Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

BackgroundVolumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels.Methods and resultsEAT and PAT volumes and CAC were measured using electron beam computed tomography scans. CAC was evaluated as (1) the presence of CAC (CAC Agatston score ≥10) and (2) the extent of any CAC (log CAC Agatston score >0). The study included 478 women aged 50.9 years (58% pre- or early perimenopausal, 10% late perimenopausal, and 32% postmenopausal). EAT was significantly associated with CAC measures, and these associations were not modified by menopausal status or estradiol. In contrast, associations between PAT and CAC measures were modified by menopausal status (interaction-P≤0.01). Independent of study covariates including other adiposity measures, each 1-SD unit increase in log PAT was associated with 102% higher risk of CAC presence (P=0.04) and an 80% increase in CAC extent (P=0.008) in postmenopausal women compared with pre- or early perimenopausal women. Additional adjustment for estradiol and hormone therapy attenuated these differences. Moreover, the association between PAT and CAC extent was stronger in women with lower estradiol levels (interaction P=0.004).ConclusionsThe findings suggest that PAT is a potential menopause-specific coronary artery disease risk marker, supporting the need to monitor and target this fat depot for intervention in women at midlife

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure.BackgroundInhibition of the renin-angiotensin system is known to raise serum potassium [K+] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K+] in people with renal insufficiency.MethodsThe study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 ± 2 years. Mean baseline serum [K+] was 4.4 ± 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 ± 5 mL/min/1.73 m2, and blood pressure was 150 ± 2/88 ± 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods.ResultsFor the total group, serum [K+] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of ≤60 mL/min/1.73 m2 who received lisinopril demonstrated significant increases in serum [K+] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K+] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K+] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of ≤60 mL/min/1.73 m2. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K+], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K+] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14).ConclusionsIn the presence of renal insufficiency, the ARB valsartan did not raise serum [K+] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K+] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K+] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency

Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause

The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation

Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers

Background: Denatonium benzoate (DB) has been shown to influence ongoing ingestive behavior and gut peptide secretion.Objective: We studied how the intragastric administration of DB affects interdigestive motility, motilin and ghrelin plasma concentrations, hunger and satiety ratings, and food intake in healthy volunteers.Design: Lingual bitter taste sensitivity was tested with the use of 6 concentrations of DB in 65 subjects. A placebo or 1 μmol DB/kg was given intragastrically to assess its effect on fasting gastrointestinal motility and hunger ratings, motilin and ghrelin plasma concentrations, satiety, and caloric intake.Results: Women (n = 39) were more sensitive toward a lingual bitter stimulus (P = 0.005) than men (n = 26). In women (n = 10), intragastric DB switched the origin of phase III contractions from the stomach to the duodenum (P = 0.001) and decreased hunger ratings (P = 0.04). These effects were not observed in men (n = 10). In women (n = 12), motilin (P = 0.04) plasma concentrations decreased after intragastric DB administration, whereas total and octanoylated ghrelin were not affected. The intragastric administration of DB decreased hunger (P = 0.008) and increased satiety ratings (P = 0.01) after a meal (500 kcal) in 13 women without affecting gastric emptying in 6 women. Caloric intake tended to decrease after DB administration compared with the placebo (mean ± SEM: 720 ± 58 compared with 796 ± 45 kcal; P = 0.08) in 20 women.Conclusions: Intragastric DB administration decreases both antral motility and hunger ratings during the fasting state, possibly because of a decrease in motilin release. Moreover, DB decreases hunger and increases satiety ratings after a meal and shows potential for decreasing caloric intak

New treatment approaches for specific diseases of the coffin joint and of the navicular bone in horses diagnosed by Magnetic Resonance Imaging

Im Zusammenhang mit „Palmar foot pain“ werden immer wieder erste Anzeichen von Strahlbeinerkrankungen beobachtet. Diese frühzeitigen Erkrankungen können im Magnetresonanztomographen mit einem erhöhten fettunterdrückten Signal im Strahlbein dargestellt werden. Ein erhöhtes fettunterdrücktes Signal, also ein Knochenmarködem, hat potentiell ein erhöhtes Osteoarthritisrisiko. Eine potentielle Behandlungsmethode für frühzeitige Strahlbeinerkrankungen bei Pferden kann Calcium dobesilate, mit der Eigenschaft eines druckdynamischen Effekts, darstellen. Ziel dieser Studie war es, die Lahmheit und die MRT- Veränderungen in 12 mit Calcium dobesilate behandelten Pferden, mit diagnostizierter chronischer Strahlbeinlahmheit und einem im MRT erhöhten fettunterdrücktem Signal im Strahlbein zu beobachten. Für die Untersuchung wurden 12 Pferde mit Vorderhandlahmheiten selektiert, die Lahmheitsdauer beschränkte sich auf einen Monat bis zwei Jahre. Einschlusskriterien waren: keine röntgenologischen Veränderungen in den Standard Projektionen und ausschließlich ein im MRT erhöhtes fettunterdrücktes Signal im Strahlbein ohne gleichzeitig auftretende Defekte im MRT in der distalen Pferdegliedmaße. Die Pferde wurden mit Calcium dobesilate behandelt und erhielten einen einheitlichen Bewegungsplan. Eine klinische und eine MRT Nachuntersuchung erfolgte im zweiten und im vierten Monat. In der ersten Nachuntersuchung zeigten 83% der Pferde und in der zweiten Nachuntersuchung 91% der Pferde eine reduzierte Lahmheit. Am Ende der Pilotstudie waren 8 von 12 Pferden lahmheitsfrei. Während der Pilotstudie konnte eine Tendenz für eine Reduktion des fettunterdrückten Signals im Strahlbein festgestellt werden. Zur Behandlung von degenerativer Osteoarthritis im Hufgelenk stellt Polyacrylamid Hydrogel eine mögliche neue Therapiemethode dar, wenn herkömmliche Behandlungsmethoden erfolglos bleiben. In dieser Fallserie wurde bei 12 Pferden je 1 ml PAAHG in die erkrankten Hufgelenke appliziert. Alle Patienten waren aufgrund Osteoarthritis des Hufgelenkes seit mindestens drei Monaten chronisch-rezidivierend lahm an einer oder beiden Vordergliedmaßen. Die Pferde waren zuvor mit einer oder mehreren konventionellen Therapiemethoden (Hyaluronsäure, Glukokortikoide, Autologes Conditioniertes Serum) mindestens zweimal erfolglos vorbehandelt. Die Diagnose Osteoarthritis wurde anhand der klinischen Befunde, Leitungsanästhesien, Gelenksanästhesien, röntgenologischer und kernspintomographischer Untersuchungen gestellt. Klinische Nachuntersuchungen erfolgten nach einem und nach sechs Monaten. Sechs Monate nach der Behandlung waren 8 Pferde lahmheitsfrei, 2 Pferde zeigten eine Verbesserung und 2 Pferde blieben unverändert. Der vorliegende Fallbericht beschreibt die Entwicklung und das Management einer Strahlbeinzyste von einem hochrangigen Springpferd mit chronisch intermittierender Vorderhandlahmheit. Die ersten Anzeichen auf eine Strahlbeinerkrankung war ein erhöhtes fettunterdrücktes Signal im rechten Strahlbeinmark, nach 24 Monaten entwickelte sich dies zu einem radiologisch nachweisbaren zystoiden Defekt. Über 2 Jahre und 2 Monate wurde dieser Krankheitsprozess mit Lahmheitsuntersuchungen, Nachuntersuchungen, Behandlungen, Röntgenbildern und sechs MRT-Nachuntersuchungen mit einem stehenden System (standing low-field) dokumentiert. In der letzten klinischen Nachuntersuchung zeigte sich das Pferd lahmheitsfrei und wurde wieder im Internationalen Springsport eingesetzt.The syndrome “Palmar foot pain” often disguises the early stages of navicular disease. These early signs can be represented by an increased signal intensity in the navicular bone in fat suppressed images on Magnetic Resonance Imaging (MRI). Increased signal intensity in these fat suppressed images probably represents bone oedema and potentiates an increased risk of osteoarthritis. One potential treatment modality for this condition is the use of Calcium dobesilate. This has an effect on pressure dynamics and could potentially be used as a treatment for navicular disease in horses if administered during the early stages of the syndrome. The aim of this study was to monitor both the degree of lameness and the MRI changes seen in twelve horses treated with Calcium dobesilate and displaying increased signal intensity from fat suppressed images in the spongiosa region of the navicular bone. Twelve horses with a front foot lameness which had been present for between one month and two years were selected for the study. Inclusion criteria were: absence of radiographic findings on standard foot radiographs and an increased signal intensity in fat suppressed images of the navicular bone spongiosa region without concurrent lesions being detected elsewhere on MRI scans of the foot. Horses were treated with Calcium dobesilate and were then subjected to a controlled exercise regime. They were re-evaluated at two and four months after treatment. In the first follow-up examination 83% of the horses showed a reduced level of lameness whilst two months later this had increased to 91%. At the end of the trial eight of the twelve horses were found to be sound. During the pilot study fat suppressed images of the navicular bone showed a reduction in the intensity of the signal from the medullary cavity following treatment. Polyacrylamide Hydrogel is a potential new treatment for degenerative osteoarthritis of the Distal Interphalangeal Joint (DIP joint) when conventional medication fails. In this case one ml of Polyacrylamide Hydrogel was applied to the DIP joint of twelve affected horses. All horses were displaying a chronic recurrent lameness on one or both fore limbs which had been present for more than three months and which had been found to be due to osteoarthritis of the DIP joint. These horses had been previously treated on at least two occasions with intra-articular medication such as Hyaluronic acid, Glucocorticoides and/or autologous conditioned serum. These treatments had proved unsuccessful. The diagnosis of osteoarthritis was based on the abolition of lameness using both regional and intra-articular anaesthesia and by using radiological and MRI findings. These cases were re-examined one and six months following treatment. Six months after treatment eight of the treated horses were now sound whilst a further two horses showed some improvement. The other two horses were unchanged. This case report demonstrates the development of an osseous cyst-like lesion in the spongiosa of the navicular bone in a “high level” show jumping horse displaying chronic intermittent fore limb lameness. The first evidence of navicular bone pathology was an increased signal intensity on fat suppressed images in the medulla of the right navicular bone. This progressed to a cystic lucency which could be identified radiographically at twenty four months of age. The horse´s progress was monitored over a period of twenty six months; this monitoring included lameness investigations, treatment, diagnostic radiographs and six follow-up standing low field MRI sessions. At the last clinical recheck the horse no longer showed signs of lameness and continued to perform in international showjumping events

Menopause and the metabolic syndrome: the Study of Women\u27s Health Across the Nation

BACKGROUND: Cross-sectional studies suggest that prevalence of the metabolic syndrome (MetS) increases from premenopause to postmenopause in women, independent of age. Little is known about why. We hypothesized that the incidence of the MetS increases with progression through menopause and that this increase is explained by the progressive androgenicity of the hormonal milieu. METHODS: This longitudinal, 9-year study of 949 participants in the Study of Women\u27s Health Across the Nation investigates the natural history of the menopausal transition. Participants of 5 ethnicities at 7 geographic sites were recruited when they were premenopausal or early perimenopausal and were eligible for this study if they (1) reached menopause during the study; (2) had never taken hormone therapy, and (3) did not have diabetes mellitus or the MetS at baseline. The primary outcome was the presence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria. Secondary outcomes were the components of the MetS. RESULTS: By the final menstrual period, 13.7% of the women had new-onset MetS. Longitudinal analyses, centered at the final menstrual period, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging. Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.18-1.30). These odds were significantly different (P \u3c .001). An increase in bioavailable testosterone or a decrease in sex hormone-binding globulin levels increased the odds. CONCLUSIONS: As testosterone progressively dominates the hormonal milieu during the menopausal transition, the prevalence of MetS increases, independent of aging and other important covariates. This may be a pathway by which cardiovascular disease increases during menopause