Plaque, Atherosclerotic – ABC CARDIOL

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Original Article

Profile of IL-6 and TNF in Foam Cell Formation: An Improved Method Using Fluorescein Isothiocyanate (FITC) Probe

Cynthia Aparecida Castro et al. Tereza Cristina Buzinari Rafael Luis Bressani Lino Heloisa Sobreiro Selistre de Araújo … Fernanda de Freitas Aníbal Roberto Mario Machado Verzola Vanderlei Salvador Bagnato Natalia Mayumi Inada Gerson Jhonatan Rodrigues

Abstract

Background

The formation of foam cells occurs due to the increase in low-density plasma lipoprotein (LDL) and dysregulation of inflammation, which is important for the development of atherosclerosis.

Objective

To evaluate the profile of tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the existing foam cell formation method, optimizing this protocol.

Methods

The LDL was isolated, oxidized, and labeled with a Fluorescein isothiocyanate (FITC) probe. Foam cells were generated from THP-1 human monocyte-derived cells and incubated in the absence (control) or presence of FITC-ox-LDL (10, 50, 100, 150, or 200 μg/mL), for 12, 24, 48, or 72 hours. The accumulated FITC-ox-LDL in the cell was quantified by microscopy. The enzyme-linked immunosorbent assay was evaluated to quantify the IL-6 and TNF-α, with p < 0.05 considered significant.

Results

All the FITC-ox-LDL concentrations tested showed a higher fluorescence when compared to the control, showing a greater accumulation of lipoprotein in cells. The higher the concentration of FITC-ox-LDL, the greater the production of TNF-α and IL-6. The production of IL-6 by foam cells was detected up to the value of 150 µg/mL of the maximum stimulus for LDL. Concentrations above 50 μg/mL LDL stimulated greater release of TNF-α compared to control.

Conclusions

Our model contributes to the understanding of the release of IL-6 and TNF-α in response to different concentrations of ox-LDL, using an optimized method for the formation of foam cells.

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Editorial

Cost-Effectiveness of Using the Coronary Calcium Score to Guide Therapeutic Decisions in Primary Prevention in the Brazilian Population

Cardiovascular diseases (CVD) statistics never fail to impress even the most hardened and experienced physician. One-third of deaths worldwide are still due to cardiovascular causes (85% of those are myocardial infarction and stroke), and 75% occur in mid-to-low income countries.^, Half the people who died of myocardial infarction never had symptoms before the tragic event, and most never had the diagnosis of coronary artery disease. Despite our best efforts, the prevalence of ischemic heart disease (IHD) has been steadily rising for the last 30 years worldwide due to population aging, but even if we standardize by age, the prevalence has been stable, and notwithstanding fallen. This fact highlights the importance of lifestyle changes that allow for a healthier heart and the need to focus on implementing existing cost-effective policies and interventions.

Coronary calcification is almost always a marker of atherosclerosis. The coronary calcium score (CCS) is a number that quantifies coronary calcification as a surrogate for total coronary atherosclerotic burden. Even though calcification results from plaque healing, higher-risk plaques tend to have proportionately greater non-calcified components; CCS has been proven to be a strong predictor of CVD and IHD events in multiple large, solid, population-based studies.

[…]

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Editorial

Angiographic Scores in Prediction of No-Reflow, Myocardial Injury May not end with Reperfusion

Adriano Ossuna Tamazato et al. Thais Chang Valente Tamazato Cristiano Guedes Bezerra

The ST segment elevation infarction (STEMI) is usually precipitated by the rupture or erosion of an atherosclerotic plaque and the consequent formation of an occlusive thrombus. Early percutaneous coronary intervention is the treatment of choice for providing a more complete revascularization and less bleeding complications when compared to fibrinolysis.^,

In the last decades, we observed a substantial development in the pharmacological and invasive treatments of STEMI, which significantly reduced early mortality. Several variables affect clinical outcomes, including patient age, time to reperfusion, angiographic complexity and the occurrence or not of the no-reflow (NR) phenomenon during percutaneous intervention.^, NR is defined by inadequate myocardial perfusion in a given territory, in the absence of mechanical obstruction of the epicardial coronary and is associated with a worse clinical prognosis.^,

[…]

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Original Article

Carotid Artery Atherosclerotic Profile as Risk Predictor for Restenosis After Coronary Stenting

Cássia da Silva Antico Rodrigues et al. Rodrigo Bazan Fabrício Moreira Reis Caroline F. S. Mazeto Pupo da Silveira … Lívia Maria Severino Hueb Fábio Cardoso de Carvalho Hélio Rubens de Carvalho Nunes Katashi Okoshi João Carlos Hueb Silméia Garcia Zanati Bazan

Abstract

Background:

The incidence of restenosis of the coronary artery after a bare-metal stent implant has been lower than in simple balloon angioplasty; however, it still shows relatively high rates.

Objective:

The aim of this study was to find new risk indicators for in-stent restenosis using carotid ultrasonography, that, in addition to the already existing indicators, would help in decision-making for stent selection.

Methods:

We carried out a cross-sectional prospective study including 121 consecutive patients with chronic coronary artery disease who had undergone percutaneous coronary intervention with repeat angiography in the previous 12 months. After all cases of in-stent restenosis were identified, patients underwent carotid ultrasonography to evaluate carotid intima-media thickness and atherosclerosis plaques. The data were analyzed by Cox multiple regression. The significance level was set a p<0.05.

Results:

Median age of patients was 60 years (1^st quartile = 55, 3^rd quartile = 68), and 64.5% of patients were male. Coronary angiography showed that 57 patients (47.1%) presented in-stent restenosis. Fifty-five patients (45.5%) had echolucent atherosclerotic plaques in carotid arteries and 54.5% had echogenic plaques or no plaques. Of patients with who had echolucent plaques, 90.9% presented coronary in-stent restenosis. Of those who had echogenic plaques or no plaques, 10.6% presented in-stent restenosis. The presence of echolucent plaques in carotid arteries increased the risk of coronary in-stent restenosis by 8.21 times (RR=8.21; 95%CI: 3.58-18.82; p<0.001).

Conclusions:

The presence of echolucent atherosclerotic plaques in carotid artery constitutes a risk predictor of coronary instent restenosis and should be considered in the selection of the type of stent to be used in coronary angioplasty.

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Original Article

Gensini Score and Thrombus Burden Add Predictive Value to the SYNTAX Score in Detecting No-Reflow after Myocardial Infarction

Luís Carlos V Matos et al. Luiz Sergio Carvalho Rodrigo Modolo Simone Santos … José Carlos Quinaglia e Silva Osório Luis Rangel de Almeida Andrei C. Sposito

Abstract

Background

No-reflow after percutaneous coronary intervention is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). SYNTAX score is a good predictor of no-reflow.

Objective

We aimed to evaluate whether atherosclerotic burden (Gensini score) and thrombus burden in the culprit coronary artery would improve the ability of the SYNTAX score to detect no-reflow.

Methods

In this prospective cohort study, consecutive patients with STEMI who presented within 12 h of onset of symptoms were selected for this study. No-reflow was defined as TIMI flow < 3 o r TIMI flow = 3 but myocardial blush grade <2. Thrombus burden was quantified according to the TIMI thrombus grade scale (0 to 5).

Results

A total of 481 patients were included (mean age 61±11 years). No-reflow occurred in 32.8%. SYNTAX score (OR=1.05, 95%CI 1.01–1.08, p<0.01), thrombus burden (OR=1.17, 95%CI 1.06–1.31, p<0.01), and Gensini score (OR=1.37, 95%CI 1.13–1.65, p0) (0.54 [0.035–0.73], p<0.001) showed improvement in the predictive ability of no-reflow in the combined model, with integrated discrimination improvement (IDI) of 0.07 (0.04–0.09, p<0.001).

Conclusions

Our findings suggest that, in patients with STEMI undergoing percutaneous coronary intervention, atherosclerotic burden and thrombus burden in the culprit artery add predictive value to the SYNTAX score in detecting the no-reflow phenomenon. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

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Editorial

Our Precious Calcium Score

Some things are strong, robust. In imaging in general, those are based on solid principles of physics that can resist the inequities of daily use. In computed tomography (CT), the main tissue densities are solid, measured in Hounsfield Units (HU), and some are really strong, calcium-strong, so to speak. Contrast resolution is an issue in CT imaging in general, mainly in the wide range of structures inside the water density spectrum. But the densities on both ends of the whole HU spectrum, i.e., air and fat on one side and bone and metal on the other, are depicted clearly. Also, they could be measured with a great deal of accuracy, and, as these images were mathematical in origin, there is a lot more than the eye can see that could be measured on a CT image, and there are several measurements that could be done on rather simple scans. But let’s revise this latter.

Measuring the amount of calcification in coronary arteries is rather old. It is termed coronary calcium score (CCS). It has been developed, tested and implemented, has had its clinical value shown, but still lacks consensus of use and insurance coverage in medical procedures around the world.^– At first, it had to be done in electron beam tomography and then, with the new generation of CT scans. In this issue of Arquivos Brasileiros de Cardiologia, Souza et al. elegantly show how this CCS measurement has excellent correlation as done in the “usual” manner as well as from a standard chest CT. This was shown in the past, to a wide variety of scans and with good accuracy, some comparing with semiquantitative and visual methods, with a consensus of the Society of Cardiovascular Computed Tomography, including a recent great work from this same group of researchers. But now, crunching the numbers, the correlation is excellent, as has been shown by others before, and the suggestion is that we could accurately measure CCS, this important tool in coronary artery disease risk stratification, from a rather more common exam.

[…]

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Original Article

Impact of Atherogenic Indexes in Saphenous Vein Graft Stenosis

Fethi Yavuz et al. Salih Kilic Mehmet Kaplan Arafat Yıldırım … Mehmet Kucukosmanoglu Mustafa Dogdus

Abstract

Background

Saphenous vein grafts (SVG) are frequently used in patients that have undergone coronary artery bypass graft (CABG) surgery. Objectives: To evaluate the relationship between atherogenic indexes and SVG stenosis.

Methods

Altogether, 534 patients (27.7% women, mean age 65±8.4 years) that underwent CABG and elective coronary angiography were included in the study. Patients with at least one SVG stenosis ≥50% were allocated to the stenosis group SVG (+) (n=259) and patients without stenosis were categorized as SVG (-) (n=275). Atherogenic index of plasma (AIP) and atherogenic coefficient (AC) were calculated from the patients’ routine lipid parameters. The level of significance was p<0.05.

Results

The number of patients with a history of hypertension (HT), diabetes mellitus (DM), stroke, and heart failure was significantly higher in the SVG (+) group than in the SVG (-) group. Total cholesterol, triglycerides, LDL-C were significantly higher and HDL-C was lower in the SVG (+) group than in the SVG (-) group. AIP (p<0.001) and AC (p<0.001) were significantly higher in the SVG (+) group than in the SVG (-) group. The receiver operating characteristic (ROC) analysis show that both AIP and AC were better than HDL-C, LDL-C and non-HDL-C at predicting SVG stenosis. In the multivariate analysis, history of DM, HT, stroke, heart failure (HF), number of saphenous grafts, HDL-C, LDL-C, non-HDL-C, AIP and AC were found to be independent risk factors for SVG stenosis.

Conclusion

AIP and AC were independent predictors of SVG stenosis. Moreover, both AIP and AC have better performance in predicting SVG stenosis than LDL-C, HDL-C and non-HDL-C. (Arq Bras Cardiol. 2020; 115(3):538-544)

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Original Article

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

Bárbara Campos Abreu Marino et al. Nermina Buljubasic Martijn Akkerhuis Jin M. Cheng … Hector M. Garcia-Garcia Evelyn Regar Robert-Jan van Geuns Patrick W. Serruys Eric Boersma Isabella Kardys

Abstract

Background:

Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.

Objective:

To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.

Methods:

In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.

Results:

In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm² (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).

Conclusion:

In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

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Original Article

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography

Fabíola Santos Gabriel et al. Luiz Flávio Galvão Gonçalves Enaldo Vieira de Melo Antônio Carlos Sobral Sousa … Ibraim Masciarelli Francisco Pinto Sara Melo Macedo Santana Carlos José Oliveira de Matos Maria Júlia Silveira Souto Flávio Mateus do Sacramento Conceição Joselina Luzia Menezes Oliveira

Abstract

Background:

In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature.

Objective:

To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA).

Methods:

This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted.

Results:

The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable.

Conclusions:

The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers.

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Original Article

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol

Walter Masson et al. Martín Lobo Graciela Molinero Daniel Siniawski

Abstract

Background:

Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk.

Objectives:

Methods:

Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define “lipid discordance” if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed.

Results:

The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found.

Conclusion:

Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

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Original Article

Which Coronary Lesions Are More Prone to Cause Acute Myocardial Infarction?

Taner Sen et al. Mehmet Ali Astarcioglu Osman Beton Lale Dinc Asarcikli Celal Kilit

Abstract

Background:

According to common belief, most myocardial infarctions (MIs) are due to the rupture of nonsevere, vulnerable plaques with < 70% obstruction. Data from recent trials challenge this belief, suggesting that the risk of coronary occlusion is, in fact, much higher after severe stenosis. The aim of this study was to investigate whether or not acute ST-elevation MIs result from high-grade stenoses by evaluating the presence of coronary collateral circulation (CCC).

Methods:

We retrospectively included 207 consecutive patients who had undergone primary percutaneous coronary intervention for acute ST-elevation MI. Collateral blood flow distal to the culprit lesion was assessed by two investigators using the Rentrop scoring system.

Results:

Out of the 207 patients included in the study, 153 (73.9%) had coronary collateral vessels (Rentrop 1-3). The Rentrop scores were 0, 1, 2, and 3 in 54 (26.1%), 50 (24.2%), 51 (24.6%), and 52 (25.1%) patients, respectively. Triglycerides, mean platelet volume (MPV), white cell (WBC) count, and neutrophil count were significantly lower in the group with good collateral vessels (p = 0.013, p = 0.002, p = 0.003, and p = 0.021, respectively).

Conclusion:

More than 70% of the patients with acute MI had CCC with Rentrop scores of 1-3 during primary coronary angiography. This shows that most cases of acute MI in our study originated from underlying high-grade stenoses, challenging the common believe. Higher serum triglycerides levels, greater MPV, and increased WBC and neutrophil counts were independently associated with impaired development of collateral vessels.

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Original Article

Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed Tomography Angiography

Joselina Luzia Menezes Oliveira et al. Mario Hiroyuki Hirata Amanda Guerra de Moraes Rego Sousa Fabíola Santos Gabriel … Thiago Dominguez Crespo Hirata Irlaneide da Silva Tavares Luiza Dantas Melo Fabiana de Santana Dória Antônio Carlos Sobral Sousa Ibraim Masciarelli Francisco Pinto

Background:

Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined.

Objective:

To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH.

Methods:

Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH.

Results:

HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9).

Conclusion:

Hypertensive men had multivessel disease more often than women. Male gender was a determinant factor of significant CAD, multivessel disease, CS ≥ 100 and calcified and partially calcified plaques, whereas SAH was predictive of partially calcified plaques.

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Artigo Original

Coronary tomography for predicting adverse events in patients with suspected coronary disease

Márcio Vinicius Lins Barros et al. Daniel Rocha Rabelo Maria do Carmo Pereira Nunes Maria Helena Albernaz Siqueira

BACKGROUND: Although studies have demonstrated a high diagnostic accuracy of multi-detector Coronary CT (MDCT) in the detection of Coronary Artery Disease (CAD), data on the prognostic value of this method are limited. OBJECTIVE: Determine the value of MDCT in predicting adverse clinical outcomes in patients with suspected CAD. METHODS: We prospectively evaluated 355 consecutive patients (mean age 58 ± 12 years, 252 males) with suspected CAD between January 2008 and June 2010. CAD at MDCT was defined as the presence of atheromatous plaque observed in any coronary artery. The adverse clinical outcomes were defined as death, myocardial infarction, unstable angina or myocardial revascularization. RESULTS: During a mean follow-up of 15 months, there were 55 cardiac events. In the multivariate analysis using the Cox regression model, NYHA functional class, diabetes, smoking and atherosclerosis at the MDCT were predictors of adverse clinical outcome, and the presence of plaque at the MDCT was strongly associated with adverse clinical outcomes, regardless of established risk factors for CAD (hazard ratio 5.29; 95% confidence interval: 2.4 -11.8, p <0.001). CONCLUSION: The presence of atherosclerosis demonstrated by MDCT in patients with suspected CAD showed independent and incremental value when compared to conventional risk factors in the prediction of adverse clinical outcomes, and may prove useful in risk stratification of these patients.

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