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<\/h3>\nThe clinical assessment of coronary artery calcium (CAC) has undergone a paradigm shift over the past three decades, evolving from a research tool to a central instrument in cardiovascular risk stratification. Central to this transformation is the concept of the coronary artery calcium score of zero\u2014commonly referred to as the \u201cpower of zero\u201d\u2014which has emerged as one of the most powerful negative risk markers in preventive cardiology [1]. In appropriately selected populations, a CAC score of zero confers substantial short- and intermediate-term prognostic reassurance. However, the interpretation of CAC = 0 is not uniform across clinical contexts. Residual risk diverges significantly between asymptomatic individuals undergoing primary prevention screening and symptomatic patients presenting with chest pain.<\/p>\n
The presence of coronary calcium represents a biologic response to chronic lipid infiltration and inflammation within the arterial intima [2]. Calcification reflects advanced atherosclerotic remodeling involving osteogenic differentiation and extracellular matrix changes. However, calcification detectable on non-contrast CT captures only macroscopic mineralization and does not quantify non-calcified plaque components, including lipid-rich necrotic cores and fibrous tissue [3]. Thus, absence of calcium does not equate to absence of atherosclerosis.<\/p>\n
<\/h3>\nCAC scoring is performed using non-contrast, ECG-gated CT imaging. The Agatston score multiplies plaque area by a density weighting factor derived from peak attenuation \u2265130 Hounsfield Units (HU) [2]. Lesions below this threshold are not considered calcified.<\/p>\n
In contrast-enhanced coronary CT angiography (CCTA), plaque characterization differentiates necrotic core, fibrofatty, fibrous, and calcified components based on attenuation ranges [3]. Importantly, rupture-prone plaques frequently contain large necrotic cores with thin fibrous caps and minimal macrocalcification [4].<\/p>\n
A critical mechanistic distinction exists between macrocalcification and microcalcification. Dense macrocalcification visible on CT often reflects plaque stabilization and healing. In contrast, microscopic calcifications\u2014below CT resolution\u2014can generate mechanical stress within the fibrous cap and increase rupture susceptibility [5]. Therefore, CAC = 0 excludes macroscopic calcification but does not exclude microcalcific activity or vulnerable plaque biology.<\/p>\n
In the Multi-Ethnic Study of Atherosclerosis (MESA), approximately 50% of middle-aged asymptomatic adults demonstrated CAC = 0 at baseline [6]. Long-term follow-up revealed 10-year ASCVD event rates of approximately 1\u20131.7% among these individuals, corresponding to an annualized risk near 0.1% [6,7]. These event rates are substantially lower than predicted by traditional risk models in many intermediate-risk individuals.<\/p>\n
Even minimal calcification (CAC 1\u201310) confers approximately a threefold increase in coronary heart disease risk compared with CAC = 0 [6]. Thus, CAC = 0 represents a biologically distinct low-risk phenotype rather than merely the lowest point on a continuum.<\/p>\n
Risk increases stepwise with rising calcium burden [7,8]:<\/p>\n
Individuals with CAC \u22651000 exhibit cardiovascular mortality rates comparable to stable secondary-prevention cohorts, including those similar to FOURIER trial participants [8]. This observation supports aggressive lipid-lowering strategies in extreme CAC categories.<\/p>\n
CAC scoring refines statin allocation efficiency. Among intermediate-risk individuals:<\/p>\n
Most absolute statin benefit accrues to patients with measurable calcified burden. The 2018 ACC\/AHA cholesterol guidelines recommend that statin therapy may be deferred in asymptomatic individuals with CAC = 0 unless diabetes, smoking, or strong family history is present [9].<\/p>\n
The Miami Heart Study demonstrated that approximately 16% of asymptomatic individuals with CAC = 0 have non-calcified plaque on CCTA [10]. However, obstructive stenosis (\u226550%) was present in only 0.8%, and high-risk plaque features were uncommon. Thus, while soft plaque is detectable, it rarely reaches clinical significance in asymptomatic zero-CAC individuals.<\/p>\n
A prospective study of 9,715 asymptomatic individuals demonstrated that CAC = 0 confers a 15-year mortality \u201cwarranty period\u201d in low-to-intermediate risk populations [11]. Annual mortality remained below 1% during this interval. However, this warranty is shortened in diabetics and heavy smokers due to accelerated plaque progression [12].<\/p>\n
Women generally exhibit lower absolute CAC prevalence compared with men but may harbor a greater proportion of non-calcified plaque [13]. Consequently, while CAC = 0 remains prognostically powerful in women, symptomatic female patients may require more cautious interpretation. Women presenting with chest pain frequently demonstrate non-obstructive CAD or microvascular dysfunction, conditions not reliably captured by CAC scoring alone.<\/p>\n
MESA demonstrated significant ethnic heterogeneity in CAC prevalence [6]. White individuals exhibit the highest CAC prevalence, followed by Hispanic, Black, and Chinese American populations. Despite differences in prevalence, event rates at comparable CAC levels are similar across ethnic groups, reinforcing that CAC = 0 confers prognostic reassurance across diverse populations.<\/p>\n
In patients presenting with stable chest pain, CAC = 0 does not exclude coronary disease. Approximately 7\u201316% demonstrate plaque on CCTA, and 1\u20132% have obstructive CAD \u226550% [14]. In the PROMISE trial, 16.5% of symptomatic zero-CAC patients had non-obstructive CAD, and 1.5% had obstructive disease [15].<\/p>\n
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<\/h3>\nPooled analyses demonstrate that 15\u201320% of patients presenting with acute coronary syndrome (ACS)\u2014particularly younger individuals\u2014may have CAC = 0 at presentation [16]. These findings reflect the predominance of non-calcified, rupture-prone plaque. Accordingly, the 2021 AHA\/ACC Chest Pain Guideline recommends CCTA rather than CAC scoring when evaluating possible acute coronary syndrome [17].<\/p>\n
The ICONIC trial quantified plaque components in symptomatic zero-CAC patients who subsequently developed ACS [4]:<\/p>\n
These quantitative differences confirm that substantial vulnerable plaque burden may exist in the absence of detectable calcification.<\/p>\n
Diagnostic performance depends on pre-test probability [18]. In asymptomatic individuals with low baseline risk, CAC = 0 reduces post-test probability to near-negligible levels. In symptomatic patients with higher pre-test probability, residual risk remains clinically meaningful despite a zero score.<\/p>\n
Additional risk modifiers must be considered. Parental premature cardiovascular disease independently increases risk, even among individuals with CAC = 0 [19]. Furthermore, an elevated Atherogenic Index of Plasma (AIP) correlates with calcification burden and major adverse cardiovascular events independent of traditional risk factors [20].<\/p>\n
The coronary artery calcium score of zero is among the most powerful negative risk markers in cardiovascular medicine. In asymptomatic individuals, it confers a prolonged mortality warranty and supports selective de-escalation of pharmacotherapy. In symptomatic patients, however, CAC = 0 represents a \u201csoft shield\u201d\u2014associated with lower risk than positive scores but insufficient to exclude obstructive or vulnerable plaque. Future risk stratification must integrate calcified and non-calcified plaque assessment, clinical phenotype, and individualized risk modifiers rather than relying solely on binary calcium absence.<\/p>\n
De klinische beoordeling van coronaire arteriekalk (CAC) heeft de afgelopen drie decennia een paradigmashift ondergaan, waarbij het is ge\u00ebvolueerd van een onderzoekshulpmiddel tot een centraal instrument bij cardiovasculaire risicostratificatie. <\/p>","protected":false},"author":16,"featured_media":9496,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[229,230,219,223],"tags":[],"class_list":["post-9487","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-imaging-and-detection","category-imaging-and-testing","category-lipids-medications-and-testing","category-plaque-arteries-and-disease"],"acf":[],"yoast_head":"\n