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.
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