In This Issue

Meet Chuck Masur, MD, Scientific Support Physician

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Recently, we introduced the most comprehensive cardiovascular risk profile available from a single overnight fasted blood draw. The test has been praised by some of the most renowned physicians who specialize in cardiovascular disease (CVD) management, prevention and rehabilitation.

Despite my 26 years of research in lipid biochemistry and atherosclerosis, since we’ve begun offering the test I have been amazed by the horrifying results we’ve seen—especially for middle-aged women. The results no doubt help physicians develop individualized intervention protocols, and we hope they will also motivate patients.

The test is designed to help identify heightened risk for CVD. For educational purposes, however, I am presenting a case of extensive coronary artery disease in which the DDI Comprehensive Cardiovascular Risk and follow-up Methylation Profile results demonstrate excellent clinical specificity.

The Patient

The patient is a 71-year-old, sedentary woman who never smoked, but had an extensive family history of CVD and type II diabetes. She presented with fatigue, hypertension and excessive visceral fat, and was described as a classic case of metabolic

syndrome. At 69, she had a massive, acute myocardial infarction (MI) followed by quadruple bypass surgery. Two years later she was diagnosed with type II diabetes and initiated insulin therapy. The Comprehensive Cardiovascular Risk Profile, ordered shortly thereafter, indicated a markedly elevated level of serum homocysteine, so a DDI Methylation Profile was ordered to help identify specific aberrations in methionine metabolism (methylation and transsulfuration).

Test Results and Significance

The patient’s Comprehensive Cardiovascular Risk Profile indicated overall high risk for deteriorating CVD with significantly compromised kidney function, chronic hyperglycemia, cardio-specific inflammation and heightened risk for plaque instability and thrombosis. Standard assessment of lipid and lipoprotein metabolism indicated mixed dyslipidemia—moderately elevated total cholesterol, elevated LDL-cholesterol (LDL-C) and fasting triglycerides, plus very low HDL-cholesterol (HDL-C). Associated traditional lipid risk factors included high ratios of total cholesterol to HDL-C and LDL-C to HDL-C. Stronger risk factors than LDL-C and HDL-C were the associated apolipoproteins apo-B and apo-AI, respectively. The ratio of apo-B to apo-AI was higher than desirable

due to very elevated apo-B and moderately low apo-AI. The apolipoproteins are more indicative of the associated lipoprotein particle numbers and appear to provide a better indirect estimate of reverse cholesterol transport activity.

The clinical significance of the dyslipidemia and potential for acceleration of the atherosclerotic process and future events is bolstered by DDI’s inclusion of more focused lipoprotein analysis—oxidized LDL (ox-LDL), small dense LDL (sdLDL) and Lp(a). None of these LDL-related lipoprotein species are correlated with LDL-C levels, the importance of which is obviated by the fact that 50% of MI victims do not have elevated total or LDL cholesterol levels. Such high levels of ox-LDL are plaque-specific, associated with accelerated atherogenesis and plaque instability and rupture. High levels of sdLDL also accelerate atherogenesis as they more readily penetrate the protective arterial endothelial barrier and are readily oxidized by infiltrated macrophages that have become oxidized. The significance of the patient’s markedly elevated level of Lp(a) is exacerbated by concomitantly abnormal levels of fibrinogen and hsCRP. Fibrinogen is only one component of the body’s general

C A S E R E P O R T :

High Cardiovascular Risk with Aberrant Methionine Metabolism by DaviD Quig, PhD

2 N D Q UA R T E R 2012

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Are some iodine-sufficiency test methods deficient?Find out why DDI and ICP-MS are your best answer for superior iodine detection. Read all about it on the back page.

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DDI Selected for its Trace Elements Expertise by European Commission Joint Research Center

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clotting cascade and is not necessarily associated with thrombogenesis. However, in the environment of atherosclerotic lesions, adherent platelets and high levels of Lp(a), high circulating fibrinogen levels warrant greater consideration. Lp(a) increases risk for plaque thrombosis due to its direct role as an inhibitor of fibrinolytic activity as well as its effect of stimulating secretion of plasminogen activator inhibitor-1 (PAI-1). Knowing the levels of ox-LDL, sdLDL and Lp(a) provides invaluable information regarding risk for CVD that would not be detected through traditional lipoprotein risk factors alone.

Diabetes is an independent risk factor for CVD and kidney disease. The patient’s high HbA1c level is consistent with her diabetes, and from the very elevated level of cystatin C, it appears that she has significantly compromised glomerular filtration. Published data suggest that elevated cystatin C may also be independently associated with CVD.

DDI reports the status of circulating levels of key cardioprotective nutrients. In this case, CoQ10, vitamin E (mixed tocopherols) and RBC Mg levels were all well within the normal range. This indicates that the patient has complied with her prescribed supplement schedule and confirms that doses, sources and forms of the specific nutrients are appropriate.

The serum level of homocysteine was markedly elevated for this patient, raising questions about methionine metabolism. The DDI Methylation Profile indicated that her Methylation Index (SAM:SAH) is much lower than desirable. Homocysteine is normally cleared via remethylation to methionine by the enzymes MTHFR, Methionine synthase (MS) and Betaine homocysteine methyltransferase, as well as transsulfuration to cysteine initiated by B-6 dependent Cystathionine beta-synthase (CBS). Accumulation of homocysteine drives retroconversion back to S-adenosylhomocysteine (SAH), a potent inhibitor of methyl transferase reactions. SAH may also be a better predictor of CVD than homocysteine, but analysis is not readily available by commercial laboratories. In this case, plasma methionine was well within the normal range, but all downstream metabolites were very elevated, including S-adenosylmethionine

(SAM). The reason for this is not clear, but high levels of SAM downregulate MS and upregulate CBS (transsulfuration). These Methylation Profile results led to initiation of a supplement protocol including folinic acid, methylcobalamine, betaine (homocysteine to methionine cycle) and B-6, to lower homocysteine and SAH and correct a potentially sluggish transsulfuration pathway.

The DDI Comprehensive Cardiovascular Risk Profile and Methylation Profile provided a wealth of information that guided appropriate intervention to modify specific traditional and advanced risk factors. Through a change in lifestyle, diet and dietary supplementation, this patient may at least reduce her risk factors for CVD and, we hope, slow the atherosclerotic process.

CAse RePORT CONTINUED FROM COVER

Assess 17 primary and secondary risk factors, including emerging markers that provide unprecendented insight into risk.

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Dr. Chuck Masur joined the DDI Scientific Support department in 2008, working with nutritional biochemist and DDI vice president Dr.

David Quig and registered dietician Barb Berta. As part of the scientific support team, Chuck assists clients in interpreting the results of tests performed at DDI. He also authors scientific papers and is often seen presenting at medical conferences.

After receiving his MD from The University of Calgary Faculty of Medicine in 1979, he went on to complete family medicine and community health sciences residencies there in 1981 and 1995. For nearly 30 years, Chuck practiced family medicine in rural and urban settings in Alberta, Canada. During that time, he also served as a deputy provincial health consultant at Alberta Health and as assistant medical officer of health for the City of Calgary.

Throughout his career, Dr. Masur has been exceedingly active in international health and community development and has managed more than 40 community-based development projects around the world. He has served on volunteer missions in Central and South America, the Middle East, South Asia and Russia. He has published works in several fields, including laboratory medicine, public health, pharmacology and therapeutics, and strategic planning.

B E H I N D T H E S C E N E S A T D D I

Meet Chuck Masur, MD, Scientific Support Physician

We need more iodine.

Iodine is an important micronutrient, used by the body to produce thyroid hormones essential to normal growth, development and metabolism. In fact, iodine deficiency is the single most preventable cause of mental retardation and brain damage in the world. Generally speaking, the U.S. population has better access to iodine in their diet than many third world countries; however, the Centers for Disease Control and Prevention (CDC) NHANES reports indicate that urine iodine levels today are almost half what they were in the mid 1970s. They currently estimate that 14.6% of women of reproductive age have moderate to severe iodine deficiency and 57.5% have less-than-adequate levels.

According to the CDC and the International Council for the Control of Iodine Deficiency Disorders, the best way to assess iodine deficiency is through a urine iodine measurement. In addition, Dr. Guy Abraham of Optimox Corporation has developed an iodine loading test, which he has reported as the best way to assess iodine sufficiency and has been found useful by doctors worldwide. This test involves giving a large dose of iodine and looking at the excretion of iodine in the urine. DDI provides reporting of urine results which meet the parameters recommended by the CDC as well as Optimox and Dr. Abraham.

DDI measures iodine and bromine by the gold standard, ICP-MS. Although ICP-MS is often too expensive for smaller laboratories to own and operate, it offers superior detection limits and better quality results compared to other methods. DDI uses ion-selective electrode methods to measure fluoride.

Long recognized as a leader in producing quality elemental results, Doctor’s Data offers an accurate halide panel that includes iodine, bromine and fluoride. In fact, we are the only clinical laboratory in the world that has clinically validated both ICP-MS and the ion-selective electrode methods to CLSI standards.

What’s more, DDI has consistently performed well in independent laboratory comparisons conducted by Optimox Corporation, making us an approved Optimox iodine testing partner. And for the past decade, the CDC has offered an iodine proficiency testing program called Ensuring Quality of Urinary Iodine Procedures, or EQUIP. Doctor’s Data is one of the few U.S. commercial clinical laboratories recognized in their 10-year anniversary publication.

Advanced, precise technology and unparalleled quality continue to make DDI your choice for iodine and all elemental testing.

Sources:

Abraham GE. The combined measurement of the four stable halides by ion-selective electrode following their chromatographic separation on a strong anion-exhange resin; clinical applications. The Original Internist. December, 2006:171-195.

Abraham GE, Flechas JD, Hakala JC. Measurement of urinary iodide levels by ion-selective electrode; improved sensitivity and specificity by chromatography on anion-exhange resin. The Original Internist. 2004;11(4):19-32.

Centers for Disease Control and Prevention. Ensuring the quality of urine iodine procedures and reports on NHANES studies. September, 2011.

The International Council for the Control of Iodine Deficiency Disorders.

Assessing Iodine Deficiency at the Highest Level of Qualityby Dean bass, PhD

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