Jul
01
2006

Better Blood Pressure Control With New Drug

Numerous medications for blood pressure control are in circulation. Treatment of high blood pressure patients is crucial in the prevention of strokes, but despite the multitude of drugs that are on the market, the treatment has its challenges. Some of the drugs have side effects, like an irritating cough, and a suitable medication has to be tried out first. Even, when all is well and there are no unpleasant side effects, many patients have a problem with compliance. Pills that have to be taken several times per day are forgotten. As a result, the patient will have poor blood pressure control.
Blood pressures must be controlled on an ongoing basis. Ideally there are no big fluctuations, whether it is day or night. For this purpose, a medication has to stay in the system of the patient long enough. This time stretch is called the half-life of a drug.
The first drug in a new class of agents for the treatment of high blood pressure does exactly that: it has a long half-life, so blood pressure control is smooth and continuous, day or night. The oral direct renin inhibitor aliskiren has the potential to protect the heart and other organs with a once-daily dosage of 150 mg or 300 mg. The drug is being developed by Novartis, and clinical trials are on their way.
The medication in combination with a diuretic provides significant additional blood pressure reduction. The agent at work is a renin inhibitor (also known medically as “renin antagonist” as it blocks the effects of renin). In the past, renin inhibitors for treatment of hypertension (high blood pressure) could only be used as intravenous solution and this was only effective for a short time.

Better Blood Pressure Control With New Drug

Better Blood Pressure Control With New Drug

The new development is a breakthrough, as the medication is taken by mouth and it continues to work even when the drug is gone from the blood stream. It is ideal for daily dosing, and there is no apparent buildup in the body.

More information about hypertension (high blood pressure): http://nethealthbook.com/cardiovascular-disease/high-blood-pressure-hypertension/

Reference: The Medical Post, June 13, 2006, page 38

Comment on Nov. 13, 2012: Aliskiren  (brand name “Tekturna”) was approved by the FDA in March of 2007. However, as all drugs, it does have some side-effects like headaches, cough, angioedema, skin rash, elevated uric acid with gout etc. (see this Wikipedia link).

Last edited Nov. 1, 2014

May
01
2005

Burgers, Fries and High Healthcare Costs

“Everything in moderation” and “A little bit cannot harm” are the deceptively soothing terms that can lull consumers into the belief, that fast foods cannot be so bad after all. A study, called the” Coronary Artery Risk Development in Young Adults” however gives us the facts, that paint a more realistic picture: the “little bit” actually has fairly serious consequences!
In this U.S. study a wide cross section of young adults were followed in four U.S centers: Birmingham, Ala., Chicago, Minneapolis and Oakland Calif. 3031 people in the age of 18 to 30 years were recruited in 1985 and followed until 2001.

Lifestyle habits, such as smoking, watching TV and intake of other foods were recorded, and insulin resistance was measured. In addition there were detailed studies of weight, height, waist size and other body measurements. Some interesting facts emerged: women ate fast foods less frequently than men. Fast food intake was associated with lower education, more TV watching, lower physical activity, high intake of trans fats and alcohol intake. In short: fast foods and other unhealthy lifestyle choices were correlated.

Dr. Mark Pereira, PhD of the University of Minnesota School of Public Health, who is one of the authors of the study, points out that it is extremely difficult to eat in a healthy way in a fast foods restaurant. The menus still include foods high in fat, sugar and calories and low in fiber and nutrients. Dr. Arne Astrup from the RVA University in Copenhagen found the same issues: besides the fact that serving sizes have increased two to five fold over the past fifty years, the energy density is twice as high in fast foods as compared to food in healthy diets. Dr. Astrup also points out in his publication, that humans have only a weak innate ability to recognize foods with high energy density and then down-regulate the amount eaten to meet and not exceed energy requirements.

Burgers, Fries and High Healthcare Costs

Burgers, Fries and High Healthcare Costs

If a person ate more than 2 fast food meals per week, which would be a modest increase of the control group that ate less than 1 fast food meal per week, the 2 meals per week group was about 5 kg heavier after 15 years, as opposed to 11 kg in the control group. The insulin resistance increased by an alarming 230 %. This finding is of significance, as insulin resistance (=metabolic syndrome) promotes the occurrence of cardiovascular disease and cancer, especially breast and colorectal cancers. The data are showing that even a modest increase has a unique effect in increasing the risks for these disease patterns, and the message is, that health care costs will only come down, if the root cause of disease is attacked at the societal and lifestyle level.

More information about the metabolic syndrome (insulin resistance): http://nethealthbook.com/hormones/metabolic-syndrome/

Reference: The Medical Post, March 8, 2005, page 20

Last edited October 28, 2014

Oct
01
2004

What Went Wrong With VIOXX

Merck &. Co., Inc. announced on Sept. 30, 2004 that VIOXX® (rofecoxib), an arthritis and acute pain medication, would be withdrawn voluntarily worldwide. VIOXX was FDA approved as a new anti-inflammatory drug for osteoarthritis in 1999. Later it was also cleared for rheumatoid arthritis. As a Cox-2 inhibitor it was different from aspirin and the conventional anti-inflammatory drugs such as Naproxen, Motrin or Voltaren.

In a study called VIGOR , which is detailed more under this link, VIOXX was compared to Naproxen in terms of gastrointestinal side-effects. It was found that the risks of bleeding ulcers, perforation and bowel obstruction were 50% reduced (frequency of cases with naproxen 1.22% versus VIOXX with a frequency of 0.52%). Surprisingly, in this study of 4000 patients over 1 year the cardiovascular risks such as heart attacks, strokes, blood clots for VIOXX was 1.8%, 3-fold higher than Naproxen, which had only 0.6% such complications. In addition it was noted that high blood pressure was more common in rheumatoid patients. The FDA made Merck add a warning on the drug label regarding these added risks, but this went more or less unnoticed by the public.

It has been known for some time that aspirin (ASA) has polyp preventative action on the colon and thus reduces the risk of colon cancer. A specific study, called APPROVe (Adenomatous Polyp Prevention on VIOXX) trial, was designed to show that VIOXX could do the same as aspirin, but with less toxic side effects. In 2000 Merck started enrolling patients into this 3 year long trial.

What Went Wrong With VIOXX

What Went Wrong With VIOXX

After 18 months into the trial cardiovascular side-effects started to show up that were statistically significant when compared to controls. This is what prompted the recent press release that VIOXX would be taken off the market altogether.

More info on treatment of osteoarthritis: http://nethealthbook.com/arthritis/osteoarthritis/treatment-osteoarthritis/

Comments: One of the potential problems with receptor specific medications is that they can be so specific that the metabolism in the human body is changed. What’s good for the gut may not be good for the circulation, blood pressure and the heart. Merck did the right thing to withraw the medication altogether. It is not known at this time whether other similar medications such as Celebrex, which has a different molecular configuration, will stand up in the future to post-marketing testing.

Addendum on Nov. 6, 2012: In 2005 Bextra was also taken off the market by the FDA, but Celebrex was allowed to stay, but required to label their product with warnings about potentially serious side-effects.

Last edited October 27, 2014

Aug
01
2004

Uric Acid Blood Test Predicts Future Health Problems

A 12 year prospective, well controlled follow-up study from Finland determined that uric acid blood tests are not only useful in following patients with gout or kidney stones, but are also predictive for future health problems including death. Dr. Leo K. Niskanen from Kuopio University in Finland and colleagues followed 1,423 middle-aged Finnish men who at the beginning of the study were free from cancer, heart disease, strokes and diabetes. After about 12 years the researchers found that 157 men had died, 55 from heart disease or strokes. When men with elevated uric acid levels were classified into low, medium and high levels, an interesting observation was made when subclasses were compared with each other. Those men in the upper range of uric acid levels had a risk of more than 2.5-fold to die from a heart attack or stroke when compared to men with uric acid levels in the lower range. Also, men in the higher range were 1.7-fold more at risk to die from any cause than men in the lower range of uric acid levels.

Dr. Niskanen said that uric acid simply seems to be another good marker for spotting troubles in health. The mechanism of this connection is not known at this point in time, but the test is easy to do and is very useful in screening a middle aged population.

Risk of Developing a Heart Attack or Stroke with Elevated Uric Acid Blood Test

Uric Acid Blood Test Predicts Future Health Problems1

Uric Acid Blood Test Predicts Future Health Problems

 

 

 

 

 

 

 

 

 

Other investigators in the past have also observed a similar association, but this seems to be the first longterm and prospective study.

More info on:

1.heart attacks: http://nethealthbook.com/cardiovascular-disease/heart-disease/heart-attack-myocardial-infarction-or-mi/

2. strokes: http://nethealthbook.com/cardiovascular-disease/stroke-and-brain-aneurysm/

3. Gout: http://nethealthbook.com/arthritis/gout/

Reference: Arch Intern Med 2004;164:1546-1551

Last edited October 26, 2014

Aug
01
2004

Birth Control Pill Increases Strokes And Heart Attacks

At the recent 86th Annual Meeting of the Endocrine Society in New Orleans/Louisiana a Canadian delegation presented data from a meta-analysis of 14 trials regarding side effects of the birth control pill (BCP) when taken on a prolonged basis. The researchers were interested to know the risk of heart attacks or strokes that would be associated with the prolonged use of the low dose estrogen BCP. All of the studies between 1980 and October of 2002 were examined and 14 independent studies qualified for the meta-analysis. The strength of such a meta-analysis lies in the pooling of data and the fact that the data is derived from a much larger patient population, which generally makes the results more reliable. Dr. J. Baillargeon from the Centre Hospitalier Universitaire in Sherbrooke, Quebec/Canada, stated that they found a 1.85-fold risk for developing heart attacks with longterm use of the BCP and at the same time there was a risk of 2.54-fold of hemorrhagic strokes with longterm use of the low-dose BCP.

I have depicted these findings below in graph form where the risk is readily seen when compared to women who did not use any birth control pills. In discussions following this presentation the authors explained that with short-term use of the BCP using the modern low dose formulations heart attacks and strokes would likely not be noticeable.

Birth Control Pill Increases Strokes And Heart Attacks

Birth Control Pill Increases Strokes And Heart Attacks

But women should know that long-term use does have this risk. These decisions of whether to take the BCP and for how long needs to be discussed with the treating physician also in the view that other risks such as high blood pressure, diabetes or the metabolic syndrome would be added risks where heart attacks and strokes can occur more frequently. In these conditions the BCP likely should be avoided.

Risk of Developing Heart Attack or Stroke after Longterm Use of The Birth Control Pill
 Birth Control Pill Increases Strokes And Heart Attacks1

 

 

 

 

 

 

 

 

 

Dr. Ricardo Azziz, chairman of obstetrics and gynecology at the Cedars-Sinai Medical Centre in Los Angeles, California, stated that these findings from this meta-analysis would be very important because it was based on such a large data base and was measuring the effect of the BCP over a long period of time. He stressed that the benefits of any medication must always be weighed against the risks by the treating physician. In diabetic patients on the BCP, for instance, the benefits likely outweigh the risks as the metabolism is stabilized through an improved insulin sensitivity, improved managability of the diabetes and avoidance of the high risk pregnancies in diabetics.

More info on:

Heart attacks: http://nethealthbook.com/cardiovascular-disease/heart-disease/heart-attack-myocardial-infarction-or-mi/

Strokes: http://nethealthbook.com/cardiovascular-disease/stroke-and-brain-aneurysm/

Reference: The Medical Post, Vol.40, July 20, 2004, page 20

Comments on Nov. 6, 2012: What was not discussed by these experts is the fact that the BCP contains a mix of two artificial hormones (estrogen and progesterone equivalents) that the body’s estrogen and progesterone hormone receptors cannot recognize. Bio-identical estrogen and progesterone creams on the other hand would be recognized by these receptors, but nobody has researched their use for BCP purposes, only for post-menopausal hormone replacement.

Last edited Oct. 26, 2014

May
01
2004

Age-Related Macular Degeneration Can Be Postponed

In a well-controlled study that was published earlier in 2004 Dr. Johanna M. Seddon

has shown that age-related blindness (AMD) is caused from an inflammation in the blood vessels, which is associated with an elevated blood marker, called C-reactive protein (CRP). The authors of this study also showed that the dry form of AMD would tend to deteriorate with age and/or from smoking cigarettes into the more serious wet form, a common cause of blindness.

The inflammatory component of cardiovascular disease is known to be controlled by the use of aspirin (ASA) or the statins, medication that is known to lower the bad LDL cholesterol. It is with this background that the author of the study that I am reviewing here, Dr. Jacque L. Duncan from the University of California at San Francisco, has examined the effects of ASA and of statins on AMD. 326 patients with AMD (204 with dry AMD, 104 with wet AMD from blood vessels forming underneath the retina and 18 with geographic atrophy) were followed between January 1990 and March 2003. Patients were at least 60 years old or older and followed at the San Francisco VA Hospital Eye Clinic.
Dr. Duncan found that patients with blindness due to wet AMD used ASA or statins significantly less than patients with stable AMD. Moreover, he found that patients who had AMD and took statins were 49% less likely to develop wet AMD and if they took ASA the were 37% less likely to develop wet AMD.

Age-Related Macular Degeneration Can Be Postponed

Age-Related Macular Degeneration Can Be Postponed

The study also suggests that there is a link between the inflammatory process that leads to heart attacks and strokes on the one hand and the further deterioration to blindness when dry AMD is not treated on the other hand. The notion that inflammation is the missing link in both of these processes is a relatively new finding.

More information about Macular Degeneration here.

Based on article by Dr. Jacque L. Duncan in the American Journal of Ophthalmology 2004;137: 615-624.

Last edited October 26, 2014

Mar
01
2004

Ankle Blood Pressure Reveals Diabetic Problems

One of the complications of diabetes is that ity leads to clogged arteries from peripheral artery disease and this can lead to heart attacks, strokes and circulation problems in the legs.

Recommendations were recently given to physicians in the December edition of the medical journal Diabetes Care that circulation problems in diabetics need to be monitored more stringently to avoid needless amputations.

Medically these circulation problems that affect mainly lower legs and feet are known as “peripheral vascular disease” (or PVD for short). PVD can be detected by the physician checking for ankle pulses. Another valuable and very simple test is to measure the blood pressure in the arm and at each ankle (using the stethoscope just under the inside (medial) ankle bone. If there is a major discrepancy between the arm and ankle blood pressure or if the ankle pulse is missing, this would be a sign of possible PVD. With a diabetic patient it would still be important to get the hemoglobin A1C under control through exercise, a low glycemic diet and possibly anti-diabetic medication. But the patient likely would have to be referred to a cardiovascular surgeon for further testing in order to find out whether there would be hardening of the arteries with circulation problems in the lower leg, the ankle or foot.

Ankle Blood Pressure Reveals Diabetic Problems

Ankle Blood Pressure Reveals Diabetic Problems

Dr. Peter Sheehan, the director of the Diabetes Foot & Ankle Center at the New York University school of medicine, stated that many patients and doctors overlook how frequent this condition is. About 33% of diabetic patients who are older than 50 years have PVD, but only a fraction know about it until it is too late. Once a patient has PVD in one of the legs there is a 4-fold risk of getting a heart attack or a stroke, because the hardening of the arteries is happening simultaneously in all of the body’s arteries. If the blood pressure is normal at the ankle, Dr. Sheehan recommends to check it again in 5 years.

Who should have the blood pressure check at the ankle? Here is a table that summarizes Dr. Sheehan’s recommendations.

Which diabetic needs the ankle blood pressure check?
High risk group: Remarks or more detail:
Anyone with leg PVD* symptoms legs tired or hurting when walking
Young diabetics
with other risks
smoking, high blood pressure, high cholesterol, diabetes present for more than 10 years are such risk factors
diabetics 50 years of age and over particularly when the hemoblobin A1C is high and other risk factors are present
*PVD peripheral vascular disease

Why is it so important to screen for circulation problems in the lower legs? Because this is the area where diabetics tend to get problems that often result in amputations of a foot or lower leg below the knee. With early detection of these problems and intervention by a cardiovascular surgeon often disastrous outcomes can be avoided.

More info is available at:

Diabetes: http://nethealthbook.com/hormones/diabetes/type-2-diabetes/

High blood pressure: http://nethealthbook.com/cardiovascular-disease/high-blood-pressure-hypertension/

Last edited October 26, 2014

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Mar
01
2004

Inflammatory Marker Linked To Blindness

Up to now age-related blindness or “age-related macular degeneration” (AMD) as it is medically called, has been a mystery. The retina is the light-sensitive area of the eye similar to the film in a camera. The “macula” is that part of the retina that has the highest visual acuity. Several studies have been conducted lately regarding age-related blindness that shed more light on this important health hazard of old age, studies that one day might even lead to a cure or powerful preventative measures to avoid it from ever developing.

One such study is the one by Dr. Johanna M. Seddon and co-workers published in the Feb. 11, 2004 issue of the Journal of the American Medical Association. Almost 1000 patients with various degrees of age-related degrees of blindness from the Age-Related Eye Disease Study (AREDS) were classified by the degree of their macular degeneration. I have produced the bar graphs below based on these studies.

Four groups were defined, namely those with no AMD who served as controls, those with mild AMD, those with moderate AMD and those with severe AMD who were legally blind. They suspected that an inflammatory marker in the blood stream of these patients, called C-reactive protein (CRP), might be present in the more severe cases of blindness when compared to the control group who did not have any inflammatory changes in the macula. As can be seen by the bar graph above this is exactly what the test results indicated. They also found that smokers (blue bars) tended to have slightly worse blood tests in terms of CRP (more inflammatory substances circulating in the system) within the same severity category of the age-related eye changes.

CRP (mg/L) Levels in Various Degrees of Severity of Age-related Macular Degeneration (AMD)

Inflammatory Marker Linked To Blindness

Inflammatory Marker Linked To Blindness

When the investigators studied the risk for the highest percentile of the CRP tests within various subgroups to show AMD they found several differences as is shown in the next table. First there was a low probability to develop AMD in a person with a normal looking macula and that risk was set at 1.0 as comparison. In contrast a person with a normal looking macula who smokes has a 1.5-fold risk of developing AMD later. Patients with a moderate degree of AMD have about a 2-fold risk of getting a severe degree of AMD later (smoking or not). It seems that once the inflammatory cycle has started, the process of causing a moderate degree of AMD is so strong that the effect of smoking will not add that much in comparison.

This is the first study of this kind that has established that CRP can be used as a screening for the risk to develop AMD. CRP has already been established as a test for monitoring progress in rheumatoid arthritis or to monitor for the risk of developing a heart attack or stroke.

Another study by Dr. Johanna M. Seddon and co-workers was published recently in the Archives of Ophthalmology. 261 people aged 60 years and older with established AMD were followed for 4.6 years and checked for deterioration. 101 patients had deterioration of their AMD.

Risk of Developing Age-Related Macular Degeneration (AMD) in Highest CRP Percentile
 Inflammatory Marker Linked To Blindness1

The authors analyzed the patients’ diet habits and found that increased fat intake was a high risk factor for deteriorating AMD. Both vegetable and animal fat had a 2-to 3-fold increased risk for deterioration of the AMD to a more severe stage (legal blindness). Fish, omega-3 fatty acid and nuts had a protective effect, but only when omega-6 fatty acid (linoleic acid) intake was low in the same group. The studies showed that the risk of age-related blindness was reduced by 40% when patients ate nuts at least once per week. The authors concluded that a “fat conscious diet” would be good for “maintaining good eye health” and at the same time be beneficial for prevention of heart attacks and strokes.

The authors will do further studies to investigate potential ways of helping patients with AMD and to understand the mechanisms of the disease process better.

References: 1. JAMA 2004;291:704-710  2. Arch Ophthalmol – 01-DEC-2003; 121(12): 1728-37

Last edited December 8, 2012

Dec
01
2003

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

With newer knowledge about the process of hardening of the arteries from the ongoing Framingham study it is not surprising that the drug companies are shifting the development of cholesterol-lowering drugs to those substances that will reduce inflammation of the arteries as well. In previous issues of the health newsletter I summarized a paper that was published on the importance of the C-reactive protein (also called CRP) in connection with the diagnosis of heart attacks and strokes. I also reviewed an article that pointed out that both CRP and LDL cholesterol are important in determining who is at risk for developing a heart attack or stroke.

In a press release to Reuters on Nov. 13, 2003 Merck & Co. Inc. and Schering-Plough Corp. announced that ezetimib (Zetia), a new cholesterol-lowering drug that is marketed by both companies, was found by their researchers to lower C-reactive protein (CRP) significantly. At the annual meeting of the American Heart Association in Orlando/Fla. these researchers presented a clinical trial showing that ezetimib when used in combination with small amounts of simvastatin (Zocor) lowered CRP by 33%. However, simvastatin alone lowered CRP only by 14.3%. Dr. Christie Ballantyne, a Baylor College cardiologist, pointed out that this new finding was very important. It was important, because it shows that these drugs do not only lower LDL cholesterol, which according to the Framingham study is a known risk factor for heart attacks and strokes. In addition it has now also been proven to lower CRP significantly at the same time, which is another known inflammatory component produced by the blood vessels also associated with heart attacks and strokes.

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

New Cholesterol-Lowering Drug Reduces Inflammatory Marker

Merck and Schering-Plough are now developing a new formulation containing both of these medications as one pill (Vytorin). This has the advantage to lower the risk on liver cells of Zocor by being able to lower the dose in the pill. The Zocor component will mainly lower the LDL cholesterol in the blood (and the CRP somewhat as well) and the Zetia component will provide the beneficial effect of the CRP lowering (anti-inflammatory component and LDL lowering). There is another advantage of this combination: Zetia works by inhibiting absorption of cholesterol by the gut, Zocor works by inhibiting cholesterol synthesis in the liver cells. Whenever the mechanism of action is different two drugs in combination are usually better tolerated than if both would work through the same mechanism. However, the companies pointed out that more research and clinical trials are needed to check out side-effects of Zetia before it would be submitted to the FDA for approval for general prescription by physicians.

P.S. on Oct. 31, 2012: Read the following article about Zetia and Vytorin (the combination pill): http://www.nytimes.com/2008/01/14/business/14cnd-drug.html?_r=0

Links regarding further information about heart disease (Net Health Book).

Last edited December 9, 2012

Nov
01
2003

Stroke Risk Increases With Carotid Artery Disease

An important study about the risk of strokes and mini-strokes (called”transient ischemic attacks”) was published in the Oct. 27 edition of the Archives of Internal Medicine. Dr. Daniel J. Bertges and his group followed 1,004 patients between 1988 and 1997 with ultrasound studies of the carotid arteries (carotid artery duplex ultrasound scans). The studies took place at the Pittsburgh Veterans Affairs Medical Center/University of Pittsburgh School of Medicine. Patients were followed with regard to events such as strokes on the side of where the narrowed carotid artery was.

Reversible mini-strokes (medically correct term:”transient ischemic attack” or TIA) were also registered. A total of 1,701 narrowed arteries (called “stenotic arteries”) were found with this ultrasound method. All of the patients initially had no symptoms of the carotid artery stenosis (no dizziness, no fainting, no absence spells or symptoms of TIA or stroke). In 75% of the patients the carotid stenotic lesions were less than 50% meaning that the carotid artery blood flow was acceptable.

Here are some of the risks as the study went on over the years: both TIA and CVA risk in a given patient occurred at a rate of 3.3% per year. Regarding a specific involved artery the risk of developing a TIA as a result of this was 2% per year and the risk to develop a stroke was 2.1% per year. The investigators found that two main factors determined the ultimate progression into a TIA or a stroke and they were as follows. First, if the artery was severely stenosed at the outset, the probability was high that this would progress and be the cause of a stroke. Secondly, the degree of progression when checked with a follow-up duplex ultrasound was another important factor in terms of leading to a subsequent TIA or stroke.

Stroke Risk Increases With Carotid Artery Disease

Carotid artery clot can cause stroke

The composite risk of developing either a TIA or a stroke with a worsening stenotic carotid artery lesion was 1.68-fold. To develop a stroke alone in this scenario the risk was 1.78-fold. Clinical risk factors were of no help in predicting which cases would go on to develop TIA’s or strokes. However, the finding of further progression of a stenotic carotid artery lesion documented on serial duplex ultrasound studies was highly significant.

The authors concluded that there is value in doing serial carotid artery duplex scan studies in the same patient to screen for progressing stenotic lesions in the carotid arteries. When a stenotic lesion is significant enough or progressing fast, intervention by a cardiovascular surgeon with carotid endarterectomy can be done to prevent a stroke or TIA.

Here is a link to a chapter on strokes from the Net Health Book.

Last edited October 26, 2014