Carotid Plaque Characteristics Predict Recurrent Ischemic Stroke and TIA: The PARISK (Plaque At RISK) Study

BackgroundPatients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making.ObjectivesThe PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging.MethodsThe authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score.ResultsDuring 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78).ConclusionsIPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025)     

Subclinical Atherosclerosis and Brain Metabolism in Middle-Aged Individuals: The PESA Study

BackgroundAtherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.ObjectivesThis study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals.MethodsThis study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography. Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3-dimensional vascular ultrasound.ResultsGlobal FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS) (β = ?0.15, p < 0.001). This association was mainly driven by the presence of hypertension (d = 0.36, p < 0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β = ?0.16, p < 0.001), even after adjusting for 30-year FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus.ConclusionsIn asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain’s midlife vulnerability to future cognitive dysfunction.     

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women

Background and aimsMany dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women.Methods and resultsDairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers’ Cohort (MTC) study who were free of CVD or cancer. We categorized participants according to total dairy intake and consumption of four mutually exclusive dairy groups: high-fat, low-fat, yogurt, and dairy with added sugars. IMT and atherosclerotic plaque were measured by B-mode ultrasonography. Subclinical atherosclerosis was defined as an IMT ≥0.8 mm and/or the presence of plaque. Multivariable linear regression and logistic regression models were used to respectively assess the mean percentage difference of mean IMT and odds ratios (OR) for subclinical atherosclerosis across quantiles of dairy consumption. Mean (±SD) age was 45.4 ± 5.0 years and the median (interquartile range: IQR) total dairy consumption was 11.0 (6.6, 17.1) servings/week. After adjusting for lifestyle, clinical, and dietary factors, comparing the highest category of consumption, to the lowest, total dairy was associated with increased IMT (2.6%, 95% confidence interval (CI): 0.6, 4.3; p-trend<0.01). Moreover, yogurt consumption was associated with lower odds of subclinical atherosclerosis (OR = 0.65, 95% CI: 0.47, 0.91; p-trend = 0.01).ConclusionsWhile total dairy consumption was associated with carotid wall thickening, yogurt consumption was related to lower subclinical atherosclerosis.     

Complement C5 Protein as a Marker of Subclinical Atherosclerosis

BackgroundThe mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking.ObjectivesThe purpose of this study was to analyze the temporal and topologically resolved protein changes taking place in human aortas with early atherosclerosis to find new potential diagnostic and/or therapeutic targets.MethodsThe protein composition of healthy aortas (media layer) or with early atheroma (fatty streak and fibrolipidic, media and intima layers) was analyzed by deep quantitative multiplexed proteomics. Further analysis was performed by Western blot, immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Plasma levels of complement C5 were analyzed in relation to the presence of generalized (>2 plaques) or incipient (0 to 2 plaques) subclinical atherosclerosis in 2 independent clinical cohorts (PESA [Progression of Early Subclinical Atherosclerosis] [n = 360] and NEFRONA [National Observatory of Atherosclerosis in Nephrology] [n = 394]).ResultsProteins involved in lipid transport, complement system, immunoglobulin superfamily, and hemostasis are increased in early plaques. Components from the complement activation pathway were predominantly increased in the intima of fibrolipidic plaques. Among them, increased C5 protein levels were further confirmed by Western blot, enzyme-linked immunosorbent assay and immunohistochemistry, and associated with in situ complement activation. Plasma C5 was significantly increased in individuals with generalized subclinical atherosclerosis in both PESA and NEFRONA cohorts, independently of risk factors. Moreover, in the PESA study, C5 plasma levels positively correlated with global plaque volume and coronary calcification.ConclusionsActivation of the complement system is a major alteration in early atherosclerotic plaques and is reflected by increased C5 plasma levels, which have promising value as a novel circulating biomarker of subclinical atherosclerosis.     

Evolving Role of Calcium Density in Coronary Artery Calcium Scoring and Atherosclerotic Cardiovascular Disease Risk

Coronary artery calcium (CAC) is a specific marker of coronary atherosclerosis that can be used to measure calcified subclinical atherosclerotic burden. The Agatston method is the most widely used scoring algorithm for quantifying CAC and is expressed as the product of total calcium area and a quantized peak calcium density weighting factor defined by the calcification attenuation in HU on noncontrast computed tomography. Calcium density has emerged as an important area of inquiry because the Agatston score is upweighted based on the assumption that peak calcium density and atherosclerotic cardiovascular disease (ASCVD) risk are positively correlated. However, recent evidence demonstrates that calcium density is inversely associated with lesion vulnerability and ASCVD risk in population-based cohorts when accounting for age and plaque area. Here, we review calcium density by focusing on 3 main areas: 1) CAC scan acquisition parameters; 2) pathophysiology of calcified plaques; and 3) epidemiologic evidence relating calcium density to ASCVD outcomes. Through this process, we hope to provide further insight into the evolution of CAC scoring on noncontrast computed tomography.     

New 3-Dimensional Volumetric Ultrasound Method for Accurate Quantification of Atherosclerotic Plaque Volume

BackgroundCarotid and femoral plaque burden is a recognized biomarker of cardiovascular disease risk. A new electronic-sweep 3-dimensional (3D)–matrix transducer method can improve the functionality and image quality of vascular ultrasound atherosclerosis imaging.ObjectivesThis study aimed to validate this method for plaque volume measurement in early and intermediate–advanced plaques in the carotid and femoral territories.MethodsPlaque volumes were measured ex vivo in pig carotid and femoral artery specimens by 3-dimensional vascular ultrasound (3DVUS) using a 3D-matrix (electronic-sweep) transducer and its associated 3D plaque quantification software, and were compared with gold-standard histology. To test the clinical feasibility and accuracy of the 3D-matrix transducer, an experiment was conducted in intermediate–high risk individuals with carotid and femoral atherosclerosis. The results were compared with those obtained using the previously validated mechanical-sweep 3D transducer and established 2-dimensional (2D)–based plaque quantification software.ResultsIn the ex vivo study, the authors assessed 19 atherosclerotic plaques (plaque volume, 0.76 µL-56.30 μL), finding strong agreement between measurements with the 3D-matrix transducer and the histological gold-standard (intraclass correlation coefficient [ICC]: 0.992; [95% CI: 0.978-0.997]). In the clinical analysis of 20 patients (mean age 74.6 ± 4.45 years; 40% men), the authors found 64 (36 carotid and 28 femoral) of 80 scanned territories with atherosclerosis (measured atherosclerotic volume, 10 μL-859 μL). There was strong agreement between measurements made from electronic-sweep and mechanical-sweep 3DVUS transducers (ICC: 0.997 [95% CI: 0.995-0.998]). Agreement was also high between plaque volumes estimated by the 2D and 3D plaque quantification software applications (ICC: 0.999 [95% CI: 0.998-0.999]). Analysis time was significantly shorter with the 3D plaque quantification software than with the 2D multislice approach with a mean time reduction of 46%.Conclusions3DVUS using new matrix transducer technology, together with improved 3D plaque quantification software, simplifies the accurate volume measurement of early (small) and intermediate–advanced plaques located in carotid and femoral arteries.     

Short-Term Progression of Multiterritorial Subclinical Atherosclerosis

BackgroundAtherosclerosis progression predicts cardiovascular events; however, progression of multiterritorial subclinical atherosclerosis is incompletely understood.ObjectivesThis study sought to study short-term progression of atherosclerosis using different noninvasive imaging techniques and their relationship with cardiovascular risk.MethodsThe study included 3,514 PESA (Progression of Early Subclinical Atherosclerosis) study participants (45.7 ± 4.2 years of age; 63% men). Participants underwent 2-dimensional vascular ultrasound (2DVUS) of abdominal aorta, carotid, iliac, and femoral territories to determine a plaque number score; 3DVUS to quantify carotid and femoral plaque volume; and coronary artery calcium score (CACS) at baseline and 2.8 years later. The authors calculated the rate of new disease incidence and changes in disease extent. Logistic regression models were used to evaluate associations of progression rates with baseline cardiovascular risk factors and estimated 10-year risk.ResultsImaging detected short-term (3-year) atherosclerosis progression in 41.5% of participants (26.4% by 2DVUS, 21.3% by 3DVUS, and 11.5% by CACS), particularly in peripheral territories examined by vascular ultrasound. New atherosclerosis onset accounted for approximately one-third of total progression, also more frequently by 2DVUS and 3DVUS (29.1% and 16.6%, respectively), than by CACS (2.9%). Participants with baseline disease by all 3 modalities (n = 432) also showed significant atherosclerosis progression (median: 1 plaque [interquartile range (IQR): −1 to 3 plaques] by 2DVUS; 7.6 mm³ [IQR: −32.2 to 57.6 mm³] by 3DVUS; and 21.6 Agatston units [IQR: 4.8 to 62.6 Agatston units] by CACS). Age, sex, dyslipidemia, hypertension, smoking, and family history of premature cardiovascular disease contributed to progression, with dyslipidemia the strongest modifiable risk factor. Although disease progression correlated with cardiovascular risk, progression was detected in 36.5% of participants categorized as low risk.ConclusionsWith this multimodal and multiterritorial approach, the authors detected short-term progression of early subclinical atherosclerosis in a substantial proportion (41.5%) of apparently healthy middle-aged men and women, more frequently by peripheral 2D/3DVUS than by CACS. Disease progression, as defined in this study, correlated with almost all cardiovascular risk factors and estimated risk. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Triglycerides and Residual Atherosclerotic Risk

BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Neck circumference predicts development of carotid intima-media thickness and carotid plaque: A community-based longitudinal study

Background and aimsCarotid intima-media thickness (C-IMT) is an important index for evaluating subclinical atherosclerosis. Neck circumference (NC), a new anthropometric index of the upper body fat, is closely related to cardiovascular disease (CVD) and CVD risk factors. This study investigated the relationship between NC, C-IMT, and carotid plaque in a community-based cohort.Methods and resultsParticipants recruited from Shanghai communities were followed up for 1.1–2.9 years. All participants underwent anthropometric and biochemical measurements. Elevated NC was defined as NC ≥ 38.5 cm and NC ≥ 34.5 cm in men and women, respectively. Elevated C-IMT, determined by ultrasound, was defined as a level higher than the 75th percentile in the study population (>0.75 mm). In total, 1189 participants without carotid plaque at baseline were included, with an average age of 59.6 ± 7.3 years. After a mean follow-up of 2.1 ± 0.2 years, 203 participants developed carotid plaques. After adjusting for various atherosclerosis risk factors, the logistic regression showed that the higher NC group had a significantly greater risk of developing carotid plaque than the lower NC group (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.12–2.14; P = 0.008). Of those without carotid plaque at follow-up, 495 participants developed elevated C-IMT. Compared to the lower NC group, the higher NC group had a significantly increased risk of elevated C-IMT (OR, 1.49; 95% CI, 1.14–1.95; P = 0.003).ConclusionHigher NC was significantly positively correlated with the risk of carotid plaque and elevated C-IMT.     

Predicting Long-Term Absence of Coronary Artery Calcium in Metabolic Syndrome and Diabetes: The MESA Study

ObjectivesThe purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies.BackgroundIndividuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk.MethodsWe included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging.ResultsThe mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76).ConclusionSMore than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.     

Sugar- and artificially-sweetened soda consumption and subclinical atherosclerosis among Mexican women

Background and aimsSugar-sweetened soda consumption is associated with most cardiometabolic risk factors. The role of artificially-sweetened beverages in cardiovascular disease (CVD) is inconclusive, but their consumption correlates with health impairment. Little is known about the contribution of soda consumption in subclinical stages of atherosclerosis. Therefore, we evaluated the relation between sugar- and artificially-sweetened soda consumption and carotid intima-media thickness (IMT) among Mexican women.Methods and resultsWe cross-sectionally evaluated 1093 women enrolled in the Mexican Teachers’ Cohort who were free of CVD, diabetes or cancer. Sugar- and artificially-sweetened soda consumption was estimated from a validated 140-item food frequency questionnaire in 2008 and all women underwent a carotid ultrasound assessment three years later. Participants were categorized into tertiles of soda consumption in servings/week. Subclinical atherosclerosis was defined as a mean left and/or right IMT ≥0.8 mm or the presence of plaque on either common carotid artery. In multivariable regression models, women in the highest tertile of sugar-sweetened soda consumption had 2.6% (95%CI: 0.8, 4.5) mean increased IMT, and had 2-fold the risk of carotid atherosclerosis (PR: 2.0, 95%CI: 1.3, 3.2) compared to those in the lowest tertile. In stratified analyses, older and postmenopausal women who consumed sugar-sweetened soda had an increased IMT and atherosclerosis risk. Artificially-sweetened soda consumption was not associated with IMT or carotid atherosclerosis.ConclusionsSugar-sweetened soda consumption was associated with subclinical atherosclerosis among disease-free Mexican women. Public health strategies to decrease CVD should consider the impact of sugar-sweetened soda consumption, particularly in older women.     

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.     

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease

ObjectivesThe aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.BackgroundCoronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.MethodsThis analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).ResultsCPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = –0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = –0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.ConclusionsCalcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)     

Elevated serum uric acid was associated with pre-inflammatory state and impacted the role of HDL-C on carotid atherosclerosis

Background and aimsUric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with atherosclerosis, respectively. UA and HDL-C are involved in the balance of proinflammatory and anti-inflammatory processes in atherosclerosis. However, it is still unclear whether UA affects the effect of HDL-C on atherosclerosis.Methods and resultsIn this retrospective study, we enrolled 1437 patients with multiple risk factors for atherosclerosis. Patients were categorized into two groups according to their baseline UA level. Multivariate logistic regression analysis and restricted cubic spline curves were used to assess the relationship between HDL-C and carotid atherosclerosis (abnormal carotid intima–media thickness [cIMT] and carotid artery plaque) at different UA levels. Compared to patients with normouricemia, patients with hyperuricemia were older and had a more extensive history of disease and unhealthy behavior. In the normouricemia group, multivariate-adjusted odds ratios (95% CIs) for HDL-C were 0.55 (0.33–0.92) for abnormal mean cIMT, 0.59 (0.35–1.00) for abnormal maximum cIMT, and 0.53 (0.29–0.94) for the occurrence of carotid artery plaque, while the correlation between each of these three indicators with HDL-C were not significant in those with hyperuricemia. Spline regression models yielded similar results. The effect of UA on the association between HDL-C and carotid atherosclerosis remained in the subset of patients with optimal low-density lipoprotein cholesterol.ConclusionElevated UA marks a pre-inflammatory state and impacts the role of HDL-C on carotid atherosclerosis.     

Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events

ObjectivesThis study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD)BackgroundCoronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis.MethodsThe multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization.ResultsAmong the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events.ConclusionsThe CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662)     

Triglyceride glucose index and carotid atherosclerosis incidence in the Chinese population: A prospective cohort study

Background and aimsThe association of the triglyceride glucose (TyG) index with carotid atherosclerosis has not been reported in longitudinal studies. The present study aimed to investigate whether the TyG index increases the risk of carotid atherosclerosis incidence.Methods and resultsThis study included data from the Beijing Health Management Cohort (BHMC; n = 6955) and the Beijing Physical Examination Cohort (BPEC; n = 8473). Participants without a history of carotid atherosclerosis who underwent health examination in 2011 or 2012 were annually followed until 2019. The TyG index was denoted as ln [triglycerides (mmol/L)1fasting glucose (mmol/L)/2]. During a median follow-up of 5.02 years and 5.36 years, 1441 individuals in the BHMC group and 2181 individuals in the BPEC group developed carotid plaque, respectively. The adjusted hazard ratios (HRs) of the continuous TyG index were 1.253 (95% CI, 1.044 to 1.505) and 1.252 (95% CI, 1.091 to 1.437) for the BHMC and BPEC groups, respectively. Individuals in the highest quartile of the TyG index were associated with an increased risk of carotid plaque compared with those in the lowest quartile (BHMC: HR, 1.366; 95% CI, 1.101 to 1.695, P for trend = 0.010; BPEC: HR, 1.379; 95% CI, 1.196 to 1.591, P for trend = 0.013).ConclusionThese findings suggested that a higher TyG index increases the risk of carotid atherosclerosis incidence in the general population.     

Cognitive Decline Before and After Incident Coronary Events

BackgroundPrevious studies have suggested that coronary heart disease (CHD) may be associated with accelerated cognitive decline. However, the temporal pattern of cognitive decline before and after incident CHD remains largely unknown.ObjectivesThe purpose of this study was to determine the cognitive trajectory before and after incident CHD diagnosis in a national representative cohort age ≥50 years.MethodsThis study included 7,888 participants (mean age 62.1 ± 10.2 years) with no history of stroke or incident stroke during follow-up from the English Longitudinal Study of Ageing. Participants underwent a cognitive assessment at baseline (wave 1, 2002 to 2003), and at least 1 other time point (from wave 2 [2004 to 2005] to wave 8 [2016 to 2017]). Incident CHD was identified as a diagnosis of myocardial infarction and/or angina during follow-up.ResultsIncident CHD was associated with accelerated cognitive decline during a median follow-up of 12 years. The annual rate of cognitive decline before CHD diagnosis among individuals who experienced incident CHD was similar to that of participants who remained CHD-free throughout follow-up. No short-term cognitive decline was observed in participants with CHD diagnosis after the event. In the years following CHD diagnosis, global cognition, verbal memory, and temporal orientation scores declined significantly faster than they did before the event, after multivariable adjustment. Sensitivity analyses yielded similar results.ConclusionsIncident CHD is associated with accelerated cognitive decline after, but not before, the event. Attention should be drawn to the long-term cognitive deterioration related to CHD. Careful monitoring of cognitive function is warranted in CHD patients in the years following the event.     

Machine Learning Adds to Clinical and CAC Assessments in Predicting 10-Year CHD and CVD Deaths

ObjectivesThe aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.BackgroundThe CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.MethodsThe study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).ResultsThe AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001).ConclusionsThe comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.     

Coronary Artery Calcium for Risk Stratification of Sudden Cardiac Death: The Coronary Artery Calcium Consortium

BackgroundCoronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.ObjectivesSCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.MethodsThe authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors.ResultsThe mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC >0. Compared with CAC = 0, there was a stepwise higher risk (P trend < 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC >1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk <7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk >20% (ΔC-statistic = +0.01; P = 0.54).ConclusionsHigher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.