Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish

Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.
We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.
Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.
Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.
I’ve been utilizing CAC (also termed  heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for

adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain

Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.
To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.

Significant Of CAC Score

As the new ACC/AHA guidelines state:

If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.

A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.
Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years
Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400
Patients with a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.
On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.

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Patients with CAC who were prescribed a statin had a significantly reduced risk of MACE (aSHR: 0.76; 95% CI: 0.60 to 0.95; p = 0.015), whereas patients without CAC had no associated MACE reduction (aSHR: 1.00; 95% CI: 0.79 to 1.27; p = 0.99). p = 0.097 for interaction between statin treatment and CAC presence. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s)

The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.
Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.

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Benefit of statin therapy was significantly related to CAC group with benefit in patients with CAC score >100 but not in patients with CAC <100. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s).

But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).
Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)
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Benefits of CAC Testing In The Young

So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.

But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.
The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events.  It was  a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.
The conclusions:

Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.

screen shot 2019-01-19 at 12.36.44 pmI read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.
The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them  10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.

Other Risk-Enhancing Factors To Consider In The Young

The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.
screen shot 2019-01-19 at 7.33.39 am
Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?
What about nontraditional lipid/biomarkers?  I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.
Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.
Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.
It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.
Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.
Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.
Skeptically Yours,
-ACP

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32 thoughts on “Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish”

  1. Thanks for this post. I was feeling chicken about starting Praluent 150 but this reminded me not to screw around (high LDL, lpa(a), and coronary calcium of 330 at 57 (33 at 51). Muscular and gastro side effects from statins, which I gamely tried for most of 8 years.

    Reply
  2. Are there any tests you recommend for a 26yr old suffering from organic erectile dysfunction, elevated lipids and a family history of CVD. I know erectile dysfunction can be a sign of future CVD/atherosclerosis.
    Perhaps having LP(a), ApoB, LDL-P, CRP tested possibly along with penile ultrasound (by urologist) and possibly cardiac imaging?

    Reply
    • those blood tests would be a great start.
      I defer on penile testing to the urologist.
      The only possible cardiac imaging I would consider would be carotid IMT or coronary calcium scan.The CAC would almost certainly be a zero score in someone your age but if it were nonzero it would put you in a very high risk category. The carotid IMT would have to be done by an extremely good lab to be of any value and even then we don’t have good data in subjects in your age range.

      Reply
  3. Hi Dr Pearson,

    I wrote on here before, and you provided great advice. To sum, about 3 years ago, I had a CT angio w/contrast. I went to the ER when I developed sudden onset of thousands of PVC’s / PAC’s from exercising. They ran troponin and D-Dimer, and D-Dimer was high but troponin was normal. Rest of blood labs were normal, although total cholesterol was a big high. Radiology report said coronary artery disease with distal and mid segments of LAD artery having some calcification. Had a follow up with the on -call cardiologist, and then subsequently saw another guy to do 24 hr holter. He also wanted to do a stress echo, but I never followed up. Bad move. My PVC’s and PAC’s eventually got lot better, and I was started running and exercising again.

    So, after 3 years, I decided to follow up with the original cardiologist when I saw the report again of coronary artery disease. He saw me, did an EKG, said I had slight ST elevation, and said to go for the CAC and stress echo. CAC report came back, and I’m pretty floored. I’m 46, non-diabetic, normal labs including most cardiac markers like hsCRP and lp(A) being normal, but just high total cholesterol (210) with LDL / HDL ~ 2.5. My CAC scores were around 400 in the LAD with diffuse calcification, and ~300 in the RCA. The cardiologist that did the report is suggesting a nuclear stress echo. Still no word about the regular stress echo. I hit 14.0 for MET and was able to go 110% of max HR. The next follow up with the cardiologist is in 3 months from now — only available opening. I’m pretty sure I’m going on a statin and some other meds.

    So, I feel like I’ve got this ticking time bomb. What do you normally advise in younger patients like me with really terrible scores like this? Will a statin and diet modification keep scores fairly level? I’ve read in your other posts that CAC scores typically rise by 10% every year, even on a statin like what Donald Trump is on. At what point do you advise surgical intervention? I’m now wondering if my PVC / PAC’s were brought on by my coronary artery disease.

    Much thanks for all you do.

    Reply
    • John,
      Glad I was able to help previously.
      I’ve seen a fair number of youngish patients with high CAC scores like you. Most of them inherited a tendency to plaque formation/atherosclerosis rather than it being due to lifestyle.
      For these patients if their stress echo was normal at that level of exercise then no other testing is warranted.
      With proper medical therapy you can do very well.
      For patients like you I recommend a statin and would start it and 81 mg aspirin right away.
      Studies (like the ISCHEMIA and COURAGE trials which I’ve written about on this website) show that no surgical or stent intervention is warranted in patients with good exercise tolerance and no symptoms despite large build up of atherosclerosis in their coronary arteries and despite significantly blocked arteries.

      Your CAC score will continue to rise but that # will no longer be important.

      Reply
  4. What does it mean if my calcium score is zero but early plaques were seen in a carotid ultrasound? Is it important to have a follow up calcium screening in several years in this situation? I wish the Mesa app accounted for ultrasound carotid findings in its calculations.

    Reply
    • I’ve written a fair amount on vascular screening with IMT and plaque search in earlier posts.
      If a true plaque (and I say that because it takes a lot of experience to identify real plaque) was noted in the carotid then in my mind the patient has atherosclerosis and is in a high risk category irrespective of the CAC. Follow up CAC is warranted after several years. I’ve seen carotid plaque and especially increased IMT precede development of non zero CAC.

      Reply
    • I’m about to publish a post on a superior risk calculator for use with coronary calcium scores called the MESA coronary risk calculator.
      It allows ages of 40-84. Not sure what happened for you.

      Reply
  5. Dr. Anthony,
    I want to say thank you for all the work you do in helping us learn more about cardiovascular disease. As a youngish, 36 year old with family history of pre-mature cardiovascular disease, I had a calcium score this last year and scored a 44. This puts me in the 95th percentile. Is there anything that can be done to reduce plaque in the coronary arteries?
    Thank you

    Reply
    • Yes. Quite a bit. The best evidence for reducing plaque is for statin therapy. Lifestyle optimization helps but when the risk is inherited and plaque has developed despite optimal lifestyle statins and other risk modifying medications are immensely helpful. See my post on Dealing With The Cardiovascular Cards You’ve BEEn Dealt.

      Reply
      • Well I definitely need to read that post about the cards your’e dealt. Had the Boston Heart study done and I have drawn all the short straws. The good news is, neither of my parents died of CVD. Dad was 82 with Pancreatic cancer and Mom was 89 with dementia and an undiagnosed cancer. She did have stents placed at 80. And they re-occluded, but she was not dietary or drug treatment compliant. In her defense, the statins killed her legs and no other treatment options were available to her. No siblings have had a coronary event. But I have Lp(a) and, untreated, my HDL was 90 and my LDL was 215. I am 5’5″ and weigh 125. I work out vigorously 4-6 times a week and have for years. I am 59. I am asymptotic of CVD, with the exception of a bout with PVCs for a while. But reading Dr. Hyman’s book on nutrition…he urges people who have high LDL and Lp(a) to have the calcium score bc a lot of his nutritional advice would be counter-indicated. So I decided to do it. And guess what? I scored 300 with moderate calcification in the LAD. And I also had that MRI of my lipid particles and I have the small sticky ones. In the beginning, I didn’t want to take the statins…bc i have a genetic predisposition to the myopathy. So I became a vegan and lowered my LDL from 215 to 160. Not bad but clearly not enough. I went through 3 different statins – all caused major muscle pain in my legs that kept me from working out. So that’s not good. Got approved for Praluent 7 months ago. And I take Zetia. LDL is down to 70, but they want it below 50. Yikes. So switching to the 150 mg soon. So bc of the calcium score i was told to have the nuclear stress test. Which I did. And that came back normal. Which is puzzling to me. So i see you do not suggest that approach. And am wondering why. And also, what nutritional or supplament advice do you have for people on Praluent. Finally…your daughter is my new PCP and I love her!

        Reply
        • My cardiologist recommended the NMR LipoProfile test for me.
          Since my results were good, I don’t have to take statins.

          Reply
        • Terri,
          Congratulations on getting my daughter, Chelsea Pearson, as your PCP. I’m a little biased but I think she is a fantastic internist!
          To your questions:
          1. You had high calcium score but normal stress test. This is very common. The high scores indicates a lot of plaque build up in the coronary arteries putting you at risk for heart attack but you can have lots of plaque and have no significant blockage of the blood flow which causes symptoms. Stress tests are designed to identify significantly blocked arteries , typically more than 70%.
          Thus although you have built up plaque it is not creating any problems right now.
          Whether high calcium score patients without symptoms should get stress tests is an area of controversy which I hope to address soon in a post.
          2. My nutritional advice for people on Praluent is no different than for those not on it. So check out my writings on diet and nutrition. Chelsea and I tend to be on the same page for nutritional advice.
          I would not advise supplements, something I’ve written a lot about elsewhere on the site.

          Reply
      • Hey Doc,
        I take 10mg Crestor every other day, 10mg zeta daily, try to be a consistent exerciser, eat a realativley low carbohydrate diet, try to manage my stress. As a side I also take Metformin 500mg ER. My understanding is there might be some anti-inflammatory/longevity properties. LDL-P is about 1000. Small ldl-p is just above 500. Anything else that should be done? Anything I’m missing? Thank you again for all your knowledge

        Reply
        • I’m not sure about the value of metformin outside the setting of diabetes.
          Otherwise, don’t smoke, eat plenty of fresh vegetables, maintain ideal body weight, strive for restful sleep, perform regular aerobic and muscle-strengthening exercise, find somebody to love and listen to good music on a regular basis.

          Reply
  6. Hi Anthony,
    Really nice piece as usual. I agree this investigation is becoming increasingly useful and a bigger and bigger part of daily practice.
    You didn’t touch on troponin which I think will almost certainly become part of this equation in future although I accept is still not at the guideline stage yet.
    A more practical question – I wonder what your approach is to further investigation of those asymptomatic patients with high scores (say >400 or >age adjusted 75th centile). We’re now looking for ischaemia in these but I am somewhat sceptical as to whether this is right. Your thoughts?

    Reply
    • Thanks for the kind words.
      I don’t see the value of troponin outside the setting of acute chest pain and concern about MI. Newer, more sensitive troponins have been developed and we’ll see how they are to be utilized.
      The question on whether asymptomatic patients with high CACs should have assessment with stress testing or other techniques is a great one.
      I know the nuclear medicine societies recommend stress testing for these people but I don’t agree with that. I hope to summarize the data in a future post.

      Reply
      • Interesting – there’s quite a lot of observational data from large cohorts relating troponin values independently to risk. It’s been looked at in the WOSCOPS, JUPIITER cohorts and others. You are right that it all leverages use of high sensitivity assays. Also the relevant values are well below the 99th centiles that we are familiar with for chest pain/MI evaluation and hence why it has to be hs assays. Given the regulatory problems getting these available in US has perhaps diminished interest thus far but I suspect it will come soon. Some of these cohorts suggest that the independent value of troponin to predict risk is superior to CRP and almost certainly more use than carotid scanning (this is pretty useless in the era of CTCS I would say)

        Reply
  7. Once a person has been on a statin regime for several and his Cholesterol is undercontrol, is it helpful to continue to have a coronary calcium test, day every 10 years?

    Reply
      • Why not, Doc. Is it because the statin will actively increase the CAC score? So, improving one’s risk with a statin will worsen his risk as evidenced by his increased CAC. ??
        And, what about the large soft vulnerable plaques that aren’t stabilized with calcification? There’s a whole range of calcification causes and presentations out there, no?
        Just trying to understand this.

        Reply
        • Jeff,
          Good questions as usual.
          The value of a follow up CAC is extremely limited and I don’t recommend it to my patients.
          I think I’ve discussed this elsewhere on the blog but I’ll try to post an update soon.

          Reply

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