Posts Tagged ‘Angina’
Which Comes First the Chicken or the Egg?
Recently a study was published in the Journal of Sexual Medicine regarding the association of depression, erectile dysfunction and cardiovascular events. J Sex Med 2010; 10.1111/j.1743-6109.2010
Erectile dysfunction has become another issue in patients with cardiovascular disease and risk factors and is fairly common in our society. It is estimated that one in ten males suffer from it. Its definition is the inability to develop or maintain an erection for satisfactory sexual performance. This, of course, is subjective and varies from patient to patient. It is also subjective from couple to couple; and I have had many discussions in my office with couples who are for or against the prescription of drug therapy for this problem.
Erectile dysfunction has been identified and treated as early as the 6th century, and in the past, required various devices or surgical procedures. In 1983, a British physiologist injected himself with phentolamine producing the vasodilatation necessary for erection which heralded a shift in therapy to drugs. And then Viagra came along.
Sildenafil was synthesized in England and patented in 1996. It is an inhibitor of cGMP specific phosphodiesterase type 5 and is responsible for vasodilatation of blood vessels. It was thought to have potential as a treatment for hypertension and angina and was first tested on angina. In Phase I trials for angina, it was found to have no effect on angina but a profound effect on producing erections. The rest, as they say, is history. Viagra was released to market in 1998 and annual sales exceed one billion dollars a year.
Erectile dysfunction is often found in individuals who have hypertension, smoke and have high cholesterol. This also may be an early warning marker of advanced atherosclerosis. It may become another “risk” factor for coronary disease.
The article relates that patients who have erectile dysfunction and are depressed, those with the most depression have the most cardiovascular events; and that depression is an independent factor in their problem. The authors point is that if you are depressed, we as physicians need to find out if you have erectile dysfunction. And if you do, a higher degree of suspicion is warranted for the evaluation of cardiovascular disease. The emphasis on treatment should also be greater and directed against the depression as well as the erectile dysfunction.
Does the depression give you erectile dysfunction or does erectile dysfunction give you depression? Either way this probably goes beyond a locker room joke — although we may as men be fixated on these issues. The issues may well be an early warning sign of deeper problems. If your partner has erectile dysfunction, it may be time to remove it from the bedroom and place it in the doctor’s office.
Do statins make you immortal?
My blogs over the past week have been concerned about the screening of asymptomatic patients for coronary artery disease and whether we make a difference in their morbidity and mortality if we find it.
That’s really all we are concerned with: Can we, as physicians, change a patient’s outcome by putting in place a medicine or a lifestyle? What good is it to find a problem if you can’t act on it?
To date, what we do when we find a patient who we believe to be at risk is tell them to stop smoking, control their blood pressure and their diabetes. And, we put them on statins. As those that read my blogs know, statins are our first line of defense against progression of coronary artery disease when a patient already has an infarct, angioplasty or coronary artery bypass surgery.
An article was published in Arch Intern Med 2010;170:1024-1031 which addresses this question. It is titled Statins and All-Cause Mortality in High -Risk Primary Prevention: A Meta-Analysis of 11 Randomized Controlled Trials involving 65,229 Participants.
This represents over 244,000 person- years of follow up. The average LDL cholesterol was 138 mg/dl and the results of giving statins yielded an average LDL of 94 mg/dl. An average of 3.7 years of follow up occurred in these studies and there was no evidence of benefit in these findings (7 fewer deaths for every 10,000 person years of treatment).
Although compelling, I believe that this study is flawed by the short follow up. Remember, this is not a randomized clinical trial which is the highest level of significance; it is a Meta-Analysis and only collates the data already collected in like studies.
Statins were approved because they were tested in randomized clinical trials against placebo and there was always a statistically significant reduction in a triple endpoint of unstable angina, myocardial infarction and death. Death however is usually the least affected because we are much better at preventing it if patients who are affected by an acute event present to hospitals. Patients who are found to be “at risk” will continue to be offered statins and the data shows that the lower the LDL is driven, the lower the vent rate. There seems to be no plateau. Every time a study drives the number lower, the event rate follows and some studies have the LDL as low as 50 mg/dl. The study known as TNT, or Treating to new targets,
showed this result in a study with over 10,000 patients.
The real study we want to do can not be done because it is not ethical anymore. Withholding statins from patients would never pass muster. It could be done in patients who refuse statins but the numbers would never be great enough. We will just have to accept the premise for the time being until science moves ahead of need.
Time to relax
Two studies were recently published concerning the cardiovascular risk of working overtime. The first published in Occupational and Environmental Medicine (there is a journal for everyone) and the second in the European Heart Journal. The first studied nurses and the second London civil servants.
Over a 15-year period, 12,116 nurses were studied. They were originally between the ages of 45 and 64 years old. Over this period of time, there were 580 cases of angina or myocardial infarctions. In addition, there were 73 cases of “other” ischemic events but they were not otherwise characterized. When adjusted, the nurses who felt that work pressure was “much too high” had a 1.4 fold increased risk of developing symptomatic heart disease.
The London-based study began in 1985 and looked at participants who were 39 to 61 years old. The study follow up was completed in 2004. Adjusting for all factors, working three to four hours of overtime per day was associated with a 60% higher rate of fatal and nonfatal myocardial infarction or angina.
Although interesting, the reasons for these findings are pure speculation. One could postulate that it is all “stress” and that this is manifested in unhealthy lifestyle choices and high blood pressure. Is there more stress working at a job or not having one? Is it more stressful losing your insurance or working to keep it? Similar findings have occurred when life events such as death of a spouse or child, or divorce have been studied.
It all relates back to keeping your blood pressure under control and trying to reduce stress in your life in anyway that it applies to you. Everyone is different. Some people exercise, some read, some listen to music. Whatever it is, just do it to relieve stress and possibly stay disease-free.
Correcting Urban Legends in Medicine
Urban legends are situations or things that are thought to exist but don’t. Their power is such that they can lead to excessive attempts to change behavior that didn’t need to be done in the first place.
Urban legends in medicine lead to an overuse of resources and an enormous increase in the overall cost of medical care in spite of contrary evidence. I don’t claim to know how to stamp it out. Education is one way, but people and physicians are incredibly resistant to it.
One such “Urban Medical Legend” is preoperative cardiac risk evaluation. The legend holds that it is possible to identify and then rectify the condition of patients who are at risk for cardiovascular incident and death before they have an operation. This is the so called cardiac clearance for surgery. It comes in two flavors the “emergency clearance” and the classical “elective clearance.”
Although there are Guidelines published by The American College of Cardiology in conjunction with The American Heart Association, neither are closely followed by most practitioners. The guidelines suggest that patients who have no evidence of angina or congestive heart failure are at no adverse risk for any surgery. In the process of screening for “problems” patients are generally subjected to nuclear stress tests and these tests identify those lesions that are “significant.” However, significant lesions cause angina and not myocardial infarctions and many myocardial infarctions are from lesions that are not considered significant.
The most important study done on this was a study that identified these patients and then randomized them to medical therapy and “corrective” therapy, either angioplasty or coronary artery bypass surgery. This study revealed that the “corrected group” had a statistically significant worse outcome than the medically treated group because of the incidents that occurred during the correction. This included the data for the surgery that they then went for after they were cleared.
The medical therapy most often applied is the use of preoperative beta blockers. These are drugs like Toprol and atenolol which control heart rate and blood pressure. This too has been called into question in that the routine use of these drugs can have important consequences for patients.
There is no perfect answer but what we presently do is unjustified by the data. The use of selective functional testing and the selective correction and treatment is evidence based but not necessarily the current standard of practice. This arises from legal concerns, compensation from testing and procedures and possibly from surgeons.
We as physicians need to do better. This is one area that we can make a difference in the quality and cost of health care. Beware of clearance that requires testing that you would not have gotten without the pending surgery.
Different Paths Lead to the Cath Lab
It might seem that using angiography to determine whether a coronary lesion is significant would be easy. Sometimes it is; sometimes it is not.
Patients arrive in the cath lab by different routes. Some come from the hospital because of unstable angina or myocardial infarctions. Some come because of classic symptoms of angina and multiple risk factors. Some come because of a positive stress test, stress echo test, or nuclear stress test.
The problem occurs because coronary arteries are three dimensional and they are being represented in two dimensions. To get around this, multiple views are obtained during the exam by rotating the camera around during the catheterization to obtain multiple angles. Heavy calcification and overlap often obscure vessels.
Confounding this problem further if you take a cath film to multiple doctors there is significant inter-observer variation in reporting of the severity of a stenosis in an artery. In fact if you ask the same doctor at different times the reports can vary.
This is a critical problem. The stenting of a coronary artery that is not significant can produce long lasting poor consequences for a patient. As I have written about in other blogs, medical management is an excellent way to treat much of what we find in the cath lab. Regardless of the extent of disease in one’s coronary arteries, management of the illness is medical and life long. Angioplasty is for those patients that have failed medical management and had life limiting angina. Surgery is for patients that can not have angioplasty or have poor heart function.
There is a way to discriminate coronary lesions that are considered “indeterminate.” Sometimes, even lesions that correspond to nuclear stress test results do not appear significant.
Next…what’s a doctor to do?
Best outcome for those with Diabetes and Coronary Disease
In my last blog reviewing the BARI 2D, I discussed the results of the diabetic issues. As an interventional cardiologist, I am most interested in the revascularization issues. First, some background. Dr. Andreas Gruentzig invented coronary angioplasty in the mid 1970s. He built the original balloons by hand in his kitchen. The first human angioplasty took place in September 1975. This patient was recatheterized on live TV 10 years later and was found to have an open artery. Dr. Gruentzig believed that angioplasty was to be used to treat symptomatic angina that was not responding to medical management. At the time, angioplasty started coronary bypass surgery was the only option; so, many patients had single artery bypass.
As angioplasty developed, attempts were made to determine if one treatment was superior — angioplasty or bypass surgery. A study was conducted comparing the two called BARI.
BARI, the Bypass Angioplasty Revascularization Investigation began in 1988 and was published in the Journal of the American College of Cardiology 2000; 35: 1122-1129.
The first patient was enrolled in August 1988 and the last in August 1991, for a total of 1,829 patients at 18 sites in North America. The patients were symptomatic and had multi vessel disease. They were randomized between surgery and angioplasty. There was no medical treatment group. At the end of 7 years, the survival rate of 86% was the same whether you had angioplasty or surgery if you did not have diabetes. Estimates of the 7 year survival with surgery and diabetes were 76% vs. 55% if you had angioplasty and diabetes. Clearly, having diabetes alters the equation in favor of surgery in those patients who have multi vessel disease.
This was the background for BARI 2D. The best outcome in BARI 2D was obtained in the patients who had multi vessel disease and prompt revascularization with surgery and took oral insulin medications. Forty-two percent of those randomized to medical management eventually underwent revascularization again, pointing out the ongoing disease process of diabetes and coronary disease. Angioplasty did not reduce major cardiovascular events compared to medical management.
An accompanying editorial asked the question whether this outcome will change what we as physicians offer our patients who come to us for answers to important health care problems. More than one million angioplasty procedures with drug eluting stents are done annually. The evidence-based approach would indicate that for symptomatic relief of angina in patients with diabetes and multi vessel coronary disease bypass surgery is the preferred choice.
NOGA and Protein Combine to Beat Angina
Our team has begun enrolling participants in our third stem cell therapy trial. This trial is unique in many ways.
First and foremost, we will be utilizing the NOGA machine to restudy patients at the study’s conclusion. At this time, we will obtain some very unique data not usually collected on participants. Most of the “success” of trials for heart failure and angina depends on a decrease in the symptoms that the patient had at the study’s start. Treadmill and walking tests are also used. However, the NOGA enables us to revisit the exact sites of injections so those areas of heart muscle can be analyzed for improvement in blood supply and movement.
The second unique part of this study is it does not use cells but rather a manufactured human protein which has been altered slightly. This protein is understood to provide stimulation of the growth of new blood vessels and of new muscle. This may allow those patients that need this type of therapy to not have to endure the arduous and expensive process of harvesting the cells from each donor. The manufactured protein can go in any patient without concern for rejection.
Like the BAXTER study before it (see blogs on 06-25-09 and 06-29-09), this study is enrolling patients who are limited by their angina and have failed medical management and are not angioplasty or coronary bypass candidates.
Candidates must walk on the treadmill and qualify, then undergo catheterization and nuclear stress testing. If they pass all the qualifying tests, they are then injected by NOGA mapping with either active protein or placebo. This is a safety study and does not have the statistical power to determine whether the treatment works or not. We know from other work that patients can have marked benefit. You will soon be able to hear some of these patient success via video on our website toward the end of the summer.
If you have angina and would like to discuss treatment options with us further, we can be reached at 954-229-8400.
Adult Stem Cell Therapy Offers Options
In my blog on June 04, 2009, I discussed angina. In spite of all physicians have to offer patients who suffer from coronary atherosclerotic heart disease, some individuals end up with no further treatment options. They often have had coronary artery bypass surgery and multiple angioplasties. They are on maximal medical therapy and still they have disabling angina. Coronary bypass requires an adequate vessel to bypass into. Often the heart arteries are 1 mm or less at these sites and cannot accept the bypass grafts. Similarly, angioplasty requires adequate vessel size to be possible.
Humans are the only species on earth who develop collaterals. Collaterals are natural connections from one heart artery to another that develop because of restricted blood flow. Sometimes these collaterals are quite robust. Sometimes they are not. When they are present, heart damage can be very limited in a heart attack situation because the heart still gets blood in spite of the upstream artery blockage. When they are not present, the damage can be profound and often death or severe disability occurs. The mechanisms for the creation of collaterals are not known. It is not well understood how to improve them.
Over the past years it has become possible to promote the collateral blood flow by various treatments. One such treatment is stem cell therapy in the form of CD34+ cells. We participated in the Baxter Phase II ACT34-CMI study to document the safety of stem cell injections. This study involved 26 study sites. We were the 7th highest enrollers. There were a total of 167 patients, and we enrolled 10.
The study enrolled patients with no options. There were three treatment groups, placebo, low dose and high dose. This was a safety study and not powered to show effect. In spite of this, the study proved that it was safe to perform and did provide a significant benefit to the patients. In fact, it is the first time that this patient population showed a significant improvement in treadmill walking times. A third phase is scheduled to begin early next year.
Next: How it’s done.
Atherosclerosis: A Lifelong Enemy
In my last blog I reviewed some basic information about statin use for the treatment of atherosclerotic disease. Atherosclerosis manifests itself in many forms. In the heart it manifests itself as angina and myocardial infarction; in the brain, as strokes — either minor or major; in the legs, it manifests as painful calves or buttocks when you walk. We call this claudication. In the abdomen, as abdominal aneurysms, which rupture and can cause a quick death. In fact, most deaths in the United States are due to this process; in all, over one million deaths a year.
At least once a week I hear the phrase “but my cholesterol has always been good.” Unfortunately, as physicians, we do not have a practical way to determine the differences between two people who have the same cholesterol and different outcomes. Cholesterol is a combination of the components triglycerides, LDL cholesterol and HDL cholesterol. These three components are in constant motion with triglyceride being added to LDL to form HDL. Our livers manufacture cholesterol because it is a basic building block of our body. We, in general, only eat 10% of our total cholesterol level — so diet alone is never enough to treat documented atherosclerosis.
Since the Vietnam War, we have known that atherosclerosis starts at a very early age. Most of the autopsies done at that time showed some atherosclerosis and in some individuals it was quite advanced. Once you have atherosclerosis you can not get rid of the damage. Early treatment is warranted and now, in some instances, we have started treating children.
Next: The HPS and the dawn of a new paradigm.
Treating Cardiac Disease
Angina is what we call the symptom of chest discomfort that is caused by lack of blood flow to the heart muscle. It has multiple causes but the one that is most common is atheroscelerotic blockages in the heart arteries causing limitation of blood flow. It can be at rest or exercise because the symptom is a result of a combination of a person’s heart rate and blood pressure. These same blockages can lead to heart attack in other circumstances.
The most common treatment for angina is medication. These drugs fall into various classes of medication. The oldest is nitroglycerine, which has been in use since 1870 when it was first used by Thomas Bruton in England for the treatment of angina and reported in The Lancet in 1879. It is only recently that the mechanism of action of nitroglycerine has been understood as an example of how long it takes for science to catch up with the practice of medicine.
Beta-Blockers are a mainstay of treatment. They were invented by a brilliant Scottish doctor and pharmacologist Dr. James Whyte Black in the late 1950s. Interestingly, he also invented Cimetidine, which was a new class of drugs to treat stomach ulcers known to most people as Tagamet. For these and other advances, he was awarded the Nobel Prize for Medicine in 1988. Beta blockers are used to control both the heart rate and the blood pressure in patients with angina. This allows the heart to receive sufficient oxygen carrying blood for energy utilization.
Calcium channel blockers are medications that have predominantly heart rate slowing or vasodilatation mechanisms of action. These are commonly used as drugs such as Norvasc, Cardizem, Procardia or Calan. They lower the heart rate and overall blood pressure much as the Beta Blockers.
Next week I will discuss what is probably the most important advance, in atherosclerotic heart disease, the statin drugs.
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