Saturday, June 30, 2007

Systemic inflammation may underlie poor lung function link with CVD

Systemic inflammation may underlie poor lung function link with CVD

Thorax 2007; Advance online publication

MedWire News:

The link between poor lung function and cardiovascular disease (CVD) may be mediated by an inflammatory mechanism, says an international team of researchers.

The team identified an association between lung volumes and serum C-reactive protein (CRP) levels in young adults, which was of similar strength in men and women and was independent of smoking, asthma, and body mass index.

"Impaired lung function not only leads to increased respiratory mortality, but is also associated with adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death," write Robert Hancox (University of Otago, Dunedin, New Zealand) and colleagues.

Furthermore, some studies have shown a reduction in the lung function measure forced expiratory volume in 1 second (FEV1) is a stronger indicator of cardiovascular risk than are traditional measures such as cholesterol levels, they add.

To investigate the extent to which this link is mediated by smoking, chronic airway disease, and/or established atherosclerosis, the researchers studied associations between spirometric lung function measures and serum CRP levels in a population-based birth cohort of around 1000 New Zealanders at ages 26 and 32 years.

The mean FEV1 was significantly lower at age 32 years than age 26 years (p=0.0003), and the fall in FEV1 between the two ages was greater for men (0.22 liters) than for women (0.05 liters; p<0.0001).

Analysis of CRP levels categorized as low, medium, and high according to American Heart Association guidelines showed that increasing CRP was associated with decreasing percentage of predicted FEV1 at both ages in women and at 32 years in men (p<0.01).

Further analysis showed that FEV1 values were inversely associated with log-CRP levels at both age 26 and 32 years after adjusting for gender, height, body mass index, smoking, and asthma (both p<0.001).

Associations between lung function and CRP were not significantly different between women and men or between Maori and non-Maori individuals, the team notes.

Finally, the decrease in FEV1 between age 26 and 32 years was a significant predictor of log-CRP at age 32 years, and this longitudinal association was of similar magnitude in men and women.

The authors conclude in the journal Thorax: "While the underlying reason for this association is uncertain, the findings suggest a plausible mechanism by which a reduced FEV1 is associated with an increased risk of CVD in a manner that is independent of smoking and known respiratory disease."

Symptomless Hypertension Too Often Ignored

Symptomless Hypertension Too Often Ignored

High blood pressure, the "silent killer," too often gets overlooked by people who have conditions that cause them pain or severe distress, a new study finds.

A survey of more than 51,000 people enrolled in a Pennsylvania state prescription drug program found that people with either physical or psychological problems were markedly less likely to take the pills needed to control their blood pressure, according to a report in the June 28 issue of Hypertension. "It's not so surprising," said study author Dr. Philip Wang. "But what was notable was the consistency with which the presence of other conditions decreased use of antihypertensives [drugs for high blood pressure].

" A wide array of conditions affected use of those drugs, said Wang, an assistant professor of psychiatry, medicine and health-care policy at Harvard Medical School. For example, someone with both high blood pressure and asthma or another chronic lung disease was 57 percent less likely to take blood pressure medication than someone without such a condition. Use of blood pressure medication was 50 percent lower in people with depression, 41 percent lower for people with gastrointestinal complaints, and 37 percent less likely for people with osteoarthritis. The blame lies with both patients and doctors, Wang said.

"A patient with several conditions might deal with those that cause discomfort, even though hypertension is probably as important an issue," he said. "And patients may have financial barriers to taking multiple medications. Or maybe they just run out of time." Doctors know that high blood pressure is a major risk factor for heart attack and stroke, Wang said, so they also play a role in its neglect, though "probably not intentionally.

" He pointed out that doctors usually have a limited amount of time to spend with individual patients "and if you have to deal with multiple conditions in 15 minutes, hypertension might get short shrift."

The study illustrates "the complexity of the illnesses that older people have these days, and the challenge of dealing with them," said Dr. Daniel W. Jones, dean of the University of Mississippi School of Medicine and a spokesman for the American Heart Association. The complexity of the American health-care system also plays a role, Jones said. "It's hard to tell what part cost plays in it," he added.

The overall lesson "for patients and their physicians is that blood pressure medications are effective at improving the length and quality of life," Jones said. "Physicians should take care that the problem doesn't fall between the cracks."

A report in the June 28 issue of Circulation highlighted the importance for older people of another silent risk factor -- C-reactive protein. A study of nearly 4,000 people aged 65 and older found that a high blood level of C-reactive protein is an independent risk factor for heart disease, comparable to high cholesterol levels, the report said. People with the highest levels of C-reactive protein had a 45 percent increase in the risk of developing heart disease over the 10-year course of the study.

"There have been other studies with a shorter-term follow-up, three or four years," said study co-author Dr. Bruce M. Psaty, a professor of pathology and biochemistry at the University of Vermont. "This is the first long-term prospective study in the elderly."

C-reactive protein was almost unknown a decade ago, but a blood test now "is widely available, and is becoming more so over time," Psaty said. There are several ways to lower levels of the protein, including the use of cholesterol-busting statin drugs, he said. And since "one of the biggest things associated with C-reactive protein is obesity, one of the best ways to control it is to lose weight," Psaty added.

Friday, June 29, 2007

ADOPT analysis shows rosiglitazone increases risk of fracture in women

ADOPT analysis shows rosiglitazone increases risk of fracture in women

June 29, 2007

Chicago, IL - Not unlike a prizefighter battered and bruised, rosiglitazone (Avandia, GlaxoSmithKline) continued to take it on the chin this week, with a new analysis from A Diabetes Outcome Progression Trial (ADOPT) expanding upon the risks of the thiazolidinedione (TZD) and showing an increase in the risk of fracture in women taking the controversial medication.

"In ADOPT, the increased risk of bone fractures in women with type 2 diabetes was accentuated with rosiglitazone," said lead investigator Dr Steven Kahn (University of Washington, Seattle) during a late-breaking clinical-trials session here at the American Diabetes Association 2007 Scientific Sessions this week. "It appears to increase fractures principally in the upper and lower limbs, and there was no observed increase in spinal fractures with rosiglitazone."

Kahn, however, pointed out that this adverse effect of rosiglitazone is also observed with pioglitazone (Actos, Takeda Pharmaceuticals). Based on these data, the ADOPT investigators say that "special attention should be paid to bone health in women with type 2 diabetes who are receiving thiazolidinediones."

A bad month altogether for rosiglitazone

Previously reported by heartwire, ADOPT was a multicenter, randomized, double-blind clinical trial involving 4360 patients who had not received pharmacologic treatment for recently diagnosed type 2 diabetes. Patients were treated with rosiglitazone, metformin, or glyburide, and investigators showed that initial treatment with rosiglitazone slowed the progression to monotherapy failure more effectively than either metformin or glyburide. Investigators concluded that there was a clinically meaningful difference between rosiglitazone and glyburide, but the difference between rosiglitazone and metformin, based on glucose control, was less significant.

As noted during the trial, however, the side-effect profile differed significantly among the agents, with the risk of congestive heart failure associated with rosiglitazone similar to metformin, a risk that was higher in both drugs compared with glyburide. In addition, investigators also observed an increased risk of fracture in female rosiglitazone-treated patients, and the purpose of this analysis, compiled from adverse- and serious-adverse-events data during follow-up, was to further analyze and quantify that risk.

In terms of the overall fracture risk in men, there was no significant difference when investigators compared those treated with rosiglitazone with those treated with metformin, nor was there a difference in fracture risk in a comparison between rosiglitazone and glyburide. In women, however, there was 81% increase in the incidence of fracture among those treated with rosiglitazone compared with those treated with metformin. The risk of fracture was even higher in a comparison between the rosiglitazone- and glyburide-treated female patients. This increased risk of fracture appears to start after about one year of treatment with the TZD, said Kahn.

In looking to determine when women at increased risk could be identified, Kahn said there were more postmenopausal women included in the study, and those taking metformin and glyburide had less fracture risk than those taking rosiglitazone. Regarding premenopausal women, there was significantly less fracture in the glyburide-treated patients, but only a trend toward less fracture in the metformin-treated patients. Overall, more fractures were observed in the lower and upper limbs, including the hand, humerus, and foot, but no difference in fracture rates in the spine and hip. The baseline characteristics, including medication use, were similar in the three study arms, and there was no observed difference in fracture risk among ADOPT women taking estrogen or calcium supplements. There was a greater risk of fracture among women taking a bisphosphonate, investigators found.

Not to leave pioglitazone out of the mix, Kahn also analyzed existing pioglitazone data involving more than 8000 patients treated with the TZD and compared the risk of fracture with approximately 7400 patients taking a comparator drug. Treated, on average, for 3.5 years, there was no increased fracture risk in men, but a similar risk to rosiglitazone was observed in women treated with pioglitazone.

"It would appear that this is a class effect," said Kahn. At this time, however, no clear recommendations can be made, he said, except for clinicians to continue to monitor their patients. He noted that type 2 diabetes alone increases the risk of fracture, and this risk increases with the duration of disease.

Kahn S, on behalf of the ADOPT investigators. Increased incidence of fractures in women who received rosiglitazone in ADOPT. American Diabetes Association 2007 Scientific Sessions; June 26, 2007; Chicago, IL.

Related links:

A house divided: No clear answers on rosiglitazone safety or political backstory [HeartWire > Cardiometabolic risk; Jun 07, 2007]
The rosiglitazone aftermath: Legitimate concerns or hype? [HeartWire > Cardiometabolic risk; May 24, 2007]
Rosiglitazone increases MI and CV death in meta-analysis [HeartWire > Cardiometabolic risk; May 21, 2007]
Pioglitazone beneficial in diabetes patients with previous MI? [HeartWire > Acute coronary syndromes; Apr 20, 2007]
ADOPT: Rosiglitazone delays treatment failure in patients with type 2 diabetes [HeartWire > Cardiometabolic risk; Dec 04, 2006]
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Cardiomyopathy: An Overview

Cardiomyopathy: An Overview

Cell Therapy in MI

Cardiologists express cautious optimism for cell therapy in MI

29 June 2007

Lancet 2007; 369: 2142-2143

MedWire News: Continued research will hopefully lead to stem cell transfer therapies that can improve outcomes for myocardial infarction (MI) patients, conclude experts in a Lancet comment article.

But Harald Arnesen (Ullevål University Hospital, Oslo, Norway) and co-authors challenge the proposal that studies should now be conducted in large populations based on methods used in the recent REPAIR-AMI study.

The researchers reviewed studies published to date of autologous bone marrow cell (BMC) transfer in patients with acute MI. They say results of a 2002 trial and other small uncontrolled trials using the same method "were encouraging," but that three randomized trials were negative for the primary endpoint of improvement in left ventricular ejection fraction (LVEF).
The larger REPAIR-AMI (Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute MI) study included 204 patients with acute MI who received either an intracoronary infusion of BMC or placebo into the infarct artery after successful revascularization by percutaneous coronary intervention.

Patients who received BMC experienced a "modest" improvement in LV function compared with the placebo group at 4 months, at a mean greater increase in LVEF of 2.5%, and a surprisingly significant reduction in events at 12 months, Arnesen and colleagues write.

But the authors say they are concerned at the REPAIR-AMI investigators' conclusion that large-scale trials based on the methods used are now warranted. They believe the benefits in LV function were based on suboptimal measurements of LVEF and volumes, and that the positive clinical effect seems to be driven by the poor outcome in the placebo group.

They suggest that the apparently worse outcomes in the REPAIR-AMI placebo group compared with control groups in other trials could be due to harmful effects of the cell culture medium used for the placebo infusion.

Although the same medium was used for the BMC infusion, they write, "a metabolizing process had been operating during the incubation period which could have attenuated the possible deleterious effects to the injured coronary vessel wall."

The authors conclude: "While results of ongoing adequately powered clinical trials with satisfactory methods for endpoint assessment are awaited, research should also move 'from bed to bench' and focus on unsolved problems, such as the selection of optimum cell type, dosing, timing, and mode of delivery, which will hopefully bring cell therapies close to clinical application."


Thursday, June 28, 2007

Adopting healthy lifestyle in middle age gives ‘prompt’ CV benefits

Cardiovascular News

Adopting healthy lifestyle in middle age gives ‘prompt’ CV benefits

28 June 2007MedWire


Adopting a healthier lifestyle in middle-age is not too late to gain cardiovascular (CV) benefits, US researchers say.

Their study, published advance online by the American Journal of Medicine, showed that adopting four modest healthy habits in middle-age lowered the risk of CV disease (CVD) and mortality by 35% and 40%, respectively, after just 4 years.

Dana King (Medical University of South Carolina, Charleston) and colleagues studied 15,708 participants in the Atherosclerosis Risk in Communities study, aged 45-64 years.

The researchers evaluated each individual’s participation in an overall healthy lifestyle, characterized by having all four of the lifestyle habits: eating at least five fruits and vegetables daily; exercising (at least walking) a minimum of 2.5 hours per week; maintaining a body mass index (BMI) between 18.5 and 30 kg/m2; and not smoking.

At the start of the study, 1344 (8.5%) participants engaged in all four healthy lifestyle factors. Three-yearly follow-up visits revealed that 970 (8.4%) of the remainder had newly adopted a healthy lifestyle 6 years on.

Over the next 4 years, these individuals who had switched to the healthy lifestyle were less likely to have experienced a subsequent CVD event (11.7% vs 16.5%, p<0.001) p="0.009)">

After adjusting for demographics, socioeconomic status, and disease history, people who adopted a healthy lifestyle had an odds ratio (OR) of 0.60 for all-cause mortality and an OR of 0.65 for CVD events over the next 4 years, relative to those who did not.

People with fewer than two healthy habits at the beginning of the study who then adopted one more healthy habit had a reduction in mortality (OR=0.75) but not CVD (OR=0.88).

Men, African Americans, people with lower socioeconomic status, and those with a history of hypertension or diabetes were less likely to change to a healthy lifestyle.

“The potential public health benefit from adopting a healthier lifestyle in middle-age is substantial,” the authors write.

“The findings emphasize that making the necessary changes to adhere to a healthy lifestyle is extremely worthwhile, and that middle-age is not too late to act.”

LINK: Am J Med 2007; Advance online publication

Guidelines Updated for Treatment of Pulmonary Arterial Hypertension

Guidelines Updated for Treatment of Pulmonary Arterial Hypertension

June 19, 2007 — The American College of Chest Physicians provides an update of the evidence-based treatment recommendations for patients with pulmonary arterial hypertension. The new guidelines are published in the June issue of Chest.

"Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure (PAPm) ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation," write David B. Badesch, MD, FCCP, from the University of Colorado Health Sciences Center in Denver, and colleagues. "Irrespective of its etiology, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function."

Since a consensus panel convened by the American College of Chest Physicians developed guidelines for PAH treatment that were published in 2004, several important clinical trials have been published and new treatments have received regulatory approval. Add-on and combination therapy are being explored as potential new therapeutic options.

These updated guidelines, taking into consideration studies published before September 1, 2006, provide a summary of the original guidelines, a discussion of new studies, and a revised treatment algorithm taking into account recent developments in therapy.

"Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended," the authors write. "The pace of developments in the treatment for PAH has quickened, with several important clinical trials having been published over the past 2 years that have led to regulatory approval of newer drugs and experience with combinations of existing drugs. These advances are likely to impact on the way physicians should now approach the treatment of PAH."

The treatment algorithm provided summarizes the current approach to therapy for PAH, based on functional class. However, the authors note that functional class is difficult to quantify, may vary among patients and care providers, and may not always correlate with other indexes of disease severity, although it does correlate with outcome (in patients with IPAH [idiopathic PAH]).

When making decisions regarding treatment, one should therefore consider not only functional class but also cardiopulmonary hemodynamics, 6-minute walk distance, signs and symptoms of right-sided heart failure, adverse effect profile, and drug-drug interactions, as well as cost.

Functional class II: The only treatments currently approved for patients with PAH in functional class II are sildenafil and subcutaneous and intravenous treprostinil. Because of the ease of administration and relative efficacy, sildenafil may be the first choice for most of these patients. Clinical trials with sitaxsentan and ambrisentan have included patients with PAH in functional class II, and a trial with bosentan is ongoing. Patients should be encouraged to enroll in clinical trials.

Functional class III: For the treatment of patients with PAH in functional class III, there are now 5 drugs approved by the US Food and Drug Administration, in 3 therapeutic classes, allowing rational therapeutic decisions based on available evidence, knowledge of an individual patient's specific situation, clinical judgment, and patient preferences.
For patients with "early" PAH in functional class III, most experts now consider 1 of the 2 approved oral therapies (bosentan or sildenafil, listed in no specific order). When choosing between these agents, one should take into account relative toxicities (eg, patients with hepatic abnormalities may do better with sildenafil, whereas patients with ocular disease or recurrent epistaxis may do better with bosentan). Sildenafil is generally less expensive.

Patients with more advanced class III disease may need a prostanoid, such as intravenous epoprostenol or treprostinil, inhaled iloprost, or subcutaneous treprostinil. While awaiting additional evidence regarding the use of add-on and combination therapy, one might consider these in the context of enrollment into clinical trials.

Functional class IV: All currently labeled therapies are approved for patients with PAH in functional class IV. However, based on the quality of the evidence and the net risk-benefit profile, the guidelines strongly recommend intravenous epoprostenol as the treatment of choice. Most experts are familiar with how to titrate intravenous epoprostenol in the acute setting, and it has a rapid and predictable onset of action.

As experience with intravenous treprostinil is accumulating, this may be a suitable alternative to intravenous epoprostenol in some cases. Except for patients who refuse intravenous therapy or who are not capable of managing the complex delivery system, oral, subcutaneous, and inhaled agents should generally not be used as first-line therapy for patients with PAH in functional class IV.

"Recommendations regarding therapy obviously need to be applied in light of the individual patient's specific situation," the authors conclude. "The importance of a thorough diagnostic evaluation, looking for underlying causes and contributing factors, cannot be overemphasized. Educational efforts have contributed to improved recognition of PAH, facilitating earlier initiation of therapy [which] should contribute to better clinical outcomes."

Some of the authors have disclosed various financial relationships with pharmaceutical companies and organizations, including the National Institutes of Health, GlaxoSmithKline, United Therapeutics/LungRx, and Actelion. A complete listing of financial relationships is available in the original article.

Chest. 2007;131:1917-1928.

Clinical Context

PAH is defined by a mean pulmonary artery pressure of at least 25 mm Hg along with a pulmonary capillary wedge pressure of 15 mm Hg or less. PAH may be an intrinsic process within the pulmonary vasculature, or it may be secondary to other disease states such as connective tissue disease or congenital heart conditions.

The American College of Chest Physicians last published guidelines for the management of PAH in 2004. Since then, new research has mandated a rethinking of treatment of PAH. The current clinical practice guidelines highlight this research.

Study Highlights
An expert panel reviewed pertinent literature published prior to September 1, 2006, to shape the current guidelines. Only studies published in English were included, and the authors focused on trials of prostanoids, endothelin receptor antagonists, and phosphodiesterase inhibitors. The etiology of PAH was not considered in the decision whether to include a study in the literature review.
Patients with PAH and a favorable response to short-term vasodilator testing during cardiac catheterization, defined as a decrease in mean pulmonary artery pressure of at least 10 mm Hg to a level of 40 mm Hg or below, may be amenable to therapy with calcium channel blockers.

The authors recommend long-acting nifedipine or diltiazem along with amlodipine for this small subgroup of patients, but verapamil should be avoided. If the patient does not improve to functional class I or II following 3 months of treatment with calcium channel blockers, other therapy should be considered.

Treprostinil and sildenafil are indicated for the treatment of patients with PAH in functional class II. Because sildenafil is delivered orally and treprostinil via either the subcutaneous or intravenous route, sildenafil might be preferred by most patients. Trials of sitaxsentan, ambrisentan, and bosentan for patients with PAH in functional class II are underway.

Sildenafil or bosentan may be considered for patients with PAH in functional class III whose symptoms are not too severe. The authors recommend consideration of the toxicities of these agents in choosing treatment. Patients with headache, epistaxis, and ocular disease should avoid therapy with sildenafil if possible. Also, patients with liver disease should preferably not receive bosentan. Sildenafil is somewhat more affordable than bosentan.

Patients with more advanced PAH in functional class III should receive epoprostenol, treprostinil, or iloprost. There is little evidence regarding the benefits for combination therapy with different treatments if monotherapy is insufficient, and this management strategy may be considered in the context of enrollment into clinical trials.

The authors strongly recommend intravenous epoprostenol for the treatment of patients with PAH in functional class IV. Intravenous epoprostenol has a rapid and predictable onset of action, and many clinicians have good experiences with this medication. Evidence of the efficacy of intravenous treprostinil is increasing, and this medication may be considered as an alternative to epoprostenol. The use of oral, subcutaneous, or inhaled agents among patients with PAH in functional class IV is discouraged.

Pearls for Practice

Treprostinil and sildenafil are indicated for the treatment for patients with PAH in functional class II, and sildenafil may be the preferred agent because of ease of administration and cost.

Intravenous epoprostenol as the first-line treatment for patients with PAH in functional class IV is strongly recommended.

Tuesday, June 26, 2007

Using Framingham for primary prevention cardiovascular risk assessment | Therapeutics Initiative

Using Framingham for primary prevention cardiovascular risk assessment Therapeutics Initiative

STEMI and NSTEMI have similar prognoses

STEMI and NSTEMI have similar prognoses

25 June 2007

Patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) have similar prognoses, and similar correlates of adverse outcomes, report French researchers.

However, NSTEMI patients are less likely than STEMI patients to undergo reperfusion and to receive secondary prevention, say Gilles Montalescot (Pitié-Salpétrière University Hospital, Paris) and colleagues.

A European Society of Cardiology/American College of Cardiology(ESC/ACC) committee recently redefined MI to include any amount of necrosis resulting from ischemia, Montalescot et al explain in the European Heart Journal.

This means that patients who would previously have been diagnosed with unstable angina are now diagnosed with MI. Yet most registries analyze data for NSTEMI patients along with that for unstable angina patients and separately from STEMI patient data, the team notes.

As part of the OPERA study, the researchers described all acute MI patients’ in-hospital and long-term management and outcomes, taking the new definition into account.

A total of 2176 patients were diagnosed with MI at 56 centers in France. The majority (70.8%) were diagnosed with STEMI, and the remainder with NSTEMI. The median time between symptom onset and arrival at hospital was 6 hours and was shorter in patients with STEMI versus NSTEMI patients, at 4 versus 7 hours (p<0.0001).

STEMI patients were more likely to receive fibrinolysis (28.9% vs 0.7%, p<0.0001) and to undergo percutaneous coronary intervention (71.0% vs 51.6%, p<0.0001). Conversely, bypass surgery was performed more frequently in NSTEMI patients than STEMI patients(4.9% vs 3.1%, p<0.05).

STEMI patients were more likely than NSTEMI patients to receive aggressive secondary prevention therapies at discharge, which was not due to greater disease severity.

In-hospital mortality did not differ between STEMI and NSTEMI patients, at 4.6% versus 4.3%. Using follow-up data available for 1878 patients, the cumulative death rate at 1 year was 11.6% in patients with NSTEMI and 9.0% in those with STEMI. Again, the between-group difference was not significant.

Independent correlates of in-hospital mortality were untreated dyslipidemia, advanced age, diabetes, and low blood pressure, while the strongest predictors of 1-year mortality were heart failure and age.

The authors say their findings support the new ESC/ACC definition of MI, adding that “the common definition and similar prognosis of patients with STEMI or NSTEMI should lead to more similar secondary prevention therapies to avoid recurrent ischemic events.”

Christopher Bode and Andreas Zirlik (Medizinische Universitaetslinik, Freiburg, Germany) agreed with the team’s conclusions in an accompanying editorial.

They added that more aggressive in-hospital and secondary prevention strategies, particularly for the NSTEMI population, need to be confirmed in large, randomized, clinical outcome studies.
“Until proven otherwise, STEMI and NSTEMI are no identical twins, but equally dangerous,”

LINK: Eur Heart J 2007; 28: 1409-1417

CHF patients with type-D personality

CHF patients with type-D personality fail to consult for cardiac symptoms

25 June 2007

Patients with chronic heart failure (CHF) and a type-D personality fail to seek medical assistance for increased cardiac symptoms, which may explain the poor prognosis in this group of patients, researchers report.

The authors suggest that patients with CHF and type-D personality may be in need of “more intensive interventions, such as more education, to improve self-management abilities.”

Self-management and adequate consultation behavior are essential for the successful treatment of CHF. But patients with a type-D personality, characterized by high social inhibition and negative affectivity, may delay medical consultation, the team says.

Angélique Schiffer (Tilburg University, The Netherlands) and colleagues enrolled 178 outpatients with CHF, aged 80 years or less, to investigate whether type-D personality predicts poor self-management.

All the participants completed the type-D Personality Scale at baseline, and the Health Complaints Scale and the European Heart Failure Self-care Behavior Scale at 2 months of follow-up.

At follow-up, patients with a type-D personality experienced more cardiac symptoms (odds ratio [OR]=6.4, p<0.001) color="#990000">evaluated their symptoms as worrisome (OR=2.9, p<0.01), compared with patients with other types of personality.

Patients with a type-D personality also had more cardiopulmonary symptoms (p=0.002), fatigue (p<0.001), sleep problems (p<0.001), and worries about health (p=0.001) than patients without a type-D personality.

Nevertheless, patients with type-D personality were less likely to seek medical help than patients without type-D personality, the team notes.

Of the 61 patients who failed to consult for evident cardiac symptoms, 43% had a type-D personality. Of the remaining 108 patients, only 14% had a type-D personality.
After adjusting for demographics, CHF severity/etiology, time since diagnosis, and medication, type-D personality was an independent predictor for reduced consultation (OR=2.7, p<0.05).

Schiffer and co-workers conclude in the journal Heart: “Patients with CHF with a type-D personality display inadequate self-management.”

Link: Heart 2007; 93: 814-818

Friday, June 22, 2007

Lowering Blood Pressure Improves Diastolic Function, Regardless of Regimen

Lowering Blood Pressure Improves Diastolic Function, Regardless of Regimen

Reductions in blood pressure lead to improved diastolic function — regardless of the antihypertensive drugs used reports a study in Lancet.

Researchers sought to determine whether the angiotensin-receptor blocker valsartan would be more effective than other antihypertensives at improving diastolic function. They randomized nearly 400 patients with hypertension and evidence of diastolic dysfunction to receive either the ARB or placebo. The patients also received other classes of antihypertensive agents to lower blood pressure to below 135/80 mm Hg.

After 38 weeks, tissue Doppler imaging showed improved diastolic function in both valsartan and placebo recipients, but there was no significant difference between the groups.

Authors of an accompanying commentary note that valsartan might have an advantage in patients with more advanced left ventricular remodeling. Nevertheless, they add, "the good news is that lowering blood pressure improves diastolic function, irrespective of the antihypertensive regimen used."

Lancet article (Free abstract with one-time registration; full text requires subscription)

Lancet comment (Subscription required)


The Lancet 2007; 369:2079-2087


Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial
Dr Scott D SolomonMD, et al



Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents.


Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat.


186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12·8 (SD 17·2)/7·1 (9·9) mm Hg reduction in blood pressure in the valsartan group and a 9·7 (17·0)/5·5 (10·2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0·60 (SD 1·4) cm/s from baseline in the valsartan group (p<0·0001) and 0·44 (1·4) cm/s from baseline in the placebo group (p<0·0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0·29).


Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.

Estrogen therapy decreases coronary artery calcification

Estrogen therapy decreases coronary artery calcification

N Engl J Med 2007; 356: 2591-2602

MedWire News: Postmenopausal women receiving estrogen therapy have a lower build up of calcium plaque in their coronary arteries than women who do not take hormone replacement therapy (HRT), study findings show.

Calcified plaque in the coronary arteries is a marker for atheromatous plaque burden, and is predictive of future risk of cardiovascular events.

Results from the Women's Health Initiative (WHI) randomized trial of conjugated equine estrogens indicated a reduced need for coronary revascularization among women aged 50-59 years, but not older women, who were receiving estrogen compared with those on the placebo group.

JoAnn Manson (Harvard Medical School, Boston, Massachusetts, USA) and colleagues carried out a substudy shortly after the WHI trial ended to determine whether the coronary artery calcium burden differed according to group assignment among 1064 women, aged 50-59 years, after a mean of 7.4 years of treatment.

After trial completion, women receiving estrogen had lower mean coronary artery calcium scores than those receiving placebo, at 83.1 versus 123.1 (p=0.02).

Michael Mendelsohn and Richard Karas, from Tufts University School of Medicine, Boston, wrote in a related editorial that these findings support the "potentially beneficial cardiovascular effects of HRT in younger menopausal women receiving the therapy for symptoms."

They added, however, that "it remains important to continue to emphasize that HRT should not be considered as a strategy to prevent cardiovascular disease in women; there are proven therapies for cardiovascular disease that remain underused in women."

"Clear and striking" cardioprotective effect of estrogen in young women requires confirmation"


Estrogen Therapy and Coronary-Artery Calcification

JoAnn E. Manson, M.D., Dr.P.H., Matthew A. Allison, M.D., M.P.H., Jacques E. Rossouw, M.D., J. Jeffrey Carr, M.D., Robert D. Langer, M.D., M.P.H., Judith Hsia, M.D., Lewis H. Kuller, M.D., Dr.P.H., Barbara B. Cochrane, Ph.D., Julie R. Hunt, Ph.D., Shari E. Ludlam, M.P.H., Mary B. Pettinger, M.S., Margery Gass, M.D., Karen L. Margolis, M.D., M.P.H., Lauren Nathan, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Marcia L. Stefanick, Ph.D., for the WHI and WHI-CACS Investigators

Background Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.

Methods In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.

Results The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.

Conclusions Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.

Drugs To Prevent Heart Complications During Surgery

Questions Over Drugs To Prevent Heart Complications During Surgery

The use of drugs to prevent heart complications during surgery is called into question in this week's BMJ.

Globally, about 100 million adults have non-cardiac surgery (ie. on any part of the body other than the heart) each year. Around 1% are at risk of cardiac complications, such as heart attacks and strokes, and about one in four will die each year.

Two types of drugs - Beta blockers and statins - are regularly given to patients to prevent such complications. They are given shortly before, during, or after surgery (the perioperative stage) to help lower blood pressure

But doctors in Australia now warn that the benefit of using these drugs at this time remains unclear.

They cite several large international studies that found no benefit from perioperative Beta blockers.

Two studies from Denmark and the UK reported no reduction in death or several other serious complications, such as heart attack, heart failure, and stroke 30 days after surgery in patients receiving Beta blockers. Another study found no benefit six months after surgery, and a trial currently underway has so far not reported any beneficial effects.

However, all studies did report significantly higher rates of important side effects with Beta blockers, including slow heart beat (bradycardia) and very low blood pressure (hypotension).

This has led to calls to examine the widespread use of perioperative Beta blocking drugs.

Like Beta blockers, statins have also been advocated to reduce the risk of perioperative cardiac complications, write the authors. Non-randomised trials suggest that statins confer benefit, but the evidence remains weak, and to prove a strong overall survival benefit would require a 'gold-standard' randomised controlled trial of more than 12,000 patients.

The benefits of statins in reducing cardiac complications in the general population and high risk patients are well known, but robust evidence to confirm that these drugs are valuable in routine perioperative use has not been published, they say.

So, on the basis of the evidence currently available, what should practising clinicians do?

They suggest that patients already receiving Beta blockers or statins before surgery should continue with treatment. But no patient should start taking statins or Beta blockers in the perioperative period specifically to reduce the likelihood of perioperative cardiac events.

Editorial: Beta blockers and statins in non-cardiac surgeryBMJ Volume 334 pp 1283-4

Article URL:

Wednesday, June 20, 2007

Risk of Cardiovascular and All-Cause Mortality in Individuals With Diabetes Mellitus, Impaired Fasting Glucose, and Impaired Glucose Tolerance. The Au

Risk of Cardiovascular and All-Cause Mortality in Individuals With Diabetes Mellitus, Impaired Fasting Glucose, and Impaired Glucose Tolerance. The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)


Published online before print June 18, 2007(Circulation 2007, doi:10.1161/CIRCULATIONAHA.106.685628)

Risk of Cardiovascular and All-Cause Mortality in Individuals With Diabetes Mellitus, Impaired Fasting Glucose, and Impaired Glucose Tolerance. The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)

Elizabeth L.M. Barr MPH*, Paul Z. Zimmet PhD, Timothy A. Welborn PhD, Damien Jolley MSc, Dianna J. Magliano PhD, David W. Dunstan PhD, Adrian J. Cameron MPH, Terry Dwyer MD, Hugh R. Taylor MD, Andrew M. Tonkin MD, Tien Y. Wong PhD, John McNeil PhD, and Jonathan E. Shaw MD

From the International Diabetes Institute (E.L.M.B., P.Z.Z., D.J.M., D.W.D., A.J.C., J.E.S.), Caulfield, Victoria, Australia; Department of Medicine (T.A.W.), University of Western Australia, Nedlands, Western Australia; Monash Institute of Health Services Research (D.J.), Clayton, Victoria, Australia; Murdoch Children’s Research Institute (T.D.), Royal Children’s Hospital, Prahran, Victoria, Australia; Centre for Eye Research Australia (H.R.T., T.Y.W.), University of Melbourne, East Melbourne, Victoria, Australia; and Department of Epidemiology and Preventive Medicine (A.M.T., J.M.), Monash University, Prahran, Victoria, Australia.

Background--Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality.

Methods and Results--In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2).

Conclusions--This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism

Obese Patients Are More Likely To Survive After Successful Treatment For A Heart Attack Than Normal Weight Patients

Obese Patients Are More Likely To Survive After Successful Treatment For A Heart Attack Than Normal Weight Patients

Obese and very obese patients have a lower risk of dying after they have been treated for heart attacks than do normal weight patients, according to research published in the European Heart Journal today (Wednesday 20 June). [1]

Researchers in Germany and Switzerland found that amongst patients who had received initial treatment for a specific type of heart attack, those that were obese or very obese were less than half as likely to die during the following three years as patients who had a normal body mass index (BMI).

Dr Heinz Buettner, head of interventional cardiology at Herz-Zentrum, Krozingen, Germany, who led the study, said: "Although there is no doubt that people who are overweight, obese and very obese have a higher risk of developing diabetes, hypertension and coronary artery disease, the evidence from our study shows once a coronary event has occurred and been optimally treated, obese patients switch to a more favourable prognosis compared to normal weight patients."

Dr Buettner and his colleagues followed 1,676 consecutive patients in a prospective study who had been admitted to hospital suffering from unstable angina/non-ST-segment elevation myocardial infarction between 1996 and 1999. Coronary angiography was performed to diagnose the extent of the problem and then the patients were usually treated with early coronary revascularisation, primarily by inserting stents to widen the relevant artery, or by coronary artery bypass grafting.

A third of the patients (551) had a normal BMI, half (824) were overweight, and 18% (292) were obese or very obese [2]. The obese and very obese patients tended to be younger, more likely to have hypertension and diabetes already, but less likely to have suffered an earlier heart attack. They were also more likely to be discharged from hospital after treatment with prescriptions for statins, ACE-inhibitors and beta-blockers.

"After three years of follow-up, we found that obese and very obese patients had less than half the long-term mortality when compared with normal BMI patients; 9.9% of normal BMI patients and 7.7% of overweight patients had died at the end of the three years, but only 3.6% of obese patients had died and no very obese patients had died. The reduction in mortality rates was consistent among all sub-groups and persisted after adjustment for a number of variables. These findings contrast with primary prevention studies that implicate BMI as a strong risk factor for mortality."

"The findings of this study complement and extend our knowledge regarding the impact of obesity on cardiovascular disease by suggesting that the prognostic impact of obesity is confounded by a cardiovascular event such as a heart attack. Approximately 2-2.5 million patients worldwide are hospitalised for unstable angina/non-ST-segment elevation myocardial infarction each year. Until now, the impact of obesity on outcomes after revascularisation treatment was unknown."

Dr Buettner said his study was limited to describing the association observed between obesity and improved survival, and it was not possible to say what might be causing it. "Further research is necessary to elucidate the underlying pathophysiological mechanisms responsible for the more favourable outcome in obese patients. Possible mechanisms might include treatment differences, lower age, endogenous cannabinoids, lower platelet counts and excess triglyceride content in heart tissue."

However, he believes that the adjustments they made when analysing the data rule out the possibilities that the survival effect could be a result of the obese patients being younger and more likely to be prescribed statins, ACE-inhibitors and beta-blockers on discharge from hospital. While the researchers did not have information on whether the obese patients embarked on a more vigorous programme of improved life style and weight loss after their discharge, Dr Buettner thought this probably did not affect their results either.

"Even without this additional information, our findings have considerable clinical impact as risk is typically assessed according to actual BMI rather than BMI changes. Survival in the different BMI groups started to differ significantly early on during follow-up; if body weight changes were likely to influence prognosis, a more delayed effect would be expected. Other studies have shown that even five years after coronary patients have been given advice on life-style changes, their overall BMI remains unchanged. However, our study is ongoing, and we hope that a larger cohort of patients will enable us to discover whether shifts in body weight have an additional impact on prognosis."

He said the clinical role of other potential mediators, such as the endogenous cannabinoid system (levels of endogenous cannabinoids were higher in obese patients), platelet count (which were lower in obese patients and which can affect clotting), or excess triglyceride (fat) content in heart tissue (higher levels of triglyceride might protect the damaged heart), were yet to be determined.

"Obesity was an independent predictor for reduced mortality. So any differences between obese and non-obese patients, which might have prognostic implications, are of interest. Current evidence suggests a central role of the endogenous cannabinoid system in obesity. The stimulation of the CB1 cannabinoid receptor subtype in the brain seems to be a key component in the development of diet-induced obesity and the brain level of endogenous cannabinoids increases with greater intake of food. A growing line of evidence indicates that endogenous cannabinoids can have protective roles in pathophysiological conditions such as shock, ischaemia and myocardial infarction."

He said that while the findings of his study provided important prognostic information for obese patients, people who were obese should not wait to have a heart attack before starting to make an effort to reduce their weight.

"Not all patients can be treated with early revascularisation because an acute coronary syndrome always has the risk of sudden cardiac death. It is well known that even a modest intentional weight loss can improve or prevent obesity-related cardiovascular risk factors like diabetes mellitus and arterial hypertension," he said.


[1] The impact of obesity on mortality in UA/non-ST-segment elevation myocardial infarction. European Heart Journal, doi:10.1093/eurheartj/ehm220

Tuesday, June 19, 2007

Bacterial pneumonia patients at increased risk of major heart problems

Bacterial pneumonia patients at increased risk of major heart problems

A new study suggests patients hospitalized with pneumonia may be at serious risk of new or worsening heart problems. The study is published in the July 15 issue of Clinical Infectious Diseases, currently available online.

Researchers led by Daniel Musher, MD, studied the records of all 170 patients hospitalized with pneumococcal pneumonia at a Texas Veterans Affairs medical center from 2001 to 2005. They found that 19.4 percent of them had a heart attack or other major heart problem concurrently at the time of admission, and that the presence of the heart condition significantly increased mortality from pneumonia.

In this study, the authors note, when adult patients were hospitalized with a diagnosis of bacterial pneumonia, the concurrence of pneumonia and a new cardiac event was often unrecognized, especially in the first 12-24 hours of hospitalization, which led some patients to go without antibiotics for pneumonia and others to have no cardiac monitoring or anticoagulant therapy.

The authors propose that pneumonia increases the risk of heart problems by increasing the hearts demand for oxygen while simultaneously causing a decrease in the lungs ability to transfer oxygen from the air to the blood. Also, pneumonia raises blood levels of a type of a chemical signal called a cytokine that promotes the formation of blood clots and that decreases the efficiency of the heart.

Physicians who take care of patients with pneumonia or with acute coronary syndromes need to be aware of the possible concurrence of the two diseases in an individual patient, said Dr. Musher.

Fast Facts

Nearly 20 percent of patients admitted with pneumococcal pneumonia at a Texas Veterans Affairs medical center had a heart attack or other major heart problem concurrently at the time of admission, and the heart condition significantly increased mortality from pneumonia.

When patients were diagnosed with pneumonia, the heart problem frequently went unrecognized.

Physicians should be aware of the possibility that a patient has both conditions.
Conclusions: Patients with pneumococcal pneumonia are at substantial risk for a concurrent acute cardiac event, such as MI, serious arrhythmia, or new or worsening CHF. This concurrence significantly increases mortality due to pneumonia. Admitting physicians tend to seek a unifying diagnosis, but the frequent coexistence of pneumonia and cardiac events indicates the importance of considering multiple diagnoses.

2007 American Society of Hypertension Meeting Roundup

American Society of Hypertension

Chicago, IL • May 19 - May 22, 2007

ASH: Dual-drug Treatment Accomplishes Blood Pressure Control (CME/CE) CHICAGO -- Initiating treatment with a combination of anti-hypertensive drugs gets 75% of patients’ blood pressures under control, researchers reported here.

ASH: DASH Diet Gets No Respect from Hypertensive Patients (CME/CE) CHICAGO -- The DASH diet plan apparently has not caught on among hypertensive patients. In fact, the percentage of patients adhering to DASH plummeted after the diet was incorporated in national guidelines.

ASH: More Proves Better in Treating Hypertension (CME/CE) CHICAGO -- Fixed combination doses of a calcium-channel blocker and an angiotensin-receptor blocker appear to improve hypertension treatment, researchers said here.

ASH: Obesity Linked to Diastolic Hypertension Subtypes (CME/CE) CHICAGO -- Obesity appears to be associated with an increased risk of diastolic rather than systolic hypertension subtypes, researchers said here.

ASH: Abbreviation at the Core of Choice of Diuretics (CME/CE) CHICAGO -- For the lack of a convenient abbreviation, a diuretic with a good track record for hypertension is often spurned on prescription pads, said researchers here.

New European guidelines on hypertension

New European guidelines on hypertension

Milan, Italy - New guidelines for the management of arterial hypertension have been issued at the European Society of Hypertension (ESH) meeting in Milan, Italy [1]. The recommendations, which were drawn up jointly by task forces from ESH and the European Society of Cardiology (ESC), also appear in the June 2007 issue of the Journal of Hypertension.

Cochair of the task forces, Dr Guy de Backer (University Hospital, Ghent, Belgium), told heartwire that the guidelines are essentially an update to 2003 recommendations. The new document is 82 pages long and lists 825 references, reflecting the vast amount of data published on the subject of hypertension in the past four years, he noted.

Asked to pick out highlights for heartwire, de Backer said this was a difficult task, "as there has been no one dramatic change, rather small changes in each area. The most important thing is that this is an update and the numerous references have been critically evaluated. We have kept the general framework and added what we think is most important from the literature."

For the clinician, the main messages can be found in a number of boxes in the paper, which contain position statements, he noted. "All you need to do is look at the position statements in the boxes, and read the text only if you want more detail." The task forces are working hard to produce a pocket version of the new guidelines for release at the ESC meeting in Vienna in September, he added.

No one choice of first-line therapy

The overall goal for blood-pressure reduction has remained the same—to lower BP to 140/90 mm Hg in the large majority of people. However, there has been a change in the recommendation for those with comorbidities, de Backer said. For example, there is a new goal of 130/80 mm Hg for people with established cardiovascular disease or diabetes.

In terms of treatment recommendations, he said the new guidelines shy away from recommending one particular class of antihypertensive over another as first-line therapy; rather they emphasize the importance of selecting therapy for each individual, according to any comorbidities they may have.

"We have noted the five important drug classes—diuretics, calcium-channel blockers, ACE inhibitors, beta blockers, and angiotensin-receptor blockers," he said. But from then on, "if we have to make a choice it should depend on comorbidities."

For example, the best choice of first-line agent for someone with hypertension who also has diabetes is either an ACE inhibitor or an angiotensin-receptor blocker. For those who have suffered an MI, the most appropriate drug to use first is a beta blocker, and in the elderly, the first-line drug of choice is generally a calcium-channel blocker to reduce the risk of stroke, he noted.

He added, however, that the emphasis on identification of first-line therapy is often pretty futile, because the majority of patients require multiple blood-pressure medications.

Antihypertensive treatment: Preferred drugs as per new European guidelines

Subclinical organ damage - Treatment

LVH - ACE inhibitors, calcium antagonists, angiotensin receptor blockers

Asymptomatic atherosclerosis - Calcium antagonists, ACE inhibitors

Microalbuminuria - ACE inhibitors, angiotensin receptor blockers

Renal dysfunction - ACE inhibitors, angiotensin receptor blockers

Clinical event

Previous stroke - Any BP-lowering agent

Previous MI - Beta blockers, ACE inhibitors, angiotensin receptor blockers

Angina pectoris - Beta blockers, calcium antagonists

Heart failure - Diuretics, beta blocker, ACE inhibitors, angiotensin receptor blockers, antialdosterone agents

Atrial fibrillation

—Recurrent - Angiotensin receptor blockers, ACE inhibitors

—Permanent - Beta blockers, nonhydropyridine calcium antagonists

ESRD/proteinuria - ACE inhibitors, angiotensin receptor blockers, loop diuretics

PAD - Calcium antagonists


ISH (elderly) - Diuretics, calcium antagonists

Metabolic syndrome - CE inhibitors, angiotensin receptor blockers, calcium antagonists

Diabetes mellitus - ACE inhibitors, angiotensin receptor blockers

Pregnancy - Calcium antagonists, methyldopa, beta blockers

Blacks - Diuretics, calcium antagonists

LVH=left ventricular hypertrophy; ESRD=end-stage renal disease; PAD=peripheral arterial disease; ISH=isolated systolic hypertension

Other subjects on which there is more information in the new guidelines include the taking of ambulatory BP measurements and those performed at home by patients themselves, de Backer noted, adding that the advice for interpreting ambulatory and home BP measurements "is more detailed now."

Extra information can be found on subclinical organ damage, including details about novel markers for renal damage and arterial stiffness.

Mancia G, de Backer G, Dominiczak A, et al. 2007 guidelines for the management of arterial hypertension. J Hypertens 2007; 25: 1105-1187


ESC - Summary reports and slides are available online during the Heart Failure 2007 Congress in Hamburg from 9 to 12 June 2007.

Scientific Reports

Heart Failure 2007 Congress

The following presentations were selected by the Scientific Committee of the Heart Failure Association of the ESC as of particular interest.

Please click on title to see session details.

Summary reports and slides are available online during the Heart Failure 2007 Congress in Hamburg from 9 to 12 June 2007.------------------------------------------------------------------------------------------------

Future of Biomarkers in Heart Failure Prof Eugène BraunwaldEugene Braunwald, M.D. is the Distinguished Hersey Professor of Medicine at Harvard Medical School, and Chairman of the TIMI Study Group at the Brigham and Women’s Hospital.Slides (PDF 1,7 Mb)
BNP is is an obligatory biomarker for longterm management of chronic heart failure - ProProf. Guillaume JondeauSummary: Despite advances in medical therapy of heart failure, mortality remains high. A new approach would be to improve monitoring of patients with chronic heart failure. Biomarkers such as BNP clearly rises this possibility and indications are coming from tials that use of this new parameter is associated with decreased hospitalisation rate.Report Slides

Levosimendan is a firstline drug in the management of acute heart failure - ProProf. Ferenc FollathSummary: The efficacy of levosimendan, a novel drug with positive inotropic and vasodilating actions, was well documented in patients with decomepensated chronic heart failure with high filling pressures and low cardiac output. Proper pretreatment evaluation is essential to select suitable patients for application as a firstline treatment and to avoid problems due to excessive vasodilation.Slides
Levosimendan is a firstline drug in the management of acute heart failure - ContraProf. John ClelandSummary: Levosimendan proved superior to dobutamine in terms of haemodynamics and survival when studied in patients with severe chronic heart failure in the LIDO study. However, two large studies of levosimendan in acute heart failure failed to show convincing evidence of benefit overall on morbidity or mortality. A modest improvement in symptoms was observed compared to placebo in one study which requires confirmation. Important benefits might have occurred in some subgroups of patients but this also requires confirmation.Slides

Detection and treatment of depression in routine care of patients with heart failureProf. Christiane E AngermannSummary: On systematic screeening, depression is frequently diagnosed amongst patients with chronic heart failure, and is known to carry an adverse prognosis. Up to now, no efficacy data regarding hard clinical endpoints are available for any treatment modality of depression in this patient population; however, selective serotonin re-uptake inhibition may favourably influence the mortality risk by improving health behaviour and/or via direct modulation of biological pathways.Report Slides

Haemodynamic monitoring: tool or toy? Assoc.Prof. Gerasimos FilippatosSummary: Hemodynamic variables have been considered necessary to guide treatment in critically ill heart failure patients but recent trials did not show any benefit from pulmonary artery catheter (PAC) use. However, the detrimental outcomes may not emanate from the use of a PAC per se but from the lack of effective therapies, lack of knowledge about appropriate use of information received from the PAC or because the information is obtained very late in the course of the disease. New devices could provide additional insight into the difficult problem of early evaluation and management of patients with heart failure.Slides
The adult human atrium a realistic cell source for therapy?Prof. Pieter DoevendansSummary: The human atrial auricle contains cardiomyocyte progenitor cells. These cells are present in small groups and can be grown as stem cells in a high volume and differentiated very efficiently into human cardiomyocytes. Potentially these cells can be used for cell transplantation and tissue engineering.

Lipitor or simvastatin? - Lipitor is not superior

Pfizer Backtracks on Lipitor’s Edge Over Rival

Posted by Jacob Goldstein

Earlier this year, Pfizer issued a press release trumpeting an analysis that suggested the company’s cholesterol-lowering drug Lipitor helped patients more than simvastatin, a cheaper generic competitor originally sold by Merck as Zocor.

Today Pfizer filed a two-paragraph statement with the SEC explaining that those results were wrong. By the study’s primary measure of cardiovascular risks, patients who took Lipitor didn’t fare significantly better than those who took simvastatin.

That’s quite a rowback by Pfizer, which is fighting in the medical trenches to keep Lipitor sales humming. The March press release by Pfizer quoted a study author as saying the “analysis is important for physicians, employers and formulary directors at managed care companies who are making real-world treatment decisions for patients” because it “further supports the cardiovascular benefits previously seen with Lipitor.” There was no corrective press release issued today.

Generic simvastatin has been stealing market share from Lipitor since it became available last year.

The flawed study analyzed data from about 80,000 members of a managed care organization who had taken either Lipitor or simvastatin. The primary analysis compared the rate of serious cardiovascular problems, such as heart attacks and strokes, in patients who had been taking either drug for at least three months. The study found that, after adjusting for differences in doses of the medicines, the risk of cardiovascular events was 14% lower in patients who took Lipitor.

But according to the SEC filing today, “a subsequent review by the Company” found that the difference was in fact only 10% — not enough to be considered statistically significant, the standard test of scientific validity, Pfizer said.

The mistake was due to a “programming error” and came to light after the manuscript was submitted for publication in a medical journal, Pfizer spokeswoman Vanessa Aristide told the Health Blog this afternoon. Initial results from the study were presented at an American Heart Association epidemiology and prevention conference in March.

A secondary analysis included in the study looked at the difference between patients on Lipitor and simvastatin starting on the first day they took the drugs. That analysis found that Lipitor reduced cardiovascular risk by 26% more than simvastatin. The revised findings issued today said that difference was also lower than originally reported, but at 22% it was still enough to be statistically significant.

Update: We just got Pfizer senior vice president Michael Berelowitz on the phone. He explained that the mistake occurred because the initial analysis incorrectly included some data from 2005. The study was supposed to be limited to data from between 2002 and 2004.

The error was discovered while researchers were re-analyzing the data at the request of an expert who was reviewing the manuscript, which had been submitted for publication in a journal. Berelowitz declined to name the publication.

So is Lipitor superior to simvastatin or not, we asked? “We have clinical trial data and real-world data that are intriguing, and I think it should be followed up on,” said Berelowitz, citing a previous study, called IDEAL, that directly compared the two drugs. But that study also narrowly failed to show that Lipitor was superior to simvastatin in reducing heart attacks and heart-related deaths among patients who have already had heart attacks.

He wouldn’t say whether Pfizer is funding additional head-to-head studies of the two drugs. But he encouraged those who control the preferred-drug lists known as formularies to make the comparison for themselves. “People who make formulary decisions should look at their data and see how it plays out in their world.”


Monday, June 18, 2007

Risk factors identify stroke patients at high risk of cardiac events

Risk factors identify stroke patients at high risk of cardiac events

18 June 2007

Stroke 2007; Advance online publication

MedWire News: Stroke patients at high risk for early cardiac morbidity and mortality can be identified using a model based on five clinical and demographic characteristics, say researchers.

These characteristics are a history of congestive heart failure (CHF), the presence of diabetes, baseline creatinine of more than 115 μmol/l, severe stroke, and a long heart rate-corrected QT(c) interval or ventricular extrasystoles on electrocardiogram (ECG), report Jane Prosser (Royal Melbourne Hospital, Australia) and team.

Patients with none of these characteristics have a 6.3% risk of a serious cardiac adverse event within 3 months of acute ischemic stroke, while patients with four or more characteristics have a 62.2% risk, Prosser et al report in the journal Stroke.

They explain: "Approximately 2–6% of all stroke patients die from cardiac causes in the first 3 months after ischemic stroke… Despite these relatively high risks, many patients will not have cardiac events.

"An approach to identifying patients at high risk of cardiac events is required to assess potential pre-emptive strategies, including monitoring, investigation, and treatment."

The researchers analyzed data from a trial in the Virtual International Stroke Trials archive that involved 864 participants with ischemic stroke.

By 12 weeks, 180 (21.3%) patients had died, 35 of them from cardiac causes. The risk of death from cardiac causes was highest at 14 days after stroke.

On multivariate analysis, a history of CHF was associated with an odds ratio (OR) of 3.33 for cardiac mortality within 3 months of stroke, creatinine levels of more than 115 μmol/l with an OR of 1.77, and diabetes with an OR of 2.11.

Furthermore, respective ORs of 1.98 and 1.93 were associated with severe strokes – those that scored less than the group's median score on the European Stroke Scale (ESS) – and a long QTc or ventricular extrasystoles on ECG.

Prosser et al comment: "The main points that emerge from our study are that serious cardiac adverse events are common and begin to occur very early after stroke onset.

"Furthermore, cardiac risk can be stratified with a five-point risk score derived from simple clinical and demographic variables available at the time of admission."

Echocardiography Helps Identify Heart Disease

Echocardiography Helps Identify Heart Disease

Test is more accurate than others when used in patients at risk, experts say

By Steven ReinbergHealthDay Reporter

FRIDAY, June 15 (HealthDay News) -- New uses of echocardiography to identify and stratify people with heart disease were highlighted Friday during the American Society of Echocardiography's annual meeting.

"Echocardiography has been around a long time, and it is part of the routine evaluation of heart disease," said Dr. Thomas Ryan, director of the Duke University Heart Center and the society's incoming president. "There has been a lot of technical developments and improvements over the last several years."

Echocardiography, which is basically ultrasound for the heart, is a very accurate and versatile test, Ryan noted. "It can be applied in a lot of different clinical situations," he said. "There is a new population that it is being applied to. It's useful in patients with symptoms, it's useful in patients with a high likelihood of having heart disease, and it is useful for defining the location and extent of heart disease."

In the first presentation, Dr. Farooq A. Chaudhry, director of echocardiography and associate chief of cardiology at St. Luke's-Roosevelt Hospital Center in New York City, and colleagues used stress echocardiography in 447 women to identify their risk for heart disease.

"To identify women at risk for heart disease, we used stress echocardiography, which is done at rest and then during stress," Chaudhry said. "Using this technique, you can differentiate high-risk women from others. If you have an abnormal echo-study, you are three times more likely to have a heart attack or die from heart-related causes."

Chaudhry thinks this technique is more accurate than other methods for identifying heart problems, especially in women. It is a good way to evaluate women who have risk factors for heart disease, he said.

"If women have a history of heart disease, high cholesterol, obesity or diabetes or high blood pressure, this technique should be used to risk stratify them," Chaudhry said.

In another study, Dr. Saritha Dodla and colleagues from the University of Nebraska Medical Center in Omaha found that by using echocardiography, they were able to identify diabetics who were at risk for heart disease even though they had no symptoms.

In the study, the researchers looked at 149 diabetic patients and followed them for an average of almost two years. They found that 25 of the patients had abnormalities in their cardiac arteries. Of these patients, 67 percent were alive after two years, compared with 72 percent of the normal patients.

By looking at heart abnormalities, doctors may be able to diagnose and treat more diabetes patients with blockages of the heart arteries, the researchers concluded.

In a third study, Dr. Jared J. Wyrick of Oregon Health & Science University, and colleagues found that by using echocardiography along with a contrast agent that makes abnormalities easier to see, they were able to identify patients who may be having a heart attack, compared to patients with low-risk chest pain.

In the study, researchers used myocardial contrast echocardiography to evaluate 957 patients complaining of chest pain. They found that by using myocardial contrast echocardiography, 55 percent of the patients could be discharged from the emergency department, thus avoiding admittance charges and follow-up tests. These patients could have saved about $700, plus the inconvenience of hospital stays, the researchers reported.

In the final presentation, Dr. John Postley of Columbia University and colleagues found that by using Screening Vascular Ultrasound, a type of echocardiography, they could identify patients with potential heart disease before symptoms appeared.

In the study, Postley's team used the technique to evaluate 398 patients, ages 33 to 79. The researchers found that 171 patients had plaque build-up in the arteries of the neck and thigh. Of these, 25 percent of men and 35 percent of women were at risk for heart disease.

"These findings suggest that even patients with low Framingham Risk Scores may have cardiovascular disease, as demonstrated by the presence of plaque build-up, and that Screening Vascular Ultrasound is an effective method to identify these patients," Postley said in a prepared statement. "This combination of technologies is wonderful news for the medical community, as it will help identify people with clogged arteries before they even begin showing symptoms, allowing physicians to be more proactive in treatment," he said.

The American Society of Echocardiography's annual meeting is taking place in Seattle.

More information

For more information on echocardiography, visit the American Heart Association.

SOURCES: Thomas Ryan, M.D., director, Duke Heart Center, Duke University, Durham, N.C., incoming president, American Society of Echocardiography; Farooq A. Chaudhry, M.D., director, echocardiography, associate chief of cardiology, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York City; June 15, 2007, presentations, 18th annual scientific sessions of the American Society of Echocardiography, Seattle

Sunday, June 17, 2007

Aspirin Resistance

Landmark Study On Aspirin Resistance

Aspirin is used by millions of patients for the prevention and treatment of coronary artery disease, the single leading cause of death in the world. In the largest study to date on the effectiveness of aspirin, researchers at the Center for Thrombosis Research at Sinai Hospital of Baltimore recently demonstrated that aspirin resistance is rare, less than 5 percent, at all doses (81 mg, 162 mg and 325 mg) in patients with heart disease. The results of study were recently published in the June 11 issue of Circulation, a journal of the American Heart Association (DOI: 10.1161/CIRCULATIONAHA.106.675587).

Most coronary artery disease deaths are caused by platelets sticking together and forming blood clots (thrombosis) that block blood flow within arteries, resulting in a heart attack. By inhibiting clotting, aspirin keeps platelets from sticking together by specifically blocking an important enzyme, COX-1.

"The occurrence of clotting in patients taking aspirin therapy has been attributed to the failure of aspirin blocking its target and is a hot topic in cardiovascular disease today," said Paul Gurbel, MD, lead investigator for the study and director of the Center for Thrombosis Research at Sinai Hospital of Baltimore. "However, our data suggest that aspirin blocks COX-1 with high efficiency."

The team at the Center for Thrombosis Research at Sinai Hospital studied 125 patients with a history of coronary artery disease treated with aspirin. All patients were randomly placed on 81 mg, 162 mg and 325 mg of aspirin daily for four weeks each for a total of 12 weeks. Then the response to aspirin was tested by multitude methods. When measuring the ability of aspirin to block its target, COX-1, it was found highly effective at all dose levels.

"The research also shows that aspirin may be effective at blocking other pathways that promote platelet activation, independent of COX-1. Further research is now under way to better understand these additional pathways that may cause clotting in patients in an effort to continue to improve patient outcomes," said Gurbel.

This investigator-initiated study was funded by an unrestricted educational grant from Bayer HealthCare LLC and Sinai Hospital of Baltimore.