Ep 140 – Pursuing Health Pearls: Talking to Your Doctor About Cholesterol and Statins

Ep 140 – Pursuing Health Pearls: Talking to Your Doctor About Cholesterol and Statins

We are often encountered with the question, “My doctor wants to start me on a statin for my high cholesterol, is it a good idea?” Ultimately, this is not a question that we can answer, as it is a very individual decision that comes down to a conversation between each patient and their personal physician.

However, what we hope to do in the following article is to demystify the topic of cholesterol and statin medications. We will review the guidelines that doctors are working with when it comes to deciding which patients may benefit from statin medications, as well as the potential benefits and harms of these medications.

Our goal is for you to better understand all of the factors that should be taken into consideration so that you can go to a conversation with your personal physician more informed and better able to make the best decision for your unique situation.

 

The Lipid Hypothesis 

The measurement and treatment of elevated blood cholesterol is based on the lipid hypothesis, which states that elevated blood cholesterol (and in particular, elevated LDL cholesterol) increases heart disease risk, and that lowering cholesterol with medications like statins prevents heart disease and saves lives.1  This lipid hypothesis itself has been questioned, largely due to inconsistencies in clinical trial data and conflicts of interest among members who develop and review guidelines.2

For the purpose of this article, we will not be addressing the topic of the validity of the lipid hypothesis. Instead, we’ll focus on reviewing current guidelines for lowering cholesterol to prevent cardiovascular disease. It is worth noting, however, that not everyone is on the same page with the hypothesis upon which these recommendations are based.

 

The Role of Cholesterol3

Cholesterol has gotten a bad rap over the past several decades, but it is essential for life and is made by virtually all cells in the body. Cholesterol is a structural component of cell membranes, and a precursor for steroid hormones such as cortisol, testosterone, estrogen, and Vitamin D. Cholesterol also plays a critical role in the brain, which houses 20% of the body’s total cholesterol.4 The brain doesn't take up cholesterol from the circulation like other organs, but instead makes its own.5

Cholesterol is transported throughout the body to different organs by large fat- and protein-containing molecules called lipoproteins. Lipoproteins come in different sizes and densities and have different proportions of fat, protein, and cholesterol. Subtypes of lipoproteins include: low-density lipoprotein (LDL) or as it’s often referenced, “bad cholesterol,” high-density lipoprotein (HDL) or “good cholesterol,” very-low density lipoprotein (VLDL), and chylomicrons.

 

Introduction to Statin Medications

Now that we’ve reviewed the basic functions of cholesterol and lipoproteins, let’s talk about statin medications. Statins are a class of medications used to lower cholesterol, and they primarily lower LDL cholesterol. They do this in two ways:6

  1. By blocking an enzyme called HMG-CoA reductase, which is important for synthesizing cholesterol in the body. When this enzyme is blocked, the body can’t produce as much cholesterol (Figure 1).
  2. By increasing the liver’s absorption of LDL particles, so there is less circulating in the bloodstream.

Statins also seem to have an anti-inflammatory effect which is separate from their LDL lowering effect, and is not yet fully understood.7

Figure 1. Mechanism of action of statins. Source: The evolving role of statins in the management of arteriosclerosis8

There are several different statin medications, each with slightly different properties. Depending on the statin medication and the dose, they have the potential to lower LDL by varying degrees and are considered low, moderate, or high intensity as shown in the table below:9

Table 1. Statins by intensity. Source: 2018 AHA/ACC Guidelines10

To better understand how widely statin medications are prescribed, we can look to the most commonly prescribed statin which is atorvastatin, or Lipitor. Atorvastatin was the second most commonly prescribed medication in an outpatient setting in the United States in 2017 with a total of 104 million prescriptions.11 On a global scale, the market for all statins was valued at $19.3 billion in 2016.12

 

Lowering Cholesterol for Primary Prevention

In this article, we’ll cover the current guidelines for lowering cholesterol for primary prevention of atherosclerotic cardiovascular disease. Primary prevention refers to interventions intended to prevent a disease from ever occurring.13 In this case, we’re talking about lowering cholesterol with the intention of preventing heart attacks, strokes, coronary artery disease, peripheral artery disease, and the like.

We want to make it clear that the guidelines we will review here do not apply to anyone who already has evidence of cardiovascular disease. Lowering cholesterol in these individuals would fall into the category of secondary prevention, and there are separate guidelines for this situation which will not be addressed here.

 

Introduction to the Guidelines 

Guidelines are published by professional organizations in order to synthesize the medical literature and provide a framework for physicians for treating conditions in an evidence-based and consistent way. Depending on the topic of interest, there may be several organizations who publish guideline recommendations, and they don’t always agree 100%.

It’s important to remember that guidelines are exactly that - guidelines - they are not rules or laws. They are intended to define practices meeting the needs of most patients in most situations, but should never replace clinical judgement, and recognize that each individual patient’s circumstances must be taken into consideration.

Here we’ll be reviewing guidelines published by the American College of Cardiology and American Heart Association (AHA/ACC) in 2018 for managing blood cholesterol.14 These are the most widely used guidelines when it comes to managing cholesterol, and they were developed by an expert panel of cardiologists after reviewing the available evidence.

We will also review recommendations from the United States Preventive Services Task Force (USPSTF)15, which is an independent, volunteer panel of national experts in prevention and evidence-based medicine.16 The USPSTF makes recommendations about many types of preventive services ranging from screening for breast cancer to depression. Because the USPSTF is an independent organization, it is generally thought to be less influenced by industry than speciality organizations like the AHA/ACC.17

It’s also important to note that guidelines change and are updated frequently. Prior to the 2018 AHA/ACC report, guidelines for managing blood cholesterol were updated most recently in 200218 and 2013.19

2018 AHA/ACC Guidelines for Managing Blood Cholesterol20

As a reminder, we are only reviewing guidelines for managing cholesterol for the primary prevention of cardiovascular disease, meaning the guidelines below do not apply to anyone who has already had such disease (stroke, heart attack, coronary artery disease, peripheral artery disease, etc).

In general, it is recommended that healthy adults have a discussion with their personal physician about their cardiovascular risk at least every 4 to 6 years. If risk factors are present (such as obesity, smoking, high blood pressure, elevated cholesterol, type 2 diabetes, or others), more frequent discussions may be beneficial. Here we’ll review what the AHA/ACC guidelines have to say about what factors should be considered in these discussions.

The AHA/ACC guidelines for the management of blood cholesterol for primary prevention of cardiovascular disease are outlined in the flowchart below:

Figure 2. Cholesterol management guidelines for the primary prevention of atherosclerotic cardiovascular disease. Source: 2018 AHA/ACC Guidelines21

Before we dive into the flowchart, there are a few important things to note about these guidelines:

  • Adherence to a healthy lifestyle is heavily emphasized for all patients and should be a first-line intervention
  • Risk discussions between patient and physician are emphasized when deciding whether or not to start a statin medication

LDL > 190 mg/dL

In general, the guidelines address individuals by age group, and we’ll walk through recommendations for each age group here. Before we do that, though, there is one situation that is independent of age, which is the case of very high LDL cholesterol, >190 mg/dL. In this group of individuals, statins are generally recommended. These patients should be evaluated for a condition called familial hypercholesterolemia which is a genetically elevated LDL that may put them at higher risk of heart disease. We won’t go into more detail about familial hypercholesterolemia and statins here, as that is another topic in and of itself. It is interesting to note, however, that there have been no randomized, placebo-controlled trials of statin therapy done exclusively in subjects with LDL cholesterol >190 mg/dL.

Age 0-19

There is no evidence that evaluates the benefits of checking cholesterol levels for the purpose of screening for cardiovascular disease in children of this age range. In certain situations it may be reasonable to start screening earlier, specifically when there is a strong family history of early cardiovascular disease or very high cholesterol. In general, the focus in this age group (as with all age groups), should be on promoting a healthy lifestyle.

Age 20-39

In most cases for this age group, the focus is again on lifestyle. Again, those who have a strong family history of cardiovascular disease or very high LDL cholesterol may benefit from additional investigation regardless of age. Of note, no long-term randomized-controlled trials with cholesterol-lowering drugs have been carried out in individuals of this age group.

Age 40-75

The 40-75 year old age group comprises the bulk of the 2018 AHA/ACC guidelines, and there are a few different decision points to consider:

  • One which was discussed above is the situation of LDL >190 mg/dL, in which a statin is recommended
  • Another is those 40-75 years old who have a diagnosis of type 2 diabetes. In these individuals a moderate-intensity statin is recommended, or potentially a high intensity statin depending on a risk discussion considering the presence of other risk factors. Again, it is important to note that for both diagnoses of type 2 diabetes and high cholesterol, lifestyle should be the first-line recommendation. So if this is a new diagnosis lifestyle changes could be implemented first to potentially reverse the diabetes which would then remove the patient from this category.
  • In all other patients 40-75 years old, without LDL >190 mg/dL and without a type 2 diabetes diagnosis, the decision to start a statin medication is based on a risk discussion between patient and physician.

Risk Discussions regarding whether or not to start a statin medication for primary prevention of cardiovascular disease should occur between patient and physician and take the following into consideration:

  1. Evaluation of the patient’s theoretical risk of developing a heart attack or stroke over the next 10 years using a validated risk calculator
  2. The presence of risk enhancers, listed in the box on the left side of the flowchart above
  3. The potential benefits of lifestyle and statin therapies
  4. The potential for adverse effects of statins and drug–drug interactions
  5. Consideration of the cost of statin therapy
  6. Patient preferences and values

The first step in these risk discussions is calculating the patient’s risk of having a heart attack or stroke in the next 10 years using a validated risk calculator. Information about the patient’s risk factors is entered including age, sex, race, blood pressure, smoking history, whether or not they have diabetes, and whether or not they are on medications for high blood pressure. The calculator then interprets this information and provides a percentage, which is that patient’s theoretical risk of having a heart attack or stroke at some point over the next 10 years. The patient is then stratified into one of four groups based on this percentage:

  • Low-risk (<5%): In general, statins are not recommended in this group
  • Borderline risk (5% to <7.5%): In general statins are not recommended unless there are other risk enhancers present
  • Intermediate risk (7.5% to <20%): In general statins are recommended if other risk enhancers are present
  • High risk (≥20%): Generally statins are recommended

One limitation of this risk calculator is that age is heavily weighted as a risk factor. Although age is a powerful risk factor when looking at large populations, it does not necessarily reflect individual risk as clearly. As an example, let’s compare two individuals both with a calculated 20% risk of having a heart attack or stroke over the next 10 years. Person 1 has perfect blood pressure and cholesterol, has never smoked, exercises every day, and eats well, but happens to be 75 years old. Person 2 is 50 years old but smokes, is on medication for high blood pressure, doesn’t exercise and has prediabetes. While both individuals may have a calculated 10-year risk of 20%, you can see that Person 1’s risk is driven mainly by age, and the healthy lifestyle behaviors he or she practices which are not considered by the calculator are likely much more protective than a statin medication would be. This again emphasizes the importance of the risk discussion between patient and physician and taking more than just the patient’s calculated 10-year risk into consideration.

After calculating the 10-year risk, risk enhancers (listed in the flowchart above) should also be contemplated, particularly for those individuals who fall into the borderline or intermediate risk groups. If risk status remains uncertain after all these considerations, and the patient is not in the high risk category, a CT scan examining calcium in the coronary arteries can be done to produce a coronary artery calcium (CAC) score. This can provide additional information to tip the scales in one direction or another regarding starting a statin medication.

If after all this, in addition to a trial of lifestyle therapy, and a discussion of the benefits and potential harms of statin medications, the patient and physician decide together to initiate a statin medication, the goal should be to reduce LDL cholesterol by a certain percentage depending on the patient’s calculated 10-year risk of developing a heart attack or stroke.

Age > 75

The 10-year risk calculator has not been validated in individuals >75 years old, so the decision about whether or not to start a statin medication comes down to a discussion between the patient and their personal physician. It is also worth noting that as adults grow older, they tend to become more susceptible to statin-related risks.

American Academy of Family Physicians Endorsement

The American Academy of Family Physicians (AAFP) put out a statement of endorsement for the AHA/ACC guidelines in 2019, giving them an “Affirmation of Value.” This means that the AAFP recognizes the AHA/ACC guidelines to provide valuable guidance, but they do not meet their criteria for full endorsement. They cite the fact that an independent systematic review only addressed a small portion of the guidelines, and many of the recommendations were based on low quality or insufficient evidence, as the primary reasons for not fully endorsing them.

USPSTF Recommendations for Statin Use for the Primary Prevention of Cardiovascular Disease in Adults24, 25

Next, we’ll review the United States Preventive Services Task Force (USPSTF) recommendations for using statins for primary prevention of cardiovascular disease in adults. The USPSTF’s recommendations are graded on an A, B, C, D, or I scale, depending on the strength of evidence behind the recommendation:

  • In general, A and B grades are recommendations that have good evidence and should be offered in practice
  • C grades should be offered for select patients depending on the situation
  • D grades should be discouraged, as there is evidence for harm
  • I grades mean there is insufficient evidence to assess these recommendations

The USPSTF makes 3 recommendations about statins for primary prevention. The first two recommendations pertain to individuals aged 40 to 75 years with 1 or more cardiovascular disease risk factors (i.e. dyslipidemia, diabetes, hypertension, smoking):

  • If the calculated 10-year risk of a cardiovascular event is greater than 10%, a statin medication is recommended for the prevention of cardiovascular disease events (stroke and heart attack) and mortality. This is a B recommendation, meaning it should be offered.
  • If the calculated 10-year risk in these individuals is 7.5-10%, clinicians may choose to offer a statin, recognizing that the benefit is likely to be smaller than it would be for the higher risk individuals. This is a C recommendation, meaning it should be offered to select individuals.

The final recommendation is for adults 76 years of age or older, and the USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of statin medications for primary prevention. This is an I recommendation.

Although the USPSTF is generally considered to be a less biased body, even these guidelines have been questioned.26 This is because:

  • Some of the studies used in their review included patients who already had evidence of cardiovascular disease, meaning the statin was being used for secondary, rather than primary, prevention.
  • The reviewers did not have access to the primary research data, so they had to rely on peer-reviewed published reports
  • Most of the trials used in the review were industry-sponsored, and in general, industry trials report greater benefits and less side effects than non-industry sponsored trials27

 

Potential Benefits and Harms of Statin Medications

As discussed above, the potential benefits and harms of statin medications should be considered in risk discussions prior to deciding to start the medication.

It’s important to note that the research used to assess the potential benefits and harms of statins is plagued by the same issues with research mentioned above. 28,29 The vast majority of research in this area is sponsored by industry, which means it is subject to selective publication of studies showing a significant benefit of statins and withholding of negative results. That being said, here we will review what is known about the potential benefits and harms of statins using the currently available data.

 

Potential Benefits of Statins for Primary Prevention

It’s important to note that taking a statin medication is not guaranteed to prevent a heart attack or stroke in every person, but there is potential to benefit. First, we’ll review the potential benefits for our lower risk individuals with a calculated 10-year heart attack or stroke risk <20%.30 In this group:

  • 1 in 217 people treated with a statin avoid a non-fatal heart attack
  • 1 in 313 people treated with a statin avoid a non-fatal stroke
  • There is no statistically significant mortality benefit31,32

When we look at individuals in the high risk group with a calculated 10-year heart attack or stroke risk ≥20%, evidence suggests that statins may reduce mortality in addition to heart attacks and strokes,33 although the mortality benefit is debated.34,35

 

Potential Harms of Statin Medications

One of the most common side effects of statins is muscle pain, which is reported in 1 to 4 of every 21 people, or 5-20% of individuals.36,37,38 The vast majority of these cases are mild muscle pains though there is a very small risk of more severe muscle damage as well. The muscle pains typically resolve if the patient is switched to a different statin or if a lower or different dosing regimen is used.

The supplement CoQ10 is thought to be helpful by some in reducing muscle side effects of statins,39 but this hasn’t been proven out in all studies. The rationale behind this is that the HMG-CoA reductase enzyme that statins inhibit is also important in the production of CoQ10. CoQ10 is an antioxidant that is important for energy production, and statins have been shown to reduce blood levels of CoQ10 by 16% to 54%.40

There is also a concern about liver damage from statins.41 Significant elevations in liver enzymes (AST or ALT) are seen in up to 3% of patients taking statins and are typically self-resolving. Permanent liver damage and liver failure are very rare.

Statins also seem to increase the risk of type 2 diabetes, affecting 1 in every 204 people treated with statins.42 There is also some evidence that statins blunt the adaptations to exercise training,43 and though controversial, the potential association between statins and reversible cognitive impairment has led the FDA to require it to be listed on the medication label.44 Additionally, those taking statins do have to take a pill every day, and they or their health plan have to pay for the medication.

These potential benefits and harms of statin medications should be weighed by each patient with their physician, in the context of their own personal risk factors, prior to initiating a statin for primary prevention.

 

Potential Benefits of Lifestyle Behaviors

Our discussion would not be complete without a review of the potential benefits of healthy lifestyle behaviors. As stated earlier, healthy lifestyle behaviors should be encouraged in all patients and should be used as a first-line therapy in most situations for primary prevention of cardiovascular disease. These interventions have no known side effects, and they confer benefits to overall health and well-being beyond cardiovascular disease prevention. Here are some examples of interventions that we know to have a significant benefit in cardiovascular disease prevention:

  • Mediterranean Diet: Studies show a 30% relative reduction in cardiovascular event risk in those consuming a Mediterranean Diet compared to a control low-fat diet.45
  • Physical Activity: Going from being physically inactive to achieving the recommended 150 minutes of moderate-intensity aerobic activity per week was associated with a 23% lower risk of mortality from cardiovascular disease, a 17% lower incidence of cardiovascular disease, and a 26% lower incidence of type 2 diabetes.46
  • Smoking Cessation: Quitting smoking has been shown to have a relative risk reduction of cardiovascular disease of 39%.47
  • Social Stress: Factors including social isolation, perceived loneliness, living alone,48 and low socioeconomic status49 each account for a 26-32% increased risk of mortality.

 

We’ve Covered a Lot...

Again, we want to reiterate that this discussion was pertaining only to the primary prevention of cardiovascular disease, meaning only individuals who have not already had a heart attack, stroke, peripheral artery disease, or the like. Lifestyle modifications are always first line and as discussed above, they can have a significant impact on lowering cardiovascular disease risk.

In most situations, the decision to start a statin medication comes down to a discussion between a patient and their physician about the potential benefits and harms in the context of the patient’s own unique risk factors. Above, we’ve laid out how to assess individual risk as well as some of the potential benefits and harms of statin medications for primary prevention that should be considered when having these discussions.

We do want to note that in reality, risk discussions to the level of detail described here are not always occurring in practice, and this is likely due in large part to the lack of time in primary care visits.50,51 Most patients see their doctor for 20 minutes once or twice per year, and cardiovascular risk is just one of the topics that needs to be addressed. Those 20 minutes also include a discussion of chronic health problems, other prevention topics such as cancer screening and immunizations, as well as any acute concerns or symptoms. Because of this, if you do want to have a more in-depth cardiovascular risk discussion with your physician, it may make sense to schedule a dedicated visit for that purpose only.

We hope that you’ve found this information to be helpful, and that next time you meet with your personal physician you’ll have a better understanding of the factors that should be considered prior to starting a statin medication so that you can have an informed discussion and come to the best decision about your health, together.

Disclaimer: This podcast is for general information only, and does not provide medical advice. We recommend that you seek assistance from your personal physician for any health conditions or concerns.

This post was originally published on April 21, 2020.

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