Calcified Plaque or Soft Plaque, Which One to Believe? by Jeffrey Dach MD

Calcified Coronary Plaque, Not Soft Plaque, Predicts Future Heart Attacks in Diabetic Patients

Jim is a 56 year old stock broker and has type two diabetes, and takes a statin drug for a cholesterol level of 235. His fasting blood sugar is 130, and his Hemoglobin A1C is 6.0. Jim’s coronary artery calcium score (CAC) of 12 Agatson units, indicates Jim is at very low risk for coronary artery disease, and the statin drug is of no clinical benefit. Jim’s cardiologist is an old friend of mine from the old days when I worked in the hospital as a radiologist, and I explained that Jim’s statin drug could be safely discontinued. His cardiologist disagreed and said he was still concerned about the soft plaque, and intended to continue the statin drug.

For decades, cardiologists have told us that the soft, lipid-rich, “vulnerable” plaque inside the coronary arteries is the real danger. The theory goes that these soft plaques rupture, cause clots, and trigger heart attacks. Hard, calcified plaque was considered “stable” and less worrisome. No doubt this does occur. However there is more to the story. It turns out the calcific plaque is more predictive of heart attack risk than is the soft plaque.

Rocking the Foundation of Statin Drug paradigm

The foundation of the statin drug paradigm was shaken when studies made it obvious that statin drugs increase the progression of coronary calcification. In 2015, Dr. Michael Henein comes up with the magical thinking that the increased arterial calcification while on a statin drug somehow indicates “arterial plaque repair”, writing:

Despite a greater CAC [Coronary Artery Calcium Score] increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion. (11-12)

Magical Thinking Shown False

Mainstream cardiology needed to preserve the statin drug paradigm, so they came up with magical thinking. This magical thinking says that increasing coronary calcification on a statin drug is somehow “protective arterial repair” and it is the soft plaque and not the calcified plaque that is important. This magical thinking was shown false by the 2004 study by Dr. Paolo Raggi, and by the more recent 2017 study by Dr. Farangis Lavasani. (1) (8) (10)

Header Image: Low magnification micrograph of the distal right coronary artery with complex atherosclerosis and luminal narrowing. Masson’s trichrome. The tunica intima is severely thickened; it measures up to approximately 1/3 of a millimetre. Normally, it is one cell layer thick (approximately 10 micrometres). There is fragmentation of the internal elastic lamina (a very thin black wavy layer) between the intima and media. Author: Nephron. CC 3.0. RCA artery wikimedia commons

The FACTOR-64 Trial

In 2017, Dr. Farangis Lavasani and colleagues at the Intermountain Medical Center Heart Institute, Johns Hopkins and the NIH, analyzed detailed CT coronary angiography data from 224 asymptomatic patients with diabetes who were part of the FACTOR-64 trial. Using sophisticated software, they broke down plaque into soft (non-calcified), fibrous, and calcified components and followed these patients for an average of nearly seven years to see who actually had heart attacks, unstable angina, or cardiac death. The results were unexpected and, in my view, potentially game-changing. In 2017, Dr. Farangis Lavasani writes:

In asymptomatic diabetic patients undergoing CTCA, CAC score and calcified plaque burden were the plaque compositional variables most predictive of future MACE. Soft plaque compositional variables did not predict future risk. These findings provide further evidence of the relationship between coronary calcium and cardiovascular risk.(1)  Note: CTCA = cat scan coronary angiography. CAC= Coronary Artery Calcification. MACE= Major Adverse Coronary Event.

Soft Plaque Has No Predictive Value Whatsoever! 

In the FACTOR-64 trial, patients who experienced major adverse cardiovascular events (MACE) had dramatically higher coronary artery calcium (CAC) scores (605 vs. 50 in those without events, p=0.008). The people who experienced a major cardiac event had 12 times higher calcium score than those who did not have a major cardiac event!  The amount of calcified plaque seen on imaging with on CAT Scan angiography was the strongest predictor of future heart attack risk. In contrast, the quantity of soft, lipid-laden plaque showed no predictive value whatsoever. Dr. Farangis Lavasani writes:

Median follow-up was 6.6 years. Total MACE included 18(8.0%) patients. The median CAC for patients with and without MACE was 605 versus 50 respectively (P=0.008). (1)

In plain English: the hard, calcified plaque, not the soft stuff, was the marker that best predicted future cardiac events.This reinforces observed in clinical practice: the coronary calcium score remains the most powerful predictor of future cardiac events, especially in higher-risk groups like diabetics. A zero calcium score is essentially a five-year warranty against heart attack, even in patients with elevated LDL cholesterol.

Left Image:   Figure 1. Examples of Coronary Artery Scans. (Left) Normal scan without calcified plaque. (Middle) Moderate calcified plaque in the left anterior descending and left circumflex coronary arteries. (Right) Severe calcified plaque involving the left main, left anterior descending, and left circumflex coronary arteries. Courtesy of Hecht, Harvey S. “Coronary artery calcium scanning: past, present, and future.” JACC: Cardiovascular Imaging (2015). (7)

Serum Cholesterol Has No Predictive Value and Does Not Correlate with Calcium Score and 

In 2001, Dr. Harvey Hecht did calcium score study on 930 asymptomatic people with no history coronary artery disease, and not taking statins. Dr. Hecht found there was no correlation between calcium score and the serum cholesterol level. The cholesterol level has virtually no predictive value and does not correlate with calcium score. (6)

Why this Matters for Statin Therapy

The conventional cardiology approach has been to treat elevated serum cholesterol aggressively with statin drugs in diabetic patients regardless of any other clinical findings. Yet this study raises an important question: if the calcium score is zero with no measurable atherosclerosis, and no plaque on CT angiography, is lifelong statin therapy really necessary? Obviously not.

Calcium Score is a Key Decision Tool

In my own office practice we use the coronary calcium score as a key decision-making tool. When the calcium score is zero, patients can avoid unnecessary statin therapy. When the score is high, above 100, aggressive lifestyle and dietary modification, and blood pressure control is warranted. For calcium score over 100, there is a measurable benefit from a statin drug prescribed by the cardiologist, as shown in 2018 by Dr. Joshua Mitchell using the Walter Reed Registry. (9)

Annual Progression of Calcium Score 

Another useful strategy for high risk patients is serial calcium score every year or two. This is based on the 2004 study by Dr. Paolo Raggi who found annual progression of calcium score below 15% regardless of high initial score, has a good prognosis, while those patients with annual progression of calcium score greater than 15% are high risk for near term heart attack. Dr. Raggi’s 2004 study again shows that calcium score progression while on a statin drug is not a benign event, and is actually a flashing red light on the dashboard, indicating very high risk for heart attack in the near future.

Grouping of All Calcium Scores Together on Left Chart

Another useful finding made by Dr. Raggi is shown in the left chart below of patients with less than 15% annual progression of calcium score. Notice all the colored coded lines indicating starting calcium scores were all grouped at the top of the Left chart, indicating good prognosis regardless of high starting calcium score. (see left chart below). On the Right chart however, all the color coded calcium scores are separated indicating higher starting calcium score associated with worse prognosis when progression is greater than 15%. (8)

Figure 5. Progression of CAC and Risk of First MI in 495 Asymptomatic Patients Receiving Cholesterol-Lowering Therapy.
Left Chart: CAC progression of <15% per year is associated with a benign prognosis irrespective of the baseline CAC, implying stabilization of the atherosclerotic process.
Right Chart: CAC progression of >15% per year is associated with a poor prognosis directly related to the baseline CAC, implying new plaque formation and inadequacy of treatment. CAC = coronary artery calcium; MI = myocardial infarction. (7-8) Courtesy of Paolo Raggi et al 2004. and Hecht, Harvey 2015.

Calcium Score Under 100

In 2018, Dr. Joshua Mitchell used the Walter Reed Hospital registry to show that calcium score under 100 identifies low-risk patients who may safely avoid statin drugs, even with high serum cholesterol levels. Dr. Joshua Mitchell showed statin drugs have no cardiac benefit for calcium score under 100, in which case the NNT = 100 (NNT=number needed to treat). When calcium score is greater than 100, the NNT drops to 12, a more favorable number. The amount of atherosclerosis identified by calcium score, not the serum cholesterol level, should determine who to treat with a statin drug. See data chart below. (9)

Cumulative Incidence of MACE (Major Adverse Cardiac Event) Stratified by Statin Treatment and CAC (Calcium Score) Severity. Benefit of statin therapy was significantly related to CAC group (p<0.0001 for interaction), with benefit in patients with CAC >100 but not in patients with CAC < 100. aSHR – adjusted subhazard ratio. MACE – major adverse cardiovascular event. CAC – coronary artery calcium. Courtesy of  Mitchell, Joshua D., et al. “Impact of statins on cardiovascular outcomes following coronary artery calcium scoring.” Journal of the American College of Cardiology 72.25 (2018): 3233-3242. (9)

Our Calcium Score Protocol

For those who with calcium score over 100 who cannot tolerate the adverse effects of a statin drug prescribed by the cardiologist, we have devised our own calcium score protocol, a basket of supplements in addition to diet and lifestyle modification (a Gluten-free, plant based diet, and daily exercise). This basket includes: Magnesium, Aged Garlic, Vitamin C, Tocotrienol Vitamin E, Vitamin K (MK7), Nattokinase and/or Lumbrokinase as described in my book, Heart Book. Additional Supplements are optional: Berberine and Probiotics.

More Calcium Score Studies 

In 2008, Dr. Detrano conducted the Multi-Ethnic Study of Atherosclerosis (MESA) following 6,700 asymptomatic adults with coronary artery calcium score (CAC), showing CAC is a powerful, independent predictor of coronary events across all racial and ethnic groups. (2)

In 2013, Dr. Agarwal conduct the PREDICT study in type 2 diabetes patients demonstrating that coronary calcium score strongly predicts cardiovascular mortality, confirming its utility in the very population studied in FACTOR-64. (3)

In 2022, Dr. Al-Kindi conducted the CLARIFY Registry analysis showing higher coronary calcium levels are independently associated with major adverse cardiovascular events in patients with diabetes, thus leading to more intensification of preventive therapy.(4)

In 2017, Dr. Gupta did a systematic review and meta-analysis finding that identifying calcified coronary plaque on imaging significantly increases the likelihood that physicians will initiate and continue statin and lifestyle therapies. This is what most cardiologists will follow in real-world practice. (5)

Bottom Line: The old dogma that “soft plaque ruptures and kills you” while calcified plaque is benign needs serious re-examination. In asymptomatic diabetic patients, calcified plaque burden and the coronary calcium score are the strongest predictors of who will actually have a future heart attack. This 2017 study from the FACTOR-64 investigators, along with the supportive literature, provides strong evidence that we should be focusing more on actual atherosclerotic burden, measured by calcium scoring and CT angiography and less concerned about serum cholesterol levels alone.

Number of Events Too Small

For the sake of argument and to be fair, here is the counter argument held by mainstream cardiology: In the specific FACTOR-64 subanalysis cited above there were only a small number of events, only 18 major cardiac events. The study was performed in asymptomatic diabetics, CT coronary angiography with quantitative plaque composition, median ~6.6-year follow-up, only 18 MACE events, CAC score and calcified plaque burden were the compositional variables most predictive of MACE; soft plaque variables were not. This matches the abstract and contemporaneous reporting:

Lavasani F, et al. “Prediction of Future Cardiovascular Risk by Analysis of Various CT Coronary Angiography-Determined Quantitative Plaque Compositional Characteristics Among Patients with Diabetes Enrolled in the FACTOR-64 Study: The Importance of the Calcified Coronary Plaque.” Journal of the American College of Cardiology, vol. 69, no. 11_Supplement, 2017, p. 180. (1)

Press coverage of the same work (Intermountain Medical Center / Johns Hopkins / NIH collaboration) explicitly noted the unexpected finding that calcified plaque predicted events better than soft plaque in this cohort.

Larger Studies Show the Opposite or Complementary Picture

Larger studies often show the opposite or complementary picture for soft plaque components:

In SCOT-HEART study, low-attenuation (soft/lipid-rich) plaque burden was the strongest predictor of myocardial infarction, independent of CAC and stenosis in multivariable analysis.

In the 2020 SCOT-HEART  by Dr. MC Williams, there were four types of plaques studied as listed below:

1. TOTAL Plaque burden: This is the overall amount of all atherosclerotic plaque (both calcified/hard and noncalcified/soft) in the coronary arteries, expressed as a percentage of the vessel volume in the analyzed segments. Total plaque burdern answers the question: “What fraction of the artery wall is taken up by plaque of any kind?” Higher values indicate more extensive atherosclerosis. In this study, median total plaque burden was around 39%.

2. Noncalcified plaque burden: This measures the amount of “soft” (non-calcified) plaque only, again as a percentage of vessel volume.
Noncalcified plaque consists of cholesterol, fat, fibrous tissue, and other non-hardened components (it excludes calcium deposits). It is generally considered more biologically active and potentially changeable than calcified plaque. It includes the low-attenuation subtype described below plus higher-attenuation soft components (e.g., fibrous tissue). In the study this made up the large majority of total plaque.

3. Low-attenuation plaque burden: Notice low attentuation plaque is a subset of the soft plaque category. In the above 2017 FACTOR-64 Trial by Dr. Farangis Lavasani, there was no mention of a low attenuation plaque subset, with only two types of plaque mentioned, soft plaque and hard plaque. Thus explaining their conclusion that hard plaque, not soft plaque is the most significant marker of risk. Three years later in 2020 the SCOT-HEART by Dr. Michelle Williams measured four types of plaque, including the newly decribed low attention plaque, a subset of the soft plaque category with Hounsfield units less than 30. Dr Williams writes:

In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0–5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score (r=0.34; P<0.001), strongly with coronary artery calcium score (r=0.62; P<0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r=0.83; P<0.001). Low-attenuation plaque burden (7.5% [4.8–9.2] versus 4.1% [0–6.8]; P<0.001), coronary artery calcium score (336 [62–1064] versus 19 [0–217] Agatston units; P<0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P<0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10–2.34) per doubling; P=0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06–10.5; P<0.001).
Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity.

Low attenuation plaque is a specific, high-risk subtype of noncalcified (soft) plaque defined by very low CT density—attenuation of less than 30 Hounsfield units (HU). It is expressed as a percentage of vessel volume. On the CT scan these areas appear darker (lower Hounsfield units of around 30). They correspond to lipid-rich necrotic cores (fatty, soft material with dead tissue inside the plaque). This is the plaque phenotype most strongly linked to rupture and subsequent myocardial infarction (heart attack). In the study it was the strongest independent predictor of future heart attack (even after adjusting for other risk factors, calcium score, and stenosis severity); a burden >4% was associated with roughly 4–5 times higher risk.

4. Calcified plaque burden: This measures the amount of “hard” plaque containing calcium deposits, expressed as a percentage of vessel volume. Calcified plaque has high CT attenuation (calcium appears bright/white). It is generally more stable and less likely to rupture than soft or low-attenuation plaque, although a high burden still signals advanced overall atherosclerosis. In the study the median calcified plaque burden was low (around 0.4%).

Key relationships: Total plaque burden = noncalcified plaque burden + calcified plaque burden. Low-attenuation plaque is a subset of noncalcified plaque. All four were analyzed on a continuous (often log-transformed / per-doubling) basis in the multivariable models shown in Table 4. The software used adaptive, scan-specific thresholds for most plaque components, with the fixed <30 HU cutoff specifically for low-attenuation plaque.

What is Low Attentuation Plaque?

This is a specific, high-risk subtype of noncalcified (soft) plaque defined by very low CT density—attenuation of less than 30 Hounsfield units (HU). It is expressed as a percentage of vessel volume. On the CT scan these areas appear darker. They correspond to lipid-rich necrotic cores (fatty, soft material with dead tissue inside the plaque). This is the plaque phenotype most strongly linked to rupture and subsequent myocardial infarction (heart attack). In the study it was the strongest independent predictor of future heart attack (even after adjusting for other risk factors, calcium score, and stenosis severity); a burden >4% was associated with roughly 4–5 times higher risk. (14)

Other large cohorts (PROMISE subanalyses, PARADIGM, etc.) similarly find total plaque volume and non-calcified/low-attenuation components add prognostic value beyond CAC alone.

Statins increase CAC density/progression in some patients while reducing events; this is widely interpreted as plaque stabilization (conversion of soft to more calcified phenotypes), not necessarily “repair” that eliminates risk. Progression of CAC >15% per year has been linked to higher near-term risk in observational data (Raggi et al.).

Low-attenuation plaque (LAP) is a high-risk subtype of noncalcified (“soft”) plaque on coronary CT angiography (CCTA), defined by attenuation <30 Hounsfield units (HU). It appears darker on CT and corresponds to lipid-rich necrotic cores (LRNC). In the Dr. Michelle C Williams 2020 SCOT-HEART analysis, LAP burden >4% of vessel volume was the strongest independent predictor of myocardial infarction (adjusted HR ~1.60 per doubling; patients with >4% had ~4.65-fold higher risk), outperforming traditional risk scores, calcium score, and stenosis severity. (14)

Exact histology of lipid-rich necrotic cores (contents of LAP)

LRNC (Lipid rich necrotic center, the histologic correlate of LAP, low attenuation plaque) consists of extracellular lipids (primarily plasma-derived cholesteryl esters and free cholesterol), cholesterol crystals/clefts, acellular necrotic debris from dead macrophage foam cells and other cells, amorphous liponecrotic material, and variable amounts of hemorrhage or inflammatory cell remnants. It lacks intact extracellular matrix (collagen/elastin often degraded), is hypocellular, and is typically covered by a fibrous cap. Early cores show more intact cells and proteoglycans; advanced/late cores show extensive debris, large cholesterol crystals, and matrix loss. This composition makes the plaque soft, mechanically unstable, and rupture-prone.

Low Attentuation Plaque is Microbial Biofilm or Abscess Causes by Polymicrobial Infection with live or dead micro-organisms

Studies suggesting, inferring, or demonstrating live or dead microbial organisms in atherosclerotic plaques (including those with lipid-rich necrotic cores / low-attenuation features)

Numerous studies using PCR detecting DNA, consistent with dead or live organisms, FISH targeting rRNA, often implying viable or recently viable organisms), immunohistochemistry, electron microscopy, culture, and metagenomics have identified bacterial (and occasionally other microbial) signatures in human atherosclerotic plaques, including atherectomy, endarterectomy, and autopsy specimens. Some studies specifically localize organisms or DNA to lipid cores, necrotic cores, or lipidic areas of vulnerable plaques. Causality remains debated (primary driver vs. secondary colonization/bystander), but the presence of DNA, rRNA, antigens, biofilms, and (in some cases) cultivable organisms is repeatedly documented. Below are key examples (prioritized for relevance to necrotic/lipid cores where possible, plus broader plaque findings that commonly include such cores).

1. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. “Lessons from Sudden Coronary Death: A Comprehensive Morphological Classification Scheme for Atherosclerotic Lesions.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 5, 2000, pp. 1262–1275. https://www.ahajournals.org/doi/10.1161/01.ATV.20.5.1262.

This study is a foundational histologic classification detailing necrotic cores (lipids, cholesterol crystals, cellular debris) in fibroatheromas and thin-cap fibroatheromas. Provides the structural baseline against which later microbial localization studies are interpreted.

2. Ott SJ, El Mokhtari NE, Musfeldt M, et al. “Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease.” *Circulation*, vol. 113, no. 7, 2006, pp. 929–937. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.105.579979 (PubMed https://pubmed.ncbi.nlm.nih.gov/16490835/).

This study used 16S rDNA PCR testing and FISH (Flourescent in-situ Hybridization) on atherectomy specimens from 38 patients with coronary artery disease. Bacterial DNA was identified in all atherosclerotic plaques, and none in normal arteries. More than 50 species were found with a mean of greater than 12 species per plaque. The species included staphylococci, streptococci, *Proteus*, *Klebsiella*. *Chlamydia* spp. by specific PCR in 51.5%. FISH confirmed bacterial rRNA localization within lesions.

3. Higuchi ML, et al. (related works on infectious agents in coronary atheromas, including in situ hybridization and electron microscopy). See e.g., discussions and figures in associated publications on Mycoplasma pneumoniae and C. pneumoniae in vulnerable plaques (e.g., references linking to SciELO/archived full texts showing ISH and EM). Organisms (including degenerated forms) localized to lipidic areas and necrotic lipid cores of vulnerable/ruptured plaques; higher bacterial load associated with unstable morphology, adventitial inflammation, and positive remodeling. Electron microscopy showed mycoplasmas, C. pneumoniae elementary bodies, and membranous debris consistent with degenerated bacteria within necrotic lipid cores. Suggests microbial presence (live/dead) contributes to the space-occupying necrotic core.

4. Lanter BB, et al. / related Propionibacterium acnes biofilm studies. “Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion…” *PMC* (full text available). https://pmc.ncbi.nlm.nih.gov/articles/PMC4567629/. FISH (eubacterial and *P. acnes*-specific probes) on carotid endarterectomy specimens showed biofilms/microcolonies embedded throughout plaque tissue (not just surface). Culture recovered viable *P. acnes* and other taxa; viability data + FISH indicate live bacteria in biofilm form within advanced plaques.

5. Multiple PCR studies of periodontal pathogens in plaques (examples of widely replicated findings):**
– Various groups using nested/real-time PCR or 16S sequencing on surgical (CABG, endarterectomy, atherectomy) specimens have detected *Porphyromonas gingivalis*, *Aggregatibacter actinomycetemcomitans*, *Tannerella forsythia*, *Treponema denticola*, *Prevotella intermedia*, etc., in 10–70%+ of atherosclerotic plaques (often correlating with periodontal disease severity). Meta-analyses report pooled prevalences ~40–50% for several of these in coronary plaques. DNA detection is consistent with dead or live organisms; some co-localize with inflammatory cells.

Molecular analysis showing periodontal bacterial DNA in atherosclerotic plaques from CAD patients (nested PCR; positive in subsets of CABG/angioplasty samples). These plaques routinely contain necrotic/lipid cores.

6. Viridans group streptococci studies (e.g., Tampere Sudden Death Study series and related): Real-time quantitative PCR + immunohistochemistry on coronary plaques (autopsy) and endarterectomy samples. Oral viridans streptococcal DNA most common (~42% of coronary plaques and endarterectomies). Immunopositivity correlated with severe atherosclerosis, CHD death, and MI. Organisms colonized the core of the atheroma as a biofilm (unrecognized by macrophages); some infiltrated ruptured fibrous caps. Supports biofilm (potentially viable) presence specifically in the atheroma core.

7. Metagenomic/other microbial detections:
– Metagenomic analysis of carotid atheroma plaques detected high proportions of *Toxoplasma gondii* DNA (PCR confirmed in 40% of samples); other traditional atherogenic bacteria not dominant in that cohort.
– Broader 16S surveys and pyrosequencing of plaques consistently recover diverse bacterial communities (oral, gut, environmental taxa) in essentially all advanced plaques.
– Additional FISH/culture work has recovered viable polymicrobial biofilms from carotid plaques.

Additional notes: FISH targeting rRNA and successful culture provide the strongest evidence for *live* organisms (or recently viable ones) in some plaques. DNA-only findings (most PCR studies) indicate presence of microbial genetic material (dead or live). Localization to lipid/necrotic cores is explicitly described in a subset (e.g., Higuchi EM/ISH; viridans streptococcal biofilm in core; general presence in advanced plaques that histologically contain LRNC). Experimental models (e.g., *Fusobacterium nucleatum* accelerating necrotic core formation) further infer a contributory role. No single study “proves” that *every* LAP contains microbes, but the cumulative evidence strongly supports that microbial DNA/rRNA/antigens/biofilms are common in the plaques that harbor LRNC (the histologic substrate of LAP).

Dr. Maria de Lourdes Higuchi from Brasil

Dr. Maria de Lourdes Higuchi devoted much of her career from 2002 to 2009 to the study of infectious material found within atherosclerotic plaques. Her studies confirm the presence of microbial organisms with the lipid rich necrotic core thought to be responsible for plaque rupture, subsequent thrombosis and myocardial infarction. The two microbes Dr. Higuchi found within lipidic areas/necrotic cores of atheromas are: Mycoplasma pneumoniae and Chlamydia pneumoniae. Dr. Higuchi used in situ hybridization (ISH), and electron microscopy (EM) for localization of microbial organisms within lipidic/necrotic core areas within atheromas. These area are associated with inflammation, remodeling, and represent plaque vulnerability, meaning a high risk for rupture, thrombosis and heart attack.

1. Higuchi, Maria de Lourdes, et al. “Detection of *Mycoplasma pneumoniae* and *Chlamydia pneumoniae* in Ruptured Atherosclerotic Plaques.” *Brazilian Journal of Medical and Biological Research*, vol. 33, no. 9, 2000, pp. 1023–26.
https://doi.org/10.1590/S0100-879X2000000900005
(Also: https://www.scielo.br/j/bjmbr/a/zg3RbxLtgG9cq6Vh7rTHsZx/?lang=en or PubMed https://pubmed.ncbi.nlm.nih.gov/10973132/)

Dr. Maria de Lourdes Higuchi is the first to reported the observation of Mycoplasma pneumoniae co-localized with Chlamydia pneumoniae in thrombosed ruptured atheromas. Using electron microscopy and in situ hybridization of coronary artery specimens from three patients who died of acute myocardial infarction, the authors demonstrated that mycoplasmas were present mainly in the lipid core of the ruptured thrombosed plaque. Vulnerable atheromas are noted to be rich in cholesterol, which favors growth of mycoplasmas, which is the only microorganisms that require cholesterol for survival. Dr. Maria de Lourdes Higuchi suggests that the association of the two organisms may increase virulence, promote proliferation, plaque inflammation, and rupture. The lipid-core localization directly links these microbes to the histologic equivalent of low-attenuation plaque (lipid-rich necrotic core).

2. Higuchi, Maria de Lourdes, et al. “Coinfection with *Mycoplasma pneumoniae* and *Chlamydia pneumoniae* in Ruptured Plaques Associated with Acute Myocardial Infarction.” *Arquivos Brasileiros de Cardiologia*, vol. 81, no. 1, 2003, pp. 12–22.

In 2003, Dr. Maria de Lourdes Higuchi from Brasil studied the coronary arteries from patients dying of acute myocardial infarction. She detected Chlamydia pneumoniae using immunohistochemistry and Mycoplasma pneumoniae by in situ hybridization within coronary artery specimens showing thrombosed ruptured plaques from acute myocardial infarction (AMI) leading to death, as well as non-ruptured plaques from the same patients, non-ruptured plaques from non-AMI coronary patients, and non-atherosclerotic controls.

Significantly higher mean numbers of Chlamydia pneumoniae-positive cells and higher percentage areas occupied by M. pneumoniae were found in thrombosed ruptured plaques than in non-ruptured plaques from the same patients. These higher bacterial loads correlated with the intensity of inflammation (including CD4+ T and CD20+ B lymphocytes) and with vessel diameter indicating remodeling. This study builds directly on the group’s prior demonstration of preferential localization within lipid-rich regions of vulnerable plaques.

3. Higuchi, Maria de Lourdes, and José A. F. Ramires. “Infectious Agents in Coronary Atheromas: A Possible Role in the Pathogenesis of Plaque Rupture and Acute Myocardial Infarction.” *Revista do Instituto de Medicina Tropical de São Paulo*, vol. 44, no. 4, 2002, pp. 217–24.

https://doi.org/10.1590/S0036-46652002000400007
(Also: PubMed https://pubmed.ncbi.nlm.nih.gov/12219114/; archived full text e.g. via SciELO/Wayback Machine)

In this 2002 invited review article, Dr. Maria de Lourdes Higuchi expands on localization of the necrotic/lipid-core, and explains her laboratory’s histopathological findings on plaque instability and co-infection. Using immunohistochemistry, in situ hybridization, and electron microscopy on thrombosed coronary artery segments from AMI deaths, the authors report that Mycoplasma pneumoniae and Chlamydia pneumoniae are concentrated in lipidic areas of the plaques, both in the extracellular matrix and within foam cells, predominantly in unstable plaques. Electron microscopy of the necrotic lipidic core of vulnerable plaques revealed many mycoplasmas (rounded or elliptical forms) together with C. pneumoniae elementary bodies and abundant membranous structures consistent with degenerated bacteria. In the media and adventitia the organisms appeared in larger cylindrical forms. Greater bacterial loads in vulnerable plaques correlated with adventitial inflammation (higher lymphocytes, especially CD20+ B cells correlating with C. pneumoniae-infected cells) and positive vessel remodeling (correlation between % area of M. pneumoniae DNA in the plaque and cross-sectional vessel area). Dr. Higuchi concludes that co-infection may act as an important co-factor for plaque instability and that the organisms contribute to the space-occupying nature of the necrotic core. This provides the strongest direct histologic and ultrastructural evidence linking microbial infection, both live and degenerated/dead organisms to the lipid-rich necrotic core, the exact same area called the low-attenuation plaque on CT scans.

4. Higuchi, Maria L., et al. “Co-infection Ratios versus Inflammation, Growth Factors and Progression of Early Atheromas.” *APMIS*, vol. 114, no. 5, 2006, pp. 338–44.
https://doi.org/10.1111/j.1600-0463.2006.apm_351.x
(Also: PubMed https://pubmed.ncbi.nlm.nih.gov/16725009/)

In this 2006 study,  Dr. Maria de Lourdes Higuchi compares M. pneumoniae (MP) to C. pneumoniae (CP) antigen ratios in early stable versus growing atheromas. Higher MP/CP ratios correlated with lower inflammation, and plaque stability with increased growth factors (e.g., platelet derived growth factor PDGF-B). Antigens of both organisms are already present in early lesions.

Animal models confirming aggravation by these Microbial Agents

5. Higuchi laboratory / collaborative context “Mycoplasma pneumoniae and/or Chlamydophila pneumoniae Inoculation Causing Different Aggravations in Cholesterol-Induced Atherosclerosis in apoE KO Male Mice.” BMC Microbiology, vol. 9, 2009, article 194.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2755007/ (DOI 10.1186/1471-2180-9-194)

This 2009 study by Dr. Higuchi involved experimental inoculation of apoE-knockout mice with M. pneumoniae, C. pneumoniae microbial infection. Her study showed that M. pneumoniae, C. pneumoniae, or both aggravated cholesterol-induced atherosclerosis, with the dual-inoculation group exhibiting the highest adventitial inflammation. This animal study in ApoE mice supports her observation in humans on the effects of microbial infection on atherosclerotic plaque morphology and inflammation.

6. Higuchi, Maria de Lourdes, et al. “*Mycoplasma pneumoniae* and *Chlamydia pneumoniae* in Calcified Nodules of Aortic Stenotic Valves.” Revista do Instituto de Medicina Tropical de São Paulo (related publication, ~2002).
https://doi.org/10.1590/S0036-46652002000400005

In this study by Dr. Higuchi,  immunohistochemistry, ISH, and EM was used to study aortic valve specimens, showing significantly higher amounts of both microbial organisms in calcified foci and surrounding fibrotic areas than in less-injured valve regions, suggesting a response to bacterial presence analogous to atherosclerotic damage within coronary and carotid arteries.

Key supporting references from the medical literature

Detrano, Robert, et al. “Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups.” *New England Journal of Medicine*, vol. 358, no. 13, 2008, pp. 1336–45. https://www.nejm.org/doi/full/10.1056/NEJMoa072100

This is the MESA study showing that Coroanry Artery Calcium Score (CAC) is powerful predictor for heart attack across ethnicities.

Mitchell, Joshua D., et al. “Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring.” *Journal of the American College of Cardiology*, vol. 72, no. 25, 2018, pp. 3233–42. https://www.jacc.org/doi/10.1016/j.jacc.2018.09.051

This registry study was done using Walter Reed hospital data showing statin drugs provide benefit when CAC is greater than 100, and NO beneft when CAC is less than 100.

Raggi, Paolo, et al. “Progression of Coronary Artery Calcium and Risk of First Myocardial Infarction in Patients Receiving Cholesterol-Lowering Therapy.” *Arteriosclerosis, Thrombosis, and Vascular Biology*, vol. 24, no. 7, 2004, pp. 1272–77. https://www.ahajournals.org/doi/10.1161/01.ATV.0000127024.40516.ef

Dr. Raggi showed that annual progression of calcium score greater than 15% per year is associated with higher risk for myocardial infarction (MI), while less than 15% is associated with low risk for MI

Hecht, Harvey S. “Coronary Artery Calcium Scanning: Past, Present, and Future.” JACC: Cardiovascular Imaging, vol. 8, no. 5, 2015, pp. 579–96. https://www.sciencedirect.com/science/article/pii/S1936878X15001369 (review of CAC as robust predictor; real).

Dr. Harvey Hecht reviews the medical literature showing CAC is a robust predictor of cardiac events.

Williams, Michelle C., et al. (SCOT-HEART low-attenuation plaque paper, as mentioned above).

Bottom line: Low attentuaion (soft plaque) is mechanistically what most often ruptures and causes heart attacks. Studies by Dr, Higuchi and others show that low attenuation plaque is localized to the lipid rich/necrotic core which is infected with microbial organisms.

Overall, the calcium score or amount of calcified plaque is an excellent, practical predictor of who is at higher risk because it reflects total disease burden. The FACTOR-64 composition study using CT angiography shocked the cardiology community because it showed the amount of hard plaque (using calcium score), and not the amount of soft plaque is the most improtant risk factor for future heart attack.

The SCOT study by Williams used CT angiography to study the four different types of plaque, both hard and soft finding that low attentuation plaque indicated high risk for impending rupture, thrombiosis and myocardial infarction in pateitns even though calcium score may be low , below 100. This CT angiography identifies the high risk patient with low attenuation plaque despite a low calcium score. Even though these patients may have a low calcium score, the presence of low attenuation plaque is a sign of infection within a lipid rich necrotic core, indicating impending atheroma rupture, thrombosis and myocardial infarction.

For the highest level of clinical practice, both concepts are used, Calcium Score (CAC) for risk stratification in asymptomatic patients, and advanced CT angiography in high risk or symptomatic patients looking more closely at the plaque composition to identify presence of low attenuation plaque, a high risk marker. When low attenuation plaque is found, these patients need further workup and close follow up.

My Calcium Score Protocol

Aged Garlic: See Coronary Calcium Score benefits of Aged Garlic

Vitamin C: See Linus Pauling Protocol

Tocotrienol Vitamin E: See Vitamin E and tocotrienols

Magnesium

Nattokinase

Berberine

Curcumin

Probiotics

Plant based  Diet

Gluten Free Diet (in some cases)

Heart Book: How to Keep Your Heart Healthy by Jeffrey Dach MD

My new book is available on Amazon:
Link to Kindle Version
Link to Paperback Version

Heart Book is a journey through the confusing maze of literature on coronary artery disease, the number-one killer in America. With his years of practice in vascular radiology, Dr. Dach has the background, credentials, and experience to transform your understanding of heart disease. The old medical paradigms have been upended, yet mainstream cardiology clings to these tired dogmas as if nothing has changed. Be prepared to be shocked, amazed, provoked, and gratified as this book empowers you to take control of your own heart health.

Articles with Related Interest:

The Failure of Cholesterol Lowering Drugs

Coronary Artery Disease: Questions and Answers

Does Cholesterol Cause Coronary Artery Disease ?

Calcium Score Determines Who to Treat with Statin Drug

Calcium Score Diabetes and Statin Drugs

Plant Based Diet, Health Benefits for Coronary Artery Disease

LDL-Cholesterol Does Not Cause Coronary Artery Disease

Low Level Endotoxemia, Depression, Endocrinopathy and Coronary Artery Disease

Fibrinolytic Enzymes, Nattokinase, Lumbrokinase Prevent and Reverse Atherosckerosis

Reverse Heart Disease with Coronary Calcium Score

Low Level Endotoxemia LPS Theory of Coronary Artery Disease

Calcium Score Paradigm Shift in Cardiology

Coronary Calcium Score Benefits of Aged Garlic

The Art of the Curb Side Cholesterol Consult

Evolocumab Are You Joking Me?

Cholesterol and Atherosclerosis:Autopsy Studies Show No Correlation

Statin Denialism Internet Cult with Deadly Consequences

Defending the Cholesterol Hypothesis in the Elderly

Does High Cholesterol Cause Heart Disease ?

Familial Hypercholesterolemia and Statin Drugs

Donating Blood Prevents Heart Disease

Does Cholesterol Cause Heart Disease ?  Part two

Atherosclerotic Plaque as Infected Biofilm on Electron Microscopy

Coronary Calcium Score Paradigm Shift Podcast

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my web site: https://drjeffreydachmd.com/
my personal blog: www.jeffreydachmd.com 
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit ebook
Cracking Cancer Toolkit print version
Heart Book by Jeffrey Dach MD
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

References:

1) Lavasani F, May HT, Kwan AC, et al. Prediction of Future Cardiovascular Risk by Analysis of Various CT Coronary Angiography-Determined Quantitative Plaque Compositional Characteristics among Patients with Diabetes Enrolled in the FACTOR-64 Study: The Importance of the Calcified Coronary Plaque. Journal of the American College of Cardiology. 2017;69(11_Supplement):1592.

In asymptomatic diabetic patients undergoing CTCA, CAC score and calcified plaque burden were the plaque compositional variables most predictive of future MACE. Soft plaque compositional variables did not predict future risk. These findings provide further evidence of the relationship between coronary calcium and cardiovascular risk.

2) Detrano R, Guerci AD, Carr JJ, et al. Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups. New England Journal of Medicine. 2008;358(13):1336-1345.

3) Agarwal S, Cox AJ, Herrington DM, et al. Coronary Calcium Score Predicts Cardiovascular Mortality in Diabetes: The PREDICT Study. Diabetes Care. 2013;36(4):972-977.

4) Al-Kindi S, Dong T, Chen W, et al. Relation of coronary calcium scoring with cardiovascular events in patients with diabetes: The CLARIFY Registry. Journal of Cardiovascular Computed Tomography. 2022.

5) Gupta A, Lau E, Varshney R, et al. The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies: A Systematic Review and Meta-Analysis. JACC: Cardiovascular Imaging. 2017;10(8):833-842.

6) Hecht, Harvey S., et al. “Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment.” The American journal of cardiology 87.4 (2001): 406-412.

7) Hecht, Harvey S. “Coronary artery calcium scanning: past, present, and future.” JACC: Cardiovascular Imaging 8.5 (2015): 579-596.

Figure 5. Progression of CAC and Risk of First MI in 495 Asymptomatic Patients Receiving Cholesterol-Lowering Therapy
(Left) CAC progression of <15% per year is associated with a benign prognosis irrespective of the baseline CAC, implying stabilization of the atherosclerotic process. (Right) CAC progression of >15% per year is associated with a poor prognosis directly related to the baseline CAC, implying new plaque formation and inadequacy of treatment. CAC = coronary artery calcium; MI = myocardial infarction.

8) Raggi, Paolo, Tracy Q. Callister, and Leslee J. Shaw. “Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy.” Arteriosclerosis, thrombosis, and vascular biology 24.7 (2004): 1272-1277.

9) Mitchell, Joshua D., et al. “Impact of statins on cardiovascular outcomes following coronary artery calcium scoring.” Journal of the American College of Cardiology 72.25 (2018): 3233-3242.

Cumulative Incidence of MACE Stratified by Statin Treatment and CAC Severity. Benefit of statin therapy was significantly related to CAC group (p<0.0001 for interaction), with benefit in patients with CAC >100 but not in patients with CAC < 100. aSHR – adjusted subhazard ratio. MACE – major adverse cardiovascular event. CAC – coronary artery calcium.

10) Muhlestein, Joseph B., et al. “Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial.” Jama 312.21 (2014): 2234-2243.

11) Henein, Michael, et al. “High dose and long-term statin therapy accelerate coronary artery calcification.” International journal of cardiology 184 (2015): 581-586.
Conclusions: Despite a greater CAC increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion.

12) Dykun, Iryna, et al. “Statin medication enhances progression of coronary artery calcification: the Heinz Nixdorf Recall Study.” Journal of the American College of Cardiology 68.19 (2016): 2123-2125.

13) Vossen, Liv M., et al. “Two years of menaquinone-7 supplementation and coronary artery calcification: a randomized clinical trial.” JAMA cardiology (2026). Vit K slowed coronary artery calcification ~29% vs placebo.

14) Williams Michelle C, et al. “Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial.” Circulation, vol. 141, no. 18, 2020, pp. 1452–1462.

The median coronary artery calcium score was 21 (IQI, 0–230) Agatston units. Normal coronary arteries were identified in 646 patients (37%), nonobstructive coronary artery disease in 671 patients (38%) and obstructive coronary artery disease in 452 patients (26%). The median total plaque burden for all patients (Table 2) was 39% (IQI, 0–49), with noncalcified plaque burden 36% (IQI, 0–46), low-attenuation plaque burden 4.2% (IQI, 0–6.9), and calcified plaque burden 0.4% (IQI, 0–2.8).

Clinical Events

Over a median follow-up of 4.7 years (IQI, 4.0–5.7), the primary event point of fatal or nonfatal myocardial infarction occurred in 41 patients (2.3%). Patients who suffered a fatal or nonfatal myocardial infarction had higher total plaque, noncalcified plaque, low-attenuation plaque and calcified plaque burden (Table 3; Figure 4). In univariable analysis, the total plaque, noncalcified plaque, low-attenuation plaque and calcified plaque burdens were all associated with an increased risk of fatal or nonfatal myocardial infarction (Table 4; Table II in the online-only Data Supplement). In multivariable analysis, the low-attenuation plaque burden was the strongest predictor of the primary event (HR, 1.60 [95% CI, 1.10–2.34] per doubling; P=0.014), adding incremental value to the cardiovascular risk score (HR, 1.00 [95% CI, 0.98–1.03]; P=0.821), coronary artery calcium score (HR, 1.13 [95% CI, 1.01–1.27]; P=0.041), and the presence of visually observed obstructive coronary artery disease (HR, 1.20 [95% CI, 0.58–2.48]; P=0.621) (Table 4; Table III in the online-only Data Supplement).

The Four Plaque Types

What are the definitions of the four plaque measures from Table 4 of the 2020 Williams et al. study (SCOT-HEART trial analysis published in Circulation)? These come from quantitative analysis of coronary computed tomography angiography (CCTA) images using semi-automated software (Autoplaque, Version 2.5). Analysts measured plaque in coronary segments that had any visible atherosclerosis (or set values to zero for completely normal arteries). Volumes were measured in mm³. “Burden” converts each volume into a percentage of the local vessel volume (plaque volume ÷ vessel volume × 100) and sums the results across segments for a per-patient value. This normalizes for differences in vessel size and length.

1. Plaque burden (also called total plaque burden)

This is the overall amount of all atherosclerotic plaque (both calcified/hard and noncalcified/soft) in the coronary arteries, expressed as a percentage of the vessel volume in the analyzed segments.

It answers: “What fraction of the artery wall (in the regions examined) is taken up by plaque of any kind?” Higher values indicate more extensive atherosclerosis overall. In the study, median total plaque burden was around 39%.

2. Noncalcified plaque burden

This measures the amount of “soft” (non-calcified) plaque only, again as a percentage of vessel volume.
Noncalcified plaque consists of cholesterol, fat, fibrous tissue, and other non-hardened components (it excludes calcium deposits). It is generally considered more biologically active and potentially changeable than calcified plaque. It includes the low-attenuation subtype described below plus higher-attenuation soft components (e.g., fibrous tissue). In the study this made up the large majority of total plaque.

3. Low-attenuation plaque burden

This is a specific, high-risk subtype of noncalcified (soft) plaque defined by very low CT density—attenuation of less than 30 Hounsfield units (HU). It is expressed as a percentage of vessel volume.

On the CT scan these areas appear darker. They correspond to lipid-rich necrotic cores (fatty, soft material with dead tissue inside the plaque). This is the plaque phenotype most strongly linked to rupture and subsequent myocardial infarction (heart attack). In the study it was the strongest independent predictor of future heart attack (even after adjusting for other risk factors, calcium score, and stenosis severity); a burden >4% was associated with roughly 4–5 times higher risk.

4. Calcified plaque burden

This measures the amount of “hard” plaque containing calcium deposits, expressed as a percentage of vessel volume.
Calcified plaque has high CT attenuation (calcium appears bright/white). It is generally more stable and less likely to rupture than soft or low-attenuation plaque, although a high burden still signals advanced overall atherosclerosis. In the study the median calcified plaque burden was low (around 0.4%).

Key relationships: Total plaque burden = noncalcified plaque burden + calcified plaque burden. Low-attenuation plaque is a subset of noncalcified plaque. All four were analyzed on a continuous (often log-transformed / per-doubling) basis in the multivariable models shown in Table 4. The software used adaptive, scan-specific thresholds for most plaque components, with the fixed <30 HU cutoff specifically for low-attenuation plaque.

14) Motoyama, Sadako, et al. “Computed Tomographic Angiography Characteristics of Atherosclerotic Plaques Subsequently Resulting in Acute Coronary Syndrome.” *Journal of the American College of Cardiology*, vol. 54, no. 1, 2009, pp. 49–57.
https://www.jacc.org/doi/10.1016/j.jacc.2009.02.068
(also available via PubMed: https://pubmed.ncbi.nlm.nih.gov/19555840/)

Patients with plaques showing both positive remodeling *and* low-attenuation plaque (LAP) had a markedly higher risk of subsequent acute coronary syndrome (ACS) (22.2% vs. 0.5% in those without these features). ACS was independently predicted by positive remodeling and/or LAP (HR 22.8). Culprit lesions that later caused ACS also had significantly larger LAP volume.

15) Feuchtner, Gudrun, et al. “High-Risk Criteria Low-Attenuation Plaque <60 HU and the Napkin-Ring Sign Are the Most Powerful Predictors of MACE: A Long-Term Follow-Up Study.” *European Heart Journal – Cardiovascular Imaging*, vol. 18, no. 7, 2017, pp. 772–779.

https://academic.oup.com/ehjcimaging/article-abstract/18/7/772/3060652

In a long-term follow-up study (mean ~7.8 years), low-attenuation plaque (defined as <60 HU) and the napkin-ring sign were the strongest independent predictors of major adverse cardiovascular events (MACE). LAP <60 HU carried an HR of 4.96. Prognosis was excellent with negative CCTA and worsened with increasing non-calcified/low-attenuation plaque components.

Chang, Hyuk-Jae, et al. “Coronary Atherosclerotic Precursors of Acute Coronary Syndromes: Results From the ICONIC Study.” *Journal of the American College of Cardiology*, vol. 71, no. 22, 2018, pp. 2511–2522.

https://www.jacc.org/doi/10.1016/j.jacc.2018.02.079
(also PMC full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC6020028/)

In this large nested case-control study (from the CONFIRM registry), ACS precursors showed higher volumes of fibrofatty and necrotic-core plaque (the quantitative CCTA correlates of low-attenuation/lipid-rich plaque). Necrotic-core volume and high-risk plaque features (including low attenuation) independently increased the risk of ACS, even though most culprit precursors were non-obstructive.

Discussion of CT Hounsfield Units

Approximate typical CT Hounsfield unit (HU) ranges (values are approximations that vary with scanner parameters such as kVp, reconstruction algorithms, contrast use, patient factors, and exact composition; they are not absolute): –

Air: −1000 HU (by definition). –

Abscess in liver: Typically 0 to 45 HU (often overlapping simple fluid/cysts; amebic often ~10–20 HU; pyogenic similar fluid attenuation with possible gas). –

Abscess in skin / soft-tissue abscess: Typically 0 to ~25–40 HU (fluid attenuation of pus/contents; wall may enhance; overlaps other collections). –

Fluid in sinus infection (mucus/secretions):

Acute ~−10 to 25 HU (mucoid/watery); chronic/inspissated higher, often 30–60 HU or up to ~130 HU (“high-attenuating” often >70 HU). –

Pleural effusion: Transudate typically +2 to +15 HU; exudate +4 to +33 HU (substantial overlap; means often in the single digits to low teens; some studies show limited differentiation by HU alone). –

Ascites: Simple/transudative approximately −10 to +10 or 0–20 HU (near water); exudative or complex often >15 HU (higher if hemorrhagic/proteinaceous). –

Water: 0 HU (by definition). –

Fat: −120 to −90 HU (commonly cited range; sometimes summarized as −50 to −100). –

Connective tissue: Generally soft-tissue range, overlapping muscle (~+35 to +55 HU) or broader soft tissue; loose connective tissue sometimes cited near −5 to +20 HU.

Arterial wall: Non-calcified soft-tissue attenuation, often roughly +30 to +50 HU or broader soft-tissue range (e.g., ~30–175 HU in some wall measurements); calcified components >~130 HU. – *

Bone: Cancellous/trabecular ~+300 to +400 (or up to ~800); cortical ~+500 to +1900 (or >1000; dense bone higher).

Supporting medical literature (MLA style) with URLs

Access dates approximate current context. – “Hounsfield Scale.” *Wikipedia*, Wikimedia Foundation, 29 July 2026, https://en.wikipedia.org/wiki/Hounsfield_scale. (Table of approximate values for air, fat, water, bone, pleural effusion, abscess/pus, mucus, muscle/soft tissue, etc.; notes variability.)

Häggström, Mikael. “Hounsfield Unit.” *Radlines*, https://radlines.org/Hounsfield_unit (or https://www.radlines.org/Hounsfield_scale). (Similar tabulated values with citations for fat, pleural effusion, abscess/pus, mucus, muscle, bone, etc.) – “Hounsfield Unit.” *Radiopaedia*, https://radiopaedia.org/articles/hounsfield-unit. (Definition and typical values including air −1000, water 0, fat, bone, soft tissues.) – “Ascites.” *Radiopaedia*, https://radiopaedia.org/articles/ascites. (Simple ascites −10 to +10 HU; exudative >15 HU.) –

Çullu, Naim, et al. “Efficacy of CT in Diagnosis of Transudates and Exudates in Patients with Pleural Effusion.” *Polish Journal of Radiology*, vol. 79, 2014, pp. 100–05 (or related reports citing similar ranges). Supporting pleural effusion differentiation discussions appear in multiple studies (e.g., overlapping ranges around low positive HU).

See also related work referenced in https://journals.lww.com and PubMed entries on CT attenuation for pleural fluid. – Radiology Key chapters (e.g., abdominal abscess, hepatic infections, paranasal sinuses): e.g., https://radiologykey.com/abdominal-abscess-4/ (abscess often 0–25 HU); https://radiologykey.com/focal-hepatic-infections-2/ (hepatic abscess 0–45 HU); sinus secretion ranges in inflammatory disease chapters (~−10 to 25 acute; higher chronic). –

PMC/open-access studies: e.g., “Imaging and Clinical Parameters for Distinction between Infected and Non-Infected Fluid Collections in CT…” *PMC*, https://pmc.ncbi.nlm.nih.gov/articles/PMC8870876/ (attenuation >10 HU associated with infection; examples ~8–29 HU); hepatic abscess literature consistently notes 0–45 HU range (multiple Radiology Key / Springer / AJR-derived sources). – Soft-tissue / muscle / connective references: e.g., quantitative muscle CT papers in *PMC* (https://pmc.ncbi.nlm.nih.gov/articles/PMC6260391/) noting muscle ~40–60 HU and loose connective near −5 to 20; arterial wall/plaque characterization in carotid CTA literature (soft plaque ~40–50 HU range, calcified >130). –

Additional pleural/ascites support: AJR and related papers on attenuation (e.g., https://www.ajronline.org discussions of exudate/transudate overlap around 0–30+ HU).

Disclaimer: individual decisions should be made with your personal physician after a full discussion of risks and benefits.

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my web site: https://drjeffreydachmd.com/
my personal blog: www.jeffreydachmd.com 
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit ebook
Cracking Cancer Toolkit print version
Heart Book by Jeffrey Dach MD
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com
www.drdach.com

Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements
Click Here for: Dr Dach’s Online Store for Nature’s Sunshine Supplements

Web Site and Discussion Board Links:

jdach1.typepad.com/blog/
disc.yourwebapps.com/Indices/244066.html
disc.yourwebapps.com/Indices/244067.html
http://sci.med.narkive.com/covV2Qo2/jeffrey-dach-book-announcment-natural-medicine-101

Disclaimer

All characters or patient names appearing on this web site or copied elsewhere are purely fictitious. Any resemblance to real persons, living or dead, is purely coincidental.

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Link to this Article

Copyright © 2026 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given. See Repost Guidelines.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.

Serving Areas of: Hollywood, Aventura, Miami, Fort Lauderdale, Pembroke Pines, Miramar, Davie, Coral Springs, Cooper City, Sunshine Ranches, Hallandale, Surfside, Miami Beach, Sunny Isles, Normandy Isles, Coral Gables, Hialeah, Golden Beach ,Kendall,sunrise, coral springs, parkland,pompano, boca raton, palm beach, weston, dania beach, tamarac, oakland park, boynton beach, delray,lake worth,wellington,plantation