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EDITORIAL
Hans Larsen, Editor |
ABSTRACTS
NICOTINE LOZENGE FOR SMOKING CESSATION
PITTSBURGH, PENNSYLVANIA. Smoking is the leading preventable cause of disease and death in the
Western world. Because of its highly addictive nature it is very difficult for most smokers to quit without
assistance. Acupuncture, hypnosis, nicotine patches, nicotine gum, and nicotine sprays and inhalers have
all been used as smoking cessation aids with varying degrees of success. Now researchers at the
University of Pittsburgh and GlaxoSmithKline Consumer Healthcare report that a nicotine-containing
polacrilex lozenge is quite effective in helping both low- and high-dependence smokers quit the habit.
ACCURATE TEST FOR CUSHING'S SYNDROME
BETHESDA, MARYLAND. Cushing's syndrome is characterized by excessively high cortisol levels and
symptoms such as weight gain, depression, and hypertension. Current screening tests (urine cortisol level
and dexamethasone suppression screening) are only accurate to within about 30%. Researchers at the
National Institutes of Health now report that measuring nighttime salivary cortisol levels can provide an
accurate indication of the presence of Cushing's syndrome. The researchers studied 156 patients
suspected of having Cushing's syndrome, 29 other patients known not to have the condition, and 34 healthy
volunteers. They found that the nighttime (midnight) salivary cortisol levels in patients with Cushing's
syndrome were invariably above 550 ng/dL (15.2 nmol/L) while non-Cushing's syndrome participants had
levels at or below 220 ng/dL. The researchers conclude that nighttime salivary cortisol levels above 550
ng/dL will identify 93% of all patients that actually have Cushing's syndrome and will exclude all individuals
without the disorder. They endorse the use of nighttime salivary cortisol as a simple, convenient, accurate,
and cost-effective screening test for Cushing's syndrome.
MIND CONTROL BY PARASITES
LONDON, UNITED KINGDOM. Toxoplasma gondii is a common parasite that infects 30-60% of the
world's population. It releases eggs that are spread in cat feces and can only reproduce in cats. Up to
now, medical researchers have believed that toxoplasmosis, an infection with Toxoplasma, is quite
harmless except in the case of pregnant women and those with a compromised immune system. This belief
is now being challenged.
WILL GLOBAL WARMING CAUSE MALNUTRITION?
PRINCETON, NEW JERSEY. Princeton University biologist Dr. Irakli Loladze believes that rising carbon
dioxide (CO2) levels will make plant crops increasingly nutrient deficient and eventually lead to malnutrition
for all. Over 3000 scientific studies have investigated what elevated CO2 levels do to plants. There is
general agreement that plants today are exposed to about 30% more CO2 than in pre-industrial times.
There is also general agreement that this higher CO2 level makes plants grow faster and bigger. The
problem is, according to Dr. Loladze and other increasingly concerned scientists, that the faster growth
interferes with the plant's capacity to absorb vital nutrients from the soil.
SUNLIGHT DOES AFFECT YOUR MOOD
MELBOURNE, AUSTRALIA. Serotonin is the body's main "mood hormone" with a low level being strongly
associated with depression. The depressive effect of low serotonin levels can be somewhat counteracted
by the use of selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Paxil. Seasonal affective
disorder (SAD) is a highly prevalent form of depression affecting many people during the dark winter
months. Analysis of the blood and cerebrospinal fluid of SAD patients has, however, failed to confirm the
presence of abnormally low serotonin levels.
FISH OIL DERIVATIVE REDUCES DEPRESSION
SHEFFIELD, UNITED KINGDOM. There is considerable evidence that fish oils help in combating
depression and other mental illnesses. What is not quite clear is whether it is eicosapentaenoic acid (EPA)
or docosahexaenoic acid (DHA) that is the most active component.
FISH, MERCURY, AND HEART DISEASEBALTIMORE, MARYLAND. Several studies have shown that regular fish consumption protects against cardiovascular disease. Other studies have shown that consuming mercury-contaminated fish increases the risk of coronary heart disease. The beneficial effect of fish consumption is believed to be due to the presence of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the tissue of fish and shellfish. Two recent studies have attempted to answer the question "Are the beneficial effects of fish oils (EPA and DHA) outweighed by the negative effects of mercury"?
The first study, carried out by a team of researchers from eight European countries, Israel and the United
States, involved 684 men who had suffered a first non-fatal heart attack and 724 matched controls. All
participants had their mercury level measured in toenail clippings and their level of DHA measured in a fat
tissue sample taken from the buttock. Participants with a mercury level of 0.66 mcg/gram were found to
have twice (odds ratio of 2.16) the risk of having a first heart attack when compared with participants having
a mercury level of 0.11 mcg/gram. This risk assessment was arrived at after adjusting for age, DHA level in
adipose tissue, body-mass index, waist:hip ratio, smoking status, alcohol intake, HDL cholesterol level,
diabetes, history of hypertension, family history of heart attack, blood levels of vitamin E and beta-carotene,
and toenail level of selenium.
The second study was part of the Health Professionals Follow-Up Study begun in 1986 as a cooperative
venture between the Harvard School of Public Health, the Brigham and Women's Hospital, and Harvard
Medical School. The study involved 33,737 male health professionals who had toenail clippings analyzed
for mercury in 1987. After 5 years of follow-up 470 participants had been diagnosed with coronary heart
disease. The researchers observed that dentists, who are habitually exposed to mercury, had toenail
mercury levels (0.91 mcg/gram) that were twice as high as the levels found in non-dentists (0.45 mcg/gram).
They also found a direct relationship between fish consumption and mercury level with participants
consuming an average of 357 grams (3/4 lb) of fish per week having a level of 0.75 mcg/gram while those
who consuming 145 grams (1/3 lb) per week had a level of 0.29 mcg/gram. After adjusting for age, smoking
and other risk factors for heart disease the researchers conclude that there is no clear association between
total mercury exposure and the risk of coronary heart disease, but that a weak relation cannot be ruled
out.
Editor's comment: The two studies clearly do not agree as to whether high mercury levels are
associated with an increased risk of coronary heart disease. I am inclined to believe that they are.
Furthermore, there is compelling evidence of significant associations between high mercury levels and
Alzheimer's disease, Parkinson's disease, congestive heart failure, kidney damage, hearing loss, and high
blood pressure. So definitely, mercury, from whatever source, is a very bad actor and should be avoided.
The joint European/Israeli/US study clearly confirms that DHA (fish oil) is protective against a first heart
attack, so regular consumption of low-mercury-level fish is still a healthy option. An alternative approach to
obtaining DHA (and EPA) on a regular basis is to supplement with 1 gram/day of a high quality, molecular
distilled, non-rancid fish oil containing a minimum of 220 mg EPA and 220 mg DHA. Reliable sources of
such fish oils can be found at www.consumerlab.com/results/omega3.asp
and at www.coromega.com EFFECTIVENESS OF VITAMIN B12 SUPPLEMENTATION
DENVER, COLORADO. It is estimated that about 16% of older adults are vitamin B12 (cobalamin)
deficient. This deficiency is mostly related to an inability to absorb cobalamin bound to food. Several
experiments have shown that this problem does not affect people's ability to absorb free or synthetic
cobalamin. A lack of vitamin B12 can lead to megaloblastic anemia and, if untreated, to irreversible
neurological damage that may mimic Alzheimer's disease.
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NEWSBRIEFS
Diesel fuel not so clean after all
Nicotine patches for exams
St. John's wort and cancer drugs
Diet implicated in acne
Europe to proceed with labeling of GM products
Go easy on snail consumption!
Powerful white wine
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RESEARCH REPORT
High-Sensitivity C-Reactive Protein & Cardiovascular DiseasePart I
by William R. Ware, Ph.D.Emeritus Professor of Chemistry, University of Western OntarioINTRODUCTION There is a rapidly growing body of evidence suggesting that atherosclerosis is in part an inflammatory condition [1]. C-reactive protein (CRP) is a serum marker for inflammation, which is easily and inexpensively measured and assays have recently been developed that provide very high sensitivity. Numerous epidemiologic studies have consistently shown that high-sensitivity C-reactive protein (HSCRP) levels provide a strong and independent indication of risk of future heart attacks, ischemic stroke (due to obstruction, not bleeding), and peripheral arterial disease, even among individuals who are thought to be free of vascular disease [2]. This article reviews the arguments both for and against the proposal that its measurement might advantageously be included in blood work associated with physical examinations or cardiovascular risk assessments, even for individuals with no indication of cardiovascular disease (CVD) and those thought to be a low risk on the basis of conventional parameters. CRP—BACKGROUND INFORMATION The term acute-phase response is used to describe the greatly increased synthesis and secretion of certain plasma proteins including CRP, principally by the liver, following trauma, tissue necrosis (tissue death, which for example may occur as a result of a heart attack), infections, and the acute effects of inflammatory diseases [3]. Inflammation releases cytokines, and the cytokine Interlukin-6 is thought to be largely responsible for triggering the production of CRP, which is thus generally viewed as a marker of inflammation, with very high values associated with acute inflammation. Chronic, low-level inflammation can result in near normal but nevertheless elevated values. The intense interest in CRP in the context of coronary heart disease, peripheral vascular disease and stroke is quite recent, although the protein was discovered about seventy years ago. Its original use in differential diagnosis and for following the course of treatment, which has always been controversial, appears to be limited today, at least in North America. The index of Harrison's "Principles of Internal Medicine", 14th edition published in 1998, contains no mention of CRP. Until recently, the assay used for CRP had very low sensitivity, with the result that values near the limit of detection, i.e. 3-10 mg/L, were considered normal, which was not a problem, since the acute-phase response is generally accompanied by very large increases in serum CRP levels, with values well over 100 mg/L common. As the cause of the inflammation resolves, the level usually declines over a few weeks to the normal range. As with cholesterol levels, which are sometimes expressed in mg/dL and sometimes in mmole/L, a lack of standardization is also evident in the case of CRP. Some researchers express the value in mg/L while others use mg/dL. Fortunately, the conversion is easy. One-tenth of the value in mg/L gives mg/dL. Because of the potential for confusion, it is essential that the unit always be specified when referring to CRP values. In fact, there are errors in a few CRP papers because of inadequate attention to this problem. Today the determination of serum CRP is generally accomplished with an assay of high sensitivity (HSCRP). The range of "normal" values found in one study [4] of over 5000 presumably healthy individuals varied between a low of 0.1-0.7 mg/L (found in 20% of the population) and a high of equal to or greater than 3.8 mg/L (found in 20% of the population). The median CRP (CRP will be used to indicate HSCRP in what follows) was 1.6 mg/L. Similar values have been obtained for presumably healthy individuals in other studies using modern high-sensitivity assays. These numbers clearly are very low compared to the old "normal" value of <10 mg/L, a value that still appears on some clinical laboratory printouts as a "reference range" even for the high sensitivity assay. Chronic inflammatory diseases such as rheumatoid arthritis, as well as surgery and trauma, and infections, both chronic and otherwise, can cause CRP levels to be elevated well above the 3.8 mg/L. [3]. In addition, low-level chronic inflammatory conditions that may produce no noticeable symptoms can mildly elevate CRP values. Hormone replacement therapy has been found to increase CRP levels [5], and women, especially older women, on average appear to have slightly higher normal values as compared to men. Overweight, obese and diabetic individuals typically have elevated serum CRP [6] and elevated CRP levels have been found to predict the development of adult-onset (type 2) diabetes [7]. Consistent with this is the observation that individuals with insulin resistance syndrome typically exhibit elevated CRP levels [8]. Living in an environment where air pollution is high can raise CRP values [9]. It is well known that smoking elevates serum CRP. At least two studies have shown that patients with atrial fibrillation have higher than normal CRP levels [10,11]. Cytokines responsible for acute-phase protein production also are known to play significant roles in neuropsychologic function and dysfunction [12,13]. As Kushner points out [12], it is possible that detecting CRP elevation in some individuals is merely an indirect way of detecting depression, a known risk factor for coronary artery disease. Recently reported research supports this view [14]. Thus CRP is clearly a non- specific marker of inflammation. As will be discussed below, the risk of future vascular disease increases continuously across the "normal" CRP ranges. There are a number of conditions, examples of which have been given above, that can either temporarily or chronically elevate CRP well above either the median or the lower limit of the highest quintile (the value of 3.8 mg/L given above); this complicates the task of interpreting serum CRP levels. In fact, the precise nature of the events that trigger increased CRP production that in turn predict future adverse cardiovascular (atherothrombic) events have not yet been identified [15]. CRP AS AN INDICATOR OF CARDIOVASCULAR DISEASE RISK Studies carried out in the last few years on CRP and cardiovascular disease have involved both individuals at high and low risk of disease, but nevertheless considered disease free, as well as individuals with established disease, i.e. individuals who have experienced a heart attack or stroke, have stable or unstable angina, or who have peripheral vascular disease e.g. intermittent claudication. The studies discussed below are of particular interest in the context of this review, which is concerned with primary prevention rather than the use of CRP levels as a prognostic tool for individuals who have experienced an acute cardiovascular event. One type of study, called a prospective or cohort study, attempts to correlate the incidence of a future health problem in an entire study population with parameters established at the start of the study, such as blood markers, smoking, body mass index, etc. Another type, the so-called case-control study, is frequently carried out within a prospective study, where a population of apparently healthy individuals provides the cases. That is, at a later time, individuals exhibiting a disorder of interest (the cases) are studied by comparing, for example, blood markers at baseline (at the start of the study) such as cholesterol or CRP, with those of a group selected from the same population who are thought to be free of the disorder (the controls). A prospective study just published in the "New England Journal of Medicine" [16] compares CRP with LDL cholesterol levels in the prediction of first cardiovascular events in women. American women, deemed healthy, were enrolled between November 1992 and 1995 in the Woman's Health Study and followed for a mean of eight years for the first occurrence of myocardial infarction, ischemic stroke, coronary revascularization (angioplasty or coronary bypass), or death from cardiovascular causes, and these so- called endpoints were then correlated with the baseline blood levels of LDL, CRP, and as well, the calculated ten-year risk of coronary heart disease based on the Framingham risk score [17], which is commonly used for clinical evaluation. After adjusting for confounding, the relative risks of a first cardiovascular event according to increasing quintiles (a quintile contains 20% of the study population) of CRP were 1.4, 1.6, 2.0 and 2.3 as compared to the first quintile. The corresponding numbers for LDL were 0.9, 1.1, 1.3, and 1.5. Thus CRP would appear to be a more significant marker than LDL. Also, a very interesting result was that 77% of all adverse cardiovascular events occurred among women with LDL levels below 160 mg/dL, and 46% occurred among those with LDL levels below 130 mg/dL. Thus a large proportion of the 27,939 women involved in the Woman's Health Study who suffered first adverse cardiovascular events had LDL levels at baseline that were below the threshold values for intervention and treatment under the current guidelines of the National Cholesterol Education Program (NCEP) [17]. If the results are viewed in terms of tertiles (a tertile contains 33% of the study participants) of CRP vs. tertiles of LDL, the relative risk associated with an LDL level greater than 160 mg/dL along with a CRP level greater than 3 mg/L was about 2.8. If a participant was in a high Framingham risk category (equal to or greater than 10% for the ten year risk of coronary heart disease-- see attachment for a Framingham risk calculation table), then the three tertiles of CRP alone (less than 1.0, 1.0-3.0, and greater than 3.0) gave adjusted relative risks of approximately 12, 21 and 24 ([16], Figure 4). These risk factors, which essentially combine CRP levels with age, smoking status, systolic blood pressure, as well as total and HDL cholesterol levels, are obviously huge and command attention. It is worth mentioning that for men the Framingham point scores for 10-year risk place considerable emphasis on age. For a man in the age range 70-74, a 10% 10-year risk of a heart attack or coronary death results from age alone, and can be reduced to 8% only by having a HDL value equal or greater than 60 mg/dL (1.55 mmole/L). Also interesting is that age alone for a woman in the same 70-74 range results in a 10-year risk of only 2%. A case-control study where the patients were drawn from the Physicians' Health Study (PHS), was reported in 1997 [18]. The PHS involved a cohort of over 22,000 male physicians between the ages of 40 and 84 years. Each participant who provided an adequate baseline plasma sample and who experienced an acute cardiovascular event (heart attack, stroke or venous thrombosis) was matched with one normal control selected randomly from the study participants who met the matching criteria of age, smoking history, and length of time since the beginning of the study. Men in the highest CRP quartile (greater than 2.1 mg/L) had three times the risk of a heart attack and two times the risk of an ischemic stroke when compared to men in the lowest quartile (less than 0.56 mg/L). There are a number of other studies in the literature on the relationship between CRP levels and cardiovascular disease. Ridker [4] has reviewed nine such studies published between 1996 and 2000. Relative risks calculated by comparison of the top vs. bottom quartiles yield results that range between 2.3 and 4.6. The data summarized provide consistent and convincing evidence that CPR is a risk factor independent of the TC/HDL ratio (ratio of total cholesterol to HDL cholesterol) in both men and women, with very high relative risks for the combined effect of elevated CPR and a high TC/HDL ratio, in fact a risk ratio of 8 to 9 when the data is separated into quintiles. Of the markers of cardiovascular risk, i.e. CRP, LDL cholesterol, the TC/HDL ratio, homocysteine, and lipoprotein (a), the combination of CRP and TC/HDL provided the most powerful indicator of future risk. Rifai and Ridker recently have proposed a cardiovascular risk assessment algorithm based on combined data from the Women's Health Study and the Physician's Health Study [19]. Only three parameters, CRP, total cholesterol (TC) and HDL are used, with the latter two expressed as a ratio. Quintiles rather than quartiles are employed to obtain the overall risk as assessed from these two parameters. According to this proposed assessment, a CRP level greater than 3.9 mg/L combined with a TC/HDL ratio greater than 5.5 (men) -5.8 (women) would confer a cardiovascular risk level 8.7 times greater than the risk for a person with a CRP level of 0.1-0.7 mg/L and a TC/HDL ratio of less than 3.4. The detailed relative risks by quintile of CRP and TC/HDL can be found in the attachment. The numbers in the attachment clearly illustrate the continuous increase found in the risk of cardiovascular disease with increasing serum CRP, independent of the TC/HDL ratio, such that even if one is in the lowest quintile of TC/HDL, those in the highest CRP quintile have a relative risk of 2.2 times those in the lowest quintile. The same pattern is seen with the ratio of total cholesterol to HDL at constant CRP levels. Note that there is significant risk associated even with the "normal" population median CRP of 1.6 mg/L [4]. It should also be remarked that other classical risk factors such as hypertension, smoking, LDL cholesterol and age are not use in this scheme of risk assessment, although total cholesterol is an approximate surrogate for LDL. Rifai and Ridker suggest [19] that in clinical practice, CRP evaluations should be avoided if there has been recent infection or trauma. They suggest that two weeks is sufficient for a return to basal values. However, they go on to comment that CRP values greater than 15 gm/L indicate active or perhaps transient inflammation, and suggest two CRP measurements a month apart provide a better picture, especially if a CRP value greater than 5 is obtained on the first determination. The implication of the guidelines is that the clinical assessment requires a more or less stable value, be it 0.1 or 10 mg/L, i.e., it is desirable to avoid clinical decisions based on an abnormally high value that is transitory.
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International Health News is published monthly by Hans R. Larsen MSc ChE 1320 Point Street, Victoria, BC, Canada V8S 1A5 Phone: (250) 384-2524 E-mail: health@pinc.com URL: http://www.yourhealthbase.com ISSN 1203-1933.....Copyright © 2003 by Hans R. Larsen International Health News does not provide medical advice. Do not attempt self- diagnosis or self-medication based on our reports. Please consult your health-care provider if you wish to follow up on the information presented. |