Cognitive Decline in Older Patients With Non- ST Elevation Acute Coronary Syndrome.

Background Dementia is a growing health burden of an aging population. This study aims to evaluate the prevalence of cognitive impairment and the predictors of cognitive decline at 1 year in older patients with non-ST-elevation acute coronary syndrome undergoing invasive care. Methods and Results Older patients with non-ST-elevation acute coronary syndrome were recruited into the ICON1 study. Cognition was evaluated using Montreal Cognitive Assessment. The composite major adverse cardiovascular events comprised death, myocardial infarction, unplanned revascularization, stroke, and significant bleeding at 1 year. Of 298 patients, 271 had cognitive assessment at baseline, and 211 (78%) had follow-up Montreal Cognitive Assessment at 1 year. Mean age was 80.5±4.8 years. There was a high prevalence (n=130, 48.0%) of undiagnosed cognitive impairment (Montreal Cognitive Assessment score <26) at baseline. Cognitive impairment patients were more likely to reach major adverse cardiovascular events by Kaplan-Meier analysis ( P=0.047). Seventy-four patients (35.1%) experienced cognitive decline (Montreal Cognitive Assessment score drop by ≥2 points) at 1 year. Recurrent myocardial infarction was independently associated with cognitive decline at 1 year (odds ratio 3.19, 95% confidence interval 1.18-8.63, P=0.02) after adjustment for age and sex. Conclusions In older patients undergoing invasive management of non-ST-elevation acute coronary syndrome, there is a high prevalence of undiagnosed cognitive impairment at baseline. Recurrent myocardial infarction is independently associated with cognitive decline at 1 year. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01933581

Heterogeneous plaque-lumen geometry is associated with major adverse cardiovascular events.

AIMS Prospective studies show that only a minority of plaques with higher risk features develop future major adverse cardiovascular events (MACE), indicating the need for more predictive markers. Biomechanical estimates such as plaque structural stress (PSS) improve risk prediction but require expert analysis. In contrast, complex and asymmetric coronary geometry is associated with both unstable presentation and high PSS, and can be estimated quickly from imaging. We examined whether plaque-lumen geometric heterogeneity evaluated from intravascular ultrasound affects MACE and incorporating geometric parameters enhances plaque risk stratification. METHODS AND RESULTS We examined plaque-lumen curvature, irregularity, lumen aspect ratio (LAR), roughness, PSS, and their heterogeneity indices (HIs) in 44 non-culprit lesions (NCLs) associated with MACE and 84 propensity-matched no-MACE-NCLs from the PROSPECT study. Plaque geometry HI were increased in MACE-NCLs vs. no-MACE-NCLs across whole plaque and peri-minimal luminal area (MLA) segments (HI curvature: adjusted P = 0.024; HI irregularity: adjusted P = 0.002; HI LAR: adjusted P = 0.002; HI roughness: adjusted P = 0.004). Peri-MLA HI roughness was an independent predictor of MACE (hazard ratio: 3.21, P < 0.001). Inclusion of HI roughness significantly improved the identification of MACE-NCLs in thin-cap fibroatheromas (TCFA, P < 0.001), or with MLA ≤ 4 mm2 (P < 0.001), or plaque burden (PB) ≥ 70% (P < 0.001), and further improved the ability of PSS to identify MACE-NCLs in TCFA (P = 0.008), or with MLA ≤ 4 mm2 (P = 0.047), and PB ≥ 70% (P = 0.003) lesions. CONCLUSION Plaque-lumen geometric heterogeneity is increased in MACE vs. no-MACE-NCLs, and inclusion of geometric heterogeneity improves the ability of imaging to predict MACE. Assessment of geometric parameters may provide a simple method of plaque risk stratification

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Determination of quantum numbers for several excited charmed mesons observed in B- -> D*(+)pi(-) pi(-) decays

A four-body amplitude analysis of the B − → D * + π − π − decay is performed, where fractions and relative phases of the various resonances contributing to the decay are measured. Several quasi-model-independent analyses are performed aimed at searching for the presence of new states and establishing the quantum numbers of previously observed charmed meson resonances. In particular the resonance parameters and quantum numbers are determined for the D 1 ( 2420 ) , D 1 ( 2430 ) , D 0 ( 2550 ) , D ∗ 1 ( 2600 ) , D 2 ( 2740 ) and D ∗ 3 ( 2750 ) states. The mixing between the D 1 ( 2420 ) and D 1 ( 2430 ) resonances is studied and the mixing parameters are measured. The dataset corresponds to an integrated luminosity of 4.7     fb − 1 , collected in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV with the LHCb detector

Updated measurement of decay-time-dependent CP asymmetries in D-0 -> K+ K- and D-0 -> pi(+)pi(-) decays

A search for decay-time-dependent charge-parity (CP) asymmetry in D0 \u2192 K+ K 12 and D0 \u2192 \u3c0+ \u3c0 12 decays is performed at the LHCb experiment using proton-proton collision data recorded at a center-of-mass energy of 13 TeV, and corresponding to an integrated luminosity of 5.4 fb^ 121. The D0 mesons are required to originate from semileptonic decays of b hadrons, such that the charge of the muon identifies the flavor of the neutral D meson at production. The asymmetries in the effective decay widths of D0 and anti-D0 mesons are determined to be A_\u393(K+ K 12) = ( 124.3 \ub1 3.6 \ub1 0.5) 7 10^ 124 and A_\u393(\u3c0+ \u3c0 12) = (2.2 \ub1 7.0 \ub1 0.8) 7 10^ 124 , where the uncertainties are statistical and systematic, respectively. The results are consistent with CP symmetry and, when combined with previous LHCb results, yield A_\u393(K+ K 12) = ( 124.4 \ub1 2.3 \ub1 0.6) 7 10^ 124 and A_\u393(\u3c0+ \u3c0 12) = (2.5 \ub1 4.3 \ub1 0.7) 7 10^ 124

Updated measurement of decay-time-dependent CP asymmetries in D-0 -> K+ K- and D-0 -> pi(+)pi(-) decays

A search for decay-time-dependent charge-parity (CP) asymmetry in D-0 -> K+ K- and D-0 -> pi(+)pi(-) eff decays is performed at the LHCb experiment using proton-proton collision data recorded at a center-of-mass energy of 13 TeV, and corresponding to an integrated luminosity of 5.4 fb(-1). The D-0 mesons are required to originate from semileptonic decays of b hadrons, such that the charge of the muon identifies the flavor of the neutral D meson at production. The asymmetries in the effective decay widths of D-0 and (D) over bar (0) mesons are determined to be A(Gamma)(K+ K-) = (-4.3 +/- 3.6 +/- 0.5) x 10(-4) and A(Gamma) (K+ K- ) = (2.2 +/- 7.0 +/- 0.8) x 10(-4), where the uncertainties are statistical and systematic, respectively. The results are consistent with CP symmetry and, when combined with previous LHCb results, yield A(Gamma) (K+ K-) = (-4.4 +/- 2.3 +/- 0.6) x 10(-4) and A(Gamma) (pi(+)pi(-))= (2.5 +/- 4.3 +/- 0.7) x 10(-4)

Search for the doubly charmed baryon Ω cc +

Abstract: A search for the doubly charmed baryon Ωcc+ with the decay mode Ωcc+ → Ξc+K−π+ is performed using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment from 2016 to 2018, corresponding to an integrated luminosity of 5.4 fb−1. No significant signal is observed within the invariant mass range of 3.6 to 4.0GeV/c2. Upper limits are set on the ratio R of the production cross-section times the total branching fraction of the Ωcc+ → Ξc+K−π+ decay with respect to the Ξcc++→Λc+K−π+π+ decay. Upper limits at 95% credibility level for R in the range 0.005 to 0.11 are obtained for different hypotheses on the Ωcc+ mass and lifetime in the rapidity range from 2.0 to 4.5 and transverse momentum range from 4 to 15 GeV/c

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Plaque Structural Stress: Detection, Determinants and Role in Atherosclerotic Plaque Rupture and Progression.

Atherosclerosis remains a major cause of death worldwide, with most myocardial infarctions being due to rupture or erosion of coronary plaques. Although several imaging modalities can identify features that confer risk, major adverse cardiovascular event (MACE) rates attributable to each plaque are low, such that additional biomarkers are required to improve risk stratification at plaque and patient level. Coronary arteries are exposed to continual mechanical forces, and plaque rupture occurs when plaque structural stress (PSS) exceeds its mechanical strength. Prospective studies have shown that peak PSS is correlated with acute coronary syndrome (ACS) presentation, plaque rupture, and MACE, and provides additional prognostic information to imaging. In addition, PSS incorporates multiple variables, including plaque architecture, plaque material properties, and haemodynamic data into a defined solution, providing a more detailed overview of higher-risk lesions. We review the methods for calculation and determinants of PSS, imaging modalities used for modeling PSS, and idealized models that explore structural and geometric components that affect PSS. We also discuss current experimental and clinical data linking PSS to the natural history of coronary artery disease, and explore potential for refining treatment options and predicting future events

Intravascular imaging assessment of pharmacotherapies targeting atherosclerosis: advantages and limitations in predicting their prognostic implications

Intravascular imaging has been often used over the recent years to examine the efficacy of emerging therapies targeting plaque evolution. Serial intravascular ultrasound, optical coherence tomography, or near infrared spectroscopy-intravascular ultrasound studies have allowed us to evaluate the effects of different therapies on plaque burden and morphology, providing unique mechanistic insights about the mode of action of these treatments. Plaque burden reduction, a decrease in necrotic core component or macrophages accumulation - that have been associated with inflammation - and an increase in fibrous cap thickness over fibroatheromas have been used as surrogate endpoints to assess the value of several drugs in inhibiting plaque evolution and improving clinical outcomes. However, some reports have demonstrated weak associations between the effects of novel treatments on coronary atheroma and composition and their prognostic implications. This review examines the value of invasive imaging in assessing pharmacotherapies targeting atherosclerosis. It summarizes the findings of serial intravascular imaging studies assessing the effects of different drugs on atheroma burden and morphology and compares them with the results of large-scale trials evaluating their impact on clinical outcome. Furthermore, it highlights the limited efficacy of established intravascular imaging surrogate endpoints in predicting the prognostic value of these pharmacotherapies and introduces alternative imaging endpoints based on multimodality/hybrid intravascular imaging that may enable more accurate assessment of the athero-protective and prognostic effects of emerging therapies