Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale & Objective: Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD. Study Design: Observational cohort study. Setting & Participants: We included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and 2008. Exposure: Baseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay. Outcomes: Recurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through 2019. Analytical Approach: We used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs. Results: Among participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs = 0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death. Limitations: Lipoprotein(a) was not available in molar concentration. Conclusions: Lipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure

The Contribution of Amyloid Deposition in the Aortic Valve to Calcification and Aortic Stenosis

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD

Identification and Management of Statin-Associated Symptoms in Clinical Practice : Extension of a Clinician Survey to 12 Further Countries

Statins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible

Measurement of Dijet Angular Distributions at CDF

We have used 106 pb^-1 of data collected in proton-antiproton collisions at sqrt(s)=1.8 TeV by the Collider Detector at Fermilab to measure jet angular distributions in events with two jets in the final state. The angular distributions agree with next to leading order (NLO) predictions of Quantum Chromodynamics (QCD) in all dijet invariant mass regions. The data exclude at 95% confidence level (CL) a model of quark substructure in which only up and down quarks are composite and the contact interaction scale is Lambda_ud(+) < 1.6 TeV or Lambda_ud(-) < 1.4 TeV. For a model in which all quarks are composite the excluded regions are Lambda(+) < 1.8 TeV and Lambda(-) < 1. 6 TeV.Comment: 16 pages, 2 figures, 2 tables, LaTex, using epsf.sty. Submitted to Physical Review Letters on September 17, 1996. Postscript file of full paper available at http://www-cdf.fnal.gov/physics/pub96/cdf3773_dijet_angle_prl.p

Search for charged Higgs decays of the top quark using hadronic tau decays

We present the result of a search for charged Higgs decays of the top quark, produced in $p\bar{p}$ collisions at $\surd s =$ 1.8 TeV. When the charged Higgs is heavy and decays to a tau lepton, which subsequently decays hadronically, the resulting events have a unique signature: large missing transverse energy and the low-charged-multiplicity tau. Data collected in the period 1992-1993 at the Collider Detector at Fermilab, corresponding to 18.7$\pm$0.7~pb$^{-1}$, exclude new regions of combined top quark and charged Higgs mass, in extensions to the standard model with two Higgs doublets.Comment: uuencoded, gzipped tar file of LaTeX and 6 Postscript figures; 11 pp; submitted to Phys. Rev.

Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider

We have searched in $p \bar{p}$ collisions at $\sqrt{s}$ = 1.8 TeV for events with three charged leptons and missing transverse energy. In the Minimal Supersymmetric Standard Model, we expect trilepton events from chargino-neutralino (\chione \chitwo) pair production, with subsequent decay into leptons. We observe no candidate $e^+e^-e^\pm$, $e^+e^-\mu^\pm$, $e^\pm\mu^+\mu^-$ or $\mu^+\mu^-\mu^\pm$ events in 106 pb$^{-1}$ integrated luminosity. We present limits on the sum of the branching ratios times cross section for the four channels: \sigma_{\chione\chitwo}\cdot BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and M_\chitwo > 82.2 \mgev\sp for $\tan\beta=2$, $\mu =-600$~\mgev\sp and M_\squark= M_\gluino.Comment: 9 pages and 3 figure

Inclusive jet cross section in pˉp{\bar p p} collisions at s=1.8\sqrt{s}=1.8 TeV

The inclusive jet differential cross section has been measured for jet transverse energies, $E_T$, from 15 to 440 GeV, in the pseudorapidity region 0.1$\leq | \eta| \leq$0.7. The results are based on 19.5 pb$^{-1}$ of data collected by the CDF collaboration at the Fermilab Tevatron collider. The data are compared with QCD predictions for various sets of parton distribution functions. The cross section for jets with $E_T>200$ GeV is significantly higher than current predictions based on O($\alpha_s^3$) perturbative QCD calculations. Various possible explanations for the high-$E_T$ excess are discussed.Comment: 8 pages with 2 eps uu-encoded figures Submitted to Physical Review Letter

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR