Docs debate cholesterol lowering for women in BMJ
May 15, 2007
Head to head
Should women be offered cholesterol lowering drugs to prevent cardiovascular disease?
Scott M Grundy, professor : Yes
Malcolm Kendrick, general practitioner: No
Dallas, TX and Macclesfield, UK - British general practitioner Dr Malcolm Kendrick takes on the eminent Dr Scott Grundy (University of Texas Southwestern Medical Center, Dallas) in a head-to-head debate in the May 12, 2007 issue of BMJ about whether women should be offered cholesterol-lowering treatment for the primary prevention of cardiovascular disease [1,2].
Kendrick—the author of a book recently published in the UK entitled The Great Cholesterol Con—says this discussion "is effectively about the use of statins," since no other cholesterol-lowering drug has been shown to improve survival. He maintains that statins fail to provide any overall health benefit in women and represent a massive financial drain on health resources. In addition, they cause substantial adverse effects, a problem that is underrecognized, he says.
Grundy, who supports the use of cholesterol-lowering drugs in women at moderate risk, told heartwire that his article was deliberately not statin-specific: "Statins are but one drug among others. Just because Dr Kendrick tried to frame the question in terms of statins, I made it very clear to BMJ that I would only discuss cholesterol-lowering therapy. What about the other drugs for lowering LDL—where do they fit in? And where does diet fit in? "
Lack of data should not mean lack of treatment
Grundy—a consultant to most of the major statin manufacturers—says: "The essential issue here is whether women as well as men should be considered for cholesterol-lowering drugs when their 10-year risk is 10% to 20%—that is, moderately high."
He accepts that there is insufficient evidence of the benefit of cholesterol-lowering drugs in primary-prevention trials in women and that some people use this as a reason not to give such therapy to women at risk of cardiovascular disease.
But he argues—and says most investigators believe—that primary and secondary prevention "is an artificial distinction that should give way to a strategy based on absolute risk for future cardiovascular events, regardless of whether previous events have occurred."
Clinical trials that have included both men and women at moderately high risk have shown overall risk reduction from cholesterol-lowering therapy. But post hoc analyses limited to women failed to show significant risk reduction because of a lack of statistical power. "Not enough women were included to provide a definitive result. . . . Some investigators take this result to mean lack of efficacy. But without adequate power, the results are simply not informative," Grundy maintains.
Until a large-scale trial of cholesterol lowering is performed in women at moderately high risk of CVD, there are two options, he says. One is to exclude such women from therapy; the alternative is to consider treatment based on a combination of clinical-trial evidence and epidemiological data.
He notes that dietary therapy is also important, but that there is even less clinical-trial evidence for the benefits of this intervention than for drug treatment in this specific group of women.
"Since a substantial proportion of women ultimately develop cardiovascular disease and die from it, withholding treatment in moderately high-risk women that has proved protective in men and in women at high risk seems to be stretching the restrictions of evidence-based medicine beyond reason," he concludes.
Should women receive statins at all?
GP Kendrick reduces the discussion to one on statins alone. He not only disagrees with Grundy regarding the treatment of women at moderate risk, he also questions whether women should be receiving statins at all.
"None of the large trials of secondary prevention with statins has shown a reduction in overall mortality in women. Perhaps more critically, the primary-prevention trials have shown neither an overall mortality benefit nor even a reduction in cardiovascular end points in women," he maintains.
Kendrick told heartwire that Grundy's main point "appears to be that, although there is no evidence of benefit in giving women statins (no overall mortality benefit at all, in any study, ever) that we shouldn't be too bothered about this."
Kendrick also questions Grundy's notion that the difference between primary and secondary prevention is an artificial distinction: "He states that the concept of primary prevention is arbitrary and should not really be used. Well, the major clinical trials on statins—the ones that everyone uses to quote benefit—did exactly this. Should we now go back and strike all primary-prevention trials/data from the record? In which case, you wouldn't have much data to go on and we would end up not prescribing statins at all."
Kendrick says he does prescribe statins in his practice, on the basis that in secondary prevention, in men, they have been shown to have cardiovascular and overall benefit. However, he does not prescribe statins to women, "but if other doctors in the practice do so, I do not take them off, as that is not my clinical decision to make. I try to convince as many people as I can that statins are not of value in women and only of value in secondary prevention in men."
And don't forget adverse events and costs
Kendrick also says that studies show doctors often dismiss adverse events associated with statins and that the side effects are not as benign as they have been made out to be. For example, the US FDA adverse-event reporting system shows that between November 1997 and May 2004, simvastatin was reported as a direct cause of 49 350 adverse events and 416 deaths, he notes.
"If a patient complains of side effects that I believe are related to their statin, I will not hesitate to lower the dose or take them off to see if the side effects go," he added to heartwire.
And statins represent the single greatest drug expenditure in the UK National Health Service, Kendrick notes. In 2006, the cost in England was £625 million ($1.2 billion), and this is expected to reach £1 billion in 2007. This money could be diverted to treatments of proven value, he argues.
"Spending millions on a treatment that has no proven benefit and may cause serious harm goes against the rationale of evidence-based prescribing," Kendrick concludes.
Costs trivial, decision should be made in terms of safety, efficacy.
Grundy told heartwire that the cost of statins is now "trivial" since generic versions became available. "At Wal-Mart in the US, you can get statins for 13 cents per tablet (per day). I am sure that the UK health system can get them for less. Therefore, Dr Kendrick cannot use the cost argument any longer but must argue on the basis of lack of efficacy and/or lack of safety."
Grundy continues: "The FDA's postmarketing reports are not a good way to assess safety, and the vast majority of people who take statins and other approved cholesterol-lowering drugs do not have side effects. But of course, drugs should not be taken without any expectation of benefit (efficacy).
"I personally do not believe that there is a distinction between primary and secondary prevention, but it is the absolute risk of patients that determines whether they are candidates for cholesterol-lowering drugs," he concludes.
Sources
Kendrick M. Should women be offered cholesterol-lowering drugs to prevent cardiovascular disease? No. BMJ 2007; 334: 983.
Grundy SM. Should women be offered cholesterol-lowering drugs to prevent cardiovascular disease? Yes. BMJ 2007; 334: 982.
Related links
Lancet Comment questions benefit of statins in primary prevention [HeartWire > Cardiometabolic risk; Jan 25, 2007]
Sunday, May 20, 2007
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
This article has been copublished in the August 15, 2006, issues of Circulation and the Journal of the American College of Cardiology and the August 16, 2006, issue of the European Heart Journal.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation)
LINK:
http://content.onlinejacc.org/cgi/content/full/48/4/854
OR:
American Family Physician
May 15, 2007 Vol. 75 No. 10
Practice Guidelines
Joint Guideline Released for Atrial Fibrillation
LINK:
http://www.aafp.org/afp/20070515/practice.html
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation)
LINK:
http://content.onlinejacc.org/cgi/content/full/48/4/854
OR:
American Family Physician
May 15, 2007 Vol. 75 No. 10
Practice Guidelines
Joint Guideline Released for Atrial Fibrillation
LINK:
http://www.aafp.org/afp/20070515/practice.html
Saturday, May 19, 2007
SAEM: Clinical Protocol Can Rule Out Pulmonary Embolism
SAEM: Clinical Protocol Can Rule Out Pulmonary Embolism
CHICAGO, May 17 -- Simple clinical criteria to rule out a pulmonary embolism can substitute for blood tests and CT scanning, according to researchers here.
The criteria, making up the so-called the PERC rule, consider eight clinical factors. If all eight are absent (PERC-negative) the probability of pulmonary embolism is quite low, said Jeff Kline, M.D., of the Carolinas Medical Center in Charlotte, N.C., and colleagues, at a Society for Academic Emergency Medicine meeting here.
The PERC rule includes clinical criteria such as age less than 50, pulse rate less than 100, 95% oxygen saturation level, no prior pulmonary embolism or deep vein thrombosis, and no recent surgery.
Ninety percent of the blood tests and ultrafast CT scans to detect pulmonary embolism turn out to be negative, the investigators said.
Over-testing for pulmonary embolism has emerged as a contentious issue, the researchers said. The CT scan may cost $2,500, has the potential for kidney damage in one of 12 patients, and has a heavy radiation dose. Yet physicians are ordering these tests for 2% to 3% of all emergency department patients, or 3.5 million patients a year, Dr. Kline said. Furthermore, the fear of medical malpractice has led to doing tests rather than using the data available through clinical evaluation.
To evaluate PERC, the authors from 2004 to 2006 enrolled 8,138 consecutive or random patients from 13 U.S. academic and community emergency departments staffed by emergency physicians. The patients' chief complaints were chest pain (52%), dyspnea (30%), cough (3%), syncope (2%), or other (12%).
The physicians' evaluations preceded the test results. Tests for pulmonary embolism were D-dimer (72%), CT (54%) and VQ scans (8%).
In the best case, PERC could reduce testing for pulmonary embolism by about 20% to 25%, the researchers said. Fully two-thirds of the testing was done for patients where the physician believed the probability of pulmonary embolism was less than 15%.
The authors found that the emergency physicians thought another diagnosis was more likely than pulmonary embolism in 83% of the cases, and that 67% were at low risk.
Of the patients, 524 (6.9%) were positive for image proven venous thromboembolism (pulmonary embolism or deep vein thrombosis). The median prevalence of positive venous thromboembolism across the 13 emergency departments was 6.7%.
From the entire cohort, 25% were PERC-negative, and only 1.2% of these patients were positive for venous thromboembolism. This equaled a diagnostic sensitivity of 95.6% (93.5 to 97.2%) and a specificity of 25.6% (24.6 to 26.6%).
Among low-risk patients, 1,519 (20% of the cohort) were PERC-negative, 14 (0.9%, 0.5 to 1.5%) were positive for venous thromboembolism, but none died.
Thus, low risk and PERC-negative had a sensitivity of 97.3% and specificity of 21.5%.
The combination of an emergency physician's impression that a patient is at low risk for pulmonary embolism, together with a negative PERC, provides compelling rationale to not order a test for pulmonary embolism, the researchers concluded.
This multicenter collaborative project shows that a careful history and physical examination can achieve the same degree of certainty without the cost and side effects of diagnostic testing.
The ability to document "PERC Rule negative" on the chart will provide physicians with the scientific and medicolegal backstop they need to justify not ordering a test on every patient with even a hint of pulmonary embolism, the investigators said.
Primary source:
Society for Academic Emergency Medicine 2007 MeetingSource reference: Kline J et al "Prospective, Multicenter Validation of the Pulmonary Embolism Rule-Out Criteria," presented May 16.
Abstracts are published in Vol. 14, Issue 5S, the May 2007 supplement of the official journal of the SAEM, Academic Emergency Medicine
CHICAGO, May 17 -- Simple clinical criteria to rule out a pulmonary embolism can substitute for blood tests and CT scanning, according to researchers here.
The criteria, making up the so-called the PERC rule, consider eight clinical factors. If all eight are absent (PERC-negative) the probability of pulmonary embolism is quite low, said Jeff Kline, M.D., of the Carolinas Medical Center in Charlotte, N.C., and colleagues, at a Society for Academic Emergency Medicine meeting here.
The PERC rule includes clinical criteria such as age less than 50, pulse rate less than 100, 95% oxygen saturation level, no prior pulmonary embolism or deep vein thrombosis, and no recent surgery.
Ninety percent of the blood tests and ultrafast CT scans to detect pulmonary embolism turn out to be negative, the investigators said.
Over-testing for pulmonary embolism has emerged as a contentious issue, the researchers said. The CT scan may cost $2,500, has the potential for kidney damage in one of 12 patients, and has a heavy radiation dose. Yet physicians are ordering these tests for 2% to 3% of all emergency department patients, or 3.5 million patients a year, Dr. Kline said. Furthermore, the fear of medical malpractice has led to doing tests rather than using the data available through clinical evaluation.
To evaluate PERC, the authors from 2004 to 2006 enrolled 8,138 consecutive or random patients from 13 U.S. academic and community emergency departments staffed by emergency physicians. The patients' chief complaints were chest pain (52%), dyspnea (30%), cough (3%), syncope (2%), or other (12%).
The physicians' evaluations preceded the test results. Tests for pulmonary embolism were D-dimer (72%), CT (54%) and VQ scans (8%).
In the best case, PERC could reduce testing for pulmonary embolism by about 20% to 25%, the researchers said. Fully two-thirds of the testing was done for patients where the physician believed the probability of pulmonary embolism was less than 15%.
The authors found that the emergency physicians thought another diagnosis was more likely than pulmonary embolism in 83% of the cases, and that 67% were at low risk.
Of the patients, 524 (6.9%) were positive for image proven venous thromboembolism (pulmonary embolism or deep vein thrombosis). The median prevalence of positive venous thromboembolism across the 13 emergency departments was 6.7%.
From the entire cohort, 25% were PERC-negative, and only 1.2% of these patients were positive for venous thromboembolism. This equaled a diagnostic sensitivity of 95.6% (93.5 to 97.2%) and a specificity of 25.6% (24.6 to 26.6%).
Among low-risk patients, 1,519 (20% of the cohort) were PERC-negative, 14 (0.9%, 0.5 to 1.5%) were positive for venous thromboembolism, but none died.
Thus, low risk and PERC-negative had a sensitivity of 97.3% and specificity of 21.5%.
The combination of an emergency physician's impression that a patient is at low risk for pulmonary embolism, together with a negative PERC, provides compelling rationale to not order a test for pulmonary embolism, the researchers concluded.
This multicenter collaborative project shows that a careful history and physical examination can achieve the same degree of certainty without the cost and side effects of diagnostic testing.
The ability to document "PERC Rule negative" on the chart will provide physicians with the scientific and medicolegal backstop they need to justify not ordering a test on every patient with even a hint of pulmonary embolism, the investigators said.
Primary source:
Society for Academic Emergency Medicine 2007 MeetingSource reference: Kline J et al "Prospective, Multicenter Validation of the Pulmonary Embolism Rule-Out Criteria," presented May 16.
Abstracts are published in Vol. 14, Issue 5S, the May 2007 supplement of the official journal of the SAEM, Academic Emergency Medicine
Anxiety and Coronart Artery Disease
Anxiety Worsens Prognosis in Patients With Coronary Artery Disease
J Am Coll Cardiol, 2007; 49:2021-2027
Objectives: This study examined the effect of anxiety on mortality and nonfatal myocardial infarction (MI) in patients with coronary artery disease (CAD).
Background: Inconsistent data exist regarding the impact of anxiety on the prognosis of patients with CAD.
Methods: The authors conducted a prospective cohort study at an outpatient cardiology clinic of 516 patients with CAD (mean age 68 years at entry, 82% male) by administering the Kellner Symptom Questionnaire annually. The primary outcome was the composite of nonfatal MI or all-cause mortality.
Results: During an average follow-up of 3.4 years, we documented 44 nonfatal MIs and 19 deaths. A high cumulative anxiety score was associated with an increased risk of nonfatal MI or death. Comparing the highest to lowest tertile of anxiety score, the age-adjusted hazard ratio was 1.97 (95% confidence interval 1.03 to 3.78, p = 0.04). In a multivariate Cox model after adjusting for age, gender, education, marital status, smoking, hypertension, diabetes mellitus, previous MI, body mass index, and total cholesterol, each unit increase in the cumulative mean anxiety score was associated with increased risk of nonfatal MI or total mortality; the hazard ratio was 1.06 (95% confidence interval 1.01 to 1.12, p = 0.02).
Conclusions: A high level of anxiety maintained after CAD diagnosis constitutes a strong risk of MI or death among patients with CAD.
Link: http://content.onlinejacc.org/cgi/content/abstract/49/20/2021?eaf
J Am Coll Cardiol, 2007; 49:2021-2027
Objectives: This study examined the effect of anxiety on mortality and nonfatal myocardial infarction (MI) in patients with coronary artery disease (CAD).
Background: Inconsistent data exist regarding the impact of anxiety on the prognosis of patients with CAD.
Methods: The authors conducted a prospective cohort study at an outpatient cardiology clinic of 516 patients with CAD (mean age 68 years at entry, 82% male) by administering the Kellner Symptom Questionnaire annually. The primary outcome was the composite of nonfatal MI or all-cause mortality.
Results: During an average follow-up of 3.4 years, we documented 44 nonfatal MIs and 19 deaths. A high cumulative anxiety score was associated with an increased risk of nonfatal MI or death. Comparing the highest to lowest tertile of anxiety score, the age-adjusted hazard ratio was 1.97 (95% confidence interval 1.03 to 3.78, p = 0.04). In a multivariate Cox model after adjusting for age, gender, education, marital status, smoking, hypertension, diabetes mellitus, previous MI, body mass index, and total cholesterol, each unit increase in the cumulative mean anxiety score was associated with increased risk of nonfatal MI or total mortality; the hazard ratio was 1.06 (95% confidence interval 1.01 to 1.12, p = 0.02).
Conclusions: A high level of anxiety maintained after CAD diagnosis constitutes a strong risk of MI or death among patients with CAD.
Link: http://content.onlinejacc.org/cgi/content/abstract/49/20/2021?eaf
Statin Therapy Acute Coronary Syndrome: A Systematic Review
Long-Term Benefit of Statin Therapy Initiated during Hospitalization for an Acute Coronary Syndrome: A Systematic Review of Randomized Trials.
American Journal of Cardiovascular Drugs. 7(2):135-141, 2007.
Bavry, Anthony A 1; Mood, Girish R 1; Kumbhani, Dharam J 2; Borek, Peter P 1; Askari, Arman T 1; Bhatt, Deepak L 1
Abstract:
Objective: This study sought to determine if the initiation of statin (HMG-CoA reductase inhibitor) therapy during acute coronary syndromes reduces long-term mortality and other adverse cardiac outcomes.
Background: Initiation of statin therapy during acute coronary syndromes has not been shown to reduce mortality, myocardial infarction or stroke within 4 months of follow-up.
Methods: Clinical trials that randomized patients with acute coronary syndromes to early statin therapy compared with less intensive lipid reduction (placebo/lower-dose statin/usual care), and reported long-term outcomes were included for analysis.
Results: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin therapy within 12 days of hospital presentation. The incidence of all-cause mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR] 0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to prevent one death was 84 patients. Similarly, the incidence of cardiovascular mortality in the statin versus the less intensive lipid reduction group was 2.4% versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus 5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus 12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90; 95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR 0.94; 95% CI 0.81, 1.09; p = 0.41).
Conclusions: The benefit of early initiation of statin therapy during acute coronary syndromes slowly accrues over time so that a survival advantage is seen around 24 months. Relatively few patients need to be treated to prevent one death over this time period. Furthermore, this approach significantly reduces unstable angina and the need for revascularization.
American Journal of Cardiovascular Drugs. 7(2):135-141, 2007.
Bavry, Anthony A 1; Mood, Girish R 1; Kumbhani, Dharam J 2; Borek, Peter P 1; Askari, Arman T 1; Bhatt, Deepak L 1
Abstract:
Objective: This study sought to determine if the initiation of statin (HMG-CoA reductase inhibitor) therapy during acute coronary syndromes reduces long-term mortality and other adverse cardiac outcomes.
Background: Initiation of statin therapy during acute coronary syndromes has not been shown to reduce mortality, myocardial infarction or stroke within 4 months of follow-up.
Methods: Clinical trials that randomized patients with acute coronary syndromes to early statin therapy compared with less intensive lipid reduction (placebo/lower-dose statin/usual care), and reported long-term outcomes were included for analysis.
Results: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin therapy within 12 days of hospital presentation. The incidence of all-cause mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR] 0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to prevent one death was 84 patients. Similarly, the incidence of cardiovascular mortality in the statin versus the less intensive lipid reduction group was 2.4% versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus 5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus 12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90; 95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR 0.94; 95% CI 0.81, 1.09; p = 0.41).
Conclusions: The benefit of early initiation of statin therapy during acute coronary syndromes slowly accrues over time so that a survival advantage is seen around 24 months. Relatively few patients need to be treated to prevent one death over this time period. Furthermore, this approach significantly reduces unstable angina and the need for revascularization.
Rimonabant: A novel selective cannabinoid-1 receptor antagonist
Rimonabant: A novel selective cannabinoid-1 receptor antagonist for treatment of obesity
American Journal of Health-System Pharmacy, Vol. 64, Issue 5, 481-489
PRITI N. PATEL, PHARM.D., BCPS, is Assistant Clinical Professor, College of Pharmacy and Allied Health Professions, and Director, Drug Information Center, St. John’s University, Queens, NY. ROLEE PATHAK, PHARM.D., BCPS, is Clinical Assistant Professor, Ernest Mario College of Pharmacy, Rutgers University, Piscataway, NJ, and Clinical Coordinator, Englewood Hospital and Medical Center, Englewood, NJ.
Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, and dosage and administration of rimonabant in the treatment of obesity and related metabolic factors are reviewed.
Summary. Discovery of the cannabinoid receptors has led to the development of rimonabant, a cannabinoid-1 (CB1) antagonist. Selective blockade of this receptor has been shown to lead to decreased appetite and food intake in animal models. Clinical studies have shown that rimonabant 20 mg once daily produces significant decreases in weight and waist circumference in obese human subjects and improves the lipid profile and glucose control. The frequency of metabolic syndrome also decreased significantly with rimonabant 20 mg daily. Limited data are available regarding the pharmacokinetics and pharmacodynamics of rimonabant. Preclinical data have demonstrated a long duration of action. As of yet, no drug–drug, drug–food, or drug– disease interactions have been identified with rimonabant. Adverse reactions occurred rarely, with nausea, dizziness, diarrhea, arthralgia, and back pain being the most common. Psychiatric disorders, including depression and anxiety, were the most common reasons for subjects to withdraw from rimonabant studies. Rimonabant has been shown to be safe for up to two years of treatment. Further research will clarify currently unknown areas, including pharmacokinetics, drug interactions, and the drug’s role in standard therapy.
Conclusion. Rimonabant, a selective CB1 antagonist, is a novel treatment option for obese and overweight individuals. Significant weight loss, decrease in waist circumference, and improvements in lipid profile and glucose control have been shown in clinical trials of rimonabant.
American Journal of Health-System Pharmacy, Vol. 64, Issue 5, 481-489
PRITI N. PATEL, PHARM.D., BCPS, is Assistant Clinical Professor, College of Pharmacy and Allied Health Professions, and Director, Drug Information Center, St. John’s University, Queens, NY. ROLEE PATHAK, PHARM.D., BCPS, is Clinical Assistant Professor, Ernest Mario College of Pharmacy, Rutgers University, Piscataway, NJ, and Clinical Coordinator, Englewood Hospital and Medical Center, Englewood, NJ.
Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, and dosage and administration of rimonabant in the treatment of obesity and related metabolic factors are reviewed.
Summary. Discovery of the cannabinoid receptors has led to the development of rimonabant, a cannabinoid-1 (CB1) antagonist. Selective blockade of this receptor has been shown to lead to decreased appetite and food intake in animal models. Clinical studies have shown that rimonabant 20 mg once daily produces significant decreases in weight and waist circumference in obese human subjects and improves the lipid profile and glucose control. The frequency of metabolic syndrome also decreased significantly with rimonabant 20 mg daily. Limited data are available regarding the pharmacokinetics and pharmacodynamics of rimonabant. Preclinical data have demonstrated a long duration of action. As of yet, no drug–drug, drug–food, or drug– disease interactions have been identified with rimonabant. Adverse reactions occurred rarely, with nausea, dizziness, diarrhea, arthralgia, and back pain being the most common. Psychiatric disorders, including depression and anxiety, were the most common reasons for subjects to withdraw from rimonabant studies. Rimonabant has been shown to be safe for up to two years of treatment. Further research will clarify currently unknown areas, including pharmacokinetics, drug interactions, and the drug’s role in standard therapy.
Conclusion. Rimonabant, a selective CB1 antagonist, is a novel treatment option for obese and overweight individuals. Significant weight loss, decrease in waist circumference, and improvements in lipid profile and glucose control have been shown in clinical trials of rimonabant.
Thursday, May 17, 2007
Stent implants in U.S. declined in April - Wall Street Journal
Stent implants in U.S. declined in April-WSJ
Thu May 17, 2007 4:41am ET
NEW YORK, May 17 (Reuters) - The number of coronary stents implanted in the United States dropped in April, the Wall Street Journal reported on its Web site on Thursday, citing a market research firm.
Stents are tiny wire mesh tubes used to prop open diseased heart arteries. Stent makers include Boston Scientific Corp. (BSX.N: Quote, Profile , Research), Abbott Laboratories (ABT.N: Quote, Profile , Research) and Johnson & Johnson (JNJ.N: Quote, Profile , Research).
Doctors performed about 71,200 stentings in April, the Journal reported, citing estimates from Millennium Research Group, a Toronto firm that surveys about 140 U.S. hospitals. The number was down more than 10 percent from March and more than 15 percent from a year earlier, it said.
The Journal cited doctors as saying that the drop was an unusually quick response to a study showing the devices provided little advantage over drug therapy in some patients.
Wall Street Journal - FREE PREVIEW
Stent Implants Declined in April
By Keith J. Winstein
Companies Featured in This Article: Boston Scientific, Abbott Laboratories, Johnson & Johnson
The number of coronary stents implanted in the U.S. dropped sharply in April, according to a leading market researcher, in what doctors said was an unusually quick response to a study showing the devices provided little advantage over drug therapy in some patients.
The new figures are the latest evidence that the tiny scaffolds used to prop open arteries are no longer a powerful growth engine for the medical industry. Americans spent at least $14 billion on coronary-stent procedures last year, including surgical and hospital fees. World-wide sales of the devices totaled about $6 billion.
Doctors performed about 71,200 stentings ...
THE FULL WSJ.com ARTICLE IS ONLY AVAILABLE TO SUBSCRIBERS.
IF YOU ARE ALREADY A SUBSCRIBER, PLEASE LOG IN AT THE TOP RIGHT OF THE PAGE.
Thu May 17, 2007 4:41am ET
NEW YORK, May 17 (Reuters) - The number of coronary stents implanted in the United States dropped in April, the Wall Street Journal reported on its Web site on Thursday, citing a market research firm.
Stents are tiny wire mesh tubes used to prop open diseased heart arteries. Stent makers include Boston Scientific Corp. (BSX.N: Quote, Profile , Research), Abbott Laboratories (ABT.N: Quote, Profile , Research) and Johnson & Johnson (JNJ.N: Quote, Profile , Research).
Doctors performed about 71,200 stentings in April, the Journal reported, citing estimates from Millennium Research Group, a Toronto firm that surveys about 140 U.S. hospitals. The number was down more than 10 percent from March and more than 15 percent from a year earlier, it said.
The Journal cited doctors as saying that the drop was an unusually quick response to a study showing the devices provided little advantage over drug therapy in some patients.
Wall Street Journal - FREE PREVIEW
Stent Implants Declined in April
By Keith J. Winstein
Companies Featured in This Article: Boston Scientific, Abbott Laboratories, Johnson & Johnson
The number of coronary stents implanted in the U.S. dropped sharply in April, according to a leading market researcher, in what doctors said was an unusually quick response to a study showing the devices provided little advantage over drug therapy in some patients.
The new figures are the latest evidence that the tiny scaffolds used to prop open arteries are no longer a powerful growth engine for the medical industry. Americans spent at least $14 billion on coronary-stent procedures last year, including surgical and hospital fees. World-wide sales of the devices totaled about $6 billion.
Doctors performed about 71,200 stentings ...
THE FULL WSJ.com ARTICLE IS ONLY AVAILABLE TO SUBSCRIBERS.
IF YOU ARE ALREADY A SUBSCRIBER, PLEASE LOG IN AT THE TOP RIGHT OF THE PAGE.
Higher serum phosphorus levels are associated with an increased CVD risk
Relations of Serum Phosphorus and Calcium Levels to the Incidence of Cardiovascular Disease in the Community
Ravi Dhingra, MD; Lisa M. Sullivan, PhD; Caroline S. Fox, MD; Thomas J. Wang, MD; Ralph B. D’Agostino, Sr, PhD; J. Michael Gaziano, MD, MPH; Ramachandran S. Vasan, MD
Arch Intern Med. 2007;167:879-885.
Background Higher levels of serum phosphorus and the calcium-phosphorus product are associated with increased mortality from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) or prior CVD. However, it is unknown if serum phosphorus levels influence vascular risk in individuals without CKD or CVD.
Methods We prospectively evaluated 3368 Framingham Offspring study participants (mean age, 44 years; 51% were women) free of CVD and CKD. We used multivariable Cox models to relate serum phosphorus and calcium levels to CVD incidence.
Results On follow-up (mean duration, 16.1 years), there were 524 incident CVD events (159 in women). In multivariable analyses and adjusting for established risk factors and additionally for glomerular filtration rate and for hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, a higher level of serum phosphorus was associated with an increased CVD risk in a continuous fashion (adjusted hazard ratio per increment of milligrams per deciliter, 1.31; 95% confidence interval, 1.05-1.63; P = .02; P value for trend across quartiles = .004). Individuals in the highest serum phosphorus quartile experienced a multivariable-adjusted 1.55-fold CVD risk (95% confidence interval, 1.16%-2.07%; P = .004) compared with those in the lowest quartile. These findings remained robust in time-dependent models that updated CVD risk factors every 4 years and in analyses restricted to individuals without proteinuria and an estimated glomerular filtration rate greater than 90 mL/min per 1.73 m2. Serum calcium was not related to CVD risk.
Conclusion Higher serum phosphorus levels are associated with an increased CVD risk in individuals free of CKD and CVD in the community. These observations emphasize the need for additional research to elucidate the potential link between phosphorus homeostasis and vascular risk.
Ravi Dhingra, MD; Lisa M. Sullivan, PhD; Caroline S. Fox, MD; Thomas J. Wang, MD; Ralph B. D’Agostino, Sr, PhD; J. Michael Gaziano, MD, MPH; Ramachandran S. Vasan, MD
Arch Intern Med. 2007;167:879-885.
Background Higher levels of serum phosphorus and the calcium-phosphorus product are associated with increased mortality from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) or prior CVD. However, it is unknown if serum phosphorus levels influence vascular risk in individuals without CKD or CVD.
Methods We prospectively evaluated 3368 Framingham Offspring study participants (mean age, 44 years; 51% were women) free of CVD and CKD. We used multivariable Cox models to relate serum phosphorus and calcium levels to CVD incidence.
Results On follow-up (mean duration, 16.1 years), there were 524 incident CVD events (159 in women). In multivariable analyses and adjusting for established risk factors and additionally for glomerular filtration rate and for hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, a higher level of serum phosphorus was associated with an increased CVD risk in a continuous fashion (adjusted hazard ratio per increment of milligrams per deciliter, 1.31; 95% confidence interval, 1.05-1.63; P = .02; P value for trend across quartiles = .004). Individuals in the highest serum phosphorus quartile experienced a multivariable-adjusted 1.55-fold CVD risk (95% confidence interval, 1.16%-2.07%; P = .004) compared with those in the lowest quartile. These findings remained robust in time-dependent models that updated CVD risk factors every 4 years and in analyses restricted to individuals without proteinuria and an estimated glomerular filtration rate greater than 90 mL/min per 1.73 m2. Serum calcium was not related to CVD risk.
Conclusion Higher serum phosphorus levels are associated with an increased CVD risk in individuals free of CKD and CVD in the community. These observations emphasize the need for additional research to elucidate the potential link between phosphorus homeostasis and vascular risk.
The Ottawa Aggressive Protocol for ED Management of Acute Atrial Fibrillation
Acad Emerg Med Volume 14, 5 Supplement 1 9,
The Ottawa Aggressive Protocol for ED Management of Acute Atrial Fibrillation
Ian Stiell, Catherine Clement, Garth Dickinson, Cheryl Symington, Jeffrey Perry and Christian Vaillancourt
University of Ottawa
Objectives
There is no consensus as to the optimal emergency department (ED) management of acute atrial fibrillation (AAF) or atrial flutter (AAFL). Our objective was to examine the efficacy and safety of the Ottawa Aggressive Protocol to convert and discharge ED patients with AAF/AAFL.
Methods
This 5-year cohort study included consecutive visits to a university hospital ED for adults presenting with acute-onset AAF/AAFL and who were managed with the Ottawa Aggressive Protocol. Patients were identified from the National Ambulatory Care Reporting System (NACRS) database. The Aggressive Protocol was overseen by the attending emergency physicians and included: (1) IV procainamide as infusion of 1 gram over 1 hour; (2) electrical cardioversion if necessary, by ED staff; (3) discharge from the ED with outpatient cardiology follow-up. Outcomes included conversion, adverse events, and relapse. The authors conducted descriptive data analyses with 95% CIs.
Results
Characteristics of the 660 eligible patient visits were mean age 64.5 years, mean heart rate 113.4, and mean duration symptoms 8.9 hours, AAF 95.2%, AAFL 4.9%. Overall, 96.8% of patients were discharged home from the ED and 90.3% were discharged in normal sinus rhythm. The respective discharge rates were 97.0% and 93.5% for those in AAF and 93.8% and 87.5% for those in AAFL. All patients received procainamide with a conversion rate of 58.3% (AAF 59.9%, AAFL 28.1%). Electrical cardioversion was attempted in 36.8% of visits with a success rate of 91.7% (AAF 91.0%, AAFL 100%). Adverse events occurred in 7.6% of cases: hypotension 6.7%, bradycardia 0.3%, AAF relapse within 7 days 8.6%, Torsades de Pointes 0%, cerebrovascular accident 0%, mortality 0%.
COMMENTARIES:
Acute atrial fibrillation managed in emergency department
17 May 2007
MedWire News: Over 90% of patients with acute atrial fibrillation (AAF) or atrial flutter (AAFL) can be discharged from the emergency department (ED) with a normal heart rhythm using the Ottawa Aggressive Protocol, a study from Canada shows.
The protocol involves an IV procainamide infusion of 1 g over 1 hour, electrical cardioversion if necessary, by ED staff, and discharge from the ED with outpatient cardiology follow-up. This contrasts with current practice in the USA, for example, where patients with AAF and AAFL are admitted to hospital and treated by cardiologists. Ian Stiell and colleagues from the University of Ottawa in Ontario studied the efficacy and safety of the Ottawa protocol in 660 consecutive patients, whose mean age was 64.5 years, mean heart rate 113.4 beats per minute, and mean duration of symptoms 8.9 hours. AAF was present in 95.2% and AAFL in 4.9%.
Overall, 96.8% of patients were discharged home from the ED and 90.3% were discharged with normal sinus rhythm. The corresponding discharge rates for patients in AAF and AAFL were 97.0% and 93.5%, and 93.8% and 87.5%.
All patients received procainamide with a conversion rate of 58.3% (AAF 59.9%, AAFL 28.1%) and electrical cardioversion was attempted in 36.8% patients, which was successful in 91.7% (AAF 91.0%, AAFL 100%).
Adverse events occurred in 7.6% of cases: hypotension in 6.7%, bradycardia in 0.3%, and AAF relapse within 7 days in 0.6%.
“This is the largest reported study of AAF/AAFL in the ED and demonstrates that the Ottawa Aggressive Protocol is extremely effective for the rapid cardioversion and discharge of patients by ED physicians,” said Stiell.
“This protocol is safe and could lead to a significant decrease in hospital admissions.”
The researchers presented their results at the annual meeting of the Society for Academic Emergency Medicine, held in Chicago, Illinois, USA.
Society for Academic Emergency Medicine Annual Meeting; Chicago, Illinois, USA: 16-19 May, 2007
The Ottawa Aggressive Protocol for ED Management of Acute Atrial Fibrillation
Ian Stiell, Catherine Clement, Garth Dickinson, Cheryl Symington, Jeffrey Perry and Christian Vaillancourt
University of Ottawa
Objectives
There is no consensus as to the optimal emergency department (ED) management of acute atrial fibrillation (AAF) or atrial flutter (AAFL). Our objective was to examine the efficacy and safety of the Ottawa Aggressive Protocol to convert and discharge ED patients with AAF/AAFL.
Methods
This 5-year cohort study included consecutive visits to a university hospital ED for adults presenting with acute-onset AAF/AAFL and who were managed with the Ottawa Aggressive Protocol. Patients were identified from the National Ambulatory Care Reporting System (NACRS) database. The Aggressive Protocol was overseen by the attending emergency physicians and included: (1) IV procainamide as infusion of 1 gram over 1 hour; (2) electrical cardioversion if necessary, by ED staff; (3) discharge from the ED with outpatient cardiology follow-up. Outcomes included conversion, adverse events, and relapse. The authors conducted descriptive data analyses with 95% CIs.
Results
Characteristics of the 660 eligible patient visits were mean age 64.5 years, mean heart rate 113.4, and mean duration symptoms 8.9 hours, AAF 95.2%, AAFL 4.9%. Overall, 96.8% of patients were discharged home from the ED and 90.3% were discharged in normal sinus rhythm. The respective discharge rates were 97.0% and 93.5% for those in AAF and 93.8% and 87.5% for those in AAFL. All patients received procainamide with a conversion rate of 58.3% (AAF 59.9%, AAFL 28.1%). Electrical cardioversion was attempted in 36.8% of visits with a success rate of 91.7% (AAF 91.0%, AAFL 100%). Adverse events occurred in 7.6% of cases: hypotension 6.7%, bradycardia 0.3%, AAF relapse within 7 days 8.6%, Torsades de Pointes 0%, cerebrovascular accident 0%, mortality 0%.
COMMENTARIES:
Acute atrial fibrillation managed in emergency department
17 May 2007
MedWire News: Over 90% of patients with acute atrial fibrillation (AAF) or atrial flutter (AAFL) can be discharged from the emergency department (ED) with a normal heart rhythm using the Ottawa Aggressive Protocol, a study from Canada shows.
The protocol involves an IV procainamide infusion of 1 g over 1 hour, electrical cardioversion if necessary, by ED staff, and discharge from the ED with outpatient cardiology follow-up. This contrasts with current practice in the USA, for example, where patients with AAF and AAFL are admitted to hospital and treated by cardiologists. Ian Stiell and colleagues from the University of Ottawa in Ontario studied the efficacy and safety of the Ottawa protocol in 660 consecutive patients, whose mean age was 64.5 years, mean heart rate 113.4 beats per minute, and mean duration of symptoms 8.9 hours. AAF was present in 95.2% and AAFL in 4.9%.
Overall, 96.8% of patients were discharged home from the ED and 90.3% were discharged with normal sinus rhythm. The corresponding discharge rates for patients in AAF and AAFL were 97.0% and 93.5%, and 93.8% and 87.5%.
All patients received procainamide with a conversion rate of 58.3% (AAF 59.9%, AAFL 28.1%) and electrical cardioversion was attempted in 36.8% patients, which was successful in 91.7% (AAF 91.0%, AAFL 100%).
Adverse events occurred in 7.6% of cases: hypotension in 6.7%, bradycardia in 0.3%, and AAF relapse within 7 days in 0.6%.
“This is the largest reported study of AAF/AAFL in the ED and demonstrates that the Ottawa Aggressive Protocol is extremely effective for the rapid cardioversion and discharge of patients by ED physicians,” said Stiell.
“This protocol is safe and could lead to a significant decrease in hospital admissions.”
The researchers presented their results at the annual meeting of the Society for Academic Emergency Medicine, held in Chicago, Illinois, USA.
Society for Academic Emergency Medicine Annual Meeting; Chicago, Illinois, USA: 16-19 May, 2007
Even low-level physical activity improves the cardiorespiratory fitness
Effects of Different Doses of Physical Activity on Cardiorespiratory Fitness Among Sedentary, Overweight or Obese Postmenopausal Women With Elevated Blood Pressure
A Randomized Controlled Trial
Timothy S. Church, MD, MPH, PhD; Conrad P. Earnest, PhD; James S. Skinner, PhD; Steven N. Blair, PED
JAMA. 2007;297:2081-2091.
Context Low levels of cardiorespiratory fitness are associated with high risk of mortality, and improvements in fitness are associated with reduced mortality risk. However, a poor understanding of the physical activity–fitness dose response relation remains.
Objective To examine the effect of 50%, 100%, and 150% of the NIH Consensus Development Panel recommended physical activity dose on fitness in women.
Design, Setting, and Participants Randomized controlled trial of 464 sedentary, postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg. Enrollment took place between April 2001 and June 2005 in the Dallas, Tex, area.
Intervention Participants were randomly assigned to 1 of 4 groups: 102 to the nonexercise control group and 155 to the 4-kcal/kg, 104 to the 8-kcal/kg, and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period. Target training intensity was the heart rate associated with 50% of each woman's peak O2.
Main Outcome Measure The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption ( O2abs, L/min).
Results The mean (SD) baseline O2abs values were 1.30 (0.25) L/min. The mean (SD) minutes of exercising per week were 72.2 (12.3) for the 4-kcal/kg, 135.8 (19.5) for the 8-kcal/kg, and 191.7 (33.7) for the 12-kcal/kg per week exercise groups. After adjustment for age, race/ethnicity, weight, and peak heart rate, the exercise groups increased their O2abs compared with the control group by 4.2% in the 4-kcal/kg, 6.0% in the 8-kcal/kg, and 8.2% in the 12-kcal/kg per week groups (P<.001 for each vs control; P for trend <.001). There was no treatment x subgroup interaction for age, body mass index, weight, baseline O2abs, race/ethnicity, or baseline hormone therapy use. There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group. Conclusion In this study, previously sedentary, overweight or obese postmenopausal women experienced a graded dose-response change in fitness across levels of exercise training.
COMMENTARIES Even small doses of activity boost heart fitness 16 May 2007 MedWire News: Even low-level physical activity improves the cardiorespiratory fitness of overweight, sedentary individuals, study findings reveal.
National Institutes of Health (NIH) guidelines recommend at least 30 minutes of moderate-intensity physical activity to promote general health, but it is not clear if sedentary people will benefit from lower levels of activity than this, explain Timothy Church (Louisiana State University System, Baton Rouge, USA) and colleagues.
To investigate, the researchers conducted a study in 464 sedentary, postmenopausal overweight or obese women with elevated blood pressure.
The women’s body mass indices ranged from 25.0 to 43.0 and systolic blood pressure from 120.0 to 159.9 mmHg.
The participants were randomly assigned to three different levels of exercise or to a no-exercise control group. The three exercise levels were cycling or walking sessions designed to expend 4 kcal/kg, 8kcal/kg, or 12 kcal/kg per week.
These levels corresponded to 50%, 100%, and 150% of the NIH consensus recommended activity level for such women.
Women who exercised participated in three or four training sessions each week for 6 months, at a training intensity of the heart rate associated with 50% peak oxygen consumption (VO2). Although maximal effort was obtained during exercise testing, the mean peak absolute (VO2abs) and relative (VO2rel) values were very low, at 1.30 l/min and 15.5 ml/kg/min, respectively, at baseline.
This demonstrated that the group had very low fitness levels at the start of the study, the authors note.
The 4-kcal/kg group exercised for a mean of 72.2 minutes per week over 2.6 sessions, the 8-kcal/kg group for 135.8 minutes per week during 2.8 sessions, and the 12-kcal/kg group for 191.7 minutes per week during 3.1 sessions.
There was a strong dose-response relationship between the amount of exercise and change in fitness, Church and team report in the Journal of the American Medical Association.
Peak absolute oxygen consumption VO2abs were significantly increased at all three exercise levels versus no exercise (1.33, 1.35, and 1.39 vs 1.28 l/min).
These values represented a 4.2% increase in VO2abs in the 4-kcal/kg group, a 6.0% increase in 8-kcal/kg group, and an 8.2% increase in the 12-kcal/kg group, compared with the control no-exercise group (all p<0.001 versus control; p for trend <0.001).
The dose-response relationship was seen across age, race, weight, baseline fitness, and hormone therapy subgroups.
Participants’ systolic and diastolic blood pressure levels, weight, and most other cardiovascular risk factors were not significantly altered with any level of exercise.
However, waist circumference, which was similar in each group at baseline, was significantly reduced at the end of the study in all 3 exercise groups compared with the control group (p<0.05 for each).
This was a significant finding given the importance of increased risk of insulin resistance, diabetes, and metabolic syndrome, and mortality associated with abdominal obesity, Church and team emphasize.
“Perhaps the most striking finding of our study is that even activity at the 4-kcal/kg per week level (approximately 72 min per week) was associated with a significant improvement in fitness compared with women in the nonexercise control group,” the team comments. JAMA 2007; 297: 2081-2091
A Randomized Controlled Trial
Timothy S. Church, MD, MPH, PhD; Conrad P. Earnest, PhD; James S. Skinner, PhD; Steven N. Blair, PED
JAMA. 2007;297:2081-2091.
Context Low levels of cardiorespiratory fitness are associated with high risk of mortality, and improvements in fitness are associated with reduced mortality risk. However, a poor understanding of the physical activity–fitness dose response relation remains.
Objective To examine the effect of 50%, 100%, and 150% of the NIH Consensus Development Panel recommended physical activity dose on fitness in women.
Design, Setting, and Participants Randomized controlled trial of 464 sedentary, postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg. Enrollment took place between April 2001 and June 2005 in the Dallas, Tex, area.
Intervention Participants were randomly assigned to 1 of 4 groups: 102 to the nonexercise control group and 155 to the 4-kcal/kg, 104 to the 8-kcal/kg, and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period. Target training intensity was the heart rate associated with 50% of each woman's peak O2.
Main Outcome Measure The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption ( O2abs, L/min).
Results The mean (SD) baseline O2abs values were 1.30 (0.25) L/min. The mean (SD) minutes of exercising per week were 72.2 (12.3) for the 4-kcal/kg, 135.8 (19.5) for the 8-kcal/kg, and 191.7 (33.7) for the 12-kcal/kg per week exercise groups. After adjustment for age, race/ethnicity, weight, and peak heart rate, the exercise groups increased their O2abs compared with the control group by 4.2% in the 4-kcal/kg, 6.0% in the 8-kcal/kg, and 8.2% in the 12-kcal/kg per week groups (P<.001 for each vs control; P for trend <.001). There was no treatment x subgroup interaction for age, body mass index, weight, baseline O2abs, race/ethnicity, or baseline hormone therapy use. There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group. Conclusion In this study, previously sedentary, overweight or obese postmenopausal women experienced a graded dose-response change in fitness across levels of exercise training.
COMMENTARIES Even small doses of activity boost heart fitness 16 May 2007 MedWire News: Even low-level physical activity improves the cardiorespiratory fitness of overweight, sedentary individuals, study findings reveal.
National Institutes of Health (NIH) guidelines recommend at least 30 minutes of moderate-intensity physical activity to promote general health, but it is not clear if sedentary people will benefit from lower levels of activity than this, explain Timothy Church (Louisiana State University System, Baton Rouge, USA) and colleagues.
To investigate, the researchers conducted a study in 464 sedentary, postmenopausal overweight or obese women with elevated blood pressure.
The women’s body mass indices ranged from 25.0 to 43.0 and systolic blood pressure from 120.0 to 159.9 mmHg.
The participants were randomly assigned to three different levels of exercise or to a no-exercise control group. The three exercise levels were cycling or walking sessions designed to expend 4 kcal/kg, 8kcal/kg, or 12 kcal/kg per week.
These levels corresponded to 50%, 100%, and 150% of the NIH consensus recommended activity level for such women.
Women who exercised participated in three or four training sessions each week for 6 months, at a training intensity of the heart rate associated with 50% peak oxygen consumption (VO2). Although maximal effort was obtained during exercise testing, the mean peak absolute (VO2abs) and relative (VO2rel) values were very low, at 1.30 l/min and 15.5 ml/kg/min, respectively, at baseline.
This demonstrated that the group had very low fitness levels at the start of the study, the authors note.
The 4-kcal/kg group exercised for a mean of 72.2 minutes per week over 2.6 sessions, the 8-kcal/kg group for 135.8 minutes per week during 2.8 sessions, and the 12-kcal/kg group for 191.7 minutes per week during 3.1 sessions.
There was a strong dose-response relationship between the amount of exercise and change in fitness, Church and team report in the Journal of the American Medical Association.
Peak absolute oxygen consumption VO2abs were significantly increased at all three exercise levels versus no exercise (1.33, 1.35, and 1.39 vs 1.28 l/min).
These values represented a 4.2% increase in VO2abs in the 4-kcal/kg group, a 6.0% increase in 8-kcal/kg group, and an 8.2% increase in the 12-kcal/kg group, compared with the control no-exercise group (all p<0.001 versus control; p for trend <0.001).
The dose-response relationship was seen across age, race, weight, baseline fitness, and hormone therapy subgroups.
Participants’ systolic and diastolic blood pressure levels, weight, and most other cardiovascular risk factors were not significantly altered with any level of exercise.
However, waist circumference, which was similar in each group at baseline, was significantly reduced at the end of the study in all 3 exercise groups compared with the control group (p<0.05 for each).
This was a significant finding given the importance of increased risk of insulin resistance, diabetes, and metabolic syndrome, and mortality associated with abdominal obesity, Church and team emphasize.
“Perhaps the most striking finding of our study is that even activity at the 4-kcal/kg per week level (approximately 72 min per week) was associated with a significant improvement in fitness compared with women in the nonexercise control group,” the team comments. JAMA 2007; 297: 2081-2091
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