Coronary artery calcium, or CAC, is one of the most useful noninvasive tools we have for assessing cardiovascular risk. Using a low-radiation CT scan, CAC scoring measures calcified plaque in the coronary arteries—the vessels that supply blood to the heart.
The interpretation is generally straightforward: the higher the CAC score, the greater the burden of calcified atherosclerosis, and the higher the risk of future cardiovascular events. When CAC is high, the case for aggressive risk reduction is usually clear.
The more difficult question comes at the other end of the scale.
A CAC score of zero is often reassuring—and rightly so. It tells us that there is no detectable calcified plaque in the coronary arteries at the time of the scan, and in many cases, this corresponds to low near-term risk. This is why, in selected patients—depending on age, overall risk, and LDL-C burden—current prevention guidelines allow clinicians to consider deferring lipid-lowering therapy when CAC is zero.1 For an older adult with otherwise low risk, a CAC of zero may provide meaningful reassurance.
But that raises an important question: how much reassurance should we take from a CAC of zero in a younger adult with elevated LDL-C?
What they did
To help address this, investigators looked at a subset of participants from CARDIA, the Coronary Artery Risk Development in Young Adults study.2 CARDIA enrolled several thousand young adults between the ages of 18 and 30 who had no known cardiovascular disease at baseline and followed them across 10 in-person exams spanning 35 years. Fasting lipids were measured repeatedly, CAC was measured at years 15 and 25, and cardiovascular events were tracked over subsequent follow-up—an average of 19.1 years after the year-15 scan and 9.7 years after the year-25 scan. This allowed investigators to calculate cumulative LDL-C exposure from early adulthood up to each CAC scan, then ask whether that prior lipid burden predicted cardiovascular events in the years that followed.
For this analysis, the investigators focused on participants who had a CAC of zero at each scan—2,734 at year 15 and 2,282 at year 25—and asked a clinically relevant question: among people with no detectable coronary calcium, does higher cumulative LDL-C exposure predict future cardiovascular events at subsequent follow-up?
What they found
At year 15, when participants were an average of 40 years old, cumulative LDL-C exposure was not significantly associated with future cardiovascular events after adjusting for other traditional risk factors. That null finding should be interpreted cautiously: cardiovascular events were still relatively uncommon in this young group with no detectable coronary calcium, limiting statistical power and making it harder to detect differences in risk.
But by year 25, when participants were around 50 years old, a clearer pattern emerged. Even among those who still had CAC of zero, higher cumulative LDL-C exposure was associated with higher future risk of cardiovascular events.
Participants were divided into quartiles based on their cumulative LDL-C exposure over the prior 25 years. Compared with those in the lowest quartile (mean LDL-C approximately 76 mg/dL), participants in the highest quartile (mean LDL-C approximately 140 mg/dL) had a 3.36-fold higher adjusted risk of cardiovascular events. The second and third quartiles also trended toward higher risk relative to the lowest quartile, though these differences did not reach statistical significance.
The absolute numbers are worth keeping in perspective. Over roughly 10 years of follow-up, event rates were 3.9% in the highest LDL-C exposure group versus 1.3% in the lowest—low in absolute terms, and confirmation that a zero calcium score in young adults still identifies a relatively low-risk group overall. But risk was clearly not uniform across that group. Even within this “reassuring” cohort, cardiovascular risk increased as cumulative LDL-C exposure increased. In other words, zero calcium did not erase the signal from decades of elevated lipids.
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Why a CAC of zero doesn’t mean zero risk
The explanation comes down to what CAC actually measures—and when that measurement is most informative.
Atherosclerosis begins when apoB-containing lipoproteins—primarily LDL particles—enter and become retained in the arterial wall, setting off an inflammatory cascade that unfolds over decades. Calcification develops late in that sequence, as a kind of scarring response to longstanding plaque. By the time calcium registers on a CT scan, the disease has typically been underway for years.
This is why the meaning of a zero calcium score depends heavily on context, especially age. In an older adult, a CAC of zero can be genuinely reassuring: there has been far more time for atherosclerosis to develop and calcify, so the absence of detectable calcium is stronger evidence that the overall burden of coronary plaque is low. But in a 40- or 50-year-old, the same score has a narrower meaning—early plaque may be present and progressing in the arterial wall without having calcified enough to appear on a scan. This may be even more true for women, who tend to calcify plaque later than men (previously discussed here).
Studies using coronary CT angiography (CCTA), which can detect both calcified and noncalcified plaque, back this up: in asymptomatic patients with a CAC of zero, noncalcified coronary atherosclerosis has still turned up in some patients, with estimates ranging from 5.5% to 28.2% depending on the population.3,4 In other words, the absence of calcium is not the same as the absence of disease—it may simply mean the disease hasn’t reached the stage CAC is designed to detect.
The lipid panel captures something different. While CAC reflects the current detectable burden of calcified plaque, LDL-C history reflects the cumulative biological pressure the arterial wall has been exposed to over time. A zero calcium score doesn’t erase that exposure—and in this study, that lipid signal still showed up in the event data years later.
None of this makes CAC less useful. It simply clarifies the question CAC is best suited to answer. When LDL-C is low and CAC is zero, we can be relatively confident that coronary disease burden is low—but CAC should always be interpreted in the context of age, sex, family history, and lifelong exposure to atherogenic lipoproteins. A zero calcium score is reassuring, but it is most reassuring when the rest of the risk profile points in the same direction.
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References
1. Writing Committee Members, Blumenthal RS, Morris PB, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of Dyslipidemia: A report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2026;153(17):e1154-e1276. doi:10.1161/CIR.0000000000001423
2. Peng AW, Razavi AC, Wilkins JT, et al. Impact of LDL-cholesterol when the coronary artery calcium score is 0: Long-term cardiovascular events. J Am Coll Cardiol. 2025;86(9):676-680. doi:10.1016/j.jacc.2025.06.053
3. Nasir K, Cainzos-Achirica M, Valero-Elizondo J, et al. Coronary atherosclerosis in an asymptomatic U.s. population: Miami Heart Study at baptist health south Florida. JACC Cardiovasc Imaging. 2022;15(9):1604-1618. doi:10.1016/j.jcmg.2022.03.010
4. Bergström G, Persson M, Adiels M, et al. Prevalence of subclinical coronary artery atherosclerosis in the general population. Circulation. 2021;144(12):916-929. doi:10.1161/CIRCULATIONAHA.121.055340
