Prevalence Of Noncalcified Plaques Research Articles

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

Quantification of subclinical plaque characteristics and perivascular fat using coronary computed tomography angiography (CCTA) among individuals with human immunodeficiency virus (HIV).

People infected with human immunodeficiency virus (PIWH) have a higher risk of cardiovascular events. This study was designed to compare the differences in plaque characteristics and perivascular fat between subclinical coronary atherosclerosis in PIWH and healthy controls (HC) by coronary computed tomography angiography (CCTA). We also assessed the associations between human immunodeficiency virus (HIV) infection, antiretroviral therapy (ART), and coronary artery disease (CAD). This cross-sectional study included a total of 158 PIWH and 79 controls. CCTA was used to evaluate coronary artery plaque prevalence, coronary stenosis severity, plaque composition, plaque volume, and perivascular fat attenuation index (FAI). Logistic regression analyses were used to assess the associations between the prevalence of coronary artery plaque and HIV-related clinical indicators. There was no difference in total coronary artery plaque prevalence between PIWH and controls (44.3% vs. 32.9%; P=0.09), but the prevalence of noncalcified plaque was significantly higher in PIWH compared with the controls (33.5% vs. 16.5%; P=0.006). After adjustment for age, sex, statin use, and family history of cardiovascular disease (CVD), the prevalence of noncalcified plaque remained 2 times higher in PIWH [odds ratio (OR), 2.082; 95% confidence interval (CI): 1.007-4.304; P=0.048]. The perivascular FAI measured around the left anterior descending artery (LAD) was higher in PIWH (-71.4±5.7 vs. -73.5±7.0; P=0.03) compared with that of the controls. The intra-group analyses of PIWH suggested that the decrease in nadir CD4+ T-cell count was associated with the increased prevalence of noncalcified plaque (OR, 4.139; 95% CI: 1.312-13.060; P=0.02). PIWH have a higher risk of developing noncalcified plaque and greater perivascular fat. In addition, the increased noncalcified plaque prevalence in PIWH may be associated with the immunodeficiency caused by HIV.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease

Abstract Background Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions. Purpose To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Methods 106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque. Results At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p<0,001), as well as spotty calcification (42.5% vs. 17.9%, p<0.001), positive remodeling (41.5% vs. 9.4%, p<0.001), low-attenuation plaques (24.5% vs. 3.8%, p<0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p<0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2). Conclusions Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence

Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

Prevalence of noncalcified plaques and coronary artery stenosis in patients with coronary calcium scores of zero.

ObjectivesA higher coronary artery calcium score (CACS) is associated with increased coronary artery plaque burden resulting in increased cardiovascular risk. Conversely, the absence of calcium indicates a low risk of cardiovascular events. However, coronary plaque calcification is a late manifestation of atherosclerosis; earlier stages of atherosclerosis present noncalcified plaques (NCPs) A recent study demonstrated that the absence of coronary artery calcification deposit does not preclude obstructive stenosis or the need for revascularization in patients with a high suspicion of coronary artery disease (CAD). Our study aimed to investigate the prevalence of NCP and the severity of coronary artery stenosis in symptomatic patients in our local population who were referred for coronary artery computed tomography angiogram (CCTA) with 0 CACS.MethodsA total of 299 patients who had undergone CACS and CCTA, and had scored zero for coronary artery calcium. Patients included had clinically appropriate indications, mainly chest pain with variable severity with no history of CAD. The presence of CAD risk factors, such as diabetes, hypertension, and smoking, was obtained from reviewing patient charts. The CCTA analysis was performed to evaluate for coronary artery stenosis and the presence of NCP. The severity of stenosis was quantified by visual estimation and divided into 0% stenosis, 1–25% stenosis, 26–50% stenosis, and more than 50% stenosis.ResultsThe prevalence of NCP was 6.4% (19 of the 299). Among the 19 patients with NCP, 52.6% had no identified coronary artery stenosis, 26.3% had less than 25%, and 21% had stenosis between 25 and 50%. None had stenosis greater than 50%. There was a strong association between male sex (P = 0.001), smoking (P = 0.0.004), hypertension, and NCP (P = 0.042), but no association was found between NCP and age or diabetesConclusionsIn patients with a high clinical suspicion of CAD, the absence of coronary artery calcification does not rule out CAD; up to 6.4% of these patients have early CAD as evidenced by NCP detected by CCTA, and none have more than 50% stenosis, However, future prognostic and long-term follow-up studies are needed to determine prognostic value of NCP in patients with 0 CACS.

Influence of Cigarette Smoking on Burden and Characteristics of Coronary Artery Plaques in Chinese Men.

It is generally well-known that smoking has a substantial impact on general health, and cardiovascular health in particular. The purpose of this study was to analyze the effects of different smoking status on the burden and characteristics of coronary artery plaques in Chinese men. Our study enrolled 1920 individuals with suspected coronary artery disease undergoing 256-detector-row computed tomography scan after clinical assessment. These study participants were stratified into three groups: never smoker, current smoker, and former smoker, according to their smoking status. Thereafter, the associations of different smoking status with the coronary artery plaques were assessed using both univariable and multivariable logistic regression. The prevalences of any plaque, significant stenosis and coronary artery calcium score (CACS) ≥ 10 were highest in the current smokers (all p < 0.05). The proportion of calcified plaques was the lowest and the prevalence of non-calcified plaques was the highest in current smokers (p = 0.004). The higher pack-years group had significantly elevated percentages of any plaque, significant stenosis, ≥ 2/LM vessel disease and CACS ≥ 10 than the lower pack-years group (all p < 0.001). The percent of calcified plaques was lower and the percent of non-calcified plaques was higher in the higher (> 20) pack-years group than in the lower pack-years group (≤ 20) (p = 0.024). Current smoking with higher pack-years was the independent risk factor for any plaque, significant stenosis, CACS ≥ 10, non-calcified and mixed plaques (all p < 0.05) after multivariate adjustments. The current smokers had the most serious burden of coronary artery plaques and the highest percentage of non-calcified plaques. Current smoking with higher pack-years was a significant risk factor for coronary artery plaque burden and non-calcified and mixed plaques. Chinese men; Cigarette smoking; Coronary artery calcium score; Coronary artery plaques; Non-calcified plaques.

Coronary Artery Calcification Across Ethnic Groups in Singapore

Introduction: In Singapore, the age-standardised event rates of myocardial infarction (MI) are 2- and 3-fold higher for Malays and Indians respectively compared to the Chinese. The objectives of this study were to determine the prevalence and quantity of coronary artery calcification (CAC) and non-calcified plaques across these 3 ethnic groups. Materials and Methods: This was a retrospective descriptive study. We identified 1041 patients (810 Chinese, 139 Malays, 92 Indians) without previous history of cardiovascular disease who underwent cardiac computed tomography for atypical chest pain evaluation. A cardiologist, who was blinded to the patients’ clinical demographics, reviewed all scans. We retrospectively analysed all their case records. Results: Overall, Malays were most likely to be active smokers (P = 0.02), Indians had the highest prevalence of diabetes mellitus (P = 0.01) and Chinese had the highest mean age (P &lt;0.0001). The overall prevalence of patients with non-calcified plaques as the only manifestation of sub-clinical coronary artery disease was 2.1%. There was no significant difference in the prevalence of CAC, mean CAC score or prevalence of non-calcified plaques among the 3 ethnic groups. Active smoking, age and hypertension were independent predictors of CAC. Non-calcified plaques were positively associated with male gender, age, dyslipidaemia and diabetes mellitus. Conclusion: The higher MI rates in Malays and Indians in Singapore cannot be explained by any difference in CAC or non-calcified plaque. More research with prospective follow-up of larger patient populations is necessary to establish if ethnic-specific calibration of CAC measures is needed to adjust for differences among ethnic groups. Key words: Coronary artery disease, Myocardial infarction, Race

Dynamic intravenous contrast bolus in CT fluoroscopy guided biopsy

Dynamic intravenous contrast bolus in CT fluoroscopy guided biopsy

Risk Factors for Non-calcified Plaques in Asymptomatic Population

The aims of this study were to assess the prevalence of noncalcified coronary plaques in asymptomatic patients and to investigate the risk factors. In this study, 584 patients were recruited prospectively. Patients were classified as having low, intermediate, or high pretest likelihoods of coronary artery disease according to the Morise score. Coronary computed tomographic angiography was performed in all patients using a 320-detector row dynamic-volume computed tomographic scanner. Imaging reconstruction was performed, and the postprocessed data were analyzed. Logistic regression analysis was used to evaluate the relationship between risk factors and the presence of noncalcified plaque. Coronary computed tomographic angiography revealed noncalcified plaques in 38.3% of all patients (224 of 584). The prevalence of noncalcified plaques was significantly higher in patients with calcium scores > 0 (P < .001). Significant differences were found between the degrees of luminal stenosis among patients with low, intermediate, and high pretest likelihoods of coronary artery disease (P = .001), while the prevalence of noncalcified plaques did not differ with the Morise score (P = .08). Noncalcified plaque was associated with hypercholesterolemia (P = .02) and diabetes mellitus (P = .002). Age (P = .47), gender (P = .58), estrogen status (P = .55), smoking (P = .22), hypertension (P = .27), and family history (P = .09) did not differ between patients with and those without noncalcified plaques. Hypercholesterolemia and diabetes mellitus are high risk factors for the prevalence of noncalcified plaques for asymptomatic patients.

The perimenopausal atherosclerosis transition

Women of perimenopause age experience an upward transition of cardiovascular risk possibly in association with changing hormonal status. We examined the cross-sectional relationships between the atherosclerotic plaque within the coronary and carotid arteries and aorta and the menopausal hormone levels among asymptomatic perimenopausal women. The Assessment of the Transition of Hormonal Evaluation with Noninvasive Imaging of Atherosclerosis was a prospective substudy of the Prospective Army Coronary Calcium project. We screened 126 asymptomatic perimenopausal women (mean age, 50 y) using contrast-enhanced CT angiography (multidetector CT) and carotid ultrasound. Women had coronary calcium data from 5 to 10 years earlier. The measures included cardiovascular risk factors, serum hormone levels, 64-slice multidetector CT, and carotid ultrasound. The prevalence of any coronary plaque was 35.5%. The prevalence of noncalcified plaque was 30.2%, and noncalcified plaque was the only manifestation of coronary artery disease in 10.7%. Markers of androgenicity (increased free testosterone and reduced sex hormone-binding globulin) were associated with an increased extent of calcified and noncalcified coronary artery plaque and aortic plaque. However, these relationships were not independent of cardiovascular risk factors. Follicle-stimulating hormone was directly associated with the number of aortic plaques. The levels of estrogen hormones were unrelated to plaque presence or extent. Coronary, aortic, and carotid arterial plaque is prevalent in perimenopausal women without cardiac symptoms. The assessment of perimenopausal hormone status was not independently associated with subclinical atherosclerosis beyond standard cardiovascular risk factors.

The prognostic value of multidetector coronary CT angiography for the prediction of major adverse cardiovascular events: a multicenter observational cohort study

To assess the prognostic value of coronary artery stenosis identification by coronary computed tomographic angiography (CCTA) for the prediction of major adverse cardiac events (MACE) in a multicenter prospective cohort study. We performed a prospective multicenter observational cohort study of symptomatic patients with suspected or known coronary artery disease (CAD) (n = 172; 57% male) undergoing CCTA in accordance to ACC/AHA Appropriateness Criteria from 4 sites in and around Paris, France, and followed for a mean duration of 22.0 +/- 4.5 months (interquartile range 18-26 months). Coronary arteries by CCTA were interpreted by physicians blinded to the patient characteristics for the presence or absence obstructive (>or=70% luminal diameter stenosis), as well as for plaque composition categorized as non-calcified, calcified or "mixed." MACE was defined as death, non-fatal myocardial infarction, unstable angina or target vessel revascularization. MACE event rates were compared between patients with or without obstructive plaque and with differing plaque compositions. MACE event rates were significantly higher in patients with obstructive coronary artery stenosis by CCTA compared to those without (61.1% vs. 3.9%, P < 0.01). In patients with obstructive stenosis, mixed (83.3% vs. 25.3%, P < 0.01) and calcified (94.4% vs. 50.7%, P < 0.01) plaque presence was significantly higher than in patients without obstructive stenosis, with no differences in prevalence of non-calcified plaque (27.8% vs. 20.8%, P = NS). For MACE, the negative predictive value of no observed coronary artery plaque was 100% in the follow-up period. In this prospective multicenter study of symptomatic patients with suspected or known CAD undergoing CCTAs interpreted by imagers blinded to patient characteristics, CCTA presence of plaque severity and composition successfully identifies patients at risk for incident MACE events. Importantly, a negative CCTA portends an extremely low risk for incidence MACE.

Negative calcium score and the presence of obstructive coronary lesions in patients with intermediate CAD probability

We intended to estimate how the zero coronary artery calcium (CAC) score in symptomatic patients with intermediate probability of coronary artery disease predicts the absence of obstructive non-calcified coronary plaques (NCAPs). CAC scoring and coronary arteries were evaluated by means of 64-multislice CT coronary angiography (CCTA). In 166 subject with CAC=0, Non-obstructive NCAPs (less than 50%) were found in 17 patients (10.2%), while significant stenosis were diagnosed in 3 (2%). In the female insignificant stenoses were more frequent (12%) than in men (6%), however, all 3 cases with significant stenosis were male. In our study, where CCTA has been used as diagnostic method for CAD diagnosing, the prevalence of non-calcified plaques in CAC=0 subjects is relatively high. Our study confirms a relatively low incidence of significant coronary stenosis in this subset of CAD-suspected subjects.

Prevalence of Noncalcified Coronary Plaques by 64-Slice Computed Tomography in Patients With an Intermediate Risk for Significant Coronary Artery Disease

In this prospective study, we investigated the prevalence and characteristics of clearly discernible noncalcified coronary plaques in a patient population with suspected significant coronary artery disease (CAD) by using 64-slice computed tomography (CT). The assessment of noncalcified coronary plaques by noninvasive strategies may be important to improve cardiovascular risk stratification. To rule out significant stenosis, high-resolution 64-slice coronary CT (0.6-mm collimation, 330-ms gantry rotation time) was performed in 161 consecutive patients with an intermediate risk for having CAD. Computed tomography data sets were evaluated for presence of coronary calcifications, noncalcified plaques, and/or lumen narrowing. Noncalcified coronary plaques were detected in 48 (29.8%) of 161 enrolled patients. Although noncalcified plaques together with coronary calcifications were present in 38 of 161 (23.6%) patients, the prevalence of noncalcified plaques as the only manifestation of CAD was 6.2% (10 of 161 patients). Patients with noncalcified plaques were characterized by significantly higher total cholesterol, low-density lipoprotein, and C-reactive protein levels as well as a trend for more diabetes mellitus. The majority of noncalcified plaques resulted in lumen narrowing of <50%. Of the remaining 113 patients, CAD and coronary calcifications were ruled out in 53 of 161 (32.9%) patients, whereas 60 of 161 (37.3%) patients presented with calcifications in the absence of noncalcified plaque. With the use of 64-slice CT, clearly discernible noncalcified atherosclerotic coronary plaques can be detected in a large group of patients with an intermediate risk for having CAD. The assessment of these plaques by CT angiography may allow for improved cardiovascular risk stratification.

Noninvasive Assessment of Plaque Morphology and Composition in Culprit and Stable Lesions in Acute Coronary Syndrome and Stable Lesions in Stable Angina by Multidetector Computed Tomography

The purpose of this study was to assess morphology and composition of culprit and stable coronary lesions by multidetector computed tomography (MDCT). Noninvasive identification of culprit lesions has the potential to improve noninvasive risk stratification in patients with acute chest pain. Thirty-seven patients with acute coronary syndrome (ACS) or stable angina underwent coronary 16-slice MDCT and invasive selective angiography. In all significant coronary lesions two observers measured the degree of stenosis, plaque area at stenosis, and remodeling index and assessed plaque composition. Differences between culprit lesions in patients with ACS and stable lesions in patients with ACS or stable angina were determined. We analyzed 40 lesions with excellent image quality in 14 patients with ACS and 9 patients with stable angina. Culprit lesions in patients with ACS (n = 14) had significantly greater plaque area and a higher remodeling index than both stable lesions in patients with ACS (n = 13) and in patients with stable angina (n = 13) (17.5 +/- 5.9 mm2 vs. 9.1 +/- 4.8 mm2 vs. 13.5 +/- 10.7 mm2, p = 0.02; and 1.4 +/- 0.3 vs. 1.0 +/- 0.4 vs. 1.2 +/- 0.3, p = 0.04, respectively). The prevalence of non-calcified plaque was 100%, 62%, and 77%, respectively, and the prevalence of calcified plaque was 71%, 92%, and 85%, respectively, in culprit lesions in patients with ACS and in stable lesions in patients with ACS or stable angina. We introduce the concept of noninvasive detection and characterization of coronary atherosclerotic lesions in patients with ACS by MDCT. We identified differences in lesion morphology and plaque composition between culprit lesions in ACS and stable lesions in ACS or stable angina, consistent with previous intravascular ultrasound studies.

Noninvasive evaluation of the prevalence of noncalcified atherosclerotic plaques by multi-slice detector computed tomography: results of a pilot study

Background: Multi-slice detector computed tomography (MDCT) not only allows for the determination of coronary calcifications, but also for the noninvasive visualization of noncalcified plaques. Thus, coronary artery disease (CAD) can be detected at a fairly early stage. Since data on the prevalence of potentially rupture prone noncalcified coronary lesions are still missing, it was aim of the present investigation to study this in patients with a distinct cardiovascular risk profile, but without known CAD. Methods: 68 patients with clinical suspicion of CAD and multiple cardiovascular risk factors were included in this prospective study. Calcium scoring, as well as the detection of noncalcified plaques were performed using a Somatom VZ scanner (Siemens™, Forchheim, Germany). Results: Calcium scoring could be performed in all patients on native scans; 63/68 (96%) of contrast enhanced scans showed sufficient image quality to perform a screening for noncalcified plaques. The three scans without diagnostic image quality had been performed at heart rates of 95±18/min. Coronary calcifications were found in 36/65 (55%) patients (Agatston score: 247±358). Additional noncalcified plaques were detected in 16/36 (45%) of these patients; 29/65 (45%) patients had no coronary calcifications (Agatston score: 0), but noncalcified plaques could be detected in 3/29 (10%) of these patients. Conclusions: The prevalence of noncalcified plaques was 29% in the whole study group, and even in 10% of patients without coronary calcifications. Further prospective large scale studies are required to confirm these data, and to evaluate the clinical implication of this finding.