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Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

Posted in Atherogenic Processes & Pathology, Best evidence, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Coagulation Therapy and Internal Bleeding, Congenital Heart Disease, Cytoskeleton, Diabetes Mellitus, Diagnostic Immunology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Evidence-based decision-making, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, HTN, Human Immune System in Health and in Disease, Immunodiagnostics, Innovation in Immunology Diagnostics, International Global Work in Pharmaceutical, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Pre-Clinical Animal Model Development, Proteomics, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Statistical Methods for Research Evaluation, Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Transfer: Biotech and Pharmaceutical, Theoretic convergence, Translational Effectiveness, Translational Research, Translational Science, tagged adipokine, Antiplatelet drug, atheromatous plaque, AVV genotype 2, biomarker assays, Biomarker discovery, CaKMII overactive in obesity, cardiac biomarkers, Circulation Endothelial Progenitor Cells, comorbidities - type 2 DM, Endothelial Cell Coagulation Activation, Endothelial cells, endothelial damage, Endothelial Dysfunction, epigenetic, genomics, Nutritional Supplements, plaque regression, plaque rupture, platelet activation, platelet aggregation, platelet and clot formation, resistin, subintimal plaque, target of both insulin resistance and type 2 diabetes, type 2 DM on January 5, 2014| Leave a Comment »

Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

Author and Curator: Larry H Bernstein, MD, FCAP

This introduction is to a thorough evaluation of a rich source of research literature on the genomic influences, which may have variable strength in the biological causation of atherosclerosis, microvascular disease, plaque formation, not necessarily having expressing, except in a multivariable context that includes the environment, dietary factors, level of emotional stress, sleep habits, and the daily activities of living for affected individuals. The potential of genomics is carried in the DNA, copied to RNA, and this is most well studied in the micro RNAs (miRNA). The miRNA has been explored for the appearance in the circulation of specific miRNAs that might be associated with myocyte or endothelial cell injury, and they are also being used as targets for therapeutics by the creation of silencing RNAs (siRNA). The extent to which there is evidence of success in these studies is limited, but is being translated from animal studies to human disease. There is also a long history of the measurement of circulating enzymes and isoenzymes (alanine amino transferase, creatine kinase, and lactate dehydrogenase, not to leave out the adenylate kinase species specific to myocardium), and more recently the release of troponins I and T, and the so far still not fully explored ischemia modified albumin, or of miRNAs for the diagnosis of myocardial infarction.

There is also a significant disagreement about the value of measuring high sensitivity C reactive protein (hs-CRP), which has always been a marker for systemic inflammatory disease, in both chronic rheumatic and infectious diseases having a broad range, so that procalcitonin has appeared to be better for that situation, and for early diagnosis of sepsis. The hs-CRP has been too easily ignored because of

1. the ubiquitous elevations in the population
2. the expressed concerns that one might not be inclined to treat a mild elevation without other risk factors, such as, LDL cholesterolemia, low HDL, absent diabetes or obesity. Nevertheless, hs-CRP raises an reasonable argument for preventive measures, and perhaps the use of a statin.

There has been a substantial amount of work on the relationship of obesity to both type 2 diabetes mellitus (T2DM) and to coronary vascular disease and stroke. Here we bring in the relationship of the vascular endothelium, adipose tissue secretion of adiponectin, and platelet activation. A whole generation of antiplatelet drugs addresses the mechanism of platelet activation, adhession, and interaction with endothelium. Very interesting work has appeared on RESISTIN, that could bear some fruit in the treatment of both obesity and T2DM.

It is important to keep in mind that epigenomic gene rearrangements or substitutions occur throughout life, and they may have an expression late in life. Some of the known epigenetic events occur with some frequency, but the associations are extremely difficult to pin down, as well as the strength of the association. In a population that is not diverse, epigenetic changes are passed on in the population in the period of childbearing age. The establishment of an epigenetic change is diluted in a diverse population. There have been a number of studies with different findings of association between cardiovascular disease and genetic mutations in the Han and also in the Uyger Chinese populations, which are distinctly different populations that is not part of this discussion.

This should be sufficient to elicit broad appeal in reading this volume on cardiovascular diseases, and perhaps the entire series. Below is a diagram of this volume in the series.

PART 1 – Genomics and Medicine
Introduction to Genomics and Medicine (Vol 3)
Genomics and Medicine: The Physician’s View
Ribozymes and RNA Machines
Genomics and Medicine: Genomics to CVD Diagnoses
Establishing a Patient-Centric View of Genomic Data

VIDEO: Implementing Biomarker Programs P Ridker	PART 2 – Epigenetics – Modifiable Factors Causing CVD
	Diseases Etiology
	Environmental Contributors Implicated as Causing CVD
	Diet: Solids and Fluid Intake and Nutraceuticals
	Physical Activity and Prevention of CVD
	Psychological Stress and Mental Health: Risk for CVD
	Correlation between Cancer and CVD

PART 3 Determinants of CVD – Genetics, Heredity and Genomics Discoveries

Introduction

Why cancer cells contain abnormal numbers of chromosomes (Aneuploidy)

Functional Characterization of CV Genomics: Disease Case Studies @ 2013 ASHG

Leading DIAGNOSES of CVD covered in Circulation: CV Genetics, 3/2010 – 3/2013

Commentary on Biomarkers for Genetics and Genomics of CVD

PART 4 Individualized Medicine Guided by Genetics and Genomics Discoveries

Preventive Medicine: Cardiovascular Diseases

Walking and Running: Similar Risk Reductions for Hypertension, Hypercholesterolemia,
DM, and possibly CAD
http://pharmaceuticalintelligence.com/2013/04/04/walking-and-running-similar-risk-reductions-for-hypertension-hypercholesterolemia-dm-and-possibly-cad/

Prevention of Type 2 Diabetes: Is Bariatric Surgery the Solution?
http://pharmaceuticalintelligence.com/2012/08/23/prevention-of-type-2-diabetes-is-bariatric-surgery-the-solution/

Gene-Therapy for CVD

Congenital Heart Disease/Defects

Medical Etiologies: EBM – LEADING DIAGNOSES, Risks		Pharmacogenomics for Cardio- vascular Diseases
Signaling Pathways		Response to Rosuvastatin in Patients With Acute Myocardial Infarction: Hepatic Metabolism and Transporter Gene Variants Effect http://pharmaceuticalintelligence.com/2014/ 01/02/response-to-rosuvastatin-in-patients- with-acute-myocardial-infarction-hepatic- metabolism-and-transporter-gene-variants-effect/
Proteomics and Metabolomics		Voltage-Gated Calcium Channel and Pharmaco- genetic Association with Adverse Cardiovascular Outcomes: Hypertension Treatment with Verapamil SR (CCB) vs Atenolol (BB) or Trandolapril (ACE) http://pharmaceuticalintelligence.com/2014/01/02/ voltage-gated-calcium-channel-and-pharmacogenetic- association-with-adverse-cardiovascular-outcomes- hypertension-treatment-with-verapamil-sr-ccb-vs- atenolol-bb-or-trandolapril-ace/
		SNPs in apoE are found to influence statin response significantly. Less frequent variants in PCSK9 and smaller effect sizes in SNPs in HMGCR http://pharmaceuticalintelligence.com/2014/01/02/snps-in-apoe-are-found-to-influence-statin-response-significantly-less-frequent-variants-in-pcsk9-and-smaller-effect-sizes-in-snps-in-hmgcr/

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Diagnostic Value of Cardiac Biomarkers

Posted in Atherogenic Processes & Pathology, Best evidence, Ca2+ triggered activation, Calmodulin Kinase and Contraction, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Coagulation Therapy and Internal Bleeding, Curation, Diabetes Mellitus, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Evidence-based decision-making, Evolutionary cognition, Frontiers in Cardiology and Cardiovascular Disorders, Genomic Testing: Methodology for Diagnosis, Immunodiagnostics, Inferential analysis, Medical and Population Genetics, Medical Devices R&D and Inventions, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Molecular Genetics & Pharmaceutical, Nephrology, Nutritional Supplements: Atherogenesis, lipid metabolism, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Pharmacologic toxicities, Population Health Management, Genetics & Pharmaceutical, Proteomics, Quality Assurance, Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Science, tagged 2, Acute coronary syndrome, acute myocardial infarction, American College of Cardiology ACC, Antiplatelet drug, aspartate aminotransferse (AST), Atrial fibrillation, cardiac biomarkers, cardiomyocyte, Cardiomyopathy, CK isoenzyme MB, confounders, coronary artery plaque, Coumadin, Creatine kinase, endothelial cell, hs-troponins, hypercoagulable state, INR, Lactate dehydrogenase, LD isoenzyme(s)-1, miRNAs, myocardial contraction, plaque rupture, platelet activation, practice guidelines, PT, PTT, troponin I, Troponin T, World Health Organization on January 4, 2014| Leave a Comment »

Diagnostic Value of Cardiac Biomarkers

Author and Curator: Larry H Bernstein, MD, FCAP

These presentations covered several views of the utilization of cardiac markers that have evolved for over 60 years. The first stage was the introduction of enzymatic assays and isoenzyme measurements to distinguish acute hepatitis and acute myocardial infarction, which included lactate dehydrogenase (LD isoenzymes 1, 2) at a time that late presentation of the patient in the emergency rooms were not uncommon, with the creatine kinase isoenzyme MB declining or disappeared from the circulation. The world health organization (WHO) standard definition then was the presence of two of three:

1. Typical or atypical precordial pressure in the chest, usually with radiation to the left arm

2. Electrocardiographic changes of Q-wave, not previously seen, definitive; ST- elevation of acute myocardial injury with repolarization;
T-wave inversion.

3. The release into the circulation of myocardial derived enzymes –
creatine kinase – MB (which was adapted to measure infarct size), LD-1,
both of which were replaced with troponins T and I, which are part of the actomyosin contractile apparatus.

The research on infarct size elicited a major research goal for early diagnosis and reduction of infarct size, first with fibrinolysis of a ruptured plaque, and this proceeded into the full development of a rapidly evolving interventional cardiology as well as cardiothoracic surgery, in both cases, aimed at removal of plaque or replacement of vessel. Surgery became more imperative for multivessel disease, even if only one vessel was severely affected.

So we have clinical history, physical examination, and emerging biomarkers playing a large role for more than half a century. However, the role of biomarkers broadened. Patients were treated with antiplatelet agents, and a hypercoagulable state coexisted with myocardial ischemic injury. This made the management of the patient reliant on long term followup for Warfarin with the international normalized ratio (INR) for a standardized prothrombin time (PT), and reversal of the PT required transfusion with thawed fresh frozen plasma (FFP). The partial thromboplastin test (PPT) was necessary in hospitalization to monitor the heparin effect.

Thus, we have identified the use of traditional cardiac biomarkers for:

1. Diagnosis
2. Therapeutic monitoring

The story is only the beginning. Many patients who were atypical in presentation, or had cardiovascular ischemia without plaque rupture were problematic. This led to a concerted effort to redesign the troponin assays for high sensitivity with the concern that the circulation should normally be free of a leaked structural marker of myocardial damage. But of course, there can be a slow leak or a decreased rate of removal of such protein from the circulation, and the best example of this would be the patient with significant renal insufficiency, as TnT is clear only through the kidney, and TNI is clear both by the kidney and by vascular endothelium. The introduction of the high sensitivity assay has been met with considerable confusion, and highlights the complexity of diagnosis in heart disease. Another test that is used for the diagnosis of heart failure is in the class of natriuretic peptides (BNP, pro NT-BNP, and ANP), the last of which has been under development.

While there is an exponential increase in the improvement of cardiac devices and discovery of pharmaceutical targets, the laboratory support for clinical management is not mature. There are miRNAs that may prove valuable, matrix metalloprotein(s), and potential endothelial and blood cell surface markers, they require

1. codevelopment with new medications
2. standardization across the IVD industry
3. proficiency testing applied to all laboratories that provide testing
4. the measurement on multitest automated analyzers with high capability in proteomic measurement (MS, time of flight, MS-MS)

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Curation, HealthCare System in the US, and Calcium Signaling Effects on Cardiac Contraction, Heart Failure, and Atrial Fibrillation, and the Relationship of Calcium Release at the Myoneural Junction to Beta Adrenergic Release

Posted in Accountable Care Organizations, Affordable Care Act, Atherogenic Processes & Pathology, Best evidence, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Congenital Heart Disease, Curation, Curation methodology, Cytoskeleton, De novo synthesis, Dialectic, Discovery process, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Evolutionary cognition, Experimental validation, Explanatory, Federal Budget Appropriations, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Health Economics and Outcomes Research, Healthcare costs and reimbursement, HealthCare IT, Healthcare Reform, Historical relevance, HTN, Indigent Nutrition, Ionic Transporters Na+, K, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Medicare and Medicaid, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, PKC, Population Health Management, Genetics & Pharmaceutical, Pre-Clinical Animal Model Development, Regenerative Biology and Medicine, Skilled Nursing Facilities, Stem Cells for Regenerative Medicine, Synaptic vesicle, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Theoretic convergence, Translational Effectiveness, Translational Research, Translational Science, Uninsured and Underinsured, tagged 249 SNPs associated with a number of heart-related conditions and treatments., Accountable Care Organization, acute coronary syndromes, Acute decompensated heart failure, Affordable Care Act, atherogenesis, Atherosclerosis, Atrial Fibrillation: IL6R Polymorphism in Whites and African Americans, calcium calmodulin kinase, calcium efflux, Cardiac & Vascular Repair, cardiac arrhythmias, cardiac biomarkers, Cardiogenesis, cardiomyocyte, cardiomyocyte hypertrophy, Content Curation, Coronary artery disease, Coronary circulation, Curation, efflux transporter, financial cost accounting, ion channels, ion transport, Na-K-Cl cotransporter, PKC, Pyruvate Kinase, seven CYP2C19 SNPs linked to Plavix response, SNPs, Synaptic vesicle on January 2, 2014| Leave a Comment »

Curation, HealthCare System in the US, and Calcium Signaling Effects on Cardiac Contraction, Heart Failure, and Atrial Fibrillation, and the Relationship of Calcium Release at the Myoneural Junction to Beta Adrenergic Release

Curator and e-book Contributor: Larry H. Bernstein, MD, FCAP
Curator and BioMedicine e-Series Editor-in-Chief: Aviva Lev Ari, PhD, RN

and

Content Consultant to Six-Volume e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC

This portion summarises what we have covered and is now familiar to the reader. There are three related topics, and an extension of this embraces other volumes and chapters before and after this reading. This approach to the document has advantages over the multiple authored textbooks that are and have been pervasive as a result of the traditional publication technology. It has been stated by the founder of ScoopIt, that amount of time involved is considerably less than required for the original publications used, but the organization and construction is a separate creative process. In these curations we amassed on average five articles in one curation, to which, two or three curators contributed their views. There were surprises, and there were unfulfilled answers along the way. The greatest problem that is being envisioned is the building a vision that bridges and unmasks the hidden “dark matter” between the now declared “OMICS”, to get a more real perspective on what is conjecture and what is actionable. This is in some respects unavoidable because the genome is an alphabet that is matched to the mino acid sequences of proteins, which themselves are three dimensional drivers of sequences of metabolic reactions that can be altered by the accumulation of substrates in critical placements, and in addition, the proteome has functional proteins whose activity is a regulatory function and not easily identified. In the end, we have to have a practical conception, recognizing the breadth of evolutionary change, and make sense of what we have, while searching for more.

We introduced the content as follows:

1. We introduce the concept of curation in the digital context, and it’s application to medicine and related scientific discovery.

Topics were chosen were used to illustrate this process in the form of a pattern, which is mostly curation, but is significantly creative, as it emerges in the context of this e-book.

Alternative solutions in Treatment of Heart Failure (HF), medical devices, biomarkers and agent efficacy is handled all in one chapter.
PCI for valves vs Open heart Valve replacement
PDA and Complications of Surgery — only curation could create the picture of this unique combination of debate, as exemplified of Endarterectomy (CEA) vs Stenting the Carotid Artery (CAS), ischemic leg, renal artery stenosis.

2. The etiology, or causes, of cardiovascular diseases consist of mechanistic explanations for dysfunction relating to the heart or vascular system. Every one of a long list of abnormalities has a path that explains the deviation from normal. With the completion of the analysis of the human genome, in principle all of the genetic basis for function and dysfunction are delineated. While all genes are identified, and the genes code for all the gene products that constitute body functions, there remains more unknown than known.

3. Human genome, and in combination with improved imaging methods, genomics offers great promise in changing the course of disease and aging.

4. If we tie together Part 1 and Part 2, there is ample room for considering clinical outcomes based on individual and organizational factors for best performance. This can really only be realized with considerable improvement in information infrastructure, which has miles to go.

Curation

Curation is an active filtering of the web’s and peer reviewed literature found by such means – immense amount of relevant and irrelevant content. As a result content may be disruptive. However, in doing good curation, one does more than simply assign value by presentation of creative work in any category. Great curators comment and share experience across content, authors and themes.
Great curators may see patterns others don’t, or may challenge or debate complex and apparently conflicting points of view. Answers to specifically focused questions comes from the hard work of many in laboratory settings creatively establishing answers to definitive questions, each a part of the larger knowledge-base of reference. There are those rare “Einstein’s” who imagine a whole universe, unlike the three blindmen of the Sufi tale. One held the tail, the other the trunk, the other the ear, and they all said this is an elephant!
In my reading, I learn that the optimal ratio of curation to creation may be as high as 90% curation to 10% creation. Creating content is expensive. Curation, by comparison, is much less expensive. The same source says “Scoop.it is my content marketing testing “sandbox”. In sharing, he says that comments provide the framework for what and how content is shared.

Healthcare and Affordable Care Act

We enter year 2014 with the Affordable Care Act off to a slow start because of the implementation of the internet signup requiring a major repair, which is, unfortunately, as expected for such as complex job across the US, and with many states unwilling to participate. But several states – California, Connecticut, and Kentucky – had very effective state designed signups, separate from the federal system. There has been a very large rush and an extension to sign up. There are many features that we can take note of:

1. The healthcare system needed changes because we have the most costly system, are endowed with advanced technology, and we have inexcusable outcomes in several domains of care, including, infant mortality, and prenatal care – but not in cardiology.

2. These changes that are notable are:

The disparities in outcome are magnified by a large disparity in highest to lowest income bracket.
This is also reflected in educational status, and which plays out in childhood school lunches, and is also affected by larger class size and cutbacks in school programs.
This is not helped by a large paralysis in the two party political system and the three legs of government unable to deal with work and distraction.
Unemployment is high, and the banking and home construction, home buying, and rental are in realignment, but interest rates are problematic.

3. The medical care system is affected by the issues above, but the complexity is not to be discounted.

The medical schools are unable at this time to provide the influx of new physicians needed, so we depend on a major influx of physicians from other countries
The technology for laboratories, proteomic and genomic as well as applied medical research is rejuvenating the practice in cardiology more rapidly than any other field.
In fields that are imaging related the life cycle of instruments is shorter than the actual lifetime use of the instruments, which introduces a shortening of ROI.
Hospitals are consolidating into large consortia in order to maintain a more viable system for referral of specialty cases, and also is centralizing all terms of business related to billing.
There is reduction in independent physician practices that are being incorporated into the hospital enterprise with Part B billing under the Physician Organization – as in Partners in Greater Boston, with the exception of “concierge” medical practices.
There is consolidation of specialty laboratory services within state, with only the most specialized testing going out of state (Quest, LabCorp, etc.)
Medicaid is expanded substantially under the new ACA.
The federal government as provider of services is reducing the number of contractors for – medical devices, diabetes self-testing, etc.
The current rearrangements seeks to provide a balance between capital expenses and fixed labor costs that it can control, reduce variable costs (reagents, pharmaceutical), and to take in more patients with less delay and better performance – defined by outside agencies.

Cardiology, Genomics, and calcium ion signaling and ion-channels in cardiomyocyte function in health and disease – including heart failure, rhythm abnormalities, and the myoneural release of neurotransmitter at the vesicle junction.

This portion is outlined as follows:

2.1 Human Genome: Congenital Etiological Sources of Cardiovascular Disease	2.2 The Role of Calcium in Health and Disease	2.3 Vasculature and Myocardium: Diagnosing the Conditions of Disease
Genomics & Genetics of Cardiovascular Disease Diagnoses	actin cytoskeleton	wall stress, ventricular workload, contractile reserve
Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging	calcium and actin skeleton, signaling, cell motility	hypertension & vascular compliance
Genetics of Conduction Disease	Ca+ stimulated exostosis: calmodulin & PKC (neurotransmitter)	complications & MVR
	disruption of Ca2+ homeostasis cardiac & vascular smooth muscle
	synaptotagmin as Ca2+ sensor & vesicles
	atherosclerosis & ion channels

It is increasingly clear that there are mutations that underlie many human diseases, and this is true of the cardiovascular system. The mutations are mistakes in the insertion of a purine nucleotide, which may or may not have any consequence. This is why the associations that are being discovered in research require careful validation, and even require demonstration in “models” before pursuing the design of pharmacological “target therapy”. The genomics in cardiovascular disease involves very serious congenital disorders that are asserted early in life, but the effects of and development of atherosclerosis involving large and medium size arteries has a slow progression and is not dominated by genomic expression. This is characterized by loss of arterial elasticity. In addition there is the development of heart failure, which involves the cardiomyocyte specifically. The emergence of regenerative medical interventions, based on pleuripotent inducible stem cell therapy is developing rapidly as an intervention in this sector.

Finally, it is incumbent on me to call attention to the huge contribution that research on calcium (Ca2+) signaling has made toward the understanding of cardiac contraction and to the maintenance of the heart rhythm. The heart is a syncytium, different than skeletal and smooth muscle, and the innervation is by the vagus nerve, which has terminal endings at vesicles which discharge at the myocyte junction. The heart specifically has calmodulin kinase CaMK II, and it has been established that calmodulin is involved in the calcium spark that triggers contraction. That is only part of the story. Ion transport occurs into or out of the cell, the latter termed exostosis. Exostosis involves CaMK II and pyruvate kinase (PKC), and they have independent roles. This also involves K+-Na+-ATPase. The cytoskeleton is also discussed, but the role of aquaporin in water transport appears elsewhere, as the transport of water between cells. When we consider the Gibbs-Donnan equilibrium, which precedes the current work by a century, we recall that there is an essential balance between extracellular Na+ + Ca2+ and the intracellular K+ + Mg2+, and this has been superceded by an incompletely defined relationship between ions that are cytoplasmic and those that are mitochondrial. The glass is half full!

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The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Posted in Accountable Care Organizations, Affordable Care Act, Anemia, Atherogenic Processes & Pathology, Best evidence, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Coagulation Therapy and Internal Bleeding, Computational Biology/Systems and Bioinformatics, Curation, Curation methodology, Cytoskeleton, Diabetes Mellitus, Electrophysiology, Evidence-based decision-making, Experimental validation, Federal Budget Appropriations, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, Healthcare costs and reimbursement, Healthcare Reform, Historical relevance, HTN, HTN in Youth, Indigent Nutrition, Interviews with Scientific Leaders, Ionic Transporters Na+, K, Medical Devices R&D and Inventions, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Medicare and Medicaid, Na-K transport, Na-K-ATPase, Nephrology, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmaceutical Analytics, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Prescription Drugs Costs, Regenerative Biology and Medicine, Resident-cell-based, Skilled Nursing Facilities, Stem Cells for Regenerative Medicine, Stents & Tools, Synaptic vesicle, Systematic Error (Bias), Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Science, Uninsured and Underinsured, Valves & Tools, tagged acute myocardial infarct, American College of Cardiology ACC, Antiarrhythmic drugs, arrythmias, Artificial Biosensor, Artificial cardiac pacemaker, Artificial heart, Bare-metal stent, Cardiac & Vascular Repair, cardiac myocyte regeneration, Cardiogenic Shock, Cardiology, Cardiometabolic Syndrome, CHF, Content Curation, Coronary artery disease, Coronary stent, Curation methodology, Drug-eluting stents, gene expression, Hypertension, myocardial hypertrophy, nitric oxide, Nitric oxide synthase, RNA, Stem cell on January 1, 2014| Leave a Comment »

The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Author: Larry H. Bernstein, MD, FCAP

Article ID #98: The Cost to Value Conundrum in Cardiovascular Healthcare Provision. Published on 1/1/2014

WordCloud Image Produced by Adam Tubman

I write this introduction to Volume 2 of the e-series on Cardiovascular Diseases, which curates the basic structure and physiology of the heart, the vasculature, and related structures, e.g., the kidney, with respect to:

1. Pathogenesis
2. Diagnosis
3. Treatment

Curation is an introductory portion to Volume Two, which is necessary to introduce the methodological design used to create the following articles. More needs not to be discussed about the methodology, which will become clear, if only that the content curated is changing based on success or failure of both diagnostic and treatment technology availability, as well as the systems needed to support the ongoing advances. Curation requires:

meaningful selection,
enrichment, and
sharing combining sources and
creation of new synnthesis

Curators have to create a new perspective or idea on top of the existing media which supports the content in the original. The curator has to select from the myriad upon myriad options available, to re-share and critically view the work. A search can be overwhelming in size of the output, but the curator has to successfully pluck the best material straight out of that noise.

Part 1 is a highly important treatment that is not technological, but about the system now outdated to support our healthcare system, the most technolog-ically advanced in the world, with major problems in the availability of care related to economic disparities. It is not about technology, per se, but about how we allocate healthcare resources, about individuals’ roles in a not full list of lifestyle maintenance options for self-care, and about the important advances emerging out of the Affordable Care Act (ACA), impacting enormously on Medicaid, which depends on state-level acceptance, on community hospital, ambulatory, and home-care or hospice restructuring, which includes the reduction of management overhead by the formation of regional healthcare alliances, the incorporation of physicians into hospital-based practices (with the hospital collecting and distributing the Part B reimbursement to the physician, with “performance-based” targets for privileges and payment – essential to the success of an Accountable Care Organization (AC)). One problem that ACA has definitively address is the elimination of the exclusion of patients based on preconditions. One problem that has been left unresolved is the continuing existence of private policies that meet financial capabilities of the contract to provide, but which provide little value to the “purchaser” of care. This is a holdout that persists in for-profit managed care as an option. A physician response to the new system of care, largely fostered by a refusal to accept Medicaid, is the formation of direct physician-patient contracted care without an intermediary.

In this respect, the problem is not simple, but is resolvable. A proposal for improved economic stability has been prepared by Edward Ingram. A concern for American families and businesses is substantially addressed in a macroeconomic design concept, so that financial services like housing, government, and business finance, savings and pensions, boosting confidence at every level giving everyone a better chance of success in planning their personal savings and lifetime and business finances.

http://macro-economic-design.blogspot.com/p/book.html

Part 2 is a collection of scientific articles on the current advances in cardiac care by the best trained physicians the world has known, with mastery of the most advanced vascular instrumentation for medical or surgical interventions, the latest diagnostic ultrasound and imaging tools that are becoming outdated before the useful lifetime of the capital investment has been completed. If we tie together Part 1 and Part 2, there is ample room for considering clinical outcomes based on individual and organizational factors for best performance. This can really only be realized with considerable improvement in information infrastructure, which has miles to go. Why should this be? Because for generations of IT support systems, they are historically focused on billing and have made insignificant inroads into the front-end needs of the clinical staff.

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Multivitamins – Don’t help Extend Life or ward off Heart Disease and Improve state of Memory Loss

Posted in Frontiers in Cardiology and Cardiovascular Disorders, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Population Health Management, Nutrition and Phytochemistry, tagged Annals of Internal Medicine, Brigham and Women's Hospital, Dietary supplement, Johns Hopkins Bloomberg School of Public Health, Multivitamin, United States Preventive Services Task Force on December 31, 2013| Leave a Comment »

Multivitamins – Don’t help Extend Life or ward off Heart Disease and Improve state of Memory Loss

Reporter: Aviva Lev-Ari, PhD, RN

Experts: Don’t Waste Your Money on Multivitamins – Three studies find the supplements don’t help extend life or ward off heart disease and memory loss

http://www.nlm.nih.gov/medlineplus/news/fullstory_143473.html

Monday, December 16, 2013

Related MedlinePlus Page

Dietary Supplements

MONDAY, Dec. 16, 2013 (HealthDay News) — With three new studies finding that a daily multivitamin won’t help boost the average American’s health, the experts behind the research are urging people to abandon use of the supplements.

The studies found that popping a daily multivitamin didn’t ward off heart problems or memory loss, and wasn’t tied to a longer life span.

The studies, published in the Dec. 17 issue of the journal Annals of Internal Medicine, found that multivitamin and mineral supplements did not work any better than placebo pills.

Dietary supplements are a multibillion-dollar industry in the United States, and multivitamins account for nearly half of all vitamin sales, according to the U.S. Office of Dietary Supplements.

But a growing body of evidence suggests that multivitamins offer little or nothing in the way of health benefits, and some studies suggest that high doses of certain vitamins might cause harm.

As a result, the authors behind the new research said it’s time for most people to stop taking them.

“We believe that it’s clear that vitamins are not working,” said Dr. Eliseo Guallar, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

In a strongly worded editorial on the three studies, Guallar and his co-authors urged people to stop spending money on multivitamins.

Even a representatives of the vitamin industry asked people to temper their hopes about dietary supplements.

“We all need to manage our expectations about why we’re taking multivitamins,” Duffy MacKay, vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, a trade group that represents supplement manufacturers, said in a prepared statement.

“Research shows that the two main reasons people take multivitamins are for overall health and wellness and to fill in nutrient gaps,” MacKay said. “Science still demonstrates that multivitamins work for those purposes, and that alone provides reason for people to take a multivitamin.”

However, Guallar said, it’s not clear that taking supplements to fill gaps in a less-than-perfect diet really translates into any kind of health boost.

“It would be great if all dietary problems could be solved with a pill,” he said. “Unfortunately, that’s not the case.”

For the first study, researchers randomly assigned almost 6,000 male doctors over the age of 65 to take either a daily Centrum Silver multivitamin or a look-alike placebo pill. Every few years, the researchers gave the men a battery of tests over the telephone to check their memories.

The men in the study were in pretty good health to begin with, and 84 percent said they faithfully took their pills each day.

After 12 years, there was no difference in memory problems between the two groups.

“No matter which way we broke it down, there was a null effect,” said study author Jacqueline O’Brien, a research associate at Brigham and Women’s Hospital in Boston. “Supplements are often marketed to have benefits for brain health and things like that, and this is a pretty clear takeaway message.”

The same study, however, had previously found that multivitamins might modestly reduce the risk of cancer and cataracts. Cancer risk was reduced by 8 percent, while the risk of cataracts dropped by 9 percent, compared to a placebo.

In the second study, researchers randomly assigned 1,700 heart attack survivors enrolled in a trial of therapy known as intravenous chelation to a daily regimen of high doses of vitamins and minerals or placebo pills.

Participants were asked to take six large pills a day, and researchers think many developed pill fatigue. Nearly half the participants in each part of the study stopped taking their medication before the end of the study. The average time people stuck with it was about two and a half years.

After an average of 55 months, there was no significant difference between the two groups in a composite measure that counted the number of deaths, second heart attacks, strokes, episodes of serious chest pain and procedures to open blocked arteries.

The third study, a research review, assessed the evidence from 27 studies on vitamin and mineral supplements that included more than 450,000 people. That study, conducted for the U.S. Preventive Services Task Force, found no evidence that supplements offer a benefit for heart disease or that they delay death from any cause. They found only a minimal benefit for cancer risk.

The results of the studies are so clear and consistent, the editorial writers said, that it’s time to stop wasting research money looking for evidence of a benefit.

“The probability of a meaningful effect is so small that it’s not worth doing study after study and spending research dollars on these questions,” Guallar said.

SOURCES: Eliseo Guallar, M.D., professor of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore; Jacqueline O’Brien, Sc.D., research associate, Brigham and Women’s Hospital, Boston; Dec. 16, 2013, news release, Council for Responsible Nutrition, Washington, D.C.; Dec. 17, 2013, Annals of Internal Medicine

HealthDay

SOURCES

http://www.nlm.nih.gov/medlineplus/news/fullstory_143473.html

http://consumer.healthday.com/cognitive-health-information-26/brain-health-news-80/experts-don-t-waste-your-money-on-multivitamins-683104.html

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Increased Consumption of Dietary Fiber is associated with a significantly Lower Risk of CVD and CHD

Posted in Atherogenic Processes & Pathology, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Population Health Management, Nutrition and Phytochemistry, tagged BMJ, CHD, Chemical vapor deposition, Dietary fiber, Fiber crop on December 31, 2013| Leave a Comment »

Increased Consumption of Dietary Fiber is associated with a significantly Lower Risk of CVD and CHD

Reporter: Aviva Lev-Ari, PhD, RN

LEEDS, UK — Aside from keeping you “regular,” eating fiber also appears to be good for your heart. A new review has shown that increased consumption of dietary fiber is associated with a significantly lower risk of CVD and CHD.

For every 7 g of dietary fiber eaten daily—which can be achieved by eating two to four servings of fruits and vegetables or a serving of whole grains plus a portion of beans or lentils—the risks of CVD and CHD were each lowered by 9%, according to a new meta-analysis published December 19, 2013 in BMJ ^[1].

“Lower risk of cardiovascular disease was also seen with greater intakes of insoluble, cereal, fruit, and vegetable fiber,” write Diane Threapleton (University of Leeds, UK), a PhD student, and colleagues. “In addition, reduced risk for CHD was associated with greater intake of insoluble fiber and fiber from cereal or vegetable food.”

A cardioprotective effect of dietary fiber was first suggested in the 1970s, and numerous studies have attempted to investigate the link, including the effects of fiber on CV risk factors.

In the present meta-analysis, Threapleton et al analyzed 22 cohort studies that reported total dietary-fiber intake, fiber subtypes, and fiber from food sources and CVD or CHD events. CVD events included CHD along with fatal and incident stroke. Five studies suggested that each 7-g/day increase in insoluble fiber lowered the risk of CVD and CHD by 18%, respectively. Fiber consumption from cereals lowered the risk of CVD and CHD, as did fiber from vegetables. Fiber sourced from fruit lowered the risk of CVD only.

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Putting these results in perspective, Dr Robert Baron(University of California, San Francisco) gets straight to the point in his editorial, “Eat More Fiber”^[2]. Although the study is limited by the potential for confounding—there is the possibility of an association between high fiber intake and other healthy behaviors—”clinicians should enthusiastically and skilfully recommend that patients consume more dietary fiber,” writes Baron. This includes a mix of soluble and insoluble fiber and fiber from multiple food sources, he adds.

Although the evidence for recommending higher fiber intake comes from “imperfect evidence,” including observational studies and expert opinion, the updated meta-analysis by Threapleton et al increases confidence in the recommendation, writes Baron.

The study was funded by the UK Department of Health. Threapleton reports that her PhD studentship receives funding from Kellogg’s. Baron reported no relevant financial disclosures.

References

Threapleton DE, Greenwood DC, Evans CE, et al. Dietary fiber intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 2013; 347:f6879. Available at: http://www.bmj.com.
Baron RB. Eat more fiber. BMJ 2013; 347:f7401. Available at: http://www.bmj.com.

SOURCE

http://www.medscape.com/viewarticle/818385?nlid=43303_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

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USPSTF: Evidence for Supplement Use Lacking

Posted in Nutritional Supplements: Atherogenesis, lipid metabolism on November 19, 2013| Leave a Comment »

USPSTF: Evidence for Supplement Use Lacking

Reporter: Aviva Lev-Ari, PhD, RN

See on Scoop.it – Cardiovascular and vascular imaging

There still is not enough evidence to recommend for or against vitamin and mineral supplements for primary prevention of heart disease or cancer, a draft of updated recommendations from the U.S.

See on www.medpagetoday.com

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Heart Metabolism or Metabolic Cardiology: The Role of Ribose (D-ribose) for the Ischemic Heart – The Work of John St. Cyr, M.D., Ph.D.

Posted in Abdominal Aorta, Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, CABG, Cardiac and Cardiovascular Surgical Procedures, Carotid Artery, Electrophysiology, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Heart Transplant, Heart-Lung Transplant, HTN, Indigent Nutrition, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Metabolomics, Mitral Valve: Repair and Replacement, Nutrigenomics, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Thoracic Aorta, Valves & Tools, tagged Aviva Lev-Ari, Cardiovascular disease, Cardiovascular Disorders, Heart Failure on October 23, 2013| Leave a Comment »

Heart Metabolism or Metabolic Cardiology: The Role of Ribose (D-ribose) for the Ischemic Heart -The Work of John St. Cyr, M.D., Ph.D.

Reporter: Aviva Lev-Ari, PhD, RN

REVIEW

An interview with John St. Cyr, M.D., Ph.D. on Ribose : A Key to Heart Health and Energy

By Richard A. Passwater, Ph.D.

January 2005

Ribose : A Key to Heart Health and Energy

An interview with John St. Cyr, M.D., Ph.D.

By Richard A. Passwater, Ph.D.

SOURCE

http://www.drpasswater.com/nutrition_library/John_St_Cyr.html

John St. Cyr, M.D., Ph.D. — PATENTS:

Issued:

Suture removal device, USP5250052

Double layer prophylactic incorporating pharmacological fluid and spiral barrier layer, USP5623945

Compositions for increasing energy in vivo, USP6159942

Method for determining viability of a myocardial segment, USP6339716

Method for raising the hypoxic threshold, USP6218366

Use of ribose to prevent cramping and soreness in muscles, USP6159943

Compositions for increasing athletic performance in mammals, USP6429198

Dual lumen adjustable length cannulae for liquid perfusion or lavage, USP6692473

Method for treating acute mountain sickness, USP6511964

Compositions for increasing energy in vivo, USP6534480

Compositions for the storage of platelets, USP6790603

Compositions for enhancing the immune response, USP6663859

Composition methods for improving cardiovascular function, USP7553817

Rejuvenation of stored blood, USP7687468

John St. Cyr, M.D., Ph.D. — Pending applications:

Method for improving ventilatory efficiency, SN20050277598

Storage of blood SN20070111191

Ventilatory benefits of ribose in COPD, smoking, SN

Use of ribose in recovery from anesthesia, SN20070105787

Use of ribose to alleviate rhabdomyolysis and the side effects of statin drugs, SN20060135440

Use of ribose in first response to acute myocardial infarction, SN20100055206

Compositions and methods for improving cardiovascular function, SN20100009924

Use of ribose in lessening the clinical symptoms of aberrant firing of neurons, SN20090286750

Compositions for indoor tanning, SN20090232750

Compositions for improving and repairing skin, SN20090197819

Use of ribose for recovery from anesthesia, SN20090197818

Cosmetic use of D-ribose, SN20080312169

Method for improving ventilator efficiency SN20100099630

Method and compositions for improving pulmonary hypertension, SN20080146514

Storage of blood, SN20070111191

Compositions and methods for feeding poultry, SN201100221446

Use of D-ribose for fatigued subjects, SN20100189785

Fibrin sealants and platelet concentrates applied to effect hemostasis in the interface of an implantable medical device with body tissue, SN20060190017

Compositions for reducing the deleterious effects of stress and aging, SN20120045426

John St. Cyr, M.D., Ph.D. — Provisional patents:

Use of ribose in pre-slaughtering of animals

Rescue therapy for acute decompensated heart failure

Combination of D-ribose plus caffeine

Role of ribose in reducing joint swelling in mammals

Role of D-ribose in cardiac remodeling

Role of D-ribose in cachexia

Use of ribose in stem cells

Use of ribose in cardioplegia

Use of ribose for doping blood for cardioplegia

Surgical adhesive for bleeding situations

Metabolic approach with EECP

Role of ribose in mitral regurgitation

Compositions for the preservation of morphology in stored blood

Methods and nutritional supplements for improving the quality of meat

John St. Cyr, M.D., Ph.D. — Publications 2011 to 2013

This list does not include Publication #1 to #219

220. Shecterle LM, Wagner S, St.Cyr JA. A sugar for congestive heart failure patients. Ther Adv Cardiovasc Dis 5(2):95-97, 2011.

221. Perkowski D, Wagner S, Schneider JR, St.Cyr JA. A targeted metabolic protocol with D-ribose for off pump coronary artery bypass procedures: A retrospective analysis. Ther Adv Cardiovasc Dis 5(4):185-192, 2011.

222. Foker J, Berry J, Harvey B, Befera N, Tveter K, St.Cyr J, Bianco R. Heart failure is initiated by and progresses because of normal responses of energy metabolism to stress. Circ Res , 2011.

223. Rakow N, Barka N, Gerhart R, Rothstein P, Green M, Schu C, Grassl E, St.Cyr JA, Kopcak MW, Jr. Chronic aortic root pressure-loading assessment model. J Invest Surg 25(2):137, 2012.

224. Shecterle LM, St.Cyr JA. Chapter 11; Myocardial Ischemia: Alterations in myocardial cellular energy and diastolic function, a potential role for D-ribose. In: Novel Strategies in Ischemia Heart Disease. Lakshmanadoss U(Ed). InTech, Croatia. 219-228, 2012.

225. Addis P, Shecterle LM, St.Cyr JA. Cellular protection during oxidative stress: a potential role for D-ribose and antioxidants. Journal of Dietary Supplements 9(3):178-182, 2012.

226. Holsworth R, Shecterle L, St.Cyr J, Sloop G. Letter to the Editor. Importance of monitoring blood viscosity during cardiopulmonary bypass. Perfusion 28(1):91-2, 2013.

227. Seifert JG, Frost J, ST.Cyr JA. Recovery benefits of a heat and moisture exchange mask when performing sprint exercise in cold temperature environments. Aviation, Space and Environmental Medicine. , 2013.

228. Seifert JG, McNair M, DeClercq P, St.Cyr JA. A heat and moisture mask attenuates cardiovascular stress during cold air exposure. Ther Adv Cardiovasc Dis 7(3):123-129, 2013.

229. Holsworth R, Cho Y, Weldman J, Sloop G, St.Cyr, J. Cardiovascular benefits of phlebotomy: Relationship to changes in hemorheological variables. Perfusion, 2013.

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Relationship between Adiposity and High Fructose Intake Revealed

Posted in Metabolomics, Nutrigenomics, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Population Health Management, Nutrition and Phytochemistry, tagged Adipose tissue, fructose, fructose metabolism, glyoxalase-1, glyoxalase-2, green tea extract, hepatic lipogenesis on October 14, 2013| Leave a Comment »

Relationship between Adiposity and High Fructose Intake Revealed

Reporter: Larry H Bernstein, MD, FCAP

Dietary Fructose Feeding Increases Adipose Methylglyoxal Accumulation in Rats in Association with Low Expression and Activity of Glyoxalase-2

Christopher Masterjohn^1,2, Youngki Park¹, Jiyoung Lee¹, Sang K. Noh³, Sung I. Koo¹ and Richard S. Bruno^1,4,* ¹ Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA ² Department of Comparative Biosciences, University of Illinois, Urbana, IL 61801, USA ³ Department of Food and Nutrition, Changwon National University, Changwon 641-773, Korea ⁴ Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
Nutrients 2013, 5(8), 3311-3328; http://dx.doi.org/10.3390/nu5083311

Abstract

Methylglyoxal is a precursor to advanced glycation endproducts that may contribute to diabetes and its cardiovascular-related complications.
Methylglyoxal is successively catabolized to d-lactate by glyoxalase-1 and glyoxalase-2.

The objective of this study was to determine whether dietary fructose and green tea extract (GTE) differentially regulate methylglyoxal accumulation in liver and adipose, mediated by tissue-specific differences in the glyoxalase system.

We fed six week old male Sprague-Dawley rats a low-fructose diet (10% w/w) or a high-fructose diet (60% w/w) containing no GTE or GTE at 0.5% or 1.0% for nine weeks.

Fructose-fed rats had higher (P < 0.05) adipose methylglyoxal, but GTE had no effect. Plasma and hepatic methylglyoxal were unaffected by fructose and GTE. Fructose and GTE also had no effect on the expression or activity of glyoxalase-1 and glyoxalase-2 at liver or adipose.

Regardless of diet, adipose glyoxalase-2 activity was 10.8-times lower (P < 0.05) than adipose glyoxalase-1 activity and 5.9-times lower than liver glyoxalase-2 activity.
Adipose glyoxalase-2 activity was also inversely related to adipose methylglyoxal (r = −0.61; P < 0.05).
These findings suggest that fructose-mediated adipose methylglyoxal accumulation is independent of GTE supplementation and that its preferential accumulation in adipose compared to liver is due to low constitutive expression of glyoxalase-2.

Keywords: fructose; glyoxalase I; glyoxalase II; pyruvaldehyde; rats; Sprague-Dawley

Masterjohn C, Park Y, Lee J, Noh SK, Koo SI, Bruno RS. Dietary Fructose Feeding Increases Adipose Methylglyoxal Accumulation in Rats in Association with Low Expression and Activity of Glyoxalase-2. Nutrients. 2013; 5(8):3311-3328. EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland

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New Data Dispute Calcium Cardiovascular Risk in Both Sexes

Posted in Atherogenic Processes & Pathology, Biomarkers & Medical Diagnostics, Calcium, Interviews with Scientific Leaders, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Population Health Management, Nutrition and Phytochemistry, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Statistical Methods for Research Evaluation, tagged American Society for Bone and Mineral Research, Calcium, Cardiovascular disease, Joshua Lewis, Mark Bolland, Stanford University, University of Western Australia on October 11, 2013| Leave a Comment »

Medscape Update on Calcium and Cardiovascular Risk

Curator and Reporter: Larry H. Bernstein, MD, FCAP

New Data Dispute Calcium Cardiovascular Risk in Both Sexes

Article ID #82: New Data Dispute Calcium Cardiovascular Risk in Both Sexes. Published on 10/11/2013

WordCloud Image Produced by Adam Tubman

Nancy A. Melville Oct 08, 2013

Medscape Medical News from the American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting

BALTIMORE — Two new studies contribute further to the debate over the cardiovascular risk associated with supplementary or dietary calcium, each decidedly coming down on the side of no significant risk — to men or women.

“[Based on these findings], clinicians should continue to evaluate calcium intake, encourage adequate dietary intake, and if necessary, use supplements to reach but not exceed recommended intakes,” Douglas C. Bauer, MD, from the University of California, San Francisco, the lead author of the first study, told Medscape Medical News.

Results of both studies were reported at the recent American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting.

Dr. Bauer’s observational trial is one of few contemporary studies to evaluate the level of risk among men, who are often poorly represented in calcium studies, he noted. The results showed no association between calcium dietary intake or supplementation and total or cardiovascular mortality. The second study was an updated meta-analysis of calcium supplementation among women and similarly demonstrated no increased risk for ischemic heart disease (with adjudicated outcomes) or total mortality in elderly women. It did draw some criticism for potential bias and contamination, however.

Nevertheless, says Robert Marcus, MD, a retired Stanford University bone specialist, the 2 studies are “powerful. The one involving men had very elegant, accurate reports of death and validated diagnosis of myocardial infarction, and the [study involving women] was also excellent work,” he commented.

“This field has been the subject of an enormous amount of controversy, ambiguity, and confusion for the past several years, and I think the most important thing is to help us come up with what is true,” he said. The quality of data to suggest an adverse effect of calcium is “very poor,” and there is now compelling evidence that there is little to substantiate this, he noted. But despite these reassuring new findings, public anxiety over a potential risk with calcium is unlikely to go away, he believes.

In recommendations issued in 2010, the ASBMR said that most adults 19 years of age and older require about 600 to 800 IUs of vitamin D daily and 1000 to 1200 mg of calcium daily through food and with supplements, if needed.

Contemporary Data on Calcium Intake in Men

The use of calcium supplements, predominantly with vitamin D, is an important therapy for the prevention of osteoporosis and its clinical consequences. But concerns about the cardiovascular safety of calcium have emerged periodically; in 2 alarming meta-analyses published in 2010 and 2011 by Dr. Mark Bolland and colleagues, for example, there was a 27% increase in MI among individuals allocated to calcium supplements in the first study and a 24% increased risk in the second.

More recently, a 40% increase in total mortality and up to a 50% increase in cardiovascular mortality was seen among women from a Swedish mammography cohort with a calcium intake exceeding 1400 mg per day. In that study, the effect on mortality appeared to be especially strong if a high dietary intake of calcium was combined with calcium supplements.

In their new study, Dr. Bauer and his colleagues set out to assess rates of dietary calcium intake, use of supplements, and mortality in a prospective cohort of 5967 men over the age of 65 years in the Osteoporotic Fractures in Men (MrOS) study.

The participants completed extensive surveys at baseline on their dietary calcium intake, and supplementation was verified by a review of pill bottles by trained staff.

Mean dietary calcium intake was 1142 ± 590 mg/day, with more than half — 65% — of participants reporting use of calcium supplements.

Over the 10-year follow-up, among 2022 men who died, 687 deaths were caused by cardiovascular disease. The highest mortality for CVD was seen in the quartile with the lowest intake from calcium supplementation.

And in models that adjusted for age, energy intake, and calcium use, men in the lowest quartile of total calcium intake (less than 621 mg per day) had higher total mortality compared with those in the highest quartile (more than 1565 mg of calcium per day).

Adjustment for additional confounding factors showed no association between calcium dietary intake and total or cardiovascular mortality (P for trend .51 and .79, respectfully). Likewise, there was no association between calcium supplementation and total or cardiovascular mortality.

The authors also conducted an additional analysis of calcium intake and adjudicated cardiovascular disease events in a subcohort of the study, MrOS Sleep, involving 3120 patients who took part in a 7-year follow-up, and again there was no higher risk for cardiovascular events associated with calcium intake.

The study did have is limitations, Dr. Bauer acknowledged, including the observational design, calcium intake being assessed with a food frequency questionnaire, and cause of death not being formally adjudicated. Nevertheless, the findings are important in demonstrating the level of risk among men in a contemporary setting, he pointed out.

“Contrary to the Swedish study of women, we found no evidence that calcium supplementation is harmful to men, even among those with the highest dietary calcium intake,” he concluded, recommending that future studies should include adjudicated outcomes.

Study in Men as Expected, but Female Research Questioned

In the second study reported at the ASBMR meeting, Joshua Lewis, MD, PhD, from the University of Western Australia, Perth, and colleagues reported a meta-analysis of 19 randomized controlled trials involving women over the age of 50 years who had received calcium supplementation for more than a year.

Importantly, the analysis included reports of adjudicated cardiovascular outcomes, which the researchers note is important because gastrointestinal events can be misreported as cardiac ones. They also assessed all-cause mortality.

Among 59,844 participants in the studies, there were 4646 deaths, and the relative risk for death among those randomized to calcium supplements was 0.96 (P = .18).

The relative risk for 3334 ischemic heart disease events among 46,843 participants was 1.02 (P = .053), and the risk for 1097 MI events among 49,048 participants was 1.09 (P =.21).

“The data from this meta-analysis does not support the concept that calcium supplementation with or without vitamin D increases the risk of ischemic heart disease or total mortality in elderly women,” concluded Dr. Lewis.

But bone specialist Ian Reid, MD, from the University of Auckland, New Zealand, who was a coauthor on some of the Bolland studies, said this analysis essentially repeats previous ones, but with the inclusion of 20,000 patients from the Women’s Health Initiative (WHI), many of whom continued to take their own calcium tablets, regardless of whether they were randomized to calcium or placebo.

These “contaminated” WHI data have the potential to mask the effect of calcium, he told Medscape Medical News. In addition, in a study from Denmark also included in the meta-analysis, subjects were not properly blinded to treatment assignment and the calcium and control groups were not comparable at baseline for cardiovascular risk, which introduced “major potential bias,” he added.

Regarding the results from the study in men by Dr. Bauer and colleagues, Dr. Reid said they were not surprising to him. “Generally, people who take calcium supplements have more health-conscious behaviors than those who do not and so have a lower baseline risk of heart disease” that can “obscure small adverse effects of drugs such as calcium,” he observed.

An effect has to be “very substantial” before it can be picked up in an observational study, because of the many confounders that can obscure such an effect, he concluded.

Dr. Bauer, Dr. Lewis, Dr. Reid, and Dr. Marcus have reported no financial relationships. MrOS is supported by funding from the National Institutes of Health.

American Society for Bone and Mineral Research 2013 Annual Meeting. Abstracts 1001 and 1002, presented October 4, 2013.

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Archive for the ‘Nutritional Supplements: Atherogenesis, lipid metabolism’ Category

Multivitamins – Don’t help Extend Life or ward off Heart Disease and Improve state of Memory Loss

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Increased Consumption of Dietary Fiber is associated with a significantly Lower Risk of CVD and CHD