Sunday, January 23, 2011

Cholesterol, CVD Risk, and Type 2

Deciding whether or not to use a statin to reduce cholesterol levels can be confusing.

On one hand is the medical profession, which in general thinks statins are good things and that LDL cholesterol levels above normal ranges should be treated with statins. Recently, some have been recommending statins even for people with normal cholesterol levels but elevated levels of C-reactive protein (CRP), an indication of inflammation.

In some populations, lowering cholesterol with statins has been shown to result in lower rates of cardiovascular "events" and deaths. But some people think this isn't because of lower cholesterol levels. They suggest that the statins have some other effect as well and the lower cholesterol levels are simply a "side effect" of the drug.

At the other extreme are people who think statins are poisons. Some think no one should take a statin. Others agree they're warranted in specific populations, for example middle-aged men with previous heart attacks, but they say there's no evidence that statins help women or elderly men.

A recent Cochrane Systematic Review concluded that risks of statins are greater than benefits for those at low risk of heart disease. However, when you have diabetes, you're not considered to be at low risk.

An earlier study concluded that statins don't benefit women who have not had a heart attack and in fact may increase cardiovascular risk in this population. They say CRP levels are better predictors of heart attacks in women.

Most people agree that statins do have side effects, most commonly muscle weakness or pain, which can cause permanent damage if it's serious (rhabdomyolysis). In mild cases, taking coenzyme Q10 can sometimes help with the muscle weakness. Tendons can also be weakened by statin treatment (and treatment with other drugs like niacin that reduce cholesterol).

Beatrice Golomb of the University of California at San Diego has been studying side effects of statins and has published a comprehensive review on the topic. She says the two most common side effects are muscle weakness or pain and memory impairment.

She agrees that statin benefits outweigh risks in middle-aged men with high cholesterol and existing heart disease who tolerate the drugs, and that statins probably benefit middle-aged men with high cholesterol and "significant other risk factors for heart disease."

But she says that although those without significant risk factors for heart disease do have fewer cardiovascular deaths, there is not even a trend for lower overall death rates. In other words, fewer heart attacks and strokes but more deaths from other diseases.

Golomb says that statin benefits are not clear in middle-aged men who have heart disease or significant risks but who get side effects from statins. There is some evidence that the benefits of statins don't occur in people who get side effects.

Golomb says there is currently no evidence that statins benefit women or men over 70. They do reduce heart attacks, she says, but not overall mortality.

One problem when reading about all these studies is that different studies use different patient populations and different end points, but the news media tend to report the results without emphasizing that point.

So a drug-company-sponsored trial might be headlined as "Drug X Reduces Heart Attacks by 40%" when in fact the study showed that the drug reduced heart attacks in middle-aged men who had already had several heart attacks, had high blood pressure and high blood sugar, and smoked, and the deaths from some other disease increased with the drug. But what the public, and some physicians, will remember is "Drug X prevents heart disease."

And the confusing thing for those of us with diabetes is knowing whether or not simply having diabetes constitutes a "significant other risk factor."

Most people consider simply having diabetes to give you the same risk of cardiovascular events as people who have already had a heart attack. Is that true?

A recent Spanish research group says no, at least in the Spanish patient population they studied: 4410 patients aged 30 to 74 years, 2260 with type 2 diabetes and 2150 who had already had an acute myocardial infarction but no diabetes.

They found that the 10-year hazard ratios for the type 2 patients were significantly lower than those of the MI patients.

That's encouraging. So should we stop worrying about heart disease?

Definitely NO!

For one thing, other studies have had conflicting results. Some show that people with diabetes have heart disease death risks similar to those of nondiabetics who have had heart attacks; others show the opposite. Another study showed that prior heart attacks resulted in higher risks than diabetes among men 45 to 54 years old, but in older men, the risk was reversed.

As noted by the Spanish researchers, "Part of the discrepancy may stem from differences in the duration of diabetes, type of treatment, and baseline glucose control of diabetic patients included in the studies."

The cited studies also noted differences according to the age and sex of the patients. Furthermore, the results may depend on how you define diabetes.

Someone with type 2 diabetes who was diagnosed 5 years ago, controls blood glucose levels well, eats healthy foods, gets a lot of exercise, doesn't smoke, and makes sure to keep blood pressure and lipid levels in good ranges would be different from someone who is unfortunately probably more typical: a patient who just takes a pill or two, doesn't measure blood glucose levels, continues to smoke and spend most of the evening watching TV, eats mostly fast food or convenience foods, and has high blood pressure.

And the recent Spanish study was comparing diabetic patients with patients who had already had an acute MI, not with healthy people.

When we have type 2 diabetes, we're still at increased risk of heart disease, and we should do whatever we can to reduce that risk: Keep blood glucose levels down, monitor lipid levels and treat if necessary, monitor blood pressure and treat that if necessary, get regular exercise, and eat a healthy diet, although definitions of "healthy diet" of course depend on who you're talking to.

But all these studies illustrate the need to be vigilant when reading a popular press article stating that some study has shown something or other. First, see if you can read the journal article that the popular press story refers to. Even if you can't see the full text, you can usually see the abstract for free.

Find out what populations were studied, how various parameters were measured, and how the researchers define diabetes.

This takes a lot of time, and a firm grasp of statistics helps. So it can be frustrating when you're trying to earn a living or spend time on other projects and don't have time to pour through confusing research reports all day.

Sometimes the authors of drug-company-sponsored studies have used statistics to spin the results to make their drugs look more favorable. You sometimes need to comb through the methods and the statistics to see how the results have been biased. This takes a lot of time.

When you can't track all this down, don't ignore the health news, but take the health news you hear on TV or read in your local paper with a grain of salt. If your LDL cholesterol level is high, you might want to try a statin. Some people can take them without getting side effects. But be vigilant. If you get muscle weakness, try some coenzyme Q10, which Golomb says helps about 70% who have that problem. Some people recommend taking the coenzyme Q10 even if you don't have muscle problems.

But if the muscle pain or weakness persists, talk with y0ur doctor about other alternatives, like niacin. Muscle pain that progresses to rhabdomyolysis is serious.