Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study

BACKGROUND: Detection of subclinical atherosclerosis improves risk prediction beyond cardiovascular risk factors (CVRFs) and risk scores, but quantification of plaque burden may improve it further. Novel 3-dimensional vascular ultrasound (3DVUS) provides accurate volumetric quantification of plaque burden. OBJECTIVES: The authors evaluated associations between 3DVUS-based plaque burden and CVRFs and explored potential added value over simple plaque detection. METHODS: The authors included 3,860 (92.2%) PESA (Progression of Early Subclinical Atherosclerosis) study participants (age 45.8 ± 4.3 years; 63% men). Bilateral carotid and femoral territories were explored by 3DVUS to determine the number of plaques and territories affected, and to quantify global plaque burden defined as the sum of all plaque volumes. Linear regression and proportional odds models were used to evaluate associations of plaque burden with CVRFs and estimated 10-year cardiovascular risk. RESULTS: Plaque burden was higher in men (63.4 mm3 [interquartile range (IQR): 23.8 to 144.8 mm3] vs. 25.7 mm3 [IQR: 11.5 to 61.6 mm3] in women; p < 0.001), in the femoral territory (64 mm3 [IQR: 27.6 to 140.5 mm3] vs. 23.1 mm3 [IQR: 9.9 to 48.7 mm3] in the carotid territory; p < 0.001), and with increasing age (p < 0.001). Age, sex, smoking, and dyslipidemia were more strongly associated with femoral than with carotid disease burden, whereas hypertension and diabetes showed no territorial differences. Plaque burden was directly associated with estimated cardiovascular risk independently of the number of plaques or territories affected (p < 0.01). CONCLUSIONS: 3DVUS quantifies higher plaque burden in men, in the femoral territory, and with increasing age during midlife. Plaque burden correlates strongly with CVRFs, especially at the femoral level, and reflects estimated cardiovascular risk more closely than plaque detection alone. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).The PESA study is cofunded equally by the Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain, and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund (ERDF). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Sanchez-Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Stephen J. Nicholls, MD, served as Guest Editor for this paperS

Accurate quantification of atherosclerotic plaque volume by 3D vascular ultrasound using the volumetric linear array method.

Direct quantification of atherosclerotic plaque volume by three-dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based three-dimensional (2D/3D) techniques that generate pseudo-3D volumes from summed 2D plaque areas; however, its accuracy has not been reported. We aimed to determine 3DVUS accuracy for plaque volume measurement with special emphasis on small plaques (a hallmark of early atherosclerosis). The in vitro study consisted of nine phantoms of different volumes (small and medium-large) embedded at variable distances from the surface (superficial vs. >5 cm-depth) and comparison of 3DVUS data generated using a novel volumetric-linear array method with the real phantom volumes. The in vivo study was undertaken in a rabbit model of atherosclerosis in which 3DVUS and 2D/3D volume measurements were correlated against gold-standard histological measurements. In the in vitro setting, there was a strong correlation between 3DVUS measures and real phantom volume both for small (3.0-64.5 mm(3) size) and medium-large (91.1-965.5 mm(3) size) phantoms embedded superficially, with intraclass correlation coefficients (ICC) of 0.99 and 0.98, respectively; conversely, when phantoms were placed at >5 cm, the correlation was only moderate (ICC = 0.67). In the in vivo setting there was strong correlation between 3DVUS-measured plaque volumes and the histological gold-standard (ICC = 0.99 [4.02-92.5 mm(3) size]). Conversely, the correlation between 2D/3D values and the histological gold standard (sum of plaque areas) was weaker (ICC = 0.87 [49-520 mm(2) size]), with large dispersion of the differences between measurements in Bland-Altman plots (mean error, 79.2 mm(2)). 3DVUS using the volumetric-linear array method accurately measures plaque volumes, including those of small plaques. Measurements are more accurate for superficial arterial territories than for deep territories.S

Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis

BACKGROUND The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. OBJECTIVES This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. METHODS The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63\% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style-related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. RESULTS Most PESA participants follow a Mediterranean (40\% of participants) or a Western (41\%) dietary pattern. A new pattern, identified among 19\% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95\% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. CONCLUSIONS A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318) (C) 2016 by the American College of Cardiology Foundation.This study was supported by a noncompetitive unrestricted grant shared between the National Center for Cardiovascular Research Carlos III (CNIC) and the Bank of Santander. The PESA study is a noncommercial study independent of the health care and pharmaceutical industry. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Vedanthan is supported by the Fogarty International Center of the National Institutes of Health under award K01 TW 009218-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Bueno has received advisory/speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and Servier; has received a research grant from AstraZeneca; has received advisory fees from Abbott; and has received speaking fees from Ferrer. Frank B. Hu, MD, served as Guest Editor for this paper

Mechanism of Decrease in Mitral Regurgitation After Cardiac Resynchronization Therapy: Optimization of the Force-Balance Relationship

Background: Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force–balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force–balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function. Methods and Results: We examined the effect of CRT on 34 patients with functional MR before and after CRT (209±81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocity×mitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253±111 versus 221±110 mL, P<0.001) and end-systolic volume (206±97 versus 167±91 mL, P<0.001) decreased and ejection fraction (19±6 versus 27±9%, P<0.001) increased. MR regurgitant volume decreased from 35±17 to 23±14 mL (P<0.001), MAA from 11.6±3.5 to 10.5±3.1 cm2 (P<0.001), leaflet closing area from 15.4±5 to 13.7±3.8 cm2 (P<0.001), and tenting volume from 5.7±2.6 to 4.6±2.2 mL (P<0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77±0.1 versus 0.84±0.1 before CRT versus after CRT, P=0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction. Conclusions: Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures