Monday, December 31, 2007
Inhibitors of the Renin Angiotensin System: Proven Benefits, Unproven Safety -- Parfrey 148 (1): 76 -- Annals of Internal Medicine
Saturday, December 29, 2007
24 December 2007
MedWire News: An increase in systolic blood pressure (SBP) during exercise stress testing appears to be associated with improved survival in men, researchers report.
Data suggest that exercise-induced increases in SBP are prognostic for cardiovascular (CV) mortality, independent of age, resting blood pressure, and common cardiac risk factors.
To determine whether SPB measured during exercise stress testing adds prognostic information to CV mortality, Manish Gupta, from Lenox Hill Hospital in New York City, USA, and colleagues evaluated SBP responses in 6213 consecutive men referred for exercise stress testing for clinical reasons.
Patients were grouped according to whether their median change in exercise induced SPB was ≤43 mmHg or ≥44 mmHg, representing low and normal increases in SPB, respectively.
The results demonstrated that patients with increases in baseline SBP ≥44 mmHg had significantly lower mortality than patients with increases in baseline SBP ≤43 mmHg, at 8.2% versus 13.7%, respectively. This difference in improved survival remained after controlling for age, exercise capacity, ST abnormalities, history of myocardial infarction or congestive heart failure, hypertension, and use of a beta blocker.
The researchers also found that the survival benefit was incremental, with patients in the highest quartile of increased SBP (≥76 mmHg) having significantly lower CV mortality than patients in the lowest quartile (≤42 mmHg), at 7.3% versus 16.7%, respectively. Importantly, a history of hypertension was independently and significantly associated with a higher SPB response to exercise.
The team concludes in the American Journal of Cardiology that an increase in SPB with exercise stress test predicts cardiovascular mortality independent of age, exercise capacity, and ST-segment abnormalities.
They add that "an increase in systolic BP≥ 44 mmHg from baseline [is] associated with survival even in patients with a history of hypertension," and emphasize that the findings are applicable only to men because exercise testing results have been shown to differ between genders.
Source: Am J Cardiol 2007; 100: 1609-1613
Friday, December 28, 2007
The Lancet, Current Issue, Volume 370, Number 9605, 22 December 2007
A truffle treatment for atherosclerosis is the stuff that chocolate manufacturers (and patients) dream of. But how close is such a scenario to reality? Last month, a study in Circulation showed that dark chocolate that is rich in flavanols induced coronary vasodilatation and improved coronary vascular function in 11 heart-transplant recipients compared with patients taking a cocoa-free control chocolate. Other studies have also suggested that dark chocolate has cardiovascular benefits. A recent small randomised trial showed that people who were prehypertensive or had early-stage hypertension could lower their blood pressure by eating small amounts of dark chocolate as part of their usual diet.
Great news if you happen to be a lover of dark chocolate. However, if your passion is white or milk chocolate, bad luck. Research has shown that this type of chocolate, which is often devoid of flavanols, offers no health benefit. But there is a catch for dark-chocolate fans too. Dark chocolate can be deceptive. When chocolate manufacturers make confectionary, the natural cocoa solids can be darkened and the flavanols, which are bitter, removed, so even a dark-looking chocolate can have no flavanol. Consumers are also kept in the dark about the flavanol content of chocolate because manufacturers rarely label their products with this information.
And, although flavanols, if they are present, seem to offer some health benefit, the devil in the dark chocolate is the fat, sugar, and calories it also contains. To gain any health benefit, those who eat a moderate amount of flavanol-rich dark chocolate will have to balance the calories by reducing their intake of other foods—a tricky job for even the most ardent calorie counter. So, with the holiday season upon us, it might be worth getting familiar with the calories in a bar of dark chocolate versus a mince pie and having a calculator at hand. Of course some would say that, in terms of food intake, the best and simplest health message would be to stay away from the chocolate and eat a healthy, balanced diet, low in sugar, salt, and fat, and full of fresh fruit and vegetables. We say: “Bah, humbug to that. Pass the chocolates.”
DALLAS, Dec. 20 – Several new studies on genetics and stem cell research, along with studies that continue to debate the use of stents to clear coronary artery blockages, are among the top research advances in heart disease and stroke for 2007, said Daniel W. Jones, M.D., president of the American Heart Association.
Other major milestones include a study that may change how lives are saved using a new method of cardiopulmonary resuscitation.
The American Heart Association in 1996 began compiling an annual list of the top 10 major advances in heart disease and stroke research and continues to highlight influential research annually.
Achievements in 2007 include:
1. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Genome wide association studies identify genes (strands of DNA) that may cause specific diseases and represent a powerful approach in identifying genes involved in common human diseases. This large-scale genome-wide association (GWA) study found consistent and replicable genetic markers of several complex diseases of adulthood, including atherosclerotic heart disease. Study authors said their analysis of some 17,000 people for seven common familial diseases (bipolar disorder, coronary artery disease, Crohn’s disease, hypertension, rheumatoid arthritis, type 1 diabetes and type 2 diabetes) confirms previously identified loci (DNA closely linked to genes that may identify a trait of a particular disease) and provides strong evidence for many novel disease susceptibility genes.
Source: Nature,June 7, 2007; Nature 2007. 447:661-78;www.nature.com.
Funding: Wellcome Trust was the principal funding source of this study.
2. Genomewide association analysis of coronary artery disease
This study included a joint analysis of two genomewide association studies of coronary artery disease. Researchers used the genetic patterns of the persons (cases) with coronary artery disease (CAD) from the Wellcome Trust Case Control Consortium study (described above) and tried to replicate the genetic patterning for CAD in another genomewide association study - the German MI [Myocardial Infarction] Family Study. Results identified several genetic loci that, individually and in aggregate, substantially affect the risk of developing coronary artery disease.
Source: New EnglandJournal of Medicine, Aug. 2, 2007; N Engl J Med 2007. 357:443-453; www.nejm.org.
Funding: Grants from the Wellcome Trust, the National Genome Research Network 2 of the German Federal Ministry of Education and Research and the Cardiogenics project of the European Union supported this study.
3. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-Kanto): an observational study
This work represents the first meaningful chance to improve cardiopulmonary resuscitation (CPR) in more than 50 years. Results indicate chest compression-only resuscitation by bystanders may be the preferable approach to resuscitation for adult patients with witnessed out-of-hospital cardiac arrest, especially those with apnea, shockable rhythm or short periods of untreated arrest.
Source: The Lancet, March 17, 2007. The Lancet 2007; 369:920-926; www.thelancet.com.
Funding: Grants from the Laerdal Foundation of Acute Medicine, Norway and the Ministry for Health, Labour and Welfare, Japan supported this study.
4. Implementation of a statewide system for coronary reperfusion
This study found that a statewide program focused on regional systems for quickly treating ST-elevation myocardial infarctions (STEMI – heart attacks in which the coronary artery is completely blocked) can significantly improve quality of care. The research sets the stage for collaborative, non-competitive care for patients of a region, expanding door-to-balloon initiatives into the community for a systems approach. The American Heart Association’s Mission: Lifeline program, created to establish systems to provide emergency care for STEMI patients, promotes this strategy for improving patient care.
Source: Journal of the American Medical Association, Nov. 28, 2007; JAMA 2007; 298(20);2371-23809; www.jama.org. This study was also presented at the American Heart Association Scientific Sessions 2007.
Funding: Blue Cross and Blue Shield of North Carolina supported this study.
5. Long-term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP)
This is the first major trial to document that a reduced sodium intake lowers the risk of clinical cardiovascular disease outcomes, not just blood pressure.
Sources: British Medical Journal, April 20, 2007; BMJ 2007;334;885; www.bjm.com.
Funding: The National Heart, Lung and Blood Institute, National Institutes of Health supported this study.
6. Optimal medical therapy with or without PCI for stable coronary artery disease (COURAGE)
This study compared the initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) vs. optimal medical therapy alone in reducing the risk of cardiovascular events. The authors concluded that, as an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction or other major cardiovascular events when added to optimal medical therapy.
Source: New England Journal of Medicine, April 12, 2007; N Engl J Med 2007; 35;(15);1503-16; www.nejm.org.
Funding: The U.S. Department of Veterans Affairs Office of Research and Development provided support for this study.
7. Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells
This study analyzed the complex functional properties of cardiomyocytes (heart muscle cells) derived from maGSCs in vitro and the behavior of undifferentiated maGSCs in normal hearts of mice in vivo after transplantation. The authors conclude that maGSCs provide a new source of distinct types of cardiomyocytes for basic research/potential therapeutic application.
Source: Circulation Research,June 8, 2007; Circ Res. 07 Jun 8;100(11):1615-25; www.ahajournals.org.
Funding: A grant from the Georg-August-University of Go¨ttingen supported this study.
8. HORIZONS: Harmonizing Outcomes with RevascularIZatiON and Stents
This large study examined the safety and effectiveness of anticoagulation medications and drug-eluting stents in patients experiencing a STEMI heart attack, in which the coronary artery is completely blocked, without significantly increasing the rate of death or recurrent heart attacks among these patients.
Source: Late-breaking trial at the Transcatheter Cardiovascular Therapeutics TCT 2007; www.tct2007.com. Funding: The Cardiovascular Research Foundation supported this study.
9. Effectiveness and safety of drug-eluting stents in Ontario
This large Canadian study found that drug-eluting stents are effective in reducing the need for target-vessel coronary artery bypass in patients at the highest risk for re-narrowing of previously blocked arteries, without a significantly increased rate of death or heart attack.
Source: New England Journal of Medicine, Oct. 7, 2007; N Eng J Med 2007; 14;357:1393-1402; www.nejm.org.
Funding: The Ontario Ministry of Health and Long-Term Care to the Program for Assessment of Technology in Health, the CCN of Ontario and the Institute for Clinical Evaluative Sciences supported this study in part.
10. Underdiagnosis of Hypertension in Children and Adolescents
This study of more than 14,000 children found that hypertension and prehypertension were often undiagnosed in the pediatric population. Patient age, height, obesity-related diagnoses, and magnitude and frequency of abnormal blood pressure readings all increased the odds of hypertension.
Sources: Journal of the American Medical Association, Aug. 22, 2007; JAMA 2007; 298(8):874 – 879; www.jama.org.
Funding: This research did not receive funding support.
Statements and conclusions of study authors are solely
BOSTON, Dec. 27 -- Regular use of even low-dose aspirin may interfere with androgen suppression therapy for men with prostate cancer.
Men who used baby aspirin were significantly more likely to have abnormal liver function test results (P=0.02) among men in a study of the antiandrogen flutamide (Eulexin), reported Anthony V. D'Amico, M.D., Ph.D., of the Dana-Farber Cancer Institute here, and colleagues.
Abnormal liver function test results led to premature discontinuation of flutamide in 37% of aspirin users but only 16% of non-users, they said in a letter to the editors published in the Dec. 27 issue of the New England Journal of Medicine.
Oncologists, in collaboration with the patient's cardiologist, need to decide whether he should come off aspirin during hormonal therapy or whether the cardiovascular risk is great enough to forego hormonal therapy if liver function drops, Dr. D'Amico said, especially in view of evidence that antiandrogen therapy may increase heart attack risk.
"It's a trade off," he said. "It's going to have to be decided on an individual basis."
The finding may also have implications for oncologists beyond cautioning about drug-drug interactions, said Philip W. Kantoff, M.D., of Dana-Farber, a co-author of the letter.
"From a prostate cancer standpoint," he said, "this finding raises the potential value of more complete androgen blockade being of great importance in treating early prostate cancer."
In previous studies of high-dose aspirin use for rheumatoid arthritis or osteoarthritis, abnormal liver function tests have been reported in 5% of patients. And an animal study suggested that low testosterone levels contribute to slow metabolism of aspirin.
"In men with prostate cancer," they said, this effect "could have clinical importance because the antiandrogen component of hormone therapy is discontinued when liver function tests become abnormal."
So they retrospectively analyzed the impact of low-dose aspirin in a prospective, randomized controlled trial of radiation therapy with or without at least six months of a luteinizing hormone-releasing hormone agonist and flutamide.
The study included 206 patients with clinically localized prostate cancer and a PSA of at least 10 ng/mL, a Gleason score of at least seven, or radiographic evidence of extraprostatic disease.
The primary outcomes, published in the Journal of the American Medical Association in 2004, showed increased five-year survival (88% versus 78%, P=0.04) and decreased prostate cancer-specific mortality (P=0.02) with the addition of androgen suppression therapy.
Among the other findings of the current report at 7.6 years of follow-up, men who completed six months on a luteinizing hormone-releasing hormone agonist but stopped flutamide early were at 3.50 times higher relative risk of death (95% confidence interval: 1.03 to 11.80, P=0.04) than those who completed six months of both.
Radiation therapy alone was associated with 6.10-fold risk (95% CI: 2.30 to 16.20, P<0.001) compared with radiation therapy plus six months of hormone therapy.
Whereas men who used baby aspirin were more likely to have abnormal liver function test results (P=0.02), those on another common drug, atorvastatin (Lipitor) were not (P=0.13).
"Care givers should be aware of drug-drug interactions when treating cancer patients," Dr. Kantoff concluded, "including the interactions of cancer drugs with [other] prescription and non-prescription drugs, that could decrease the ability to deliver the cancer drug or diminish its effectiveness."
For men who would normally take the occasional aspirin for pain, Dr. D'Amico suggested using non-aspirin painkillers instead during hormonal therapy.
"These medicines don't have the same implications that aspirin appears to have in the setting of hormonal therapy," he said.
Thursday, December 27, 2007
Michiel J. Bos, MD, MSc; Marie Josee E. van Rijn, MD, PhD; Jacqueline C. M. Witteman, PhD; Albert Hofman, MD, PhD; Peter J. Koudstaal, MD, PhD; Monique M. B. Breteler, MD, PhD
Context Transient neurological attacks (TNAs) are attacks with temporary (<24 hours) neurological symptoms. These symptoms can be focal, nonfocal, or a mixture of both. The prognostic significance of TNAs with focal symptoms (better known as transient ischemic attacks [TIAs]) is well understood. Conversely, hardly anything is known about the prognostic significance of TNAs with nonfocal or mixed symptoms.
Objective To study the incidence and prognosis of focal TNAs (or TIAs), nonfocal TNAs, and mixed TNAs.
Design, Setting, and Participants The study population comprised 6062 community-dwelling Rotterdam Study participants who were aged 55 years or older and free from stroke, myocardial infarction, and dementia at baseline (1990-1993). They were followed up for events until January 1, 2005. We analyzed the associations between incident TNAs and subsequent adverse events with age- and sex-adjusted Cox regression models.
Main Outcome Measures Stroke, ischemic heart disease, or dementia.
Results During 60 535 person-years, 548 participants developed TNA (282 focal, 228 nonfocal, and 38 mixed). The incidence rate per 1000 person-years was 4.7 (95% confidence interval [CI], 4.1-5.2) for focal TNA, 3.8 (95% CI, 3.3-4.3) for nonfocal TNA, and 0.6 (95% CI, 0.4-0.9) for mixed TNA. Participants with focal TNA were at higher risk of subsequent stroke than participants without TNA (n = 46 vs 540; hazard ratio [HR], 2.14; 95% confidence interval [CI]; 1.57-2.91) but had an equal risk of ischemic heart disease and dementia. Nonfocal TNA patients were at higher risk of stroke (27 vs 540; HR, 1.56; 95% CI, 1.08-2.28) and dementia (30 vs 552; HR, 1.59; 95% CI, 1.11-2.26) than participants without TNA. Mixed TNA patients were at higher risk of stroke (6 vs 540; HR, 2.48; 95% CI, 1.11-5.56), ischemic heart disease (8 vs 779; HR, 2.26; 95% CI, 1.07-4.78), vascular death (8 vs 594; HR, 2.54; 95% CI, 1.31-4.91), and dementia (7 vs 552; HR, 3.46; 95% CI, 1.72-6.98) than participants without TNA.
Tuesday, December 25, 2007
December 24, 2007
Dallas, TX - The American Heart Association (AHA) has listed several new studies on genetics and stem cell research among its top 10 research advances for 2007. AHA President Dr Daniel Jones told heartwire that this work has been included, "not because it is of immediate clinical applicability but because of the promise it holds, the optimism about these lines of research."
Also highlighted is the much discussed COURAGE study , which found no benefit of percutaneous coronary intervention over optimal medical therapy as an initial management strategy in stable coronary disease, reported at the American College of Cardiology (ACC) meeting in March, and the HORIZONS trial, reported by heartwire at the TCT 2007 meeting, in which bivalirudin proved itself in acute MI patients undergoing primary angioplasty.
Other important inclusions are the first major trial to document that a reduced sodium intake lowers not just blood pressure but the risk of clinical cardiovascular disease outcomes , and a key study on the difficulty of diagnosing hypertension in children and adults .
Jones said the latter "is important to pay attention to, because the problem of hypertension in children and adults is increasing as the epidemic of obesity spreads across the world. This paper nicely points out that diagnosis in children is complex and that even good pediatricians have difficulty with the diagnostic criteria."
Basic research and a simple approach to CPR
Among the basic research singled out by AHA this year are two papers on genome-wide association, the first of which found consistent and replicable genetic markers for several complex diseases of adulthood, including atherosclerotic heart disease . The second was a joint analysis of two genome-wide association studies of coronary artery disease—this confirmed previous work on the location of one region on chromosome 9 linked to a higher risk of MI, and identified two other novel markers associated with CAD .
Also highlighted is research on the generation of functional cardiomyocytes from adult mouse spermatogonial stem cells . Jones told heartwire: "We don't yet have those big clinically applicable breakthroughs [in stem cell research] but we continue to have incremental new knowledge for basic science."
Perhaps as an antidote to the basic science, AHA has also included a study that Jones calls "really important research," on cardiopulmonary resuscitation (CPR) by bystanders with chest compression only (SOS-KANTO) .
CPR are useful, and we've had new guidelines for bystander CPR that have cut down the training time dramatically," he explained. "And now we have this new information that chest compressions alone can move things along. This is very encouraging. This is immediately applicable and can make a difference in people's lives."
Discussing the issues raised by the COURAGE study, Jones says it "is important because it puts into perspective the utility of medical therapy. It's reassuring to know that aggressive medical therapy is an appropriate alternative in unstable angina."
However, he adds, "because COURAGE was a surprise to some people and it ruffled some feathers, I think we'll see a few studies done to try and clarify things. To see who is best suited to mechanical intervention and who is best suited for medical therapy."
Other interventional studies included in the top 10 are the RACE initiative, reported at the AHA 2007 Scientific Sessions, which established a statewide program for reperfusion of ST-segment-elevation myocardial infarction (STEMI) in North Carolina . Jones said: "This study is about applying what we know in a more effective and efficient way. In both the US and EU there is a lot of work on organizing ourselves to get people into a place where they can have state-of-the-art interventions done."
Another interventional highlight is a large Canadian study that showed no excess risk with DES versus bare metal stents in the province of Ontario .
"The key thing about all of this interventional research is that it shows that information is evolving all the time on when it is best to use a stent versus medical therapies, and when it is best to use a DES versus a non-DES, and then we have the associated use of antiplatelet agents, which is an area of intense interest. I think we'll continue to see a lot of research activity in this area over the next few years."
1. Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; DOI:10.1056/NEJMe070829. Available at: http://www.nejm.org.
2. Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of trials of hypertension prevention. BMJ 2007; DOI: 10.1136/bmj.39147.604896.5.
3. Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA 2007; 298:874-879.
4. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007; 447:661-678.
5. Samani NJ, Erdmann J, Hall AS, et al. Genomewide association of coronary artery disease. New Engl J Med 2007; 357:443-453.
6. Guan K, Wagner S, Unsšld B, et al. Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circulation Research 2007; 100:1615
7. SOS-KANTO study group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): An observational study. Lancet 2007; 369:920-926.
8. Jollis JG, Roettig ML, Aluko AO, et al. Implementation of a statewide system for coronary reperfusion for ST-segment elevation myocardial infarction. JAMA 2007; DOI:10.1001/jama.298.20.joc70124. Available at: http://jama.ama-assn.org/cgi/content/full/298.20.joc70124.
9. Tu J V, Bowen J, Chiu M, et al. Effectiveness and safety of drug-eluting stents in Ontario. New Engl J Med 2007; 357:1393-1402.
Lancet. 2007 Dec 8;370(9603):1960-73.
Stroebe M, Schut H, Stroebe W.
Research Institute for Psychology and Health, Utrecht University, Utrecht, Netherlands. M.S.Stroebe@UU.NL
In this Review, we look at the relation between bereavement and physical and mental health.
Although grief is not a disease and most people adjust without professional psychological intervention, bereavement is associated with excess risk of mortality, particularly in the early weeks and months after loss. It is related to decrements in physical health, indicated by presence of symptoms and illnesses, and use of medical services. Furthermore, bereaved individuals report diverse psychological reactions. For a few people, mental disorders or complications in the grieving process ensue. We summarise research on risk factors that increase vulnerability of some bereaved individuals. Diverse factors (circumstances of death, intrapersonal and interpersonal variables, ways of coping) are likely to co-determine excesses in ill-health. We also assess the effectiveness of psychological intervention programmes.
Intervention should be targeted at high-risk people and those with complicated grief or bereavement-related depression and stress disorders.
Thursday, December 20, 2007
Rationale and design of the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSF
Am Heart J. 2008 Jan;155(1):19-25. Epub 2007 Oct 25.
BACKGROUND: Most patients with ST-elevation myocardial infarction present to hospitals without percutaneous coronary intervention (PCI) facilities and receive fibrinolysis. The role of routine early PCI after fibrinolysis, using stents and contemporary pharmacotherapy, has not been studied in a large adequately powered randomized trial.
OBJECTIVE: To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hours after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI and delayed cardiac catheterization for patients who do not require rescue PCI).
METHODS: A total of 1200 patients with high-risk ST-elevation myocardial infarction
presenting to non-PCI centers will be randomized to a pharmacoinvasive strategy (transfer for routine PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis. The primary end point is the 30-day composite of death, reinfarction, recurrent ischemia, heart failure, or shock.
RESULTS: More than 900 patients have been enrolled as of April 2007. An interim safety analysis of the first 536 patients demonstrated no safety concerns. Enrolment is expected to be completed in late 2007.
CONCLUSIONS: This study will provide important data on whether routine early PCI within 6 hours after fibrinolysis is safe and superior to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac catheterization.
Diagnosis of Heart Attack Can Be Wrong Study finds false positives occur 9.2% of the time in emergency rooms
TUESDAY, Dec. 18 (HealthDay News) -- When doctors in the emergency room believe that someone is having a heart attack, they are mistaken 9.2 percent of the time, a new study indicates.
Given that minutes matter with these patients and doctors have to act quickly in this setting, that percentage is tolerable, say researchers from the Minneapolis Heart Institute Foundation.
"Our conclusion is that an 8 to 10 percent false positive rate is acceptable," said study co-author Dr. Timothy Henry, who is director of the institute.
However, every effort should be taken to reduce the number of false positive diagnoses of heart attack, Henry added. The report, which is published in the Dec. 19 issue of the Journal of the American Medical Association, gives a benchmark for other institutions to meet, he said.
"The whole issue of false positive has never been presented," Henry said. "This is the first time it has been presented in a systematic way."
Henry and his colleagues studied the medical records of 1,345 people treated for suspected heart attacks in a regional system between 2003 and 2006, looking at emergency room decisions to activate the cardiac catheterization laboratory to treat for suspected heart attacks. Such decisions usually must be made in a matter of minutes, often without a record of a patient's previous cardiac history.
All the patients were suspected of having a STEMI heart attack, characterized by a specific electrocardiogram pattern. It turned out that 187 of them (14 percent) did not have obvious blockage of a coronary artery, with 127 (9.5 percent) having no significant coronary artery disease and 149 (11.2 percent) having negative results on cardiac biomarker tests. There was a significant difference in survival, with a 4.6 percent 30-day death rate for those with a blocked artery and 2.7 percent for those without blockage.
Hospitals should run a continuing check on such emergency room diagnoses and decisions, Henry said. "If they are too high, corrective action should be taken," he said.
Heart attack diagnosis has been the focus of "a number of quality improvement initiatives," said Dr. Frederick A. Masoudi, an associate professor of medicine at the Denver Health Medical Center, who wrote an accompanying editorial.
"It is well known that timing is of the essence in treating these patients," Masoudi said. "The outcome is better when the artery is opened in a timely way."
False positives are inevitable in some cases, he said. "It is really impossible to say from this one study whether there are too many or too few," Masoudi said. "Ultimately, it is important for us to evaluate the extent to which it occurs and why it occurs. We must build into the system a balance, so that only those patients who need reperfusion get it."
SOURCES: Timothy D. Henry, M.D., director, research, Minneapolis Heart Institute Foundation; Frederick A. Masoudi, M.D., associate professor, medicine, Denver Health Medical Center; Dec. 19, 2007, Journal of the American Medical Association
Effectiveness of Bystander-Initiated Cardiac-Only Resuscitation for Patients With Out-of-Hospital Cardiac Arrest
Circulation - Volume 116, Issue 25; December 18/25, 2007
Taku Iwami, MD, PhD; Takashi Kawamura, MD, PhD; Atsushi Hiraide, MD, PhD; Robert A. Berg, MD; Yasuyuki Hayashi, MD, PhD; Tatsuya Nishiuchi, MD; Kentaro Kajino, MD; Naohiro Yonemoto, MPH; Hidekazu Yukioka, MD, PhD; Hisashi Sugimoto, MD, PhD; Hiroyuki Kakuchi, MD, PhD; Kazuhiro Sase, MD, PhD; Hiroyuki Yokoyama, MD, PhD; Hiroshi Nonogi, MD, PhD
Background— Previous animal and clinical studies suggest that bystander-initiated cardiac-only resuscitation may be superior to conventional cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrests. Our hypothesis was that both cardiac-only bystander resuscitation and conventional bystander CPR would improve outcomes from out-of-hospital cardiac arrests of 15 minutes’ duration, whereas the addition of rescue breathing would improve outcomes for cardiac arrests lasting >15 minutes.
Methods and Results— We carried out a prospective, population-based, observational study involving consecutive patients with emergency responder resuscitation attempts from May 1, 1998, through April 30, 2003. The primary outcome measure was 1-year survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to evaluate the relationship between type of CPR and outcomes. Among the 4902 witnessed cardiac arrests, 783 received conventional CPR, and 544 received cardiac-only resuscitation. Excluding very-long-duration cardiac arrests (>15 minutes), the cardiac-only resuscitation yielded a higher rate of 1-year survival with favorable neurological outcome than no bystander CPR (4.3% versus 2.5%; odds ratio, 1.72; 95% CI, 1.01 to 2.95), and conventional CPR showed similar effectiveness (4.1%; odds ratio, 1.57; 95% CI, 0.95 to 2.60). For the very-long-duration arrests, neurologically favorable 1-year survival was greater in the conventional CPR group, but there were few survivors regardless of the type of bystander CPR (0.3% [2 of 624], 0% [0 of 92], and 2.2% [3 of 139] in the no bystander CPR, cardiac-only CPR, and conventional CPR groups, respectively; P<0.05).
Conclusions— Bystander-initiated cardiac-only resuscitation and conventional CPR are similarly effective for most adult out-of-hospital cardiac arrests. For very prolonged cardiac arrests, the addition of rescue breathing may be of some help.
Assessing mechanical cardiac asynchrony by echography
Dr. B. Vidal and *Dr J. Brugada Barcelona, Spain*Chairman of the European Heart Rhythm Association
Assessing mechanical cardiac asynchrony by echography could enable a better use of cardiac resynchronisation therapy in patients with advanced heart failure.
Mechanical cardiac asynchrony : definition
Mechanical cardiac asynchrony is defined as the presence of a delayed contraction of certain myocardial segments. It usually appears at the end stage of a number of different cardiac diseases, together with left ventricular (LV) dilatation and systolic dysfunction.Mechanical cardiac asynchrony may or may not be associated with electrical asynchrony which is present in up to 30% of patients with heart failure, expressed mainly as a left bundle branch block (LBBB) in the surface ECG. The presence of mechanical intraventricular asynchrony contributes to aggravating LV hemodynamics , favors the apparition of functional mitral regurgitation and consequently, worsens the patient’s prognosis.
Mechanical asynchrony classes
Mechanical asynchrony can be found at the following three levels: atrioventricular, interventricular and intraventricular level. They can coexist and may be measured by echography.
Atrioventricular asynchrony consists of the decoordination of auricular contraction regarding LV filling due to an electrical conductance disturbance.
Interventricular asynchrony refers to the decoordination between right and LV contraction. Physiologically LV contraction occurs 10 to 20 ms later than the right ventricle; when this time difference is superior to 40 ms, this indicates interventricular asynchrony.
Intraventricular Asynchrony The decoordination of the contraction sequence in the different LV segments determines the presence of intraventricular asynchrony
Monday, December 17, 2007
Stem cell session overview highlights what future trials need
AHA - SCIENTIFIC SESSION 2007 - POST EDITION DECEMBER 2007
The rising number of scientific publications on cardiac stem cell repair and the extraordinary emergence of public interest on the subject necessitate a forum for separating hype from reality, said Paul W. Armstrong, M.D., professor of medicine, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
Dr. Armstrong spoke at a Late-Breaking Clinical Trials session on the final day of Scientific Sessions 2007, and offered some observations on the state of stem cell therapy in the early stages of research.
Dr. Armstrong first commented on the three stem-cell research papers presented in this session. In general, he said he was not satisfied he understood the nature of some studies’ comparative groups. Background therapies were not always clear and he could not tell that safety endpoints were always achieved. Improved LV function may indeed be the result of stem cell therapy, through myocardial regeneration, by preventing apoptosis and ventricular remodeling, or through paracrine effects, Dr. Armstrong said. “It could also be due to spontaneous improvement in LV function, medical therapy or to the revascularization,” he said. “Without considering these phenomenon, we have to be very careful about attribution of efficacy associated with stem cell therapy.”
Dr. Armstrong listed four essential questions he said must be answered as stem cell research in cardiovascular disease moves forward:
• What is the life span and destination of cells?
• Does methodology provide and maintain the effective surviving cell population?
• What is cell phenotype at the beginning and end — is there potential for transdifferentiation?
• Do paracrine effects exist?
Dr. Armstrong cited a report on stem cell research that suggests what such trials will need to further the science.
The European Society of Cardiology 2006 Consensus Task Force consensus report said preliminary trial findings suggest that the intracoronary route for cells harvested from bone marrow aspirates is efficacious, Dr. Armstrong said.
The European experts said there is also a need for consensus on surrogate markers and a need to standardize outcomes. “But outcomes studies need to recruit about 1,000 patients to provide adequate statistical power,” Dr. Armstrong said.
Where is stem cell research headed?
“Stem cell research: Quo vadis?” Dr. Armstrong asked, answering his Latinate question with four points:
• Trials must be randomized, blinded, placebo-controlled and adequately sized.
• Standardizing processing procedures of autologous stem/progenitor cells is imperative.
• Trials will need robust endpoints of efficacy and safety, adequately addressed.
• Follow-up must be complete and of adequate duration.
Be wary of comparing trials
Gerd Hasenfuss, M.D., professor, Faculty of Medicine, Gottingen University, Gottingen, Germany, emphasized the differences among the three stem cell trials presented at Scientific Sessions, suggesting that few generalizations can be made yet.
Dr. Hasenfuss urged observers to be aware that these three trials used two different stem cell populations.
In the IM-BMC randomized, double-blind trial, presented by Heikki Huikuri, M.D., lead investigator and professor of medicine and director of cardiology sector at the University of Oulu Hospital in Oulu, Finland, bone marrow cells were used.
Bone marrow cells were also delivered IM or IC to treat scarred myocardium in the IC/IM-BMC trial, a study of 63 patients reported by Manuel Galiñanes, M.D., lead author and professor of cardiac surgery in the cardiac surgery unit, Department of Cardiovascular Sciences at the University of Leicester, Leicester, United Kingdom.
Friday, December 14, 2007
Date Posted: 12/13/2007
Author(s): King S, Smith S, Hirschfeld JW, et al.
J Am Coll Cardiol. 2008;51:[Epub ahead of print].
Perspective: The following are 10 points to remember about this guideline update for percutaneous coronary intervention (PCI):
1. In patients with unstable angina (UA)/non–ST-elevation myocardial infarction (NSTEMI), an early invasive strategy is favored in the presence of recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy, elevated cardiac biomarkers (troponin T or troponin I), new or presumably new ST-segment depression, signs or symptoms of heart failure or new or worsening mitral regurgitation, high-risk findings from noninvasive testing, hemodynamic instability, sustained ventricular tachycardia, PCI within the prior 6 months, prior coronary artery bypass graft surgery or a high-risk score (e.g., TIMI, GRACE), or reduced left ventricular function (left ventricular ejection fraction <40%).
2. PCI is not indicated for a persistently occluded infarct-related artery after NSTEMI or STEMI older than 24 hours in a stable patient.
3. Creatinine clearance should be estimated in UA/NSTEMI patients, and medication dosage should be adjusted appropriately in patients with altered renal function.
4. In patients with chronic kidney disease undergoing coronary angiography or intervention, isosmolar contrast agents should be preferentially used (Level of Evidence: A).
5. In patients with STEMI, a planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI may be harmful, and is not advocated.
6. A strategy of coronary angiography with intent to perform revascularization is recommended for patients who have received fibrinolytic therapy and are in cardiogenic shock and candidates for revascularization, and have severe heart failure or pulmonary edema or hemodynamically significant ventricular arrhythmias.
7. Rescue PCI should be considered in patients with STEMI who have received a fibrinolytic agent, have evidence of failed reperfusion (ST-segment resolution <50%) 90 minutes after initiation of fibrinolytic therapy, and have a moderate or large area of myocardium at risk.
8. Given the risk of catheter thrombosis, fondaparinux should not be used as the sole anticoagulant to support PCI. For patients who undergo PCI with prior treatment with fondaparinux, additional intravenous treatment with an anticoagulant possessing anti-IIa activity (such as unfractionated heparin) should be used.
9. Before implanting a drug-eluting stent (DES), the physician should discuss with the patient the need for and duration of dual antiplatelet therapy, and confirm the patient’s ability to comply with the recommended therapy. In patients who are likely to require invasive or surgical procedures for which antiplatelet must be interrupted during the next 12 months after PCI, consideration should be given to implantation of a bare-metal stent or performance of balloon angioplasty with a provisional stent implantation.
10. Continuation of clopidogrel therapy beyond 1 year may be considered in patients treated with DES.
Hitinder S. Gurm, M.B.B.S., F.A.C.C.
Wednesday, December 12, 2007
Wall Street Journal
December 11, 2007, 9:26 pm
Usually, critics wait for a study’s results to come out before taking their shots. But in the case of a closely watched clinical test of Vytorin, a cholesterol pill marketed by Merck and Schering-Plough, the questions are already loud and pointed. They center on why the results of the study have remained a mystery for so long.
Although the study was finished in April 2006, doctors, patients and investors still don’t know how it turned out. Merck and Schering-Plough have been merrily marketing Vytorin as a potent reducer of cholesterol all along. Vytorin combines the drugs Zetia and Zocor in a single pill. But is the drug really better than plain old Zocor, now available as a cheap generic?
House Energy and Commerce Committee leaders John Dingell and Bart Stupak, both Michigan Democrats, ratcheted up the pressure on the companies today with a letter expressing their concern “with the delay…and the apparent manipulation of trial data.” (See the full text here.)
The trial at issue, called ENHANCE for short, looked at how well Vytorin slows the buildup of plaque in the arteries compared with a combination of Zocor and a placebo.
The companies said last month that the results would be presented at a meeting of the American College of Cardiology in March. But they also said then that the presentation would focus on an ultrasound measurement at only one point of the carotid artery. The study’s design called for the assessment of changes at three points of the artery as the primary endpoint. The apparent move of the carotid goal posts fueled questions about what the companies were up to.
Well, Team Vytorin has moved to placate questioning cardiologists by saying the main results will be revealed at the ACC meeting and that there will be no change in the endpoint after all.
“We have clarified today that we decided not to” change the endpoint, a Schering-Plough spokeswoman told the Health blog. The decision came after the companies got input from “leaders in the field in the U.S. and Europe,” she said. The spokeswoman said the company hasn’t formally received the letter from Congress, and she declined to comment on it.
A Merck spokesman said the company’s executives “just received and are reviewing the letter from the House Committee on Energy and Commerce and will respond in a timely manner.”
Coronary Artery Calcium Scores and Risk for Cardiovascular Events in Women Classified as "Low Risk" Based on Framingham Risk Score
The Multi-Ethnic Study of Atherosclerosis (MESA)
Susan G. Lakoski, MD, MS; Philip Greenland, MD; Nathan D. Wong, PhD, MPH; Pamela J. Schreiner, PhD; David M. Herrington, MD, MHS; Richard A. Kronmal, PhD; Kiang Liu, PhD; Roger S. Blumenthal, MD
Arch Intern Med. 2007;167(22):2437-2442.
Objective To assess coronary artery calcium (CAC) score and subsequent risk for coronary heart disease (CHD) and cardiovascular (CVD) events among asymptomatic women judged to be at low risk by the Framingham risk score (FRS), a common approach for determining 10-year absolute risk for CHD. Based on population survey data, 95% of American women are considered at low risk based on FRS.
Methods The Multi-Ethnic Study of Atherosclerosis (MESA) included 3601 women aged 45 to 84 years at baseline. The CAC score was measured by coronary computed tomography. Cox proportional hazard models were used to examine the CHD and CVD risk associated with CAC score among women classified as "low risk" based on FRS.
Results Excluding women with diabetes and those older than 79 years, 90% of women in MESA (mean ± SD age, 60 ± 9 years) were classified as "low risk" based on FRS. The prevalence of CAC (CAC score > 0) in this low-risk subset was 32% (n = 870). Compared with women with no detectable CAC, low-risk women with a CAC score greater than 0 were at increased risk for CHD (hazard ratio, 6.5; 95% confidence interval, 2.6-16.4) and CVD events (hazard ratio, 5.2; 95% confidence interval, 2.5-10.8). In addition, advanced CAC (CAC score 300) was highly predictive of future CHD and CVD events compared with women with nondetectable CAC and identified a group of low-risk women with a 6.7% and 8.6% absolute CHD and CVD risk, respectively, over a 3.75-year period.
Conclusions The presence of CAC in women considered to be at low risk based on FRS was predictive of future CHD and CVD events. Advanced CAC identified a subset of low-risk women at higher risk based on current risk stratification strategies.
Lorraine L. Lipscombe, MD, MSc; Tara Gomes, MHSc; Linda E. Lévesque, BScPhm, MSc; Janet E. Hux, MD, MSc; David N. Juurlink, BPhm, MD, PhD; David A. Alter, MD, PhD
Context Thiazolidinediones (TZDs), used to treat type 2 diabetes, are associated with an excess risk of congestive heart failure and possibly acute myocardial infarction. However, the association between TZD use and cardiovascular events has not been adequately evaluated on a population level.
Objective To explore the association between TZD therapy and congestive heart failure, acute myocardial infarction, and mortality compared with treatment with other oral hypoglycemic agents.
Design, Setting, and Patients Nested case-control analysis of a retrospective cohort study using health care databases in Ontario. We included diabetes patients aged 66 years or older treated with at least 1 oral hypoglycemic agent between 2002 and 2005 (N = 159 026) and followed them up until March 31, 2006.
Main Outcome Measures The primary outcome consisted of an emergency department visit or hospitalization for congestive heart failure; secondary outcomes were an emergency department visit or hospitalization for acute myocardial infarction and all-cause mortality. The risks of these events were compared between persons treated with TZDs (rosiglitazone and pioglitazone) and other oral hypoglycemic agent combinations, after matching and adjusting for prognostic factors.
Results During a median follow-up of 3.8 years, 12 491 patients (7.9%) had a hospital visit for congestive heart failure, 12 578 (7.9%) had a visit for acute myocardial infarction, and 30 265 (19%) died. Current treatment with TZD monotherapy was associated with a significantly increased risk of congestive heart failure (78 cases; adjusted rate ratio [RR], 1.60; 95% confidence interval [CI], 1.21-2.10; P < .001), acute myocardial infarction (65 cases; RR, 1.40; 95% CI, 1.05-1.86; P = .02), and death (102 cases; RR, 1.29; 95% CI, 1.02-1.62; P = .03) compared with other oral hypoglycemic agent combination therapies (3478 congestive heart failure cases, 3695 acute myocardial infarction cases, and 5529 deaths). The increased risk of congestive heart failure, acute myocardial infarction, and mortality associated with TZD use appeared limited to rosiglitazone.
Conclusion In this population-based study of older patients with diabetes, TZD treatment, primarily with rosiglitazone, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments.
Tuesday, December 11, 2007
Raymond J. Gibbons, MD; George D. Lundberg, MD
Medscape General Medicine. 2007;9(4):49. ©2007 Medscape
Dr. Lundberg: It was a forerunner of a lot of good things. Let's talk about cardiology, and let's talk about angina pectoris: stable, unstable. Stable is more common?
Dr. Gibbons: Stable is much more common, and I think it's of more current interest. Our management of stable angina has obviously consisted of medications. But we knew from randomized trials in bypass surgery conducted 20 years ago that certain patients with very severe problems, particularly left main disease and 3-vessel disease with prior abnormal ventricular function, benefited from surgery from the standpoint of survival. As percutaneous coronary intervention [PCI] came along, we thought that patients who had less severe coronary artery disease probably would benefit, from the standpoint of survival and myocardial infarction, from PCI.
Dr. Lundberg: That's sensible.
Dr. Gibbons: And that was incorporated into national guidelines. This year, however, there have been 2 studies that have been published, OAT and COURAGE, that have both challenged that assumption. I think the study that is most pertinent to chronic stable angina is COURAGE. In a large trial conducted in the VA [Veterans Administration], certain other academic medical centers in the United States, including my own, and Canada, the investigators showed that with optimal medical therapy.
Dr. Lundberg: Okay. What do you call that? What is optimal medical therapy?
Dr. Gibbons: Well, previous trials had focused on just relieving angina. That trial had a different comprehensive approach: risk factor reduction. They just didn't treat angina, they also treated the risk factors very aggressively, and did very well even after 5 years at meeting targets for LDL [low density lipoprotein], for blood pressure, getting patients to stop smoking, getting them to exercise. And compared to optimal therapy, optimal therapy plus PCI did not convey an advantage with respect to heart attack or death. That was news, challenging the assumption that we had all along. It has led to a decrease, already, in the use of stents in the country. And I think it poses a challenge for practicing physicians to do as well with medical therapy in treating risk factors and symptoms, as occurred in the trial.
Dr. Lundberg: And of course, one of the things they have to do is handle patient compliance in terms of long-term use of whatever they're supposed to do.
Dr. Gibbons: I think they need to be very clear on educating the patient about the importance of, not just treatment for their chest pain, but treatment for the plaque and underlying coronary artery disease to prevent events. The patients have to understand the importance of taking aspirin, the importance of lowering their cholesterol to appropriate targets -- ideally an LDL of less than 100 -- and also not to smoke.
Dr. Lundberg: Of course, we live in a society with a medical-industrial complex with huge amounts of money that flow through the system into lots of people's pockets. If you're going to do surgery, or if you're going to do percutaneous stent implants, etc, it probably accrues a lot more money to people who are doing it, and it costs the insurance companies and the government a lot more to do that. So, there must be a tension developing there.
Dr. Gibbons: There's a clear tension, and I think there is an undercurrent of concern raised about the trial. For example, there's a tendency to point out there was a modest difference in pain relief, but it was modest. It was less than 10% of the patients had more complete pain relief by PCI at a year, and that [number] diminished over subsequent management of the patients. And a very comprehensive quality-of-life cost-effectiveness analysis presented here at the American Heart Association meeting this year by Dr. Weintraub, an expert in cost-effectiveness, showed that no matter what assumption you made, the effect on quality of life was minimal and very cost-ineffective.
Dr. Lundberg: So, for a stable angina at this time, optimal medical therapy is the best way to go?
Dr. Gibbons: It's clearly the best way to go. The challenge for all of us in the healthcare system is to do the best job we can of getting patients to comply with guideline-indicated medications.
Dr. Lundberg: There you are. Thank you all for being with us today. We've been talking with Dr. Raymond Gibbons, professor of medicine at the Mayo Clinic College of Medicine and a former president of the American Heart Association. Thank you for being with us. And thank you for being with us.
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Raymond J. Gibbons, MD, Arthur M. and Gladys D. Gray Professor of Medicine, Mayo Clinic, Rochester, MinnesotaGeorge D. Lundberg, MD, Editor-in-Chief, Medscape General Medicine; Adjunct Professor of Health Policy, Harvard School of Public Health, Boston, Massachusetts; Consulting Professor, Stanford University School of Medicine, Stanford, CaliforniaAuthor's email: firstname.lastname@example.org
Myth vs Reality
John G. Canto, MD, MSPH; Robert J. Goldberg, PhD; Mary M. Hand, MSPH, RN; Robert O. Bonow, MD; George Sopko, MD, MPH; Carl J. Pepine, MD; Terry Long, BA
Arch Intern Med. 2007;167(22):2405-2413.
Background Optimal diagnosis and timely treatment of patients with an acute coronary syndrome (ACS) depends on distinguishing differences between popular "myths" about ischemic symptoms in women and men. Chest pain or discomfort is regarded as the hallmark symptom of ACS, and its absence is regarded as "atypical" presentation. This review describes the presenting symptoms of ACS in women compared with men and ascertains whether women should have a symptom message that is separate or different from that for men.
Methods MEDLINE (1970-2005), bibliographies of articles, and pertinent abstracts were reviewed, focusing on studies of ACS presentation, especially those reporting differences in symptoms by sex. This analysis included 69 of 361 possible studies. Data regarding symptom presentation were recorded.
Results The published literature lacks standardization in characterizing ACS presentation, data collection, and reporting of symptoms. Approximately one-third of patients in the large cohort studies and one-quarter of patients in the smaller reports and direct patient interviews presented without chest pain or discomfort. The absence of chest pain or discomfort with ACS was noted more commonly in women than in men in both the cumulative summary from large cohort studies (37% vs 27%) and the single-center and small reports or interviews (30% vs 17%).
Conclusions Women are significantly less likely to report chest pain or discomfort compared with men. These differences, however, are not likely large enough to warrant sex-specific public health messages regarding the symptoms of ACS at the present time. Further research must systematically investigate sex differences in the clinical presentation of ACS symptoms and must include standardized data collection efforts.
Among the findings:
Compared with men, women are more likely to present with unstable angina and less likely to present with acute myocardial infarction.
In nine large cohort studies, 27.4% of men with ACS had no chest pain at presentation; 37.5% of women had no pain.
In the single-center and small reports or interviews, 30% of women and 17% of men did not have chest pain.
In the setting of acute MI, women are more likely to have ST-elevation MI than non-STEMI.
Women are less likely to have obstruction of coronary vessels and more likely to have Prinzmetal angina, syndrome X, and mitral valve prolapse.
Even in the presence of ischemic damage, women are likely to have normal findings on angiography.
Inadequate Control of Hypertension in US Adults With Cardiovascular Disease Comorbidities in 2003-2004
Nathan D. Wong, PhD; Victor A. Lopez, BS; Gilbert L'Italien, PhD; Roland Chen, MD; Sue Ellen J. Kline, PhD; Stanley S. Franklin, MD
Arch Intern Med. 2007;167(22):2431-2436.
Background Cardiovascular risks associated with hypertension (HTN) and the importance of its control are well established; however, the prevalence and adequacy of its treatment and control in persons with cardiovascular comorbidities (CVCs) are uncertain.
Methods To examine the prevalence, treatment, and control of HTN among US adults with and without CVCs, we analyzed data from adults at least 18 years of age (n = 4646, N [projected sample size] = 192.4 million) in the National Health and Nutrition Examination Survey 2003-2004, a nationally representative cross-sectional survey of the noninstitutionalized civilian US population. Prevalence, treatment, and control rates of HTN in patients with CVCs vs those without, including coronary artery disease, congestive heart failure, stroke, chronic kidney disease, peripheral artery disease, and diabetes mellitus, and distance to blood pressure goal in those whose HTN was not controlled were the main outcomes.
Results The overall prevalence rate of HTN was 31.4% (n = 1671, N = 60.5 million), ranging from 23.1% in those without CVCs to 51.8% to 81.8% in those with CVCs (P < .01). Despite HTN treatment rates for diabetes mellitus, stroke, heart failure, and coronary artery disease that are higher (83.4%-89.3%) than the rates of those without these conditions (66.5%) (P < .01), control rates for treatment remained poor (23.2%-49.3%) (P < .001 to P = .048). Isolated systolic HTN was the most common hypertensive subtype in those with CVCs ( 63.5%) with systolic blood pressure averaging at least 20 mm Hg from goal. Conclusions Nearly three-fourths of adults with CVCs have HTN. Poor control rates of systolic HTN remain a principal problem that further compromises their already high cardiovascular disease risk.
ScienceDaily (Dec. 10, 2007) — Depression nearly triples the risk of death following a heart attack, even when accounting for other heart attack risk factors, according to research presented today at the American College of Neuropsychopharmacology (ACNP) annual meeting, which showed that among 360 depressed, post myocardial infarction patients followed for more than six years, those who did not recover from their depression in the first six months were more than twice as likely to die.
This study was one of several presented at a panel which examined the links between depression and vascular disease. "There is an unequivocal link between depression and heart disease, but it is not clear what causes this link," said Alexander Glassman, M.D., Professor of Psychiatry at Columbia University, College of Physicians and Surgeons and ACNP member.
"There is a whole series of factors that link depression and heart disease and we are just beginning to understand how antidepressants act in people who have these conditions together."
Additional risk factors that tend to be major medical predictors of death from a heart attack include the severity of the heart attack and variability in various measures of heart function during recovery.
Depression has increasingly been recognized to increase the risk for cardiovascular disease. Possible reasons for this association include sticky platelets, a condition depressed patients are likely to have, or autonomic nervous activity, which increases heart irritability.
Ronald S. Duman, Ph.D., professor of psychiatry and pharmacology at Yale University School of Medicine and an ACNP member, also presented research on this topic. His work examined molecular mechanisms and the identity of the protein, vascular endothelial growth factor (VEGF). VEGF is a key growth factor in the formation of vascular cells and was originally identified and studied for its role in the formation of vascular tissues.
"We found that different classes of antidepressants increase the expression of VEGF in the hippocampus (the part of the brain which influences memory), which may partly explain how certain antidepressants are more effective than others," said Duman. "Changes in brain levels of VEGF contribute importantly to the antidepressant response and that's why studying VEGF function may be useful in developing medications that are more effective and rapid acting."
The panel also included presentations from Kevin Tracey, M.D. and Gregory Miller, Ph.D., who presented evidence indicating the brain has significant control over the levels of inflammatory molecules called cytokines in other parts of the body, and that these levels are altered in depression and associated with an increased risk for heart disease. And Charles Nemeroff M.D., Ph.D., and professor and chair of the department of psychiatry at Emory University, presented data showing the impact of stressful events early in life on the response to stress later in life.
These events precede either depression or heart disease and could potentially contribute to vulnerability for both conditions.
Adapted from materials provided by American College of Neuropsychopharmacology.
Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest
Iwami T, et al
Circulation 2007; DOI: 10.1161/CIRCULATIONAHA.107.723411
Background—Previous animal and clinical studies suggest that bystander-initiated cardiac-only resuscitation may be superior to conventional cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrests. Our hypothesis was that both cardiac-only bystander resuscitation and conventional bystander CPR would improve outcomes from out-of-hospital cardiac arrests of 15 minutes’ duration, whereas the addition of rescue breathing would improve outcomes for cardiac arrests lasting >15 minutes.
Methods and Results—We carried out a prospective, population-based, observational study involving consecutive patients with emergency responder resuscitation attempts from May 1, 1998, through April 30, 2003. The primary outcome measure was 1-year survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to evaluate the relationship between type of CPR and outcomes. Among the 4902 witnessed cardiac arrests, 783 received conventional CPR, and 544 received cardiac-only resuscitation. Excluding very-long-duration cardiac arrests (>15 minutes), the cardiac-only resuscitation yielded a higher rate of 1-year survival with favorable neurological outcome than no bystander CPR (4.3% versus 2.5%; odds ratio, 1.72; 95% CI, 1.01 to 2.95), and conventional CPR showed similar effectiveness (4.1%; odds ratio, 1.57; 95% CI, 0.95 to 2.60). For the very-long-duration arrests, neurologically favorable 1-year survival was greater in the conventional CPR group, but there were few survivors regardless of the type of bystander CPR (0.3% [2 of 624], 0% [0 of 92], and 2.2% [3 of 139] in the no bystander CPR, cardiac-only CPR, and conventional CPR groups, respectively; P<0.05).
Conclusions—Bystander-initiated cardiac-only resuscitation and conventional CPR are similarly effective for most adult out-of-hospital cardiac arrests. For very prolonged cardiac arrests, the addition of rescue breathing may be of some help.
Circulation: Journal of the American Heart AssociationSource reference:
Canoy D, et al Circulation 2007; DOI: 10.1161/CIRCULATIONAHA.106.673756.
Background—Body fat distribution has been cross-sectionally associated with atherosclerotic disease risk factors, but the prospective relation with coronary heart disease remains uncertain.
Methods and Results—We examined the prospective relation between fat distribution indices and coronary heart disease among 24 508 men and women 45 to 79 years of age using proportional hazards regression. During a mean 9.1 years of follow-up, 1708 men and 892 women developed coronary heart disease. The risk for developing subsequent coronary heart disease increased continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the top versus bottom fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and 1.91 (1.44 to 2.54) in women after adjustment for body mass index and other coronary heart disease risk factors. Hazard ratios increased with waist circumference, but risk estimates for waist circumference without hip circumference adjustment were lower by 10% to 18%. After adjustment for waist circumference, body mass index, and coronary heart disease risk factors, hazard ratios for 1-SD increase in hip circumference were 0.80 (95% CI, 0.74 to 0.87) in men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for body mass index were greatly attenuated when we adjusted for waist-hip ratio or waist circumference and other covariates.
Conclusions—Indices of abdominal obesity were more consistently and strongly predictive of coronary heart disease than body mass index. These simple and inexpensive measurements could be used to assess obesity-related coronary heart disease risk in relatively healthy men and women.
American Journal of Medicine.
Volume 120, Issue 12, Pages 1054-1062 (December 2007)
Ravi Dhingra, MDabc, Philimon Gona, PhDad, Byung-Ho Nam, PhDad, Ralph B. D’Agostino Sr, PhDad, Peter W.F. Wilson, MDae, Emelia J. Benjamin, MD, MSaf, Christopher J. O’Donnell, MD, MPHagh
It is uncertain to what extent high C-reactive protein (CRP) concentrations reflect the presence of inflammatory conditions in the community.
We evaluated 3782 Framingham Offspring Study participants (mean age 55 years; 52% women) free of baseline cardiovascular disease. Logistic regression models examined the prevalence of common inflammatory conditions by CRP categories, while a separate matched case-referent analysis evaluated the prevalence of uncommon inflammatory conditions. Cox models were used to assess the influence of common inflammatory conditions on relations between CRP and incident cardiovascular disease.
Common inflammatory conditions were reported by nearly half of the participants; these individuals were more likely to have markedly high CRP concentrations (>10 mg/L, P for trend=.001). In multivariable models, there were increased odds of having at least one common inflammatory condition with CRP concentrations of 1-3.0, 3.01-10, and >10 mg/L, compared with the referent category (<1>10 mg/L compared with those with CRP <1 mg/L (12.1% vs 6.6%; P=.0001). In multivariable models, higher CRP categories were not associated with incident cardiovascular disease, and with additional adjustment for inflammatory conditions, results remained unchanged.
There is high prevalence of common and uncommon inflammatory conditions in individuals with high CRP concentrations. Higher CRP concentrations should be interpreted with caution in cardiovascular disease risk assessment
Cardiomyopathy represents a diverse and heterogenous group of disorders affecting the myocardium and ultimately resulting in cardiac dysfunction. The prevalence of heart failure is high (5 million symptomatic patients in the United States) and increasing. Cardiomyopathy is the leading cause of hospitalization in patients older than 65 years of age, resulting in enormous healthcare expenditure and lost productivity. Ischemic cardiomyopathy accounts for about half of these patients, but in several large clinical trials the prevalence of potentially reversible nonischemic cardiomyopathy is also significant, ranging from 20% to 50%. There is epidemiological evidence that the prognosis of these reversible nonischemic cardiomyopathies is better than ischemic or other nonreversible cardiomyopathies. Early and precise diagnosis of the etiology of heart failure is important for determining prognosis and effective treatments.
Prominent reversible etiologies of cardiomyopathies:
1. Pregnancy associated or peripartum cardiomyopathy (PPCM)
2. Takotsubo or stress-induced cardiomyopathy (SIC)
3. Siderotic cardiomyopathy or iron-induced cardiomyopathy
4. Alcoholic cardiomyopathy
5. Acromegalic cardiomyopathy
6. Thyroid or Graves cardiomyopathy
7. Tachycardia-induced cardiomyopathy (TIC)
8. Amyloid cardiomyopathy
9. Fabry's disease
Source: Developed in Collaboration With the Canadian Cardiovascular Society
Date Posted: 12/10/2007
Author(s): Antman EM, Hand M, Armstrong PW, et al., for the 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee.
Citation: J Am Coll Cardiol. 2008;51:[Epub ahead of print].
Perspective: The following are 10 points to remember about these updated guidelines:
1. Patients routinely taking nonsteroidal anti-inflammatory drugs (except for aspirin), both nonselective as well as cyclooxygenase-2 selective agents, before ST-elevation myocardial infarction (STEMI) should have those agents discontinued at the time of presentation with STEMI because of the increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.
2. Oral beta-blocker therapy should be initiated in the first 24 hours for patients who do not have any of the following: a) signs of heart failure, b) evidence of a low output state, c) increased risk for cardiogenic shock, or d) other relative contraindications to beta blockade (PR interval >0.24 seconds, second- or third-degree heart block, active asthma, or reactive airway disease).
3. STEMI patients presenting to a hospital with PCI capability should be treated with primary percutaneous coronary intervention (PCI) within 90 minutes of first medical contact as a systems goal.
4. STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI center and undergo PCI within 90 minutes of first medical contact should be treated with fibrinolytic therapy within 30 minutes of hospital presentation as a systems goal unless fibrinolytic therapy is contraindicated.
5. A strategy of coronary angiography with intent to perform PCI (or emergency coronary artery bypass graft surgery) is recommended for patients who have received fibrinolytic therapy and have any of the following: a) cardiogenic shock in patients <75 years who are suitable candidates for revascularization, b) severe congestive heart failure and/or pulmonary edema (Killip class III), or c) hemodynamically compromising ventricular arrhythmias.
6. Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a minimum of 48 hours and preferably for the duration of the index hospitalization, up to 8 days (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment). Anticoagulant regimens with established efficacy include:a) UFH (initial intravenous [IV] bolus 60 U/kg [maximum 4000 U]) followed by an IV infusion of 12 U/kg/h (maximum 1000 U/h) initially, adjusted to maintain the activated partial thromboplastin time at 1.5-2.0 times control (~50-70 seconds).b) Enoxaparin (provided the serum creatinine is <2.5 mg/dl in men and 2.0 mg/dl in women): for patients <75 years of age, an initial 30 mg IV bolus is given, followed 15 minutes later by subcutaneous injections of 1.0 mg/kg every 12 hours; for patients at least 75 years of age, the initial IV bolus is eliminated and the subcutaneous dose is reduced to 0.75 mg/kg every 12 hours. Regardless of age, if the creatinine clearance (using the Cockroft-Gault formula) during the course of treatment is estimated to be <30 ml/min, the subcutaneous regimen is 1.0 mg/kg every 24 hours. Maintenance dosing with enoxaparin should be continued for the duration of the index hospitalization, up to 8 days.c) Fondaparinux (provided the serum creatinine is <3.0 mg/dl): initial dose 2.5 mg IV; subsequently subcutaneous injections of 2.5 mg once daily. Maintenance dosing with fondaparinux should be continued for the duration of the index hospitalization, up to 8 days.
7. Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy. Treatment with clopidogrel should continue for at least 14 days.
8. Every tobacco user and family members who smoke should be advised to quit at every visit.
9. For all post-PCI STEMI stented patients without aspirin resistance, allergy, or increased risk of bleeding, aspirin 162-325 mg daily should be given for at least 1 month after bare-metal stent (BMS) implantation, 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after which long-term aspirin use should be continued indefinitely at a dose of 75-162 mg daily.
10. For all post-PCI patients who receive a drug-eluting stent, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding. For post-PCI patients receiving a BMS, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks). Debabrata Mukherjee, M.D., F.A.C.C.
Friday, December 7, 2007
Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis
Kwok M Ho, David J Sheridan, Timothy Paterson
Department of Intensive Care, Royal Perth Hospital, Perth, Australia
Objectives: To assess the effects of intravenous magnesium on converting acute onset atrial fibrillation to sinus rhythm, reducing ventricular response and risk of bradycardia.
Design and data sources: Randomised controlled trials evaluating intravenous magnesium to treat acute onset atrial fibrillation from MEDLINE (1966 to 2006), EMBASE (1990 to 2006) and Cochrane Controlled Trials Register without language restrictions.
Review methods: Two researchers independently performed the literature search and data extraction.
Results: 10 randomised controlled trials, including a total of 515 patients with acute onset atrial fibrillation, were considered. Intravenous magnesium was not effective in converting acute onset atrial fibrillation to sinus rhythm when compared to placebo or an alternative antiarrhythmic drug. When compared to placebo, adding intravenous magnesium to digoxin increased the proportion of patients with a ventricular response <100 beats/min (58.8% vs 32.6%; OR 3.2, 95% CI 1.93 to 5.42; p<0.001). When compared to calcium antagonists or amiodarone, intravenous magnesium was less effective in reducing the ventricular response (21.4% vs 58.5%; OR 0.19, 95% CI 0.09 to 0.44; p<0.001) but also less likely to induce significant bradycardia or atrioventricular block (0% vs 9.2%; OR 0.13, 95% CI 0.02 to 0.76; p = 0.02). The use of intravenous magnesium was associated with transient minor symptoms of flushing, tingling and dizziness in about 17% of the patients (OR 14.5, 95% CI 3.7 to 56.7; p<0.001).
Conclusions: Adding intravenous magnesium to digoxin reduces fast ventricular response in acute onset atrial fibrillation. The effect of intravenous magnesium on the ventricular rate and its cardiovascular side effects are less significant than other calcium antagonists or amiodarone. Intravenous magnesium can be considered as a safe adjunct to digoxin in controlling the ventricular response in atrial fibrillation.