Identifying and treating high blood pressure in men under 55 years with grade 1 hypertension: the TREAT CASP study and RCT

Background: There is uncertainty regarding whether or not younger (i.e. aged < 55 years), low-risk patients with grade 1 hypertension (i.e. a clinic blood pressure of 140–159/90–99 mmHg) should be treated with blood pressure-lowering medication. This is a heterogeneous group of patients because of variation in systolic/pulse pressure amplification from the central aorta to the brachial artery. It is hypothesised that within grade 1 hypertension, patients can be divided into those with high central aortic systolic pressure and those with low central aortic systolic pressure. Objectives: The aims of this study were to (1) evaluate whether or not non-invasive central aortic systolic pressure measurement can better identify younger patients with grade 1 hypertension, who are more likely to have an increased left ventricular mass index; and (2) determine whether or not blood pressure lowering regresses early cardiac structural change in patients with high central aortic systolic pressure. Setting: A university hospital with satellite primary care recruitment sites. Participants: A total of 726 men (aged 18 to < 55 years) were screened to identify 162 men with grade 1 hypertension and low or high central aortic systolic pressure. Blood pressure status was classified according to seated clinic blood pressure, central aortic systolic pressure and 24-hour ambulatory blood pressure. Design: (1) Evaluating the strength of the correlation between central aortic systolic pressure, clinic blood pressure and 24-hour ambulatory blood pressure with left ventricular mass index in 162 patients; (2) a 12-month randomised controlled trial in patients with grade 1 hypertension and high central aortic systolic pressure (i.e. a central aortic systolic pressure of ≥ 125 mmHg) (n = 105), using a prospective, open, blinded, end-point design; and (3) a 12-month observational study in 57 patients with grade 1 hypertension and low central aortic systolic pressure (i.e. a central aortic systolic pressure of < 125 mmHg). Interventions: Randomised controlled trial – patients with high central aortic systolic pressure randomised to blood pressure lowering medication (50–100 mg of losartan ± 5–10 mg of amlodipine once daily) versus usual care (no treatment) for 12 months. Main outcomes: Randomised controlled trial primary end point – change in left ventricular mass index as measured by cardiac magnetic resonance imaging, comparing treatment with no treatment. Results: (1) At baseline, left ventricular mass index was higher in men with high central aortic systolic pressure than in those with low central aortic systolic pressure (mean ± standard deviation 67.9 ± 8.8 g/m2 vs. 64.0 ± 8.5 g/m2; difference 4.0 g/m2, 95% confidence interval 1.1 to 6.9 g/m2; p < 0.01). Central aortic systolic pressure was not superior to clinic blood pressure as a determinant of left ventricular mass index. Univariate analysis, regression coefficients and slopes for left ventricular mass index were similar for clinic systolic blood pressure, ambulatory systolic blood pressure and central aortic systolic pressure. (2) In the randomised controlled trial, blood pressure-lowering treatment reduced central aortic systolic pressure (–21.1 mmHg, 95% confidence interval – 24.4 to –17.9 mmHg; p < 0.001) and clinic systolic blood pressure (–20.0  mmHg, 95% confidence interval – 23.3 to –16.6 mmHg; p < 0.001) versus no treatment. Treatment was well tolerated and associated with a greater change (i.e. from baseline to study closeout) in left ventricular mass index versus no treatment [–3.3 g/m2 (95% confidence interval –4.5 to –2.2 g/m2) vs. –0.9 g/m2 (95% confidence interval –1.7 to –0.2 g/m2); p < 0.01], with a medium-to-large effect size (Cohen’s d statistic –0.74). (3) Patients with low central aortic systolic pressure had no significant change in left ventricular mass index after 12 months (mean change –0.5 g/m2, 95% confidence interval –1.2 to 0.2 g/m2; p = 0.18). Conclusions: Men with grade 1 hypertension and high central aortic systolic pressure tended to have higher clinic blood pressure and more hypertension-mediated cardiac structural change than those with low central aortic systolic pressure. Central aortic systolic pressure was not superior to clinic blood pressure or ambulatory blood pressure at stratifying risk of increased left ventricular mass index. Blood pressure-lowering treatment led to a regression of left ventricular mass index in men with grade 1 hypertension and high central aortic systolic pressure compared with no treatment. Limitations: The study was limited to a moderate sample of men and there was a low prevalence of very high amplification

Pulse Wave Calibration and Implications for Blood Pressure Measurement: Systematic Review and Meta-Analysis

Central aortic systolic pressure (CASP) can be estimated via filtering of the peripheral pulse wave (PPW) following calibration to brachial blood pressure. Recent studies suggest PPW calibration to mean arterial pressure (MAP) and diastolic BP (DBP) provides more accurate CASP estimates (CASPMD) versus conventional calibration to systolic BP (SBP) and DBP (CASPSD). However, the peak of the MAP-DBP calibrated PPW, that is, SBPMD, is rarely reported or used for BP amplification calculations, despite CASPMD being derived from it. We aimed to calculate the unreported SBPMD from studies using MAP-DBP calibration for estimation of CASPMD and compared it with oscillometric brachial SBP (brSBP). Medline database was searched to March 18, 2020. Meta-analysis includes studies reporting noninvasive CASPSD, CASPMD, brSBP, and brachial DBP. SBPMD was calculated using linear function equations. Data from 21 studies used 8 different BP monitors (13 460 participants, mean age: 54±10 years, 57% female, brachial blood pressure: 130±14/79±9 mm Hg). Weighted mean difference between SBPMD and brSBP was 10 mm Hg (range, -2 to 17 mm Hg) and appeared device specific. Calibration of brachial versus radial PPWs to brachial blood pressure showed a greater disparity between SBPMD and brSBP (14 versus 2 mm Hg). BP amplification was similar comparing SBP-DBP versus MAP-DBP calibrations (brSBP-CASPSD versus SBPMD-CASPMD: 9 versus 11 mm Hg), with no instances of reverse BP amplification. PPWs calibrated to MAP-DBP to derive CASPMD generates SBPMD that differs markedly from brSBP with some oscillometric BP monitors. These findings have important implications for BP monitor accuracy, BP amplification, PPW calibration recommendations, and studies of associations between CASP versus SBP and outcomes

Genome-wide signatures of population bottlenecks and diversifying selection in European wolves

Genomic resources developed for domesticated species provide powerful tools for studying the evolutionary history of their wild relatives. Here we use 61K single-nucleotide polymorphisms (SNPs) evenly spaced throughout the canine nuclear genome to analyse evolutionary relationships among the three largest European populations of grey wolves in comparison with other populations worldwide, and investigate genome-wide effects of demographic bottlenecks and signatures of selection. European wolves have a discontinuous range, with large and connected populations in Eastern Europe and relatively smaller, isolated populations in Italy and the Iberian Peninsula. Our results suggest a continuous decline in wolf numbers in Europe since the Late Pleistocene, and long-term isolation and bottlenecks in the Italian and Iberian populations following their divergence from the Eastern European population. The Italian and Iberian populations have low genetic variability and high linkage disequilibrium, but relatively few autozygous segments across the genome. This last characteristic clearly distinguishes them from populations that underwent recent drastic demographic declines or founder events, and implies long-term bottlenecks in these two populations. Although genetic drift due to spatial isolation and bottlenecks seems to be a major evolutionary force diversifying the European populations, we detected 35 loci that are putatively under diversifying selection. Two of these loci flank the canine platelet-derived growth factor gene, which affects bone growth and may influence differences in body size between wolf populations. This study demonstrates the power of population genomics for identifying genetic signals of demographic bottlenecks and detecting signatures of directional selection in bottlenecked populations, despite their low background variability.Heredity advance online publication, 18 December 2013; doi:10.1038/hdy.2013.122

A Near-Solar Metallicity, Nitrogen-Deficient Lyman Limit Absorber Associated with two S0 Galaxies

From UV spectra of the bright quasar PHL 1811 recorded by FUSE and the E140M configuration on STIS, we have determined the abundances of various atomic species in a Lyman limit system at z = 0.0809 with log N(H I) = 17.98. Considerably more hydrogen may be in ionized form, since the abundances of C II, Si II, S II and Fe II are very large compared to that of O I, when compared to their respective solar abundance ratios. Our determination [O/H] = -0.19 in the H I-bearing gas indicates that the chemical enrichment of the gas is unusually high for an extragalactic QSO absorption system. However, this same material has an unusually low abundance of nitrogen, [N/O] < -0.59, indicating that there may not have been enough time during this enrichment for secondary nitrogen to arise from low and intermediate mass stars. In an earlier investigation we found two galaxies at nearly the same redshift as this absorption system and displaced by 34 and 87 kpc from the line of sight. An r-band image recorded by the ACS on HST indicates these are S0 galaxies. One or both of these galaxies may be the source of the gas, which might have been expelled in a fast wind, by tidal stripping, or by ram-pressure stripping. Subtraction of the ACS point-spread function from the image of the QSO reveals the presence of a face-on spiral galaxy under the glare of the quasar; although it is possible that this galaxy may be responsible for the Lyman limit absorption, the exact alignment of the QSO with the center of the galaxy suggests that the spiral is the quasar host.Comment: 74 pages, 14 figures; to be published in the Astrophysical Journal (Part 1) May 1, 2005 issue. A version of the paper with figures of better quality may be found at http://www.astro.princeton.edu/~ebj/PHL1811_paper.ps (postscript) or http://www.astro.princeton.edu/~ebj/PHL1811_paper.pdf (pdf

Alignments of the Dominant Galaxies in Poor Clusters

We have examined the orientations of brightest cluster galaxies (BCGs) in poor MKW and AWM clusters and find that, like their counterparts in richer Abell clusters, poor cluster BCGs exhibit a strong propensity to be aligned with the principal axes of their host clusters as well as the surrounding distribution of nearby (< 20/h Mpc) Abell clusters. The processes responsible for dominant galaxy alignments are therefore independent of cluster richness. We argue that these alignments most likely arise from anisotropic infall of material into clusters along large-scale filaments.Comment: 8 pages, 5 figure

Internal Dynamics, Structure and Formation of Dwarf Elliptical Galaxies: II. Rotating Versus Non-Rotating Dwarfs

We present spatially-resolved internal kinematics and stellar chemical abundances for a sample of dwarf elliptical (dE) galaxies in the Virgo Cluster observed with Keck/ESI. We find that 4 out of 17 dEs have major axis rotation velocities consistent with rotational flattening, while the remaining dEs have no detectable major axis rotation. Despite this difference in internal kinematics, rotating and non-rotating dEs are remarkably similar in terms of their position in the Fundamental Plane, morphological structure, stellar populations, and local environment. We present evidence for faint underlying disks and/or weak substructure in a fraction of both rotating and non-rotating dEs, but a comparable number of counter-examples exist for both types which show no evidence of such structure. Absorption-line strengths were determined based on the Lick/IDS system (Hbeta, Mgb, Fe5270, Fe5335) for the central region of each galaxy. We find no difference in the line-strength indices, and hence stellar populations, between rotating and non-rotating dE galaxies. The best-fitting mean age and metallicity for our 17 dE sample are 5 Gyr and Fe/H = -0.3 dex, respectively, with rms spreads of 3 Gyr and 0.1 dex. The majority of dEs are consistent with solar alpha/Fe abundance ratios. By contrast, the stellar populations of classical elliptical galaxies are, on average, older, more metal rich, and alpha-enhanced relative to our dE sample. The local environments of both dEs types appear to be diverse in terms of their proximity to larger galaxies in real or velocity space within the Virgo Cluster. Thus, rotating and non-rotating dEs are remarkably similar in terms of their structure, stellar content, and local environments, presenting a significant challenge to theoretical models of their formation. (abridged)Comment: 33 pages, 12 figures. To appear in the October 2003 Astronomical Journal. See http://www.ucolick.org/~mgeha/geha_dE.ps.gz for version with high resolution figure

Optical and Near-Infrared Imaging of the IRAS 1-Jy Sample of Ultraluminous Infrared Galaxies: II. The Analysis

The present paper discusses the results from an analysis of the images presented in Paper I (astro-ph/0207373) supplemented with new spectroscopic data obtained at Keck. All but one object in the 1-Jy sample show signs of a strong tidal interaction/merger. Multiple mergers involving more than two galaxies are seen in no more than 5 of the 118 (< 5%) systems. None of the 1-Jy sources is in the first-approach stage of the interaction, and most (56%) of them harbor a single disturbed nucleus and are therefore in the later stages of a merger. Seyfert galaxies (especially those of type 1), warm ULIGs (f_{25}/f_{60} > 0.2) and the more luminous systems (> 10^{12.5} L_sun) all show a strong tendency to be advanced mergers with a single nucleus. An analysis of the surface brightness profiles of the host galaxies in single-nucleus sources reveals that about 73% of the R and K' surface brightness profiles are fit adequately by an elliptical-like R^{1/4}-law. These elliptical-like 1-Jy systems have luminosities, half-light radii, and R-band axial ratio distribution that are similar to those of normal (inactive) intermediate-luminosity ellipticals and follow with some scatter the same mu_e - r_e relation. These elliptical-like hosts are most common among merger remnants with Seyfert 1 nuclei (83%), Seyfert 2 optical characteristics (69%) or mid-infrared (ISO) AGN signatures (80%). In general, the results from the present study are consistent with the merger-driven evolutionary sequence ``cool ULIGs --> warm ULIGs --> quasars,'' although there are many exceptions. (abridged)Comment: Correction to D.-C. Kim's affiliations. 42 pages + 3 tables + 3 multi-page jpeg figures; see http://www.astro.umd.edu/~veilleux/pubs/paper2.tar.gz for original figure

Old and young bulges in late-type disk galaxies

ABRIDGED: We use HSTACS and NICMOS imaging to study the structure and colors of a sample of nine late-type spirals. We find: (1) A correlation between bulge and disks scale-lengths, and a correlation between the colors of the bulges and those of the inner disks. Our data show a trend for bulges to be more metal-enriched than their surrounding disks, but otherwise no simple age-metallicity connection between these systems; (2) A large range in bulge stellar population properties, and, in particular, in stellar ages. Specifically, in about a half of the late-type bulges in our sample the bulk of the stellar mass was produced recently. Thus, in a substantial fraction of the z=0 disk-dominated bulged galaxies, bulge formation occurs after the formation/accretion of the disk; (3) In about a half of the late-type bulges in our sample, however, the bulk of the stellar mass was produced at early epochs; (4) Even these "old" late-type bulges host a significant fraction of stellar mass in a young(er) c component; (5) A correlation for bulges between stellar age and stellar mass, in the sense that more massive late-type bulges are older than less massive late-type bulges. Since the overall galaxy luminosity (mass) also correlates with the bulge luminosity (mass), it appears that the galaxy mass regulates not only what fraction of itself ends up in the bulge component, but also "when" bulge formation takes place. We show that dynamical friction of massive clumps in gas-rich disks is a plausible disk-driven mode for the formation of "old" late-type bulges. If disk evolutionary processes are responsible for the formation of the entire family of late-type bulges, CDM simulations need to produce a similar number of initially bulgeless disks in addition to the disk galaxies that are observed to be bulgeless at z=0.Comment: ApJ in press; paper with high resolution figures available at http://www.exp-astro.phys.ethz.ch/carollo/carollo1_2006.pdf; B, I, and H surface brightness profiles published in electronic tabular for

Integral Field Spectroscopy of the Central Regions of 3C 120: Evidence of a Past Merging Event

IFS combined with HST WFPC imaging were used to characterize the central regions of the Seyfert 1 radio galaxy 3C 120. We carried out the analysis of the data, deriving intensity maps of different emission lines and the continua at different wavelengths from the observed spectra. Applying a 2D modeling to the HST images we decoupled the nucleus and the host galaxy, and analyzed the host morphology. The host is a highly distorted bulge dominated galaxy, rich in substructures. We developed a new technique to model the IFS data extending the 2D modeling. Using this technique we separated the Seyfert nucleus and the host galaxy spectra, and derived a residual data cube with spectral and spatial information of the different structures in 3C 120. Three continuum-dominated structures (named A, B, and C) and other three extended emission line regions (EELRs, named E1, E2 and E3) are found in 3C 120 which does not follow the general behavior of a bulge dominated galaxy. We also found shells in the central kpc that may be remnants of a past merging event in this galaxy. The origin of E1 is most probably due to the interaction of the radio-jet of 3C 120 with the intergalactic medium. Structures A, B, and the shell at the southeast of the nucleus seem to correspond to a larger morphological clumpy structure that may be a tidal tail, consequence of the past merging event. We found a bright EELR (E2) in the innermost part of this tidal tail, nearby the nucleus, which shows a high ionization level. The kinematics of the E2 region and its connection to the tidal tail suggest that the tail has channeled gas from the outer regions to the center.Comment: 55 pages, 18 figures and 5 tables Accepted by AP

PKS B1545-321: Bow shocks of a relativistic jet?

Sensitive, high resolution images of the double-double radio galaxy PKS B1545-321 reveal detailed structure, which we interpret in the light of previous work on the interaction of restarted jets with pre-existing relict cocoons. We have also examined the spectral and polarization properties of the source, the color distribution in the optical host and the environment of this galaxy in order to understand its physical evolution. We propose that the restarted jets generate narrow bow shocks and that the inner lobes are a mixture of cocoon plasma reaccelerated at the bow shock and new jet material reaccelerated at the termination shock. The dynamics of the restarted jets implies that their hot spots advance at mildly relativistic speeds with external Mach numbers of at least 5. The existence of supersonic hot spot Mach numbers and bright inner lobes is the result of entrainment causing a reduction in the sound speed of the pre-existing cocoon. The interruption to jet activity in PKS B1545-321 has been brief - lasting less than a few percent of the lifetime $\sim (0.3-2)\times 10^{8} yr$ of the giant radio source. The host galaxy is located at the boundary of a large scale filamentary structure, and shows blue patches in color distribution indicative of a recent merger, which may have triggered the Mpc-scale radio galaxy.Comment: 26 pages including 1 table and 16 figures. To appear in MNRA