Note: We will cover HIV vaccines soon; these are some notes from my pharma class.

Cardiac Rhythm and Arrhythmias

Most days we don’t think about it, but our heart is pretty important.  Beating constantly, it provides a flow of blood that keeps our organs fed and keeps us alive.  To get a sense for how important it is, if your heart stopped for just 10 seconds, you’d faint.

The heart is a combination of great strength and great weakness.  On the one hand, it beats roughly 60 times a minute for the entire duration of your life without fail.  On the other, it almost never recovers from damage.  If a part of it gets cut off from oxygen and dies, it will never recover, as contrasted to our skin, which is constantly replenishing itself.

How does the heart work?

The heart has 4 major chambers: 2 atria and 2 ventricles.  The atria are the receiving rooms: they are where blood flows in from the body.  After the atria are filled properly, the blood moves into the ventricles, which are thick and muscular.  From there, the ventricles pump the blood either to the lungs – where it receives vital oxygen – and to the rest of the body.

The electrical system and failures:

Electrically, the heart works by chemical gradients.  There is a dynamic equilibrium between three key ions: potassium, sodium and calcium.  There is a lot of potassium inside the heart’s cells and a lot of sodium and calcium outside of them.

When a heart muscle needs to contract, and in response to the appropriate stimulation, it opens its sodium channels.  This allows an inflow of positive ions, which makes the cell become depolarized, or gain a positive charge.  Becoming positive makes the cell contract.

Then the sodium channels close and potassium channels open.  Because there is so much potassium inside, it tends to leave the cell and, because its positively charged, this reduces the cell’s charge.  However, for a short time, the outflow of potassium is moderated by an inflow of calcium.  Eventually the calcium channels close, allowing the cell to return to its initial charge.

Arrhythmias:

An arrhythmia is a disturbance of normal heart rate, whether to beat too fast or too slow.  Arrhythmias can be extremely dangerous and a cause of sudden death.

There are many different ways arrhythmias can arise.  One of the most important is reentry.  Reentry is when your heart, so to speak, short circuits itself, and electrical impulses start going in a loop, out of control.

Other causes include disruptions of the electrical pathways of the heart.  There are many, many potential issues that can cause that, such as high levels of ions, genetic disorders, or sudden heart failure.

Coronary heart disease (CHD) is the single biggest cause of health problems and death in the USA and the world.

Statins offer a way to help treat CHD, but have become perhaps too heavily pushed. And the target level of cholesterol to reach may have been lowered too far.

What causes CHD?

CHD is most often caused by the build up of plaques on arteries and other blood carrying vessels. The plaque is made of various components, but deposits of cholesterol tend to play a key role. When it becomes too thick, it can stop blood flow, causing a heart attack or other damage.

The plaque can also break off and float around the body. If that happens, it can harmlessly dissolve. Or it can clog a blood vessel pretty much anywhere, potentially causing a stroke, heart attack, or thrombosis.

Statins discovered

The late 1980s heralded the discovery of a class of drugs called the statins.

These medications, technically termed 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, lower levels of cholesterol. Because of the role cholesterol plays in plaque formation, the statins were found to dramatically decrease risk of serious heart damage.

Statins were so effective that a lot of influential doctors argued that the lower cholesterol levels were, the better. LDL, or low density lipoprotein, was specifically targeted. And in the early 2000s, aggressive new targets for treatment were released. LDL levels should be lowered below 100 mg/dL.

But a lot of the proponents of the new, lower levels were found to be on the pay for major drug companies. And it’s not entirely clear if aggressive lowering of LDL levels provides the most benefit.

LDL must be lowered?

It’s most likely that lowering of LDL follows a logarithmic pattern. In at risk patients, a small reduction provides a major reduction in risk of having a heart attack. As levels are lowered even further, however, the benefit becomes increasingly smaller.

A few major studies support the idea that LDL levels shouldn’t be over aggressively lowered. The HARP study showed that lowering levels below 100 mg/dL showed no increased benefit.

The WOSCOPS study gave similar results, as well as AFCAPS.  Additionally, several major studies into the non-statin drug Ezetimibe showed that its reduction of LDL did not mean better clinical results for patients.

Potential side effects:

There may be a downside to over aggressive treatment.  Low levels of LDL may theoretically contribute to hemorrhagic stroke. Statin therapy does have side effects including myopathy and we know especially little about the effects of the high doses needed to achieve the lowest levels of LDL.

Some data show a slight increase in certain types of cancer for statin use, although such an effect may be statistically insignificant.

Conclusion

There is no doubt that statins have played a major role in reducing heart disease across America. But it is also not entirely clear who should be given them, and how heavily they should be used.

With the guidelines for cholesterol treatment being written substationally by doctors on the payroll of major drug companies, skepticism is called for.

Sources:

The Aggressive Low Density Lipoprotein Lowering Controversy
“The Lower the Better” in Hypercholesterolemia Therapy: A Reliable Clinical Guideline?

Cholesterol lowering medications have been increasingly prescribed in the United States. The best selling medication of all time is Lipitor, one such drug. This blog will be exploring statin use and safety over the next week.

A recent non-statin drug is Ezetimibe. It was discovered by Shering-Plough as part of research into reducing LDL, or low density lipoprotein. And it’s pretty good at doing that.

Unfortunately, it’s not entirely clear how much clinical benefit it offers. Several large studies sponsored by the drug company showed that use of Ezetimibe alongside simvastatin did not mean less risk of adverse heart events.

And one of the studies even showed that Ezetimibe use slightly increased risk of developing cancer.

The ENHANCE study showed that Ezetimibe did not help decrease the intima-media thickness as opposed to standard treatment. The SEAS study showed that it did not have significant clinical impact.

Despite the lack of evidence, Ezetimibe is still being prescribed heavily. It’s clinical uses are not entirely clear, and it seems that it should not be a first line treatment.

Sources:

Is There a Problem With Ezetimibe or Just ENHANCEd Hype?