February 3, 2003 Research Update

James Bogash, D.C. Mesa, AZ
info@lifecarechiro.com
www.lifecarechiro.com

CRP, Metabolic Syndrome, and Risk of Cardiovascular Events

While the rest of the medical community is debating whether we should check CRP levels in patients, these authors decided more than eight years ago that is was worth checking. While the the results of this study are no big surprise, we do see that CRP values are important markers for CVD risk in patients with Syndrome X.

Circulation -- Abstracts: Ridker et al. 107 (3): 391

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IV L-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients w/ Angina and Normal Coronary Arteriograms -- Correlation w/ Asymmetric Dimethylarginine Levels

I know this title seems awfully long, but I will use this article to demonstrate an important, developing concept in regards to hypertension and CVD. Asymmetrical dimethylarginine (ADMA) is a compound that interferes with nitric oxide production. Keep in mind that nitric oxide is a potent vasidilator (this is the mechanism by which Viagra works--increased NO levels leads to greater blood flow...and so on...). Elevated ADMA levels will block the action of NO on blood vessels. Thus, anything that elevates ADMA levels will have a large impact on vasodilation and subsequently blood pressure. High insulin and homocysteine has been shown to increase ADMA levels by inactivating the enzyme that breaks down ADMA, essentially increasing ADMA levels. In this study, we see that ADMA levels are increased in patients with Cardiac Syndrome X (not to be confused with Metabolic Syndrome X--someone should've check with someone on the nomenclature on THAT one!!) and adminstration of L-arginine reverses the effect of elevated ADMA (high arginine overrides ADMA suppressive effect). If this sounds confusing, keep your ears open--this concept will be gaining great interest over the next few years.

Circulation -- Abstracts: Piatti et al. 107 (3): 429

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Are Pediatricians Adhering to Principles of Judicious Antibiotic Use for Upper Respiratory Tract Infections?

The answer in a nutshell? No. How can we have major journals (including pediatric journals) practically screaming to lower antibiotic use and yet pediatricians are not getting the message? This strongly suggests that the pediatricians are not reading their own journals. If they are not reading their own journals where are they getting their current information? This question plagues me. Are a large majority of mainstream medical doctors truly getting their continuing education from the drug companies and drug company sponsored seminars? This article would support that scary supposition.

October 2002 SMJ

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Extended longevity in mice lacking insulin receptor in adipose tissue

This study looked at mice that did not have insulin receptors in adipose cells and found an 18% increase in longevity. This strongly supports previous research in mammals that suggest caloric restriction without nutrient depletion (which would result in lowered insulin levels). With more evidence arising in regards to the harmful effects of elevated insulin I am even more firmly of the belief that refined carbs are the number one factor destroying the health of Western society.

Entrez-PubMed

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Alcohol Consumption and Plasma Concentration of CRP

Looking for ways to lower CRP levels? Moderate alcohol consumption was shown to lower CRP levels in this study. This article did not differentiate between types of alcohol intake, but my guess would be that red wine intake would affect CRP levels the most.

Circulation -- Abstracts: Albert et al. 107 (3): 443

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Physical Fitness and CRP Level in Children and Young Adults

Yet another way to lower CRP levels, and yet multi-million dollar trials are underway to determine if statin drugs (cholesterol lowering) can also lower CRP. You are in the middle of witnessing the blatant disregard for natural methods that lower CRP in favor of pharmaceutical drugs from which a huge profit can be made. In the next few years when the results of the statin drugs/CRP trial is over, the fanfare associated with this discovery (most evidence points to the lowering of CRP levels w/ statins) will be overwhelming.

Pediatrics -- Abstracts: Isasi et al. 111 (2): 332

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Multivitamin Use May Reduce C-Reactive Protein Levels

Do we really need a trial to find a prescription drug to lower CRP levels?????

(article)

Jan 21 - Multivitamin use is associated with a significant reduction in C-reactive protein (CRP) levels, which could reduce the risk of cardiovascular disease and diabetes, according to findings presented Tuesday at a nutrition meeting in San Antonio.The findings are based on a study of 88 subjects who were randomized to receive a multivitamin or placebo once daily for 6 months. CRP and vitamin levels were measured at baseline and at the end of the trial."The study was originally designed to assess the effects of multivitamin use on LDL and homocysteine levels," study author Dr. Timothy S. Church, from The Cooper Institute in Dallas, told Reuters Health. "After some reports suggested that vitamin E may decrease CRP levels, I decided to reanalyze the blood samples from our study to determine the effect of multivitamin use on CRP levels," he added.To eliminate the potential confounding effects of perimenopause, the researchers limited their analysis to blood samples taken from men or postmenopausal women.Dr. Church presented his team's findings at Nutrition Week 2003, an annual meeting sponsored by the American Society for Parenteral and Enteral Nutrition."In the multivitamin group, we observed a fairly large decrease in CRP levels," Dr. Church noted. After adjustment, the mean CRP decline was -0.58 mg/L (p = 0.02). In contrast, a slight increase in CRP levels (+0.18 mg/L) occurred in the placebo group.The magnitude of the reduction is probably too great to be accounted for by the vitamin E present in the formulation, Dr. Church said. "Based on recent reports, I think the effect was probably due to the vitamin B6 and C present," he added.Dr. Church said that his team is currently studying the effects of multivitamin use on vascular reactivity.

Glaxo Stops Study of Asthma Drug

A few important things here. First, this drug was already approved--meaning it was already on the market and this was just a larger follow up study. This study was stopped because it may be associated with an increased risk of life-threatening asthma episodes or asthma-related deaths. HUH?? An asthma drug study is stopped because of side effects of worsening asthma?? Does the word "guinea pig" ring a bell here?

(article)

Jan. 24, 2003 — The U.S. Food and Drug Administration (FDA) yesterday announced that an interim analysis of a large safety study of the approved asthma drug salmeterol xinafoate (Serevent Inhalation Aerosol) suggests that the drug may be associated with an increased risk of life-threatening asthma episodes or asthma-related deaths, particularly in some patients. At the same time, the drug's manufacturer, GlaxoSmithKline, notified investigators that it is stopping this study, mostly due to difficulties in enrollment and the likelihood the study would not give a clear result, even if fully enrolled.The interim analysis did not show a statistically significant result for the primary endpoint — a combination of respiratory-related deaths or intubations (or ventilatory failure). There was a trend, however, toward increases in asthma deaths and serious asthma episodes when all patients in the study were considered, though again this did not reach statistical significance. A further analysis of the data from the study suggested that the risk might be greater in African-American patients, who made up 17% of the study population. Further analyses showed that patients not taking inhaled corticosteroids at study entry appeared to have greater risk for serious outcomes than those who were taking inhaled corticosteroids."We don't know why there was this pattern, and would like to do further studies," Laura Bradbard, a spokesperson for the FDA, told Medscape. "Is it a socioeconomic reason? Is there a problem getting to the doctor often enough? Is the doctor following the guidelines? Or is there a physiological reason why African-Americans have more asthma? It does seem that population suffers from more asthma, and it tends to be more severe. Is it because it's not being treated, or because it's being treated too late? There are too many questions. That's why we need more studies."The halted study was designed to further investigate the safety of Serevent, particularly whether it might rarely cause serious asthma-related adverse events. It was begun in 1996, after the FDA received postmarketing reports of several asthma deaths associated with the use of salmeterol and after publication of studies raising concern about the regular use of short-acting and long-acting beta agonists, including salmeterol. Because asthma patients can sometimes suffer sudden, serious life-threatening episodes of bronchospasm as a consequence of their disease, the deaths and serious adverse events reported for salmeterol could neither be clearly attributed to use of this product, nor could it be excluded as a cause. This study was undertaken to try to help provide better information on the safety of this product. The Glaxo Data Safety Monitoring Board overseeing this trial conducted the interim data analyses that led to today's action. Approximately 26,000 subjects, representing more than 4.3 million patient-days of exposure to the drug, had participated in the study. The study was intended to enroll 60,000 patients.The FDA approved Serevent Inhalation Aerosol in 1994 to treat asthma, and later this approval was extended to use for treatment of chronic obstructive pulmonary disease (COPD). The FDA plans to meet with Glaxo soon to obtain more details about the data from the interim analyses of the study and to determine what steps are warranted to address this information, according to a talk paper posted on the FDA's Web site. The FDA is particularly interested in further evaluating the question of whether certain patients may be at a greater risk for rare, but potentially serious adverse events due to Serevent use and use of other related drugs.Despite the study stoppage, the FDA emphasizes in the talk paper that based on available data, the benefits of salmeterol for the asthma population continue to outweigh the risks and that the serious adverse events reported in the trial were rare. Patients are strongly advised that they should not stop taking salmeterol, or any other medication, for asthma or COPD, without first talking to their physicians, because abruptly stopping drugs for the treatment of asthma and COPD can result in serious exacerbations of these diseases that could be life-threatening.