Making sense of the new cholesterol and heart disease guidelines

Cardiovascular disease (CVD) is the leading cause of death in both the U.S. and the World. One of the prime contributors to heart disease is high levels of bad cholesterol (LDL) in the blood. Too much LDL can produce atherosclerosis, i.e. clogging of arteries, which can lead to heart attacks or stroke.

The big news this week was that the American Heart Association (AHA) passed new guidelines on how people should manage their cardiovascular disease risk. In the past, the emphasis was on your LDL level and getting it below a specific number. Now the focus is on calculating your cardiovascular risk which depends on other factors like diabetes, smoking, and blood pressure in addition to cholesterol. A key role will be played by statins, the primary medication for lowering LDL, because of its superior efficacy (and fewer side-effects) compared to other cholesterol-reducing medications.

Statins act by inhibiting the enzyme HMG-CoA reductase, which is the first enzyme in the pathway that synthesizes cholesterol in the liver. The lower amount of cholesterol causes liver cells to make more LDL receptors that take up LDL particles from the blood. The effect is dramatic, and on average statins can lower blood LDL by 70 mg/dL. Most of the side-effects are relatively minor (e.g. raised liver enzymes), making statins a potent medication for combating heart disease. Some commonly prescribed statins include Lipitor, Crestor, Pravachol, and Zocor.

What are the principal changes in the new guidelines? The old guidelines emphasized specific LDL thresholds for various classes of patients:

• Less than 70 mg/dL for those with heart or blood vessel disease and for other patients at very high risk of heart disease.
• Less than 100 mg/dL for high risk patients (for example: some patients who have diabetes or multiple heart disease risk factors).
• Less than 130 mg/dL otherwise.

As mentioned above, the new guidelines emphasize cardiovascular disease (CVD) risk over specific LDL numbers. The risk depends on other factors such as age, blood pressure, whether you smoke, whether you have diabetes, along with your cholesterol data. The goal is to create a more holistic approach to assessing heart disease.

Under the new guidelines, patients will fall into two risk categories:

• The high risk category are people with cardiovascular disease (e.g. have had a heart attack, stroke or severe atherosclerosis), people with high levels of LDL (190 mg/dL or higher), and people with Type 2 diabetes.
• The lower risk category are people not in the first group who possess elevated 10-year risk for atherosclerotic cardiovascular disease (ASCVD) i.e. a greater than (or equal to) 7.5% chance of having a heart attack or stroke in the next 10 years.

In both groups the primary treatment option is statin therapy, either high-intensity (reduces LDL by at least 50%) or moderate intensity (reduces LDL by 30 to 50%) therapy. In addition, there may be recommendations for lifestyle alterations (i.e. diet and exercise).

As a result, there will be changes in how some patients are treated. Here are a couple of scenarios that may arise:

Scenario 1: a person who is classified with CVD and an LDL level of 150 mg/dL. Under the old guidelines, this person would be put on statins. If the statins did not bring her LDL down below 70 mg/dL (say 75 mg/dL), then she would have to consider additional medication. Under the new guidelines she would put on a high-intensity statin program whose goal would be to reduce her LDL level 50%, and so additional medication would not be needed.

Scenario 2: a person without CVD or diabetes and possessing an LDL level below 130, e.g. 125 mg/dL. Under the old guidelines such a person would not need statins. Under the new guidelines if the risk calculator (perhaps due to high blood pressure) produced an elevated ASCVD risk, then he would be treated with statins (probably moderate-intensity).

The concept of calculating CVD risk for the larger patient population is new. The online tool for performing this calculation is an Excel spreadsheet (download link) in which you enter information about your blood pressure, and whether you smoke, your cholesterol level, etc. From these numbers, the spreadsheet outputs your 10-year ASCVD risk.

Unfortunately the calculator may be flawed. Doctors have raised concerns that the formula overestimates cardiovascular risk for some people which could lead to the overprescription of statins. For now some doctors recommend sticking to the old guidelines until the calculator is fixed:

"The answer was that the calculator overpredicted risk by 75 to 150 percent, depending on the population. A man whose risk was 4 percent, for example, might show up as having an 8 percent risk. With a 4 percent risk, he would not warrant treatment — the guidelines that say treatment is advised for those with at least a 7.5 percent risk and that treatment can be considered for those whose risk is 5 percent."

Calculating risk is a challenging problem. There is some debate over which data should be used to make the calculations. These issues are expected to be ironed out over time resulting in more accurate risk estimates.

In summary, how does one make sense of the new guidelines? There are a few takeaway points. First, the role of statin therapy is likely to increase, while the role of other medications will decrease. Many doctors view statins as excellent for reducing heart disease risk even beyond its observed effects on LDL levels, with limited side-effects. People not taking statin now may be put on statins. Second, there will be a greater emphasis on cardiovascular disease risk (which incorporates factors other than cholesterol), and less emphasis on specific LDL thresholds. People will become familiar with their ASCVD 10-year risk number, which hopefully will have a motivating effect. Third, the new system has the potential for being more flexible and tailored to the individual including introducing more patient-centered care and lifestyle recommendations. Taken together, the new guidelines should be more effective at preventing CVD mortality than the old guidelines.

Figure 1. Calculating your cardiovascular risk may entail lifestyle changes and more importantly the use of statins.