Friday
Review: The Changing Face of HDL and the Best Way to Measure It
Wednesday
Usefulness of High-Density Lipoprotein Cholesterol to Predict Survival in Pulmonary Arterial Hypertension
2016 Jul 15;118(2):292-7. doi: 10.1016/j.amjcard.2016.04.028. Epub 2016 May 5.
It has been suggested that lipoprotein abnormalities may contribute to the pulmonary arteriolar dysfunction observed in pulmonary arterial hypertension (PAH). High-density lipoprotein cholesterol (HDL) has vasodilatory, anti-inflammatory, and endothelial protective properties. We hypothesized that a higher serum HDL level may be advantageous for survival in PAH and that the serum HDL level at diagnosis would be an independent predictor of survival in PAH and be additive to previously validated predictors of survival. This study included all patients with PAH seen at the Mayo Clinic Pulmonary Hypertension Clinic from January 1, 1995, to December 31, 2009, who had a baseline HDL measurement. Mortality was analyzed over 5 years using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards ratios were calculated to evaluate the relation between baseline HDL level and survival. HDL levels were available for 227 patients. Higher HDL levels were associated with significantly lower mortality. Patients with an HDL >54 mg/dl at diagnosis had a 5-year survival of 59%.
In conclusion, HDL was an independent predictor of survival in PAH.
Abstract
1Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
2Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address:
Larsen CM1, McCully RB1, Murphy JG1, Kushwaha SS1, Frantz RP1, Kane GC2
Copyright © 2016 Elsevier Inc.
- PMID:
- 27291969
- DOI:
- 10.1016/j.amjcard.2016.04.028
Thursday
How One Biotech Company Is Helping Fight Heart Disease
Maryland Heights, MO, August 25, 2015 Lee Biosolutions is a global healthcare biotech company investing in the development and manufacture of highly purified cardiac markers for the IVD industry used in early detection of heart disease. The company’s scientific team's extensive expertise with protein chemistry has led to the development and commercialization of important cardiac biomarkers used in the industry such as CKMB, Troponin, Myeloperoxidase, Myoglobin, CRP, HDL and LDL.
Burton Lee, CEO explained, " Early detection will help save lives which is why diagnostic companies around the world seek us out because we have the scientific expertise in isolating the specific marker that they need to help in the detection of heart disease. As a cardiovascular patient, when you go in for a blood test, its very likely the enzyme you see on your report is part of a cardiac panel in which we supplied the enzyme components. Its extremely gratifying for our employees to know that the products we produce will be used in a blood test that helps save a patient’s life.”
Lee Biosolutions stands out in the clinical diagnostic industry because of its historical manufacturing experience in mammalian tissues and serum protein extraction, purification and isolation. The company can tailor the purification, development, process chromatography and protein characterization to ensure its clients obtain the right product for their final application.
About Lee Biosolutions, Inc.:
We are headquartered in a 41,000 square feet state of the art cGMP-compliant facility in Maryland Heights, MO. Lee Biosolutions is a certified, licensed ISO, FDA, EPA and USDA leader in process development and bulk manufacturing of high quality purified enzymes and related proteins for research and clinical diagnostic tests. Lee Biosolutions products are used for such pathologies as cardiovascular disease, cancer, diabetes, urine analysis, coagulation, obesity, inflammatory, neurological, autoimmune diseases and immunological disorders
According the World Health Organization , Cardiovascular Disease (CVDs) is the number one cause of death in the world with over 17 million people dying in 2012 alone. In the United States , 1 in every 4 people will die each year from heart disease. Healthcare statistics indicate that heart disease kills more people than all the cancer victims.We are excited about the future of biomarkers that will save lives
Burton Lee, CEO explained, " Early detection will help save lives which is why diagnostic companies around the world seek us out because we have the scientific expertise in isolating the specific marker that they need to help in the detection of heart disease. As a cardiovascular patient, when you go in for a blood test, its very likely the enzyme you see on your report is part of a cardiac panel in which we supplied the enzyme components. Its extremely gratifying for our employees to know that the products we produce will be used in a blood test that helps save a patient’s life.”
Lee Biosolutions stands out in the clinical diagnostic industry because of its historical manufacturing experience in mammalian tissues and serum protein extraction, purification and isolation. The company can tailor the purification, development, process chromatography and protein characterization to ensure its clients obtain the right product for their final application.
About Lee Biosolutions, Inc.:
We are headquartered in a 41,000 square feet state of the art cGMP-compliant facility in Maryland Heights, MO. Lee Biosolutions is a certified, licensed ISO, FDA, EPA and USDA leader in process development and bulk manufacturing of high quality purified enzymes and related proteins for research and clinical diagnostic tests. Lee Biosolutions products are used for such pathologies as cardiovascular disease, cancer, diabetes, urine analysis, coagulation, obesity, inflammatory, neurological, autoimmune diseases and immunological disorders
Friday
Jekyll into Hyde: Breathing auto emissions turns HDL cholesterol from 'good' to 'bad'
Academic researchers have found that breathing motor vehicle emissions triggers a change in high-density lipoprotein (HDL) cholesterol, altering its cardiovascular protective qualities so that it actually contributes to clogged arteries. In addition to changing HDL from "good" to "bad," the inhalation of emissions activates other components of oxidation, the early cell and tissue damage that causes inflammation, leading to hardening of the arteries, according to the research team, which included scientists from UCLA and other institutions.
The findings of this early study, done in mice, are available in the online edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology, a publication of the American Heart Association, and will appear in the journal's June print edition.
Emission particles such as those from vehicles are major pollutants in urban settings. These particles are coated in chemicals that are sensitive to free radicals, which have been known to cause oxidation. The mechanism behind how this leads to atherosclerosis, however, has not been well understood.
In the study, the researchers found that after two weeks of exposure to vehicle emissions, mice showed oxidative damage in the blood and liver -- damage that was not reversed after a subsequent week of receiving filtered air. Altered HDL cholesterol may play a key role in this damaging process, they said.
"This is the first study showing that air pollutants promote the development of dysfunctional, pro-oxidative HDL cholesterol and the activation of an internal oxidation pathway, which may be one of the mechanisms in how air pollution can exacerbate clogged arteries that lead to heart disease and stroke," said senior author Dr. Jesus Araujo, an associate professor of medicine and director of environmental cardiology at the David Geffen School of Medicine at UCLA.
For the study, one group of mice was exposed to vehicle emissions for two weeks and then filtered air for one week, a second was exposed to two weeks of emissions with no filtered air, and a third was exposed to only clean, filtered air for two weeks. This part of the collaborative research took place at the Northlake Exposure Facility at the University of Washington, headed by study author Michael E. Rosenfeld.
"The biggest surprise was finding that after two weeks of exposure to vehicle emissions, one week of breathing clean filtered air was not enough to reverse the damage," said Rosenfeld, a professor of environmental and occupational health sciences and pathology at the University of Washington.
Mice were exposed for a few hours, several days a week, to whole diesel exhaust at a particulate mass concentration within the range of what mine workers usually are exposed to.
After the exposures, UCLA scientists analyzed blood and tissue specimens and checked to see if the protective antioxidant and anti-inflammatory properties of HDL, known as "good" cholesterol, were still intact. They used special analytical laboratory procedures originally developed by study author Mohamad Navab at UCLA to evaluate how "good" or "bad" HDL had become. The team found that many of the positive properties of HDL were markedly altered after the air-pollutant exposure.
For example, the HDL of mice exposed to two weeks of vehicle emissions, including those that received a subsequent week of filtered air, had a much-decreased ability to protect against oxidation and inflammation induced by low-density lipoprotein (LDL) cholesterol, known as "bad" cholesterol, than the mice that had only been exposed to filtered air.
According to researchers, without HDL's ability to inhibit LDL, along with other factors, the oxidation process may run unchecked. Moreover, not only was the HDL of the mice exposed to diesel exhaust unable to protect against oxidation, but, in fact, it further enhanced the oxidative process and even worked in tandem with the LDL to promote even more oxidative damage.
Researchers also found a twofold to threefold increase of additional oxidation products in the blood of mice exposed to vehicle emissions, as well as activation of oxidation pathways in the liver. The degree of HDL dysfunction was correlated with the level of these oxidation markers."We suggest that people try to limit their exposure to air pollutants, as they may induce damage that starts during the exposure and continues long after it ends," said first author Fen Yin, a researcher in the division of cardiology at the Geffen School of Medicine.
The current research builds on the team's previous findings that ambient ultrafine particles commonly found in air pollution, including vehicle emissions, enhance the build-up of cholesterol plaques in the arteries and that HDL may play a role."Our research helps confirm that the functionality of HDL may be as important to check as the levels," said study author Dr. Alan Fogelman, executive chair of the department of medicine and director of the atherosclerosis research unit at the Geffen School of Medicine.
The study was funded by the National Institute of Environmental Health Sciences; the National Heart, Lung and Blood Institute; and the U.S. Environmental Protection Agency.
Additional authors included Akeem Lawal, Jerry Ricks, Julie R. Fox and Tim Larson.
Published: in Health & Medicine
Source: University of California, Los Angeles (UCLA), Health Sciences
Tuesday
Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein
Abstract
In addition of being an important inflammatory biomarker and a risk factor for cardiovascular disease, much evidence indicates that the C-reactive protein (CRP) contributes to the atherosclerosis development process. This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs). Previous studies showed that the 17β-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC. Therefore, we hypothesize that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms. Using human aortic ECs (HAECs), we first evaluated CRP production by vascular EC and second demonstrated its self-induction. Indeed, recombinant human CRP stimulation induces a fivefold increase of CRP expression. A 1-h pre-treatment of E2 at a physiologic dose (10−9 M) leads to an important decrease of CRP production suggesting a partial blockage of its amplification loop mechanism. Furthermore, in HAEC, E2 reduces the secretion of the most potent agonist of CRP induction, the IL-6, by 21 %. E2 pre-treatment also decreased the expression of pro-inflammatory molecules IL-8, VCAM-1, and ICAM-1 induced by CRP and involved in leukocytes recruitment. In addition, we demonstrated that E2 could restore vascular endothelial growth factor-mediated EC migration response impaired by CRP suggesting another pro-angiogenic property of this hormone. These findings suggest that E2 can interfere with CRP pro-inflammatory effects via activation signals using its rapid, non-genomic pathway that may provide a new mechanism to improve vascular repair.
Conclusion
Thus, in this study, we demonstrate that EC could express CRP and be a site for CRP self-induction. We illustrate a process of positive feedback production of the protein by vascular cells that could lead to the marked local increase concentration reported in atherosclerotic plaques. Furthermore, the present study highlights a novel vasoprotective role of E2 in the inhibition of this endogenous CRP self-induction, altering its pro-inflammatory activities in vascular EC by a non-genomic pathway. By exploring the angiogenic potential of E2, our study demonstrates for the first time that this hormone restores EC migration altered by CRP. Further investigation will be needed to clarify mechanisms of E2 vascular protection by negative regulation of important proatherogenic inflammatory pathways controlled by CRP
Sunday
Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain
BACKGROUND: Although myeloperoxidase (MPO) monitoring is predictive for cardiovascular outcomes in suspected acute coronary syndromes, the value of serial testing is unknown.
METHODS: We investigated the relationship between serial MPO concentrations in 490 individuals with acute chest pain and incident major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPO with the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott Architect assay.
RESULTS: Plasma MPO concentrations during the first 16 h were higher in individuals who experienced MACE. Higher MPO quartiles predicted a greater likelihood of 6-month MACE at baseline [OR (95%CI), 2.4 (1.4–4.1), P = 0.001 for highest vs lowest quartile] and all subsequent time points, with strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7–20.9), P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among individuals whose cTnI remained normal (<0.028 µg/L). The lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and all other time points. Serial MPO monitoring predicted MACE risk better than baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002), including in individuals whose cTnI remained normal (c statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved accuracy for predicting 6-month MACE, reduced the number of missed MACE events from cTnI testing alone, and improved risk classification in 26.1% of patients.
CONCLUSIONS: MPO concentrations are predictive of outcome up to 16 h after presentation with chest pain and predict events missed by cTnI testing, supporting a potential role in rapid patient triage.
Stephen J. Nicholls1,2,3,*, W.H. Wilson Tang1,2,3, Danielle Brennan1, Marie-Luise Brennan1,2,3, Shirley Mann2,3, Steven E. Nissen1 and Stanley L. Hazen1,2,3
1 Department of Cardiovascular Medicine, and
2 Department of Cell Biology, and
3 Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH
METHODS: We investigated the relationship between serial MPO concentrations in 490 individuals with acute chest pain and incident major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPO with the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott Architect assay.
RESULTS: Plasma MPO concentrations during the first 16 h were higher in individuals who experienced MACE. Higher MPO quartiles predicted a greater likelihood of 6-month MACE at baseline [OR (95%CI), 2.4 (1.4–4.1), P = 0.001 for highest vs lowest quartile] and all subsequent time points, with strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7–20.9), P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among individuals whose cTnI remained normal (<0.028 µg/L). The lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and all other time points. Serial MPO monitoring predicted MACE risk better than baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002), including in individuals whose cTnI remained normal (c statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved accuracy for predicting 6-month MACE, reduced the number of missed MACE events from cTnI testing alone, and improved risk classification in 26.1% of patients.
CONCLUSIONS: MPO concentrations are predictive of outcome up to 16 h after presentation with chest pain and predict events missed by cTnI testing, supporting a potential role in rapid patient triage.
Stephen J. Nicholls1,2,3,*, W.H. Wilson Tang1,2,3, Danielle Brennan1, Marie-Luise Brennan1,2,3, Shirley Mann2,3, Steven E. Nissen1 and Stanley L. Hazen1,2,3
1 Department of Cardiovascular Medicine, and
2 Department of Cell Biology, and
3 Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, OH
Monday
Proteinase 3 and prognosis of patients with acute myocardial infarction.
Abstract
A multimarker approach may be useful for risk stratification in AMI (acute myocardial infarction) patients, particularly utilizing pathways that are pathophysiologically distinct. Our aim was to assess the prognostic value of PR3 (proteinase 3) in patients post-AMI.
We compared the prognostic value of PR3, an inflammatory marker, with an established marker NT-proBNP (N-terminal pro-B-type natriuretic peptide) post-AMI. We recruited 900 consecutive post-AMI patients (700 men; age, 64.6±12.4 years) in a prospective study with follow-up over 347 (0-764) days. Plasma PR3 was significantly higher in patients who died [666.2 (226.8-4035.5) ng/ml; P<0.001] or were readmitted with heart failure [598 (231.6-1803.9) ng/ml, P<0.004] compared with event-free survivors [486.9 (29.3-3118.2) ng/ml]. Using Cox modelling, log10 PR3 [HR (hazard ratio), 3.80] and log10 NT-proBNP (HR, 2.51) were significant independent predictors of death or heart failure.
When patients were stratified by plasma NT-proBNP (median, 1023 pmol/l), PR3 gave additional predictive value for death or heart failure, in both the patients in whom NT-proBNP level was above the median (log rank for trend, 12.54; P<0.0004) and those with NT-proBNP level below the median (log rank for trend, 3.83; P<0.05). Neither marker predicted recurrent AMI.
In conclusion, this is the first report showing a potential role for the serine protease PR3 in determining mortality and incidence of heart failure following AMI, independent of established conventional risk factors. PR3 may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy.
A multimarker approach may be useful for risk stratification in AMI (acute myocardial infarction) patients, particularly utilizing pathways that are pathophysiologically distinct. Our aim was to assess the prognostic value of PR3 (proteinase 3) in patients post-AMI.
We compared the prognostic value of PR3, an inflammatory marker, with an established marker NT-proBNP (N-terminal pro-B-type natriuretic peptide) post-AMI. We recruited 900 consecutive post-AMI patients (700 men; age, 64.6±12.4 years) in a prospective study with follow-up over 347 (0-764) days. Plasma PR3 was significantly higher in patients who died [666.2 (226.8-4035.5) ng/ml; P<0.001] or were readmitted with heart failure [598 (231.6-1803.9) ng/ml, P<0.004] compared with event-free survivors [486.9 (29.3-3118.2) ng/ml]. Using Cox modelling, log10 PR3 [HR (hazard ratio), 3.80] and log10 NT-proBNP (HR, 2.51) were significant independent predictors of death or heart failure.
When patients were stratified by plasma NT-proBNP (median, 1023 pmol/l), PR3 gave additional predictive value for death or heart failure, in both the patients in whom NT-proBNP level was above the median (log rank for trend, 12.54; P<0.0004) and those with NT-proBNP level below the median (log rank for trend, 3.83; P<0.05). Neither marker predicted recurrent AMI.
In conclusion, this is the first report showing a potential role for the serine protease PR3 in determining mortality and incidence of heart failure following AMI, independent of established conventional risk factors. PR3 may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy.
Thursday
Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease
Background
The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health
Methods
We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.
Background
The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.
Full Text of Background...
Methods
We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.
Full Text of Methods...
Results
Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension.
Conclusions
Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target
Kirsten Bibbins-Domingo, Ph.D., M.D., Glenn M. Chertow, M.D., M.P.H., Pamela G. Coxson, Ph.D., Andrew Moran, M.D., James M. Lightwood, Ph.D., Mark J. Pletcher, M.D., M.P.H., and Lee Goldman, M.D., M.P.H.
N Engl J Med 2010; 362:590-599
The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health
Methods
We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.
Background
The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.
Full Text of Background...
Methods
We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications.
Full Text of Methods...
Results
Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension.
Conclusions
Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target
Kirsten Bibbins-Domingo, Ph.D., M.D., Glenn M. Chertow, M.D., M.P.H., Pamela G. Coxson, Ph.D., Andrew Moran, M.D., James M. Lightwood, Ph.D., Mark J. Pletcher, M.D., M.P.H., and Lee Goldman, M.D., M.P.H.
N Engl J Med 2010; 362:590-599
Key predictor of cardiovascular death identified
ScienceDaily (Mar. 22, 2010) — Coronary Artery Disease (CAD) hospitalizes more than 160,000 Canadians every year, and almost one quarter of those patients die from this common form of heart disease. But now a team of Vancouver-based researchers has identified a key predictor of mortality in CAD patients, which means that specialists can better determine how to treat and improve outcomes for patients with CAD.
Coronary artery disease is the most frequent cause of heart disease and occurs when important blood vessels become narrow or blocked and can no longer give enough blood to meet the heart's demand.
In an article published in the Journal of the American College of Cardiology, researchers Claire Heslop, Dr. Jiri Frohlich, and Dr. John Hill from The Providence Heart + Lung Institute and the University of British Columbia detail their discovery, that high levels of an enzyme, myeloperoxidase , in the blood of CAD patients more than doubles the risk for death over a 13 year period. Myeloperoxidase is an enzyme associated with oxidative stress, which damages arterial tissue.
The research team, funded by the Heart and Stroke Foundation of BC & Yukon, looked at blood samples and records from a group of patients admitted to hospital in the early 1990s with symptoms of heart disease. Over a 13 year period, mortality was more than double for patients with high blood levels of myeloperoxidase than for those with lower levels.
Based on this work, the researchers were able to develop a new classification of risk for CAD patients based on their levels of myeloperoxidase. Measurement of the enzyme provides added predictive value for cardiovascular death when compared to traditional risk factors such as smoking and diabetes. "We hope that the discovery of new markers of cardiovascular risk will help identify specific patients who could benefit from more aggressive treatment strategies" said lead investigator, Dr. John Hill.
Patients whose records and samples were used in this study all consented to have their information used for research.
The Heart and Stroke Foundation of Canada has funded researchers across Canada for over 50 years. Every year, the Foundation presents grants, awards and scholarships to leading stroke and heart disease researchers who are committed to reducing and eliminating the effects of stroke and heart disease.
"We are proud to support Canadian researchers, such as Dr. Hill, Dr. Frohlich and Ms. Heslop , who are combining their efforts to develop new techniques to fight heart disease and identify factors in at-risk individuals," says Bobbe Wood, President and CEO of Heart and Stroke Foundation of BC & Yukon. "Since almost 40,000 deaths occur in Canada each year due to CAD, it's crucial to focus on better methods to treat such a devastating health problem."
Coronary artery disease is the most frequent cause of heart disease and occurs when important blood vessels become narrow or blocked and can no longer give enough blood to meet the heart's demand.
In an article published in the Journal of the American College of Cardiology, researchers Claire Heslop, Dr. Jiri Frohlich, and Dr. John Hill from The Providence Heart + Lung Institute and the University of British Columbia detail their discovery, that high levels of an enzyme, myeloperoxidase , in the blood of CAD patients more than doubles the risk for death over a 13 year period. Myeloperoxidase is an enzyme associated with oxidative stress, which damages arterial tissue.
The research team, funded by the Heart and Stroke Foundation of BC & Yukon, looked at blood samples and records from a group of patients admitted to hospital in the early 1990s with symptoms of heart disease. Over a 13 year period, mortality was more than double for patients with high blood levels of myeloperoxidase than for those with lower levels.
Based on this work, the researchers were able to develop a new classification of risk for CAD patients based on their levels of myeloperoxidase. Measurement of the enzyme provides added predictive value for cardiovascular death when compared to traditional risk factors such as smoking and diabetes. "We hope that the discovery of new markers of cardiovascular risk will help identify specific patients who could benefit from more aggressive treatment strategies" said lead investigator, Dr. John Hill.
Patients whose records and samples were used in this study all consented to have their information used for research.
The Heart and Stroke Foundation of Canada has funded researchers across Canada for over 50 years. Every year, the Foundation presents grants, awards and scholarships to leading stroke and heart disease researchers who are committed to reducing and eliminating the effects of stroke and heart disease.
"We are proud to support Canadian researchers, such as Dr. Hill, Dr. Frohlich and Ms. Heslop , who are combining their efforts to develop new techniques to fight heart disease and identify factors in at-risk individuals," says Bobbe Wood, President and CEO of Heart and Stroke Foundation of BC & Yukon. "Since almost 40,000 deaths occur in Canada each year due to CAD, it's crucial to focus on better methods to treat such a devastating health problem."
Sunday
Anti-apolipoprotein A-1 IgG as an independent cardiovascular prognostic marker affecting basal heart rate in myocardial infarction
AIMS :To assess the prognostic value of anti-apolipoprotein A-1 (anti-apoA-1) IgG after myocardial infarction (MI) and its association with major cardiovascular events (MACEs) at 12 months and to determine their association with resting heart rate (RHR), a well-established prognostic feature after MI. Anti-apoA-1 IgG have been reported in MI without autoimmune disease, but their clinical significance remains undetermined.
METHODS AND RESULTS: A total of 221 consecutive patients with MI were prospectively included, and all completed a 12-month follow-up. Major cardiovascular events consisted in death, MI, stroke, or hospitalization either for an acute coronary syndrome or heart failure. Resting heart rate was obtained on Holter the day before discharge under the same medical treatment. Neonate rat ventricular cardiomyocytes (NRVC) were used in vitro to assess the direct anti-apoA-1 IgG effect on RHR. During follow-up, 13% of patients presented a MACE. Anti-apoA-1 IgG positivity was 9% and was associated with a higher RHR (P = 0.0005) and higher MACE rate (adjusted OR, 4.3; 95% CI, 1.46–12.6; P = 0.007). Survival models confirmed the significant nature of this association. Patients with MACE had higher median anti-apoA-1 IgG values at admission than patients without (P = 0.007). On NRVC, plasma from MI patients and monoclonal anti-apoA-1 IgG induced an aldosterone and dose-dependent positive chronotropic effect, abrogated by apoA-1 and therapeutic immunoglobulin (IVIG) pre-incubation.
CONCLUSIONS: In MI patients, anti-apoA-1 IgG is independently associated with MACE at 1-year, interfering with a currently unknown aldosterone-dependent RHR determinant. Knowing whether anti-apoA-1 IgG assessment could be of interest to identify an MI patient subset susceptible to benefit from apoA-1/IVIG therapy remains to be demonstrated.
Nicolas Vuilleumier1,*, Michel F. Rossier1,2, Sabrina Pagano1, Magaly Python2, Emmanuel Charbonney3, René Nkoulou4, Richard James2, Guido Reber5, François Mach4 and Pascale Roux-Lombard6
METHODS AND RESULTS: A total of 221 consecutive patients with MI were prospectively included, and all completed a 12-month follow-up. Major cardiovascular events consisted in death, MI, stroke, or hospitalization either for an acute coronary syndrome or heart failure. Resting heart rate was obtained on Holter the day before discharge under the same medical treatment. Neonate rat ventricular cardiomyocytes (NRVC) were used in vitro to assess the direct anti-apoA-1 IgG effect on RHR. During follow-up, 13% of patients presented a MACE. Anti-apoA-1 IgG positivity was 9% and was associated with a higher RHR (P = 0.0005) and higher MACE rate (adjusted OR, 4.3; 95% CI, 1.46–12.6; P = 0.007). Survival models confirmed the significant nature of this association. Patients with MACE had higher median anti-apoA-1 IgG values at admission than patients without (P = 0.007). On NRVC, plasma from MI patients and monoclonal anti-apoA-1 IgG induced an aldosterone and dose-dependent positive chronotropic effect, abrogated by apoA-1 and therapeutic immunoglobulin (IVIG) pre-incubation.
CONCLUSIONS: In MI patients, anti-apoA-1 IgG is independently associated with MACE at 1-year, interfering with a currently unknown aldosterone-dependent RHR determinant. Knowing whether anti-apoA-1 IgG assessment could be of interest to identify an MI patient subset susceptible to benefit from apoA-1/IVIG therapy remains to be demonstrated.
Nicolas Vuilleumier1,*, Michel F. Rossier1,2, Sabrina Pagano1, Magaly Python2, Emmanuel Charbonney3, René Nkoulou4, Richard James2, Guido Reber5, François Mach4 and Pascale Roux-Lombard6
Thursday
Evaluation of erectile dysfunction and associated cardiovascular risk using structured questionnaires in Chinese type 2 diabetic men
ABSTRACT
Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices.
A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire.
After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01–1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27–4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21–5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06–1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12–7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05–5.01), p = 0.037].
In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects
L. W. Yu*, A. P. Kong*†, P. C. Tong*, C. Tam*, G. T. Ko*, C.-S. Ho‡, W.-Y. So*, R. C. Ma*, C.-C. Chow* and J. C. Chan*
*Department of Medicine and Therapeutics , †Li Ka Shing Institute of Health Science , and ‡Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices.
A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire.
After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01–1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27–4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21–5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06–1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12–7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05–5.01), p = 0.037].
In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects
L. W. Yu*, A. P. Kong*†, P. C. Tong*, C. Tam*, G. T. Ko*, C.-S. Ho‡, W.-Y. So*, R. C. Ma*, C.-C. Chow* and J. C. Chan*
*Department of Medicine and Therapeutics , †Li Ka Shing Institute of Health Science , and ‡Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
Tuesday
Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification?
Clinical Chemistry. 2009;55:1462-1470
Abstract
Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed
Abstract
Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed
Thursday
Calcium and Vitamin D Status in Heart Failure Patients in Isfahan, Iran
Both calcium and vitamin D play important roles in cardiac muscle contraction and performance. In this cross-sectional study, we evaluated the status of serum calcium, PTH and 25(OH)D(3) and their correlation with left ventricular Function and NYHA Functional class in 95 heart failure patients referred to Shahid Chamran Hospital, Isfahan, Iran, by colorimetric, immunoradiometric, and Immunochemiluminescent assays, echocardiography and interview respectively. The study was performed between Oct 2007 and Feb 2008. Twenty eight women and 67 men of functional classes 1, 2, or 3 participated in the study.
Mean (SD) of age of the participants was 62(11) years. Mean (SD) serum calcium and 25(OH)D(3) were 2.41(0.16) mmol/L and 56.78(51.33) nmol/L, respectively. The overall prevalence of low vitamin D status was 84.2%. There was no correlation between serum calcium and 25(OH)D(3) with LVEF. Interestingly, patients with hyperparathyroidism (serum PTH>65 ng/L) had lower LVEF (27% versus 32.5% p = 0.03). NYHA functional class was worse in patients with hyperparathyroidism (p = 0.08). Hypovitaminosis D is very prevalent in heart failure patients. Hyperparathyroidism in these patients may adversely affect cardiac function. Vitamin D3 might serve as an adjunctive treatment for heart failure patients.
Garakyaraghi M, Kerdegari M, Siavash M.
Isfahan University of Medical Sciences, Isfahan Cardiovascular Research Center, Isfahan, Iran
Mean (SD) of age of the participants was 62(11) years. Mean (SD) serum calcium and 25(OH)D(3) were 2.41(0.16) mmol/L and 56.78(51.33) nmol/L, respectively. The overall prevalence of low vitamin D status was 84.2%. There was no correlation between serum calcium and 25(OH)D(3) with LVEF. Interestingly, patients with hyperparathyroidism (serum PTH>65 ng/L) had lower LVEF (27% versus 32.5% p = 0.03). NYHA functional class was worse in patients with hyperparathyroidism (p = 0.08). Hypovitaminosis D is very prevalent in heart failure patients. Hyperparathyroidism in these patients may adversely affect cardiac function. Vitamin D3 might serve as an adjunctive treatment for heart failure patients.
Garakyaraghi M, Kerdegari M, Siavash M.
Isfahan University of Medical Sciences, Isfahan Cardiovascular Research Center, Isfahan, Iran
Monday
Neutrophil activation precedes myocardial injury in patients with acute myocardial infarction.
Department of Cardiology and Cardiovascular Research Center, University Heart Center, D-20246 Hamburg, Germany.
Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of Myeloperoxidase predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury.
The aim of this study was to evaluate the time course of Myeloperoxidase plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for Myeloperoxidase, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls.
In contrast to all other investigated markers, Myeloperoxidase was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma Myeloperoxidase levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.
Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of Myeloperoxidase predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury.
The aim of this study was to evaluate the time course of Myeloperoxidase plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for Myeloperoxidase, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls.
In contrast to all other investigated markers, Myeloperoxidase was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma Myeloperoxidase levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.
Tuesday
Prognostic Value of Troponin I Levels for Predicting Adverse Cardiovascular Outcomes in Postmenopausal Women Undergoing Cardiac Surgery
Abstract
BACKGROUND: Adverse cardiac events that follow cardiac surgery are an important source of perioperative morbidity and mortality for women. Troponin I provides a sensitive measure of cardiac injury, but the levels after cardiac surgery may vary between sexes. Our purpose in this study was to evaluate the prognostic value of troponin I levels for predicting cardiovascular complications in postmenopausal women undergoing cardiac surgery.
METHODS: The cohort of this study were women enrolled in a previously reported clinical trial evaluating the neuroprotective potential of 17β-estradiol in elderly women. In that study, 175 postmenopausal women not receiving estrogen replacement therapy and scheduled to undergo coronary artery bypass graft (with or without valve surgery) were prospectively randomized to receive 17β-estradiol or placebo in a double-blind manner beginning the day before surgery and continuing for 5 days postoperatively. Serial 12-lead electrocardiograms were performed and serum troponin I concentrations were measured before surgery, after surgery on arrival in the intensive care unit, and for the first four postoperative days. The primary end-point of the present study was major adverse cardiovascular events (MACE) defined as a Q-wave myocardial infarction, low cardiac output state or death within 30 days of surgery. The diagnosis of Q-wave myocardial infarction was made independently by two physicians blinded to treatment and patient outcomes with the final diagnosis requiring consensus. Low cardiac output state was defined as cardiac index <2.0 L · min–1 · m–2 for >8 h regardless of treatment.
RESULTS: Troponin I levels on postoperative day 1 were predictive of MACE (area under the receiver operator curve = 0.862). A cutoff point for troponin I of >7.6 ng/mL (95% confidence interval, 6.4–10.8) provided the optimal sensitivity and specificity for identifying patients at risk for MACE. The negative predictive value of a Troponin I level for identifying a patient with a composite cardiovascular outcome was high (96%) and the positive predictive value moderate (40%). Postoperative troponin I levels were not different between women receiving perioperative 17β-estradiol treatment compared with placebo and the frequency of MACE was not influenced by 17β-estradiol treatment.
CONCLUSIONS: In postmenopausal women, elevated troponin I levels on postoperative day 1 are predictive of MACE. Monitoring of perioperative troponin I levels might provide a means for stratifying patients at risk for adverse cardiovascular events.
BACKGROUND: Adverse cardiac events that follow cardiac surgery are an important source of perioperative morbidity and mortality for women. Troponin I provides a sensitive measure of cardiac injury, but the levels after cardiac surgery may vary between sexes. Our purpose in this study was to evaluate the prognostic value of troponin I levels for predicting cardiovascular complications in postmenopausal women undergoing cardiac surgery.
METHODS: The cohort of this study were women enrolled in a previously reported clinical trial evaluating the neuroprotective potential of 17β-estradiol in elderly women. In that study, 175 postmenopausal women not receiving estrogen replacement therapy and scheduled to undergo coronary artery bypass graft (with or without valve surgery) were prospectively randomized to receive 17β-estradiol or placebo in a double-blind manner beginning the day before surgery and continuing for 5 days postoperatively. Serial 12-lead electrocardiograms were performed and serum troponin I concentrations were measured before surgery, after surgery on arrival in the intensive care unit, and for the first four postoperative days. The primary end-point of the present study was major adverse cardiovascular events (MACE) defined as a Q-wave myocardial infarction, low cardiac output state or death within 30 days of surgery. The diagnosis of Q-wave myocardial infarction was made independently by two physicians blinded to treatment and patient outcomes with the final diagnosis requiring consensus. Low cardiac output state was defined as cardiac index <2.0 L · min–1 · m–2 for >8 h regardless of treatment.
RESULTS: Troponin I levels on postoperative day 1 were predictive of MACE (area under the receiver operator curve = 0.862). A cutoff point for troponin I of >7.6 ng/mL (95% confidence interval, 6.4–10.8) provided the optimal sensitivity and specificity for identifying patients at risk for MACE. The negative predictive value of a Troponin I level for identifying a patient with a composite cardiovascular outcome was high (96%) and the positive predictive value moderate (40%). Postoperative troponin I levels were not different between women receiving perioperative 17β-estradiol treatment compared with placebo and the frequency of MACE was not influenced by 17β-estradiol treatment.
CONCLUSIONS: In postmenopausal women, elevated troponin I levels on postoperative day 1 are predictive of MACE. Monitoring of perioperative troponin I levels might provide a means for stratifying patients at risk for adverse cardiovascular events.
Monday
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Proteomics and Protein Markers
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac Troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease.
Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined Troponin I cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome .
Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 µg/L to 0.028 µg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction.
Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.
Kai M. Eggers1,a, Allan S. Jaffe4, Lars Lind2, Per Venge3 and Bertil Lindahl1
Departments of1 Medical Sciences, Cardiology,2 Medicine, and 3 Clinical Chemistry, Uppsala University Hospital, Sweden, and4 Mayo Medical School, Rochester, MN.
Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making
Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac Troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease.
Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined Troponin I cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome .
Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 µg/L to 0.028 µg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction.
Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.
Kai M. Eggers1,a, Allan S. Jaffe4, Lars Lind2, Per Venge3 and Bertil Lindahl1
Departments of1 Medical Sciences, Cardiology,2 Medicine, and 3 Clinical Chemistry, Uppsala University Hospital, Sweden, and4 Mayo Medical School, Rochester, MN.
An evaluation of the association between C-reactive protein, the change in C-reactive protein over one year
Objectives. To evaluate the association between systemic inflammation, as measured by C-reactive protein , and all-cause mortality. To also evaluate the association between change in CRP status (sub-acute, 10 mg/l and acute >10 mg/l) and all-cause mortality.
Methods. A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using Cox proportional hazards regression models (CPHMs).
Results. A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1–6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P < 0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (10 mg/l) to acute (>10 mg/l), the HR for death increased 2-fold (P < 0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571).
Conclusions. CRP level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.
Methods. A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using Cox proportional hazards regression models (CPHMs).
Results. A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1–6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P < 0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (10 mg/l) to acute (>10 mg/l), the HR for death increased 2-fold (P < 0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571).
Conclusions. CRP level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.
Tuesday
Clinical significance of cardiac troponins I and T in acute heart failure
Background
Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF).
Aims
To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF.
Methods
FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed.
Results
Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2–3.5, p = 0.01) and cTnT (OR 2.6, 95% CI 1.5–4.4, p = 0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2–13, p < 0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0–1.8, p = 0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8–0.9, p = 0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality.
Conclusions
cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.
ARTICLE
Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF).
Aims
To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF.
Methods
FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed.
Results
Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2–3.5, p = 0.01) and cTnT (OR 2.6, 95% CI 1.5–4.4, p = 0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2–13, p < 0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0–1.8, p = 0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8–0.9, p = 0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality.
Conclusions
cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.
ARTICLE
Cardiac dysfunction after burns
Objectives
Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.
Patients and methods
Ten consecutive adults (aged 36–89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36 h after the burn.
Results
Half (n = 5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36 h after the burn (p ≤ 0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.
Conclusion
Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.
ARTICLE
Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.
Patients and methods
Ten consecutive adults (aged 36–89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36 h after the burn.
Results
Half (n = 5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36 h after the burn (p ≤ 0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.
Conclusion
Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.
ARTICLE
Monday
C-reactive protein, obesity, atopy and asthma symptoms in middle-aged British adults
Recent research suggested an association between circulating C-reactive protein (CRP) and adult asthma, confined to those without evidence of allergic predisposition. We investigated the role of smoking and obesity as explanations for this relationship.
At age 44–45, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of C-reactive protein (CRP), specific IgE to grass, cat and dust mite, standing height and weight. Information on asthma and related symptoms was collected by computer aided interview at age 42. Complete data were available for 6490 subjects.
CRP levels were positively correlated with body mass index (BMI), higher among women than men and among heavy smokers (>=20 cigarettes·day-1) than never smokers. Adjusted for sex and region, odds ratios comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first were 1.85 (95% confidence interval 1.15 to 2.99) for non-atopics and 0.94 (0.62 to 1.41) for atopics changing to 1.36 (0.80 to 2.32) and 1.07 (0.67 to 1.69) respectively when additionally adjusted for smoking and BMI.
Any association between C-reactive protein (CRP) and asthma prevalence confined to non-atopics may be due to confounding or may reflect a more general association of CRP with smoking-related obstructive airways disease.
At age 44–45, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of C-reactive protein (CRP), specific IgE to grass, cat and dust mite, standing height and weight. Information on asthma and related symptoms was collected by computer aided interview at age 42. Complete data were available for 6490 subjects.
CRP levels were positively correlated with body mass index (BMI), higher among women than men and among heavy smokers (>=20 cigarettes·day-1) than never smokers. Adjusted for sex and region, odds ratios comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first were 1.85 (95% confidence interval 1.15 to 2.99) for non-atopics and 0.94 (0.62 to 1.41) for atopics changing to 1.36 (0.80 to 2.32) and 1.07 (0.67 to 1.69) respectively when additionally adjusted for smoking and BMI.
Any association between C-reactive protein (CRP) and asthma prevalence confined to non-atopics may be due to confounding or may reflect a more general association of CRP with smoking-related obstructive airways disease.
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