Total Plaque Area Research Articles

Relationship between Atherosclerosis and Cancer: An observational outcome study

Background and aims: It was investigated whether there is a relationship between advanced atherosclerosis of the carotid artery and cancer. Method: The carotid Total Plaque Area (TPA), the maximum plaque thickness, and the cardiovascular risk based on Framingham calculator using body-mass-index were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was collected as part of occupational health check-ups. Result: In 4207 healthy men aged 35-65 years (50±8 years) we found 578 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 566 (97.9%) subjects. The average follow-up time was 48 months (range 0 to 139 months). Ten subjects were excluded because of missing data on treatment. A total number of 230 subjects was treated with a statin, 326 received no statin. Within the group of these subjects (54±6 years), 33 men died (15 cancer, 4 strokes, 11 heart attacks, 1 COPD, 1 sepsis, 1 cirrhosis of the liver). In the group with CVD death, two subjects were treated with a statin, 13 were untreated. In the group with cancer death, two subjects were treated with a statin, 13 were untreated. The death rate because of cancer and CVD was 1.7% for the treated subjects and 8.0% for the untreated subjects. In the group with low risk (n= 1890), six men died (2 traffic accidents, 1aneurysm bleeding, 2 cancer, 1 unclear, a follow-up examination has been completed for 43.9% (n= 830) of the subjects, mean follow-up time of 65 months (0-137 months). One man died (Parkinson) within the group with intermediate risk. In this group (n= 482) a follow-up examination has been completed for 55% (n= 265) with a mean follow-up time of 55 months (total range: 0-130 months). In the reference group (no atherosclerosis; n= 1257) follow-up has been completed in 38.3% (n= 482) with a mean follow-up time of 60 (0-145) months and nobody died. In 3203 healthy women aged 35-65 years nobody died of cancer. Conclusion: The development of cancer in men with advanced atherosclerosis of the carotid artery appears to be noticeable. The question of whether there is a causal relationship requires further investigations.

Skin autofluorescence, a measure of tissue accumulation of advanced glycation end products, is associated with subclinical atherosclerosis in coronary and carotid arteries

Background and aimsSkin autofluorescence (AF), a measure of tissue accumulation of advanced glycation end products (AGEs), has been associated with diabetes and cardiovascular disease. However, the association of skin AF with subclinical coronary atherosclerosis in the general population is largely unknown. Our study aimed to examine the associations between skin AF and subclinical atherosclerosis in coronary and carotid arteries in a middle-aged population. MethodsSkin AF and subclinical atherosclerosis were measured in 4416 subjects (aged 50–64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Skin AF was measured non-invasively using an autofluorescence reader. Subclinical atherosclerosis was assessed by ultrasonography of carotid arteries for evaluation of carotid plaques and computed tomography for the evaluation of the coronary artery calcium score (CACS). ResultsA total of 615 (13.9%) individuals had CACS >100 and 1340 (30.3%) subjects had bilateral carotid plaques (median total plaque area: 8 mm2). After controlling for confounding factors, there were significant associations between skin AF (per 1 standard deviation (SD) increase) and CACS >100: odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.06–1.29, p = 0.001. Total carotid plaque area and occurrence of bilateral carotid plaques (OR per 1 SD increase: 1.10, 95%CI: 1.01–1.19, p = 0.02) were similarly associated with skin AF after multivariable adjustments. ConclusionsElevated skin AF was significantly associated with subclinical atherosclerosis in coronary and carotid arteries independently of conventional risk factors. Skin AF, a measure of accumulation of AGEs, could be a marker for the identification of middle-aged subjects with elevated atherosclerotic risk.

Carotid plaque is strongly associated with coronary artery calcium and predicts incident coronary heart disease in a population-based cohort

Background and aimsCoronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events. MethodsThe REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1–100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors. ResultsCombined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories. ConclusionsCarotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

Background and aimsThe severity of the atherosclerotic burden is hardly quantifiable in subjects at high cardiovascular (CV) risk under intensive pharmacological therapy. Several molecules have been proposed as circulating biomarkers of atherosclerosis, but none has emerged as clinically meaningful. MethodsCirculating proteins involved in inflammation, plaque remodeling, smooth muscle cell migration, apoptosis and endothelial activity were measured by Proximity Extension Assay in the SUMMIT study cohort (n = 1500), including patients with type 2 diabetes (66%) and established CV disease (50%), who underwent ultrasound assessment of carotid atherosclerosis with total plaque area quantification. ResultsIn patients with evidence of carotid artery atherosclerosis (n = 1174), seven biomarkers were identified as the more closely related to atherosclerosis extension. Compared with a multivariable model including major traditional CV risk factors, the percentage gain of explained variability in total plaque area was the greatest (33%) after inclusion of CD40 receptor (CD40R) ligand, followed by PDGF (30%), CD40R (26%), EGF (22%), CXCL1 (15%), HBEGF and MMP-17 (both 11%). The relationship of total plaque area with CD40R, PDGF was hyperbolic. In the whole study cohort, including subjects without carotid plaques, CD40R was the strongest predictor of the presence and extension of carotid atherosclerosis. Subjects in the third CD40R tertile had a more than two-fold greater atherosclerotic burden compared with lower CD40R tertiles, despite an only marginally higher load of CV risk factors. ConclusionsCD40R stands among an extended set of plausible atherosclerosis-related biomarkers as the most powerful predictor of carotid atherosclerosis burden in a high CV risk cohort.

Prevalence and Predictors of Cerebral Microangiopathy Determined by Pulsatility Index in an Asymptomatic Population From the ILERVAS Project.

Background: Little is known about the prevalence of cerebral microangiopathy (CM), which is related to cognitive impairment, in an asymptomatic population. Pulsatility index (PI) is an easily measurable parameter of cerebral vascular resistance in transcranial duplex of the middle cerebral artery (MCA) study. We aimed to determine the prevalence of CM measured by PI of MCA in low to moderate vascular risk subjects.Methods: We included 3,721 subjects between 45 and 70 years without previous history of vascular disease or diabetes mellitus and with at least one other vascular risk factor from the cross-sectional study ILERVAS (Lleida, Spain). Patients underwent transcranial duplex to determine MCA-PI. Possible CM was defined by MCA-PI >1.1. Carotid and femoral arteries ultrasound registration was done to determine the presence, the number, and the area of atheromatous plaques. Body mass index (BMI), pulse pressure (PP) and laboratory data were also recorded.Results: 439 (11.8%) subjects were excluded due to the low quality of transcranial duplex images. Median age was 57 [IQR 52, 62] years. Possible CM was found in 424 (12.9%) subjects. CM patients had higher prevalence of plaques than non-CM (77.4 vs. 66.4%, p < 0.001). PI showed a positive linear correlation with the number of territories with plaques (r = 0.130, p < 0.001), and the total plaque area (r = 0.082, p < 0.001). The predictors of possible CM were the age, male gender, and PP.Conclusions: In low-to-moderate vascular risk asymptomatic population, the proportion of abnormal brain microvascular bed determined by MCA-PI is not negligible. The planned 10-year follow-up will describe the clinical relevance of these findings.

Carotid-femoral pulse wave velocity acquisition methods and their associations with cardiovascular risk factors and subclinical biomarkers of vascular health.

Different methods to measure carotid-femoral pulse wave velocity (CFPWV) may affect the measurements obtained and influence the association between CFPWV, cardiovascular risk factors and biomarkers of subclinical vascular health. The estimation of distance between the carotid and femoral artery measurement sites (the arterial path length) is particularly problematic. We determined if CFPWV and equation-based estimates of CFPWV were influenced by arterial path length and if this affected the association of CFPWV with cardiovascular risk factors and subclinical vascular biomarkers. The CFPWV derived from the measurement of surface distance (CFPWV-D), arterial path length formula (CFPWV-F), and estimated CFPWV (ePWV) were obtained from 489 older adults (67.2 ± 8.8 years). Macrovascular [carotid artery: lumen diameter (LD), inter-adventitial diameter (IAD), intima-media thickness (IMT) and total plaque area (TPA)] and microvascular [reactive hyperaemia index and urinary albumin-creatinine ratio (UACR)] biomarkers were also measured. CFPWV-D was significantly greater than CFPWV-F [9.6 (8.0-11.2) vs. 8.9 (7.6-10.5) m/s, P < 0.001], because of estimated path length being longer in CFPWV-D than CFPWV-F (495.4 ± 44.8 vs. 465.3 ± 20.6 mm, P < 0.001). ePWV was significantly greater than both CFPWV-F and CFPWV-D [11.0 (10.0-12.2) m/s, P < 0.001]. The three CFPWV methods were similarly associated with LD, IAD, IMT, TPA and UACR but not with cardiovascular risk factors. Different methods to measure CFPWV affect the derived measurement values and the association with cardiovascular risk factors but not the association with subclinical biomarkers of vascular health. These hitherto unreported observations are important considerations in experimental design, data interpretation and of particular importance, comparison between studies where CFPWV is measured.

Mean Versus Peak Coronary Calcium Density on Non-Contrast CT: Calcium Scoring and ASCVD Risk Prediction

ObjectivesThis study sought to assess the relationship between mean vs peak calcified plaque density and their impact on calculating coronary artery calcium (CAC) scores and to compare the corresponding differential prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) mortality. BackgroundThe Agatston CAC score is quantified per lesion as the product of plaque area and a 4-level categorical peak calcium density factor. However, mean calcium density may more accurately measure the heterogenous mixture of lipid-rich, fibrous, and calcified plaque reflective of ASCVD risk. MethodsWe included 10,373 individuals from the CAC Consortium who had CAC >0 and per-vessel measurements of peak calcium density factor and mean calcium density. Area under the curve and continuous net reclassification improvement analyses were performed for CHD and ASCVD mortality to compare the predictive abilities of mean calcium density vs peak calcium density factor when calculating the Agatston CAC score. ResultsParticipants were on average 53.4 years of age, 24.4% were women, and the median CAC score was 68 Agatston units. The average values for mean calcium density and peak calcium density factor were 210 ± 50 HU and 3.1 ± 0.5, respectively. Individuals younger than 50 years of age and/or those with a total plaque area <100 mm2 had the largest differences between the peak and mean density measures. Among persons with CAC 1-99, the use of mean calcium density resulted in a larger improvement in ASCVD mortality net reclassification improvement (NRI) (NRI = 0.49; P < 0.001 vs. NRI = 0.18; P = 0.08) and CHD mortality discrimination (Δ area under the curve (AUC) = +0.169 vs +0.036; P < 0.001) compared with peak calcium density factor. Neither peak nor mean calcium density improved mortality prediction at CAC scores >100. ConclusionMean and peak calcium density may differentially describe plaque composition early in the atherosclerotic process. Mean calcium density performs better than peak calcium density factor when combined with plaque area for ASCVD mortality prediction among persons with Agatston CAC 1-99.

Abstract 10940: Leptin Treatment Protects the Endothelium from Inflammation, Increased Permeability and Endothelial-to-Mesenchymal Transition

Introduction: Patients with lipodystrophy (LD) are characterized by a loss of adipose tissue and are associated with a higher risk for cardiovascular diseases (CVD). As a consequence of adipose tissue reduction in LD patients, the systemic concentration of the adipokine leptin decreases, representing the pathological cause of this disease. Hypothesis: We hypothesized that the reduction of leptin may impair endothelial cells, leading to the development of CVD. Therefore, we analyzed the effects of leptin treatment on vascular inflammation, endothelial-to-mesenchymal transition (EndMT), endothelial permeability and atherosclerotic plaque characteristics. Methods &amp; Results: Treatment of endothelial cells with leptin (200 ng/ml, 6 h) potently reduced IL1β-induced inflammation, as measured by expression of ICAM1 (-25.1%) and E-Selectin (-22.7%), (both p&lt;0.05). Leptin further reduced the induction of EndMT, as determined by expression of calponin (-41.3%) and SM22 (-23.8%), (both p&lt;0.05), as well as the EndMT-induced endothelial permeability (-20.7%, p&lt;0.05). These data were confirmed in a combined lipodystrophic and atherosclerosis prone mouse model (LDLR -/- ;aP2-nSREBP). Treatment with leptin (3.0 mg/kg) for 8 w reduced the number of EndMT-positive endothelial cells (-69%, p&lt;0.05) as well as the total number of mesenchymal cells in the atherosclerotic lesions (-34.8%), (both p&lt;0.05). Further analysis of the atherosclerotic lesions revealed a reduction of atherosclerotic plaque protrusion into the vessel lumen (-31%) and reduced macrophage infiltration (-21.9%) (p&lt;0.05), which is a hallmark of instable atherosclerotic plaques that are prone to rupture, whereas the total plaque area was not affected. The expression of the leptin receptor (LepR) was reduced in endothelial cell inflammation, EndMT (-69%, p&lt;0.05) and in atherosclerotic lesions, suggesting reduced leptin effects under these conditions. Conclusions: Leptin treatment exerts beneficial effects protecting endothelial function and identity in lipodystrophy. Downregulation of the leptin receptor in diseased endothelial cells is likely to reduce the identified positive vascular effects of leptin signaling in lipodystrophy.

Effect of Statin Treatment in Patients With Advanced Carotid Atherosclerosis: An Observational Outcome Study

Background: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular disease. The aim of the study was to investigate whether treatment with statins improved the prognosis. Methods: Sum of all plaque areas (total plaque area (TPA)) and the maximum plaque thickness were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was recorded during follow-up examinations as part of preventive occupational health examinations or by personal communication. Results: In 7,106 subjects aged 35 - 65 years (50 ± 8 years, 43% women), we found 669 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 640 (95.4%) subjects. In these subjects (54 ± 8 years, 20.4% women), 94 (88 men) had cardiovascular events (35 myocardial infarctions, 13 bypass operations, 32 stent implantations, and 14 strokes) with a mean follow-up time of 3.9 (1 - 12) years. Two hundred sixty subjects were treated with a statin, while 339 received no statin. Fourteen cardiovascular events occurred in the treated group (eight stent implantations, two heart attacks, two bypass operations, and two strokes). In the untreated group, 80 cardiovascular events occurred (12 strokes, 11 bypass operations, 33 heart attacks, and 24 stent implantations). The event rate was 5.4% for the subjects treated with a statin and 23.6% for the untreated subjects. Both groups were well matched for the baseline presence of cardiovascular risk factors. Conclusion: Statin treatment in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding on ultrasound) significantly improves the prognosis in a non-randomized observational cohort study. Cardiol Res. 2021;000(000):000-000 doi: https://doi.org/10.14740/cr1318

Effect of Statin Treatment in Patients With Advanced Carotid Atherosclerosis: An Observational Outcome Study.

BackgroundAdvanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular disease. The aim of the study was to investigate whether treatment with statins improved the prognosis.MethodsSum of all plaque areas (total plaque area (TPA)) and the maximum plaque thickness were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was recorded during follow-up examinations as part of preventive occupational health examinations or by personal communication.ResultsIn 7,106 subjects aged 35 - 65 years (50 ± 8 years, 43% women), we found 669 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 640 (95.4%) subjects. In these subjects (54 ± 8 years, 20.4% women), 94 (88 men) had cardiovascular events (35 myocardial infarctions, 13 bypass operations, 32 stent implantations, and 14 strokes) with a mean follow-up time of 3.9 (1 - 12) years. Two hundred sixty subjects were treated with a statin, while 339 received no statin. Fourteen cardiovascular events occurred in the treated group (eight stent implantations, two heart attacks, two bypass operations, and two strokes). In the untreated group, 80 cardiovascular events occurred (12 strokes, 11 bypass operations, 33 heart attacks, and 24 stent implantations). The event rate was 5.4% for the subjects treated with a statin and 23.6% for the untreated subjects. Both groups were well matched for the baseline presence of cardiovascular risk factors.ConclusionStatin treatment in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding on ultrasound) significantly improves the prognosis in a non-randomized observational cohort study.

Reduced progression of carotid intima media thickness by pictorial presentation of subclinical atherosclerosis 3-year follow-up from VIPVIZA a randomized controlled trial

Abstract Background Reduced progression of carotid intima media thickness (cIMT) and atherosclerotic plaque assessed by carotid ultrasound has been reported in pharmacological intervention studies. We have previously provide evidence for improved primary prevention of cardiovascular diseases by pictorial presentation of subclinical atherosclerosis severity based on reduction in traditional risk scores in 1-year follow-up. Purpose We aimed to investigate if pictorial presentation of subclinical atherosclerosis severity affected cIMT and plaque progression over a 3-year follow-up period in comparison with a routine primary prevention program. Methods Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) study is a population-based, randomized controlled trial with blinded evaluators (PROBE design). Participants aged 40, 50 and 60 years were enrolled from a prevention program within the routine primary care. Carotid ultrasound examinations were made at baseline and at 3-year follow-up (n: 3154). The ultrasound examinations included standardized measurements of cIMT in the far wall of common carotid artery at predefined angles due to Meijer's arc. Used angles was 240 degrees for left-mean-cIMT and 120 degrees for right-mean-cIMT. Detection of plaque was based on Mannheim consensus and plaque prevalence was evaluated as absent, unilateral or bilateral plaques. Total plaque area (TPA) was a sum of plaque areas and measured off-line form the longitudinal 2D B-mode images. At baseline, the intervention group (n: 1575) and their primary care physicians received a pictorial presentation describing the severity of subclinical atherosclerosis with graphs and colored figures based on measured cIMT and plaque prevalence (Figure 1). The control group with respective physician (n: 1579) did not receive any information about ultrasound results. The bilateral, left and right mean cIMT, plaque prevalence and TPA at 3-year follow-up were compared between groups. Analysis was performed by analysis of covariance and ordinal proportional odds models. Bonferroni correction was applied to account for multiple comparisons, each individual test was performed using α = 0.01. Results Reduced cIMT progression in the intervention group was found in left-mean-cIMT with an estimated group difference of −0.011 mm (p=0.001). Estimated group difference of right- and bilateral-mean-cIMT were both −0.005 mm (p=0.223 and 0.036, respectively) (Figure 2). No significant difference between groups was found for plaque prevalence or TPA. Conclusion Intervention by pictorial presentation of subclinical atherosclerotic severity reduced the progression of cIMT in comparison with a traditional cardiovascular preventive program only. This was largely driven by changes in the left carotid artery. Long-term follow-up will be required to elucidate if the intervention will have a protective effect on future risk of cardiovascular events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Heart Foundation of Northern Sweden, Västerbotten County Council. Figure 1Figure 2

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype.

Background and PurposeCD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. MethodsSoluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. ResultsBoth plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. ConclusionsHigher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

Household Air Pollution and Blood Pressure, Vascular Damage, and Subclinical Indicators of Cardiovascular Disease in Older Chinese Adults.

BackgroundLimited data suggest that household air pollution from cooking and heating with solid fuel (i.e., coal and biomass) stoves may contribute to the development of hypertension and vascular damage.MethodsUsing mixed-effects regression models, we investigated the associations of household air pollution with blood pressure (BP) and vascular function in 753 adults (ages 40–79 years) from 3 diverse provinces in China. We conducted repeated measures of participants’ household fuel use, personal exposure to fine particulate air pollution (PM2.5), BP, brachial–femoral pulse wave velocity (bfPWV), and augmentation index. Ultrasound images of the carotid arteries were obtained to assess intima–media thickness (CIMT) and plaques. Covariate information on sociodemographics, health behaviors, 24-h urinary sodium, and blood lipids was also obtained.ResultsAverage estimated yearly personal exposure to PM2.5 was 97.5 µg/m3 (SD: 79.2; range: 3.5–1241), and 65% of participants cooked with solid fuel. In multivariable models, current solid fuel use was associated with higher systolic (2.4 mm Hg, 95% CI: −0.4, 4.9) and diastolic BP (1.4 mm Hg, 95% CI: −0.1, 3.0) and greater total area of plaques (1.7 mm2, 95% CI: −6.5, 9.8) compared with exclusive use of electricity or gas stoves. A 1 − ln(µg/m3) increase in PM2.5 exposure was associated with higher systolic (1.5 mm Hg, 95% CI: 0.2, 2.7) and diastolic BP (1.0 mm Hg, 95% CI: 0.4, 1.7) and with greater CIMT (0.02 mm, 95% CI: 0.00, 0.04) and total area of plaques (4.7 mm2, 95% CI: −2.0, 11.5). We did not find associations with arterial stiffness, except for a lower bfPWV (−1.5 m/s, 95% CI: −3.0, −0.0) among users of solid fuel heaters.ConclusionsThese findings add to limited evidence that household air pollution is associated with higher BP and with greater CIMT and total plaque area.

Abstract MP47: Assessment Of Atherosclerosis In A Novel Transgenic Mouse Expressing Pathogenic Levels Of Human Lipoprotein(a)

Studying the role of elevated plasma levels of lipoprotein(a) (Lp(a)) in atherogenesis is challenging given that the LPA gene encoding apo(a) is absent in typical animal models. As such we created a novel transgenic mouse line expressing both human apolipoprotein(a) (apo(a)) and human apoB100 ((Tg(LPA +/0 ;APOB +/0 )) . The LPA transgene, assembled in the pLIV vector, produces a physiologically relevant 12-kringle apo(a) isoform. The APOB transgene contains the entire human APOB gene with a mutation preventing APOB editing. In our atherosclerosis model, male and female mice were injected weekly with an antisense oligonucleotide targeting the mouse LDL receptor (IONIS Pharmaceuticals), and fed a high-fat, high-cholesterol diet for 12 weeks. High plasma Lp(a) levels were observed in both male and female Tg(LPA +/0 ;APOB +/0 ) mice (219.0±11.9 and 133.7±12.1 mg/dL, respectively; n=12/group). Importantly, high levels of Lp(a) in plasma did not result in metabolic alterations, including differences in weight gain, energy expenditure, activity, RER, VO 2 /VCO 2 consumption/output, and glucose tolerance compared to Tg(APOB +/0 ) control mice. Both male and female Tg(LPA +/0 ;APOB +/0 ) and Tg(APOB +/0 ) mice exhibited enhanced proatherogenic lipoprotein profiles with the majority of the cholesterol and TG present in the VLDL and LDL fractions. Complex lesions developed in all transgenic mice, including large, lipid-rich necrotic cores, with overlying fibrous caps and intimal calcium deposition. Immunohistochemistry with a monoclonal apo(a) antibody revealed the presence of Lp(a) in the plaques of Tg(LPA +/0 ;APOB +/0 ) mice. Analysis of aortic sinus lesions revealed a 23% increase in total plaque area in female Tg(LPA +/0 ;APOB +/0 ) mice compared to female Tg(APOB +/0 ) mice (p=0.0836). Moreover, atherosclerotic plaques in female Tg(LPA +/0 ;APOB +/0 ) mice contained significantly more calcium deposition than female Tg( APOB +/0 ) mice (1.79±0.4% vs. 2.96 ±0.3% of total plaque area (p&lt;0.05)). No differences in plaque area or calcium were observed in male mice. In this ongoing study, detailed analyses of atherosclerotic plaque components in Tg(LPA +/0 ;APOB +/0 ) mice will be required to uncover the unique contribution of Lp(a) to atherogenesis.

Femoral plaque burden by ultrasound is a better indicator of significant coronary artery disease over ankle brachial index

The ankle-brachial index is a commonly used tool for identifying peripheral artery disease for cardiovascular risk stratification. An abnormal ankle-brachial index occurs only following extensive peripheral atherosclerosis occlusion, and thus has poor sensitivity for coronary atherosclerosis. There is a critical need for the development of tools that can detect risk prior to advanced stages of atherosclerosis. We sought to determine the sensitivity of femoral ultrasound for coronary artery disease. In this prospective, cross-sectional study, participants (n = 124) underwent ankle-brachial index measurement and femoral ultrasound for assessment of intima-media thickness, maximal plaque height, and total plaque area following coronary angiography. Receiver operating characteristic areas under the curve were plotted for identifying significant coronary artery disease (≥ 50% stenosis). Logistic regression was utilized to evaluate associations. 64% of participants had significant, angiography-confirmed coronary artery disease. Femoral ultrasound plaque area yielded the highest area under the curve for detecting significant coronary disease (area under the curve = 0.731). In contrast, an abnormal ankle-brachial index (≤ 0.90) produced an area under the curve of 0.568. Femoral ultrasound had a higher sensitivity (85%) than the ankle-brachial index (25%) for ruling out significant coronary artery disease. Both ankle-brachial index and femoral ultrasound have similar capacity to detect peripheral artery disease. Femoral ultrasound has a significantly greater discriminatory power than ankle-brachial index to detect clinically significant coronary artery disease. Ultrasound-captured femoral plaque burden directly delineates the extent of peripheral arterial disease and is better at ruling out significant coronary atherosclerosis than the ankle-brachial index.

Carotid total plaque area as a marker of asymptomatic lower extremity arterial disease

Objective: to examine the prognostic value of ultrasound markers of carotid atherosclerosis in relation to the presence of asymptomatic lower extremity peripheral artery disease (PAD). Materials and Methods: the study included 193 patients with carotid atherosclerosis. All patients underwent duplex ultrasound scanning (DUS) of carotid and lower limb arteries. The carotid plaque score (cPS) was determined as the total height of all plaques in the carotid arteries. The carotid total plaque area (cTPA) was estimated in the longitudinal position, the area of plaque was measured in the manual trace mode.Results: asymptomatic lower extremity PAD was diagnosed in 31.6% of patients. The increase in cTPA, in contrast to cPS and the degree of carotid stenosis, was independent predictor of lower extremity PAD and was associated with an increase in the relative risk of its presence by 6.78 times (95% CI 2.48-18.5; p &lt;0.0001). cTPA ≥42.5 mm2 made it possible to diagnose asymptomatic lower extremity PAD with a sensitivity of 70.2% and specificity of 73.0%. Conclusion: In patients with carotid atherosclerosis among carotid atherosclerosis markers only cTPA, in contrast to cPS and the degree of carotid stenosis, had an independent predictive value regarding the presence of asymptomatic lower extremity PAD.

Deep Learning-Based Carotid Plaque Segmentation from B-Mode Ultrasound Images

Carotid ultrasound measurement of total plaque area (TPA) provides a method for quantifying carotid plaque burden and monitoring changes in carotid atherosclerosis in response to medical treatment. Plaque boundary segmentation is required to generate the TPA measurement; however, training of observers and manual delineation are time consuming. Thus, our objective was to develop an automated plaque segmentation method to generate TPA from longitudinal carotid ultrasound images. In this study, a deep learning-based method, modified U-Net, was used to train the segmentation model and generate TPA measurement. A total of 510 plaques from 144 patients were used in our study, where the Monte Carlo cross-validation was used by randomly splitting the data set into 2/3 and 1/3 for training and testing. Two observers were trained to manually delineate the 510 plaques separately, which were used as the ground-truth references. Two U-Net models (M1 and M2) were trained using the two different ground-truth data sets from the two observers to evaluate the accuracy, variability and sensitivity on the ground-truth data sets used for training our method. The results of the algorithm segmentations of the two models yielded strong agreement with the two manual segmentations with the Pearson correlation coefficient r = 0.989 (p < 0.0001) and r = 0.987 (p < 0.0001). Comparison of the U-Net and manual segmentations resulted in mean TPA differences of 0.05 ± 7.13 mm2 (95% confidence interval: 14.02–13.02 mm2) and 0.8 ± 8.7 mm2 (17.85–16.25 mm2) for the two models, which are small compared with the TPA range in our data set from 4.7 to 312.8 mm2. Furthermore, the mean time to segment a plaque was only 8.3 ± 3.1 ms. The presented deep learning-based method described has sufficient accuracy with a short computation time and exhibits high agreement between the algorithm and manual TPA measurements, suggesting that the method could be used to measure TPA and to monitor the progression and regression of carotid atherosclerosis.

Role of artificial intelligence in cardiovascular risk prediction and outcomes: comparison of machine-learning and conventional statistical approaches for the analysis of carotid ultrasound features and intra-plaque neovascularization.

The aim of this study was to compare machine learning (ML) methods with conventional statistical methods to investigate the predictive ability of carotid plaque characteristics for assessing the risk of coronary artery disease (CAD) and cardiovascular (CV) events. Focused carotid B-mode ultrasound, contrast-enhanced ultrasound, and coronary angiography were performed on 459 participants. These participants were followed for 30days. Plaque characteristics such as carotid intima-media thickness (cIMT), maximum plaque height (MPH), total plaque area (TPA), and intraplaque neovascularization (IPN) were measured at baseline. Two ML-based algorithms-random forest (RF) and random survival forest (RSF) were used for CAD and CV event prediction. The performance of these algorithms was compared against (i) univariate and multivariate analysis for CAD prediction using the area-under-the-curve (AUC) and (ii) Cox proportional hazard model for CV event prediction using the concordance index (c-index). There was a significant association between CAD and carotid plaque characteristics [cIMT (odds ratio (OR) = 1.49, p = 0.03), MPH (OR = 2.44, p < 0.0001), TPA (OR = 1.61, p < 0.0001), and IPN (OR = 2.78, p < 0.0001)]. IPN alone reported significant CV event prediction (hazard ratio = 1.24, p < 0.0001). CAD prediction using the RF algorithm reported an improvement in AUC by ~ 3% over the univariate analysis with IPN alone (0.97 vs. 0.94, p < 0.0001). Cardiovascular event prediction using RSF demonstrated an improvement in the c-index by ~ 17.8% over the Cox-based model (0.86 vs. 0.73). Carotid imaging phenotypes and IPN were associated with CAD and CV events. The ML-based system is superior to the conventional statistically-derived approaches for CAD prediction and survival analysis.

Indocyanine Green-Assisted and LED-Light-Activated Antibacterial Photodynamic Therapy Reduces Dental Plaque.

Aim: This study aimed to determine the feasibility and first efficacy of indocyanine green (ICG)-assisted antimicrobial photodynamictherapy (aPDT) as activated using LED light to the dental plaque. Methods: Fifteen healthy adults were assigned to this four-day randomized study. After rinsing with ICG, 100 J/cm2 of 810 nm LED light was applied to the aPDT-treatment area. Plaque area and gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) were measured, and plaque bacteriomes before and after the study were analyzed using 16S rRNA sequencing. Results: aPDT administration was preformed successfully and plaque-specifically with the combination of ICG and the applicator. Total plaque area and endpoint MMP-8 levels were reduced on the aPDT-treatment side. aPDT reduced Streptococcus, Acinetobacteria, Capnocytophaga, and Rothia bacteria species in plaques. Conclusion: ICG-assisted aPDT reduces plaque forming bacteria and exerts anti-inflammatory and anti-proteolytic effects.

Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study

IntroductionPatients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. Material and methodsPart of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. ResultsWe included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. ConclusionsA significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.