ErinPharm Gazette April 2008
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Erinpharm celebrates the birthday and life of Edna Parker, who reached the age of 115 years on April 20, 2008. She is still in good health. As a supercentenarian Edna reached her first century of age as modern genome based investigation of longevity began to come of age. Edna Parker, born April 20, 1893
This month is notable for the media attention around the issues of lowering LDL-cholesterol and quenching of the inflammation that causes atherosclerotic plaque rupture. The importance of a sufficient amount of supplemental Vitamin D3 to maintain circulating plasma levels appropriate for protection against various kinds of cancer has been placed on a firmer foundation while use of Vitamin D3 in infants to reduce the incidence of juvenile diabetes is under investigation. Interventional Radiology gains more attention and shows great future promise in minimally invasive techniques with remarkable success treating lung cancer and kidney cancers.
A review of April 2008. A selection of topics.
This web page is one of a number of ErinPharm web pages designed by me as a synopsis of topics that interest me as well as being a quick reference page for my newsletter subscribers and myself. I have no affiliation of any kind to any pharmaceutical company or medical group. The opinions expressed are my own. I welcome communication and debate. I am an optimist. I look forward to the future with wonder.
The Life Extension Foundation
Keep up to date with advances in the prevention, diagnosis, and treatment of colorectal cancer.
Know about the latest treatment guidelines for addiction.
Patients should know everything there is to know about Gastro-esophageal Reflux Disease (GERD)
Advances in lung cancer therapies are moving ahead. Keep up to date.
University of Kansas research scientist, Dr. Ann Manzardo, is exploring the link between thiamine deficiency and a genetic predisposition to alcoholism.
The first comprehensive map of Genomic copy number variations has been developed. Such copy numbers influence genetic diversity and susceptibility to disease.
The American Cancer Society is your main source of information in the ongoing battle against cancer.
Are you trying to lose weight and have been misled by the multi-billion dollar industry selling pills, potions, and 'magic cures'? You are not alone. A survey backed by a commercial drug company reports that approximately 70% of American dieters have tried scientifically unproven methods to lose weight. That's an astounding number of people who have tried dietary supplements in the form of pills and powders. About half of survey respondents incorrectly think supplements are approved by the federal Food and Drug Administration, while about two-thirds believe such products must carry warning labels for side effects. All that happens is maybe temporary loss of weight and the emptying of your pocket. Resist the temptation to believe in those seductive commercials. The only way you can lose weight and keep it off is by a commitment to a change in lifestyle. I recommend lifestyle changes.
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Keep up to date with advances in the use of statins.
Report Adverse Drug Events. Help facilitate drug safety.
Have you done an act of kindness today? Have you sent 1.1 cups of food to an impoverished hungry person in the underdeveloped world just by clicking this link: http://www.thehungersite.com ? Sponsors will pay the cost. All you do is click and acknowledge you have visited the page. You can do it every day. As an introduction to the high quality of Life Extension Foundation vitamins and supplements readers of Erinpharm web pages can buy Coenzyme Q10 Ubiquinol, Omega-3 EPA/DHA fish oils, Vitamin D3, Folic Acid with Vitamin B12, Gamma E Tocopherol, Super Booster with Advanced K2 complex, and Super K with advanced K2 complex directly from Erinpharm as a low price single item: click here.
It is entirely appropriate that a storm of media attention reaching to Congressional committees should occur when a marketed pharmaceutical goes from 0.2% of prescriptions in 2002 to 15.2% of prescriptions in 2006 and then clinical trial data shows no benefit and accusations of marketing a useless drug arise, reviving thoughts among some of 'snake oil' and suspicions of others toward the entire pharmaceutical industry. The issue here, of course, is Vytorin and the results of the ENHANCE trial. Now the storm is subsiding and calmer more rational debate is coming to the fore it is instructive to examine the facts of this trial and to recognise that this is not the first, and likely will not be the last, setback on the road toward an efficient method of reversing accretion of arterial plaque. That it has reached the stage of national attention is good. The general population is now alert to the objectives of modulating lipid levels to cause regression of arterial plaque. Advances and setbacks in the next few years will now receive more scrutiny as well as arousing recognition that research pharmaceutical companies and medical research professionals are intent upon eliminating the causes of heart attack and stroke. It would be invidious to think otherwise. The trial, ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia), led by Dr. John Kastelein of the Academic Medical Center, Amsterdam, the Netherlands, showed that Vytorin (Ezetimibe/Simvastatin ie Zetia/Zocor:Vytorin) has no additional benefit over Simvastatin (Zocor) alone in reducing carotid artery plaque. Carotid artery plaque directly relates to coronary artery disease risk. The Ezetimibe component of this Vytorin drug combination is not a statin: it is a bile sequestering agent. That Zocor is available as a generic and thus much less expensive than Vytorin is not an inconsequential factor of note. The ability of statins in general to stop or even reverse plaque accretion when plasma LDL-cholesterol is lowered below 70 mg/dL is not in doubt. As Dr. Steve Nissen, a leader in atherosclerotic reversal studies, points out: "when you have no evidence of clinical benefit....what do you do in the meantime?" Practically speaking it should not be suprising in retrospect that the significant lowering of LDL-cholesterol and C-reactive protein observed in the trial did not lead to an effect on the progression of carotid artery plaque. This very large and expensive study enrolled patients (363) with an average LDL-cholesterol of 317.8 mg/dL and reduced it to 192.7 mg/dL over 24 months. Readers of Erinpharm web pages will recognise that these LDL-cholesterol numbers as way above the level needed to cause arterial plaque regression. So basically what it all comes down to is succinctly expressed by Dr. Steve Nissen: "statins first, statins second, and statins third". And, of course, as Erinpharm readers are fully aware: regular daily exercise, good nutrition, no smoking, very moderate alcohol, pomegranate or other high anti-oxidant fruit juice, an anti-oxidant regimen, and following medical progress toward raising HDL-cholesterol levels substantially, with Merck's CETP inhibitor anacetrapib the favorite candidate so far. Schering-Plough and Merck stock have taken a hit with this news; Pfizer's also did when the torcetrapib trials were terminated. That cost Pfizer almost a billion dollars. Yes, clinical research is expensive. There will be setbacks as well as advances. But it will not stop our leading research pharmaceutical companies and leading medical researchers to lose sight of the ultimate objective - the elimination of heart attack and stroke.
As the Vytorin debacle became a major news item, little attention has been paid to a logical reason why a bile sequestering agent (Ezetimibe/Zetia) should not be expected to reduce heart attack risk nor arterial plaque at the level of LDL-cholesterol values for the patients entered in that trial. Although reduction of LDL-cholesterol levels is indeed important it does not have a clinically important result until LDL-cholesterol levels fall below 70 mg/dL as was shown in the dramatic data on the aggressive dosing of Lipitor announced in late 2004. In those trials it was shown that lowering LDL-cholesterol below 70 mg/dL resulted in the halting or even reversal of arterial plaque progression. In trials since that time it has been shown that 'lower is better' and as yet it is not known how low LDL-cholesterol levels can be taken safely to increase the rate of plaque regression. The other important and suprising result of those pivotal trials was that aggressive dosing of Lipitor resulted in a major anti-inflammatory effect as measured by reduction of C-reactive protein levels. This additional effect has received less attention than it should despite an announcement March 31, 2008 by Astra-Zeneca that Crestor in its latest statin trial shows a major advance in reducing heart attack. In that 15,000 patient trial, halted early because reduction of heart attack significantly exceeded the protocol objectives, the entrance criteria included the provision that patients have a high C-reactive protein level. Thus it is proven that evidence indicating plaque rupture (due to inflammation) and not plaque severity is the causative factor in heart attack (and most likely stroke). Thus for those intent on avoiding heart attack and stroke the objectives should be two-fold: to lower LDL-cholesterol below 70 mg/dL and to lower C-reactive protein below 0.10 mg/L. The first will cause plaque aggregation to go into reversal and the second will create a quenching of inflammation making plaque rupture unlikely. Thus a person taking a statin for LDL-cholesterol reduction, and taking Coenzyme Q10 (Ubiquinol) to offset the statin's known reduction of the person's endogenous production of Coenzyme Q10, should next focus on bringing C-reactive protein levels down to the safe level of less than 0.10 mg/dL. C-reactive protein levels are a biomarker for inflammation and can be high without outward evidence of a clinical problem. C-reactive protein levels can also fluctuate markedly with the condition of a person's generalized inflammation. Thus a person, and his/her physician, must carefully find the reason for, and treatment of, that inflammation. In the absence of overt infection or illness it could be as simple as gum inflammation, helicobacter pylori infection or other sub-clinical condition. Quenching inflammation can be done with a number of different approaches including, but not restricted to, low dose aspirin, low dose statin, and gram quantities of omega-3 fish oils (EPA/DHA). This two-pronged approach, though known by medical professionals, does not receive anywhere near the attention it should. This trial, the Jupiter trial, should receive widespread attention. Dr. Paul Ridker, Director of the Center for Cardiovascular Disease Prevention at Brigham & Women's Hospital and AstraZeneca Chief Executive David Brennan are to be commended for their commitment to running this trial.
Of course, as Erinpharm readers know well, inducing plaque regression by lowering LDL-cholesterol below 70 mg/dL is just one factor in modulating the 'reverse cholesterol transport system'. The next step is to find a molecule that will safely raise HDL-cholesterol levels by a substantial amount. The major research pharmaceutical companies are vigorously competing to be the first to bring such a molecule to market with CETP inhibitors the leading focus of attention. Merck's anacetrapib is probabably the furthest advanced in research. Erinpharm is following the research with an RSS feed for anacetrapib. Maybe you would like to do the same?
Omega-3 fish oils are excellent for quenching inflammation as well as having many other benefits. Scientists have identified a number of dietary supplements and prescription drugs that can reduce levels of the pro-inflammatory cytokines. The docosahexaenoic acid (DHA) fraction of fish oil is the best documented supplement to suppress TNF-a, IL-6, IL-1(b), and IL-8 (Jeyarajah et al. 1999; James et al. 2000; Watanabe et al. 2000; Yano et al. 2000). A study on healthy humans and those with rheumatoid disease shows that fish oil suppresses these dangerous cytokines by up to 90% (James et al. 2000).
Quenching Inflammation: A full perspective and review of inflammation and guide to lowering C-reactive protein levels .
There is more evidence that higher plasma levels of Vitamin D3 have a strong protective effect against various kinds of cancers; sufficient evidence that Dr. Michael Holick, of Boston University Center, supports raising the recommended amount of the vitamin to 1,000 IU. As reported by the Seattle Times, a study published by researchers at Creighton University in Omaha focused on 1,179 healthy women with an average age of 67 to examine the effects of calcium ion and Vitamin D3 (1,000 IU) supplements daily in order to study bone health over four years. Although monitoring cancer incidence was secondary the reduction of cancer risk by up to 77% in this group was remarkable.
Building on prior evidence that Finnish babies born in the 1960s and raised on mega doses of Vitamin D had dramatically lower risk of developing type 1 diabetes as well as the report from British researchers last month that a collective analysis of previous studies showed that children taking Vitamin D from infancy reduced their risk of type 1 diabetes by up to one third with the greatest benefits to infants taking 2,000 IU, which is 10 times the current US daily recommendation, researchers at the Pacific Northwest Diabetes Initiative (PDRI) are tracking children at high risk to get more rigorous proof of this benefit of Vitamin D3. A 2001 review of 31 years of medical records for more than 10,000 Finnish babies born during 1966 showed that those babies who took less than Finland's recommended dose of 2,000 IU at that time later developed type 1 diabetes five times more often than those who took the full dose. Though studies of these benefits will extend up into the participants
teenage years the evidence already seems very clear... a minimum of 1,000 IU daily of Vitamin D3 is a reasonable objective for many people.
The Society of Interventional Radiology held its 33rd Annual Scientific Meeting March 15-20, 2008. As this discipline grows with the number of Interventional Radiologists becoming Board certified it is clear that minimally invasive percutaneous treatment for various disorders formerly subject to more invasive surgical options is becoming a preferred option for many patients. The development of sophisticated technology is opening the ability to perform wonders. Radiofrequency ablation of small lung tumors offers patients who are ineligible for surgery a chance for a curative treatment.
Dr. Thierry de Baere, from the Institut Gustave Roussy in Villejuif, France, reported a success rate of more than 90% for tumors up to 3.5 cm, lower when tumors were larger, for 244 patients who underwent radiofrequency ablation (RFA) for either lung metastases or primary non-small-cell lung cancer. He reported a follow-up where 70% of the patients were still alive after 2 years. Since such patients usually have less than 12 months to live this is a significant advance. Among the 49 patients with tumors less than 4 cm diagnosed as primary non-small-cell lung cancers RFA treatment resulted in no viable lung tumor for 85% at one year and 77% at two years.
Dramatic success has been reported in a minimally invasive cryoablation technique for small kidney tumors. Dr. Christos Georgiades, of Johns Hopkins University in Baltimore, Maryland, presented data on 60 patients with primary renal cell carcinoma with 70 lesions treated with cryoablation and reported a success rate of 95% for tumors that were 4 cm or smaller and nearly 90% for tumors up to 7 cm. Dr. Hussein Aoun and Dr. Peter Littrup, from Wayne State University in Detroit, Michigan, presented data on 100 tumors in 90 patients, mean tumor size 3.1 cm (range 1.2 - 7.6 cm), and reported a success rate of 94% after a follow-up of about 16 months. Now that technology has led to small probes suitable for a percutaneous procedure coupled to imaging sophisticated enough for probe placement and monitoring there should be growth in this minimally invasive procedure. It is not yet standard of care but with more studies it has the potential to become a gold standard.
Several imaging techniques are used for the optimal management of patients with cardiovascular disease and the recent introduction of multi-slice computed tomography (MSCT) for coronary artery evaluation has raised issues of radiation doses associated with MSCT and other currently available cardiovascular imaging techniques. This review gives a perspective on radiation dosage for physicians and patients alike.
Clinical trials for cancer therapies are showing good success rates, ranging from 25% to 50%. This interesting article describes a review of 624 trials involving 216,451 patients conducted by Dr. Benjamin Djulbegovic and colleagues at the H. Lee Moffitt Cancer Center in Tampa, Florida, and they are to be commended for this perspective.
Debate has begun on the utility of beta-blockers, the most prescribed drugs for hypertension in the United States, drugs promoted by international and national guidelines. Since nearly one billion people worldwide have hypertension, reports over the last few years suggest that patients with uncomplicated hypertension are at a greater risk of stroke when treated with beta-blocker monotherapy are troubling. These drugs have been prescribed for three decades and yet one large meta-analysis from 1998 demonstrated that lowering blood pressure with a beta-blocker was not effective in preventing coronary artery disease, cardiovascular events, and all-cause mortality.
America is preparing to build on past efforts to involve itself in expanded investments aimed at improving the health status of the populations of impoverished nations. This video editorial, by Dr. Roger Bulger, former President of the Association of Academic Health Centers, suggests means to properly develop co-ordinated plans and strategies to implement this mission.
The Ashville Project does show that a co-ordinated, well organized, community based program to reduce blood pressure values in a population will result in an impressive reduction in cardiovascular events.
New technology is making it possible to sequence an individual's entire genome in two months at a cost of less than $1 million. How long now to Craig Venter's aim of the $1,000 genome?
In a chilling and provocative essay by Kevin Sack published by the New York Times we get details of a most unusual trend for an industrialised country: that some of our communities are experiencing a decline in life expectancy against a backdrop of rising life expectancy for the nation as a whole. That socioeconomic status is a predominant factor is indisputable, that lack of access to quality medical care is a contributing factor is clear, and that a profound lack of awareness by many disadvantaged of the advances in preventative and early detection options for disease gives us a reason for serious concern as well as a window into the future. As options for healthy longevity become more available in the decades to come will the young of coming generations have the will and the drive to generate societal programs to combat such inequalities, not only nationally but on a global scale? To not do so is a horror to contemplate.