Archief Roodbont

he study should be interpreted in the context of the Losartan Intervention for Endpoint (LIFE) reduction in hypertension study in high-risk patients with hypertension and left ventricular hypertrophy.[7,8] This randomised, double-masked, parallel-group comparison of losartan and the ß-adrenoceptor antagonist atenolol showed that losartan-based therapy was more effective than atenolol-based treatment in reducing the primary combined endpoint of cardiovascular death, stroke and myocardial infarction in patients with hypertension.[7] Importantly, the most pronounced effect was the reduction in fatal and non-fatal stroke, which was 25% lower in the losartan group, an effect that was beyond that expected from blood pressure control alone. Contrary to common belief, stroke occurs more frequently than myocardial infarction, as a meta-analysis of 11 major studies[3] and the LIFE study[7,8] have shown. On the basis of these findings, the LIFE investigators concluded that losartan should be used more widely in hypertensive patients in clinical practice.[7] As well as blocking the angio-tensin II type 1 receptor, losartan also acts as an antagonist at the thromboxane A2 receptor and has uricosuric effects, which may provide additional mechanisms by which losartan provides protective benefits against stroke beyond its antihypertensive action.[8,9]

Our study was not designed to evaluate 'hard' endpoints. However, it shows that in general practice the majority of hypertensive patients have more than one risk factor, including left ventricular hypertrophy, diabetes and/or nephropathy, and therefore carry a substantial risk of future stroke: more than a quarter of unselected patients in primary care will have a stroke within the next 10 years. Losartan treatment is capable of reducing this risk substantially. It should be noted that this calculated effect takes into account only the blood pressure-lowering effect of the drug, and according to the results of the LIFE study, a further beneficial effect beyond blood pressure control versus atenolol can be expected.

It is well known that blood pressure control is more difficult in patients who have concomitant diabetes and/or nephropathy. Furthermore, the target levels in these high-risk patients are lower than those in other hypertensive patients in order to address the extravascular risk carried by these patients.[10-12] In the present study, the antihypertensive effect of losartan in both the diabetes and nephropathy subgroups was of the same magnitude as that seen in the total cohort, and the calculated stroke risk reduction was only slightly less pronounced. While two-thirds of patients in the two subgroups achieved the 'normal' blood pressure target of =140/90mm?Hg – a much higher proportion than that reported in the LIFE study (45%)[7] – only 22% of the diabetes group and 25% of the nephropathy group met the =130/80mm?Hg threshold for these groups. Physicians and patients should be aware that despite the substantial blood pressure-lowering effect of losartan, patients in the two subgroups at study end still faced a substantial 10-year stroke risk of 30% (diabetes) or 36% (nephropathy), respectively. Consequently, further efforts have to be made either through lifestyle intervention (diet and exercise) or, with a higher prospect of success, addition of further antihypertensive drugs to the current regimen.

In the LIFE study,[7] patients taking losartan experienced significantly fewer AEs and had significantly lower discontinuation rates than those taking atenolol. As antihypertensive therapy is usually life-long, good drug tolerability has direct practical implications on patient compliance and persistence.[13] In our study, the absolute number of AEs was very low irrespective of the losartan dosage, and irrespective of diuretic combination treatment. As Law et al. have pointed out in a large meta-analysis, ARBs do not have a dose-response curve in terms of AEs, as opposed to the other major drug classes.[14] We also showed that addition of hydrochlorothiazide at a low dose of 12.5mg did not compromise tolerability and safety. Most hypertensive patients need combination therapy to achieve treatment targets, and diuretics are a central component of such combinations.[15]

When interpreting the results of the present trial, several limitations must be taken into account. As a result of the real-life, observational study design, the study was not blinded, which might have led to an overestimation of treatment effects.[16] In addition, patient selection cannot be excluded. We aimed to estimate the risk reduction in a typical unselected population, which was not limited to patients without previous cerebrovascular events (7% of patients had a previous cerebrovascular event). While the Framingham Stroke Risk Score has not been investigated in a secondary prevention cohort, the major risk factors in primary and secondary prevention are the same. Furthermore, the study was of short duration, and no statement about the persistence of treatment effects can be derived from these data. However, the long-term LIFE data, in which the SBP- and DBP-lowering effects of losartan were -30mm Hg and -17mm?Hg, respectively, unequivocally showed a sustained effect for the drug.[7] Finally, the documented number of AEs was substantially lower than in controlled studies, which is a typical finding of observational studies: physicians tend to under-report AEs that they expect to occur with the assigned drug therapy

tik: coronnair in Google afbeeldingen.
kies eerste beeldje : coronair lijden omvat de afzetting
zeer fraai artikel met beelden

eigenlijk was bedoeld het onderste beeldje van pag 1 : hetgeen in praktijk soms
het eerste onderste beeldje van de onderste rij

Obesity Cuts Risk of Dying After Heart Attack
In what doctors admit is a paradox, new European research shows that obese patients have half the risk of dying after a heart attack compared with normal-weight patients.

"Once a heart attack has occurred and been optimally treated, obese patients switch to a more favorable prognosis compared to normal-weight patients," said lead researcher Dr. Heinz Joachim Buettner, the head of interventional cardiology at Herz-Zentrum Bad Krozingen, Germany.

But the finding is no license for Americans to pile on the pounds, since obesity has long been known as a major factor for bringing on heart attack in the first place.

"Every effort should continue to prevent and treat obesity, and this study should not be taken to mean that it is good for one's health to be overweight or obese," said Dr. Gregg C. Fonarow, director of the Ahmanson-UCLA Cardiomyopathy Center at the University of California, Los Angeles.

He was not involved in the new study, which is published in the June 20 issue of the European Heart Journal.

In the study, Buettner's group tracked the health outcomes of almost 1,700 people who were hospitalized and treated for a common type of heart attack known as unstable angina/non-ST-segment elevation.

Among the patients, a third were normal weight, half were overweight, and 18 percent were either obese or very obese. The obese and very obese patients were by-in-large younger and more likely to have high blood pressure and diabetes.

In addition, for most of the obese patients, this was their first heart attack. They were also more likely to leave the hospital with prescriptions for heart medications, such as statins, ACE-inhibitors and beta-blockers.

During three years of follow-up, Buettner's team found that obese and very obese patients had less than half the risk of dying compared with normal weight patients. Among all the patients, 9.9 percent of normal-weight patients died, compared to 7.7 percent of overweight patients. However, only 3.6 percent of obese patients had died, and none of the very obese patients died. How might obesity lessen risk for death after heart attack?

The reasons for the paradox remain unclear, but Fonarow speculates that obese people may have more biological resources to draw on than thinner people.

"Patients who are overweight and obese may be able to drawn on greater metabolic reserve than patients who are in the underweight or healthy weight categories," Fonarow said.

"We have previously published on an obesity paradox in patients with acute as well as chronic heart failure, so this paradox applies to a number of cardiovascular disease states," he added. Buettner stressed that, despite these findings, staying slim dramatically lowers your risk for having a heart attack in the first place.

"It is well known that even a modest intentional weight loss can improve or prevent obesity-related cardiovascular risk factors like diabetes mellitus and arterial hypertension," he said. This means that "obese people have a great potential to influence their prognosis, and they should start the effort before an acute coronary event occurs," he added.

Fonarow agreed that becoming obese is definitely not a good way to protect yourself from having a heart attack or even dying after suffering one.

"The findings from this study further confirm the finding of a number of prior studies that demonstrated an obesity paradox exists in patients with established cardiovascular disease, including those presenting with acute coronary syndromes receiving therapy," he said.

However, even though obese patients with acute coronary syndrome had a lower risk of post-heart attack death, obesity strongly contributes to an increased risk of heart trouble, diabetes, and cardiovascular death, Fonarow added.

2007 HMP Communications | Privacy Policy/Copyright | Contact Us

Als je een hoeveelheid cholesterol wil omrekenen van mg/dl naar mmol/l, moet je delen door 38,6.
Een cholesterolgehalte van 220mg/dl is dus gelijk aan 220/38,6 = 5,7 mmol/l.

Wil je de hoeveelheid triglyceriden omrekenen van mg/dl naar mmol/l, moet je het door 88,5 delen.
Een triglyceridengehalte van 183mg/dl is 183/88,5 = 2,06 mmol/l.

New England journal of Medicine 2003



Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline
Sarah E. Vermeer, M.D., Ph.D., Niels D. Prins, M.D., Tom den Heijer, M.D., Albert Hofman, M.D., Ph.D., Peter J. Koudstaal, M.D., Ph.D., and Monique M.B. Breteler, M.D., Ph.D.

ABSTRACT

Background Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline.

Methods We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions.

Results During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts.

Conclusions Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.


Source Information

From the Departments of Epidemiology and Biostatistics (S.E.V., N.D.P., T.H., A.H., M.M.B.B.), and Neurology (S.E.V., N.D.P., T.H., P.J.K.), Erasmus Medical Center, Rotterdam, the Netherlands.

Address reprint requests to Dr. Breteler at the Department of Epidemiology and Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands, or at m.breteler@erasmusmc.nl.

Full Text of this Article

Prevalence of Stroke --- United States, 2005

Posted 06/11/2007

J.R. Neyer; K.J. Greenlund, PhD; C.H. Denny, PhD; N.L. Keenan, PhD; M. Casper, PhD; D.R. Labarthe, MD, PhD; J.B. Croft, PhD
Author Information
CME
Nocturnal GERD: Definitions, Diagnosis, and Evolving Treatment Directions
Peter J. Kahrilas, MD presents provides an overview of pH montioring in presenting 'Esophageal Acid Exposure: Measurement, meaning and therapeutic implications.'

* Click here to read more

Content

Stroke is the third most common cause of death in the United States.[1] Stroke also results in substantial health-care expenditures; the mean lifetime cost resulting from an ischemic stroke is estimated at $140,000 per patient.[1] Nationwide, costs related to stroke are expected to reach an estimated $62.7 billion in 2007.[1] Stroke death rates are higher in the southeastern United States, compared with other regions of the country; blacks, American Indians/Alaska Natives (AI/ANs), Asians/Pacific Islanders, and Hispanics die from stroke at younger ages than whites.[1-3] Regional and national data on self-reported stroke prevalence have been published previously;[1,4] however, state-specific prevalence data for persons with a history of stroke have not. To provide national-level stroke prevalence estimates by age group, sex, race/ethnicity, and education level and overall prevalence estimates for each of the 50 states, the U.S. Virgin Islands (USVI), the District of Columbia (DC), and Puerto Rico, CDC analyzed data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report summarizes the results of that analysis and provides the first state-based prevalence estimates of stroke. The results indicated that, in 2005, substantial differences existed in the prevalence of stroke by state/territory, race/ethnicity, age group, and education level. To lower the incidence of stroke and meet the Healthy People 2010 objective* to reduce stroke deaths (objective no. 12-7) and the overall goal to eliminate health disparities, public health programs should augment stroke risk-factor prevention and educational measures in disproportionately affected regions and populations.

BRFSS is a state-based, random-digit_dialed telephone survey of the noninstitutionalized, U.S. civilian population aged >18 years and is administered by state health departments in collaboration with CDC. In 2005, the median response rate among states, based on Council of American Survey and Research Organizations guidelines, was 51.1% (range: 34.6%--67.4%). This rate accounts for the efficiency of the telephone sampling method used and participation rates among eligible respondents who were contacted. A total of 356,112 respondents from all 50 states, DC, Puerto Rico, and USVI participated in the survey. State (including DC) and territory sample sizes ranged from 2,422 (USVI) to 23,302 (Washington). The racial/ethnic national sample sizes ranged from 5,535 (AI/ANs) to 279,419 (whites). All prevalence estimates in this report have a numerator >50 and a relative standard error <30% to ensure that estimates are stable.†

Survey respondents answered the question, "Has a doctor or other health professional ever told you that you had a stroke?" Differences in prevalence were assessed by age group, sex, race/ethnicity, education level, and state or territory of residence. Data were weighted to reflect the population aged >18 years in each state and territory and were age adjusted to the 2000 U.S. standard population to allow for more meaningful comparisons between states and between demographic groups. The weighted state prevalence values were used to estimate the number of persons with a history of stroke in various demographic groups and in each state or territory. Respondents provided racial/ethnic identification; those who identified themselves as multiracial were included in a separate category.

In 2005, 2.6% (95% confidence interval [CI] = 2.5--2.7) of noninstitutionalized U.S. adults (approximately 5,839,000 persons) had a history of stroke ( Table 1 ). The prevalence of stroke increased with age: 8.1% of respondents aged >65 years reported a history of stroke, compared with 0.8% of persons aged 18--44 years. The prevalence of stroke among men (2.7%) and women (2.5%) was similar. Among persons with less than 12 years of education, 4.4% reported a history of stroke, approximately twice the proportion among college graduates (1.8%).

The overall prevalences of stroke among AI/ANs (6.0%), multiracial persons (4.6%), and blacks (4.0%) were higher than the prevalence among whites (2.3%). The prevalences of stroke among Asians/Pacific Islanders (1.6%) and Hispanics (2.6%) were similar to the prevalence among whites.

The prevalence of stroke ranged from 1.5% in Connecticut to 4.3% in Mississippi ( Table 2 ). States and territories with the highest prevalence of stroke had approximately twice the prevalence of those with the lowest (Figure 1). Wyoming, with an estimated state population of 509,000 in 2005, had the lowest estimated number of persons reporting a history of stroke (10,000); California, with an estimated population of approximately 36 million in 2005, had the highest (641,000).

Click to zoom
Figure 1. (click image to zoom)

Percentage of respondents aged ≥18 years who reported a history of stroke, by state/area–Behavioral Risk Factor Surveillance System, United States, 2005*

Figure 1. ATP Classification of LDL. Adapted from: Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) National Heart Lung and Blood Institute. National Cholesterol Education Program. 2001. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm Accessed May 22, 2007.

Totaal cholesterol minder dan 200mg/deciliter
low density cholesterol minder dan 100 mg /deciliter
High density cholesterol hoger dan 60 mg/deciliter

Atrial fibrillation the latest advances
Medscape cardiology
13-06-2007

Medscape: So just to summarize, can you give us a brief rundown of what your treatment continuum would be in a patient with HF and AF?

Dr. Strickberger: If they have a low EF,(ejection fraction) I would get them anticoagulated and then try to get them in normal rhythm at least once. I personally would probably give them an antiarrhythmic drug if I thought their EF would improve in normal rhythm, but I would avoid any drugs in which I had concerns about proarrhythmia. That eliminates a lot of the antiarrhythmic drugs, except for sotalol and amiodarone. Many of the large studies suggest that sotalol is safe, at least for patients with ischemic cardiomyopathy. My bias is towards amiodarone, although I think the data suggest that it is safe to use either agent. If you can maintain the patient in normal rhythm using this strategy and their EF improves, then you've achieved the primary goal. You also know that they have a tachycardia-induced cardiomyopathy and you have avoided having to give them a prophylactic defibrillator because their EF has improved. Obviously, their treatment also includes beta-blockers, an angiotensin-converting enzyme inhibitor, and perhaps other drugs.

If a patient has diastolic dysfunction and persistent AF, I might not give them a drug. Depending on the circumstances, I might just perform a cardioversion and see how long they stay in sinus rhythm. Some people will stay in sinus rhythm for a long time; in most cases, however, they don't, but given that the drugs have issues, if you can get something that works without a drug, it is worth a try. If the AF recurs relatively quickly, then I would give them a drug. If all of that fails, we would be limited to anticoagulation and rate control.

Medscape: When would you move to AF ablation or AV node ablation?

Dr. Strickberger: If they have diastolic dysfunction, I might consider a curative ablation for AF as opposed to AV node ablation. But I think for the people with dead hearts, most physicians would probably choose AV node ablation -- although I think that's a moving target today.

Supported by an independent educational grant from St. Jude Medical

Conclusions

Since PV (pulmonary vene) isolation was first described for treating AF in 1998, the patient population undergoing AF ablation has greatly expanded. Patients are older, with larger left atrial size, are more likely to have persistent/permanent AF, and have been subjected to fewer prior antiarrhythmic agents. Compared with the gender-specific rates of AF in the population, the majority of patients referred for ablation are men, suggesting a referral bias against this invasive procedure for women. These findings are important for interpreting the outcome of ablation in the current era and for designing prospective trials in the future

Summary and Comment
Creation of Embryonic Stem Cells Without Using Embryos, in Mice

New technique could circumvent the ethical debates surrounding stem cell biology.

Scientists used to believe that a differentiated cell could never return to a less mature state, much less revert into an embryonic state. Yet, nuclear transfer experiments in animals have shown that the nucleus of a differentiated adult cell can be reprogrammed by the egg into which it is inserted, creating an early embryo containing embryonic stem cells. However, the creation of a human embryo by this technique has not been accomplished and would raise ethical issues for some.

Several research groups now report that they have transformed fibroblasts from the skin of adult mice into cells with all the qualities and potential of embryonic stem cells. Investigators used viral vectors to insert four genes into the fibroblasts. The genes reprogrammed the cell to become an embryonic stem cell, without involving the creation of an embryo. Two of the genes are oncogenes.

Comment: If the same technique can be made to work in humans, genetically identical embryonic stem cells could be created for anybody, avoiding both immune rejection and ethical issues. Investigators will now try to replicate these results in human cells and to avoid two potential problems in humans: the cancer-causing potential of oncogenes and the use of viruses to introduce the necessary reprogramming genes. No one can predict whether this work will be successful or how long success may take. But no one would have predicted that this breakthrough in mice would come as quickly as it did.

— Anthony L. Komaroff, MD

Published in Journal Watch General Medicine June 21, 2007

ATRIAL FIBRILLATION


Paroxysmal Persistant

No therapy unless severe symptoms Accept permanent AF
e.s. Hypotension hf and angina pectoris plus aticoagulation

use: anticoagulantia
or
Consider arrhithmic
drug therapy
or
cardioversion
Long term anti-arrhythmic
Role primary care therapy unnecessary
anticoagulation
rate controle
Beta-blocker
Calcium channel blocker
Beta-blocker
Calcium channel blocker



Tot de risk factors behoren
History of hypertension1,6
and age 1,4



Beta blocker (Losartan zou beter zijn dan atenolol)
Amiodarone zou beste
zijn voor rhythme control
liefst met Calcium channel blocker

* Statins are typically safe and well tolerated at standard doses and are metabolized in the liver. Those that are metabolized primarily by the cytochrome P-450 system can interact with other commonly prescribed drugs (itraconazole, ketoconazole, miconazole, gemfibrozil, bezafibrate, fenofibrate, ciprofibrate, erythromycin, clarithromycin, telithromycin, nefazodone, verapamil, amiodarone, and HIV protease inhibitors) and regular ingestion of grapefruit juice.
* Myopathy typically occurs in fewer than 1 in 10,000 patients receiving standard statin doses, but this risk varies between statins and increases with use of higher doses and interacting drugs. Measurement of CK levels in patients with muscle pain can rule out myopathy and allow safe continuation of treatment. Both myopathy and rhabdomyolysis occur more often with higher statin doses and are reversed by stopping statin use, usually leading to full recovery.

About.com Cholesterol
Omacor®: A New Drug to Treat High Triglyceride Levels
From Jennifer Moll,
Your Guide to Cholesterol.
Stay up to date!

Omacor® is a new medication that consists of a high concentration of highly purified omega-3 fatty acid ethyl esters. Approved by the Food and Drug Administration in November 2004, this new drug is used to treat hypertriglyceridemia and is meant to serve as an adjunctive therapy in addition to healthy eating habits, and the control of heart disease risk factors, such as high blood pressure, diabetes, and high cholesterol levels. Hypertriglyceridemia is a condition in which triglyceride levels exceed 500 mg/dL and could be a precursor to serious heart disease if not properly addressed. This medication, which is manufactured by Pronova Biocare and Reliant Pharmaceuticals, was released on the US market in the fall of 2005.

What does Omacor® do and how does it work?
Omacor® consists of two main omega-3 fatty acids, eicosapentaenoic acid and docosahexanoic acid, that function in lowering triglyceride levels. High triglyceride levels are strongly correlated to the development of coronary heart disease. Omacor® has been also noted to reduce VLDL levels. This drug may be used alone or in combination with other cholesterol-lowering medications.

The mechanism of action of this drug is completely known; however there are many theories surrounding how omega-3 fatty acids may work. These mechanisms may include reducing the amount of triglycerides made in the liver, inhibition of the esterification of other fatty acids, and the inhibition of diacylglycerol O-acyltransferase, which is an enzyme that catalyzes the final step of triglyceride synthesis.

How is Omacor® different than the omega-3 fatty acid products I can get over-the-counter at my local pharmacy?
The manufacturers of Omacor® state that they use a highly modified purification process than differs from what you obtain on the shelves at your local pharmacy. In addition, Omacor ® contains 1 gram of omega-3 fatty acids that should be taken four times a day. Some variations of omega-3 fatty acids already on the shelves may be less than this, causing you to take more capsules at a time (and therefore decreasing compliance).

How should I take Omacor®?
Omacor® should be taken with meals. The typical dosage is 4 grams a day, which may be taken as one 1-gram capsule four times a day or two 1-gram capsules twice daily. This dosing is up to the discretion of your health care practitioner.

What are the side effects associated with Omacor®?
Side effects include:rash, possible increase in LDL levels, belching (often called a “fish burp”), upset stomach, an increase in the AST and ALT liver enzymes, prolongation of bleeding time, changes in taste, and flu-like symptoms.

Who should not take this medication?
Patients who are under 18 years of age, pregnant or nursing mothers, patients with bleeding disorders or who are on anticoagulation therapy, and patients with liver disease should consult their health care practitioner before using this drug. Patients demonstrating an allergy to the drug or components that make up the drug should not take this medication.



~ Jennifer Moll, M.S.

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Foods Containing Omega-3 Fatty Acids
Omega-3 fatty acids are polyunsaturated fatty acids that have been known to increase HDL (good cholesterol), decrease triglycerides, prevent irregular heart beats, and prevent blood clot formation. Although there are many over-the-counter and prescription medications containing omega-3 fatty acids, they may also be obtained through a variety of foods in your diet. Find out which foods have high amounts of omega-3 fatty acids.


de becel met extra omega-3 bevat per 100 gram 0,75 gram EPA plus DHA. Deze worden uit visolie bereid. Ook 3 gram alfa-linoleen zuur Uit alfa-linoleen zuur, dat een essentiëel vetzuur is maakt het lichaam de omega-3 vetzuren, dezefde als in walnoten en in geringe mate ook in bladgroeten.Omdat visolie ook nadelen heeft, denk aan kwaliteit en kwik is er ook een preparaat Omacor dat zeer zuiver is.

About.com Cholesterol
Fish Oil, Fish Consumption, and Omega-3 Fatty Acids: Do They Lower Cholesterol?
From Jennifer Moll,
Your Guide to Cholesterol.
Stay up to date!

Omega-3 fatty acids are polyunsaturated fats found in fish, fish oil, and in the form of supplements. They typically consist of a combination of polyunsaturated fatty acids that include DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid). Polyunsaturated fats, especially EPA and DHA, have a reputation for being heart-friendly fats because they do not promote atherosclerosis associated with causing heart disease. Previous research has shown that individuals consuming omega-3 fatty acids have decreased risk of sudden death from heart disease. Recent research has indicated that it may also lower the risk for heart disease by improving your lipid profile. So, does it help lower triglyceride and cholesterol levels?
The Studies Look Promising…
The usual dose used in these studies ranges between 900 mg and 5 grams a day of a combination of EPA and DHA. In order to achieve this amount, one would need to consume a lot of fish. Therefore, supplements are typically used. Ingesting 900 mg of omega-3 fatty acids each day resulted in a 4-percent decrease in triglyceride levels after six months. The average effective dose used in most studies was between 2 to 4 grams, and this resulted in an average drop in triglycerides between 25 to 45 percent. The effectiveness of omega-3 fatty acids on triglycerides is dose-dependent, meaning that the more omega-3 fatty acids ingested, the lower your triglyceride levels will fall. This works best when following a healthy diet. Omega-3 fatty acids seemed to affect recently ingested triglycerides more. Additionally, individuals with extremely high triglyceride levels (greater than 500 mg/dL) seem to derive the most benefit from omega-3 fatty acid supplementation.

Although it can lower triglyceride levels, it may slightly raise low density lipoproteins (known also as LDL or the “bad” cholesterol). This change, however, is modest and ranges from 3 to 10 percent. High density lipoproteins (also known as HDL or the “good” cholesterol) do not seem to be affected by omega-3 fatty acid supplementation, if not slightly increased.
How Much Should I Take Each Day?
Omega-3 fatty acids are either available as a prescription or as a supplement at your local pharmacy or nutritional store. One gram of omega-3 fatty acid supplementation a day would cause a decrease in triglycerides and would help prevent sudden death from heart disease. An average of four grams of omega-3 fatty acids are typically used to reduce triglycerides in individuals with high trigylceride levels. It is recommended that individuals taking more than 3 grams a day should be under the supervision of a health-care provider, since high doses of omega-3 fatty acids decrease the aggregation of platelets, which may cause bleeding to occur more easily.
What is the Difference Between Prescription Omega-3 Fatty Acids and Over-The-Counter Supplements?
Prescription omega-3 fatty acids (Omacor®) contain a certain amount of EPA and DHA, are purified, and are thoroughly rid of impurities such as trans-fats, mercury, or other contaminants. Supplements that are available over the counter are classified as “foods” by the Food and Drug Administration. Therefore, they do not have to undergo the rigorous purification processes or efficacy studies that prescription drugs have to go through. Sources:

McKenney JM, Sica D. Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia. Am J Health Syst Pharm.2007 Mar 15;64(6):595-605.

Balk EM, Lichtenstein AH, Chung M et al. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006 Nov;189(1):19-30.

Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002; 106:2747-2757.

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Medscape from WebMD
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A Suicide Right for the Mentally Ill? A Swiss Case Opens a New Debate

Jacob M. Appel

Hastings Cent Rep. 2007;37(3):21-23. ©2007 The Hastings Center
Posted

Advocates for the legalization of assisted suicide in the United States, including those who sponsored Oregon's Death with Dignity Act in 1994 and current backers of California's proposed Compassionate Choices Act, have sought to permit the practice only under highly limited circumstances—namely, when the requesting patient is terminally ill.[1] In contrast, the Netherlands allows physician-assisted suicide in nonterminal cases of "lasting and unbearable" suffering, and Belgium authorizes physician-assisted suicide for nonterminal patients when their suffering is "constant" and "cannot be alleviated."[2] Yet no country has laws on the subject as liberal as those of Switzerland, where assisted suicide has been legal since 1918. It remains the only jurisdiction that allows nonresidents to terminate their own lives.[3] It is also the only jurisdiction that does not require that a physician be involved in the process.

Now, a recent decision by the Swiss Federal Supreme Court threatens to undermine yet another longstanding taboo in the debate over assisted suicide and euthanasia. In its ruling on November 3, 2006, the high tribunal in Lausanne laid out guidelines under which, for the first time, assisted suicide will be available to psychiatric patients and others with mental illness.[4]

The case was that of an unnamed fifty-three-year-old manic depressive with two prior suicide attempts who sought a prescription for fifteen grams of sodium pentobarbital in order to end his own life.[5] He claimed a right to self-determination under Article 8 of the European Convention on Human Rights and alleged that no physician would prescribe him this lethal dose for fear of legal or professional repercussions.[6] Dignitas, a Zurich-based advocacy group, supported his suit. The Swiss high court responded with a sweeping opinion upholding the right of those suffering from "incurable, permanent, severe psychological disorders" to terminate their own lives.[7] According to the court, a distinction should be made between temporarily impaired individuals who wish to die as "an expression of treatable psychological disturbances" and those individuals with severe, long-term mental illness who have made "rational" and "well-considered" decisions to end their lives to avoid further suffering.[8] Since serious mental disorders could make life seem as unbearable to some patients as serious somatic ailments do to others, the court reasoned, those who repeatedly expressed a wish to end their lives under such circumstances should be permitted to do so. (The court also ruled that the plaintiff in this case would have to obtain a thorough psychiatric evaluation to determine whether he met these standards before he could end his life.)

Both supporters and opponents of assisted suicide have been highly critical of extending suicide rights to psychiatric patients.[9] One set of objections is directed against the practice of assisted suicide itself—for a host of reasons ranging from a belief in the inherent sanctity of human life to a fear of sliding down a slippery slope toward involuntary euthanasia; that debate has been extensively addressed elsewhere. Another set of objections are from those who support a basic right to assisted suicide in certain situations, such as those of terminal disease, but do not wish to extend it to cases of severe and incurable mental illness. This resistance may be inevitable, considering the increased emphasis that contemporary psychiatry places on suicide prevention, but the principles favoring legal assisted suicide lead logically to the extension of these rights to some mentally ill patients.[10]

At the core of the argument supporting assisted suicide are the twin goals of maximizing individual autonomy and minimizing human suffering. Patients, advocates believe, should be able to control the decision of when to end their own lives, and they should be able to avoid unwanted distress, both physical and psychological. While these two principles might explain why a victim of amyotrophic lateral sclerosis or cancer would choose assisted suicide, they apply equally well in many cases of purely psychological disease: a victim of repeated bouts of severe depression, particularly in cases where treatment has consistently proven ineffective, rationally might prefer dignified death over future suffering.

Obviously, there is a difference in kind between the terminally ill cancer patient and the acutely depressed teenager who transiently desires to end his life after a romantic setback; it seems logical to prevent patients from committing suicide until they have considered all of their options over an extended period of time, and to be certain that they are not acting in haste. But the difference between a patient who desires suicide after enduring the long-term agonies of rheumatoid arthritis or trigeminal neuralgia and the patient who wants to end his life after years of debilitating anxiety or intermittent psychotic episodes is not so clear.

One crucial distinction between chronic mental illness and terminal disease is that death is inevitable in the latter cases. Yet "inevitable" is really not quite right. From today's vantage point, a rapid cure for ALS or certain cancers appears highly unlikely, yet the history of modern medicine is replete with examples of illnesses (type I diabetes, acute lymphoblastic leukaemia, choriocarcinoma) that have rapidly gone from universally fatal to highly manageable. What we really mean when we speak of inevitability is that we believe the patient should be able to weigh the unlikely possibility of a cure against her other interests. While the window of opportunity for discovering effective treatment may be longer in cases of chronic mental illness, it seems reasonable to afford the patient the same choice in balancing likelihoods against other values. And if the offer is that an effective treatment may eventually be found, but a person will have to suffer for some decades more until that happens, then it might still be rational to prefer suicide.

A second concern in cases of mental illness is that of the competence of the decision-maker. For example, a severely depressed patient might substantially underestimate her long-term prognosis. But rather than arguing against assisted suicide, this might indicate even further the depth of the patient's present suffering. Clearly, patients who experience psychosis or are incapable of making general medical decisions should not be able to take their own lives until they can think rationally. Morever, the finality of a life-terminating decision indicates that a higher threshold of competence should be required in suicide cases than in more run-of-the-mill health care choices. But one can be both deeply depressed and capable of making rational decisions. If the values championed by assisted suicide advocates are maximization of autonomy and minimization of suffering—even when they conflict with the extension of life—then it follows that chronically depressed, competent individuals would be ideal candidates for the procedure. At the very least, a patient with a history of mental illness who is currently experiencing a temporary remission of symptoms will certainly be competent enough to make such a choice before the return of the disease. (An additional concern might be the increased suffering endured by families of assisted suicide victims—but why this suffering should trump that of the patient is not clear.)

The most compelling argument against extending assisted suicide rights to the mentally ill relates to the role of physicians. The nature of psychiatric therapy differs from that of other medical treatment in the degree of attachment between caregiver and patient. This distinction is recognized in various regulatory codes, and most glaringly in the rules banning romantic relations between psychiatrists and former patients, even many years after care has ceased. Moreover, psychiatrists are trained to prevent suicide—an outcome widely regarded by the profession as a failure. This conflict of interest places the psychiatrist in the unpleasant bind of choosing between a patient's wish and the standard of care in the field. Psychiatrists might even attempt to avoid treating such rational but chronically suicidal patients in an effort to avoid this choice. Any meaningful discussion of the subject of assisted suicide for the mentally ill should include an exploration of alternative mechanisms by which such patients might obtain help in ending their lives, possibly including the use of full-time thanatologists specially trained for the act.

Most likely, the taboo against assisted suicide for the mentally ill is a well-meaning yet misplaced response to the long history of mistreatment that those with psychiatric illness have endured in western societies. Psychiatrists and mental health advocates may fear that their patients will be coerced to "choose death" against their wishes, or that, once suicide is an acceptable option, the care for those who reject assisted suicide will be diminished. But as the plaintiff argued before the Swiss high court, in challenging "medical paternalism," we are entering an era during which psychiatric patients do not need to be protected, but empowered.[11] Our goal should be to maximize the options available to the mentally ill.

The Swiss case is not the first in which a nation's high court has suggested a right to suicide for those with mood disorders. In 1993, the Dutch Supreme Court refused to impose a penalty on psychiatrist Boudewijn Chabot for assisting in the suicide of his patient, Hilly Bosscher, a chronically depressed fifty-year-old woman who insisted she did not wish to continue living after the death of both of her adult sons.[12] Boudewijn nevertheless received a reprimand from his local medical disciplinary tribunal, creating a strong civil deterrent for others to follow his lead.[13] The Bosscher case arose when the euthanasia movement was still in its infancy, however. Since assisted suicide for the terminally ill was itself taboo fifteen years ago, it was unrealistic to expect that a mainstream debate would arise over the issue of suicide rights for psychiatric patients. But now that several Western nations and one U.S. state have liberalized their laws, it seems reasonable to question the policies that universally deny such a basic opportunity to the mentally ill.

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References

1. Oregon Revised Statutes 127.800-995; California Assembly Bill 374 (2007).
2. Termination of Life on Request and Assisted Suicide Review Procedures Act (2002), 26 691, no. 137 of the 2000-2001 parliamentary session that went into effect April 1, 2002, available at http://www.nvve.nl/nvve2/pagina.asp?pagkey=72087; Act of Belgain Parliament on Euthanasia (May 28, 2002), parliament document no. 50K1488, available at http://www.lachambre.be/kvvcr/showpage.cfm?section=flwb&language=fr&rightmenu=right&cfm=flwbn.cfm?lang=F&legislat=50&dossierID=1488.
3. S.A. Hurst and A. Mauron, "Assisted Suicide and Euthanasia in Switzerland: Allowing a Role for Non-Physicians," British Medical Journal 326 (2003): 271-73.
4. Ruling 03.11.2006 2A.48/2006 of the Federal High Court of Switzerland.
5. "Ärztliche Suizidhilfe auch für psychisch Kranke," Basler Zeiting, February 2, 2007.
6. "Mentally Ill Now Included in Swiss Assisted Suicide Laws," February 1, 2007, available at http://euthanasie.org/nvve2/pagina.asp?pagkey=74297&metkey=375.
7. Ruling 03.11.2006 2A.48/2006 of the Federal High Court of Switzerland.
8. Ibid.
9. See B. Russell and M. Firth, "Swiss Clinic Wants to Offer Assisted Suicide to the Mentally Ill," The Independent, September 21, 2006.
10. For a discussion of the increased emphasis that psychiatry places on suicide prevention, see S. Burgess and K. Hawton, "Suicide, Euthanasia and the Psychiatrist," Philosophy, Psychiatry & Psychology 5, no. 2 (1998): 113-26.
11. S. Arsever, "Les Patients Psychiques Ont Droit a l'Aide au Suicide. Par un Medecin," Le Temps, February 3, 2007.
12. "Doctor Unpunished For Dutch Suicide," New York Times, June 22, 1994.
13. Ibid.

Statins Could Cut Lung Cancer Risk
But promising findings need to be replicated elsewhere, experts say.

By Alan Mozes
HealthDay Reporter
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(SOURCES: Vikas Khurana M.D., associate professor, medicine, Temple University Hospital, Philadelphia; Neil Schachter, M.D., professor, pulmonary medicine, and medical director, respiratory care department, Mount Sinai Medical Center, New York City; Walid G. Younis, M.D., pulmonary fellow, University of Oklahoma Medical Center, Oklahoma City; May 2007, Chest)

MONDAY, May 7 (HealthDay News) -- In addition to their well-established role in preventing heart disease, cholesterol-lowering statins may also dramatically reduce the risk for lung cancer among men, a new study suggests.

U.S. researchers found that patients taking a statin for at least six months experienced a drop in lung cancer risk of 55 percent. Almost all the patients in the study were men.

"What these researchers have done is to examine a large collection of data that's already out there to show that the use of statins is a plausible preventive treatment for patients with lung cancer, or patients who are going to develop lung cancer," said Dr. Neil Schachter, medical director of the respiratory care department at Mount Sinai Medical Center in New York City.

Schachter, who is also a professor of pulmonary medicine, did not work on the study, which is published in the May issue of Chest.

"Whether statins are really useful in this kind of situation has not been firmly established as yet," stressed Schachter. "But there has been a lot of work to suggest that they might be. Particularly because chronic obstructive pulmonary disease -- which is the most common of lung diseases caused by cigarette smoking -- usually occurs with other diseases, so that most people who die of lung disease die of something else. And one of the major things they die of is heart disease. So, treating the heart disease with statins, perhaps, would not surprisingly be expected to prolong life."

Lung cancer remains the biggest cancer killer in the United States. According to the American Cancer Society, in 2007, almost 214,000 new cases of lung cancer will be diagnosed. More than 160,000 men and women will die of the disease this year, which in more than 80 percent of cases is linked to smoking. Approximately 60 percent of lung cancer patients do not live one year after diagnosis.

Millions of Americans already take statins -- commonly known by brand names such as Lipitor, Mevacor, Pravachol, and Zocor -- to diminish their risk for heart disease.

In recent years, many studies have explored a possible connection between statins and reduced cancer risk, based on the theory that statins may inhibit the onset and growth of malignancy at the molecular level. However, studies on skin, colorectal, and, more recently, lung cancer risk have so far proven inconclusive.

Exploring further, a team led by Dr. Vikas Khurana, of the department of medicine at Overton Brooks VA Medical Center in Shreveport, La., pored over six years of data amassed by the VA Health Care System (VAHCS). The information concerned almost 484,000 patients between the ages of 18 and 100 from eight southern states.

Almost 98 percent of the patients were men, all of who had sought treatment either at the VAHCS primary care clinic or hospital between 1998 and 2004.

About 1.5 percent of the patients had lung cancer, of whom nearly three-quarters were smokers. Just over a quarter of the cancer patients had been taking statins prior to their diagnosis.

Irrespective of race, body mass index, diabetes status, age, or smoking and drinking histories, statin use exceeding six months was linked to a significant lung cancer risk reduction of 55 percent, the researchers found.

This protective effect rose along with the length of time statins were used. Those patients who took a statin for four years or more had a 77 percent reduction in lung cancer risk, the team noted.

However, statin use of less than six months was associated with an increased risk for developing lung cancer.

But Khurana and his colleagues dismissed the notion that statin use actually caused this bump in risk. Instead, they attributed the finding to pre-existing conditions that went unnoticed or misstated in the early stages of study participation.

While encouraging, the new findings need to be replicated among a more diverse group of patients, including more women and non-veterans, the researchers said.

"We have very strong data based on actual patient chart review, not simply patient recall," noted Khurana, who is currently an associate professor of medicine at Temple University Hospital in Philadelphia. "But there have been conflicting reports about statins being protective or not, and we were surprised by the high percentage of protection we saw. So we will need to look at this some more to see if other factors correlated with stain use is related to the cancer protection we found."

Future studies should also consider statin dosage and type, as well as other contributing risk factors for cancer such as diet, genetic background, and the possibility of underlying lung disease, his team said.

"What we need to do with future research is get to the point where we can start patients on this medication specifically for cancer prevention," according to Khurana. "Because, right now, we still cannot say that people should take statins to protect against cancer. But we can say that if they have a cholesterol problem and they're taking statins already, they might be deriving additional benefits against cancer from the medications."

Dr. Walid G. Younis, a pulmonary fellow at the University of Oklahoma Medical Center in Oklahoma City, said he was a little surprised at the study findings.

"We did a statin study about one year ago that did not show any benefit in decreasing lung cancer incidence," he cautioned. "It was a much smaller study, but still it makes me wonder if these conclusions will hold true. Especially because the mechanism by which statins might reduce the risk of lung cancer is not very clear. But, certainly, it's absolutely worth continuing to look at the protective possibility of statins."

Schachter agreed that further research is needed.

"Does this study prove that statins are useful for the treatment of lung cancer?" he posited. "No. Will the FDA now approve statins as safe and effective for the treatment of lung cancer? No, not based on this study. It's not definitive. But this work is certainly interesting, and it will spark interest in more research."

More information

For additional information on lung cancer, visit the American Cancer Society.

Copyright © 2007 ScoutNews, LLC. All rights reserved.
HealthDayNews articles are derived from various sources and do not reflect federal policy. healthfinder.gov does not endorse opinions, products, or services that may appear in news stories. For more information on health topics in the news, visit the healthfinder.gov health library.

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Selection from: LDL-C -- How Low Should You Go?

LDL-C -- How Low Should You Go? CME/CE

William Virgil Brown, MD Disclosures
Introduction

In the United States, more than 1 million deaths each year are attributable to cardiovascular disease (CVD).[1] Currently, CVD affects over 70 million Americans, 27 million of whom are older than 65 years of age.[1] By the year 2010 there will be 40 million Americans over the age of 65; as the population ages, the incidence of CVD is expected to rise exponentially. In recent years, there has been a growing awareness of the importance of evaluating multiple risk factors and pathways when assessing and treating an individual's risk for CVD.[2] Dyslipidemia has been identified as one of the leading risk factors for coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD). According to the World Health Organization, elevated cholesterol levels are estimated to cause 56% of global CHD and 18% of global cerebrovascular disease.[3]

Studies suggest that a 10% decrease in total cholesterol levels would result in an estimated 30% reduction in the occurrence of CVD if sustained over a lifetime.[4] Low-density lipoprotein cholesterol (LDL-C) accounts for approximately 60% to 70% of total serum cholesterol, and plays a central role in the development of atherosclerosis and CVD. In 1988, the National Cholesterol Education Program (NCEP) in the United States identified LDL-C as the primary target of cholesterol-lowering therapy. Their guidelines for LDL-C included goals adjusted according to the total impact of other CHD risk factors.[5] Over the past 20 years, with continued research into the benefit of LDL-C reduction, the goals for LDL-C have been reduced repeatedly for those individuals considered to be at very high risk.[6,7] In those considered appropriate for drug treatment, the reduction should achieve at least a 30% reduction from the baseline level. The "optimal LDL-C" for all adults in the United States was initially recommended to be < 130 mg/dL but in 2001, this was reduced to < 100 mg/dL.[7] (Figure 1)
ATP Classification of LDL.

Omega-3 vetzuren

Omega-3 vetzuren zijn essentieel voor onze gezondheid. Visolie bevat deze essentiële vetzuren. De meest belangrijke omega-3 vetzuren die in visolie voorkomen zijn EPA (eicosapentaëenzuur) en DHA (docosahexaëenzuur). Omega-3 vetzuren zijn goed voor hart en bloedvaten, verlaging van de bloeddruk en het cholesterolgehalte, maar ook voor onze hersenen, gewrichten en voor zwangere vrouwen, baby’s en opgroeiende kinderen. Het is niet alleen belangrijk dat we voldoende omega-3 vetzuren binnenkrijgen, maar met name de verhouding tussen omega-3 en omega-6 vetzuren is van belang. Voor een juiste balans in het lichaam moet deze 1:4 zijn. Omega-6 vetzuren zijn ook essentiële vetzuren, maar ze komen, in tegenstelling tot omega-3 vetzuren, wel veel in ons voedsel voor. Met name zonnebloemolie, chips, dressings, mayonaise en frituurproducten bevatten veel omega-6 vetzuren. Veelal krijgen we dus te veel omega-6 vetzuren en te weinig omega-3 vetzuren, waardoor de verhouding niet meer klopt. Daarom is het belangrijk het gehalte aan omega-3 vetzuren te verhogen. Het is dan ook belangrijk een visolieproduct te kiezen met alleen omega-3 vetzuren.
EPA en DHA

EPA en DHA, ook wel eicosapentaeenzuur en docosahexaeenzuur genoemd, zijn beide omega-3 vetzuren. EPA is essentieel voor de bescherming van onder meer hart en bloedvaten in het menselijk lichaam en DHA is essentieel voor onder meer de opbouw van celwanden in het menselijk lichaam.

DHA is met name van belang voor:

* vrouwen die zwanger willen worden
* vrouwen die zwanger zijn
* vrouwen die net bevallen zijn
* baby’s
* opgroeiende kinderen.

DHA is belangrijk voor onder meer de opbouw van celwanden bij de groei en ontwikkeling van het (ongeboren) kind. Tijdens de zwangerschap wordt een gedeelte van het DHA-gehalte van de moeder gebruikt voor de vrucht in ontwikkeling. Daarom is het voor aanstaande moeders belangrijk om voor en tijdens de zwangerschap, maar ook tijdens de borstvoeding, voldoende DHA in te nemen.

Voor baby’s en jonge kinderen zijn omega-3 vetzuren van belang omdat deze bijdragen aan de ontwikkeling van de hersenen en een essentiële rol spelen bij de ontwikkeling van het immuunsysteem. Zo bestaat 20% van de kinderhersenen uit DHA. Voor opgroeiende kinderen zijn omega-3 vetzuren goed omdat de concentratie wordt ondersteund. Dit helpt schoolprestaties te verbeteren. De juiste verhouding EPA en DHA voor deze groepen is 1:5.

EPA is met name van belang voor:

* kinderen vanaf ± 12 jaar
* volwassenen.

Bij kinderen vanaf ± 12 jaar en volwassenen gaat het namelijk niet zozeer meer om de opbouw van cellen, maar juist om de bescherming van cellen, waaronder hart en bloedvaten. Hiervoor is EPA verantwoordelijk. Bij deze groepen is het van belang dat de verhouding EPA en DHA 1,5:1 is.
Visolie, een bewuste keuze

Er zijn tegenwoordig veel soorten visolie op de markt. Het is dan ook aan te raden goed te letten op de kwaliteitsaspecten van de verschillende soorten visolie.

Het is verstandig visolie te kiezen die alleen omega-3 vetzuren bevat. Er zijn ook visolieproducten met omega-6 en/of omega-9 vetzuren, maar onze voeding levert deze vetzuren meer dan voldoende.

Naast de samenstelling speelt ook de zuiverheid van visolie een belangrijke rol. Helaas is het zo dat de zee voor een groot deel met zware metalen en giftige chemicaliën verontreinigd is. Het eten van verontreinigde visolie kan gevaarlijk zijn voor de gezondheid. Kies daarom voor visolie die wordt gemaakt van vis uit een schone zee, bijvoorbeeld het gebied ten Westen van Zuid-Amerika, de Stille Oceaan.

Zeer belangrijk is de verhouding EPA/DHA die het visolieproduct bevat. Voor kinderen vanaf ± 12 jaar en volwassenen is de juiste verhouding EPA/DHA 1,5:1. Voor zwangere vrouwen, vrouwen die net bevallen zijn, baby’s en kinderen tot ± 12 jaar is de aanbevolen verhouding EPA/DHA 1:5.

Met een juiste, natuurlijke behandeling hoeft u visolie niet te ruiken. Er zijn capsules en druppels die reukloos zijn en een neutrale smaak hebben en dus geen vervelende oprispingen veroorzaken. Dit is niet alleen aangenaam voor uzelf, maar ook voor uw omgeving.

From the Divisions of Cardiovascular Diseases (A.J., V.L., P.A.F., J.M.T., S.L.K., D.L.P., S.C.H., W.-K.S., B.J.G.) and Biostatistics (D.O.H.), Mayo Clinic, Rochester, Minn.

Correspondence to Paul A. Friedman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail friedman.paul@mayo.edu

Received June 7, 2006; accepted March 30, 2007.

Background— The long-term natural history of lone atrial fibrillation is unknown. Our objective was to determine the rate and predictors of progression from paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk of heart failure, thromboembolism, and death compared with a control population.

Methods and Results— A previously characterized Olmsted County, Minnesota, population with first episode of documented atrial fibrillation between 1950 and 1980 and no concomitant heart disease or hypertension was followed up long term. Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion criteria (mean age at diagnosis, 44.2±11.7 years; male, 78%). Mean duration of follow-up was 25.2±9.5 years. Of 71 patients with paroxysmal or persistent atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15 and 30 years, respectively, similar to 86% and 57% survival for the age- and sex-matched Minnesota population. Observed survival free of heart failure was slightly worse than expected (P=0.051). Risk for stroke or transient ischemic attack was similar to the expected population risk during the initial 25 years of follow-up but increased thereafter (P=0.004), although CIs were wide. All patients who had a cerebrovascular event had developed ≥1 risk factor for thromboembolism.

Conclusions— Comorbidities significantly modulate progression and complications of atrial fibrillation. Age or development of hypertension increases thromboembolic risk.


CLINICAL PERSPECTIVE





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Copyright © 2007 by the American Heart Association.

The British Atherosclerosis Society
HUGH SINCLAIR
The Hugh Sinclair Lecture is currently normally given during the autumn meeting of the Society, by an established scientist judged by the Society to have made a notable contribution to knowledge of atherosclerosis or thrombosis. At present the lecturer’s honorarium is generously supported by Glaxo SmithKline.

Dr Hugh Sinclair (1910 – 1990) was a nutritionist and a founder member of the Atherosclerosis Discussion Group (the forerunner of this Society). He enjoyed fine wines, fast cars, and was an astute collector of rare and historical medical texts. He never achieved his ambition of a Chair at the University of Oxford, not because of lack of talent, but because of his inability to bow to authority. He was a scientific prophet before his time, but his wayward manner and driving ambition made him difficult to work with. His extensive, detailed and potentially very important records of human nutrition during and after the second world war were never fully analysed and published; the latter part of his career was spent continually struggling to raise money to pursue his research independently at his own International Nutrition Foundation, based in his large house and converted stables in a village outside Oxford.

It is only now that the seminal importance of Hugh Sinclair’s ideas and observations is apparent. He single-handedly championed the links between essential fatty acids (EFA) in the diet and protection from atherosclerosis, thrombosis and other degenerative diseases at a time when EFA had only just been described and long before the discovery of eicosanoids. He published a very long letter to the Editor advancing the hypothesis in The Lancet in 1956 (1), anticipating the controversy it would produce by noting towards the end of the letter (in a style typical of his writings but unusual in scientific discourse) that “You will now conclude, Sir, if indeed you have not done so long ago, that I have strayed into the realms of fantasy”.

Having first examined the diet of Eskimos in the early 1950s and noted their remarkably low incidence of ischaemic heart disease despite a diet consisting almost entirely of fish and seal meat, he visited Greenland in 1976 (at the age of 66) to confirm their plasma lipid profile, and in 1979 embarked on the most notorious of several nutrional self-experiments, eating only seal and fish for 100 days, measuring changes in his plasma lipids and recording the extreme prolongation of his bleeding time (2). Acceptance of the importance of Hugh Sinclair’s findings of the different roles of saturated and unsaturated dietary fatty acids, with invitations for him to speak at international conferences, was just beginning as he approached his eightieth birthday: he died less than six months later. After his death, the assets from the Foundation were used to endow in 1995 the Hugh Sinclair Chair in Human Nutrition at the University of Reading (where he had lectured regularly towards the end of his life), so that although Hugh Sinclair himself had not been promoted beyond Reader in Oxford (a post he achieved in 1947), his Chair lives on.

A full biography of Hugh Sinclair has been published (3), but the most entertaining and informative summary is provided in two articles in 1991, the second of which is by Hugh Sinclair himself and reprinted from an earlier publication (4,5).

1. Sinclair HM (1956). Deficiency of essential fatty acids and atherosclerosis, etcetera. Lancet i: 381-383.
2. Sinclair HM (1982). The relative importance of essential fatty acids of the linoleic and linolenic families: studies with an eskimo diet. Progr Lipid Res 20: 897-899.
3. Ewin J (2002). Fine wines & fish oil. Oxford University Press.
4. Jukes TH (1991). Hugh Sinclair (1910-1990). J Nutr 121: 1297-1299.
5. Sinclair HM (1991). Diseases of civilisation and EFA. J Nutr 121: 1299-1304.


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High Triglycerides - Overview
What are triglycerides?

Triglycerides are a type of fat found in your blood. They are a major source of energy and the most common type of fat in your body.

When you eat, your body uses the calories it needs for quick energy. Any extra calories are turned into triglycerides and stored in fat cells to be used later. The excess calories are stored as fat regardless of what kind of food you eat-fat, carbohydrate, or protein. If you regularly eat more calories than you burn, you may have high triglycerides.

In normal amounts, triglycerides are important to good health. When triglyceride levels are high, it is not clear whether these high levels directly increase your risk for heart disease. But high triglycerides are often part of a group of conditions called metabolic syndrome.

Metabolic syndrome is the combination of increased blood pressure, high blood sugar, excess weight, low HDL ("good") cholesterol, and high triglycerides. This syndrome does increase your risk for heart disease as well as for diabetes and stroke.

Triglycerides are measured as part of a blood test that measures your cholesterol. Normal triglyceride levels are below 150. Levels above 200 are high.
What causes high triglycerides?

Obesity, poorly controlled diabetes, underactive thyroid (hypothyroidism), kidney disease, and regularly eating more calories than you burn can cause high triglycerides.

Certain medicines may also increase triglycerides. These include tamoxifen, steroids, beta-blockers, some diuretics, estrogen, and birth control pills. Drinking a lot of alcohol may also cause high triglycerides.

Certain types of high cholesterol and high triglycerides run in families.
What are the symptoms?

High triglycerides do not usually cause symptoms. People who have a family history (genetic cause) of very high triglycerides may have visible fatty deposits under the skin called xanthomas.

In rare cases, people who have very high triglycerides may develop inflammation of the pancreas (pancreatitis). This can cause sudden, severe abdominal pain, loss of appetite, nausea, vomiting, and fever.
How can I lower my high triglycerides?

You may be able to lower your triglycerides by eating fewer calories and increasing your activity. Reducing fats in your diet and not drinking alcohol may also help.

If increasing your activity and watching calories do not work, you may also need medicine. Medicines called statins are commonly used to lower LDL ("bad") cholesterol. But drugs called nicotinic acids and fibrates seem to work better for lowering triglycerides. If you have high triglycerides, high LDL cholesterol, and low HDL ("good") cholesterol, it may help you to take a combination of medicines, such as a statin and a fibrate.

plasma triacylglycerol and the ratio of total to HDL cholesterol.
These Inuit had higher n3 fatty acid (EPA+DHA) concentrations
in their plasma phospholipids proportional to the intakes
of typical Eskimo marine foods. However, plasma total and
LDL-cholesterol concentrations correlated positively with n3
fatty acid concentrations. The divergent effects of n3 fatty
acids to reduce plasma triacylglycerol and elevate LDL may be
explained by a dietary background high in cholesterol and saturated
fat as well as in n3 fatty acids. The 2 situations are completely
compatible. In a feeding experiment by Nordoy et al
(15), a diet high in n3 fatty acids but also high in cholesterol
and saturated fat decreased plasma triacylglycerol and VLDL
and at the same time increased plasma LDL. The optimal diet
would be one high in n3 fatty acids and low in cholesterol and
saturated fat, thus reducing both triacylglycerol and LDL concentrations
in the plasma.
This pronounced effect of fish oil on hyperlipidemia is especially
well documented by precise dietary studies in which a diet
rich in salmon oil was fed and contrasted with a vegetable oil
diet and a diet high in saturated fat (16). Fish oil lowers plasma
triacylglycerol concentrations by inhibiting the synthesis of triacylglycerol
and VLDL in the liver. Apolipoprotein B production
is lower after consumption of fish oil than after consumption of
vegetable oils such as safflower or olive oil. This mechanism of
action is further substantiated by cultures of rabbit and rat hepatocytes
in which EPA, for example, in contrast with oleic acid,
inhibited triacylglycerol synthesis and stimulated the synthesis
of membrane phospholipid.
Pronounced postprandial lipemia occurs after the absoprtion
of fat from diets with high fat contents. Postprandial lipoproteins
are known to be atherogenic. They are also thrombogenic
because postprandial lipemia increases activated factor VII, a
procoagulant. Pretreatment with fish oil greatly lessens postprandial
lipemia (17), and this effect should be considered both
anti-atherogenic and anti-thrombotic.
The emphasis on fish and fish oil for coronary prevention does
not mean that vegetarians could not benefit from the consumption
of n3 fatty acids. The precursor to EPA and DHA in the
n3 fatty acid synthetic pathway is -linolenic acid (18:3n3),
which is especially rich in certain vegetable oils such as canola,
soy, flaxseed, and walnut oils. In the Lyon Heart Study, which
emphasized linolenic acid consumption from canola margarine,
blood EPA concentrations increased and the death rate from
coronary artery disease was reduced by 70% with a concomitant
reduction in sudden death (18). A vegetarian diet, then, can still
benefit from an increased n3 fatty acid content.
In summary, n3 fatty acids from fish and fish oil are natural
food substances that prevent coronary artery disease and sudden
death. Physicians should become acquainted with the powerful
therapeutic potential of these fatty acids. n3 Fatty acids have
immense public health significance for the control of the current
coronary epidemic.
REFERENCES
1. Bang HO, Dyerberg J. The composition of food consumed by
Greenlandic Eskimos. Acta Med Scand 1973;200:69–73.
2. Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma
lipids in Greenland Eskimos. Am J Clin Nutr 1975;28:958–66.
3. Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated
fatty acids in Eskimos. Lancet 1979;2:433–5.
4. Dewailly E, Blanchet C, Lemieux S, et al. n3 Fatty acids and cardiovascular
disease risk factors among the Inuit of Nunavik. Am J
Clin Nutr 2001;74:464–73.
5. Connor WE. n3 Fatty acids and heart disease. In: Kritchevsky D,
Carroll KK, eds. Nutrition and disease update: heart disease. Champaign,
IL: American Oil Chemist’s Society, 1994:7–42.
6. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and
cell membrane levels of long-chain n3 polyunsaturated fatty acids
and the risk of primary cardiac arrest. JAMA 1995;274:1363–7.
7. Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption
and risk of sudden cardiac death. JAMA 1998;279:23–8.
8. Kromhout D, Bosschieter EB, Coulander C. The inverse relation
between fish consumption and 20-year mortality from coronary
heart disease. N Engl J Med 1985;312:1205–9.
9. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish,
and fibre intakes on death and myocardial reinfarction: diet and
reinfarction trial (DART). Lancet 1989;2:757–61.
10. GISSI Prevenzione Investigators. Dietary supplementation with n3
polyunsaturated fatty acids and vitamin E after myocardial infarction:
results of the GISSI-Prevenzione Trial. Lancet 1999;354:447–55.
11. Kang JX, Leaf A. Antiarrhythmic effects of polyunsaturated fatty
acids. Circulation 1996;94:1774–80.
12. Goodnight SH Jr, Harris WS, Connor WE. The effects of dietary
omega-3 fatty acids upon platelet composition and function in man:
a prospective, controlled study. Blood 1981;58:880–5.
13. Harker LA, Kelly AB, Hanson SR, et al. Interruption of vascular
thrombus formation and vascular lesion formation by dietary n3
fatty acids in fish oil in non human primates. Circulation 1993;87:
1017–29.
14. Davis HR, Bridenstine RT, Vesselinovitch D, Wissler RW. Fish oil
inhibits development of athersclerosis in rhesus monkeys. Arteriosclerosis
1987;7:441–9.
15. Nordoy A, Hatcher LF, Ullmann DL, Connor WE. Individual effects
of dietary saturated fatty acids and fish oil on plasma lipids and
lipoproteins in normal men. Am J Clin Nutr 1993;57:634–9.
16. Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR.
Reduction of plasma lipids, lipoproteins, and apoproteins by dietary
fish oils in patients with hypertriglyceridemia. N Engl J Med 1985;
312:1210–6.
17. Harris WS, Connor WE, Alam N, Illingworth DR. The reduction of
postprandial triglyceridemia in humans by dietary n3 fatty acids.
J Lipid Res 1988;29:1451–60.
18. De Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alphalinolenic
acid-rich diet in secondary prevention of coronary heart
disease. Lancet 1994;343:1454–9.
416 EDITORIAL
TABLE 1
Actions of n3 fatty acids to prevent coronary heart disease and sudden
death
1) Prevent cardiac arrhythmias (ventricular tachycardia and fibrillation)
2) Act as antithrombotic agents
3) Inhibit the growth of atherosclerotic plaques
4) Act as antiinflammatory agent (inhibit synthesis of cytokines and
mitogens)
5) Stimulate endothelial-derived nitric oxide
6) Lower plasma concentration of triacylglycerol and VLDL cholesterol
and increase plasma concentrations of HDL cholesterol
Downloaded from www.ajcn.org by on June 18, 2007

William E Connor

The steps in the development of important medical discoveries
rest first on intuition and then on associations of a certain
factor with a disease, followed by scientifically designed experiments.
The history of the importance of the n3 polyunsaturated
fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) illustrates this point beautifully. Early Arctic explorers
commented on the rarity of coronary artery disease in Eskimos
despite their consumption of a very-high-fat, high-cholesterol
diet. This finding was indeed a paradox until it was resolved
by 2 Danish scientists, Bang and Dyerberg (1). When these
investigators looked at the coronary mortality statistics in Greenland
Eskimos and in Danish persons living in Greenland but
having a vastly different lifestyle, they found few deaths from
coronary artery disease in Greenland Eskimos but many deaths in
Danes. The answer to this riddle came from an analysis of the diet
of the Eskimos compared with that of the Danes (1). The latter
group ate a diet high in saturated fat and cholesterol from meat
and dairy products similar to the diet eaten in the homeland of
Denmark. The Eskimos, on the other hand, ate seal, whale, and
fish, all of which are extremely rich in EPA and DHA. This was
in contrast with the lower n3 fatty acid content of the typical
Danish diet. In the Greenland Eskimos also, the content of these
same n3 fatty acids in the blood was high (2), and the tendency
of the blood to form thrombi was lessened because the n3 fatty
acids were taken up by the blood platelets (3).
The same situation prevails in present-day Eskimos, as illustrated
by the study by Dewailly et al (4) in this issue of the Journal.
The Nunavik Inuit of Quebec, despite some Westernization,
still partly consume the diet of their ancestors, which is rich in
fish and marine mammals. Mortality from coronary artery disease
in the Inuit is 50% less than that in the Quebec province as
a whole. The Inuit’s high blood content of EPA and DHA reflects
their consumption of these foods from the sea.
Why the n3 fatty acids from fish and marine oils prevent
coronary artery disease has now been delineated in hundreds of
experiments in animals and tissue culture cells and in population
and clinical trials (5). Of the nutritional modalities thought to
prevent heart disease, the evidence for the efficacy of n3 fatty
acids is strong. This evidence may be best summarized in Table 1
and by answering the following question: have other population
studies and clinical trials shown that fish consumption is associated
with a lowered incidence of coronary artery disease? Japanese,
Dutch, and US studies indicate that deaths from coronary
artery disease are reduced by ≥50% by the consumption of 1–2 fish
meals/wk (6–8). The most important finding is of a reduction in
sudden death from ventricular fibrillation and tachycardia. About
300 000 such deaths occur in the United States each year. Direct
clinical trials of fish and fish oil have also shown a striking
reduction in sudden deaths (9, 10); these findings have great public
health significance. Furthermore, animal studies and experiments
in isolated myocytes showed that ventricular arrhythmias
are inhibited by EPA, which affects sodium and calcium ion
channels in the heart (11).
Thrombosis is a major complication of coronary atherosclerosis
and leads to myocardial infarction. The n3 fatty acids from
fish oil have powerful antithrombotic actions. EPA inhibits the
synthesis of thromboxane A2 from arachidonic acid in platelets.
Thromboxane A2 causes platelet aggregation and vasoconstriction.
By blocking thromboxane A2 synthesis, fish oil ingestion by
humans increases the bleeding time and decreases the number of
platelets that stick to glass beads (12). In addition, administration
of fish oil enhances the production of prostacyclin, a
prostaglandin that produces vasodilation and less sticky platelets.
In an in vivo baboon model, dietary fish oil prevented platelet
deposition in a plastic vascular shunt (13). Injury to the intima of
the carotid artery of the baboon invariably caused a marked proliferative
and inflammatory lesion, greatly thickening the wall.
When the animals were fed fish oil, this damage and intimal
thickening were completely blocked.
The EPA and DHA contained in fish oil inhibit the development
of atherosclerosis. There is evidence in both pigs and monkeys that
dietary fish oil prevents atherosclerosis by actions other than the
lowering of plasma cholesterol concentrations (14). These actions
may be associated with the inhibition of monocyte migration into
the plaque, with less cytokine and interleukin 1 production, and
with stimulation of the endothelial production of nitric oxide.
Dyerberg and Bang also found that the blood of Greenland
Eskimos had lower triacylglycerol and cholesterol concentrations,
particularly triacylglycerol, than the blood of Danes (2).
Dewailly et at (4) found that n3 fatty acids in the plasma
phospholipids of Nunavik Inuit were positively associated with
HDL-cholesterol concentrations and inversely associated with

Am J Clin Nutr 2001;74:415–6. Printed in USA. © 2001 American Society for Clinical Nutrition

Submitted on November 3, 2006
Accepted on April 9, 2007
Small or Large Isolation Areas Around the Pulmonary Veins for the Treatment of Atrial Fibrillation? Results From a Prospective Randomized Study
Thomas Arentz MD*, Reinhold Weber MD, Gerd Bürkle MD, Claudia Herrera MD, Thomas Blum MD, Jochem Stockinger MD, Jan Minners MD, PhD, Franz Josef Neumann MD, and Dietrich Kalusche MD

From Herz-Zentrum, Bad Krozingen, Germany.

* To whom correspondence should be addressed. E-mail: thomas.arentz@herzzentrum.de.

Background--Pulmonary vein (PV) isolation is a promising new treatment for atrial fibrillation (AF). We hypothesized that isolation of large areas around both ipsilateral PVs with verification of conduction block is more effective than the isolation of each individual PV.

Methods and Results--A total of 110 patients, 67 with paroxysmal AF and 43 with persistent AF, were randomly assigned to undergo either isolation of each individual PV or isolation of large areas around both ipsilateral PVs. The isolation of each individual PV was an electrophysiologically guided, ostial segmental ablation with a 64-pole basket catheter or a 20-pole circular mapping catheter (group I). Isolation of large areas was performed around the 2 ipsilateral veins with a nonfluoroscopic navigation system and a circular 20-pole mapping catheter for verification of conduction block (group II). In both groups, an irrigated-tip ablation catheter (25 to 35 W) was used to achieve complete isolation. Procedure and ablation times were longer in group II, whereas fluoroscopic time was significantly shorter (P≤0.001). After a follow-up period of 15±4 months, 27 patients in group I (49%) and 37 patients in group II (67%) remained free of symptoms of AF and had no AF or atrial flutter during repetitive Holter monitoring without antiarrhythmic drug treatment after a single procedure (P≤0.05).

Conclusions--The rate of success was significantly higher and fluoroscopy times were significantly lower in the group with large isolation areas around both ipsilateral PVs than in those who underwent individual PV isolation.


Key words: arrhythmia • mapping • catheter ablation • fibrillation • tachyarrhythmias






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juli 2004

Hooked On The Cash From Cholesterol
Statins are massive moneyspinners. But can Big Pharma sidestep expiring patents?

There's no overstating the importance of cholesterol-lowering drugs to the pharmaceutical industry. They bring in $20 billion a year in sales, the single biggest market in the $492 billion global prescription-drug business. Sales are growing at a healthy 15% clip. And with the government releasing new recommendations on July 12 encouraging doctors to drop targets for LDL -- or so-called bad cholesterol -- even lower for patients at high risk for heart attacks, sales are likely to shoot ahead even faster.

Statins ‘well tolerated’ by most patients

8 June 2007

MedWire News: Statins are well tolerated in the majority of patients, according to a comprehensive review of their safety published in The Lancet.

The main adverse effects of statins on muscle – rhabdomyolysis and myopathy – are rare at standard doses and those on the liver are “unusual,” writes the review’s author Jane Armitage (University of Oxford, UK).

“For most people, statins are safe and well-tolerated, and their widespread use has the potential to have a major effect on the global burden of cardiovascular disease,” she concludes.

Armitage reports that collective results from large randomized controlled trials of statin therapy show that maintaining low cholesterol for at least 5 years is “not only safe but beneficial.”

Neither overall, nor in any individual trial, was there an increase in non-vascular deaths suggested by observational data, she writes.

Furthermore, a meta-analysis of 14 controlled statin trials including more than 90,000 patients revealed similar rates of non-vascular deaths in statin-treated versus control-treated patients (3.8% vs 4.0%). This applied both overall and for specific types of non-vascular death such as cancer, hepatic, or respiratory disease.

Three trials of standard-doses of statins (producing 30-45% reduction in LDL-cholesterol) with more extended follow-up have provided reassuring long-term safety information. Meanwhile trials so far of more intensive statin therapy have shown no adverse effect associated with sustained substantial reductions in LDL-cholesterol to below 2.0 mmol/l (77 mg/dl).

Armitage finds that all statins occasionally cause myopathy that can progress to rhabdomyolysis but says it is rare with standard doses, and, although it seems to increase with higher doses, remains very low with atorvastatin 80 mg.

She adds that both myopathy and rhabdomyolysis are usually reported in association with concomitant use of interacting drugs, especially fibrates.

Data from randomized trials do not indicate that statins are hepatoxic, and it is not clear whether cases of hepatitis and liver failure reported simultaneously with staitns are causally related or whether the risk is higher than background risk of sporadic liver failure.

Furthermore, the review indicates that only minor and non-significant numbers of patients with raised liver enzymes – specifically alanine or aspartate transaminases – have been reported in large randomized trials. These increases in transaminase are reversible with dose reduction, usually occurring in the first few months of randomization, and there is no convincing evidence that they are associated with liver damage.

In contrast to myopathy, the increased likelihood of raised transaminases with increasing doses of statin could be tied to the degree of cholesterol lowering, Armitage notes.

“With a few caveats, and while awaiting good-quality randomized data for the newer drugs, statins seem to be a remarkably safe group of drugs when used at their usual doses,” she concludes.

Lancet 2007; Advance online publication



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Meta-Analysis Suggests Folic Acid Reduces Risk for Initial Stroke

Marlene Busko

Medscape Medical News 2007. © 2007 Medscape

June 1, 2007 — A meta-analysis of 8 randomized controlled trials reports that, overall, folic-acid supplementation reduced the risk for a first stroke by 18%. The stroke risk reduction was approximately 25% in subgroups who received supplements for more than 3 years, had blood homocysteine levels that decreased by 20% or more, or lived in regions with no folate grain fortification. There was no significant risk reduction in the corresponding subgroups without these characteristics.

The findings are published in the June 2 issue of the Lancet.

Lead author Xiaobin Wang, MD, from Northwestern University Feinberg School of Medicine, in Chicago, Illinois, told Medscape that as the controversy over folic-acid supplementation in the prevention of cardiovascular disease (CVD) continues to evolve, the group feels that it is important to identify whether a targeted group of individuals might benefit from this "relatively simple, safe intervention." She added: "Our analysis showed that folic-acid supplementation can lower stroke risk. . . . I think we have pretty coherent evidence. We also further demonstrated that certain populations would benefit even more from folic-acid supplementation."

Focus on Stroke

The use of folic-acid supplements to reduce cardiovascular risk remains controversial, the group writes. "The controversy stems from the fact that the efficacy of homocysteine-lowering therapy to reduce cardiovascular risk hasn't been confirmed by randomized trials," said Dr. Wang.

She added that several observations and studies led the group — with researchers in Chicago and China — to investigate whether stroke may be the disease end point that could particularly benefit from folic-acid supplementation.

First, compared with the United States, in China, the incidence of stroke is 3 to 5 times higher, and average blood folic-acid levels are lower and homocysteine levels are higher. Second, an "intriguing" trial in China showed that supplementation with folate and other vitamins and minerals reduced mortality from cerebrovascular disease by 37% (Mark SD et al. Am J Epidemiol. 1996;143:658-664). Third, although the second Heart Outcomes Prevention Evaluation (HOPE-2) study was negative for other cardiovascular end points, it found that folic-acid supplementation reduced stroke risk by 24% (Lonn E et al. N Engl J Med. 2006;354:1567-1577). Finally, a recent study reported that after the 1998 fortification of grain with folic acid in the United States and Canada, the decline in stroke mortality accelerated in the 1998–2002 period (Yang Q et al. Circulation. 2006;113:1335-1343).

The team searched the literature to April 2007, and 8 randomized controlled trials, consisting of 16,841 individuals, met their criteria. In 7 of the 8 trials, patients had no previous stroke.

Pooling the data from the 8 trials, they found that, overall, folate supplements reduced the risk of stroke by 18%, and this vitamin had an even greater effect in certain subgroups.

Relative Risk of Stroke, Subjects Receiving Folic Acid vs Control Subjects
Subgroup*/All Subjects

Relative Risk (95% CI)

P
> 36 months of supplementation

0.71 (0.57 – 0.87)

.001
> 20% homocysteine lowering

0.77 (0.63 – 0.94)

.012
No folic-acid grain fortification

0.75 (0.62 – 0.91)

.003
No history of stroke

0.75 (0.62 – 0.90)

.002
All subjects

0.82 (0.68 – 1.00)

.045
*In the 4 corresponding subgroups (eg, < 36 months supplementation, etc), the relative risk for stroke did not decrease significantly.

More Folate Study Needed

The group writes that the different observations seen with stroke vs CVD might be because stroke is associated with small blood vessel pathology whereas CVD tends to involve larger blood vessels.

Dr. Wang noted that this meta-analysis was not able to determine what dosage of folic acid is best or whether it should be given alone or in combination with 1 of the B vitamins. She added that more studies are needed to establish this and to determine the efficacy and causality of folic-acid supplementation. The trials should be 4 years or longer in populations who have not had strokes and live in regions without fortified grain.

Editorial: "Widespread Use Still Not Recommended"

In an accompanying editorial, Cynthia M. Carlsson, MD, from the University of Wisconsin School of Medicine and Public Health, in Madison, cautions that "although this meta-analysis helps clarify answers to some questions about the role of homocysteine-lowering in CVD prevention, ongoing randomized trials are needed before we can conclude that the benefit of continued use of previously deemed 'safe' vitamin supplements outweighs the risk of other adverse CVD outcomes." She notes that several large randomized trials have shown that lowering homocysteine with folic acid does not improve CVD outcomes, and when it is combined with B vitamins, it may accelerate CVD risk.

She told Medscape: "While [this meta-analysis] raises the question of whether there are certain subgroups of people who would benefit from folic-acid therapy, it still remains controversial, because large clinical trials have shown negative effects of the vitamin. . . . Widespread use is still not recommended for primary stroke prevention because of its possible adverse effects on heart disease outcomes."

She added that it is hoped that the large randomized trials that are still under way will answer some of those questions, "to help us understand which patient who walks in through our clinic door should be treated with folic acid."

Author: "Folate Supplementation Alone Is Not Harmful"

Dr. Wang noted: "Although we didn’t focus on CVD, and we do want to caution others not to generalize our findings to CVD, for stroke, [folic acid] is definitely beneficial, and we don’t believe folate supplementation alone [without the 2 B vitamins] is harmful even among subjects with CVD." She pointed out that the meta-analysis by Bazzano et al (Bazzano LA et al. JAMA. 2006;296:2720-2226), which analyzed 12 randomized trials, did not demonstrate any combined harmful (or beneficial) effect on cardiovascular outcomes. The 2 studies that reported increased cardiovascular risk showed this only in the groups that took all 3 supplements (folate and high doses of vitamins B6 and B12), as Dr. Wang and colleagues noted in an earlier commentary (Wang X et al. N Engl J Med 2006;355:207-209).

She added that they acknowledge that the current analysis is limited by the existing data. "That's why we concluded only that folic acid can reduce the risk of stroke in primary prevention. For primary prevention, we have 7 trials, so we have a good amount of data to pull together to come up with convincing evidence."

Lancet. 2007;369:1876-1882, 1841-1842.