Coronary artery calcium scan

Coronary artery calcium scan
(click the link above to view on the website)
Greetings –

After last week’s deep dive into the relationship between LDL cholesterol, systolic blood pressure, and cardiovascular disease, I thought it would not hurt to go a bit deeper in the weeds. You’ll recall that atherosclerosis takes the greatest proportion of lives when people are in their later years, but it’s a disease that takes a long time to evolve, starting in the first two decades of life. That’s right, the process begins almost as soon as you’re born. By the time you’re in your 30s, and certainly into your 40s, there is ample evidence of the disease at autopsy.

The etymology of atherosclerosis derives from athero—meaning a gruellike substance, and sclerosis—meaning a hardening. This porridge of oxidized sterols, lipids, cholesterol, macrophages, calcium, fibrin, and other cellular materials make up the lesions, or plaques, within the walls of the arteries. Influenced by multiple risk factors, the atherogenic process begins early in life and slowly progresses until the plaque narrows, erodes, or ruptures causing ischemic clinical events (e.g., fatal or non-fatal heart attack or stroke). 

If there is one benefit to a disease that takes so long to progress from microscopic (i.e., subclinically, at the cellular level) to macroscopic (i.e., clinically, at the organ level), it’s this: there is ample time to do something about it. When you think of atherosclerosis, think of saving for retirement. It’s a multivariate compounding problem that takes time. What determines the outcome?

  1. At what age do you want to retire?
  2. Will you inherit any money or is there some other windfall awaiting you?
  3. How much do you plan to spend after you retire? (And how long do you expect to live to spend it?)
  4. Have you budgeted for catastrophic loss (e.g., 10 years of high-priced assisted living at the end of life)?
  5. How much do you make before you retire?
  6. How much can you save during that time?
  7. What is the net-of-fees, after-tax rate of return on that invested capital?
  8. At what age do you start saving/investing?

Given that I’m not a financial planner, I’m sure some of you will mock the simplicity of my analogy, but I think you get the point. And you’ll hopefully appreciate that as you manipulate one variable, others need to flex in response. For example, the earlier you want to retire and/or the more you want to spend in retirement and/or the later you wait to start saving, guess what? The more you need to save and/or the higher the rate of return you’ll need. I could go on and on with permutations, but you already know this.

How does this apply to atherosclerosis? 

  1. How old do you want to be before atherosclerosis goes from being subclinical (i.e., no risk of hurting you) to clinically relevant? 
  2. What is your family history of atherosclerosis? 
  3. Do you smoke or have high blood pressure? 
  4. Is your Lp(a) elevated?
  5. On a scale of 1-10, how metabolically healthy are you?  
  6. What is your current burden of disease? 
  7. What are your biomarkers for atherosclerosis? 
  8. What is your appetite for pharmacologic intervention? 
  9. Do you have contraindications to such interventions? 
  10. How soon are you willing to start such interventions? 

I could go on, but I think you get the point. One concern I have with 14-minutes-per-year medicine is that not enough people ask these questions. Especially the first one, believe it or not. Why is this first question so important? No one, not a soul, is immune to this disease, even the genetically gifted centenarians who will outlive us all. So it absolutely matters that you handicap question #1. If you’re interested in longevity—both the lifespan and healthspan part of the equation—it means you want to live longer. That means you want to delay death. That means you want to delay the onset of the most inevitable disease to our species.

Which brings us to the point of today’s post. How can one assess the risk of an individual at a point in time? I’ve written extensively on some of these, but today I want to shine a light on #6—what is the current burden of atherosclerosis?

In fact, I want to shine that light on a subset of the population: those without any clinical evidence of disease (i.e., those who have not already had a heart attack or shown symptoms of heart disease, such as chest pain on exertion). Think of this as a backward-looking proxy for risk (versus biomarkers, which are a forward-looking proxy for risk). If the biomarkers tell you how dangerous your neighborhood is, a backward-looking test will tell you if anyone has tried to break into your home.

There is a tool that is gaining more recognition from academics, guidelines, clinicians, and patients called a coronary artery calcium (CAC) scan. The CAC scan, using computed tomography (better known as CT), assesses the presence and extent of coronary artery calcification (calcium being radio-opaque). The test reports on location and quantification of calcium within the three main coronary arteries and yields a numerical CAC score in a metric called Agatston Units (named after the tool’s developer, Arthur Agatston). A patient with no calcification will have a score of “0” which escalates as vascular calcification increases. A score of “1” and above indicates the presence of calcification, most often in the form of hard plaque. Importantly, and discussed in more detail below, soft plaques can escape detection using a CAC scan. CAC score results fall into four categories which correlate with the severity of disease and range from no disease to severe disease.

Table 1. Categories of CAC scores.

When I talk about CAC, I often use an analogy of atherosclerosis as a crime scene involving breaking, entering, and vandalizing. A criminal went into your house while you were on vacation and did some damage to your home, damage that was somewhat irreparable in that you couldn’t repair your home back to a state where you never would’ve known there was a break-in. Holes in the walls of your home needed to spackle to patch them up. The repair work left clues of damage. In the case of atherosclerosis, a lesion is a damaged artery, and the calcium deposits are a sign of repair to the artery.

A CAC score above zero tells you that there’s been a bad enough break-in to require repair. However, a lot can go on in the disease process leading up to that point that goes unnoticed by a CAC scan. Additionally, a CAC scan does not necessarily identify the plaques that might do the most damage.

A 2013 study, for example, looked at a group of 17 patients who died from an acute myocardial infarction (AMI) and compared them to 15 age-matched controls without a history of cardiovascular disease (CVD). The investigators studied 960 coronary segments in these patients and found calcification in 47% of the segments in the AMI group and in 24.5% in the controls. The calcification was not correlated with the presence of unstable plaques. The study’s conclusions are summed up by the article’s title: “Coronary calcification identifies the vulnerable patient rather than the vulnerable plaque.”

In other words, more than half of the lesions leading to sudden death in the AMI group exhibited little to no calcium. Unstable plaques, the ones more likely to cause grave damage, showed a lower degree of calcification compared to stable plaques. A low to zero CAC score suggests a lower risk of future events, but it does not mean a zero risk of future events. A CAC score is predictive (multiple clinical studies of varied populations have validated the CAC scan as a valuable risk-assessing tool as the extent of CAC accurately predicts 15-year mortality in asymptomatic patients) and diagnostic, certainly a tool worth having in the toolbox, but it doesn’t tell you what else is under the hood.

One study compared CAC with standard coronary heart disease risk factors (e.g., LDL cholesterol, HDL cholesterol, hypertension, current smoking, triglycerides) for predicting CVD events in 4,903 asymptomatic men and women between the ages of 50-70. They found that, after 4.3 years of follow-up, for CAC scores 100 or greater compared to scores below 100, the relative risk was 9.6 for all CVD events (95% CI, 6.7-13.9), 11.1 for all CHD events (95% CI, 7.3-16.7), and 9.2 for non-fatal heart attacks and death (95% CI, 4.9-17.3). The CAC score predicted events independently of standard risk factors and was better than the Framingham risk score in the prediction of events. To get a sense of the absolute risk, take a look at the event rates in Table 2 of the paper (shown below).

Table 2. CAC score and all coronary disease events.*

In another study analyzing outcome data from the Multi-Ethnic Study of Atherosclerosis, investigators found that 10-year event rates for individuals between the ages of 55-64 with a CAC score of zero were 3.1% compared to 16.7% for people with a CAC score 300 or above.

A CAC score of zero may be the best predictor we have of low estimated CVD risk, but it does not grant one cardiac immortality, as you can see from these studies. There are a number of modifiable risk factors that should not be ignored because of a score of zero, for example, managing blood pressure, lipoproteins, insulin, smoking status, inflammation, glucose, stress, exercise, and sleep may all play a role in disease progression.

How do I use a CAC scan in my practice? Basically, I find it helpful in two scenarios (and this is discussed in great length in my interview with Dr. Ethan Weiss):

  1. A zero score in someone very “old” who is otherwise low risk and who has a low appetite for pharmacologic primary prevention, and
  2. A non-zero score in someone young (i.e., ~50 or younger) who is otherwise reluctant to engage in pharmacologic primary prevention.

A zero score in a 40-year-old only tells me they are “age-appropriate”—not at all that they are immune to atherosclerosis.

I’ll take a CAC of zero over non-zero all day long, make no mistake about it. If you only concern yourself with a 10-year risk horizon, it’s a mighty fine tool. But if you want to think about risk beyond that, you need to concern yourself not only with how many times you’ve had a break-in, but also the risk posed by the neighborhood you live in.

– Peter