Tuesday, July 31, 2007

The EVASTENT Matched-Cohort Registry

Risk Factors for Stent Thrombosis After Implantation of Sirolimus-Eluting Stents in Diabetic and Nondiabetic Patients

The EVASTENT Matched-Cohort Registry

Objectives: We sought to assess the frequency and causes of stent thrombosis in diabetic and nondiabetic patients after implantation of sirolimus-eluting stents.

Background: Safety concerns about late stent thrombosis have been raised, particularly when drug-eluting stents are used in less highly selected patients than in randomized trials.

Methods: The EVASTENT study is a matched multicenter cohort registry of 1,731 patients undergoing revascularization exclusively with sirolimus stents; for each diabetic patient included (stratified as single- or multiple-vessel disease), a nondiabetic patient was subsequently included. Patients were treated with aspirin + clopidogrel for at least 3 months and were followed for 465 (range 0 to 1,062) days (1-year follow-up in 98.5%). The primary end point was a composite of stent thrombosis (according to Academic Research Consortium definitions), cardiovascular death, and nonfatal myocardial infarction (major adverse cardiac events [MACE]).

Results: During follow-up, MACE occurred in 78 patients (4.5%), cardiac death in 35 (2.1%), and stent thrombosis in 45 (2.6%): 30 definite, 23 subacute, and 22 late, including 9 at >6 months. In univariate analysis, the 1-year stent thrombosis rate was 1.8 times higher in diabetic than in nondiabetic patients (3.2% vs. 1.7%; log rank p = 0.03), with diabetic patients with multiple-vessel disease experiencing the highest rate and nondiabetic single-vessel disease patients the lowest (4.3% vs. 0.8%; p < 0.001). In multivariate analysis, in addition to the interruption of antithrombotic treatment, independent stent thrombosis predictors were previous stroke, renal failure, lower ejection fraction, calcified lesion, length stented, and insulin-requiring diabetes.

Conclusions: The risk of sirolimus stent thrombosis is higher for multiple-vessel disease diabetic patients.

Heart rate and microinflammation in men: a relevant atherothrombotic link

High resting heart rate (HR) is associated with a microinflammatory response in healthy men and in those with atherothrombotic risk factors, which might explain why individuals with increased HR have a poor cardiovascular prognosis, Israeli researchers report.

Heart rate and microinflammation in men: a relevant atherothrombotic link

Rogowski et al.

Heart.2007; 93: 940-944


Objective and background: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR.

Methods: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors.

Results: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001)>/=79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 µmol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74x109/l.

Conclusions: Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.

Smoking during pregnancy increases offspring infant SBP

Smoking during pregnancy increases offspring infant SBP

Hypertension 2007; Advance online publication

MedWire News: Infants born to mothers who smoked during pregnancy have increased systolic blood pressure (SBP) levels, a report shows.

MedWire News - Cardiology - Smoking during pregnancy increases offspring infant SBP

Cause of cardiac fibrosis is studied

Cause of cardiac fibrosis is studied

BOSTON, July 30 (UPI)

U.S. scientists studying cardiac fibrosis -- a stiffening of the heart muscle that can lead to heart failure -- have identified a possible treatment.

The animal study, led by the Beth Israel Deaconess Medical Center, demonstrates a bone morphogenic molecule known as rhBMP7 can reverse the cardiac fibrosis process, offering the possibility of a therapeutic target for the debilitating condition.

"Heart disease is the No. 1 cause of death in the Western world," the study's lead author Dr. Elisabeth Zeisberg said. "And most people who suffer from heart disease have developed scarring of the heart tissue, known as fibrosis." Fibrosis develops when excessive production of matrix proteins, such as collagen, results in pathological scarring. In the heart, the buildup of matrix leaves the organ stiff and inflexible, unable to properly relax and function.

"Fibrosis can develop in any organ in the body," Zeisberg said. "While it's known that fibroblast cells are responsible for cardiac fibrosis, the source of these fibroblasts has remained unknown until now."

The study, funded in part by the National Institutes of Health and the Novartis Corp., appears in the advance online edition of the journal Nature Medicine.

Inherited Arrhythmic Disorders

Inherited Arrhythmic Disorders

Tex Heart Inst J. 2007; 34(1): 67–75.
Copyright © 2007 by the Texas Heart® Institute, Houston
Inherited Arrhythmic Disorders
Long QT and Brugada Syndromes

Inherited arrhythmic disorders comprise a group of syndromes with unique genetic abnormalities and presentations but with very similar clinical outcomes and complications, the most terrifying of which are life-threatening arrhythmias and sudden cardiac death. Advances in molecular biology have enabled us to define and pinpoint many such disorders, which were previously labeled as idiopathic, to specific genes on various chromosomes. The current trend in the management of these potentially deadly disorders is to use pharmacotherapy (antiarrhythmic agents) and defibrillators for the prevention of sudden death; however, targeted therapy at a molecular level appears to be the path of the future. Herein, we review long QT and Brugada syndromes and focus on the genetics, pathophysiology, and clinical manifestations of these inherited arrhythmogenic disorders that affect patients with structurally normal hearts.

Monday, July 30, 2007

FDA Advisers Vote to Keep Rosiglitazone (Avandia) But Cite Risks

FDA Advisers Vote to Keep Rosiglitazone (Avandia) But Cite Risks

MedPage Today Action Points


FDA advisers agreed today that although rosiglitazone (Avandia) increases ischemic heart risks for type 2 diabetes patients, it should stay on the market.

Members of two FDA advisory panels, meeting jointly, voted 22 to one in favor of continued marketing. Arthur Levin, M.P.H., of the Center for Medical Consumers in New York cast the lone dissenting vote, citing public health issues.

Meanwhile, GlaxoSmithKline, said it applauded the FDA advisers' recommendation as "a positive for patients," according to press release.

Although advisors voted overwhelmingly to recommend that the FDA keep the drug on the market, they also made it clear that they want to see a much narrower market for rosiglitazone.

Almost every one of advisers who said they wanted the drug to stay on the market offered the same advice about future labeling of the drug—additional warnings.

Clifford Rosen, M.D., the Bangor, Me., endocrinologist who chaired the meeting, said the drug should not be used by patients requiring insulin, those with a history of coronary heart disease, those with congestive heart failure, and those who are long-time users of nitrates.

The advisers didn't sort out specifics of the new warnings although nearly all used terms like black box or boxed warning. But Robert Meyer, M.D., director of new drug evaluation at the FDA's Center for Drug Evaluation and Research, said at a press conference that it wasn't clear to him that black box warnings had been recommended.

In any case, Dr. Meyer pointed out, while the FDA might follow the advice given by advisory committees the exact actions—and the timing of those regulatory actions—are up to the agency.

He also noted that the FDA has already asked GlaxoSmithKline and Takeda, which makes pioglitazone (Actos), another thiazolidinedione, to add a boxed warning about the risk of congestive heart failure to the labels of their respective drugs.

In an unusual move for agency officials, who normally are reluctant to make on-the-record comments about drugs under review, both Gerald Dal Pan, M.D., M.P.H., director of the FDA's Office of Surveillance and Epidemiology, and David Graham, M.D., M.P.H. associate director of that office, said during the meeting they thought rosiglitazone should be taken off the market.

Dr. Graham said the "point estimates of the relative risk of cardiovascular deaths and non-fatal MIs range from 1.20 to 1.40 to 1.70 for rosiglitazone.

"Using those estimates, Dr. Graham calculated that there are "1,600 to 2,500 excess MIs and ischemic heart disease deaths for every month that rosiglitazone stays on the market."

The panel also agreed that the strongest evidence of ischemic heart disease risk with rosiglitazone came from three meta-analyses of randomized clinical trials—one by GSK, another by FDA staffers, and an analysis done by Steven Nissen, M.D., of the Cleveland Clinic.

Dr. Nissen's analysis, which was published online May 21 by the New England Journal of Medicine, was widely regarded as the spark that turned mild concern about the cardiovascular safety of the drug into a cause célèbre. The analysis, which included data from 42 trials, found a 43% increase in risk of myocardial infarction with rosiglitazone.

Dr. Nissen was asked to serve as a consultant to the advisory panel, but he functioned under a strict set of ground rules that prevented him from sitting at the table with other consultants. He was also allowed to speak only in answer to questions about his meta-analysis and was instructed to refrain from commenting on any of the data presented at the meeting.

Before the meeting Dr. Nissen hinted broadly that he thought the drug should be pulled from the market, but in an interview immediately after the meeting he said he was pleased with the advisers’ actions. Noting that the advisers agreed with his finding of excess risk with rosiglitazone, he said the recommended warnings will be helpful "physicians follow those warnings."

Saturday, July 28, 2007

Air Pollution Link To Clogged Arteries

Air Pollution Link To Clogged Arteries

27 Jul 2007

Should we be watching our exposure to airborne pollution as well as our cholesterol levels?

Research now indicates that air pollution has a role to play in atherosclerosis (artery hardening), which can contribute to heart attacks or strokes.

Findings published in the open access journal, Genome Biology, show how the fats that clog arteries work together with air pollution particles, triggering the genes behind inflammation.

A research team drawn from medical and environmental engineering disciplines at the Universities of California, Los Angeles, investigated the relationship between oxidized phospholipids found in the low density lipoprotein (LDL) particles, the 'bad' fats that clog arteries, and diesel exhaust particles. They exposed cells that line human blood vessels (microvascular endothelial cells) to both exhaust particles and oxidised phospholipids, and measured the effect on genes by using microarray expression profiling. This allowed the identification of gene modules containing a high number of co-expressed genes. These modules appear to be activated by a combination of phospholipids and diesel particles and are linked to vascular inflammation pathways. To confirm these findings, the team exposed mice with high cholesterol levels to the pollutant diesel particles, and saw some of the same gene modules upregulated.

The American Cancer Society has reported a six percent increase in cardiopulmonary deaths for every 10 µg/m3 rise in particulates. Exactly how airborne pollutant particles cause cardiovascular injury is poorly understood. But it is known that these particles are generally coated with a number of chemicals such as organic hydrocarbons, transition metals, sulfates and nitrates. Organic hydrocarbons and transition metals inflame airways by generating reactive oxygen species and oxidative stress when combined with oxidised phospholipids in the arteries. This can lead to vascular inflammation, which can in turn lead to increased lesions in the clogged arteries, potentially giving rise to blood clots that trigger heart attack or stroke. These findings bring us closer to understanding the impact our environment has on our health.

"Air pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells"

Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo

Genome Biology

Friday, July 27, 2007

Avandia raises heart risks, FDA finds

Avandia raises heart risks, FDA finds

The strongest available warning against the widely used diabetic drug is recommended.

By Thomas H. Maugh II and Denise Gellene, Times Staff Writers

July 27, 2007

The widely used diabetes drug Avandia increases the chance of serious heart problems, including a 30% to 40% higher risk of myocardial ischemia, or decreased flow of blood to the heart, according to documents released by the Food and Drug Administration on Thursday.

Diabetics taking the GlaxoSmithKline drug in combination with insulin were at even greater risk, the FDA found in a review of dozens of drug studies.

The analysis also found hints that pre-diabetics taking Avandia with ACE inhibitors, a class of heart drugs used for lowering blood pressure, faced a higher risk of myocardial ischemia.

FDA's division of drug risk evaluation concluded that the agency should issue the strongest available warning about the risk of myocardial ischemia in people who use Avandia, the documents showed.

The proposed "black box" warning would state that patients with heart disease or who are taking insulin should not use the drug.

Actos, or pioglitazone, a drug manufactured by Takeda Pharmaceutical Co. and in the same class as Avandia, carried no similar risks, according to the FDA analysis.

The documents were released in advance of an FDA advisory panel meeting on Monday to review the drug's safety. The panel could recommend stronger warnings or withdraw the drug from the market. The FDA isn't required to follow the advice of its outside experts but typically does.

In May, a study in the New England Journal of Medicine linked Avandia to a 43% increase in the risk of heart attacks. The study was led by Dr. Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio and a nonvoting member of the FDA panel.

After publication of that study, the FDA issued an alert reassuring patients that it had two studies that showed Avandia was safe.

But in the newly released documents, Dr. David Graham, a safety reviewer, said one of the studies was unreliable and could not be used to resolve safety concerns.

Used daily by nearly a million Americans with Type 2 diabetes to control blood sugar, Avandia had sales of $3.4 billion in 2006. However, sales have slumped 20% since May and could further drop if the panel recommends additional warnings.

Dr. Anne Phillips, vice president of clinical development at GlaxoSmithKline, said company studies of 400,000 patients showed "no increase in cardiovascular mortality, no increased risk of myocardial infarctions [heart attacks] and no increase in mortality from all causes.

"The findings were not available to FDA staffers when they prepared the documents released Thursday, she said.

Thiazoladinediones increase HF risk

Thiazoladinediones increase HF risk

27 July 2007

Diabetes Care 2007; 2007: Advance online publication

MedWire News:

Thiazolidinediones used to lower blood glucose levels in Type 2 diabetes patients may double the risk of heart failure (HF), review findings indicate.

Based on the review of studies and case reports, researchers estimate that one additional patient with Type 2 diabetes would develop HF for every 50 patients taking one of the drugs over a 26-month period.

"These drugs are currently used by more than 3 million diabetic patients in the USA alone, suggesting that several thousand could be harmed," said lead author Sonal Singh, from Wake Forest University in Winston-Salem, North Carolina, USA.

Singh and colleagues analyzed evidence from randomized controlled trials (RCTs), controlled observational studies, anecdotal case reports, case-series, and spontaneous reports in the Canadian Adverse Events Database (CADRMP).

They identified three RCTs including 10,731 patients who provided numerical information on HF events. A meta-analysis of these trials revealed an odds ratio for HF of 2.1 (p=0.03) in patients receiving a thiazolidinedione compared with those on placebo.

Based on this odds ratio, the estimated number-needed-to-harm with thiazolidinediones would be 50 over a 2.2 year follow-up period, the authors note in the journal Diabetes Care.

Meanwhile, results of four observational studies including 67,382 patients gave a pooled odds ratio for HF of 1.5 (p<0.00001) for those taking thiazolidinediones.

A Dose-Time-Susceptibility analysis of 28 published reports and 214 spontaneous reports from CADRMP showed that HF was more likely to appear after several months, with a median duration for HF onset of 24 weeks (range 1 to 260 weeks). Patients on low doses were also at risk of developing HF soon after treatment.

One patient on low-dose (=15 mg) pioglitazone and nine patients on low-dose (=4 mg) rosiglitazone developed HF within the first 4 weeks of therapy. And HF did not develop much earlier overall in patients receiving high doses of the drugs compared with those on low doses.

"The occurrence of HF several months after initiation of treatment suggests a long-term effect of the drugs, which may not be avoided by beginning with low doses," Singh commented.

Furthermore, the increased risk was not limited to the elderly, with one-quarter of cases of HF occurring in people younger than 60 years old. HF occurred with equal frequency in men and women.

Package inserts for the drugs warn against their use in patients with severe heart failure, and of an increased risk of HF in patients on insulin. But the current analysis indicates that the risk is not confined to patients with HF risk factors or those who are on insulin, the authors report.

"Our findings support current efforts by the [US] Food and Drug Administration to add a black box warning to the labeling of those agents," commented co-investigator Curt Furberg, also of Wake Forest University.

Thursday, July 26, 2007

Cardiovascular risk prediction based on home blood pressure measurement: The Didima Study.

Cardiovascular risk prediction based on home blood pressure measurement: The Didima Study.

Journal of Hypertension. 25(8):1590-1596, August 2007.

Stergiou, George S; Baibas, Nikos M; Kalogeropoulos, Petros G


Objective: Although home blood pressure (HBP) is being used increasingly in clinical practice, the evidence on its prognostic value is still limited. This study in the general population investigated the value of HBP compared to office measurements (OBP) in predicting cardiovascular risk.

Subjects and methods: In 1997 all adults of the Didima area in Greece were invited to participate in a cross-sectional study involving OBP (two visits) and HBP measurements (3 days). Incident cardiovascular morbidity and cause-specific mortality were assessed after 8.2 +/- 0.2 years (mean +/- SD). Average OBP and HBP were used in Cox regression analysis of fatal and non-fatal cardiovascular events with age, gender, history of cardiovascular disease, use of antihypertensive medication, smoking and diabetes as covariates.

Results: A total of 662 subjects were analysed (mean age at baseline 54.1 +/- 17.6 years). During follow-up 78 deaths (42 cardiovascular) and 67 cardiovascular events (fatal and non-fatal) were documented. Unadjusted hazard ratios for cardiovascular events per 1 mmHg blood pressure increase were for HBP systolic 1.034 (P < 0.001) and diastolic 1.037 (P < 0.01) and for OBP systolic 1.035 (P < 0.001) and diastolic 1.021 (P = 0.07). After adjustment for all available cardiovascular risk predictors, only diastolic OBP remained significant. The addition of HBP in the models already including OBP did not significantly improve the predictive ability. White coat but not masked hypertensives were at high risk.

Conclusions: This study showed that both HBP and OBP are significant predictors of cardiovascular risk in the general population. However, no prognostic superiority of HBP compared to OBP has been demonstrated.

Low LDL cholesterol levels tentatively linked to cancer risk

Cardiovascular News

Low LDL cholesterol levels tentatively linked to cancer risk

26 July 2007

MedWire News: An explorative analysis has found an association between the risk for cancer and achieved level of low-density lipoprotein (LDL) cholesterol in statin trials.

“This analysis doesn’t implicate the statin in increasing the risk of cancer,” stressed study author Richard Karas (Tufts University School of Medicine, Boston, Massachusetts, USA).

“The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research.”

The investigators included statin-treated participants from 23 trials in their analysis, giving 309,506 person-years of follow-up.

The magnitude of LDL cholesterol reduction achieved by patients was not associated with cancer risk, or with the patients’ risk for elevated liver enzymes or rhabdomyolysis.

Their results are published in the Journal of the American College of Cardiology. In a related comment, journal editors Anthony DeMaria and Ori Ben-Yehuda (University of California at San Diego, USA) observed that over the past 5 years, “no other manuscript has stimulated such intense scrutiny and discussion.”

The only clear treatment-related effect that the researchers detected was an increasing risk for elevated liver enzymes with rising statin dose.

This rate of elevated liver enzymes rose from about 100 per 100,000 person-years with low statin doses to about 250 per 100,000 person-years with high doses. The absolute and percent LDL cholesterol reductions were not associated with the risk for cancer.

But the team found an inverse relationship between achieved LDL cholesterol levels and the risk for cancer, at an R2 of 0.43. In other words, 43% of the variance in cancer incidence could be accounted for by achieved cholesterol levels, although this was not adjusted for confounders.

In their discussion, Karas et al observe that their findings are consistent with epidemiologic studies showing a link between low cholesterol levels and cancer. But they also note that researchers who previously compiled a review of such studies failed to draw any definitive conclusions, and suggested that the proposed association could be due to confounding.

“One potential explanation is the possibility that low cholesterol levels are simply the effect of the disease rather than the cause, and is present before clinical manifestation of the cancer,” say Karas and team.

In an accompanying editorial, John LaRosa (State University of New York Downstate Medical Center, USA) noted that the link between LDL cholesterol levels and cancer can be further studied without the need for more trials, as many LDL-lowering studies have not published data on cancer.

“Lowering LDL represents an intervention of long duration, and we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk,” he said.

“On the other hand, we must not allow that vigilance to deny the benefits of LDL lowering to those who need it.”


Primary source: Journal of the American College of CardiologySource reference: Alsheikh-Ali AA et al. "Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer." J Am Coll Cardiol 2007;50:409-418.

J Am Coll Cardiol 2007; 50: 409–418

Obesity Seems to Spread Through Social Networks

Obesity Seems to Spread Through Social Networks

Obesity appears to spread from person to person through social ties, according to a New England Journal of Medicine study.

The research evaluated a network of about 12,000 people over 32 years. All were members of the Framingham Heart Study. Researchers found, for example, that a person's chances of becoming obese increased by 57% in a given period if a friend became obese, 40% if a sibling did, and 37% if a spouse did. The effects were seen even if the obese acquaintance lived far away.

The authors speculate that someone who sees a friend gain weight may regard putting on weight as more acceptable. An editorialist says the work suggests that "friends have an even more important effect on a person's risk of obesity than genes do"


NEJM article (Free)
NEJM editorial (Free)
New York Times story (Free)

Wednesday, July 25, 2007

Association Between Increased Mortality and Mild Thyroid Dysfunction in Cardiac Patients

Association Between Increased Mortality and Mild Thyroid Dysfunction in Cardiac Patients

Giorgio Iervasi, MD; Sabrina Molinaro, PhD; Patrizia Landi, BSc; Maria Chiara Taddei, BSc; Elena Galli, MD; Fabio Mariani, PhD; Antonio L’Abbate, MD; Alessandro Pingitore, MD, PhD

Arch Intern Med. 2007;167:1526-1532.

Background The effects of subclinical thyroid dysfunction on cardiac outcome are not well defined.

Methods To assess the relationship between mild thyroid dysfunction and the incidence of death in cardiac patients, we evaluated 3121 cardiac patients. Cardiac and overall deaths were considered. Four groups were defined: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low triiodothyronine syndrome (low T3).

Results After mean follow-up of 32 months, there were 65 and 140 cardiac and overall deaths (3.4% and 7.3%), respectively, in euthyroidism, 15 and 27 (7.2% and 13.0%) in SCH, 8 and 9 (8.2% and 9.2%) in SCT, and 59 and 119 (6.5% and 13.1%) in low T3. Survival rates for cardiac death were lower in SCH, SCT, and low T3 than in euthyroidism (log-rank test; ² = 19.46; P < .001). Survival rates for overall death were lower in SCH and low T3 than in euthyroidism (log-rank test; ² = 26.67; P < .001). After adjustment for several risk factors, hazard ratios (HRs) for cardiac death were higher in SCH (HR, 2.40; 95% confidence interval [CI], 1.36-4.21; P = .02), SCT (HR, 2.32; 95% CI, 1.11-4.85; P = .02), and low T3 (HR, 1.63; 95% CI, 1.14-2.33; P = .007) than in euthyroidism; HRs for overall death were higher in SCH (HR, 2.01; 95% CI, 1.33-3.04; P < .001) and low T3 (HR, 1.57; 95% CI, 1.22-2.01; P < .001) but not in SCT.

Conclusion A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease.

Specific Gene Suppressor Described As A 'Dictator With A Conscience'

Specific Gene Suppressor Described As A 'Dictator With A Conscience'

25 Jul 2007 University of New South Wales (UNSW) researchers have uncovered an important naturally occurring mechanism in the body where "bad" cells that cause blockages in our blood vessels are kept under strict growth control, while "good" cells that keep our blood vessels free of clots and growths are left unaffected.

The discovery is expected to benefit those who will need heart coronary bypass surgery, an angioplasty -- the mechanical widening of a narrowed or totally blocked blood vessel -- or will undergo haemodialysis.

Professor Levon Khachigian, from UNSW's Centre for Vascular Research, who previously pioneered "molecular assassin" drug technology, describes this novel mechanism he discovered as "a molecular dictatorship with a conscience".

"The dictator is a specific gene suppressor called YY1, which has the therapeutically appealing capacity to differentiate between certain cell types when it goes about its activity," says Professor Khachigian.

This key finding has just been published in the world's premier cardiovascular research journal, Circulation Research.

Professor Khachigian's research provides new hope in tackling the global problems of coronary bypass graft failure, and restenosis -- the closing or narrowing of an artery that was previously opened by a procedure such as angioplasty.

"While the most effective way to head off restenosis is a drug-coated stent, the drugs that sit on these stents inhibit the growth of good cells as well as the bad.

"If you had to have catheter intervention to re-open an occluded artery, for sustained symptom-free benefit you would be hoping for suppressed smooth muscle cell growth, without affecting endothelial cell growth," says Professor Khachigian.

"And that's exactly what happens when we simply top up blood vessels with the body's natural reserves of YY1."

Article adapted by Medical News Today from original press release.

Tuesday, July 24, 2007

Low Cholesterol Levels And Cancer

Low Cholesterol Levels And Cancer

Millions of Americans take statins to lower their cholesterol, but how low should you go" A number of scientific studies support the benefits of lowering low-density lipoprotein (LDL) cholesterol, and achieving low LDL cholesterol levels is one of the most important steps in preventing heart disease. New research, however, provides evidence for an association between low LDL levels and cancer risk.

The authors of the study, reported in the July 31, 2007, issue of the Journal of the American College of Cardiology (JACC), set out to understand how and why statins cause side effects, especially damage to the liver and muscle cells. The study findings support taking multiple medications rather than high-dose statins to minimize those side effects. The scientists did not expect to find the increased cancer risk (one additional incident per 1,000 patients) from low LDL levels, and additional studies have already begun to investigate this potential risk further. A key component in future studies will be to confirm the risk and to identify whether the risk may be a side effect of statins or just low LDL.

This analysis doesnt implicate the statin in increasing the risk of cancer, said lead author Richard H. Karas, M.D., F.A.C.C., professor of medicine at Tufts University School of Medicine. The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research.

The scientists found one additional incident of cancer per 1,000 patients with low LDL levels when in comparison to patients with higher LDL levels. In their evaluation of randomized controlled statin trials published before November 2005, the scientists looked at 13 therapy arms consisting of 41,173 patients.

Scientists assessed absolute change and percentage of change in LDL reduction and the resulting achieved LDL levels in relation to rates of newly diagnosed cancer in each therapy arm. They also looked at the relationship between low, intermediate and high doses of statins and rates of newly diagnosed cancer. Eventhough they did not find a relationship between percent of change and absolute change in LDL levels, they observed higher rates of newly diagnosed cancer among patients with lower achieved LDL levels. In addition, the new cancers were not of any specific type or location.

Recent data from large-scale statin trials have shown that more intensive LDL lowering can provide significant cardiovascular benefits to higher-risk patients. In response to these findings, recent national guidelines have advocated for lower LDL goals and higher doses of statins to reach them. However, informal observations linking intensive LDL lowering and higher occurence rate of reported health problems, including liver and muscle toxicity and cancer, has introduced some concern over the safety of such therapys.

These concerns in part prompted the current study. However, the current findings are not definitive, as limitations of the study show. Scientists performed their analysis from summary data taken directly from published manuscripts of each trial. An analysis based on data for each individual patient would have yielded more specific and potentially more compelling results, said Dr. Karas.

These current findings provide insufficient evidence that there is any problem with LDL lowering that outweighs its significant benefits on vascular disease, said John C. La Rosa, M.D., who wrote an accompanying editorial in the July 31 issue of JACC. However, we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk.

Eventhough the cancer risk was surprising, the scientists primarily sought to determine how and why statins cause side effects, especially damage to the liver and muscle cells. For this portion of the study, scientists analyzed 23 statin therapy arms that included 75,317 patients with a combined 309,506 years of follow up. A link between LDL lowering and liver or muscle irritation was not found. However, liver toxicity levels increased with higher statin dosage. Based on their findings, the scientists concluded that moderate-dose treatment with multiple medications including statins may prove to be preferable to high-dose treatment with statins alone. Dr. Karas emphasized that patients are advised to continue their statin therapys and, as always, consult their doctor before discontinuing use of any medication.

While these results raise important new questions about statin use, they do not demonstrate a causal relationship between statins and cancer, said James Dove, M.D., F.A.C.C., president of the American College of Cardiology. This study is hypothesis-generating, not hypothesis-proving.

Saturday, July 21, 2007

Fewer Stents Implanted

Wall Street Journal

July 20, 2007

Fewer Stents Implanted in June,Signaling Impact of New Studies

By KEITH J. WINSTEINJuly 20, 2007; Page B2

U.S. doctors implanted fewer coronary stents in June than any other month in the last year, according to a market researcher, indicating that medical studies critical of the devices appear to be having a sustained impact.

Stents are tiny scaffolds that prop open clogged arteries. Doctors flocked to them until late last year because they quickly relieve the chest pains and shortness of breath caused by a blocked artery. Last year, Americans spent more than $14 billion on stent procedures, with doctors implanting about 130,000 stents a month, according to various estimates.

But data from Goodroe Healthcare Solutions LLC, of Norcross, Ga., which surveys 75 U.S. hospitals with catheterization facilities for stenting, indicated that rate has significantly slowed.

According to Goodroe, doctors in June performed fewer artery-inflating angioplasties -- 11% below January levels. Fewer of those procedures involve a stent -- 92%, down from 94% in January. And doctors in June used about 1.48 stents per procedure, down 4% from January.

Those numbers indicate stent usage, in total, fell about 16%. (See more data from Goodroe1.)
Goodroe didn't provide usage numbers in units of stents. In the past, its numbers have largely agreed with figures released by manufacturers and market researchers.

In late March, the New England Journal of Medicine published a study indicating that patients with mild chest pains could safely delay stenting in favor of treatment with drugs. Some of those patients may return for stenting later in the year if their pain persists.

Stent use has also been hurt by studies linking the most popular and expensive kind -- those coated with drugs to prevent reclogging -- with blood clots more than a year after implantation. In response, doctors have shifted back to older, bare-metal stents.

That has been good news for Abbott Laboratories, whose U.S. sales of bare-metal stents were up 179% in the last year. But the makers of drug-coated stents -- Johnson & Johnson, whose U.S. stent sales fell 41%, and Boston Scientific Corp., which reports its quarterly results today -- have been hit hard. Boston Scientific and Abbott said they predicted an eventual recovery in the market. J&J declined to comment.

Friday, July 20, 2007


Three year follow-up from the ICTUS trial: Early intervention or selective-based treatment for coronary heart disease?

Christopher CannonTIMI Study Group, Boston, MA, USA19 June 2007

Globally, coronary artery disease (CAD) is the leading cause of mortality, with non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) being the most common manifestations of this condition.

There has been much debate over the past decade regarding the optimal management of patients with CAD.

Should we provide routine early invasive strategies, or do we need to adopt a more “conservative” approach based on selective intervention focused towards high-risk patients?

Cardiac catheterization and revascularization: The two main approaches
There are two general approaches to the use of cardiac catheterization and revascularization in UA/NSTEMI.

The “early invasive” strategy involves routine early cardiac catheterization and revascularization with percutaneous coronary intervention (PCI), or bypass surgery depending on the coronary anatomy.

The “conservative” strategy involves providing initial medical management, with catheterization and revascularization only for recurrent ischemia either at rest or on a non-invasive stress test.

The ACC/AHA guidelines were updated in 2002, and were based on the results of the FRagmin and Fast Revascularization during InStability in coronary artery disease (FRISC II) and Treat Angina with aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy - Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trials, both of which compared early invasive strategies with the conservative approach.

The results of these trials suggested that patients who received early invasive therapy benefited more than those who underwent conservative treatment.

However, to date, 10 randomized trials have studied the relative merits of an invasive versus a conservative strategy. These include the FRISC-II, RITA-3, and TACTICS. These trials yielded varying results.

Of note, the other recent long-term follow-up data available from the RITA-3 trial demonstrated a benefit of a significantly lower cardiovascular mortality rate in the early invasive arm which was observed over five years. [1] A meta-analysis of the contemporary trial has confirmed an overall significant reduction in death, MI or rehospitalization during follow-up was observed. [2]

The most recent trial, Invasive Treatment Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), examined an invasive versus conservative approach in 1200 patients. All patients received aspirin, enoxaparin, abciximab for PCI and intensive statin therapy. At one, year there was no significant difference in the rate of the primary endpoint, death, MI, or rehospitalization for angina. [3]

During the index hospitalization, there was a higher rate of MI in the invasive arm, although this trial used a definition of MI that included any elevation of any biomarker following PCI, and thus had a much higher peri-procedural MI rate compared with prior trials.

Throughout the three year follow-up period, the higher overall rate of MI (again using their definition of MI) persisted, with rates of 18 versus 12 (p=0). No difference in mortality was seen. [4]

How do we incorporate this new information? Based on multiple randomized trials, an early invasive strategy remains the recommended approach to higher risk patients with UA/NSTEMI who have either ST-segment changes, positive troponin, or other other high-risk indicators, such as recurrent ischemia, evidence of congestive heart failure. [5]


de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005; 353:1095-104.

Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol 2006; 48:1319-25.

Hirsch A, Windhausen F, Tijssen JG, Verheugt FW, Cornel JH, de Winter RJ. Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet 2007; 369:827-35.

Fox KAA, Poole-Wilson P, Clayton TC, et al. 5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005; 366:914-920.

Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: Summary Article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002; 106:1893-900.

Hypertension Combo Works, With Risks

Wall Street Journal - July 20, 2007

Novartis’s Hypertension Combo Works, With Risks

When you sell as many blood pressure drugs as Novartis, it’s natural to get creative, mixing and matching medicines to create new combinations.

But while combinations may lower blood pressure more effectively than a single drug, they may also heighten risk, as a [1] study published in this week’s Lancet shows.

The company’s blood pressure drugs already include single agents Tekturna and Diovan, as well as combination pills Exforge and Lotrel. (For an analysis of the sales of all these drugs, see [2] this Health Blog post.)

The new study enrolled 1797 patients and compared a combination of Tekturna and Diovan against each drug individually and against placebo. Diastolic blood pressure (the second number in a blood pressure reading) went down an average of 12.2 millimeters of mercury for patients who received the combination, compared with 9.7 mm Hg for Diovan, 9.0 mm Hg for Tekturna and 4.1 mm Hg for placebo. The study was funded by Novartis, which also paid medical writers to edit the manuscript.

The authors note that the percentage of patients with a high level of potassium in the blood was higher for patients who received the combination — 4%, compared with 3% for placebo and 2% for each of the single drugs. But they point out that the increase was not associated with serious medical problems and tended to return to normal by the study’s eight-week endpoint.

“Physicians have managed these mild increases in potassium very successfully for over 20 years,” the study’s [3] lead author, Suzanne Oparil of the University of Alabama Birmingham, said in a [4] statement issued by Novartis.

But a [5] commentary accompanying the study strikes a more cautious note about the heightened potassium levels, which, the authors note, can be associated with severe complications including paralysis and cardiac arrest. (One of the commentary’s authors, Willem H Birkenhäger of Erasmus University Rotterdam, claims no conflicts of interest; the other, Jan A Staessen of University of Leuven, reports funding from AstraZeneca and Pfizer, among other companies.)

The commentary argues that there may be a small group of patients suited to the Tekturna-Diovan combination. “However,” they conclude, “because of the potential life-threatening side-effects, which require biochemical monitoring, this concept of treatment is unlikely to make it to general practice or even to primary prevention in specialist care.”

Depression and the risk for cardiovascular diseases

Research Article

Depression and the risk for cardiovascular diseases: systematic review and meta analysis

email: Hein van Hout (

Correspondence to Hein van Hout, VU University Medical Center, Amsterdam, The Netherlands.


Depression and cardiovascular diseases are both common among elderly. Depression is suspected to be an independent risk factor for the onset of coronary heart disease, yet it is not clear to what extent and if depression also is associated with the onset of other diseases of the circulatory system.

To estimate the risk of depression as an independent risk factor for various cardiovascular diseases (CVD) and explore the effects of heterogeneity and methodological quality.

Meta-analyses and meta-regression analyses of longitudinal cohort and case-control studies reporting depression at baseline and CVD outcomes at follow-up.

Of the 28 studies that met the inclusion criteria, 11 were assesed as high quality studies. Although depressed mood increased the risk for a wide range of CVDs, heterogeneity was substantial in most cases. Only the overall combined risk of depression for the onset of myocardial infarctions (n=8, OR=1.60, 95%CI 1.34-1.92) was homogenous. Clinically diagnosed major depressive disorder was identified as the most important risk factor for developing CVD.

Depression seems to be an independent risk factor for the onset of a wide range of CVDs, although this evidence is related to a high level of heterogeneity.

International Journal of Geriatric Psychiatry

Volume 22, Issue 7 , Pages 613 - 626

Rosiglitazone (Avandia) Seen No Better than Other Drugs in Diabetic Control

Teaching Brief® - MedPage Today

Rosiglitazone (Avandia) Seen No Better than Other Drugs in Diabetic Control

Primary source: Cochrane Database of Systematic ReviewsSource reference: Richter B et al "Rosiglitazone for type 2 diabetes mellitus." Cochrane Database of Systematic Reviews 2007; Issue 3 Art.No.: CD006063. DOI: 10.1002/14651858.CD006063.pub2.

In many ways the Cochrane review echoed conclusions of a systematic review published Monday in the Annals of Internal Medicine which found that older drugs were as effective as rosiglitazone and pioglitazone and were less expensive as well. ( See For Type 2 Diabetes, Older Drugs Seem Tried and True)

Gene Scan Finds Links to Coronary Disease

Gene Scan Finds Links to Coronary Disease - Breaking Medical News + CME Teaching Brief® - MedPage Today

An increased risk of coronary artery disease has been linked -- for the third time in as many months -- to a region on chromosome nine.

The new study is one of a trilogy published online by the New England Journal of Medicine and Nature Genetics, all of which used genome-wide association scanning to find genetic links to diseases.

Thursday, July 19, 2007

Nonfasting Triglycerides and Risk of Myocardial Infarction, Ischemic Heart Disease, and Death in Men and Women

Børge G. Nordestgaard, MD, DMSc; Marianne Benn, MD, PhD; Peter Schnohr, MD; Anne Tybjærg-Hansen, MD, DMSc

JAMA. 2007;298:299-308.

Context Elevated nonfasting triglycerides indicate the presence of remnant lipoproteins, which may promote atherosclerosis.

Objective To test the hypothesis that very high levels of nonfasting triglycerides predict myocardial infarction (MI), ischemic heart disease (IHD), and death.

Design, Setting, and Participants A prospective cohort study of 7587 women and 6394 men from the general population of Copenhagen, Denmark, aged 20 to 93 years, followed up from baseline (1976-1978) until 2004.

Main Outcome Measures Hazard ratios (HRs) for incident MI, IHD, and total death according to baseline nonfasting triglyceride level categories of 1 to 1.99 mmol/L (88.5-176.1 mg/dL), 2 to 2.99 mmol/L (177.0-264.6 mg/dL), 3 to 3.99 mmol/L (265.5-353.0 mg/dL), 4 to 4.99 mmol/L (354.0-441.6 mg/dL), and 5 mmol/L or more (442.5 mg/dL) vs triglyceride levels of less than 1 mmol/L (<88.5 mg/dL).

Results With increasing levels of nonfasting triglycerides, levels of remnant lipoprotein cholesterol increased. During a mean follow-up of 26 years, 1793 participants (691 women and 1102 men) developed MI, 3479 (1567 women and 1912 men) developed IHD, and 7818 (3731 women and 4087 men) died. For MI, among women, the age-adjusted HRs and multifactorially adjusted HRs (aHRs) for each respective category per 1-mmol/L increase in nonfasting triglyceride levels were 2.2 (aHR, 1.7), 4.4 (aHR, 2.5), 3.9 (aHR, 2.1), 5.1 (aHR, 2.4), and 16.8 (aHR, 5.4); for both, P for trend < .001. For MI, among men, the values were 1.6 (aHR, 1.4), 2.3 (aHR, 1.6), 3.6 (aHR, 2.3), 3.3 (aHR, 1.9), and 4.6 (aHR, 2.4); for both, P for trend < .001. For IHD, among women, the values were 1.7 (aHR, 1.4), 2.8 (aHR, 1.8), 3.0 (aHR, 1.8), 2.1 (aHR, 1.2), and 5.9 (aHR, 2.6); for both, P for trend < .001. For IHD, among men, the values were 1.3 (aHR, 1.1), 1.7 (aHR, 1.3), 2.1 (aHR, 1.3), 2.0 (aHR, 1.2), and 2.9 (aHR, 1.5); P for trend < .001 for age-adjusted and P for trend = .03 for multifactorially adjusted. For total death, among women, the values were 1.3 (aHR, 1.3), 1.7 (aHR, 1.6), 2.2 (aHR, 2.2), 2.2 (aHR, 1.9), and 4.3 (aHR, 3.3); for both, P for trend < .001. For total death, among men, the values were 1.3 (aHR, 1.2), 1.4 (aHR, 1.4), 1.7 (aHR, 1.5), 1.8 (aHR, 1.6), and 2.0 (aHR, 1.8); for both, P for trend < .001.

Conclusion In this general population cohort, elevated nonfasting triglyceride levels were associated with increased risk of MI, IHD, and death in men and women.
Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks

Cochrane Database of Systematic Reviews 2007 Issue 3 (Status: New) Copyright © 2007 The Cochrane Collaboration.

This version first published online: 18 July 2007 in Issue 3,

This record should be cited as: Aguilar MI, Hart R, Pearce LA.


Non-valvular atrial fibrillation (AF) carries an increased risk of stroke mediated by embolism of stasis-precipitated thrombi originating in the left atrial appendage. Both oral anticoagulants and antiplatelet agents have proven effective for stroke prevention in most patients at high risk for vascular events, but primary stroke prevention in patients with non-valvular AF potentially merits separate consideration because of the suspected cardio-embolic mechanism of most strokes in AF patients.

To characterize the relative effect of long-term oral anticoagulant treatment compared with antiplatelet therapy on major vascular events in patients with non-valvular AF and no history of stroke or transient ischemic attack (TIA).

Search strategy
We searched the Cochrane Stroke Group Trials Register (June 2006). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2006) and EMBASE (1980 to June 2006). We contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials.

Selection criteria
All unconfounded, randomized trials in which long-term (more than four weeks) adjusted-dose oral anticoagulant treatment was compared with antiplatelet therapy in patients with chronic non-valvular AF.

Data collection and analysis
Two review authors independently selected trials for inclusion, assessed quality and extracted data. The Peto method was used for combining odds ratios after assessing for heterogeneity.

Main results
Eight randomized trials, including 9598 patients, tested adjusted-dose warfarin versus aspirin (in dosages ranging from 75 to 325 mg/day) in AF patients without prior stroke or TIA. The mean overall follow up was 1.9 years/participant. Oral anticoagulants were associated with lower risk of all stroke (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.54 to 0.85), ischemic stroke (OR 0.53, 95% CI 0.41 to 0.68) and systemic emboli (OR 0.48, 95% CI 0.25 to 0.90). All disabling or fatal strokes (OR 0.71, 95% CI 0.59 to 1.04) and myocardial infarction (OR 0.69, 95% CI 0.47 to 1.01) were substantially but not significantly reduced by oral anticoagulants. Vascular death (OR 0.93, 95% CI 0.75 to 1.15) and all cause mortality (OR 0.99, 95% CI 0.83 to 1.18), were similar with these treatments. Intracranial hemorrhages (OR 1.98, 95% CI 1.20 to 3.28) were increased by oral anticoagulant therapy.

Authors' conclusions
Adjusted-dose warfarin and related oral anticoagulants reduce stroke, disabling stroke and other major vascular events for those with non-valvular AF by about one third when compared with antiplatelet therapy.

Plain language summary
Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacksAtrial fibrillation (AF) is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the bloodstream to the brain and cause a stroke. Drugs that slow clotting, such as oral anticoagulants (warfarin and other coumarin derivates) and antiplatelet agents (aspirin and others), reduce the risk of stroke in patients with atrial fibrillation. In this review of eight randomized trials, including 9598 patients, oral anticoagulants are shown to reduce the risk of stroke in patients with non-valvular AF and with no prior stroke or transient ischemic attack by one-third when compared with antiplatelet agents alone. Antiplatelet agents reduce stroke by about 20% in AF patients compared with no therapy, offering a less efficacious therapeutic option for those deemed not eligible for anticoagulation therapy. The threshold of absolute benefit that warrants anticoagulation remains controversial and depends on patient's preferences and availability of optimal anticoagulation monitoring.

Peripheral Arterial Disease: Adding Warfarin to Antiplatelet Therapy Only Increases Bleeding Risk

Peripheral Arterial Disease: Adding Warfarin to Antiplatelet Therapy Only Increases Bleeding Risk

The addition of anticoagulants to antiplatelet therapy does not improve outcomes in peripheral arterial disease and significantly increases the risk for life-threatening bleeding, according to a study in the current New England Journal of Medicine.

In the international WAVE trial, researchers randomized some 2100 patients with peripheral arterial disease either to antiplatelet therapy alone or to combination therapy with anticoagulants. After 35 months of follow-up, there were no significant differences between the groups in MI, stroke, severe peripheral or coronary ischemia, or death from cardiovascular causes.

Life-threatening bleeding, and in fact bleeding of any severity, was significantly higher with combination therapy.

Writing in Journal Watch General Medicine, Allan S. Brett comments that although combination therapy in peripheral arterial disease is no longer in general use, "patients with PAD sometimes receive warfarin for other reasons and are continued on that drug even after the non-PAD indication disappears; this study strongly suggests that such patients would be better off taking aspirin alone."


NEJM article (Free abstract; full text requires subscription)

Related Journal Watch link(s):

Journal Watch General Medicine summary (Free)Journal Watch Cardiology summary (Free)

Wednesday, July 18, 2007

Nonfasting Trigylceride Levels and Risk for Heart Disease

Nonfasting Trigylceride Levels Seem Better at Defining Risk for Heart Disease

Two studies measuring triglycerides in the nonfasting state show a strong association between elevated levels and risk for cardiovascular disease or death. Both appear in today's JAMA.

One study, using a population sample from Copenhagen, followed nearly 14,000 men and women for an average of 26 years. Researchers found that the risk for MI, ischemic heart disease, or death increased with increasing levels of nonfasting triglycerides, especially among women.

Another study, performed within the Women's Health Initiative, followed some 26,500 women for a median of 11 years and compared the effects of fasting versus nonfasting triglycerides on risk for cardiovascular events. When measured in the nonfasting state (especially 2 to 4 hours postprandially), triglyceride levels showed a strong, independent association with future risk, which persisted in fully adjusted analyses. Fasting levels, according to the authors, "showed little independent association with cardiovascular events."

According to an editorialist, the results "suggest that using 2- to 4-hour postprandial triglyceride measurements may be more predictive [of risk] than LDL-C."


JAMA article on risk in Copenhagen population (Free abstract; full text requires subscription)

JAMA article on risk in Women's Health Initiative participants (Free abstract; full text requires subscription)

JAMA editorial (Subscription required)

Monday, July 16, 2007

For Diabetes Drugs, Old and Cheap Are Good

Wall Street Journal

For Diabetes Drugs, Old and Cheap Are Good

Old, cheap diabetes drugs — especially a generic called metforminare as good as or better than newer, more expensive drugs at lowering blood sugar. And for the most part the older drugs don’t carry more serious side effects than the newer ones, according to a [1] review of more than 200 studies.

The analysis, funded by the federal government, looked at oral medicines given to patients with type-2 diabetes.

The finding, published today in the Annals of Internal Medicine, is consistent with [2] recommendations from the American Diabetes Association and other groups that call for starting patients on metformin before trying other drugs. When metformin alone doesn’t work, it’s often prescribed in combination with other medicines.

Metformin, also sold under the brand name Glucophage, costs about $100 per year, and “looks to be the safest” of the drugs, the study’s lead author [3] told the Associated Press.

But it does carry a rare side effect called lactic acidosis, and isn’t recommended for patients with heart failure or moderate kidney disease.

Also reviewed in the study was an old class of drugs called sulfonylureas and several newer classes, including TZDs, the class that includes GlaxoSmithKline’s Avandia.

Avandia Bonus: The FDA is waiving conflict-of-interest rules to allow several physicians to sit on an advisory committee meeting later this month, Bloomberg [4] reports. The committee will discuss the possible [5] heart-attack risk associated with Avandia, and could recommend anything from waiting for more data to removing the drug from the market. Many top academic physicians have financial connections to the pharmaceutical industry, and the FDA often waives conflict of interest rules for its advisory committees. But the practice has been attacked by some who claim that the agency is too cozy with the drug industry.

Women more depressed after heart attack

ACC - Cardiosource

CV News Digest – What Your Patients Are Reading

Women more depressed after heart attack

EDMONTON, Alberta, July 14 (UPI) -- Women are more likely than men to have lingering depression after suffering heart attacks, Canadian researchers said.

A study by the University of Alberta and McGill University found that 14.3 percent of women had worsening depression one year after their initial myocardial infarctions. Eleven percent of men studied had a similar experience.

Results of the study were published in the European Journal of Cardiovascular Nursing.

"The findings are of concern because depression impedes recovery and ultimately, the quality of life in patients following a heart event," said lead author Colleen Norris, an associate professor in the Faculty of Nursing at the University of Alberta in Edmonton, said Friday in a release.

Norris said women are less likely to be referred to or to attend cardiac rehabilitation, and therefore don't have access to the support and assistance to make necessary lifestyle changes

Saturday, July 14, 2007

Criteria of metabolic syndrome in children and adolescentscriteria

Criteria of metabolic syndrome in children and adolescents

International Diabetes Federation IDF - criteria

Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction -- Sorajja et al. 28 (14): 1709 -- European Heart Journal

Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction --

Sorajja et al. 28 (14): 1709 -- European Heart Journal

Aims: We sought to investigate the impact of multivessel coronary artery disease (CAD) on reperfusion success and prognosis following primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). The influence of multivessel disease on myocardial reperfusion and subsequent survival after primary PCI has not been studied.

Conclusion: Patients with extensive CAD in vessels remote from the infarct-related artery have reduced reperfusion success and an adverse prognosis following primary PCI in AMI. Future studies regarding the optimal treatment of patients with multivessel disease and AMI are warranted.

Friday, July 13, 2007

High Blood Pressure May Mask Potentially Deadly Heart Condition - Correlation Between Hypertension And Chest Pain, May Help Explain Silent Ischemia

Medical News Today News Article

High Blood Pressure May Mask Potentially Deadly Heart Condition - Correlation Between Hypertension And Chest Pain, May Help Explain Silent Ischemia

New research published in Psychophysiology finds a relationship between increased blood pressure and decreased pain perception in a variety of circumstances, including among individuals with heart disease. This phenomenon extends to those who typically suffer chest pain during exercise, and may be correlated with a potentially deadly heart condition.

The new study draws on data collected from over 900 patients undergoing exercise stress testing to diagnose possible myocardial ischemia (MI), a condition where oxygenated blood is prevented from reaching the heart because an artery has become blocked or constricted.

Generally, exercise should produce pain in these situations; however some patients experience "silent" cases of MI in which no pain is felt. Previous studies have suggested that high blood pressure and silent ischemia may be correlated, and this new research provides further validation.

"This has implications for several areas, such as the effects of stress, non-adherence to treatment and silent myocardial ischemia," says Bianca D'Antono, author of the study. "Further research will be needed to better understand the relationship between blood pressure, pain perception and heart disease."

Psychophysiology is the oldest, first, and most established journal in its field. This prestigious international journal plays a key role in advancing psychophysiological science and human neuroscience, covering research on the interrelationships between the physiological and psychological aspects of brain and behavior

Many Activities And Events, From Waking Up To Earthquakes, Can Trigger Heart Attacks, Strokes, And Cardiac Arrests

Medical News Today News Article

Many Activities And Events, From Waking Up To Earthquakes, Can Trigger Heart Attacks, Strokes, And Cardiac Arrests

Heart attacks, strokes, and cardiac arrests seem like they come out of the blue, but most don't. They usually appear after cholesterol-rich plaque has festered in the arteries that nourish the heart and brain. So what makes one happen at a particular time? A trigger, reports the July 2007 issue of the Harvard Heart Letter.

Important triggers include:

Waking from sleep. Before you wake up, your body trickles stress hormones into the bloodstream. This helps you get up, but also slightly stresses the heart. That, along with dehydration that occurs overnight and the overnight fade in protection from heart medicines, may explain why heart attacks are most common in the morning.

Heavy physical exertion. Shoveling snow, running, and other strenuous activities can be triggers. But don't be afraid to exercise exertion is much less likely to cause trouble in people who exercise regularly.

Anger. A bout of anger can increase the chances of having a heart attack up to 14-fold during the following two hours.

Infections. Pneumonia, flu, and other infections can be potent triggers for heart attacks and strokes.

Other triggers include sexual activity, overeating, severe hot or cold weather, air pollution, natural disasters, drug use, grief, and lack of sleep.

Of course, most people with heart disease get out of bed in the morning, shovel snow, make love, get angry, and suffer through the flu just fine. Still, knowing what sets off heart attacks, strokes, or cardiac arrests can help you avoid triggers or blunt their power, says the Harvard Heart Letter.

Harvard Health PublicationsHarvard Medical School 10 Shattuck St., Ste. 612Cambridge, MA 02115United States

Thursday, July 12, 2007

Beta-Blockers and Coronary Artery Disease

Beta-Blockers Slow, Even Reverse Coronary Artery Disease

Cleveland Clinic Study Shows - 12 Jul 2007

A Cleveland Clinic study is reporting that beta-blockers, a class of drugs used to lower blood pressure and prevent symptoms in a variety of heart conditions, can slow progression and can even induce regression of coronary artery disease.

The study appears in the July 3, 2007, issue of the Annals of Internal Medicine and suggests that all patients with coronary disease can benefit from this class of agents.

Coronary artery disease or clogging of vessels supplying the heart is one of the most common causes of death in the United States and other developed countries. Currently, more than 15 million Americans have coronary artery disease.

Researchers aimed to identify whether beta-blockers have any effect on progression of coronary disease in a group of more than 1,500 patients with this disease.

They began by measuring the amount of fatty plaque found in the arteries of these patients, using high-resolution intravascular ultrasound.

This required the insertion of tiny ultrasonic transducers in the coronary arteries to provide a baseline examination. Subsequently, the ultrasound examination was repeated after 18 to 24 months and the progression rate of coronary disease was compared in patients who were treated with beta-blockers and those who were not treated with these agents.

The researchers found that patients treated with beta-blockers had a significant reduction in the amount of fatty plaque at the follow-up examination, whereas those not on a beta-blocker experienced no change in the amount of plaque. "Our results have important implications," said Ilke Sipahi, M.D., F.A.C.C., a Cardiologist at the Cleveland Clinic and the study's lead author. "Up to now, we thought that beta-blockers were beneficial only to preserve heart muscle function in patients with a previous injury to their heart due to a heart attack. Now we learn that these drugs also have favorable effects on the coronary arteries by reducing clogging of these vessels in a similar fashion to cholesterol-lowering statin drugs. Our results indicate that all patients with coronary disease, such as those with coronary stents, previous bypass surgery and even patients with earlier stages of coronary artery disease can benefit from treatment with beta-blockers."

Wednesday, July 11, 2007

PCI benefits over fibrinolysis found in diabetic patients

MedWire News - Cardiology - PCI benefits over fibrinolysis found in diabetic patients

PCI benefits over fibrinolysis found in diabetic patients

11 July 2007

Arch Intern Med 2007; 167: 1353-1359

MedWire News: The beneficial effects of primary percutaneous coronary intervention (PCI) over reperfusion therapy in diabetic patients with ST-segment elevation myocardial infarction (STEMI) are consistent with those for non-diabetic patients, meta-analysis findings indicate.

Writing in the Archives of Internal Medicine, Jan Paul Ottervanger (Isala Klinieken, Zwolle, The Netherlands) and colleagues note that an increasing amount of evidence indicates that primary PCI improves outcomes of STEMI compared with fibrinolysis in the general population. But effects of both reperfusion and fibrinolysis may differ in diabetic patients, they say, and previous trials comparing the strategies in diabetic patients have produced conflicting data.

"In our analysis including a large number of patients, it was more clearly demonstrated that primary PCI is associated with improved survival after 30 days in both patients with and without diabetes," the team reports.

The researchers analyzed data from 19 trials that compared primary PCI with fibrinolysis for STEMI in a total of 6315 patients, 877 (14%) of whom had diabetes.

At 30 days, 401 (6.3%) patients had died. Mortality was significantly higher in patients with than without diabetes (9.4% vs 5.9%, p<0.001).

Primary PCI was associated with lower mortality than fibrinolysis in both non-diabetic patients (4.8% vs 6.9%, unadjusted odds ratio [OR]=0.69; p=0.001) and diabetic patients (6.6% vs 12.4%, OR=0.49; p=0.001).

Recurrent MI and stroke were also less common with PCI in patients with and without diabetes, with corresponding ORs of 0.33 and 0.60, and 0.58 and 0.40.

After adjusting for potential confounders, including age, gender, time to randomization, treatment delay, systolic blood pressure, anterior MI, previous MI, heart rate, and randomized treatment, primary PCI was independently associated with reduced 30-day survival (OR=0.64). This association held true in patients with diabetes (OR=0.50) and without diabetes (OR=0.68).

The authors note that these point estimates indicate a greater benefit of PCI in diabetic patients, in whom the absolute risk is higher than in non-diabetic patients.

"This observation may be the result of delay in initiation of therapy and longer ischemic time in diabetic patients, which may be related in part to atypical symptoms," they write. "In particular, thrombolytic therapy seems to be negatively influenced by longer time to initiation of therapy."

They add that impairment of microvascular flow after fibrinolysis in diabetic patients could also contribute to a more favorable effect with PCI.

"Wider application of timely primary PCI could be an important strategy to improve outcomes in the high-risk population of diabetic patients," Timmer and co-authors conclude.

Free abstract

HRT and Cardiac Risk - Debate

Medical News Today News Article

Wall Street Journal Examines Women's Health Initiative Findings On HRT's Effect On Heart Attack Risk

11 Jul 2007

The Wall Street Journal on Monday examined findings from the 15-year, $725 million NIH-sponsored Women's Health Initiative on hormone replacement therapy's effects on heart attack risk. According to the Journal, in the five years since the study was released, many in the medical community have said "some aspects" of the initial findings "were either misleading" or "overgeneralized in large part because they excluded many of the study's own investigators and physicians from the first review" (Parker-Pope, Wall Street Journal, 7/9).

NIH researchers in July 2002 ended the WHI study on combination HRT three years early because they determined that the treatment might increase the risk for heart disease, invasive breast cancer and other health problems. A later WHI analysis, published in the April 4 issue of the Journal of the American Medical Association, found that HRT use among women in their 50s does not increase their risk for heart attack (Kaiser Daily Women's Health Policy Report, 4/4).

In addition, a study published last month in the New England Journal of Medicine found that women in their 50s who took estrogen on a regular basis were 60% less likely than those who took a placebo to have large amounts of plaque in their arteries, an indicator of heart attack risk. Participants who took estrogen were 30% to 40% less likely than those who took a placebo to have large amounts of plaque in their arteries. However, participants who took estrogen had a higher risk for stroke than those who took a placebo, according to the study (Kaiser Daily Women's Health Policy Report, 6/22).

According to the Journal, the WHI's 40 researchers in 2002 were told 11 days before the initial WHI study report in JAMA was released that it had been halted early. Although some of them were concerned that the results were "too broadly interpreted," it was "too late to make meaningful changes" to the JAMA article, the Journal reports. Two ongoing studies are examining the role of estrogen in the development of heart disease, the Journal reports. Both studies also will examine whether using natural progesterone, instead of synthetic progestin used in WHI, reduces or eliminates breast cancer risk.


Jacques Rossouw, a physician with the National Heart Lung and Blood Institute who had overseen the WHI since its inception, said it was an "NIH decision supported by the WHI executive committee to keep it to a small group because we realized it was a sensitive paper." He said that the handling of the study's results was "based on what we knew at the time," adding, "Our main job ... was to turn around the prevailing notion that hormones would be useful for a long-term prevention of heart disease." It was a "worthy objective, which we achieved," Rossouw said.

Robert Langer -- former principal investigator for WHI's clinical center at the University of California-San Diego, who has since spoken as a witness for HRT maker Wyeth -- said, "I think that had the initial report been written by a broader group, as almost all of our later papers have been, it would have been framed differently."

According to the Journal, key questions about long-term use of HRT are "far from resolved." Most experts agree that HRT is a reasonable option for women to treat menopausal symptoms, but the "bigger question" is whether the drugs should be used to prevent heart-related conditions, the Journal reports. NHLBI says that HRT should not be used to prevent heart disease because of its potential to increase risk for breast cancer, blood clots and strokes. According to the health care information company IMS Health, HRT sales have declined 30% since the WHI results were published in 2002 (Wall Street Journal, 7/9).

Atrial Fibrilation / Atrial Ablation / Debate

Medical News Today News Article

Debate Over Atrial Ablation Highlights Challenges Posed By Costly Experimental Procedures

11 Jul 2007

An experimental treatment for atrial fibrillation known as ablation, which costs between $25,000 and $50,000, "stands out as another potentially budget-straining medical commitment" for health care payers including the federal government, the New York Times reports. Medicare and private insurers spend billions of dollars per year to treat atrial fibrillation -- which affects at least 2.2 million U.S. residents -- primarily on hospitalizations, tests and off-label prescription drugs.

Atrial ablation involves neutralizing portions of the heart muscle that are the sources of abnormal electrical pulses that set off irregular heart beats. The original atrial ablation procedure included the use of surgical tools, but most of the procedures now are minimally invasive and involve the burning or freezing of heart muscle. Because the procedure has not been approved by FDA, doctors either use experimental equipment or equipment that has been approved for other uses.

Doctors and hospitals can bill Medicare or private insurers using codes for "somewhat similar" procedures, but they say the reimbursements "usually fall far short of full compensation for atrial ablation, which can take four hours or more to perform and requires an overnight stay at the hospital," the Times reports. As a result, the procedures usually are performed at teaching hospitals and other centers where doctors are paid a salary, as well as by some specialty practices.

Debate Over Merits

Advocates for the procedure say that it is more cost-effective over the long run than prescription drugs and improves patient outcomes, but some regulators and doctors say that clinical trials examining the procedure were poorly designed, that the "cure" rate touted by supporters possibly is being exaggerated and that the risks are being minimized. Full-scale clinical trials have not yet demonstrated long-term benefits of minimally invasive atrial ablation, although less-rigorous studies have produced promising results.

Daniel Schultz, head of FDA's Center for Devices and Radiological Health, said, "This is one of those areas where the practice of medicine has moved faster than the approval process," adding, "This is very high on our list of areas that need concerted attention." Schultz said that FDA soon will schedule a public meeting to discuss drugs and devices that are used off-label as treatments for atrial fibrillation.

Carolyn Clancy, director of the Agency for Healthcare Research and Quality, said that any situation where off-label therapies become widespread "spotlights where we lack good evidence of which patients can benefit from which therapies." Clancy said that gathering information on atrial fibrillation is particularly challenging because the severity of the condition varies greatly among patients, most of whom also have other conditions that affect the risks and benefits of competing procedures.

The American Heart Association, the American College of Cardiology and four other major U.S. and European doctors' groups last month recommended that atrial ablation become the standard treatment for patients who do not respond to drugs (Feder [1], New York Times, 7/7).
Additional Coverage

The Times on Saturday also examined how doctors once viewed atrial fibrillation as "relatively benign" but have come to recognize that the condition "allows blood to pool in the atria and form clots, which in turn may explain why such patients are prone to strokes and heart attacks" (Feder [2], New York Times, 7/7).

Another Times article profiles the history of treatments for atrial fibrillation (Feder [3], New York Times, 7/7).
The Times also published FAQ about the condition (New York Times, 7/7).

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