326 research outputs found

    Prevention of cardiovascular disease in patients with familial hypercholesterolaemia: the role of PCSK9 inhibitors

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    Familial hypercholesterolaemia is an autosomal dominant inherited disorder characterised by elevated low-density lipoprotein cholesterol levels and consequently an increased risk of atherosclerotic cardiovascular disease (ASCVD). Familial hypercholesterolaemia is relatively common, but is often underdiagnosed and undertreated. Cardiologists are likely to encounter many individuals with familial hypercholesterolaemia; however, patients presenting with premature ASCVD are rarely screened for familial hypercholesterolaemia and fasting lipid levels are infrequently documented. Given that individuals with familial hypercholesterolaemia and ASCVD are at a particularly high risk of subsequent cardiac events, this is a missed opportunity for preventive therapy. Furthermore, because there is a 50% chance that first-degree relatives of individuals with familial hypercholesterolaemia will also be affected by the disorder, the underdiagnosis of familial hypercholesterolaemia among patients with ASCVD is a barrier to cascade screening and the prevention of ASCVD in affected relatives. Targeted screening of patients with ASCVD is an effective strategy to identify new familial hypercholesterolaemia index cases. Statins are the standard treatment for individuals with familial hypercholesterolaemia; however, low-density lipoprotein cholesterol targets are not achieved in a large proportion of patients despite treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce low-density lipoprotein cholesterol levels considerably in individuals with familial hypercholesterolaemia who are concurrently receiving the maximal tolerated statin dose. The clinical benefit of PCSK9 inhibitors must, however, also be considered in terms of their cost-effectiveness. Increased awareness of familial hypercholesterolaemia is required among healthcare professionals, particularly cardiologists and primary care physicians, in order to start early preventive measures and to reduce the mortality and morbidity associated with familial hypercholesterolaemia and ASCVD

    A retrospective observational study to determine baseline characteristics and early prescribing patterns for patients receiving Alirocumab in UK clinical practice

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    Background Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) and has been previously shown, in the phase III ODYSSEY clinical trial program, to provide significant lowering of lowdensity lipoprotein cholesterol (LDL-C) and reduction in risk of major adverse cardiovascular events. However, real-world evidence to date is limited. Objective The primary objective was to describe baseline characteristics, clinical history, and prior lipid-lowering therapy (LLT) use of patients initiated on alirocumab in UK clinical practice following publication of health technology appraisal (HTA) body recommendations. Secondary objectives included description of alirocumab use and lipid parameter outcomes over a 4-month follow-up period. Methods In this retrospective, single-arm, observational, multicenter study, data were collected for 150 patients initiated on alirocumab. Results Mean (standard deviation; SD) age of patients was 61.4 (10.5) years and baseline median (interquartile range; IQR) LDL-C level was 4.8 (4.2–5.8) mmol/l. Alirocumab use occurred predominantly in patients with heterozygous familial hypercholesterolemia (HeFH) (n = 100/150, 66%) and those with statin intolerance (n = 123/150, 82%). Most patients started on alirocumab 75 mg (n = 108/150 [72%]) and 35 (23.3%) were up-titrated to 150 mg. Clinically significant reductions in atherogenic lipid parameters were observed with alirocumab, including LDL-C (median [IQR] change from baseline, − 53.6% [− 62.9 to − 34.9], P < 0.001). Conclusion This study highlights the unmet need for additional LLT in patients with uncontrolled hyperlipidemia and demonstrates the clinical utility of alirocumab in early real-world practice, where dosing flexibility is an important attribute of this therapeutic option

    Two years after molecular diagnosis of familial hypercholesterolemia: Majority on cholesterol-lowering treatment but a minority reaches treatment goal

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    Background: The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings: In 2008, we sent questionnaires to all subjects (aged 18-65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance: The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through

    Auditory temporal resolution and evoked responses to pulsed sounds for the Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis)

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    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 197 (2011): 1149-1158, doi:10.1007/s00359-011-0677-y.Temporal cues are important for some forms of auditory processing, such as echolocation. Among odontocetes (toothed whales, dolphins, and porpoises), it has been suggested that porpoises may have temporal processing abilities which differ from other odontocetes because of their relatively narrow auditory filters and longer duration echolocation signals. This study examined auditory temporal resolution in two Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis) using auditory evoked potentials (AEPs) to measure: (i) rate following responses and modulation rate transfer function for 100 kHz centered pulse sounds and (ii) hearing thresholds and response amplitudes generated by individual pulses of different durations. The animals followed pulses well at modulation rates up to 1250 Hz, after which response amplitudes declined until extinguished beyond 2500 Hz. The subjects had significantly better hearing thresholds for longer, narrower-band pulses similar to porpoise echolocation signals compared to brief, broadband sounds resembling dolphin clicks. Results indicate that the Yangtze finless porpoise follows individual acoustic signals at rates similar to other odontocetes tested. Relatively good sensitivity for longer duration, narrow-band signals suggests that finless porpoise hearing is well-suited to detect their unique echolocation signals.The work was supported by the Office of Naval Research, a WHOI Mellon Joint Initiatives Award , the Chinese National Natural Science Foundation (grant No: 30730018) and the Institute of Hydrobiology of the Chinese Academy of Sciences2012-09-1

    The effects of diets enriched in omega-3 polyunsaturated fatty acids on systemic vaccinia virus infection

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    Omega-3 polyunsaturated fatty acids (PUFA, n-3 fatty acids), the key components of fish and flaxseed oils, are increasingly consumed by the public because of their potential health benefits and are available by prescription for hypertriglyceridemia. However, numerous studies have shown that these compounds are immunoregulatory and immunosuppressive and thus may increase susceptibility to infection. In this study, we tested the effects of the amount of fat and the types of fatty acid in the diet on infection by vaccinia virus, an acute infection that begins in the respiratory tract and spreads by viremia to internal organs. Male C57Bl6 mice (~5 week old) were fed for 3 weeks prior to infection and continuing during infection and recovery one of the following: 1) a normal low fat (13% kcal) diet, 2) a low fat diet containing n-3 PUFAs, 3) a high fat (41% kcal) diet rich in n-3 PUFAs, 4) a high fat n-6 PUFA diet, or 5) a high fat monounsaturated diet. We found no statistically significant differences in the susceptibility of mice to viral infection, morbidity, viral organ titers, recovery time, or mortality with these diets, indicating that, over this approximately 6-week time period, dietary fats did not substantially affect responses to poxviral infection

    Efficacy and Safety of Alirocumab in Individuals with Diabetes Mellitus:Pooled Analyses from Five Placebo-Controlled Phase 3 Studies

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    Introduction: Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. Methods: Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout. The primary endpoint was percentage change in LDL-C from baseline to week 24. Results: In the alirocumab 150 mg pool (n = 2416), baseline LDL-C levels were 117.4 mg/dL (DM) and 130.6 mg/dL (without DM), and in the 75/150 mg pool (n = 1043) 112.8 mg/dL (DM) and 133.0 mg/dL (without DM). In the 150 mg Q2W group, week 24 LDL-C reductions from baseline were observed in persons with DM (− 59.9%; placebo, − 1.4%) and without DM (− 60.6%; placebo, + 1.5%); 77.7% (DM) and 76.8% (without DM) of subjects achieved LDL-C < 70 mg/dL. In the alirocumab 75/150 mg group, 26% (DM) and 36% (without DM) of subjects received dose increase. In this group, week 24 LDL-C levels changed from baseline by − 43.8% (DM; placebo, + 0.3%) and − 49.7% (without DM; placebo, + 5.1%); LDL-C < 70 mg/dL was achieved by 68.3% and 65.8% of individuals, respectively. At week 24, alirocumab was also associated with improved levels of other lipids. Adverse event rates were generally comparable in all groups (79.8–82.0%). Conclusions: Regardless of DM status, alirocumab significantly reduced LDL-C levels; safety was generally similar. Funding Sanofi and Regeneron Pharmaceuticals, Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s13300-018-0439-8) contains supplementary material, which is available to authorized users

    Incidental cardiac findings on computed tomography imaging of the thorax

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    <p>Abstract</p> <p>Background</p> <p>Investigation of pulmonary pathology with computed tomography also allows visualisation of the heart and major vessels. We sought to explore whether clinically relevant cardiac pathology could be identified on computed tomography pulmonary angiograms (CTPA) requested for the exclusion of pulmonary embolism (PE). 100 consecutive CT contrast-enhanced pulmonary angiograms carried out for exclusion of PE at a single centre were assessed retrospectively by two cardiologists.</p> <p>Findings</p> <p>Evidence of PE was reported in 5% of scans. Incidental cardiac findings included: aortic wall calcification (54%), coronary calcification (46%), cardiomegaly (41%), atrial dilatation (18%), mitral annulus calcification (15%), right ventricular dilatation (11%), aortic dilatation (8%) and right ventricular thrombus (1%). Apart from 3 (3%) reports describing cardiomegaly, no other cardiac findings were described in radiologists' reports. Other reported pulmonary abnormalities included: lung nodules (14%), lobar collapse/consolidation (8%), pleural effusion (2%), lobar collapse/consolidation (8%), emphysema (6%) and pleural calcification (4%).</p> <p>Conclusions</p> <p>CTPAs requested for the exclusion of PE have a high yield of cardiac abnormalities. Although these abnormalities may not have implications for acute clinical management, they may, nevertheless, be important in long-term care.</p
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