conclude in the European Heart Journal.

Associations between tooth loss cardiovascular disease (CVD) and cancer mortality.

Associations between tooth loss and mortality patterns in the Glasgow Alumni Cohort

Tu et al. Heart.2007; 93: 1098-1103



To use data from the Glasgow Alumni Cohort to investigate whether oral health in young adulthood is independently associated with later life cardiovascular disease (CVD) and cancer mortality.

Methods and results:

Of the original cohort (n = 15 322), 12 631 subjects were traced through the National Health Service Central Register.

Of these, 9569 men and 2654 women were 30 years or younger at baseline.

During up to 57 years of follow-up, 1432 deaths occurred among subjects with complete data, including 509 deaths from CVD and 549 from cancer.

After adjusting for potential confounders, no substantial association was found between the number of missing teeth (as a continuous variable) and all-cause mortality (hazard ratio (HR) for each extra missing tooth = 1.01; 95% confidence interval (CI) 1.00 to 1.02), CVD mortality (HR = 1.01; 95% CI 0.99 to 1.03) or cancer mortality (HR = 1.00; 95% CI 0.98 to 1.02).

When the number of missing teeth was treated as a categorical variable, there was evidence that students with nine or more missing teeth at baseline had an increased risk of CVD (HR = 1.35; 95% CI 1.03 to 1.77) compared with those with fewer than five missing teeth.

When the number of missing teeth was transformed using fractional polynomials, there seemed to be a non-linear relation between missing teeth and CVD mortality.


Although some evidence was found to support the relation between tooth loss and CVD mortality, causal mechanisms underlying this association remain uncertain.

Stop Paying for Drug-Coated Stents

Wall Street Journal (Health Blog)
August 27, 2007

UK Gov’t Could Stop Paying for Drug-Coated Stents

Posted by Jacob Goldstein

This week’s installment in drug-coated stents’ never-ending tale of woe comes from Britain, where the National Health Service could soon stop paying for the devices altogether.

A recent report (available here) commissioned by the government found that drug-coated stents, which cost about $2,300, aren’t worth the extra money compared to older bare metal stents, which cost about $700.

Tomorrow is the last day for the public to comment on the report, and the country’s National Institute for Health and Clinical Excellence will meet next week to review the evidence, the Associated Press reports.

“We are seeing the pendulum swing too far the other way,” a cardiologist and spokesman for the European Society of Cardiology told the AP. The British Cardiovascular Society said it was “surprised, disappointed and very concerned” by the proposal.

The British will likely will stop short of denying reimbursement altogether, Morgan Stanley analyst Glenn Reicin argues in a note to investors. But Reicin, who puts the U.K.’s drug-coated stent market at $80 million to $100 million, adds that “one cannot totally rule out something more dramatic.”

Clogged arteries propped open with drug-coated stents are less likely to re-clog than those supported by bare-metal stents. But the drug-coated devices may carry a slightly higher risk of causing blood clots long after being inserted. And one recent study found that many patients who receive stents might do just as well receiving only drug treatment.

Those findings have sent sales of drug-coated stents way down for Johnson & Johnson and Boston Scientific. So far, though, there’s no sign that insurers in this country plan to stop paying for the devices.

Monday, August 27, 2007

Statins and Alzheimer's disease

Heart Drug May Hold Off Alzheimer's
By Alice Park

The long goodbye of Alzheimer's disease may become increasingly common as our population ages in coming years, but scientists in Seattle provide reassuring evidence that at least some of the disease's gradual mental decline can be held off with, of all things, cholesterol-lowering drugs.

In a study of 110 elderly volunteers, aged 65 to 79, who donated their brains for research and whose cognitive functions were monitored over several years prior to their death, scientists led by Dr. Eric Larson of the Group Health Center for Health Studies found that those who had taken statin drugs to lower their cholesterol had fewer nerve-damaging plaques and tangles — protein deposits that form in and around neurons — in their brains than those not taking the medications. Buildup of these protein plaques and tangles are the hallmark of Alzheimer's disease; they inexorably disrupt the critical connections between neurons that govern thought processes and sabotage everything from the storage and retrieval of memories to learning and language skills.

The new findings are the latest and most definitive results linking the popular statin drugs to Alzheimer's. Earlier studies had produced conflicting results: some found that statins reduced the risk of the brain disorder, while others found no effect. Larson's study is the first to directly compare the brains, on autopsy, of statin users and non-users (Alzheimer's can be conclusively diagnosed only after death, when pathologists confirm the presence of the plaques and tangles in the brain). "This data does give us some additional hope that statins may turn out to have a useful relationship in slowing Alzheimer's disease," says William Thies, vice president of medical and scientific relations of the Alzheimer's Association.

How do cholesterol-lowering drugs work on the brain? As experts learn more about Alzheimer's, they believe that it's less a disease of the brain than of the vasculature, or blood vessel system. It turns out that many of the risk factors for Alzheimer's are the same ones for heart disease, and that the build up of protein in the brain is not unlike the gradual accumulation of plaque in the heart vessels. "We are learning that Alzheimer's disease isn't just plaques and tangles appearing through a series of biochemical processes, but that vascular stress may play a role in their development," says Larson. "Anything we can do to lower the vascular risk profile could lower the risk of Alzheimer's." Statins, then, could be inhibiting the development of Alzheimer's by keeping the brain's neural highways free of potentially bottlenecking protein plaques. In addition, says Larson, statins may be working on a more molecular level, by actually blocking the formation of the sticky, fibrous tangles that can jam nerve connections.

To learn more about exactly how statins could be thwarting the Alzheimer's disease process, Larson acknowledges that the first step involves having another, independent group replicate his team's findings. In the meantime, he plans to continue his study by adding more volunteers. Within the next year, Thies expects two more trials to produce results and hopefully solidify the effect statins have on the brain.

Stem Cells Help Rat Hearts Recover After Attack

Article abstract

Nature Biotechnology
Published online: 26 August 2007

Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts

Michael A Laflamme, Kent Y Chen, Anna V Naumova, Veronica Muskheli, James A FugateSarah, K Dupras Hans Reinecke, Chunhui Xu, Mohammad Hassanipour, Shailaja Police, Chris O'Sullivan, Lila Collins, Yinhong Chen, Elina Minami, Edward A Gill, Shuichi Ueno, Chun Yuan, Joseph Gold & Charles E Murry


Cardiomyocytes derived from human embryonic stem (hES) cells potentially offer large numbers of cells to facilitate repair of the infarcted heart.

However, this approach has been limited by inefficient differentiation of hES cells into cardiomyocytes, insufficient purity of cardiomyocyte preparations and poor survival of hES cell–derived myocytes after transplantation.

Seeking to overcome these challenges, we generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4. We then identified a cocktail of pro-survival factors that limits cardiomyocyte death after transplantation.

These techniques enabled consistent formation of myocardial grafts in the infarcted rat heart. The engrafted human myocardium attenuated ventricular dilation and preserved regional and global contractile function after myocardial infarction compared with controls receiving noncardiac hES cell derivatives or vehicle.

The ability of hES cell–derived cardiomyocytes to partially remuscularize myocardial infarcts and attenuate heart failure encourages their study under conditions that closely match human disease.

Action Points

Explain to interested patients that human embryonic stem cells are regarded as a potential therapy for a range of illnesses and organ damage, since they can, in principle, develop into any type of cell.

Note that this study shows that -- in rats, after an experimentally induced heart attack -- human embryonic stem cells can be used to reduce the damage and improve function.

Caution that the research took place in animals and further study is needed.

Gmail - [ProCOR] Hormone Replacement Therapy in Postmenopausal Women

Gmail - [ProCOR] Hormone Replacement Therapy in Postmenopausal Women

Title: Main Morbidities Recorded in the Women's International Study of Long Duration Oestrogen After Menopause (WISDOM): A Randomised Controlled Trial of Hormone Replacement Therapy in Postmenopausal Women

Authors: MR Vickers, AH MacLennan, B Lawton, D Ford, J Martin, SK Meredith, BL DeStavola, S Rose, A Dowell, HC Wilkes, JH Darbyshire, TW Meade

Reference: BMJ 2007; 335: 239,
Reviewer: Robert Goldberg, PhD, ProCor contributing editor

Results of the study below suggest that postmenopausal women starting or restarting hormone replacement therapy are at increased risk for developing coronary heart disease than women not treated with this drug regimen.

Problem addressed: Long-term risks and benefits associated with use of hormone replacement therapy (HRT) in postmenopausal women.

Purpose of study: To assess the long-term benefits as well as risks associated with HRT in a large sample of postmenopausal women recruited from nearly 500 general practices in the UK, Australia and New Zealand.

Location of study: London, England, UK

Study design: RCT

Results: The WISDOM Trial recruited a large number of postmenopausal womenbetween the ages of 50-69 years from a total of 499 general practices in the UK (# of practices = 384), Australia (n=91) and New Zealand (n=24) to the receipt of estrogen only therapy, combined hormone therapy, or to placebo medication. A total of more than 56,000 women were screened for trial entry, 8,980 entered a trial run-in phase, and 5,692 were randomly assigned to the different treatment modalities. Recruitment to the trial began in 1999 and 2000; of the women enrolled in the trial, the vast majority was from the UK.

The trial randomization schema was stratified based on hysterectomy status and intended use of HRT. Women with an intact uterus were randomly assigned to the receipt of either combined estrogen plus progestogen therapy or to placebo. In parallel, women without a uterus or who were unwilling to take placebo therapy were randomly assigned to estrogen therapy, combined estrogen plus progestogen therapy or to placebo treatment.

A number of predefined primary as well as secondary study outcomes were examined in this trial. The primary trial outcomes were the occurrence of a major CHD event (e.g., unstable angina, fatal or nonfatal MI, or SCD), osteoporotic fractures, and breast cancer. The secondary trial outcomes included mortality from breast and other cancers, deaths from all causes, venous thromboembolic disease, cerebrovascular disease and dementia. The mean age of participating women at the time of study enrollment was 63 years, the majority were white, the average BMI was 28 and the primary comparison groups were relatively well balanced on the trial entry characteristics.

Over an average follow-up of approximately one year, women taking combined HRT had markedly increased rates of CVD and venous thromboembolic disease, and a nonsignificant reduction in the risk of developing osteoporatic fractures (31% reduction), as compared to those taking placebo. The incidence rates of cerebrovascular disease, breast cancer and other cancers were not significantly different between the respective comparison groups. The incidence rates of serious adverse events did not significantly differ in either of the randomized comparisons performed.

While there were no significant differences in the incidence rates of CVD events or venous thrombosis between women prescribed estrogen therapy, as compared to those taking estrogen plus progestogen treatment, there were suggestions of an increase in these primary endpoints in women prescribed combination therapy. Twice as many women in the combined therapy versus placebo groups withdrew from the trial while the rates of study withdrawal were similar in the combined versus estrogen therapy groups. This trial was prematurely stopped because of the results of the Women's Health Initiative Study which were published in 2002.

Comments: The results of the WISDOM Trial suggest that postmenopausal women starting or restarting combined estrogen and progestogen therapy are at increased risk for developing CHD than women not treated with this drug regimen. On the other hand, treatment with HRT was associated with a decreased risk of osteoporotic practices and decreased risk of osteoporotic fractures and no apparent impact on the risk of stroke or malignancy. Despite the large number of women included in this study, and rigorous trial design, appropriate caveats need to be placed in interpreting the results of this investigation given the premature discontinuation of this trial, relatively short duration of follow-up, and small number of events accrued at the time of study completion.

Similar to the Women's Health Initiative, the WISDOM trial tested the hypothesis that the use of HRT in elderly asymptomatic postmenopausal women might reduce the risk of developing several major comorbidities including CHD, stroke and cancer and have possible beneficial effects on reducing the risk of osteoporotic fractures.

A considerable amount of adverse publicity and patient concern and confusion has resulted from the results of the Women's Health Initiative trial. The results of the WISDOM trial and the Women's Health Initiative call into question any health benefits that might be accrued from the initiation of HRT in postmenopausal women in their 60s, especially on the occurrence of CVD. Decisions about the use of HRT in peri and postmenopausal women need to be carefully considered by patients and their physicians, together with considerations about quality of life, with benefits and risks carefully weighed in both absolute and relative terms.

Sunday, August 26, 2007

Hormone therapy and thromboembolic disease.

Hormone therapy and thromboembolic disease.

Hemostasis and thrombosis Current Opinion in Hematology. 14(5):488-493, September 2007.

Battaglioli, Tullia; Martinelli, Ida


Purpose of review:

Hormone therapy increases the risk of venous thromboembolism (VTE). To reduce this risk, changes in dosage, composition and route of administration have been made over the years. This review provides a summary of the available evidence and an update on the most recent findings on the issue.

Recent findings:

Contraceptives containing third-generation progestagens confer a higher risk of VTE than second-generation compounds. Little data are available on preparations containing less than 30 [mu]g of estrogen, new progestagens or levonorgestrel-releasing intrauterine devices. Hormone replacement therapy increases the risk of VTE by 2 to 3-fold. Transdermal administration may be less thrombogenic than oral administration, while different estrogens and progestagens may carry a different risk. VTE risk is further increased in carriers of inherited thrombophilia. Despite a similar increase in relative risk of thrombosis associated with hormone therapy, absolute risk is lower in fertile women and higher in postmenopausal ones. Universal screening for thrombophilia before prescribing hormone replacement therapy might be cost-effective.


Careful evaluation of individual risk factor is warranted before prescribing hormone therapy. Further investigations are needed to establish whether or not newer compounds are safer than older ones with respect to the risk of thrombosis.

Oxidation May Be New Blood Pressure Regulator

Medical News Today News Article

Oxidation May Be New Blood Pressure Regulator

A novel way of regulating blood pressure has been discovered by British scientists.

This breakthrough could lead to innovative drugs that fight heart attacks and stroke.

"Cysteine Redox Sensor in PKGI Enables Oxidant-Induced Activation" Joseph R. Burgoyne, Melanie Madhani, Friederike Cuello, Rebecca L. Charles, Jonathan P. Brennan, Ewald Schröder, Darren D. Browning, Philip EatonScience DOI: 10.1126/science.1144318

Click here to view abstract online

Saturday, August 25, 2007

Discontinuing aspirin or warfarin optional before cataract surgery - Patient oriented evidence that matters: practice recommendations from key studies - Author Abstract

Journal of Family Practice: Discontinuing aspirin or warfarin optional before cataract surgery - Patient oriented evidence that matters: practice recommendations from key studies - Author Abstract

Katz J, Feldman MA, Bass EB, et al. Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery. Ophthalmology 2003; 110:1784-1788.


Neither warfarin nor aspirin need to be stopped before cataract surgery: patients who continue to use warfarin or aspirin are not at increased risk of ocular hemorrhagic events. Conversely, those who discontinue warfarin or aspirin prior to cataract surgery have no increased risk of thromboembolic or cardiovascular events.

POEM (Patient-Oriented Evidence that Matters)

Discontinuing aspirin or warfarin is optional for cataract surgery

Question Should anticoagulants and antiplatelet agents be stopped before cataract surgery?

Synopsis In theory, having cataract surgery while taking anticoagulants might increase the risk of ocular haemorrhage. Is there any benefit to continued anticoagulation? Although this isn't the best possible study, it is the best available evidence to date on this question. In this cohort study, the authors looked at all patients undergoing cataract surgery who were older than 50 years and had no history of acute myocardial infarction and whose surgery used general anaesthesia.

Patients who took aspirin were considered to have stopped if their last dose occurred 14 days before surgery, and those who took warfarin were considered non-users if the last dose occurred four days before surgery. Of 19 354 patients undergoing 20 775 operations, 94.1% agreed to participate, and 99.8% of the participants provided an interview seven days after the surgery.

Regarding aspirin, 76.7% did not routinely use aspirin, 5.2% used aspirin and discontinued its use, and 18% continued to use aspirin through surgery.

Regarding warfarin, 96.1% did not use it, 1.1% discontinued use, and 2.8% continued use.

There was no significant difference between groups in the risk of ocular haemorrhage between patients who continued or discontinued aspirin, and no ocular haemorrhage occurred among warfarin users.

The risk of myocardial infarction, haemorrhagic cystitis, myocardial ischaemia, stroke, or deep vein thrombosis did not differ.

If anything, there was a slightly greater risk for those who continued use of warfarin and aspirin, perhaps because the providers felt that their patients were at increased risk.

Bottom line It seems that continued use of warfarin or aspirin puts patients at little risk of ocular haemorrhage during cataract surgery.

Conversely, the risk of thromboembolic or cardiovascular events does not seem to be increased if these agents are discontinued.

Level of evidence 2b (see Individual cohort study or low quality randomised controlled trials (< 80% follow up).

Katz J, Feldman MA, Bass EB, et al. Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery. Ophthalmology 2003;110:

Thursday, August 23, 2007

Gout increases risk for CVD, CHD death

Gout increases risk for CVD, CHD death

By Caroline Price (MedWire News)

23 August 2007

Circulation 2007; 116: 894-900

MedWire News: In men without pre-existing coronary heart disease (CHD), gout increases mortality due to an increased risk for cardiovascular disease (CVD) death, in particular due to CHD, clinicians report.

The study provides the first prospective data on the impact of gout on mortality, they say, and supports aggressive management of CV risk factors in patients with gout.

Hyon Choi (University of British Columbia, Vancouver, Canada) and colleagues prospectively evaluated the association between gout and future risk for death and MI in 51,297 men participating in the Health Professionals Follow-Up study.

Over 12 years of follow-up, the relative risks (RRs) in men with history of gout but no history of CHD compared with those with no history of gout or CHD at baseline were 1.28 for all-cause mortality, 1.38 for CVD deaths, and 1.55 for fatal CHD.

Corresponding RRs among men with history of gout and pre-existing CHD relative to those without history of gout but pre-existing CHD were 1.25, 1.26, and 1.24, the team reports in the journal Circulation.

When the researchers repeated the analysis every 2 years during follow-up using data updated for gout and CHD status, meaning more deaths were assigned to men with a history of gout, CHD, or both categories, the overall findings were similar.

Results were also similar using only incident cases of gout after excluding cases of gout at baseline, they note.

“Of note, the magnitude of the excess risk for CHD deaths (55%) was similar to that for nonfatal myocardial infarction associated with incident cases of confirmed gout (59%),” Choi et al comment.

“These associations were independent of age, body mass index, smoking, family history of MI, use of diuretic and aspirin, dietary risk factors, and risk conditions such as diabetes mellitus, hypercholesterolemia, and hypertension.”

In an accompanying editorial, Michael Alderman welcomed the study, noting that “most present-day clinicians would be surprised that this is the first prospective study linking gout to mortality.”

He said that “despite the absence of women and the narrow professional range of the men studied, there is little reason to quibble with the assertion that the biological impact of gout is probably similar in other groups as well.”

Free abstract

Wednesday, August 22, 2007

Lower Weight From Surgery Shows Benefit


Lower Weight From Surgery Shows Benefit

By WILLIAM M. BULKELEYAugust 23, 2007; Page D6

Two studies and an editorial in today's New England Journal of Medicine support gastric-bypass surgery as a way to significantly improve mortality rates in obese people. But the author of the editorial stopped short of endorsing more surgery because of economic concerns about expanding use of the $25,000 operation.

Gastric-bypass surgery has become an increasingly popular response to the obesity epidemic. The surgery, which shrinks the stomach and sometimes reroutes the intestines, has been widely shown to provide long-term weight loss.

Last year, surgeons performed 177,600 gastric-bypass operations in the U.S., according to the American Society for Metabolic and Bariatric Surgery.

Until now, evidence that the lower weight resulting from the surgery actually saves lives has been scant.

The first of the studies, from Utah, involving gastric-bypass patients and a control group, found the surgery patients' mortality rate improved by 40%. The other study, from Sweden, followed overweight people who had different kinds of weight-loss operations. It found they had 29% improved mortality during the study against comparably overweight people who didn't have surgery.

The Journal's editorialist, George Bray, chief of the division of clinical obesity at Pennington Biomedical Research Center at Louisiana State University, said in an interview that the studies are the equivalent of "the statin trials that showed the drugs reduced death rates and not just cholesterol." Following those studies, cholesterol-fighting statins became a huge business for the pharmaceutical industry.

Dr. Bray said the studies -- which included people who had surgery at relatively low levels of obesity -- make it clear that the National Institutes of Health should reconsider guidelines that suggest the surgery as an option for patients whose body-mass indexes surpass 40. Normal BMIs range up to 25, and people with BMIs above 30 are considered obese. However, Dr. Bray said he isn't willing to come out in favor of a lower standard because, "You'll break the bank."

The Swedish Obese Subjects Study followed 2,010 patients from when they had the operation for as long as 16 years and compared them with a group of comparable subjects based on BMI, gender and other factors. The study found that the surgical patients after 10 years had kept off between 14% and 25% of their original weight, depending on whether they had older surgery types or the more modern gastric bypass.

In the Swedish study, 101 of those who had the surgery died in the study period; of those who didn't have the surgery, 129 died. Deaths from heart disease and cancer were both sharply lower in the group that received surgery.

The Utah study, led by Ted Adams of the University of Utah, compared 7,925 people who had gastric-bypass surgery after 1984 with a similar number of severely obese people culled from driver's license rolls. Those who received surgery had 213 deaths, compared with 321 for the control group. Surgery patients had 56% fewer deaths from cardiovascular events, 60% fewer from cancer and 92% fewer deaths from diabetes. However, people who had the surgery had 15 deaths from suicide compared with five suicides among the control group. The study didn't theorize about reasons for the higher suicide rate.

Write to William M. Bulkeley

Comparative effectiveness of Beta-adrenergic antagonists (atenolol, metoprolol tartrate, carvedilol) on the risk of rehospitalization in adults with h

Comparative effectiveness of Beta-adrenergic antagonists (atenolol, metoprolol tartrate, carvedilol) on the risk of rehospitalization in adults with heart failure

Am J Cardiol. 2007 Aug 15;100(4):690-6. Epub 2007 Jun 26.

Go AS, Yang J, Gurwitz JH, Hsu J, Lane K, Platt R.

Division of Research, Kaiser Permanente of Northern California, Oakland, California; Departments of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco, San Francisco, California.

Placebo-controlled randomized trials have demonstrated the efficacy of selected beta blockers on outcomes in chronic heart failure (HF), but the relative effectiveness of different beta blockers in usual clinical care is poorly understood.

We compared 12-month risk of rehospitalization for HF associated with receipt of different beta blockers in 7,883 adults hospitalized for HF within 2 large health plans between January 1, 2001 and December 31, 2002.

Beta-blocker use was ascertained from electronic pharmacy databases and readmissions within 12 months were identified from hospital discharge databases.

Extended Cox regression was used to examine the association between receipt of different beta blockers and risk of readmission for HF after adjustment for potential confounders.

During follow-up, there were 3,234 person-years of exposure to beta blockers (39.3% atenolol, 42.0% metoprolol tartrate, 12.3% carvedilol, and 6.4% other).

Crude 12-month rates of readmissions for HF were high overall (42.6 per 100 person-years).

After adjustment for potential confounders, cumulative exposure to each beta blocker, and propensity to receive carvedilol compared with atenolol, adjusted risks of readmission were not significantly different for metoprolol tartrate (adjusted hazard ratio 0.95, 95% confidence interval 0.85 to 1.05) or for carvedilol (adjusted hazard ratio 0.92, 95% confidence interval 0.74 to 1.14).

In conclusion, in a contemporary cohort of high-risk patients hospitalized with HF, we found that adjusted risks of rehospitalization for HF within 12 months were not significantly different in patients receiving atenolol, shorter-acting metoprolol tartrate, or carvedilol.

Implantable Cardioverter Defibrillators Studied In Systematic Review

Implantable Cardioverter Defibrillators Studied In Systematic Review

Annals of Internal Medicine

22 Aug 2007

A systematic review finds that implantable cardioverter defibrillators (ICDs) are safe and significantly reduce death for adults with left ventricular systolic dysfunction (Review, p. 251).

In this review of eight randomized controlled trials that reported on mortality and 76 observational studies that examined safety or effectiveness, ICDs reduced death from all causes in patients with left ventricular systolic dysfunction by 20 percent.

This reduction came mostly from a 54 percent relative reduction in sudden cardiac deaths, which are usually caused by dangerous heart rhythms. ICDs are small machines placed under the skin below the collarbone.

They monitor the heart's rhythm and give the heart an electrical shock if a dangerous rhythm occurs. Left ventricular systolic dysfunction -- heart muscle weakened from coronary artery disease or heart attack -- carries a high risk for sudden cardiac death.

Article adapted by Medical News Today from original press release.

Annals of Internal Medicine is published by the American College of Physicians.

Source: Susan Anderson American College of Physicians

Stem cell therapy for the treatment of heart failure.[Miscellaneous]

Patel, Amit N a; Genovese, Jorge A b

(a)University of Pittsburgh Medical Center, USA(b)Cardiac Regeneration Lab, Heart, Lung, and Esophageal Surgery Institute, McGowan Institute of Regenerative Medicine, University of Pittsburgh, USA

Stem cell therapy for the treatment of heart failure.[Miscellaneous]

Current Opinion in Cardiology. 22(5):464-470, September 2007.


Purpose of review: Congestive heart failure is a complex clinical syndrome resulting from myocardial dysfunction that impairs the cardiovascular system's function.

Medical and surgical therapy both still result in a large number of patients with very few options and persistent ventricular dysfunction.

The major process to reverse ventricular remodeling would be the enhancement of regeneration of cardiac myocytes, as well as the stimulation of neovascularization within the affected area of the myocardium.

This can be achieved by introducing progenitor cells that are capable of differentiating into cardiac myocytes, or that promote neovascularization and restore the normal characteristics of myocardium environment.

A number of issues remain as to the type of cells, delivery, timing, and mechanisms involved, however.

Recent findings: There have been a number of clinical trials in patients with heart failure that have been based on animal data related to stem cell therapy. Most have utilized whole bone marrow cells or myoblasts.

The majority of the studies demonstrate an improvement in ventricular function, reduction in scarring, and improvement in symptoms. Some trials have shown no improvement at all.

Summary: This review examines the bench-to-bedside developments of stem cell therapy related to congestive heart failure.

Lessons from hormone replacement therapy trials for primary prevention of cardiovascular disease.[Miscellaneous]

Mohandas, Bhavna; Mehta, Jawahar L

Division of Cardiovascular Medicine, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Lessons from hormone replacement therapy trials for primary prevention of cardiovascular disease.[Miscellaneous]

Current Opinion in Cardiology. 22(5):434-442, September 2007.

Purpose of review: Coronary heart disease in women is a common cause of morbidity and mortality, particularly after menopause. It was thought that estrogen and progesterone protected women from coronary heart disease. The recommendations of the recent Women's Health Initiative, however, are that hormone replacement therapy should not be used for primary prevention of coronary heart disease in women.

Here, we have made a comprehensive review of major studies and comment on the validity of this recommendation.
We have also analyzed the importance of dietary modification in primary prevention. In addition, we have delineated the important predictors of cardiovascular disease in women from prior observational and clinical studies.

Recent findings: Recent major studies, including the Women's Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS), studied the role of hormone replacement therapy in protecting women from coronary heart disease. These studies showed no significant reduction in coronary heart disease events. In addition, the dietary modification component of the Women's Health Initiative did not show any significant reduction in the incidence of coronary heart disease.

Summary: It can be summarized that hormone replacement is not generally recommended in postmenopausal women for primary prevention of coronary heart disease.
Although the dietary modification trials did not show any significant reduction in the incidence of coronary heart disease, it is currently recommended to continue using a heart-healthy diet.

Valvular Aortic Stenosis in the Elderly.[Review]

Aronow, Wilbert S. MD, FACC, FAHAInstitution

From the Cardiology Division, Department of Medicine, New York Medical College, Valhalla, New York.

Valvular Aortic Stenosis in the Elderly.[Review]

Cardiology in Review. 15(5):217-225, September/October 2007.


Elderly patients with valvular aortic stenosis have an increased prevalence of coronary risk factors, of coronary artery disease, and evidence of other atherosclerotic vascular diseases.

Statins may reduce the progression of aortic stenosis (AS).
Angina pectoris, syncope or near syncope, and congestive heart failure are the 3 classic manifestations of severe AS.
Prolonged duration and late peaking of an aortic systolic ejection murmur best differentiate severe AS from mild AS on physical examination.
Doppler echocardiography is used to diagnose the prevalence and severity of AS.
The indications for cardiac catheterization and the medical management of AS are discussed.
Once symptoms develop, aortic valve replacement (AVR) should be performed in patients with severe or moderate AS.
Other indications for AVR are discussed.
Warfarin should be administered indefinitely after AVR in patients with a mechanical aortic valve and in patients with a bioprosthetic aortic valve who have either atrial fibrillation, prior thromboembolism, left ventricular systolic dysfunction, or a hypercoagulable condition.
Patients with a bioprosthetic aortic valve without any of these 4 risk factors should be treated with aspirin 75-100 mg daily.

Hypertension Typically Undiagnosed in Kids

Hypertension Typically Undiagnosed in Kids

Pediatric hypertension may go undiagnosed almost 85% of the time, reports a study in JAMA.

Researchers evaluated data, extracted from electronic medical records, on some 14,000 children and teenagers who had at least three well visits at a large urban health system over a 7-year period.

About 500 children met criteria for hypertension, defined as elevated blood pressure readings during three or more visits. However, true hypertension diagnoses were documented in the EMR for only 16% of these children. Nearly 500 additional children met criteria for prehypertension, of whom 11% were documented as having hypertension or elevated BP.

The authors say that "because normal blood pressure in children is a function of age, sex, and height percentile, clinicians typically cannot remember normal blood pressures for the wide range of children" seen in primary care.

They stress the importance of early diagnosis, noting that "evaluation guidelines and effective treatment" do exist.

JAMA article (Free abstract; full text requires subscription)

Tuesday, August 21, 2007

Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleedingJoseph

Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding

Joseph A. Delaney, MSc, Lucie Opatrny, MD MSc, James M. Brophy, MD PhD and Samy Suissa, PhD

From the Division of Clinical Epidemiology (Delaney, Opatrny, Brophy, Suissa), the Department of Epidemiology, Biostatistics and Occupational Health (Delaney, Brophy, Suissa), and the Division of Internal Medicine (Opatrny), McGill University Health Centre, Montréal, Que.
Correspondence to: Dr. Samy Suissa, Division of Clinical Epidemiology, Ross 4.29, Royal Victoria Hospital, 687 Pine Ave. W, Montréal QC H3A 1A1; fax 514 843-1493;

Background: Anticoagulants and antiplatelet drugs (e.g., warfarin, clopidogrel and acetylsalicylic acid) are key therapeutic agents in the treatment of cardiovascular diseases. However, drug–drug interactions may lead to a greatly increased risk of gastrointestinal bleeding when these drugs are combined. We assessed whether antithrombotic drug combinations increased the risk of such bleeding in a general practice population.

Methods: We conducted a population-based, retrospective case–control study using records in the United Kingdom General Practice Research Database from 2000 through 2005. Cases were identified as patients over 18 years of age with a first-ever diagnosis of gastrointestinal bleeding. They were matched with controls by physician practice, patient age and index date (date of diagnosis of bleeding). All eligible patients had to have at least 3 years of follow-up data in the database. Drug exposure was considered to be any prescription issued in the 90 days before the index date.

Results: There were 4028 cases with a diagnosis of gastrointestinal bleeding and 40 171 matched controls. The prescribing of acetylsalicylic acid with either clopidogrel (adjusted rate ratio [RR] 3.90, 95% confidence interval [CI] 2.78–5.47) or warfarin (adjusted RR 6.48, 95% CI 4.25–9.87) was associated with a greater risk of gastrointestinal bleeding than that observed with each drug alone. The same was true when a nonsteroidal anti-inflammatory drug was combined with either clopidogrel (adjusted RR 2.93, 95% CI 1.74–4.93) or warfarin (RR 4.60, 95% CI 2.77–7.64).

Interpretation: Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of gastrointestinal bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk–benefit profiles.


CMAJ • August 14, 2007; 177 (4).

ECG parameters predict prognosis in CABG patients

Quantitative Measures of Electrocardiographic Left Ventricular Mass, Conduction, and Repolarization, and Long-Term Survival After Coronary Artery Bypass Grafting

Michael S. Lauer, MD; Derlis Martino, MD; Hemant Ishwaran, PhD; Eugene H. Blackstone, MD
From the Department of Cardiovascular Medicine (M.S.L.), the Department of Thoracic and Cardiovascular Surgery (D.M., H.I., E.H.B.), and the Department of Quantitative Health Sciences (H.I., E.H.B.), The Cleveland Clinic Foundation, and the Department of Epidemiology and Biostatistics (M.S.L.), Case Western Reserve University School of Medicine, Cleveland, Ohio.

Correspondence to Dr Michael S. Lauer, Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, 6701 Rockledge Dr, Room 10122, Bethesda, Md 20892. E-mail

Received April 12, 2006; accepted June 8, 2007.

Background— Quantitative ECG measures of left ventricular mass and repolarization predict outcome in population-based cohorts and patients with hypertension. We assessed the prognostic value of preoperative quantitative electrocardiography in patients who underwent isolated coronary artery bypass grafting.

Methods and Results— For 6 years we followed 8166 patients who underwent primary isolated coronary artery bypass grafting between 1990 and 2003, all of whom had routine preoperative ECGs. With use of specialized digital software, quantitative measures were recorded on ventricular rate, P duration, PR interval, QRS duration, QT interval, QRS axis, Sokolow-Lyon and Cornell voltages, and ST-segment depression and slope. There were 1516 deaths. After adjustment for age, gender, clinical characteristics, left ventricular ejection fraction, and other confounders, death was independently predicted by ventricular rate (adjusted hazard ratio [AHR] for 90 versus 60 beats per minute, 1.34; 95% confidence interval [CI], 1.21 to 1.50; P<.0001), PR interval (AHR for 200 versus 150 ms, 1.05; 95% CI, 1.00 to 1.10; P<.0001), QRS duration (AHR for 120 versus 80 ms, 1.24; 95% CI, 1.07 to 1.44; P<.0001), Sokolow-Lyon voltage (AHR for 3.5 versus 1.5 mV, 1.18; 95% CI, 1.05 to 1.31; P<.0001), and ST-segment slope (AHR for –0.1 versus 0 mV, 1.16; 95% CI, 1.02 to 1.31; P<.0001). We derived a quantitative ECG score and demonstrated that, with the exception of age, it was the most powerful predictor of long-term death.

ConclusionsQuantitative ECG measures of left ventricular rate, mass, and repolarization are predictive of mortality among patients who underwent isolated coronary artery bypass grafting. These findings suggest that quantitative electrocardiography may be valuable for risk stratification in patients with severe coronary artery disease.

Circulation 2007; 116: 888-893

Stable isolated angina gives no warning of major events

Stable isolated angina gives no warning of major events

By Caroline Price

21 August 2007

Eur Heart J 2007; 28: 1928-1935

MedWire News: Patients with stable isolated angina have an excellent prognosis in terms of major cardiovascular (CV) events, investigators report.

But they note that since most deaths and CV events that occur in this group are not preceded by clear warning symptoms such as chest pain requiring hospitalization, measures to prevent such events should be targeted to all patients with isolated angina.

Philip Poole-Wilson (Imperial College London, UK) and colleagues looked at the clinical history and outcome of patients with isolated angina using data from ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS), which compared long-acting nifedipine with placebo in a wide range of stable, symptomatic angina patients.

“Contemporary data that specifically documents the clinical course of patients with isolated angina is lacking,” they observe.

Of 7665 patients included in the trial, 2170 (28%) had isolated angina, defined as stable angina due to coronary heart disease (CHD) without a history of CV events or revascularization.
During a mean follow-up of 4.9 years, 147 (1.4 per 100 patient-years) of this isolated angina group died, while 761 (8.7 per 100 patient-years) died or had a cardiac event or procedure.
This mortality rate in angina patients was similar to that of patients with a history of coronary revascularization, whereas the rate of cardiac events and procedures was lower, the authors note. Meanwhile, mortality as well as event and procedure rates for isolated angina patients were lower than those for the subgroup of patients with history of myocardial infarction, heart failure, or stroke.

The first event among isolated angina patients was death in 82 patients, myocardial infarction or heart failure in 112, coronary revascularization in 171, and chest pain requiring hospitalization in 396.

But just 68 (30%) of 262 deaths or major cardiac events were preceded by chest pain requiring hospitalization or revascularization.

Coronary angiography (CAG) was performed at least once in 612 (28%) isolated angina patients during follow up. In comparison with rates up to CAG or the end of follow-up, both death and CV event rates were higher after CAG.

“Patients with stable isolated angina have low rates of death and major cardiac events, but relatively high rates of chest pain requiring hospitalization despite contemporary management,” the authors conclude in the European Heart Journal.

“Since the main clinical implication is that the majority of deaths and major CV events are not preceded by clear warning symptoms, the main clinical implication is that measures to prevent such events must target all patients.”

Free abstract

Monday, August 20, 2007

Cardiac Resynchronization Therapy (CRT) in heart failure (HF)

UK NICE guidance for CRT published

By Caroline Price
20 August 2007

Heart 2007; 93: 1134-1135

MedWire News: A summary of the UK National Institute for Health and Clinical Excellence (NICE) guidance on the use of cardiac resynchronization therapy (CRT) in heart failure (HF) has been published by the journal Heart.

The “technology appraisal guidance” provides additional treatment options for some patient subgroups covered in the earlier NICE guidance on implantable cardioverter defibrillators (ICDs).

It recommends CRT with a pacing device (CRT-P) for HF patients who have New York Heart Association (NYHA) Class III or IV symptoms despite optimal medical therapy, are in sinus rhythm, have a left ventricular ejection fraction (LVEF) of 35% or less, and have ventricular dyssynchrony.

Ventricular dyssnchrony is indicated by either QRS duration of 150 ms or longer as estimated by standard electrocardiogram (ECG) or QRS duration 120-149 ms as estimated by ECG and mechanical dyssynchrony confirmed by echocardiography.

CRT with a defibrillator (CRT-D) may be considered for patients meeting the above criteria who separately also fulfill criteria for use of an ICD as previously recommended.

The guidance was based on evidence from four randomized controlled trials, with particular attention placed on the largest of these, the COMPANION and CARE-HF trials. Pooled analysis of these studies demonstrated a significant reduction in death from HF for CRT-P compared with optimal medical treatment alone.

These studies also indicated that CRT-P significantly reduced the risk for worsening HF, improved NYHA Class and quality of life, and reduced admissions to hospital for HF, explain David Barnett and colleagues from the University of Leicester.

Similar results were reported for CRT-D, they say. Noting that only COMPANION provided the basis for a direct comparison of CRT-P and CRT-D, and that this was not powered to detect differences, they point out that only CRT-D produced a significant reduction in death from all cardiac causes and sudden cardiac death in this trial.

The team reports that the cost of both CRT-P and CRT-D, at a cost per quality-adjusted life year (QALY) of £16,000 (US$31,700) and £23,000 ($45,600), respectively, is considered to be a cost-effective use of resources in comparison with medical therapy alone.

Using all available evidence in the absence of a head-to-head trial comparison, the NICE guidance committee found that implanting a CRT-D rather than CRT-P would have a cost per QALY of £40,000 ($79,300), and would not normally be deemed cost-effective.

But Barnett et al explain that “the committee accepted that the cost effectiveness of CRT-D is likely to be considerably improved in people with additional risk factors for sudden cardiac death over and above those associated with cardiac dyssynchrony.”

In an accompanying editorial, Christophe Leclercq, from Hôpital Pontchaillou in Rennes, France, commented that the inclusion of echocardiographic criteria “seems logical but is not yet clearly supported by the results of clinical trials.”

He wrote: “Echocardiography is an attractive tool for selecting and, especially, for optimizing the selection of patients as candidates for CRT, but it has also to be validated.”

Free abstract