High levels of homocysteine (Hcy), or a high "H score," predicts risk for over 100 diseases like cardiovascular disease (CVD), cerebrovascular accident (CVA), diabetes, and renal disease. Elevated plasma Hcy is an important, strong, and modifiable risk factor that can predict higher long-term mortality when elevated at baseline. Hcy levels are affected by genetic mutations, nutritional deficiencies, diseases, and drugs, and testing is recommended for those with vascular diseases or risk factors. Elevated Hcy can damage arteries in several ways and is a stronger predictor of CVD risk than cholesterol.
This is a presentation that I gave to my graduate level Vitamins and Minerals class depicting how the amino acid homocysteine effects cardiovascular disease.
This is a presentation that I gave to my graduate level Vitamins and Minerals class depicting how the amino acid homocysteine effects cardiovascular disease.
Comprehensive description of various primary dyslipidemias, cholesterol transport and molecular mechanisms involved.
View in slideshow after downloading for better experience.
Prepared in Dec 2013.
Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Normally, these metabolites are not found in appreciable quantities in blood or urine.
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
Comprehensive description of various primary dyslipidemias, cholesterol transport and molecular mechanisms involved.
View in slideshow after downloading for better experience.
Prepared in Dec 2013.
Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Normally, these metabolites are not found in appreciable quantities in blood or urine.
Learning Objectives:
Introduction
Definition of CML
Philadelphia Chromosome
Normal Granulopoiesis
Pathogenesis of CML
Aetiology
Incidence
Clinical Features
Phases of CML
Lab Diagnosis of CML
Course & Prognosis
Differential Diagnosis
Brief Overview of Treatment
Pukhraj Aloe Vera juice helps with blood pressure because it dilates capillaries and enhances circulation. Aloe vera has vitamin C which has been shown to help lower blood pressure,
It decreases total cholesterol levels, triglyceride, phosholipid, nonesterified fatty acid levels.
It increases HDL cholesterol (the "good" cholesterol) levels and also HDL/Total cholesterol ratios.
Pukhraj Aloe Vera contains major Antioxidents like Vitamin C, a and E. They reduce risk of heart attack and offer a vital protection against death from coronary disease.
Lifestyle Diseases - An Emerging Issue in Working WomenIndus Health Plus
The daily 'multitask' requirement on working women is affected on their health and hence working female's are suffering from some life-style diseases such as obesity, depression, chronic backache, diabetes, hypertension, high cholesterol, heart and kidney diseases.
For this it is advisable that the women has to aware about specific women health problems & need to take preventive health checkup to identify the future potential health risk factors.
Indus Health Plus provides best preventive health checkup packages such as heart checkup, full body checkup packages, fitness checkup, annual corporate checkup, executive checkup, couple checkup and family health checkup at 50% less than market cost with same day reports.
Get your checkup done today @ http://bit.ly/2gmXBNk
Call Us: 0-90490-22222
Final Program of 2nd International Conference on #Cardiovascular Medicine and #Cardiac Surgery to be held in London, UK during March 15-16, 2017. The conference provides speakers and delegates with the opportunity to consolidate their knowledge and understanding of the latest scientific advancements. Cardiovascular 2017 is known for being a collaborative forum to exchange ideas and network through the symposium, panel discussions, poster sessions, and opportunities for the companies to exhibit at our event.
This World Cancer Day, know alarming statistics about smoking. Know how smoking affects your body very badly and how quit smoking change your body towards healthy life. Quitting smoking greatly reduces your risk for numerous diseases like cancers, COPD, and many more.
Indus Health Plus provides best preventive health checkup packages such as heart checkup, full body checkup packages, fitness checkup, annual corporate checkup, executive checkup, couple checkup and family health checkup at 50% less than market cost with same day reports.
Get avail health checkup packages at http://bit.ly/2m2nQf3
Call Us: 0-90490-22222
Diabetes is a rapidly and serious health problem in Pakistan. This chronic condition is associated with serious long-term complications, including higher risk of heart disease and stroke. Aggressive treatment of hypertension and hyperlipideamia can result in a substantial reduction in cardiovascular events in patients with diabetes 1. Consequently pharmacist-led diabetes cardiovascular risk (DCVR) clinics have been established in both primary and secondary care sites in NHS Lothian during the past five years. An audit of the pharmaceutical care delivery at the clinics was conducted in order to evaluate practice and to standardize the pharmacists’ documentation of outcomes. Pharmaceutical care issues (PCI) and patient details were collected both prospectively and retrospectively from three DCVR clinics. The PCI`s were categorized according to a triangularised system consisting of multiple categories. These were ‘checks’, ‘changes’ (‘change in drug therapy process’ and ‘change in drug therapy’), ‘drug therapy problems’ and ‘quality assurance descriptors’ (‘timer perspective’ and ‘degree of change’). A verified medication assessment tool (MAT) for patients with chronic cardiovascular disease was applied to the patients from one of the clinics. The tool was used to quantify PCI`s and pharmacist actions that were centered on implementing or enforcing clinical guideline standards. A database was developed to be used as an assessment tool and to standardize the documentation of achievement of outcomes. Feedback on the audit of the pharmaceutical care delivery and the database was received from the DCVR clinic pharmacist at a focus group meeting.
Journal Club presentation- Mood stabilizers and risk of stroke in bipolar dis...RachitSharma132
To investigate the association between acute exposure to mood stabilizers and risk of stroke in patients with bipolar disorder
To explore the effects of combination therapy of mood stabilizers and antipsychotic drugs on the risk of stroke
Potential role of uric acid in correlation with epidemics of hypertension and...Apollo Hospitals
Diabetic nephropathy (DN) is a microvascular complication of Type 2 diabetes mellitus. Uric acid (UA) is the end product of purine nucleotide metabolism and its primary mode of clearance is by renal excretion. Modifiable factors such as blood pressure, albuminuria, glycemic control, etc., play an important role in the progression of DN and none of them are curative. Hence, there is a pressing interest to identify other potentially modifiable factors such as UA in the progression of DN.
Hemorheological indexes, living habits, medical history and genetics factor are primary risk factors in Coronary Heart Disease (CHD). In the present study the relation of all factors to the severity of CHD was examined. The data of 282 patients (mean age: 60±9 years) diagnosed with CHD and 229 healthy controls (mean age: 59±7 years) from Wenzhou Medical University were analyzed.
Blood And Its Clinical Aspects - Dr. Gunjan Barot.pptxGunjanBarot
Blood is a valuable component of the human body. One needs in depth knowledge in medicine regarding blood. In Dentistry too one deals with the blood and its clinical implications on daily basis. This presentation includes Blood as a whole : Its components as well the clinical aspects along with the newer researches. Being a Pediatric Dentistry Resident the viewpoint has been inclined a bit more towards the same in the presentation.
Cardiovascular disease is the most prevalent class of diseases in the world. Every year more individuals die from cardiovascular diseases than any other illness. Diagnosis and treatment options are limited despite current and past efforts. The molecular mechanisms that lead to the onset and progression of detrimental phenotypes in the heart remain largely elusive. To battle against the ever-increasing number of cardiovascular disease-related deaths, major goals of cardiovascular proteomics studies include the development and
utilization of cutting-edge proteomics technologies to map the dynamic cardiac and vascular proteomes, elucidate cardiovascular disease mechanisms, identify candidate therapeutic targets and provide a clinically useful diagnosis as well as risk prediction. Current emphasis is given to promoting the development and adoption of quantitative protein assays targeting highly relevant cardiovascular proteins, such that translation of proteomics technologies may be expedited. Current proteomic approaches in cardiovascular proteomics are discussed.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Homocysteine: An Overlooked Biomarker in Clinical Medicine
1. Homocysteine – The “H factor”
Dr. Furquan Alam
MD (Biochemistry)
Assistant Professor
Glocal Medical College, SSH & RC, Saharanpur
An Overlooked Biomarker in
Clinical Medicine
4. • High levels of homocysteine, or a high "H
Score," predicts the risk of more than 100
diseases and medical conditions including
CVD, CVA, Diabetes, Renal Disease etc.
• Elevated Plasma Homocysteine is an
important, Strong, Graded and
Modifiable Risk Factor.
• ↑ Hcy at baseline also Predicts higher long
term Mortality.
07 March 2017
Dr. Furquan Alam 4
7. Introduction
• Homocysteine (Hcy), a sulphur containing amino acid
with a molecular weight of 135.2 Dalton.
• Derived from Methionine
• First isolated from a urinary bladder stone in 1933 by
Vincent du Vigneaud.
• Later Vincent du Vigneaud received the Nobel Prize in
chemistry in 1955.
07 March 2017 Dr. Furquan Alam 7
10. • Varying forms
• 1% free
• 70-80% bound to albumin via a disulfide link
• 20-30% either as a homocysteine dimer or a
cysteine-homocysteine-mixed disulfide.
* The type(s) of species responsible for the CVD
pathology have yet to be determined.
07 March 2017 Dr. Furquan Alam 10
11. Homocysteine
• Normal levels :
• In serum: 13-18 µmol/L
• In plasma: 10- 15 µmol/L
• In pediatric patients: 3.7-10.3 µmol/L
• Desirable Serum Level: <10 µmol/lit, preferably between
7-8 µmol/lit.
Hyperhomocysteinemia:
Mild
• 15 – 30
µmol/lit
Moderate
• 30 -100
µmol/lit
Severe
• >100
µmol/lit
07 March 2017 Dr. Furquan Alam 11
16. Etiology of Hyperhomocysteinemia
• Genetic mutations
• Nutritional deficiencies
• Disease states
• Drugs
07 March 2017 Dr. Furquan Alam 16
17. Genetic Mutations
5-methyleneterahydrofolate reductase (MTHFR)
polymorphism due to a point mutation on chromosome 1.
Prevalence MTHFR
15% in European, Middle Eastern and Japanese
1.4% or less in African Americans.
Mild to moderate condition
Higher risk of neural tube defects and pregnancy loss
Mother with the MTHFR mutation who have normal
homocysteine levels are not at increased risk for clots.
07 March 2017 Dr. Furquan Alam 17
18. Nutritional deficiencies
• Folate deficiency
• Vitamin B12 (Cobalamine) deficiency
• Vitamin B6 (Pyridoxine) deficiency
07 March 2017 Dr. Furquan Alam 18
19. Disease states
• Cystathione β-synthase deficiency
• Homocysteinuria
• Methionine synthase deficiency
* Both are rare autosomal recessive disorders that are
correlated with Hyperhomocysteinemia and vascular
thrombosis.
• Chronic renal failure regardless of etiology, duration,
or type of dialysis
• Severe psoriasis
• Possibly through increased cell turnover
• Pernicious anemia
• Cobalamine deficiency
07 March 2017 Dr. Furquan Alam 19
20. Drugs That Raise Homocysteine Levels
• A number of prescription drugs and natural compounds
can elevate blood levels of homocysteine by interfering
with folate absorption or metabolism of homocysteine.
Caffeine Niacin
Cholestyramine Nitrous oxide
Colestipol Pemetrexed
Fenofibrate Phenytoin
Levodopa Pyrimethamine
Metformin Sulfasalazine
Methotrexate Carbamazepine
07 March 2017 Dr. Furquan Alam 20
21. Drugs
• Cholestyramine (reduces cholesterol in blood)
• Impairs folate absorption
• Methotrexate (treatment of psoriasis)
• Depletes folate metabolites
• Anti-epileptics (carbamazepine, phenytoin)
• Lower folate concentrations
Tobacco and caffeinated coffee
07 March 2017 Dr. Furquan Alam 21
22. Who should have their
Homocysteine level tested?
07 March 2017 Dr. Furquan Alam 22
23. Sample Collection & Patient Preparation
Sample type: Blood (Serum/Plasma)
It can be measured at any time of day but preferably
overnight fasting and morning Sample. No special
preparations.
Once blood is drawn, Serum should separated within
1 hour.
serum or plasma is first treated with a reducing agent
that converts all Hcy species into the reduced form which
is measured either directly or after derivatization.
Homocysteine levels increase ~10% for every hour the
serum/plasma is not separated from the RBCs at room temperature.
07 March 2017 Dr. Furquan Alam 23
24. How is the Homocysteine level measured ?
Currently, there are three main tHcy test methods
available to the clinical laboratories. They include:
• Chromatographic method (HPLC) :
• developed in the early 1980s, and is mainly used in
research laboratories.
• Immunoassay method:
• developed in the mid 1990s, and has been
automated for special immunoassay instruments.
• Enzyme cycling method:
• Latest, developed in last few years, Used on any
Automated clinical chemistry analyzer, and is quickly
becoming the preferred method for clinical
laboratories.07 March 2017 Dr. Furquan Alam 24
27. Hyperhomocysteinemia and CVD
Cardiovascular Disease is the world’s
number one killing disease.
constituting about 30% of annual
worldwide deaths.
Up to 80% of all heart attacks occur in
people with normal cholesterol
In 25% of adults, the first sign of heart
disease is sudden death from a heart
attack.
Copyright 2010 - Drjoeesposito.com
July, 2006 Vol. 3 No. 4 Homocysteine - Revisited
07 March 2017 Dr. Furquan Alam 27
28. The right idea but the wrong era
Dr Kilmer McCully, a researcher who graduated
from Harvard Medical School in the mid-1960s and
came up with the hypothesis that moderate
elevations of homocysteine could lead to heart
attacks and strokes.
It was the time that the cholesterol-heart-attack
theory was gaining tremendous momentum and Mc
Cully’s hypothesis clearly challenged its future.
He found himself moved down to the basement,
funding for his research dried up and he was
eventually asked to leave Harvard.
07 March 2017 Dr. Furquan Alam 28
29. Prevalence of hyperhomocysteinemia is
not insignificant:
• General population: 5 - 10%
• Elderly population: 30 - 40%
• Pts with vascular disease: 20 - 40%.
Epidemiology
Annu Rev Med 1998;49:31-62. HCY and cardiovascular disease. Refsum H,
Ueland PM, et.al.
Jacques PF, Bostom AG, Wilson PW, et.al. Determinants of plasma total HCY
concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73:613-
621
07 March 2017 Dr. Furquan Alam 29
30. Why is Homocysteine harmful?
Experiments on arteries of both animals
and humans with an elevated level of
homocysteine showed that homocysteine
level in blood is an independent risk
factor for atherosclerotic vascular disease
affecting the coronary (arteries supplying
the heart), cerebral (arteries supplying the
brain) and peripheral arteries (supplying
the rest of the body).
Copyright 2010 - Jeremy E. Kaslow, M.D. - all rights reserved
07 March 2017 Dr. Furquan Alam 30
32. Risk Factors for CVD
Non-modifiable
Advancing age
Heredity or family
history
Gender
Ethnicity or race
Major modifiable
High blood pressure.
Abnormal blood lipids
Tobacco use.
Physical inactivity
Obesity
Diabetes mellitus
Unhealthy diets
Novel Risk Factors
Excess homocysteine in
blood
Inflammation e.g. CRP
Abnormal blood coagulation:
e.g. Fibrinogen
Lp ( a)
07 March 2017 Dr. Furquan Alam 32
33. What Homocysteine Does to Arteries
Homocysteine Lysyl residues of collagen
Interferes collagen crosslinking & bind to fibrillin
endothelial dysfunction.
Homocysteine thiolactone (free radical)
Thiolates LDL particles
Aggregate
Endocytosed by macrophages
↑ed tendency for atherogenesis07 March 2017
Dr. Furquan Alam
33
34. What Homocysteine Does to Arteries
It changes coagulation factor levels so as to encourage
blood clot formation
It causes the smooth muscle cells that support the
arterial wall to multiply-part of the atherogenic process.
Homocysteine activation of Hageman factor
↑platelet adhesiveness life threatening intravascular
thrombosis.
The net result is a threefold increase in heart attack risk
(Loscalzo et al., 1998;Maxwal., 2000 )
07 March 2017 Dr. Furquan Alam 34
36. If cholesterol and a high-fat diet are
the key culprits in heart disease,
why haven't we seen more of a
reduction in our number-one
disease killer over these past
several decades?
07 March 2017 Dr. Furquan Alam 36
37. Homocysteine vs. Cholesterol
Researchers conclude that homocysteine
is up to 40 times more predictive than
cholesterol in assessing cardiovascular
disease risk.
Many studies concluded that the risk of
arteriosclerotic vascular disease does in
fact increase with the homocysteine level,
regardless of whether cholesterol is
normal or elevated.
heart44; 11-01-2004
07 March 2017 Dr. Furquan Alam 37
38. Abnormally raised insulin seen in
most diabetics stops the body from
lowering and maintaining a healthier
homocysteine level.
One third of the diabetic patients had
elevated blood Homocysteine
Type 2 diabetic patients with elevated
homocysteine levels are nearly 200%
more likely to die from a heart attack
within 5 years than those with normal
Homocysteine levels
Homocysteine & Diabetes
Vasc Health Risk Manag. 2010; 6: 327–332.
07 March 2017 Dr. Furquan Alam 38
41. • tHcy levels are highly elevated in renal failure
patients.
• Impaired renal excretion and/or tubular
metabolism of Hcy, and extra renal factors, like
secondary vitamin deficiencies (e.g., in
connection with hemodialysis), genetic causes
and altered Hcy metabolism are among the
reasons.
Homocysteine & Renal Disease/Failure
07 March 2017 Dr. Furquan Alam 41
42. Homocysteine & Osteoporosis
An increased homocysteine level appears to be a
strong and independent risk factor for
osteoporotic fractures in older men and women
high serum homocysteine concentration may
weaken bone by interfering with collagen cross-
linking, thereby increasing the risk of
osteoporotic fracture
N Engl J Med. 2004;350:2033-2041
07 March 2017 Dr. Furquan Alam 42
43. Homocysteine & Pregnancy
Homocysteine conc. decreased in pregnancy due to
• Hemodilution
• Raised GFR
• Hormonal changes of pregnancy
• Increased fetal uptake
07 March 2017 Dr. Furquan Alam 43
45. Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004
The American College of Obstetricians and Gynecologists as accessed on 29th April 2012
NTDs
Other congenital
defects
spontaneous
miscarriage recurrent abortion
IUGR
Pre-eclampsia
placental abruption
Pre-term labour
Intrauterine fetal death
Hyperhomocysteinemia
07 March 2017 Dr. Furquan Alam 45
46. Homocysteine & Pregnancy Complication
Values in Early Pregnancy are more reliable.
Folic acid supplements decrease homocysteine
levels during pregnancy and substantially
reduce the risk of central nervous system
malformations
2004 issue of "Clinical Chemistry
07 March 2017 Dr. Furquan Alam 46
47. 5,883 women in Norway were followed through
14,492 pregnancies with their outcomes and
complications recorded against their
homocysteine levels.
The Hordaland Homocysteine Study. JAMA 1995;274:1526–33
07 March 2017 Dr. Furquan Alam 47
48. Higher homocysteine level and % Rise in
Risk of Complications
0
20
40
60
80
100
120
Pre -
eclampsia Premature
Birth Very Low
Birth Weight
32
38
101
07 March 2017 48
49. Homocysteine & PCOS
• In PCOS early atherosclerosis is not exclusively
dependent on hyperinsulinemia and elevated
lipid profile – PCOS patients are exposed to
significantly higher homocysteine levels which
might increase the cardiovascular disease risk.
Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine
levels are increased in polycystic ovary syndrome. Gynecologic and obstetric
investigation. 2002 Jun 6;53(3):157-62.
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50. Homocysteine and Alzheimer's Disease
People with the highest levels of blood homocysteine had
almost double the risk of Alzheimer's and other dementia as
compared to people with lower blood homocysteine.
Increase of 5 micromoles of homocysteine per liter of blood
increased the risk of Alzheimer's Disease by 40%.
The mechanism linking Hcy and Alzheimer’s disease is
poorly understood, it is possible that Hcy is toxic to brain
cells, possibly by excessive stimulation, resulting in
neuronal damage due to CNS ischemia.
New England Journal of Medicine", 2002;346(7):466-468.
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52. CANCER – CUT YOUR RISK BY A THIRD
Cancer is triggered by damage to DNA – and having
a high homocysteine level means your DNA is more
vulnerable to damage
homocysteine levels have been found to be a very
good indicator of whether cancer therapies are
working. The homocysteine level rises when tumours
grow, and falls when they shrink.
Cancer Council Victoria 2011
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53. REDUCE YOUR RISK OF DEATH FROM ALL
CAUSES
One of the best ways to extend your lifespan is by
reducing your homocysteine level. With every five-
point decrease in your H score, you will gain:
A 49% reduced risk of death from all causes.
A 50% reduced risk of death from cardiovascular
disease .
A 26% reduced risk of death from cancer .
A 104% reduced risk of death from causes other
than cancer or heart disease
2005 Orthomolecular conference
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55. Homocysteine New studies
Raised Homocysteine levels are seen in sufferers
of chronic fatigue syndrome [CFS]
Homocysteine accelerates the aging process by
shortening telomeres.
RA patients are 20-30% more likely to have
higher Homocysteine levels than the normal
population
In traditionally-treated dialysis patients, 91% of
HD and 67% of PD patients have elevated Hcy
levels
Nutridisk 2011
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56. Should Hyperhomocysteinemia Be Treated?
Arguments favoring treatment
Approximately 80 clinical and epidemiological studies
suggest that elevated homocysteine is a risk factor for
coronary heart , cerebro vascular, and peripheral
vascular diseases
Risk factor treatment of cardiovascular disease is an
accepted clinical practice
Treatment is inexpensive and unobtrusive under
medical supervision
Coronary Heart Disease ,Homocysteine,heart disease and stroke 2008
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57. Should Hyperhomocysteinemia Be Treated?
Arguments against treatment
Many prospective studies shows that
Lowering homocysteine with folic acid
supplementation is safe, but does not reduce
the risk of vascular events
The American Heart Association has not yet
called hyperhomocysteinemia (high
homocysteine level in the blood) a major risk
factor for cardiovascular disease.
Coronary Heart Disease ,Homocysteine,heart disease and stroke 2008
07 March 2017 Dr. Furquan Alam 57
58. Reduction in Homocysteine Levels
• Supplementation of B vitamins
• Folate, B6, and B12
• Restriction of methionine containing
substances
• Sesame seeds, brazil nuts, fish, meats
• Exercise
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59. Homocysteine and Nutrition:
The Vitamin Connection
Screening for HCY may indirectly assess a
patient’s vitamin B6, B12 and folate status, thus
offering a useful window into the patient’s
nutrition profile.
Total homocysteine measurements are now
recommended to screen for vitamin deficiency in
both the general and high risk populations.
Homocysteine may, in fact, be a more sensitive
marker of Vitamin B12 , B6 or folate deficiency
and… may precede deficiency of circulating
vitamins.
Screening for vitamin B12 and folate deficiency in older persons. Am J
Clin Nutr 2003; 77: 1241-7.
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61. Vitamins and Food sources
Folic acid - Green leafy vegetables (e.g.
spinach, broccoli), legumes (e.g. lentils,
chick peas, lima beans), orange
Vitamin B6 - Meat, poultry, fish, green
leafy vegetables, legumes, seeds,
potatoes, cantaloupe, milk, egg yolks,
cereals, grains, wheat, wheat germ.
Vitamin B12 - Beef, poultry, fish
(particularly crab, oyster, salmon and
herring), liver, kidney, soy, fruit juice, dairy
products, egg yolks, fortified cereals, breads
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62. Folic acid fortification of enriched grain
products in the late 1990’s appears to
have resulted in a decline in stroke and
ischemic heart disease deaths.
There has been evidence of three-fold
acceleration in the decline of stroke
related mortality that has been
temporarily related to folic acid
fortification.
American Journal of Clinical Nutrition, Vol. 86, No. 5, 1563S-1568S, November 2007
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63. RDA for Vitamins B6, B12 and Folate
Vitamin B6 2 mg
Vitamin B12 6 mcg
Folate 400 mcg
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65. Take Home Message
The lower the Hcy level, the lower the risk of
developing coronary artery disease and
suffering fatal heart attacks and strokes .
Your Homocysteine level is excellent single
indicator of whether you are going to live a long
and healthy life, or die young. A high
Homocysteine level is a greater risk factor for
many health problems
Without any doubt, the demand for plasma
homocysteine testing will increase soon,
perhaps explosively.
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66. Take Home Message
Hcy test is Costly but definitely not costlier than you
Life.
Tobacco, caffeine and excessive intake of
Methionine rich diet (Meat, Fish etc.) should be
avoided.
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