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Pubblicazioni recenti - cardiovascular disease
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An electrochemical and fluorescence dual-signal assay based on FeO@MnO and N-doped carbon dots for determination of hydrogen peroxide.
Mikrochim Acta2020 Feb;187(3):187. doi: 10.1007/s00604-020-4163-5.
Zhu Wanying, Zhou Ying, Tao Mengdan, Yan Xiaoqiang, Liu Yan, Zhou Xuemin,
Abstract
A novel electrochemical and fluorescence dual-signal assay was developed for the determination of hydrogen peroxide (HO) based on FeO@MnO and N-doped carbon dots (NCDs). FeO@MnO was not only applied as the recognizer for HO but also served as the fluorescence quencher and electrochemical enhancer. This permits the dual-signal readout of the analytical system. In the absence of HO, the NCDs were quenched by FeO@MnO, and the oxidation of the electrochemical probe ferrocene (Fc) was catalyzed by FeO@MnO. In the presence of HO, MnO was reduced to Mn leading to the fluorescence recovery of NCDs and the reduction in the oxidation signal of Fc. By combining the electrochemical method and the fluorescence assay, more comprehensive and valuable information for HO determination was provided to meet different analytical demands. The method exhibits good repeatability and selectivity with a detection limit of 1.0 ?M for the fluorescence assay and 0.6 ?M for the electrochemical method. The proposed approach holds great potential for probing released targets from living cells. Graphical abstract.
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Clinical significance of the prognostic nutritional index in patients undergoing cardiovascular surgery.
Gen Thorac Cardiovasc Surg2020 Feb;():. doi: 10.1007/s11748-020-01300-x.
Hayashi Jun, Uchida Tetsuro, Ri Sho, Hamasaki Azumi, Kuroda Yoshinori, Yamashita Atsushi, Sadahiro Mitsuaki,
Abstract
OBJECTIVE:
The prognostic nutrition index is an immunonutritional indicator and postoperative predictor of oncological surgery. However, its prognostic value in cardiovascular disease is unknown. This study assessed the value of the prognostic nutrition index in cardiovascular surgery.
METHODS:
This retrospective study included 453 patients who underwent cardiovascular surgery. The patients were divided according to cutoff values of the prognostic nutrition index:
RESULTS:
Old age, a low body mass index, and elevated creatinine levels correlated significantly with a low prognostic nutrition index. Logistic regression analysis demonstrated that a high prognostic nutrition index status was statistically related to a shorter length of intensive care unit stay, shorter intubation time, and lower incidences of mediastinitis and pneumonia. Multivariate analysis revealed that male sex (hazard ratio 3.93; 95% confidence interval 1.29-11.91, p?=?0.016), age (hazard ratio 3.35; 95% confidence interval 1.11-10.15 p?=?0.032), and the prognostic nutrition index (hazard ratio 0.40; 95% confidence interval 0.18-0.90, p?=?0.026) were independently associated with postoperative survival.
CONCLUSIONS:
A low prognostic nutrition index was significantly associated with postoperative complications and survival. The prognostic nutrition index may be useful and reliable as a preoperative assessment of nutritional status, and it should be considered in the indication and strategy of cardiovascular surgery.
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Strategies for implementation of guideline recommended cardiovascular risk management for patients with rheumatoid arthritis: results from a questionnaire survey of expert rheumatology centers.
Rheumatol Int2020 Feb;():. doi: 10.1007/s00296-020-04533-4.
Weijers Julia M, Semb Anne G, Rollefstad Silvia, Kitas George D, van Riel Piet L C M, ,
Abstract
The aim was to study the different strategies used to implement cardiovascular risk evaluation and management for patients with rheumatoid arthritis (RA) in daily clinical practice. A questionnaire survey was performed among both the members of the international Trans-Atlantic Cardiovascular Risk Consortium for Rheumatoid Arthritis (ATACC-RA) as well as the Survey of cardiovascular disease risk factors (CVD-RF) in patients with RA (SURF-RA) group. The questionnaire included 18 questions with the overarching topics: (1) organization and responsibility of cardiovascular risk management (CVRM); (2) screening of CVD-RFs; (3) overview current CVRM status; and (4) availability of data regarding CVRM. Based on the answers, two researchers (JW, PR) independently categorized the different strategies. Thirteen out of 27 rheumatology centers responded to the questionnaire. One rheumatology center did not have organized CVRM for their RA patients. Among the other centers, three strategies to organize CVRM in daily practice were distinguished: (1) the rheumatologist performs CVRM during outpatient visits (n?=?6); (2) cardiologists and rheumatologists co-operate in a cardio-rheuma-clinic/team with different tasks and responsibilities (n?=?3); and (3) the general practitioner screens and intervenes on CVD-RFs (n?=?3). Each CVRM strategy was based on agreements between medical professionals and was also dependent on the national healthcare system and available financial resources. Three strategies were identified for CVRM implementation in daily clinical practice based on who is primarily responsible for performing CVRM. More research is warranted to compare their relative merits and effectiveness in relation to CVRM.
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Finerenone Reduces Intrinsic Arterial Stiffness in Munich Wistar Frömter Rats, a Genetic Model of Chronic Kidney Disease.
Am J Nephrol2020 Feb;():1-10. doi: 10.1159/000506275.
Gil-Ortega Marta, Vega-Martín Elena, Martín-Ramos Miriam, González-Blázquez Raquel, Pulido-Olmo Helena, Ruiz-Hurtado Gema, Schulz Angela, Ruilope Luis M, Kolkhof Peter, Somoza Beatriz, Kreutz Reinhold, Fernández-Alfonso Maria S,
Abstract
BACKGROUND:
Development of albuminuria and arterial stiffness in Munich Wistar Frömter (MWF) rats, a model of chronic kidney disease, is related to alterations in extracellular matrix, increased oxidative stress, and endothelial dysfunction. Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity. We hypothesize that FIN reduces arterial stiffness in this model associated to the reduction in albuminuria and matrix metalloproteinase (MMP)-2/9 activity.
METHODS:
Twelve-week-old MWF rats with established albuminuria and age-matched normoalbuminuric Wistar (W) rats were treated with FIN (10 mg/kg/day, once-daily oral gavage) or with vehicle (control, C) for 4 weeks.
RESULTS:
Arterial stiffness was significantly higher in mesenteric arteries (MA) of MWF-C as compared to W-C. FIN treatment significantly lowered ?-index, a measure of intrinsic stiffness independent of geometry, in MWF (?MWF-FIN = 7.7 ± 0.4 vs. ?MWF-C = 9.2 ± 0.5, p < 0.05) positively correlating with urinary albumin excretion. Elastin fenestrae area in the internal elastic lamina of MA from MWF-FIN was significantly larger (+377%, p < 0.05). FIN increased plasma pro-MMP-2 and decreased plasma MMP-2 and MMP-9 activities, correlating with reductions in ?-index. MA from MWF-FIN exhibited higher NO bioavailability and reduced superoxide anion levels compared to MWF-C.
CONCLUSION:
FIN treatment reduces intrinsic arterial stiffness in MA from MWF rats associated with changes in elastin organization, normalization of MMP-2 and MMP-9 activities, and reduction of oxidative stress. Moreover, reduction of arterial stiffness correlates with reduction in albuminuria.
© 2020 S. Karger AG, Basel.
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Evaluation of cardiovascular risk factors in people living with HIV in Săo Paulo, Brazil.
J Infect Dev Ctries2020 Jan;14(1):89-96. doi: 10.3855/jidc.11326.
Melo Elizabete Santos, Antonini Marcela, Costa Christefany Régia Braz, Sorensen William, Gir Elucir, Reis Renata Karina,
Abstract
INTRODUCTION:
HIV infection as a chronic disease has emerged from treatment advances over the past three decades. From this perspective, the diseases associated with AIDS are not a main threat for patients who use Antiretroviral Therapy (ART). A new set of HIV associated complications have emerged resulting in comorbidities related to aging and ART exposure as cardiovascular disease (CVD). This study aimed to evaluate the cardiovascular risk factors in people living with HIV (PLWH) in Brazil.
METHODOLOGY:
This was a cross-sectional study carried out at all Specialized Care Services for people living with HIV in the Southeast of Brazil. A sociodemographic and clinical questionnaire was used and cardiovascular risk assessed through the Framingham Score. Data analysis was performed by Chi-square, Fisher's exact test and logistic regression.
RESULTS:
The majority were male, over 40 years old and they showed a mean age of 44 years. Current hypertension, diabetes, altered body mass index, presence of metabolic syndrome and altered abdominal circumference were also associated with cardiovascular risk. After regression analysis, male sex, older age, smoking, diabetes, hypertension and metabolic syndrome were related as predictive factors for a higher cardiovascular risk.
CONCLUSIONS:
The results demonstrate that combination of the prevention of modifiable risk factors with considerable changes in lifestyle are determining factors for success in the therapeutic of PLWH. High levels of motivation are essential for behavioral changes, and nurses are ideally position to provide safe care with nonpharmacological strategies for CVD risk reduction.
Copyright (c) 2020 Elizabete Santos Melo, Marcela Antonini, Christefany Regiz Braz Costa, William Sorensen, Elucir Gir, Renata Karina Reis.
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Effects of Turmeric on Cardiovascular Risk Factors, Mental Health, and Serum Homocysteine in Overweight, Obese Females.
Altern Ther Health Med2020 Feb;():. doi: AT6135.
Latif Rabia, Mumtaz Sadaf, Al Sheikh Mona Hmoud, Chathoth Shahanas, Nasser Al Naimi Shaykhah,
Abstract
Context:
The prevalence of overweight and obesity and associated comorbidities has progressively risen. Curcumin, the active ingredient in turmeric, and turmeric aqueous extract, a concentrated form, have been reported to have beneficial effects in treatment of cardiovascular diseases and their risk factors. However, turmeric has not been studied in its natural form.
Objective:
The present study planned to evaluate the beneficial effects of turmeric in its natural form on obesity-related, cardiovascular-disease risk factors in overweight or obese females.
Design:
The study used a pre-post, single-arm design.
Setting:
The study took place in the Department of Physiology at Imam Abdulrahman Bin Faisal University (Dammam, Saudi Arabia).
Participants:
The participants were 36 young female students at the university, with a body mass index ? 23 kg/m2.
Intervention:
Participants received a daily dose of 2 g/d of turmeric in capsules for 90 d.
Outcome Measures:
Anthropometric measures, blood pressure, serum homocysteine, and mental health status- stress, anxiety, depression scores-were recorded at baseline and postintervention. Dietary intake and physical activity (confounding variables) were also measured.
Results:
The following anthropometric measures were reduced significantly between baseline and postintervention: (1) body weight-73.47 vs 72.45 kg (P = .04), (2) body mass index-28.75 vs 28.27 kg/m2 (P = .02), (3) waist circumference-81.85 vs 77.96 cm (P = .01), (4) hip circumference-102.72 vs 98.10 cm (P = .001), (5) body fat %-34.34 vs 32.58 (P = .00), (6) systolic blood pressure-119.12 vs 115.92 mm Hg (P = .04), and (7) anxiety scores-7.88 vs 4.73 (P = .03), as compared by paired t test. Homocysteine levels and stress and depression scores showed no significant changes. Dietary intake and physical activity did not vary significantly throughout the study period.
Conclusion:
Turmeric has the ability to reduce weight, decrease body fat percentage, lower systolic blood pressure, and relieve anxiety for young, obese and overweight females, when given at 2 g/d for 90 d.
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Low levels of antibodies for the oral bacterium Tannerella forsythia predict cardiovascular disease mortality in men with myocardial infarction: A prospective cohort study.
Med Hypotheses2020 Jan;138():109575. doi: S0306-9877(19)31187-9.
Lund Hĺheim Lise, Schwarze P E, Thelle D S, Nafstad P, Rřnningen K S, Olsen I,
Abstract
Antibody levels to periodontal pathogens in prediction of cardiovascular disease (CVD) mortality were explored using data from a health survey in Oslo in 2000 (Oslo II-study) with 12 1/2 years follow-up. IgG antibodies to four common periodontal pathogens; Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all termed collectively the "red complex", and Aggregatibacter actinomycetemcomitans(AA) were analysed. The study sample consisted of 1172 men drawn from a cohort of 6,530 men who participated in the Oslo II-study, where they provided information on medical and dental history. Of the study sample, 548 men had reported prior myocardial infarction (MI) at baseline whereas the remaining 624 men were randomly drawn from the ostensibly healthy participants for comparative analyses. Dental anamnestic information included tooth extractions and oral infections. An inverse relation was found for trend by the quartile risk level of TF predicting CVD mortality, p-value for trend = 0.017. Comparison of the first to fourth quartile of TF antibodies resulted in hazard ratio (HR) = 1.82, 95% confidence interval 1.12-2.94, p = 0.015, adjusted for age, education, diabetes, daily smoking, and systolic blood pressure. Specificity comparing decile 1 to deciles 2-10 of TF predicting mortality was 92.3%. We found an increased HR by low levels of antibodies to the bacterium T. forsythia predicting CVD mortality in a 12 ˝ years follow-up in persons who had experienced an MI but not among non-MI men. This novel finding constitutes a plausible causal link between oral infections and CVD mortality.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Corrigendum to "Effect of resveratrol combined with atorvastatin on re-endothelialization after drug-eluting stents implantation and the underlying mechanism" [Life Sci. 245 (2020) 117349].
Life Sci2020 Feb;247():117434. doi: S0024-3205(20)30182-X.
Chen Changzhe, Song Chenxi, Zhang Dong, Yin Dong, Zhang Rui, Chen Jingzhou, Dou Kefei,
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F-53B and PFOS treatments skew human embryonic stem cell in vitro cardiac differentiation towards epicardial cells by partly disrupting the WNT signaling pathway.
Environ Pollut2020 Feb;261():114153. doi: S0269-7491(19)34986-3.
Yang Renjun, Liu Shuyu, Liang Xiaoxing, Yin Nuoya, Ruan Ting, Jiang Linshu, Faiola Francesco,
Abstract
F-53B and PFOS are two per- and polyfluoroalkyl substances (PFASs) widely utilized in the metal plating industry as mist suppressants. Recent epidemiological studies have linked PFASs to cardiovascular diseases and alterations in heart geometry. However, we still have limited understanding of the effects of F-53B and PFOS on the developing heart. In this study, we employed a human embryonic stem cell (hESC)-based cardiac differentiation system and whole transcriptomics analyses to evaluate the potential developmental cardiac toxicity of F-53B and PFOS. We utilized F-53B and PFOS concentrations of 0.1-60 ?M, covering the levels detected in human blood samples. We demonstrated that both F-53B and PFOS inhibited cardiac differentiation and promoted epicardial specification via upregulation of the WNT signaling pathway. Most importantly, the effects of F-53B were more robust than those of PFOS. This was because F-53B treatment disrupted the expression of more genes and led to lower cardiac differentiation efficiency. These findings imply that F-53B may not be a safe replacement for PFOS.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Cellular signaling in Abdominal Aortic Aneurysm.
Cell Signal2020 Feb;():109575. doi: S0898-6568(20)30052-8.
Li Zhiqing, Kong Wei,
Abstract
Abdominal aortic aneurysms (AAAs) are highly lethal cardiovascular diseases without effective medications. However, the molecular and signaling mechanisms remain unclear. A series of pathological cellular processes have been shown to contribute to AAA formation, including vascular extracellular matrix remodeling, inflammatory and immune responses, oxidative stress, and dysfunction of vascular smooth muscle cells. Each cellular process involves complex cellular signaling, such as NF-?B, MAPK, TGF?, Notch and inflammasome signaling. In this review, we discuss how cellular signaling networks function in various cellular processes during the pathogenesis and progression of AAA. Understanding the interaction of cellular signaling networks with AAA pathogenesis as well as the crosstalk of different signaling pathways is essential for the development of novel therapeutic approaches to and personalized treatments of AAA diseases.
Copyright © 2020. Published by Elsevier Inc.
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Frailty - A promising concept to evaluate disease vulnerability.
Mech Ageing Dev2020 Feb;():111217. doi: S0047-6374(20)30012-9.
Ribeiro Ana Rita, Howlett Susan E, Fernandes Adelaide,
Abstract
With the emergence of diseases, people become frailer and are expected to be less tolerant of adverse outcomes. Frailty was first described to explain the variability in life expectancy in individuals of the same age. Nowadays, it is described as a syndrome and as a state. It is used to explain the heterogeneity of people not only in their responses to biological ageing but also in their responses to illness. In this review, we explore the role of frailty both in age-related diseases, including dementia, cancer and cardiovascular disease, and in non-age-related diseases, such as Human Immunodeficiency Virus. We describe how high levels of frailty in such disorders predict worse outcomes and play a direct role in disease progression and in prognostic prediction. Overall, the potential for frailty to predict adverse health outcomes among young people as well as in non-age-related diseases is an evolving topic. Understanding how frailty contributes to poor health and how it can be modified to prevent or delay disease progression will ultimately enhance quality of life in affected individuals.
Copyright © 2020. Published by Elsevier B.V.
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Phytohormones: Multifunctional nutraceuticals against metabolic syndrome and comorbid diseases.
Biochem Pharmacol2020 Feb;():113866. doi: S0006-2952(20)30094-0.
Woo Kim Seo, Goossens Alain, Libert Claude, Van Immerseel Filip, Staal Jens, Beyaert Rudi,
Abstract
Metabolic syndrome is characterized by the co-occurrence of diverse symptoms initiating the development of type 2 diabetes, cardiovascular diseases, and a variety of comorbid diseases. The complex constellation of numerous comorbidities makes it difficult to develop common therapeutic approaches that ameliorate these pathological features simultaneously. The plant hormones abscisic acid, salicylic acid, auxin, and cytokinins, have shown promising anti-inflammatory and pro-metabolic effects that could mitigate several disorders relevant to metabolic syndrome. Intriguingly, besides plants, human cells and gut microbes also endogenously produce these molecules, indicating a role in the complex interplay between inflammatory responses associated with metabolic syndrome, the gut microbiome, and nutrition. Here, we introduce how bioactive phytohormones can be generated endogenously and through the gut microbiome. These molecules subsequently influence immune responses and metabolism. We also elaborate on how phytohormones can beneficially modulate metabolic syndrome comorbidities, and propose them as nutraceuticals.
Copyright © 2020 Elsevier Inc. All rights reserved.
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A Randomized Placebo Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate to Severe Plaque Psoriasis (VIP-S).
J Invest Dermatol2020 Feb;():. doi: S0022-202X(20)30157-3.
Gelfand Joel M, Shin Daniel B, Duffin Kristina Callis, Armstrong April W, Blauvelt Andrew, Tyring Stephen K, Menter Alan, Gottlieb Scott, Lockshin Benjamin N, Simpson Eric L, Kianifard Farid, Sarkar Rajendra Prasad, Muscianisi Elisa, Steadman Jennifer, Ahlman Mark A, Playford Martin P, Joshi Aditya A, Dey Amit K, Werner Thomas J, Alavi Abass, Mehta Nehal N,
Abstract
BACKGROUND:
Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has demonstrated high efficacy with a favorable safety profile in various psoriatic disease manifestations.
TRIAL DESIGN AND METHODS:
Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, moderate-to-severe psoriasis patients received secukinumab for 40 weeks. Vascular inflammation using FDG-PET/CT imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52.
RESULTS:
The difference in change in aortic inflammation from baseline to Week 12 for secukinumab (N=46) versus placebo (N=45) was -0.053 (95% CI: -0.169, 0.064; P=0.37). Small increases in total cholesterol, LDL, and LDL particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At Week 52, reductions in TNF-? (P=0.0063) and ferritin (P=0.0354), and an increase in fetuin A (P=0.0024), were observed with secukinumab treatment compared to baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared to baseline.
CONCLUSION:
Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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ABCG5 and ABCG8 genetic variants in familial hypercholesterolemia.
J Clin Lipidol2020 Jan;():. doi: S1933-2874(20)30007-6.
Reeskamp Laurens F, Volta Andrea, Zuurbier Linda, Defesche Joep C, Hovingh G Kees, Grefhorst Aldo,
Abstract
BACKGROUND:
Familial hypercholesterolemia (FH) is a common inherited disease characterized by elevated low-density lipoprotein cholesterol (LDL-C) plasma levels and increased cardiovascular disease risk. Most patients carry a mutation in the low-density lipoprotein receptor gene (LDLR). Common and rare variants in the genes encoding adenosine triphosphate-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) have been shown to affect LDL-C levels.
OBJECTIVE:
The objective of this study was to investigate whether and to which extent heterozygous variants in ABCG5 and ABCG8 are associated with the hypercholesterolemic phenotype.
METHODS:
We sequenced ABCG5 and ABCG8 in a cohort of 3031 clinical FH patients and compared the prevalence of variants with a European reference population (gnomAD). Clinical characteristics of carriers of putative pathogenic variants in ABCG5 and/or ABCG8 were compared with heterozygous carriers of mutations in LDLR. Furthermore, we assessed the segregation of one ABCG5 and two ABCG8 variants with plasma lipid and sterol levels in three kindreds.
RESULTS:
The frequencies of (likely) pathogenic LDLR, APOB, PCSK9, ABCG5, and ABCG8 variants in our FH cohort were 11.42%, 2.84%, 0.69%, 1.48%, and 0.96%, respectively. We identified 191 ABCG5 and ABCG8 variants of which 53 were classified as pathogenic or likely pathogenic. Of these 53 variants, 51 were either absent from a reference population or more prevalent in our FH cohort than in the reference population. LDL-C levels were significantly lower in heterozygous carriers of a (likely) pathogenic ABCG5 or ABCG8 variant compared to LDLR mutation carriers (6.2 ± 1.7 vs 7.2 ± 1.7 mmol/L, P < .001). The combination of both an ABCG5 or ABCG8 variant and a LDLR variant was found not to be associated with significant higher LDL-C levels (7.8 ± 2.3 vs 7.2 ± 1.7 mmol/L, P = .259). Segregation analysis in three families (nine carriers, in addition to the index cases, and 16 noncarriers) did not show complete segregation of the ABCG5/G8 variants with high LDL-C levels, and LDL-C levels were not different (3.9 ± 1.3 vs 3.5 ± 0.6 mmol/L in carriers and noncarriers, respectively, P = .295), while plasma plant sterol levels were higher in carriers compared to noncarriers (cholestanol: 10.2 ± 1.7 vs 8.4 ± 1.6 ?mol/L, P = .007; campesterol: 22.5 ± 10.1 vs 13.4 ± 3.5 ?mol/L, P = .008; sitosterol: 17.0 ± 11.6 vs 8.2 ± 2.6 ?mol/L, P = .024).
CONCLUSIONS:
2.4% of subjects in our FH cohort carried putative pathogenic ABCG5 and ABCG8 variants but had lower LDL-C levels compared to FH patients who were heterozygous carriers of an LDLR variant. These results suggest a role for these genes in hypercholesterolemia in FH patients with less severely elevated LDL-C levels. We did not find evidence that these variants cause autosomal dominant FH.
Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.
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Homozygous familial hypercholesterolemia in a young woman with dual gene mutations of low-density lipoprotein receptor and proprotein convertase subtilisin/kexin type 9.
J Clin Lipidol2020 Jan;():. doi: S1933-2874(20)30009-X.
Suppressa Patrizia, Carbonara Concetta, Scialpi Natasha, Ciavarella Alessandro, Sabbŕ Carlo,
Abstract
A 28-year-old woman with a rare combination of homozygous LDLR and heterozygous PCSK9 mutations had a phenotype consistent with homozygous familial hypercholesterolemia. She reported a clinical history of coronary and extracoronary atherosclerosis treated with 3 coronary stenting procedures, one coronary bypass, and aortic and mitral valve replacements. Because the patient refused lipoprotein apheresis, lipid-lowering therapy with statins, ezetimibe, and evolocumab was started. The desired low-density lipoprotein cholesterol target was not achieved. Dose-escalated lomitapide therapy (up to 30 mg/d) was added, enabling achievement of low-density lipoprotein cholesterol levels of 45 mg/dL during 24 months' follow-up. During this period, no cardiovascular events or clinical evidence of side effects occurred. In this case, lomitapide has been used in combination with maximum-tolerated statin therapy to successfully treat a patient with a rare combination of mutations in both LDLR and PCSK9 genes.
Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.
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Answers to "Comment on "Cardiovascular disease and long-term occupational exposure to ultrafine particles: A cohort study of airport workers" by Mřller KL et al., 2019".
Int J Hyg Environ Health2020 Feb;():113477. doi: S1438-4639(20)30100-0.
Mřller Karina Lauenborg, Brauer Charlotte, Mikkelsen Sigurd, Bonde Jens Peter, Helweg-Larsen Karin, Thygesen Lau Caspar,
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Discovery of 1,8-naphthyridin-2-one derivative as a potent and selective sphingomyelin synthase 2 inhibitor.
Bioorg Med Chem2020 Feb;():115376. doi: S0968-0896(20)30172-3.
Yukawa Takafumi, Nakahata Takashi, Okamoto Rei, Ishichi Yuji, Miyamoto Yasufumi, Nishimura Satoshi, Oikawa Tatsuo, Kubo Kazuki, Adachi Ryutaro, Satomi Yoshinori, Nakakariya Masanori, Amano Nobuyuki, Kamaura Masahiro, Matsunaga Nobuyuki,
Abstract
Sphingomyelin synthase 2 (SMS2) has attracted attention as a drug target for the treatment of various cardiovascular and metabolic diseases. The modification of a high throughput screening hit, 2-quinolone 10, enhanced SMS2 inhibition at nanomolar concentrations with good selectivity against SMS1. To improve the pharmaceutical properties such as passive membrane permeability and aqueous solubility, adjustment of lipophilicity was attempted and 1,8-naphthyridin-2-one 37 was identified as a potent and selective SMS2 inhibitor. A significant reduction in hepatic sphingomyelin levels following repeated treatment in mice suggested that compound 37 could be an effective in vivo tool for clarifying the role of SMS2 enzyme and developing the treatment for SMS2-related diseases.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Cardiac adverse events during stem cell transplantation for hematological malignancies: A single centre experience.
Transfus Apher Sci2020 Feb;():102653. doi: S1473-0502(19)30217-4.
Aladag Elifcan, Demiroglu Haluk, Buyukasik Yahya, Karakulak Ugur N, Tekin Fatma, Aksu Salih, Goker Hakan,
Abstract
Hematopoietic stem cell transplantation (HSCT) is a highly successful treatment option for many hematological malignancies. Several adverse effects can be seen in HSCT due to the infusion and damage caused by the conditioning regimens. Cardiovascular adverse effects are relatively common during HSCT, and they have the potential to cause devastating complications. The aim of present study was to evaluate the transplantation-related cardiac adverse effects and determine the risk factors in patients undergoing HSCT at our institution. A retrospective analysis has been performed in 662 patients who was treated at Hacettepe University Stem Cell Transplantation Unit. Amongst the 622 patients, 318 (51.1 %) underwent autologous and 304 (48.9 %) underwent allogeneic HSCT. The frequency of the cardiac adverse effects was found to be 10.8 % in all the study population. The most common adverse effect was tachyarrhythmia, constituting 7.9 % of all population. These adverse effects were mostly occurred in lymphoma patients (14 %). Nineteen (3.0 %) of all patients developed atrial fibrillation mostly on the 4th day (range of 1-9 days) after transplantation. Life-threatening events are extremely rare. These adverse effects appear to be related to the type of transplantation rather than the underlying disease. Therefore, close follow-up of patients is important during the peri-transplantation period.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation.
J Heart Lung Transplant2020 Jan;():. doi: S1053-2498(20)31363-2.
Kirk Richard, Dipchand Anne I, Davies Ryan R, Miera Oliver, Chapman Gretchen, Conway Jennifer, Denfield Susan, Gossett Jeffrey G, Johnson Jonathan, McCulloch Michael, Schweiger Martin, Zimpfer Daniel, Ablonczy László, Adachi Iki, Albert Dimpna, Alexander Peta, Amdani Shahnawaz, Amodeo Antonio, Azeka Estela, Ballweg Jean, Beasley Gary, Böhmer Jens, Butler Alison, Camino Manuela, Castro Javier, Chen Sharon, Chrisant Maryanne, Christen Urs, Danziger-Isakov Lara, Das Bibhuti, Everitt Melanie, Feingold Brian, Fenton Matthew, Garcia-Guereta Luis, Godown Justin, Gupta Dipankar, Irving Claire, Joong Anna, Kemna Mariska, Khulbey Sanjeev Kumar, Kindel Steven, Knecht Kenneth, Lal Ashwin K, Lin Kimberly, Lord Karen, Möller Thomas, Nandi Deipanjan, Niesse Oliver, Peng David M, Pérez-Blanco Alicia, Punnoose Ann, Reinhardt Zdenka, Rosenthal David, Scales Angie, Scheel Janet, Shih Renata, Smith Jonathan, Smits Jacqueline, Thul Josef, Weintraub Robert, Zangwill Steve, Zuckerman Warren A,
Abstract
The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.
Copyright © 2020 International Society for Heart and Lung Transplantation. All rights reserved.
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[Update on cholesterol crystal embolism].
Rev Med Interne2020 Feb;():. doi: S0248-8663(20)30044-8.
Denis Le Seve J, Gourraud Vercel C, Connault J, Artifoni M,
Abstract
Cholesterol crystal embolism is a systemic pathology associated with diffuse atherosclerosis. Pathophysiology corresponds to tissue necro-inflammation secondary to arteriolar occlusion associated with microembolism from atherosclerotic plaques of large diameter arteries. The clinical presentation is heterogeneous and polymorphic. Multiple organs may be the targets, but preferential damage is skin, kidneys and digestive system. It is a serious pathology, underdiagnosed, with a poor prognosis. The risk factors for developing the disease remain the same risk factors as atheroma. The factors favouring migration of microembolism remain mainly vascular interventional procedures; easy to diagnose, they oppose spontaneous embolic migrations or secondary to the introduction of antithrombotic treatment, whose diagnosis is more difficult and the prognosis more severe. The diagnosis of the disease remains mostly a diagnosis of elimination and often refers to a bundle of clinical, biological, morphological and histologic arguments. The treatment is poorly codified and the subject of few publications. It will favour both symptomatic treatment (and mainly that of pain) and complications (high blood pressure, renal insufficiency). The aetiological support remains less consensual. The treatment of atherosclerotic plaques consists, of course, in the correction of classical cardiovascular risk factors, the introduction of a statin. It will be discussed in the implementation of surgery or angioplasty to exclude potentially responsible atherosclerotic lesions. Eviction of antithrombotic therapy should be considered in terms of the benefit-risk balance, but often in favour of maintaining it. Finally, other treatments may be proposed in a case-by-case basis, such as oral or intravenous corticosteroid therapy, colchicine or LDL aphaeresis.
Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.
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