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.
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 without 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.
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.
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)
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.
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.
I 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.
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.