ONLINE FIRST
The following articles were published at www.nejm.org on June 5, 2007. They will appear in the July 5, 2007 issue of the Journal.
Original ArticleRosiglitazone Evaluated for Cardiovascular Outcomes — An Interim Analysis P.D. Home and Others
EditorialRosiglitazone — Continued Uncertainty about Safety J.M. Drazen, S. Morrissey, and G.D. Curfman
EditorialRosiglitazone and Cardiotoxicity — Weighing the Evidence D.M. Nathan
EditorialThe Record on Rosiglitazone and the Risk of Myocardial Infarction B.M. Psaty and C.D. Furberg
Tuesday, June 5, 2007
Prognostic Value of the New York Heart Association Classification in End-Stage Renal Disease
Prognostic Value of the New York Heart Association Classification in End-Stage Renal Disease
Maurizio Postorino; Carmen Marino; Giovanni Tripepi; Carmine Zoccali; on behalf of the Calabrian Registry of Dialysis and Transplantation*
Nephrol Dial Transplant. 2007;22(5):1377-1382. ©2007 Oxford University Press
Abstract and Introduction
Abstract
Background:
The New York Heart Association (NYHA) classification is a strong predictor of mortality and an established instrument for risk stratification in patients with heart disease but data on the validity of this classification in end-stage renal disease (ESRD) are sparse.
Methods:
In this study, we tested the predictive value of the NYHA in patients with ESRD and compared it with that of two established indexes of disease severity, i.e. the Khan index and the renal disease severity score (RDSS). The study cohort was composed of 1322 incident patients in a dialysis registry (772 male and 550 female, age 61 ± 16 years).
Results:
During the follow-up period (41 ± 27 months) 551 patients died. A multivariate COX model including the NYHA classification explained 39% of the variation in mortality, a figure almost identical to that of a model based on the RDSS (37%) and superior (P < 0.001) to that provided by the Khan index-based model (32%). The area under the receiver operating characteristic curve of NYHA classification, as related to all-cause mortality, was 0.74 (95% CI: 0.71-0.77, P < 0.001). Again, RDSS had a predictive value for mortality (0.74, 95% CI: 0.72-0.77) identical to that of NYHA and higher than that of the Khan index (0.70, 95% CI: 0.67-0.72).
Conclusion:
The NYHA is a powerful predictor of mortality in ESRD and provides prognostic information equal or superior to that given by other established indexes of disease severity. Given the pervasive nature of cardiovascular disease in ESRD, this classification may be recommended for risk stratification in this population.
More:
Link: http://www.medscape.com/viewarticle/557267_print
Maurizio Postorino; Carmen Marino; Giovanni Tripepi; Carmine Zoccali; on behalf of the Calabrian Registry of Dialysis and Transplantation*
Nephrol Dial Transplant. 2007;22(5):1377-1382. ©2007 Oxford University Press
Abstract and Introduction
Abstract
Background:
The New York Heart Association (NYHA) classification is a strong predictor of mortality and an established instrument for risk stratification in patients with heart disease but data on the validity of this classification in end-stage renal disease (ESRD) are sparse.
Methods:
In this study, we tested the predictive value of the NYHA in patients with ESRD and compared it with that of two established indexes of disease severity, i.e. the Khan index and the renal disease severity score (RDSS). The study cohort was composed of 1322 incident patients in a dialysis registry (772 male and 550 female, age 61 ± 16 years).
Results:
During the follow-up period (41 ± 27 months) 551 patients died. A multivariate COX model including the NYHA classification explained 39% of the variation in mortality, a figure almost identical to that of a model based on the RDSS (37%) and superior (P < 0.001) to that provided by the Khan index-based model (32%). The area under the receiver operating characteristic curve of NYHA classification, as related to all-cause mortality, was 0.74 (95% CI: 0.71-0.77, P < 0.001). Again, RDSS had a predictive value for mortality (0.74, 95% CI: 0.72-0.77) identical to that of NYHA and higher than that of the Khan index (0.70, 95% CI: 0.67-0.72).
Conclusion:
The NYHA is a powerful predictor of mortality in ESRD and provides prognostic information equal or superior to that given by other established indexes of disease severity. Given the pervasive nature of cardiovascular disease in ESRD, this classification may be recommended for risk stratification in this population.
More:
Link: http://www.medscape.com/viewarticle/557267_print
Coronary Heart Disease (CHD)--One or Several Diseases?
[This article proposes an alternative causation for the emergence and decline of the coronary heart disease "epidemic" experienced by many developed countries. A consistent explanation by the authors addressing the emergence of CHD in developing countries would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.]
Title: Coronary Heart Disease (CHD)--One or Several Diseases?
Author: MI Azambuja, R Levins
Reference: Perspectives in Biology and Medicine 2007; 50(2): 228,
http://muse.jhu.edu/journals/perspectives_in_biology_and_medicine/toc/pbm50.2.html
Reviewer: Carlos Mendoza Montano, PhD, APRECOR, Guatemala, ProCOR contributing editor, e-mail: projhouse@intelnet.net.gt
The current article presents an interesting perspective about the causation of CHD. It revisits evidence that may have been overlooked or misinterpreted during the heights of the CHD epidemic in the United States and other developed countries due to the prevalent framework of multicausality, and the hegemony of the lipid over alternative hypotheses to CHD causation. The authors of the article propose a fresh look at some old evidence which leads to new ways of thinking about CHD, its trends and its causes, and new ways of thinking about chronic disease occurrence in general.
According to the multifactorial model of causality, CHD is conceived as resulting from possible alternative and interconnected chains of exposures component causes) that would eventually become sufficient to initiate the disease in an individual. Azambuja and Levins argue that, 40 years after its introduction, we still lack a sound biologic theory to explain the development of CHD and its progression to death, which allows them to question both this causal model and the degenerative idea behind it.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker\'s hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker's hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention
Title: Coronary Heart Disease (CHD)--One or Several Diseases?
Author: MI Azambuja, R Levins
Reference: Perspectives in Biology and Medicine 2007; 50(2): 228,
http://muse.jhu.edu/journals/perspectives_in_biology_and_medicine/toc/pbm50.2.html
Reviewer: Carlos Mendoza Montano, PhD, APRECOR, Guatemala, ProCOR contributing editor, e-mail: projhouse@intelnet.net.gt
The current article presents an interesting perspective about the causation of CHD. It revisits evidence that may have been overlooked or misinterpreted during the heights of the CHD epidemic in the United States and other developed countries due to the prevalent framework of multicausality, and the hegemony of the lipid over alternative hypotheses to CHD causation. The authors of the article propose a fresh look at some old evidence which leads to new ways of thinking about CHD, its trends and its causes, and new ways of thinking about chronic disease occurrence in general.
According to the multifactorial model of causality, CHD is conceived as resulting from possible alternative and interconnected chains of exposures component causes) that would eventually become sufficient to initiate the disease in an individual. Azambuja and Levins argue that, 40 years after its introduction, we still lack a sound biologic theory to explain the development of CHD and its progression to death, which allows them to question both this causal model and the degenerative idea behind it.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker\'s hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker's hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention
Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials
Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials
Thavendiranthan et al have undertaken a study to examine the role of statins in primary prevention of cardiovascular disease (1)
Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. The authors included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model
seven trials with 42,848 patients were included. Note that the analysis also included primary prevention patients from the HPS trial (more than 80% were in secondary prevention) and the patients from the CARDS trial
mean follow-up was 4.3 years
statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = 0.02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively
statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = 0.13)
no significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed
the authors affirm that statin therapy could reduce the absolute risk of coronary events during the next 4.3 years by 0.75% in low-risk patients (NNT= 133), by 1.63% (NNT=61) in moderate-risk patients and by 2.51% (NNT=40) in high-risk patients. They also conclude that it could be cost-effective in patients with an absolute risk over 20% of having a coronary event in the following 10 years. It would not be cost-effective in patients with a risk <10%, and its use would be controversial in the risk-group of 10-20%
the study authors concluded that, in patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality
Reference:
1. Thavendiranathan P et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.
Thavendiranthan et al have undertaken a study to examine the role of statins in primary prevention of cardiovascular disease (1)
Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. The authors included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model
seven trials with 42,848 patients were included. Note that the analysis also included primary prevention patients from the HPS trial (more than 80% were in secondary prevention) and the patients from the CARDS trial
mean follow-up was 4.3 years
statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = 0.02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively
statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = 0.13)
no significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed
the authors affirm that statin therapy could reduce the absolute risk of coronary events during the next 4.3 years by 0.75% in low-risk patients (NNT= 133), by 1.63% (NNT=61) in moderate-risk patients and by 2.51% (NNT=40) in high-risk patients. They also conclude that it could be cost-effective in patients with an absolute risk over 20% of having a coronary event in the following 10 years. It would not be cost-effective in patients with a risk <10%, and its use would be controversial in the risk-group of 10-20%
the study authors concluded that, in patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality
Reference:
1. Thavendiranathan P et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.
Specialist care cuts heart deaths
Specialist care cuts heart deaths
Swift treatment to re-open the arteries at a specialist centre significantly increases the chances of surviving a heart attack, a study has found.
Doctors at Harefield Hospital found under 3% of patients treated with angioplasty at the specialist heart centre had died after 30 days.
But of those patients taken first to a general hospital before referral to the centre, more than 10% died.
The study was presented at a British Cardiovascular Society Conference.
This gives better long-term results - time is muscle Dr Miles Dalby
The British Heart Foundation estimates that 230,000 people in the UK have a heart attack each year, and that about 30% of these are fatal.
Dr Miles Dalby, a consultant cardiologist at Harefield Hospital, and colleagues looked at 180 patients who received direct primary angioplasty at their hospital.
Fast treatment
The patients were taken there directly by ambulance staff trained to identify patients who would benefit from the treatment.
Dr Dalby says patients at the hospital's heart attack centre receive treatment and have their blood flow restored within an average of 24 minutes after arrival.
They compared these with 181 patients who had received the treatment after being referred to the centre from a general hospital.
Cardiologists perform primary angioplasty to clear blockages in the heart's arteries - the artery is unblocked using a thin tube, then opened by inflating a small balloon, and held open with a metal tube, or stent.
In non-specialist centres treatment is often by thrombolysis drugs which dissolve the blood clots, but the study found in patients treated with thrombolysis in the preceding two years, around 9% died.
Dr Dalby said prompt treatment is vital for effective primary angioplasty, and that taking patients directly to heart attacks centres could reduce the number of deaths "significantly."
He said: "During a heart attack, blood flow to the heart muscle is blocked which damages it.
"The sooner the patient receives treatment enabling the blood flow to return to the coronary arteries, the less damage occurs.
"This gives better long-term results - time is muscle."
More detail needed
Dr Clive Weston, associate director of Royal College of Physician's Myocardial Infarction National Audit Project, which collects data on heart attack patients, said the results were "quite remarkable".
However he warned that in rural areas, where it make take some time to travel to a specialist centre, methods such as delivering thrombolytic treatments in ambulances could be more effective.
And he said the data needed to be explored in more detail to check there were no biases.
Thrombolysis is very effective if delivered soon after heart attack symptoms develop.
However, as time passes, angioplasty becomes the more effective treatment.
And Dr Weston said another benefit of primary angioplasty was that it allowed to doctors to see more of the coronary anatomy so they could see what had caused the heart attack and help prevent future attacks.
Judy O'Sullivan, cardiac nurse at the British Heart Foundation, said: "The study published by the Harefield team shows promising results for recent advances in the treatment of heart attacks at such specialist centres."
She said in the future angioplasty was likely to supercede thrombolysis as the treatment of choice for heart attacks,and added that patients' speed of response in dialling 999 could also affect their survival chances.
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/6719075.stm
Published: 2007/06/05 07:31:17 GMT
Swift treatment to re-open the arteries at a specialist centre significantly increases the chances of surviving a heart attack, a study has found.
Doctors at Harefield Hospital found under 3% of patients treated with angioplasty at the specialist heart centre had died after 30 days.
But of those patients taken first to a general hospital before referral to the centre, more than 10% died.
The study was presented at a British Cardiovascular Society Conference.
This gives better long-term results - time is muscle Dr Miles Dalby
The British Heart Foundation estimates that 230,000 people in the UK have a heart attack each year, and that about 30% of these are fatal.
Dr Miles Dalby, a consultant cardiologist at Harefield Hospital, and colleagues looked at 180 patients who received direct primary angioplasty at their hospital.
Fast treatment
The patients were taken there directly by ambulance staff trained to identify patients who would benefit from the treatment.
Dr Dalby says patients at the hospital's heart attack centre receive treatment and have their blood flow restored within an average of 24 minutes after arrival.
They compared these with 181 patients who had received the treatment after being referred to the centre from a general hospital.
Cardiologists perform primary angioplasty to clear blockages in the heart's arteries - the artery is unblocked using a thin tube, then opened by inflating a small balloon, and held open with a metal tube, or stent.
In non-specialist centres treatment is often by thrombolysis drugs which dissolve the blood clots, but the study found in patients treated with thrombolysis in the preceding two years, around 9% died.
Dr Dalby said prompt treatment is vital for effective primary angioplasty, and that taking patients directly to heart attacks centres could reduce the number of deaths "significantly."
He said: "During a heart attack, blood flow to the heart muscle is blocked which damages it.
"The sooner the patient receives treatment enabling the blood flow to return to the coronary arteries, the less damage occurs.
"This gives better long-term results - time is muscle."
More detail needed
Dr Clive Weston, associate director of Royal College of Physician's Myocardial Infarction National Audit Project, which collects data on heart attack patients, said the results were "quite remarkable".
However he warned that in rural areas, where it make take some time to travel to a specialist centre, methods such as delivering thrombolytic treatments in ambulances could be more effective.
And he said the data needed to be explored in more detail to check there were no biases.
Thrombolysis is very effective if delivered soon after heart attack symptoms develop.
However, as time passes, angioplasty becomes the more effective treatment.
And Dr Weston said another benefit of primary angioplasty was that it allowed to doctors to see more of the coronary anatomy so they could see what had caused the heart attack and help prevent future attacks.
Judy O'Sullivan, cardiac nurse at the British Heart Foundation, said: "The study published by the Harefield team shows promising results for recent advances in the treatment of heart attacks at such specialist centres."
She said in the future angioplasty was likely to supercede thrombolysis as the treatment of choice for heart attacks,and added that patients' speed of response in dialling 999 could also affect their survival chances.
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/6719075.stm
Published: 2007/06/05 07:31:17 GMT
Men With Inflammatory Marker Have Three Times Higher Risk Of Heart Disease
Men With Inflammatory Marker Have Three Times Higher Risk Of Heart Disease
05 Jun 2007
Men whose blood tests positive for the auto-antibody rheumatoid factor have a three times higher risk of heart disease, according to a study published online ahead of print in Heart .
This increased risk was similar to that found for the well-known risk factors of diabetes (2.5 times) and high blood pressure (4.4 times). However, rheumatoid factor was not found to increase the risk of heart disease in women.
The findings add more weight to the growing evidence that inflammation is implicated in atherosclerosis - a hardening of the arteries, when fats are deposited in the artery walls. It also raises the possibility that auto-immune processes and rheumatoid factor in particular may actually have a role in the disease process itself.
This build up of fatty deposits reduces blood supply to the heart (known as ischaemic heart disease) leading to angina and an increased risk of heart attack.
Rheumatoid factor is an auto-antibody present in up to 15% of adults and is strongly associated with rheumatoid arthritis. Chronic inflammatory diseases, such as rheumatoid arthritis, have been shown previously to increase the risk of ischaemic heart disease. However, the prevalence of rheumatoid arthritis in men in the UK is only about 0.4 per cent, so rheumatoid factor therefore seems to be an independent risk factor in men. Rheumatoid factor can be measured by a simple blood test available in all hospitals.
The study involved 567 men and 589 women born in Hertfordshire between 1931 and 1937 who were assessed for a history of ischaemic heart disease, rheumatoid factor and traditional risk factors for heart disease. They were also assessed for other common auto-antibodies (antinuclear antibodies and anticardiolipin antibodies), but no link to increased risk of ischaemic heart disease was found.
Another inflammatory marker C-reactive protein has also been linked to the development of ischaemic heart disease in previous studies.
The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men
Online First Heart 2007;0:1-5. doi: 10.1136/hrt.2006.097816
www.heart.bmj.com
Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=73015
05 Jun 2007
Men whose blood tests positive for the auto-antibody rheumatoid factor have a three times higher risk of heart disease, according to a study published online ahead of print in Heart .
This increased risk was similar to that found for the well-known risk factors of diabetes (2.5 times) and high blood pressure (4.4 times). However, rheumatoid factor was not found to increase the risk of heart disease in women.
The findings add more weight to the growing evidence that inflammation is implicated in atherosclerosis - a hardening of the arteries, when fats are deposited in the artery walls. It also raises the possibility that auto-immune processes and rheumatoid factor in particular may actually have a role in the disease process itself.
This build up of fatty deposits reduces blood supply to the heart (known as ischaemic heart disease) leading to angina and an increased risk of heart attack.
Rheumatoid factor is an auto-antibody present in up to 15% of adults and is strongly associated with rheumatoid arthritis. Chronic inflammatory diseases, such as rheumatoid arthritis, have been shown previously to increase the risk of ischaemic heart disease. However, the prevalence of rheumatoid arthritis in men in the UK is only about 0.4 per cent, so rheumatoid factor therefore seems to be an independent risk factor in men. Rheumatoid factor can be measured by a simple blood test available in all hospitals.
The study involved 567 men and 589 women born in Hertfordshire between 1931 and 1937 who were assessed for a history of ischaemic heart disease, rheumatoid factor and traditional risk factors for heart disease. They were also assessed for other common auto-antibodies (antinuclear antibodies and anticardiolipin antibodies), but no link to increased risk of ischaemic heart disease was found.
Another inflammatory marker C-reactive protein has also been linked to the development of ischaemic heart disease in previous studies.
The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men
Online First Heart 2007;0:1-5. doi: 10.1136/hrt.2006.097816
www.heart.bmj.com
Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=73015
Monday, June 4, 2007
Treatment-risk paradox
Treatment-risk paradox highlighted
04 June 2007
Arch Intern Med 2007; 167: 1009-1016; 1019-1025
MedWire News:
Two studies in the Archives of Internal Medicine highlight concerns that high-risk heart disease patients who are most likely to benefit from evidence-based therapy are the least likely to receive it.
Andrew Yan (University of Toronto, Ontario, Canada) and colleagues studied the use of in-hospital cardiac catheterization in relation to risk among non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in the prospective, multicenter, Canadian ACS Registry 1 and Registry 2, which enrolled patients between 1999 and 2001 and 2002 and 2003, respectively.
The team stratified 4414 patients into low-, intermediate-, and high-risk groups based on tertiles of the Global Registry of Acute Coronary Events (GRACE) score.
The recommendation by the American College of Cardiology and American Heart Association of an early-invasive strategy in the management of NSTE-ACS patients appears to have been effective, with in-hospital use of cardiac catheterization increasing significantly from 38.8% in ACS Registry 1 to 63.5% in Registry 2 (p<0.001). color="#000099">In the second study, Finlay McAlister (University of Alberta, Edmonton, Canada) and team explored why clinicians are less likely to prescribe new therapies in low-risk than high-risk coronary artery disease (CAD) patients.
They studied 3871 patients diagnosed with CAD by angiography at three cardiac centers in Alberta between February 2004 and December 2005. The team defined patients as being at low, medium, or high risk according to the Duke Coronary Index.
The results showed that at 1 month after an angiogram, high-risk patients were less likely to be taking angiotensin-converting enzyme inhibitors, aspirin, and statins than lower-risk patients (25.8% vs 32.3%, odds ratio=0.73; risk ratio=0.80).
A similar relationship was seen across individual drug classes, although the strongest association was seen with statins.
However, adjusting for exertional capacity and depressive symptoms caused the relationship between risk and level and use of medications to almost completely disappear.
The authors report that there was no relationship between risk and symptom-relieving anti-anginal medications in unadjusted analyses and that it is therefore unlikely that clinicians preferentially avoid treating these patients. The more likely explanation, they say, is that patients who have depression, poor functional status, or both are less likely than those without to adhere to therapy.
"The treatment-risk paradox reported in administrative database analyses is attributable to clinical factors not typically captured in these databases," the authors write.
In an accompanying editorial, John Spertus and Mark Furman (University of Massachusetts, Worcester, USA) argued: "To overcome this paradox, what is needed is a transparent method for objectively calculating the risks of an adverse prognosis in our patients and, ideally, the expected benefits of treatment."
They said that barriers to the deployment of current models include: the complexity of employing multivariable regression models; the absence of data projecting the outcomes as a function of alternative treatment strategies; the limited range of meaningful outcomes predicted; and clinical inertia in substituting complex decision aids for anecdotal decision making.
They propose the creation of a national research agenda to "instill a new model of clinical practice."
Journal
04 June 2007
Arch Intern Med 2007; 167: 1009-1016; 1019-1025
MedWire News:
Two studies in the Archives of Internal Medicine highlight concerns that high-risk heart disease patients who are most likely to benefit from evidence-based therapy are the least likely to receive it.
Andrew Yan (University of Toronto, Ontario, Canada) and colleagues studied the use of in-hospital cardiac catheterization in relation to risk among non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in the prospective, multicenter, Canadian ACS Registry 1 and Registry 2, which enrolled patients between 1999 and 2001 and 2002 and 2003, respectively.
The team stratified 4414 patients into low-, intermediate-, and high-risk groups based on tertiles of the Global Registry of Acute Coronary Events (GRACE) score.
The recommendation by the American College of Cardiology and American Heart Association of an early-invasive strategy in the management of NSTE-ACS patients appears to have been effective, with in-hospital use of cardiac catheterization increasing significantly from 38.8% in ACS Registry 1 to 63.5% in Registry 2 (p<0.001). color="#000099">In the second study, Finlay McAlister (University of Alberta, Edmonton, Canada) and team explored why clinicians are less likely to prescribe new therapies in low-risk than high-risk coronary artery disease (CAD) patients.
They studied 3871 patients diagnosed with CAD by angiography at three cardiac centers in Alberta between February 2004 and December 2005. The team defined patients as being at low, medium, or high risk according to the Duke Coronary Index.
The results showed that at 1 month after an angiogram, high-risk patients were less likely to be taking angiotensin-converting enzyme inhibitors, aspirin, and statins than lower-risk patients (25.8% vs 32.3%, odds ratio=0.73; risk ratio=0.80).
A similar relationship was seen across individual drug classes, although the strongest association was seen with statins.
However, adjusting for exertional capacity and depressive symptoms caused the relationship between risk and level and use of medications to almost completely disappear.
The authors report that there was no relationship between risk and symptom-relieving anti-anginal medications in unadjusted analyses and that it is therefore unlikely that clinicians preferentially avoid treating these patients. The more likely explanation, they say, is that patients who have depression, poor functional status, or both are less likely than those without to adhere to therapy.
"The treatment-risk paradox reported in administrative database analyses is attributable to clinical factors not typically captured in these databases," the authors write.
In an accompanying editorial, John Spertus and Mark Furman (University of Massachusetts, Worcester, USA) argued: "To overcome this paradox, what is needed is a transparent method for objectively calculating the risks of an adverse prognosis in our patients and, ideally, the expected benefits of treatment."
They said that barriers to the deployment of current models include: the complexity of employing multivariable regression models; the absence of data projecting the outcomes as a function of alternative treatment strategies; the limited range of meaningful outcomes predicted; and clinical inertia in substituting complex decision aids for anecdotal decision making.
They propose the creation of a national research agenda to "instill a new model of clinical practice."
Journal
Sunday, June 3, 2007
Changes Related To Diabetic Cardiomyopathy Occur Soon After Diabetes Appears
Changes Related To Diabetic Cardiomyopathy Occur Soon After Diabetes Appears
"Dramatic" losses of a key biochemical substance in heart muscle tissue occur in the very earliest stages of diabetes induced in laboratory mice, scientists in Missouri are reporting ACS' Biochemistry, a weekly journal. Xianlin Han and colleagues did the study as part of a broader medical effort to understand diabetic cardiomyopathy. Heart abnormalities are the relatively common complication of diabetes and account for much of the increased mortality from heart disease in patients with diabetes.
The researchers used a powerful new technology termed "shotgun lipidomics" to show that hearts of diabetic mice lose large amounts of cardiolipin (CL), fatty materials essential for the heart's production of the energy needed for normal contraction. The changes, which involved a loss of CL followed by changes in the remaining CL, occurred as early as 5 days after rats became diabetic through administration of a compound that impairs insulin-producing cells in the pancreas.
Researchers observed the changes in two models of diabetes commonly used to study the two types of human diabetes. The changes happen before the appearance of toxic fatty materials regarded as a hallmark of diabetic cardiomyopathy and might be used as very sensitive biomarkers for the condition, the report indicates.
"Alterations in Myocardial Cardiolipin Content and Composition Occur at the Very Earliest Stages of Diabetes: A Shotgun Lipidomics Study"
CONTACT:
Xianlin Han, Ph.D.Washington University School of MedicineSt. Louis, Missouri 63130
"Dramatic" losses of a key biochemical substance in heart muscle tissue occur in the very earliest stages of diabetes induced in laboratory mice, scientists in Missouri are reporting ACS' Biochemistry, a weekly journal. Xianlin Han and colleagues did the study as part of a broader medical effort to understand diabetic cardiomyopathy. Heart abnormalities are the relatively common complication of diabetes and account for much of the increased mortality from heart disease in patients with diabetes.
The researchers used a powerful new technology termed "shotgun lipidomics" to show that hearts of diabetic mice lose large amounts of cardiolipin (CL), fatty materials essential for the heart's production of the energy needed for normal contraction. The changes, which involved a loss of CL followed by changes in the remaining CL, occurred as early as 5 days after rats became diabetic through administration of a compound that impairs insulin-producing cells in the pancreas.
Researchers observed the changes in two models of diabetes commonly used to study the two types of human diabetes. The changes happen before the appearance of toxic fatty materials regarded as a hallmark of diabetic cardiomyopathy and might be used as very sensitive biomarkers for the condition, the report indicates.
"Alterations in Myocardial Cardiolipin Content and Composition Occur at the Very Earliest Stages of Diabetes: A Shotgun Lipidomics Study"
CONTACT:
Xianlin Han, Ph.D.Washington University School of MedicineSt. Louis, Missouri 63130
Saturday, June 2, 2007
Friday, June 1, 2007
Caution With All Pain Medications
Use Caution With All Pain Medications, Reports The 'Harvard Heart Letter'
Not long ago, choosing a pain reliever meant finding one that eased your pain without being too hard on the stomach. Now, research suggests that some commonly used pain medications -- not just the now-banned Vioxx -- can raise the risk of having a heart attack or stroke. New step-by-step recommendations from the American Heart Association (AHA) can help you choose a pain reliever that's good for both the heart and stomach, reports the June 2007 issue of the "Harvard Heart Letter."
The AHA suggests starting with aspirin or acetaminophen (Tylenol) to quell muscle or joint pain. Aspirin is good for the heart, and acetaminophen doesn't affect blood clotting. If they don't work, the next step for most people would be a nonsteroidal anti-inflammatory drug (NSAID). Try naproxen (Aleve) first, then ibuprofen (Advil). Next is diclofenac, but more caution is needed with this drug (which is available only by prescription). Celebrex, the only drug in the class known as COX-2 inhibitors that remains on the market, should be the last resort for managing pain. In addition to the side effect of increasing the risk of clots in the bloodstream, COX-2 inhibitors can also reduce blood flow through the kidneys and raise blood pressure. For short-term pain in some people, a narcotic pain reliever such as tramadol (Ultram), codeine, or fentanyl (Actiq, Duragesic) may be an option.
The "Harvard Heart Letter" notes that you shouldn't be afraid to take aspirin, Tylenol, Advil, or Aleve for occasional aches and pains. But if you need a pain reliever several times a week, pay closer attention to your choices and talk with your doctor.
Harvard Heart Letter
http://www.health.harvard.edu/heart
Not long ago, choosing a pain reliever meant finding one that eased your pain without being too hard on the stomach. Now, research suggests that some commonly used pain medications -- not just the now-banned Vioxx -- can raise the risk of having a heart attack or stroke. New step-by-step recommendations from the American Heart Association (AHA) can help you choose a pain reliever that's good for both the heart and stomach, reports the June 2007 issue of the "Harvard Heart Letter."
The AHA suggests starting with aspirin or acetaminophen (Tylenol) to quell muscle or joint pain. Aspirin is good for the heart, and acetaminophen doesn't affect blood clotting. If they don't work, the next step for most people would be a nonsteroidal anti-inflammatory drug (NSAID). Try naproxen (Aleve) first, then ibuprofen (Advil). Next is diclofenac, but more caution is needed with this drug (which is available only by prescription). Celebrex, the only drug in the class known as COX-2 inhibitors that remains on the market, should be the last resort for managing pain. In addition to the side effect of increasing the risk of clots in the bloodstream, COX-2 inhibitors can also reduce blood flow through the kidneys and raise blood pressure. For short-term pain in some people, a narcotic pain reliever such as tramadol (Ultram), codeine, or fentanyl (Actiq, Duragesic) may be an option.
The "Harvard Heart Letter" notes that you shouldn't be afraid to take aspirin, Tylenol, Advil, or Aleve for occasional aches and pains. But if you need a pain reliever several times a week, pay closer attention to your choices and talk with your doctor.
Harvard Heart Letter
http://www.health.harvard.edu/heart
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