[ed. note: We feature the writings of Doc Gumshoe, our favorite medical scribe, every few weeks here at Stock Gumshoe. He is not a doctor, but we value his insight, research, contrariness and skepticism … and, most importantly, his ability to explain complex health issues for our readers. You can see all of Michael’s previous commentaries here.]
By now nearly everyone has heard about these controversial new statin guidelines, announced on Tuesday, November 12, by the American Heart Association and the American College of Cardiology. In the event that you have been paying attention to far more important matters, such as whether Alex Rodriguez will ever play baseball again, I will briefly summarize the main points. And, to give you an advance peek at where I stand: no, I don’t go with the narrative that holds that this is a conspiracy by the AHA and the ACC to throw more business to Big Pharma. But, also, no, I emphatically don’t believe this is the best way to address the huge issue of interlinked cardiovascular diseases.
Here are the essentials of what these AHA/ACC guidelines do:
- They attempt to quantify total cardiovascular risk by arriving at a percentage figure for a ten-year risk of cardiovascular events (heart attack or stroke). Individuals aged 40 – 75 whose ten-year risk is 7.5% or higher are recommended to take statins.
- They recommend that persons whose LDL-cholesterol levels are 190 mg/dL or higher should take statins.
- The also recommend that persons with existing heart disease or Type 2 diabetes should take statins.
- But specific LDL-cholesterol goals are not part of the new guidelines.
- And regular monitoring of blood cholesterol levels is not necessary. The effects of treatment should not be based on how much cholesterol-lowering takes place.
There’s more, but those are the essentials.
As soon as AHA/ACC announced the guidelines, the fur began to fly. Many of the most eminent cardiologists in the country registered vigorous exceptions. One in particular, Dr Paul Ridker, of the Harvard Medical School, examined the algorithm used to calculate the CV event risk, and came to the conclusion that it tended to overestimate risks by a very large percentage, from about 75% to 150%. This would mean that some people would erroneously be placed in the category deemed to need statins when they probably did not need statins at all.
Another critic is Dr Steven Nissen, of the Cleveland Clinic. Dr Nissen did a couple of calculations in men who would be considered healthy by any usual standard – normal blood pressure, normal total cholesterol and HDL-cholesterol, not diabetics or smokers – and the algorithm in both cases (one African American, one white, both age 60) put their risk factors as 7.5%, therefore recommending statins for both men.
A specific criticism leveled at the risk calculator is that it is excessively quantitative – for example, it gives equal weight to a 30 point difference in systolic blood pressure, whether it’s between 100 and 130 mm Hg or 150 and 180 mm Hg. The risk calculator just factors in the number and spits out the answer.
And how about not monitoring cholesterol once the patient is started on the statin? Is the patient supposed to take it on blind faith that the statin is good for him or her? The AHA/ACC folks essentially say “yes – don’t just go by the numbers” (having put the patient on the statin by the numbers in the first place.) But if you’re the patient, what do you go by? In the opinion of many top cardiologists, this would result in low patient compliance, i.e., patients would just not take their pills. And, cardiologists will realize that and not follow the guidelines.
By the way, as these guidelines were being developed, the National Heart, Lung, and Blood Institute – the body that includes the National Cholesterol Education Program (NCEP) – took itself out of the picture. That should tell us something! NCEP has in the past issued treatment guidelines including guideline for statin therapy, and these guidelines have included risk assessment algorithms, i.e., the Framingham Risk Calculator. But those guidelines were much, much more conservative with regard to recommending statin treatment.
What I can say about the new guidelines is that they constitute an attempt to address the entire spectrum of cardiovascular disease (CVD). That’s one thing that I strongly agree needs to be done. Let’s take a look at the whole CVD spectrum.
Cardiovascular disease and homeostasis
Diseases, illnesses, maladies, disorders, conditions … whatever we call them, have origins that can be grouped under different headings. There are infections caused by invaders such as microbes, bacteria, viruses. There are the maladies caused by nothing more complex than wear and tear, such as osteoarthritis. There are many highly complex diseases of genetic origin. There are the conditions caused by malfunctions in our immune system, such as allergies and autoimmune disorders. Among the diseases and disorders that arise out of disregulation of our own homeostatic mechanisms, cardiovascular disease stands out.
Homeostasis encompasses all the mechanisms of the organism to keep operating in an optimal range. If you build up too much carbon dioxide in your bloodstream, sensors take notice and send a message to your lungs to take a really deep breath. If you get too hot, you sweat, and the evaporation of the perspiration from your skin cools you off very effectively. Those are only two of the multitude of homeostatic mechanisms that are constantly operating in our bodies.
So, let’s look at three homeostatic mechanisms that keep critical body functions operating on an even keel: those that maintain levels of glucose and lipids in the blood and also blood pressure itself at optimal levels. All of these mechanisms are complex and several employ highly sensitive negative feedback processes that keep the physiologic functions that they might be said to supervise within fairly narrow bounds.
It would be natural to suppose that disregulation of these homeostatic mechanisms would occur one at a time. In other words, if the regulation of glucose levels in your blood goes off the track, you tend to develop diabetes, and the effects on your health are limited to that particular disease. Unfortunately, it isn’t that easy. When any one of those three homeostatic mechanisms is not operating as it’s supposed to, the others are affected also, with the result that there is a great deal of overlap among the conditions that these mechanisms are supposed to prevent.
What are these homeostatic mechanisms and how do they work?
It may help to think of our circulatory system as a kind of irrigation machine for our bodies. The heart is the pump, the blood is the fluid in the system, and the arteries and veins are the hoses that carry this fluid to where it’s needed – i.e., everywhere in our bodies. The pressure in the system depends on how much fluid the pump is pushing into the system, but also on the total quantity of fluid in the system, and on how much flexibility, or resistance, the hoses exert on the fluid. If the pump is pushing too hard, if the amount of fluid in the system is too great, or if the hoses have no flexibility, – if any of those three is happening, the result is an increase in the pressure within the system.
The pumping action of the heart and the pressure in our circulatory system is mostly controlled by the autonomic nervous system. It goes up when we’re more active, or under stress. It goes down as we relax.
The quantity of blood in our circulatory system largely depends on the salt concentration in the blood. This is being monitored constantly and exquisitely, so that if the concentration is too high, we’re thirsty and take in more water to bring it to optimal levels. Then, when the salt concentration is back to normal levels, we get rid of the excess fluid in the usual way.
All of these mechanisms are interlinked, and a number of physiologic agents play a part. One of the most important is called angiotensin II, which is converted from renin, a substance that we make in a gland near our kidneys. Angiotensin II triggers increases in blood pressure by raising cardiac output and also tightens the muscles in our circulatory system.
Cholesterol and blood lipids
Let me say it right off the bat: there’s no such thing as “bad” versus “good” cholesterol. Those are terms adopted by the simplifiers who thought that describing the reality would be beyond the great majority of the public, and what they wanted people to latch onto was those two easy adjectives, “bad” vs. “good.”
Cholesterol is a fairly simple molecule, solid at body temperature, and not soluble in water. Therefore, in order to be transported in our bloodstream, it has to hitch a ride with substances that can be carried around in blood. These are lipoproteins – little particles containing both proteins and lipids, not in any fixed chemical combination, but bundles of varying sizes. Cholesterol attaches to the lipid part of these bundles, and the protein part permits them to be transported in blood.
These particles range in size and density. The low-density, loosely packed bundles, called low-density lipoprotein cholesterol, or LDL-cholesterol, are the ones nicknamed “bad” cholesterol, because they are the ones that are apt to shed the cholesterol molecules themselves, which can attach to the walls of the arteries. But, we have to remember, the LDL-C is absolutely essential to our lives, because those particles are the ones that convey cholesterol to where it’s needed, which is pretty nearly everywhere in our bodies.
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The smaller, denser bundles, called high-density lipoprotein cholesterol, or HDL-cholesterol, carries cholesterol back to the liver, where it is taken up by the bile and carried in the bile duct to the colon for excretion in the feces. Therefore, HDL-C is dubbed “good cholesterol.”
It’s worth just mentioning that only about 15% to 20% of the total cholesterol in our bodies enters our digestive systems as cholesterol. The rest we make ourselves. Some of the foods we eat are more easily transformed into cholesterol, such as solid fats, especially partially hydrogenated fats (transfats). But no matter what we eat or don’t eat, we’ll go on making cholesterol, because we need it.
In the case of cholesterol, the homeostatic mechanism is exactly that balance between LDL-C and HDL-C. Those two types of particles have properties beyond their role as cholesterol delivery systems. LDL-C appears to be highly susceptible to oxidative damage, and may also inhibit the synthesis of nitric oxide, which is thought to be one of the body’s natural mechanisms to combat atherosclerosis. And HDL-C has the opposite effect. Its principal lipoprotein, apo A-1, plays a part in preventing particles involved in atherosclerosis from adhering to arterial walls.
So, not only do LDL-C and HDL-C play different roles in cholesterol transport, they do the same with regard to arterial damage. We could say that the nicknames “bad” and “good” cholesterol are fully justified.
Any sugar we eat, as well as starches, and parts of other foods, is converted to glucose. The more complex the food is, the more work the body has to do to convert it to glucose, but glucose is where a lot of our food intake winds up, because it’s our chief source of energy. The conversion from sugar to glucose is easy as pie and happens very, very quickly. When we eat that piece of pie, a lot of the sugar in it goes into our bloodstream as glucose in minutes. When we drink soda pop, it’s even faster.
But that glucose by itself is useless to our bodies. It has to be metabolized to be converted to energy, and this metabolism can’t take place unless there is insulin present in our system to activate insulin receptors in our cells and trigger the metabolic process.
Insulin is produced in beta cells in the pancreas, partly in response to the presence of food in our stomachs, but also at a fairly constant background rate. The insulin response is the homeostatic mechanism that keeps blood glucose within optimal levels – enough for an energy reserve, but not so much that it can harm our bodies.
And glucose in our bloodstream can indeed harm our bodies, mostly by damaging our smaller blood vessels. Excess glucose in the bloodstream, as in diabetes, is a major cause of organ failure, especially kidney failure, of damage to the retina sometimes causing blindness and also of gangrenous infections leading to amputation.
The progression of diabetes is gradual and, unfortunately, insidious. The disease might be oversimplified as exhaustion of the entire glucose metabolism process. As a person consumes foods that contain or can be converted to glucose, the pancreatic beta cells respond by producing insulin. But the glucose in the circulation can overwhelm the capacity of the system. Insulin receptors throughout the body don’t respond the way they’re supposed to – they are, in effect, worn out. The person develops a condition termed insulin resistance and then hyperinsulinemia – too much insulin in the circulation, which in itself can have bad consequences. In the meantime, glucose levels keep rising.
The reason I said the disease is insidious is that most people who are going through these stages have no idea what’s going on. They mostly feel just fine. In fact, many people who have passed the line defining frank type 2 diabetes – a fasting plasma glucose level of at least 126 milligrams per deciliter – aren’t aware of symptoms severe enough to seek treatment. Thus, although about 14 million adults in the US have received a diagnosis of diabetes, it’s thought that about 6 million more have diabetes but are undiagnosed.
Clustering of risk factors associated with cardiovascular disease
A rational assumption would be that risk factors for cardiovascular disease (CVD) would be additive – that is, that having two risk factors would double one’s risk, having three would triple it, and so forth. Unfortunately, the increased risk is more than additive. And, on top of that, the evidence is fairly strong that these risk factors don’t come along singly. If you have one, you’re more than likely to have at least two, and quite possibly three or four. Here’s some statistics, gathered by the Framingham Study, which has been tracking CVD statistics on several hundred thousand subjects for more than three decades. The risk factors tracked by the Framingham investigators are hypertension (HTN), high levels of triglycerides or LDL-cholesterol, low levels of HDL-cholesterol, impaired glucose tolerance, hyperinsulinemia, obesity, and left ventricular hypertrophy. For persons with HTN, here are the percentages of persons with additional risk factors:
|No additional risk factors||19%||17%|
|One additional risk factor||26%||27%|
|Two additional risk factors||25%||24%|
|Three additional risk factors||22%||20%|
|Four or more additional risk factors||8%||12%|
So the majority of both men and women with HTN have at least two additional risk factors for CVD, and fewer than 20% have HTN with no additional risk factors.
When we look at the combination of HTN and elevated cholesterol, what we find is that having both conditions increases mortality from coronary heart disease exponentially. These data come from a study called MRFIT, which followed more than 300,000 white men for 12 years. The blood pressure and total cholesterol values for these subjects were divided into quintiles, and the mortality risk was assessed.
As we might suppose, when the mortality risks for HTN and elevated cholesterol alone were calculated, persons in the higher quintiles had higher risks. But in the unfortunate group that was in the highest quintile for both HTN and elevated cholesterol, the mortality risk was 11 times higher – 33.7 per 10,000 patient-years –than in the lucky persons in the lowest quintiles, whose mortality risk was about 3.1 per 10,000 patient years.
Let’s look at diabetes as a risk factor for heart disease and stroke. These data are from the Centers for Disease Control, and they echo the evidence cited above. Persons with diabetes are 3.2 times more likely to have coronary heart disease, 2.9 times more likely to have a stroke, and 1.9 times more likely to experience another type of heart condition. About two-thirds of persons with diabetes die of heart disease or stroke.
Why do we need cut points for defining disease?
Cut points for defining disease are attempts to guide clinicians in the important decision-making process regarding when to initiate treatment.
A major reason why guidelines are out there is to publicize the need for treatment. And why does the need for treatment need to be publicized? Because, in contrast with diseases/conditions/disorders that produce symptoms, most people with hypertension, dyslipidemia, or diabetes experience no symptoms until the disease has progressed to the point of causing real, irreversible damage. Or, sometimes, death.
So, there have to be guidelines, and the public has to be made aware of them. The underlying question is, how closely should they be followed?
Returning to the AHA/ACC guidelines, they seem to me to have one major virtue: they call attention to the clustering of cardiovascular risk factors – not just total cholesterol or LDL-C levels, but the whole spectrum of risk factors, including smoking, nutrition, obesity, gender, age, and race. It’s good for all of us to know this.
But it’s not good for a treatment plan to be calculated by a one-size-fits-all algorithm. An algorithm, or a set of guidelines, should not be a substitute for the clinical acumen, experience, and judgment of a physician who has closely examined and interacted with a patient.
So, what’s to be done?
I suggest that all this brouhaha about the AHA/ACC guidelines may turn out to be a good thing – not that the guidelines themselves are a good thing, but that the discussion may bring more attention to the clustering of risk factors. In other words, individual patients with any of those risk factors may become more aware of the total risks that they run.
That certainly doesn’t mean that doctors should go along with the one-size-fits-all AHA/ACC guidelines, or that great numbers of people should demand prescriptions for statins based on the publicity. Many people clearly have benefited from taking statins; the evidence is the large decrease in the rate of cardiovascular events. A huge decrease in cardiovascular mortality happened in the years from 1963 to 1999, largely due to better treatment for high blood pressure and also to people taking prophylactic aspirin for stroke prevention. And there has been a continuation of this decrease since the introduction of statins in the mid 1990s, so statins are clearly good for lots of people. But that doesn’t mean they’re good for all the people that would be swept under the AHA/ACC guidelines.
A risk factor that I suspect the new AHA/ACC algorithm overweighs is age. (This was also true of the Framingham risk calculator.) Thus, even if you have no other risk factors at all, age by itself could put you over that 7.5% cut point and recommend you for statin treatment.
Doc Gumshoe doesn’t buy that.
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Many thanks for all your comments. I’ll try to save up questions and answer them in a future piece. Right now, I’m trying to collect some more cheerful tidbits so I can send along some good news before the holidays. Best to all, Michael Jorrin (aka Doc Gumshoe)