Tuesday, August 29, 2006
"Background— Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, <50% style="font-weight: bold;">Methods and Results— A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38% for women with nonobstructive to 3-vessel CAD (P<0.0001).> 12% for 1-vessel to 3-vessel CAD; P=0.001). For women with nonobstructive CAD, average lifetime cost estimates were $767 288 (95% CI, $708 480 to $826 097) and ranged from $1 001 493 to $1 051 302 for women with 1-vessel to 3-vessel CAD (P=0.0003).
Conclusions— Symptom-driven care is costly even for women with nonobstructive CAD. Our lifetime estimates for costs of cardiovascular care identify a significant subset of women who are unaccounted for within current estimates of the economic burden of coronary heart disease. "
Friday, August 25, 2006
Fixed-dose unfractionated heparin, given subcutaneously, as effective as low-molecular-weight heparin for VTE
"August 22, 2006 Michael O'Riordan
Hamilton, ON - Fixed-dose subcutaneous unfractionated heparin, without monitoring of activated partial thromboplastin time (APTT), is as effective as fixed-dose low-molecular-weight heparin in patients with acute venous thromboembolism, according to the results of a new study . In addition, the administration of unfractionated heparin was safe, with no increased bleeding risks, and could be considered an alternative for outpatient use, say investigators.
'We're pleased with the results, and we feel the findings are consistent with our expectations, that there would not be a difference between outcomes when you use unfractionated heparin and low-molecular-weight heparin in the same way,' lead investigator Dr Clive Kearon (McMaster University, Hamilton, ON) told heartwire. 'I think the data will be of interest to the medical community because it departs from what has been usual practice with a drug that has been in use clinically now for over 50 years.'
The results of the study are published in the August 23, 2006 issue of the Journal of the American Medical Association."
According to a population-based, nested case-control study of 36,387 pregnant women in Quebec province, women who filled NSAID prescriptions early in pregnancy had more than twice the risk for any congenital defect, reported Anick Berard, Ph.D., of Sainte-Justine Hospital, and colleagues, in the September issue of Birth Defects Research Part B.
Women who took first-trimester NSAIDs also and more than three times the risk of anomalies related to cardiac septal closure, mainly ventricular and atrial septal defects, the investigators found.
The effect of NSAID exposure on the fetus toward the end of pregnancy, causing premature closure of the ductus arteriosus and patent ductus arteriosus, are well documented, but the risks related to NSAID use in early pregnancy are less well defined, they said."/.../
Wednesday, August 23, 2006
Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the “vulnerable patient.” These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement.
In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45–75 years of age and asymptomatic women 55–75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima–media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations.
Anis Rassi, Jr., M.D., Ph.D., Anis Rassi, M.D., William C. Little, M.D., Sérgio S. Xavier, M.D., Ph.D., Sérgio G. Rassi, M.D., Alexandre G. Rassi, M.D., Gustavo G. Rassi, M.D., Alejandro Hasslocher-Moreno, M.D., Andrea S. Sousa, M.D., Ph.D., and Maurício I. Scanavacca, M.D., Ph.D.
Background Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease.
Methods We retrospectively evaluated 424 outpatients from a regional Brazilian cohort. The association of potential risk factors with death was tested by Cox proportional-hazards analysis, and a risk score was created. The model was validated in 153 patients from a separate community hospital.
Results During a mean follow-up of 7.9 years, 130 patients in the development cohort died. Six independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: New York Heart Association class III or IV (5 points), evidence of cardiomegaly on radiography (5 points), left ventricular systolic dysfunction on echocardiography (3 points), nonsustained ventricular tachycardia on 24-hour Holter monitoring (3 points), low QRS voltage on electrocardiography (2 points), and male sex (2 points). We calculated risk scores for each patient and defined three risk groups: low risk (0 to 6 points), intermediate risk (7 to 11 points), and high risk (12 to 20 points). In the development cohort, the 10-year mortality rates for these three groups were 10 percent, 44 percent, and 84 percent, respectively. In the validation cohort, the corresponding mortality rates were 9 percent, 37 percent, and 85 percent. The C statistic for the point system was 0.84 in the development cohort and 0.81 in the validation cohort.
Conclusions A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort. "
Tuesday, August 22, 2006
Method and Results— Subjects presenting to an Olmsted County facility with a troponin T value 0.03 ng/mL between November 2002 and March 2005 were prospectively classified through the use of standardized MI criteria, relying on cardiac pain, Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs were identified versus 327 with creatine kinase and 427 with only the MB fraction of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to 79%) increase above the number of MIs identified with creatine kinase and a 41% (95% CI, 37% to 46%) increase above the number identified with criteria including only its MB fraction. When relying on single values of troponin, increases in the number of MIs were always large but varied widely according to the threshold used for troponin. Cases meeting only troponin-based criteria were less likely to have electrocardiographic ST-segment elevation and had better survival than those identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95% CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI, 69% to 78%) for MIs meeting the previous criteria (P<0.001).
Monday, August 21, 2006
"BMI Fails as a Cardiovascular Risk Factor
By Judith Groch, Senior Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
August 18, 2006
MedPage Today Action Points
ROCHESTER, Minn., Aug. 18 -- Because body mass index (BMI) cannot discriminate between fat and lean mass, it cannot reliably predict the outcome for patients with coronary artery disease, according to researchers here.
In fact, in a meta-analysis of 40 studies, including 250,152 patients with established coronary artery disease, outcomes for cardiovascular and total mortality were better for overweight and mildly obese groups compared with normal-BMI patients, found a study reported in the Aug. 19 issue of The Lancet. Adjustment for confounding factors did not change the findings.
"Rather than proving that obesity is harmless, our data suggest that alternative methods might be needed to better characterize individuals who truly have excess fat, compared with those in whom BMI is raised because of preserved muscle mass," said Francisco Lopez-Jimenez, M.D., of the Mayo Clinic here, and colleagues.
The meta-analysis, with a mean follow-up of 3.8 years, included studies with sufficient information to allow the calculation of unadjusted and adjusted relative risks or studies that gave the actual risk estimate for each BMI group, said Dr. Lopez-Jimenez. Most data were collected in the late 1980s and 1990s.
Coronary artery disease was defined as history of percutaneous coronary intervention, coronary artery bypass graft, or myocardial infarction. BMI was used as a measure of obesity.
The findings were:
Patients with a low BMI) (<20) had a one-third increased relative risk (RR)
for total mortality (RR=1.37, 95% CI 1.32-1.43), and cardiovascular mortality
(RR 1.45, CI 1.16-1.81) compared with risks for normal-BMI patients who served
as the reference group.
Overweight patients (BMI 25-29.9) had the lowest
risk for total mortality (RR=0.87, CI 0.81-0·94) and cardiovascular mortality
(RR=0.88, CI 0.75-1.02).
Obese patients (BMI 30-35) had no increased risk
for total mortality (RR=0.93, CI 0.85-1.03) or cardiovascular mortality (RR
0.97, CI 0.82-1.15). However, obesity was associated with higher total mortality
specifically among patients with a history of coronary artery bypass surgery.
Severely obese patients (≥35) did not have an increase in total mortality
(RR 1.10, CI 0·87-1.41), but they had an almost 90% higher risk for
cardiovascular mortality (RR 1.88 CI, 1.05-3.34).
These findings, the researchers wrote, could be explained by the failure of BMI to discriminate between body fat and lean mass. The better outcomes for overweight people may be because they have more muscle than normal-weight people.
In addition, lower BMI values have been related to low lean body mass, and BMI might not adequately reflect adiposity, the authors wrote.
Also, they suggested, because low and normal BMI groups were almost consistently associated with a lower prevalence of established cardiovascular risk factors, these groups were less likely to receive effective secondary prevention therapies, such as exercise, a healthy diet, and treatment for other risk factors.
Finally, they said, extensive data have shown that central obesity poses a greater risk for cardiovascular disease than BMI.
Among the study's limitations, the researchers mentioned the lack of individual data and possible publication bias (papers suggesting no connection between BMI were not submitted or accepted). However, this bias was probably not a factor in their study, they said. Finally, and most important, they wrote, is the substantial heterogeneity of the results, making it difficult to detect small differences across studies.
From a clinical standpoint, the researchers said, a fundamental question is whether weight loss or maintaining a normal weight can decrease cardiovascular event in patients with coronary artery disease.
Because exercise and diet are the main components of a weight-loss program, it can be assumed that interventions for overweight patients with coronary disease will reduce cardiovascular outcomes, including mortality. However, Dr. Lopez-Jimenez said, no randomized controlled trials have yet been undertaken to address this relationship.
Additional studies with different methods are needed, he said, particularly those with different weight-loss strategies and those that use other methods of identifying obesity. These might include body composition techniques to measure body fat and distribution that also account for lean mass.
Pending further information, patients with coronary artery disease who are truly obese should be encouraged to pursue interventions that reduce body fat, the researchers said.
In an accompanying comment in the same Lancet issue, Maria G. Franzosi, M.D., of the Istituto Mario Negri in Milan, Italy, asked the question: "Is the debate on the relation between BMI and mortality over?" Her answer: "The meta-analysis does not provide new information, but some useful implications can be drawn from it. BMI can definitely be left aside as a clinical and epidemiological measure of cardiovascular risk for both primary and secondary prevention."
She explained that the "BMI is not a good measure of visceral fat, the key determinant of metabolic abnormalities that contribute to cardiovascular risk. Estimates of the effect of obesity based on BMI are therefore too low."
She also pointed out that "the better outcomes in overweight and mildly obese people might be because these individuals have a greater lean mass than normal weight and severely obese people. An increased lean mass is related to physical activity and independently contributes to reduced coronary artery disease risk."
The contribution of body fat to cardiovascular risk requires integrated basic research to which retrospective analyses of existing databases cannot add relevant insights, she wrote. However, she emphasized, "Uncertainty about the best index of obesity should not translate into uncertainty about the need for a prevention policy against excess bodyweight, which must be strongly supported."
Sunday, August 20, 2006
Coronary heart disease: from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s
Methods and results Data were used from two large cross-sectional health examination surveys representing the entire Finnish adult population in 1980 and 2000. In the 1978–80 survey, the sample covered 5101 individuals aged ≥45, of whom 88% participated. The 2000–2001 survey comprised 5310 individuals in the same age range. Participation rate in the health examination was 87%. Prevalence of CHD decreased in men and women under the age of 65 and increased among those aged ≥75. Prevalence of large Q-waves indicating previous myocardial infarction decreased in all male age groups and in women aged 65–74. The total estimated number of persons with CHD increased by 18% (95% CI=6–30) during the past 20 years in Finland. In 1980, the most dominant CHD group was men aged 45–64, whereas in 2000, women aged ≥75 comprised the largest CHD group.
Conclusion Although the prevalence of CHD has decreased among middle-aged persons, the number of CHD cases has increased during the past 20 years in Finland."
Friday, August 18, 2006
Cardiovascular disease prevention with a multidrug regimen
in the developing world: a cost-eff ectiveness analysis
Thomas A Gaziano, Lionel H Opie, Milton C Weinstein
Background Cardiovascular disease is the leading cause of death, with 80% of cases occurring in developing countries.
We therefore aimed to establish whether use of evidence-based multidrug regimens for patients at high risk for cardiovascular disease would be cost-eff ective in low-income and middle-income countries.
Methods We used a Markov model to do a cost-eff ectiveness analysis with two combination regimens. For primary prevention, we used aspirin, a calcium-channel blocker, an angiotensin-converting-enzyme inhibitor, and a statin, and assessed them in four groups with diff erent thresholds of absolute risks for cardiovascular disease. For secondary prevention, we assessed the same combination of drugs in one group, but substituted a β blocker for the
calcium-channel blocker. To compare strategies, we report incremental cost-eff ectiveness ratios (ICER), in US$ per quality-adjusted life-year (QALY).
Findings We recorded that preventive strategies could result in a 2-year gain in life expectancy. Across six developing World Bank regions, primary prevention yielded ICERs of US$746–890/QALY gained for patients with a 10-year absolute risk of cardiovascular disease greater than 25%, and $1039–1221/QALY gained for those with an absolute risk greater than 5%. ICERs for secondary prevention ranged from $306/QALY to $388/QALY gained.
Interpretation Regimens of aspirin, two blood-pressure drugs, and a statin could halve the risk of death from cardiovascular disease in high-risk patients. This approach is cost-eff ective according to WHO recommendations, and is robust across several estimates of drug effi cacy and of treatment cost. Developing countries should encourage the use of these inexpensive drugs that are currently available for both primary and secondary prevention.
In January 2006, the U.S. Food and Drug Administration (FDA) approved a new antianginal agent for the treatment of chronic stable angina, ranolazine (Ranexa™; CV Therapeutics, Inc.). The drug, patented in 1986 as a new molecular entity, is approved for use as combination therapy when angina is not adequately controlled with other antianginal agents.
Ranolazine was originally thought to have its greatest effect as a partial fatty oxidation inhibitor.12 Fatty acids rise precipitously in response to stress, including acute myocardial ischemia. " /.../
Thursday, August 17, 2006
The total cost of ischemic stroke from 2005 to 2050, in 2005 dollars, is projected to be $1.52 trillion for non-Hispanic whites, $313 billion for Hispanics, and $379 billion for African Americans, added up Devin Brown, M.D., M.S., of the University of Michigan, and colleagues.
The high cost of stroke care is an example of a perfect demographic storm -- an aging population, combined with an increase in ethnic groups at risk for stroke, and an health care system that emphasizes acute rather than preventive care. " /.../
Monday, August 07, 2006
The association of an irregular pulse with morbidity has been recognised since antiquity, and as long ago as 1628 William Harvey observed cardiac irregularity directly in animals. The modern emphasis on electrical demonstration of atrial fibrillation (AF) dates back a mere 100 years to the first publication by William Einthoven of an electrocardiogram showing the abnormality. Even the treatment of this disorder has a long and venerable history: William Withering published An account of the foxglove and some of its medical uses in 1785, and digoxin, the active extract of his remedy, remains in use today.
A patient developing AF in 2006 is faced with a wide array of potential therapies. A number of drugs can be employed to control the rapid heart rate, which is often an intrinsic part of AF; attempts can be made to restore sinus rhythm using drugs or direct current electrical shock; and an increasing number of surgical procedures are described. Despite the wide number of options available, there is an acknowledgement that AF is too frequently treated with the almost
automatic prescription of monotherapy with digoxin: this is still a useful drug over 200 years on but the best option for only a minority of patients. This failure to appreciate or implement proper treatment options in such a common condition makes AF an excellent topic for a national clinical guideline.
The guideline covers aspects of diagnosis and the management of AF in a number of different circumstances. It covers paroxysmal, persistent and permanent AF, considers AF developing after surgical procedures, and offers advice on haemodynamically unstable AF. Many of the recommendations relate to control of AF and the important decision of whether to attempt to restore sinus rhythm or concentrate on control of the heart rate. In a linked set of recommendations, the importance of considering anticoagulation in all these patients is emphasised.
This is sometimes neglected in clinical practice, but anticoagulation is of enormous potential benefit because of its role in stroke prevention, and one of the key recommendations in the guideline is that the risk of thromboembolism should be formally assessed. A simple clinical model that includes advice on appropriate prophylaxis is suggested for this purpose. Other key
recommendations cover the use of the electrocardiogram in diagnosis, and the preference in most patients for beta-blockers or rate-limiting calcium antagonists over digoxin for rate control.
The work of producing the guideline has been in the hands of a Guideline Development Group (GDG) comprising a small team from the National Collaborating Centre for Chronic Conditions working together with patients and health professionals with particular interest and experience in the management of AF. They have used the available evidence and their own clinical and personal judgement to produce guidance that is both clinically relevant and methodologically sound.
The GDG has had to evaluate a large amount of evidence during this process, and debate on some of the recommendations has been lively. The members have been driven throughout by the desire to produce a guideline that will be of value throughout the NHS. I am grateful to them for their hard work and for their expertise, and I am confident that they have produced a guideline that deserves to meet that aim.
Dr Bernard Higgins MD FRCP
Director, National Collaborating Centre for Chronic Conditions
Friday, August 04, 2006
RAS inhibitors 'protect against AF'
Drugs that inhibit the renin-angiotensin system (RAS) protect against new-onset atrial fibrillation (AF), particularly in patients with heart failure, a meta-analysis has shown. Kishlay Anand and co-workers from Creighton University in Omaha, Nebraska, searched PubMed for randomized controlled clinical trials reporting the incidence of AF in patients receiving ACE inhibitors or angiotensin II type 1 receptor blockers (ARBs). Their meta-analysis included a total of nine studies with 72,469 participants conducted between 1999 and 2005. The median follow-up period was 3.4 years, during which time 3738 new cases of AF were diagnosed. The pooled risk ratio for new-onset AF associated with RAS inhibition was 0.82, Anand and co-authors report in the American Heart Journal. Of the nine trials, just two – STOP-2 (enalapril/lisinopril) and VALUE (valsartan) – failed to show a benefit of treatment on AF incidence. In subgroup analyses, ACE inhibitors had a greater protective effect than ARBs (Risk Ratio [RR]=0.75 vs 0.81) and patients with heart failure benefited the most from RAS blockade (RR=0.57). There was no significant benefit on incident AF in patients with hypertension or myocardial infarction. A test for heterogeneity was significant, however, and the authors were unable to exclude the possibility of publication bias. "Currently, there is not sufficient evidence to recommend the use of ACE inhibitors and ARBs in routine clinical practice for prevention of AF," Anand and team conclude. "Our meta-analysis is hypothesis-generating and will lead to further investigation."
Am Heart J 2006; 152: 217–222
Adding an inhibitor of the renin-angiotensin system (RAS) to low-dose amiodarone is more effective than amiodarone alone for preventing arrhythmias in patients with paroxysmal atrial fibrillation (AF), study results have shown. Yuehui Yin (Chongqing University of Medical Sciences, China) and colleagues undertook a randomized study involving 177 patients with lone paroxysmal AF. The patients were randomly assigned to receive one of three open-label treatment regimens: (1) amiodarone 600 mg/day decreasing to 200 mg/day; (2) low-dose amiodarone plus losartan 50–100 mg/day; or (3) low-dose amiodarone plus perindopril 2–4 mg/day The primary endpoint, AF incidence between 14 days and 24 months of randomization, was reached by 41% patients in group 1, 19% in group 2, and 24% in group 3, reflecting a statistically significant difference between group 1 and groups 2 and 3. Furthermore, AF recurrence was significantly reduced in groups 2 and 3 versus group 1, although there was no difference in AF recurrence-free survival. Interestingly, left atrial diameter was significantly smaller in groups 2 and 3 than in group 1, the first time such an effect has been demonstrated. Writing in the European Heart Journal, Yin and co-authors say several mechanisms may underlie the beneficial effects of losartan and perindopril observed in their study. The drugs may reverse electrical remodeling caused by AF; they may inhibit AF-induced structural remodeling; or they may cause sympatholytic effects by reducing plasma norepinephrine levels. "The combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF," Yin et al conclude. "Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients."
Eur Heart J 2006; 27: 1841-1846"
This was the first study to identify a significant risk of acute MI among men with gout and no history of coronary artery disease, wrote Eswar Krishnan, M.D., M.P.H., and colleagues, of the University of Pittsburgh and the University of Pennsylvania in the August issue of Arthritis & Rheumatism. /.../
Thursday, August 03, 2006
Implementation of a clinical prediction rule based on three simple factors would reduce futile resuscitation efforts by almost 63%, reported the Termination of Resuscitation (TOR) trial investigators in the Aug. 3 issue of the New England Journal of Medicine.
"The prediction rule had a positive predictive value of 99.5% [for death] and a specificity of 90.2% [for death]," wrote Laurie J. Morrison, M.D., of the University of Toronto, and colleagues there and at Owen Sound (Ontario) Hospital.
The investigators analyzed data from 1,240 adult patients treated by 24 emergency medical systems in the province of Ontario from Jan. 1, 2002 to Jan. 30, 2004.
Wednesday, August 02, 2006
(Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) WRITING COMMITTEE MEMBERS, Valentin Fuster et al
Circulation published 2 August 2006, 10.1161/CIRCULATIONAHA.106.177031