Title: Preliminary Results Indicate Carotid Intima-Media Thickness Is Biomarker of Atherosclerosis: Presented at DALM
"Preliminary Results Indicate Carotid Intima-Media Thickness Is Biomarker of Atherosclerosis: Presented at DALM"By Crina Frincu-Mallos, PhD NEW YORK, NY -- October 12, 2007 -- Overall data from the IMPROVE trial support the concept that carotid intima-media thickness (IMT) and IMT progression constitute novel biomarkers of atherosclerotic disease, according to a study presented here on at the XVI International Symposium on Drugs Affecting Lipid Metabolism (DALM).
Elena Tremoli, MD, Professor and Director, Department of Pharmacological Sciences, University of Milan, and Research Coordinator, Centro Cardiologico Monzino, IRCCS, Milan, Italy, presented the data on October 6.
The Carotid IMT and IMT-PROgression as Predictors of Vascular Events in a High Risk European Population (IMPROVE) study is an ongoing prospective, multicentre, longitudinal study with 3,711 patients from six European countries. All patients were classified as being at high risk for cardiovascular disease with at least three vascular risk factors, said Dr. Tremoli.
Patient enrollment ended in April 2005; patients were recruited from Finland (n=1,050), Sweden (n=533), The Netherlands (n=532), France (n=501), and Italy (n=1,095).
This patient population consists of men and women in approximately a 1:1 ratio (aged 64 +- 5 years). The largest percentage of patients have familial hypercholesterolaemia (78.6%); 23.9% of patients have diabetes.
The study is designed to determine whether it is feasible to predict new vascular events based on the progression of carotid IMT, "alone or after integration with conventional and nonconventional risk factors," explained Dr. Tremoli. IMT, a novel surrogate marker of atherosclerosis, is measured by high-resolution B-mode ultrasound.
Preliminary results indicate a significant connection between high sensitivity C-reactive protein (hs-CRP) and gender in the overall population. "Hs-CRP is a determinant of carotid IMT in men only," said Dr. Tremoli. However, cigarette smoking unmasks the association between hs-CRP and carotid IMT in women, she added.
The study monitored the occurrence of cardiovascular events over a period of 36 months.
A total of 135 first events occurred in the 3,393 patients enrolled in the trial, the most common event being angina pectoris (n=45), angioplasty/stent (n=39), stroke (n=21), and coronary bypass (n=16).
In addition, the researchers observed a geographic (North-South) gradient in carotid IMT when they analysed the baseline data.
The preliminary data support the concept that carotid IMT is a biomarker of atherosclerotic disease, concluded Dr. Tremoli. Data on the predictive capacity of carotid IMT-progression should be available by the end of next year.
Funding for this study was provided by the Italian Ministry of Health, European Commission, and the IMPROVE project.
Presentation title: Carotid Intima Media Thickness as Marker of Atherosclerosis: Results of the IMPROVE Study. Abstract 159.
Showing posts with label Atherosclerosis. Show all posts
Showing posts with label Atherosclerosis. Show all posts
Sunday, October 14, 2007
Wednesday, August 15, 2007
The Association of Differing Measures of Overweight and Obesity With Prevalent Atherosclerosis
The Association of Differing Measures of Overweight and Obesity With Prevalent Atherosclerosis
J Am Coll Cardiol, 2007; 50:752-759,
The Dallas Heart Study
Division of Cardiology, Department of Internal Medicine Donald W. Reynolds Cardiovascular Clinical Research Center, the University of Texas Southwestern Medical Center, Dallas, Texas
Manuscript received January 29, 2007; revised manuscript received March 23, 2007, accepted April 1, 2007.
Objectives: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort.
Background: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden.
Methods: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging.
Results: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC).
Conclusions: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.
J Am Coll Cardiol, 2007; 50:752-759,
The Dallas Heart Study
Division of Cardiology, Department of Internal Medicine Donald W. Reynolds Cardiovascular Clinical Research Center, the University of Texas Southwestern Medical Center, Dallas, Texas
Manuscript received January 29, 2007; revised manuscript received March 23, 2007, accepted April 1, 2007.
Objectives: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort.
Background: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden.
Methods: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging.
Results: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC).
Conclusions: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.
Wednesday, August 8, 2007
Researchers At Cleveland Clinic Identify Site Of 'Dysfunction' In HDL, Carrier Of Good Cholesterol
Researchers At Cleveland Clinic Identify Site Of 'Dysfunction' In HDL, Carrier Of Good Cholesterol0l
8 Aug 2007
Researchers at Cleveland Clinic have identified the region within high density lipoprotein (HDL), the major carrier of "good" cholesterol, that can become dysfunctional within the artery wall, inhibiting the body's ability to fight cholesterol buildup.
The work of the researchers led by Stanley Hazen, M.D., Ph.D., Head of the Section of Preventive Cardiology and Rehabilitation at Cleveland Clinic appears online Aug. 5 in the journal Nature Structural & Molecular Biology in a paper entitled "The Refined Structure of Nascent HDL Reveals a Key Functional Domain for Particle Maturation and Dysfunction." It builds upon the researchers' previous work which determined that not all HDL helps protect arteries from becoming clogged with fatty deposits.
The findings are important because raising HDL levels represents a major target for new treatment strategies of atherosclerosis, the accumulation of harmful plaque in the arteries, by the pharmaceutical industry. Yet it appears that the function as well as the level of the HDL is important. This may also help explain research earlier this year which found that despite raising the level of HDL (good) cholesterol, the drug torcetrapib did not slow the progression of artery disease.
"In this study we describe a refined molecular model of a nascent HDL molecule that is dramatically improved upon its predecessors," Dr. Hazen said. "With our enhanced detail of the HDL molecule structure we are better able to understand the location and mechanics of dysfunction in HDL.
HDL becomes dysfunctional when a specific region on HDL is modified by myeloperoxidase (MPO), an enzyme present in white blood cells and found in atherosclerotic plaque. This inhibits HDL's ability to mature and effectively carry cholesterol cargo from cells of the artery wall. In their paper, the researchers describe the HDL as having a "solar flare" structure.
Zhiping Wu, Ph.D., a research fellow at Cleveland Clinic is the paper's first author. Valentin Gogonea, Ph.D., an Associate Professor in the Department of Chemistry at Cleveland State University collaborated in the research.
Tuesday, July 31, 2007
Heart rate and microinflammation in men: a relevant atherothrombotic link
High resting heart rate (HR) is associated with a microinflammatory response in healthy men and in those with atherothrombotic risk factors, which might explain why individuals with increased HR have a poor cardiovascular prognosis, Israeli researchers report.
Heart rate and microinflammation in men: a relevant atherothrombotic link
Rogowski et al.
Heart.2007; 93: 940-944
ABSTRACT
Objective and background: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR.
Methods: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors.
Results: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001)>/=79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 µmol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74x109/l.
Conclusions: Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.
Heart rate and microinflammation in men: a relevant atherothrombotic link
Rogowski et al.
Heart.2007; 93: 940-944
ABSTRACT
Objective and background: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR.
Methods: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors.
Results: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001)>/=79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 µmol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74x109/l.
Conclusions: Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.
Saturday, July 28, 2007
Air Pollution Link To Clogged Arteries
Air Pollution Link To Clogged Arteries
27 Jul 2007
Should we be watching our exposure to airborne pollution as well as our cholesterol levels?
Research now indicates that air pollution has a role to play in atherosclerosis (artery hardening), which can contribute to heart attacks or strokes.
Findings published in the open access journal, Genome Biology, show how the fats that clog arteries work together with air pollution particles, triggering the genes behind inflammation.
A research team drawn from medical and environmental engineering disciplines at the Universities of California, Los Angeles, investigated the relationship between oxidized phospholipids found in the low density lipoprotein (LDL) particles, the 'bad' fats that clog arteries, and diesel exhaust particles. They exposed cells that line human blood vessels (microvascular endothelial cells) to both exhaust particles and oxidised phospholipids, and measured the effect on genes by using microarray expression profiling. This allowed the identification of gene modules containing a high number of co-expressed genes. These modules appear to be activated by a combination of phospholipids and diesel particles and are linked to vascular inflammation pathways. To confirm these findings, the team exposed mice with high cholesterol levels to the pollutant diesel particles, and saw some of the same gene modules upregulated.
The American Cancer Society has reported a six percent increase in cardiopulmonary deaths for every 10 µg/m3 rise in particulates. Exactly how airborne pollutant particles cause cardiovascular injury is poorly understood. But it is known that these particles are generally coated with a number of chemicals such as organic hydrocarbons, transition metals, sulfates and nitrates. Organic hydrocarbons and transition metals inflame airways by generating reactive oxygen species and oxidative stress when combined with oxidised phospholipids in the arteries. This can lead to vascular inflammation, which can in turn lead to increased lesions in the clogged arteries, potentially giving rise to blood clots that trigger heart attack or stroke. These findings bring us closer to understanding the impact our environment has on our health.
"Air pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells"
Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo
Genome Biology
http://genomebiology.com/
27 Jul 2007
Should we be watching our exposure to airborne pollution as well as our cholesterol levels?
Research now indicates that air pollution has a role to play in atherosclerosis (artery hardening), which can contribute to heart attacks or strokes.
Findings published in the open access journal, Genome Biology, show how the fats that clog arteries work together with air pollution particles, triggering the genes behind inflammation.
A research team drawn from medical and environmental engineering disciplines at the Universities of California, Los Angeles, investigated the relationship between oxidized phospholipids found in the low density lipoprotein (LDL) particles, the 'bad' fats that clog arteries, and diesel exhaust particles. They exposed cells that line human blood vessels (microvascular endothelial cells) to both exhaust particles and oxidised phospholipids, and measured the effect on genes by using microarray expression profiling. This allowed the identification of gene modules containing a high number of co-expressed genes. These modules appear to be activated by a combination of phospholipids and diesel particles and are linked to vascular inflammation pathways. To confirm these findings, the team exposed mice with high cholesterol levels to the pollutant diesel particles, and saw some of the same gene modules upregulated.
The American Cancer Society has reported a six percent increase in cardiopulmonary deaths for every 10 µg/m3 rise in particulates. Exactly how airborne pollutant particles cause cardiovascular injury is poorly understood. But it is known that these particles are generally coated with a number of chemicals such as organic hydrocarbons, transition metals, sulfates and nitrates. Organic hydrocarbons and transition metals inflame airways by generating reactive oxygen species and oxidative stress when combined with oxidised phospholipids in the arteries. This can lead to vascular inflammation, which can in turn lead to increased lesions in the clogged arteries, potentially giving rise to blood clots that trigger heart attack or stroke. These findings bring us closer to understanding the impact our environment has on our health.
"Air pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells"
Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo
Genome Biology
http://genomebiology.com/
Friday, June 22, 2007
Estrogen therapy decreases coronary artery calcification
Estrogen therapy decreases coronary artery calcification
N Engl J Med 2007; 356: 2591-2602
MedWire News: Postmenopausal women receiving estrogen therapy have a lower build up of calcium plaque in their coronary arteries than women who do not take hormone replacement therapy (HRT), study findings show.
Calcified plaque in the coronary arteries is a marker for atheromatous plaque burden, and is predictive of future risk of cardiovascular events.
Results from the Women's Health Initiative (WHI) randomized trial of conjugated equine estrogens indicated a reduced need for coronary revascularization among women aged 50-59 years, but not older women, who were receiving estrogen compared with those on the placebo group.
JoAnn Manson (Harvard Medical School, Boston, Massachusetts, USA) and colleagues carried out a substudy shortly after the WHI trial ended to determine whether the coronary artery calcium burden differed according to group assignment among 1064 women, aged 50-59 years, after a mean of 7.4 years of treatment.
After trial completion, women receiving estrogen had lower mean coronary artery calcium scores than those receiving placebo, at 83.1 versus 123.1 (p=0.02).
Michael Mendelsohn and Richard Karas, from Tufts University School of Medicine, Boston, wrote in a related editorial that these findings support the "potentially beneficial cardiovascular effects of HRT in younger menopausal women receiving the therapy for symptoms."
They added, however, that "it remains important to continue to emphasize that HRT should not be considered as a strategy to prevent cardiovascular disease in women; there are proven therapies for cardiovascular disease that remain underused in women."
"Clear and striking" cardioprotective effect of estrogen in young women requires confirmation"
ABSTRACT
Estrogen Therapy and Coronary-Artery Calcification
JoAnn E. Manson, M.D., Dr.P.H., Matthew A. Allison, M.D., M.P.H., Jacques E. Rossouw, M.D., J. Jeffrey Carr, M.D., Robert D. Langer, M.D., M.P.H., Judith Hsia, M.D., Lewis H. Kuller, M.D., Dr.P.H., Barbara B. Cochrane, Ph.D., Julie R. Hunt, Ph.D., Shari E. Ludlam, M.P.H., Mary B. Pettinger, M.S., Margery Gass, M.D., Karen L. Margolis, M.D., M.P.H., Lauren Nathan, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Marcia L. Stefanick, Ph.D., for the WHI and WHI-CACS Investigators
Background Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.
Methods In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.
Results The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.
Conclusions Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.
N Engl J Med 2007; 356: 2591-2602
MedWire News: Postmenopausal women receiving estrogen therapy have a lower build up of calcium plaque in their coronary arteries than women who do not take hormone replacement therapy (HRT), study findings show.
Calcified plaque in the coronary arteries is a marker for atheromatous plaque burden, and is predictive of future risk of cardiovascular events.
Results from the Women's Health Initiative (WHI) randomized trial of conjugated equine estrogens indicated a reduced need for coronary revascularization among women aged 50-59 years, but not older women, who were receiving estrogen compared with those on the placebo group.
JoAnn Manson (Harvard Medical School, Boston, Massachusetts, USA) and colleagues carried out a substudy shortly after the WHI trial ended to determine whether the coronary artery calcium burden differed according to group assignment among 1064 women, aged 50-59 years, after a mean of 7.4 years of treatment.
After trial completion, women receiving estrogen had lower mean coronary artery calcium scores than those receiving placebo, at 83.1 versus 123.1 (p=0.02).
Michael Mendelsohn and Richard Karas, from Tufts University School of Medicine, Boston, wrote in a related editorial that these findings support the "potentially beneficial cardiovascular effects of HRT in younger menopausal women receiving the therapy for symptoms."
They added, however, that "it remains important to continue to emphasize that HRT should not be considered as a strategy to prevent cardiovascular disease in women; there are proven therapies for cardiovascular disease that remain underused in women."
"Clear and striking" cardioprotective effect of estrogen in young women requires confirmation"
ABSTRACT
Estrogen Therapy and Coronary-Artery Calcification
JoAnn E. Manson, M.D., Dr.P.H., Matthew A. Allison, M.D., M.P.H., Jacques E. Rossouw, M.D., J. Jeffrey Carr, M.D., Robert D. Langer, M.D., M.P.H., Judith Hsia, M.D., Lewis H. Kuller, M.D., Dr.P.H., Barbara B. Cochrane, Ph.D., Julie R. Hunt, Ph.D., Shari E. Ludlam, M.P.H., Mary B. Pettinger, M.S., Margery Gass, M.D., Karen L. Margolis, M.D., M.P.H., Lauren Nathan, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Marcia L. Stefanick, Ph.D., for the WHI and WHI-CACS Investigators
Background Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.
Methods In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.
Results The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.
Conclusions Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways.
Sunday, May 27, 2007
Chronic Inflammation And Atherosclerosis
Insights Into Chronic Inflammation And Atherosclerosis
Rheumatoid arthritis, lupus, and other inflammatory rheumatic diseases are linked to a high rate of death from heart disease. One explanation is a greater susceptibility to atherosclerosis. Eventhough atherosclerosis is associated with inflammation in healthy individuals as well, the mechanism of inflammation and the reason for accelerated atherosclerosis in patients with inflammatory rheumatic disease remain unclear. Does atherosclerosis result from systemic inflammation, a hallmark of these rheumatic diseases, or from local inflammation of vessels?
To shed light on the link between chronic inflammation and atherosclerosis, a team of scientists in Norway and the United States, affiliated with the Cleveland Clinic Foundation and Brigham and Women's Hospital in Boston, focused on the aortas of recent recipients of coronary artery bypass graft (CABG) surgery, comparing biopsy specimens from patients with inflammatory rheumatic disease to those from patients without it. Their study, presented in the June 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), affirms inflammatory rheumatic disease and smoking as independent predictors of vessel wall inflammation. The vascular inflammation might be a factor that promotes atherosclerosis and the formation of aneurysms.
Aortic samples were obtained during CABG surgery, performed at two cardiac centers in Norway, from 66 patients with inflammatory rheumatic disease and 51 control patients. The inflammatory rheumatic disease group included patients with rheumatoid arthritis, psoriatic arthritis, lupus, ankylosing spondylitis, polymyalgia and other diseases. Age, body mass index, family history of heart disease, and other traditional cardiovascular risk factors were similar in both groups. All specimens were reviewed, by light microscope, for evidence of chronic inflammatory cell infiltration in the aortic wall. This was achieved by counting and measuring the mononuclear cell infiltrates (MCI) in the aorta, with particular attention to the adventitia, the deepest layer of vascular tissue. Using statistical analysis, the relationship between these inflammatory infiltrates and established lifestyle risk factors for heart disease was also assessed.
In the adventitia, MCIs occurred more frequently in patients with inflammatory rheumatic disease -- 47 percent of this group, compared with 20 percent of the control group. Along with greater prevalence, these inflammatory cells were larger in size. In the middle layer of the vessel wall (the media), MCIs were detected only in patients with inflammatory rheumatic disease. What's more, MCIs were observed in 6 of 7 patients with a history of aortic aneurysm.
In addition to inflammatory rheumatic disease, current smoking was independently linked to more pronounced chronic inflammatory infiltration in the inner adventitia.
"The opportunities for detecting aortic inflammation are limited," acknowledges the study's spokesperson, Ivana Hollan, M.D. "Our method of tissue examination allows the condition to be diagnosed in patients undergoing CABG surgery without increasing the preoperative risk".
Despite the limitations of its small sample size, this groundbreaking study of aortic inflammation in patients with inflammatory rheumatic disease indicates the need for further investigation into an inflammatory process that may increase vulnerability to dying from a heart attack or aneurysm.
Rheumatoid arthritis, lupus, and other inflammatory rheumatic diseases are linked to a high rate of death from heart disease. One explanation is a greater susceptibility to atherosclerosis. Eventhough atherosclerosis is associated with inflammation in healthy individuals as well, the mechanism of inflammation and the reason for accelerated atherosclerosis in patients with inflammatory rheumatic disease remain unclear. Does atherosclerosis result from systemic inflammation, a hallmark of these rheumatic diseases, or from local inflammation of vessels?
To shed light on the link between chronic inflammation and atherosclerosis, a team of scientists in Norway and the United States, affiliated with the Cleveland Clinic Foundation and Brigham and Women's Hospital in Boston, focused on the aortas of recent recipients of coronary artery bypass graft (CABG) surgery, comparing biopsy specimens from patients with inflammatory rheumatic disease to those from patients without it. Their study, presented in the June 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), affirms inflammatory rheumatic disease and smoking as independent predictors of vessel wall inflammation. The vascular inflammation might be a factor that promotes atherosclerosis and the formation of aneurysms.
Aortic samples were obtained during CABG surgery, performed at two cardiac centers in Norway, from 66 patients with inflammatory rheumatic disease and 51 control patients. The inflammatory rheumatic disease group included patients with rheumatoid arthritis, psoriatic arthritis, lupus, ankylosing spondylitis, polymyalgia and other diseases. Age, body mass index, family history of heart disease, and other traditional cardiovascular risk factors were similar in both groups. All specimens were reviewed, by light microscope, for evidence of chronic inflammatory cell infiltration in the aortic wall. This was achieved by counting and measuring the mononuclear cell infiltrates (MCI) in the aorta, with particular attention to the adventitia, the deepest layer of vascular tissue. Using statistical analysis, the relationship between these inflammatory infiltrates and established lifestyle risk factors for heart disease was also assessed.
In the adventitia, MCIs occurred more frequently in patients with inflammatory rheumatic disease -- 47 percent of this group, compared with 20 percent of the control group. Along with greater prevalence, these inflammatory cells were larger in size. In the middle layer of the vessel wall (the media), MCIs were detected only in patients with inflammatory rheumatic disease. What's more, MCIs were observed in 6 of 7 patients with a history of aortic aneurysm.
In addition to inflammatory rheumatic disease, current smoking was independently linked to more pronounced chronic inflammatory infiltration in the inner adventitia.
"The opportunities for detecting aortic inflammation are limited," acknowledges the study's spokesperson, Ivana Hollan, M.D. "Our method of tissue examination allows the condition to be diagnosed in patients undergoing CABG surgery without increasing the preoperative risk".
Despite the limitations of its small sample size, this groundbreaking study of aortic inflammation in patients with inflammatory rheumatic disease indicates the need for further investigation into an inflammatory process that may increase vulnerability to dying from a heart attack or aneurysm.
Tuesday, April 17, 2007
ILLUSTRATE - Considerações
Title: Effect of Torcetrapib on the Progression of Coronary AtherosclerosisNissen SE, Tardif JC, Nicholls SJ, et al., on behalf of the ILLUSTRATE Investigators.
Citation: N Engl J Med. 2007;356:1304-1316.
Study Question: Does torcetrapib, a novel cholesteryl ester transfer protein (CETP) inhibitor that raises high-density lipoprotein cholesterol (HDL-C) by more than 50%, impact progression of coronary atherosclerosis?
Methods: A total of 1,188 patients with coronary disease underwent intravascular ultrasonography (IVUS). After treatment with atorvastatin to reduce levels of low-density lipoprotein cholesterol (LDL-C) to <100 mg/dl (2.59 mmol/L), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated IVUS in 910 patients (77%). Each target site for the primary analysis was required to have <50% obstruction throughout a segment of 40 mm or longer.
Results: Mean age was 57 years, 70% were men, and 91% were on a statin at baseline. Baseline mean LDL-C was 84 mg/dl and HDL-C was 45.5 mg/dl, and median LDL-C:HDL-C was 1.89. After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib–atorvastatin therapy was an approximate 61% relative increase in HDL-C (43.9 mg/dl vs. 72.1 mg/dl) and a 20% relative decrease in LDL-C, reaching a ratio of LDL-C to HDL-C of <1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib–atorvastatin group (p = 0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (p = 0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment.
Conclusions: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL-C and decrease in LDL-C. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects.
Perspective: Previous similar IVUS studies have shown that intense lowering of LDL-C by statins decreases the total atheroma volume by as much as 14.7 mm3 at 24 months, and the infusion of A-1 Milano resulted in a 14.1 mm3 reduction in atheroma volume at 1 month. It would appear that increasing HDL particle cholesterol content with a CETP inhibitor does not result in better functioning HDL particles, and there are experimental data that these cholesterol-rich HDL particles may have proinflammatory effects. The clinical morbidity–mortality trial of torcetrapib–atorvastatin was prematurely terminated because of an increase in event rates that might be explained by both the increase in systolic blood pressure and dysfunctional HDL particles. In addition to niacin, several novel drugs/devices are currently being studied in randomized trials to determine their effect on atherosclerosis progression and events. Melvyn Rubenfire, M.D., F.A.C.C.
Tuesday, April 10, 2007
The REACH (Reduction of Atherothrombosis for Continued Health
One-Year Cardiovascular Event Rates in Outpatients With Atherothrombosis
Reference: JAMA 2007; 297: 1197-1206,http://jama.ama-assn.org/cgi/content/abstract/297/11/1197
This study suggests that outpatients with established atherosclerotic arterial disease and those with multiple risk factors for atherosclerosis, experience relatively high annual CVD event rates. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that fatal and nonfatal events can be prevented or delayed to an older age.
Authors: PG Steg, DL Bhatt, PWF Wilson, R D'Agostino, EM Ohman, J Röther, C-SLiau, AT Hirsch, J-L Mas, Y Ikeda, MJ Pencina, S Goto, for the REACH RegistryInvestigators
Reviewer: Robert Goldberg, PhD, ProCOR Contributing Editor
Problem addressed: Contemporary natural history of outpatients with atherosclerotic disease or multiple risk factors for CVD.Purpose of study: To examine contemporary, and multinational, one year even trates of CVD in outpatients with established arterial disease or with multiple coronary risk factors.
Location of study: Paris, France.
Study design: Prospective
Results: The REACH (Reduction of Atherothrombosis for Continued Health) registry includes data on adult (>= 45 years) outpatients with established CVD, CAD, or peripheral vascular disease, as well as in those with at least three riskf actors for atherothrombosis being present. These high-risk patients were recruited from nearly 5600 physician practices in 44 countries between December 2003 and June 2004. Follow-up data were collected at approximately one year after study enrollment and information was collected about the occurrence of fatal and non-fatal eventsof stroke, MI, or CVD in the study sample. A total of nearly 65,000 patients were enrolled in this study. Approximately two-thirds were men, 44% had a history of diabetes, 82% had prior hypertension, nearly one in three were obese, and the average age of the study sample was 69 years. Approximately three quarters of study enrollees were being treated with antiplatelet therapy, nearly half were prescribed beta blockers, 69% were on statin therapy, and nearly 40% were on an antidiabetic agent at the time of study entry. As expected, both the frequency of coronary risk factors and treatment practices varied between the different geographic locales under study.Over the course of the one-year follow-up, all-cause mortality was 2.6%; the death rates were nearly twice as high in those with established arterial diseaseas compared to those with multiple coronary risk factors (2.8% vs. 1.5%). The overall rate of combined events of CVD death, MI, or stroke was 4.2%, again being approximately two fold higher in those with established atheroscleroticarterial disease (4.7%) as compared to those with multiple risk factors only(2.2%). Moreover, the one-year event rates of CVD, MI, stroke, or related hospitalizations also varied inversely with the presence of established arterial disease as compared to those with multiple risk factors only.In addition to the occurrence of these fatal and nonfatal events, the frequency of the pooled CVD endpoint increased with the number of symptomatic arterial disease locations present. For example, 5.3% of patients with multiple CHD riskfactors developed this aggregate endpoint compared to 12.6%, 21.1%, and 26.3% of patients with one, two, and three symptomatic arterial disease locations,respectively. In terms of geographic variation, participants from Japan experienced the lowest rates of all study endpoints whereas the highest event rates were observed in the Middle East and Eastern Europe.
Discussion: The results of this large multi-site international study suggestthat outpatients with established atherosclerotic arterial disease, as well as those with multiple risk factors for atherosclerosis, experience relatively high annual event rates of CVD, with these rates varying according to the underlying burden of disease. Indeed, over the course of the one-year follow-up period, approximately one in every seven patients with underlying arterial disease experienced either a hard CVD endpoint or required hospitalization for anatherosclerotic event. These events were noted despite the relatively high use of secondary preventive modalities in the study sample, though the utilization of several agents was less than optimal, and relatively few patients were attarget goals for body weight, BP, or serum cholesterol levels.The present results clearly identify groups at increased risk for adverse events in whom lifestyle modifications and more optimal management with proven treatment regimens remain needed. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that both fatal and nonfatal events of the various manifestations of this disease process can be prevented or delayed to an olderage.
Colin Rose MD PhD, Cardiologist, Associate Professor of Medicine, McGill University, faz severas crítcas ao artigo e particularmente questões vinculadas aos conflitos de intereese (financial disclosure) dos pesquisadores e também do editorialista da JAMA.
Readers should be made aware of the disclosure of Dr. McDermott, the editorialist:
Financial Disclosures: Dr McDermott reports that she has received honoraria from Bristol-Myers Squibb, Sanofi-Aventis, NicOx, and Otsuka Pharmaceutical, has served as a consultant for Hutchinson Technology, and is currently receiving support from research grants from the National Heart, Lung, and Blood Institute.
Comentários de Colin Rose:
Why couldn’t JAMA find an editorialist with no connection to “industry”, particularly the company funding the study which was editorialized?
If you wonder why this is a “free” publication just look at the disclosures and funding:
Financial Disclosures:
Dr Bhatt reports that he has received honoraria for consulting on scientific advisory boards from AstraZeneca, Bristol-Myers Squibb, Centocor, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company; honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company; and provided expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization).
Dr Röther reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Steg reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis and has received research grants from Sanofi-Aventis.
Dr Steg reports having served as a member of the speakers’ bureau for Boehringer Ingelheim, Servier, GlaxoSmithKline, Merck, Sharp & Dohme, and Nycomed and also on a consultant ad board for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Sanofi-Aventis, Servier, and Takeda.
Dr Ohman reports that he has received research grants from Berlex, Sanofi-Aventis, Schering-Plough, Eli Lilly, Bristol-Myers Squibb, and Millennium. Dr Ohman reports that he has stock ownership in Medtronic, Savacor, and Response Biomedical and is a consultant for Invoise, Response Biomedical, Savacor, and Liposcience.
Dr Hirsch reports that he has received research grants from Bristol-Myers Squibb and Sanofi-Aventis; honoraria from Sanofi-Aventis; and speaker’s bureau fees for Sanofi-Aventis.
Dr Wilson reports that he has received a grant from Sanofi-Aventis.
None of the other authors reported disclosures.
Funding/Support: The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), who assisted with the design and conduct of the study and data collection.
Comentários de Colin Rose:
Call me paranoid but I have a suspicion that the conclusion of the next paper from REACH will be that “dual anti-platelet” therapy (read ASA and Plavix) is underused. Thus the “reduction” in REACH.
Comentários finais do Dr. Colin Rose:
In the final analysis, what is the point in studying atherosclerosis in a population in which 80% are overweight or obese, 44% are diabetic, 82% are hypertensive and 16% are smoking? The causes of their atherosclerosis are obvious, food and/or tobacco addictions as we have known for many years.
If sanofi-aventis and Bristol-Myers Squibb really want to reduce “atherothrombosis” and improve health they should fund programs for fighting these addictions instead of doing more surveys to try to justify more drug sales. From their own data it is clear that drugs do not increase life expectancy.
Reference: JAMA 2007; 297: 1197-1206,http://jama.ama-assn.org/cgi/content/abstract/297/11/1197
This study suggests that outpatients with established atherosclerotic arterial disease and those with multiple risk factors for atherosclerosis, experience relatively high annual CVD event rates. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that fatal and nonfatal events can be prevented or delayed to an older age.
Authors: PG Steg, DL Bhatt, PWF Wilson, R D'Agostino, EM Ohman, J Röther, C-SLiau, AT Hirsch, J-L Mas, Y Ikeda, MJ Pencina, S Goto, for the REACH RegistryInvestigators
Reviewer: Robert Goldberg, PhD, ProCOR Contributing Editor
Problem addressed: Contemporary natural history of outpatients with atherosclerotic disease or multiple risk factors for CVD.Purpose of study: To examine contemporary, and multinational, one year even trates of CVD in outpatients with established arterial disease or with multiple coronary risk factors.
Location of study: Paris, France.
Study design: Prospective
Results: The REACH (Reduction of Atherothrombosis for Continued Health) registry includes data on adult (>= 45 years) outpatients with established CVD, CAD, or peripheral vascular disease, as well as in those with at least three riskf actors for atherothrombosis being present. These high-risk patients were recruited from nearly 5600 physician practices in 44 countries between December 2003 and June 2004. Follow-up data were collected at approximately one year after study enrollment and information was collected about the occurrence of fatal and non-fatal eventsof stroke, MI, or CVD in the study sample. A total of nearly 65,000 patients were enrolled in this study. Approximately two-thirds were men, 44% had a history of diabetes, 82% had prior hypertension, nearly one in three were obese, and the average age of the study sample was 69 years. Approximately three quarters of study enrollees were being treated with antiplatelet therapy, nearly half were prescribed beta blockers, 69% were on statin therapy, and nearly 40% were on an antidiabetic agent at the time of study entry. As expected, both the frequency of coronary risk factors and treatment practices varied between the different geographic locales under study.Over the course of the one-year follow-up, all-cause mortality was 2.6%; the death rates were nearly twice as high in those with established arterial diseaseas compared to those with multiple coronary risk factors (2.8% vs. 1.5%). The overall rate of combined events of CVD death, MI, or stroke was 4.2%, again being approximately two fold higher in those with established atheroscleroticarterial disease (4.7%) as compared to those with multiple risk factors only(2.2%). Moreover, the one-year event rates of CVD, MI, stroke, or related hospitalizations also varied inversely with the presence of established arterial disease as compared to those with multiple risk factors only.In addition to the occurrence of these fatal and nonfatal events, the frequency of the pooled CVD endpoint increased with the number of symptomatic arterial disease locations present. For example, 5.3% of patients with multiple CHD riskfactors developed this aggregate endpoint compared to 12.6%, 21.1%, and 26.3% of patients with one, two, and three symptomatic arterial disease locations,respectively. In terms of geographic variation, participants from Japan experienced the lowest rates of all study endpoints whereas the highest event rates were observed in the Middle East and Eastern Europe.
Discussion: The results of this large multi-site international study suggestthat outpatients with established atherosclerotic arterial disease, as well as those with multiple risk factors for atherosclerosis, experience relatively high annual event rates of CVD, with these rates varying according to the underlying burden of disease. Indeed, over the course of the one-year follow-up period, approximately one in every seven patients with underlying arterial disease experienced either a hard CVD endpoint or required hospitalization for anatherosclerotic event. These events were noted despite the relatively high use of secondary preventive modalities in the study sample, though the utilization of several agents was less than optimal, and relatively few patients were attarget goals for body weight, BP, or serum cholesterol levels.The present results clearly identify groups at increased risk for adverse events in whom lifestyle modifications and more optimal management with proven treatment regimens remain needed. These findings reinforce the continued efforts that need to be directed toward the primary and secondary prevention of underlying atherosclerosis so that both fatal and nonfatal events of the various manifestations of this disease process can be prevented or delayed to an olderage.
Colin Rose MD PhD, Cardiologist, Associate Professor of Medicine, McGill University, faz severas crítcas ao artigo e particularmente questões vinculadas aos conflitos de intereese (financial disclosure) dos pesquisadores e também do editorialista da JAMA.
Readers should be made aware of the disclosure of Dr. McDermott, the editorialist:
Financial Disclosures: Dr McDermott reports that she has received honoraria from Bristol-Myers Squibb, Sanofi-Aventis, NicOx, and Otsuka Pharmaceutical, has served as a consultant for Hutchinson Technology, and is currently receiving support from research grants from the National Heart, Lung, and Blood Institute.
Comentários de Colin Rose:
Why couldn’t JAMA find an editorialist with no connection to “industry”, particularly the company funding the study which was editorialized?
If you wonder why this is a “free” publication just look at the disclosures and funding:
Financial Disclosures:
Dr Bhatt reports that he has received honoraria for consulting on scientific advisory boards from AstraZeneca, Bristol-Myers Squibb, Centocor, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka, Paringenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company; honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company; and provided expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization).
Dr Röther reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Steg reports that he has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis and has received research grants from Sanofi-Aventis.
Dr Steg reports having served as a member of the speakers’ bureau for Boehringer Ingelheim, Servier, GlaxoSmithKline, Merck, Sharp & Dohme, and Nycomed and also on a consultant ad board for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Sanofi-Aventis, Servier, and Takeda.
Dr Ohman reports that he has received research grants from Berlex, Sanofi-Aventis, Schering-Plough, Eli Lilly, Bristol-Myers Squibb, and Millennium. Dr Ohman reports that he has stock ownership in Medtronic, Savacor, and Response Biomedical and is a consultant for Invoise, Response Biomedical, Savacor, and Liposcience.
Dr Hirsch reports that he has received research grants from Bristol-Myers Squibb and Sanofi-Aventis; honoraria from Sanofi-Aventis; and speaker’s bureau fees for Sanofi-Aventis.
Dr Wilson reports that he has received a grant from Sanofi-Aventis.
None of the other authors reported disclosures.
Funding/Support: The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), who assisted with the design and conduct of the study and data collection.
Comentários de Colin Rose:
Call me paranoid but I have a suspicion that the conclusion of the next paper from REACH will be that “dual anti-platelet” therapy (read ASA and Plavix) is underused. Thus the “reduction” in REACH.
Comentários finais do Dr. Colin Rose:
In the final analysis, what is the point in studying atherosclerosis in a population in which 80% are overweight or obese, 44% are diabetic, 82% are hypertensive and 16% are smoking? The causes of their atherosclerosis are obvious, food and/or tobacco addictions as we have known for many years.
If sanofi-aventis and Bristol-Myers Squibb really want to reduce “atherothrombosis” and improve health they should fund programs for fighting these addictions instead of doing more surveys to try to justify more drug sales. From their own data it is clear that drugs do not increase life expectancy.
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