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BACKGROUND: The "Place Standard Tool" (PST) offers a practical framework for structuring conversations about physical and social dimensions of Place which impact on health and well-being. The aim of this study was to survey citizens' perceptions of Place across diverse settings in Cyprus. While the PST has been extensively used in the context of community engagement, its properties as a measurement tool haven't been explored. METHODS: An open call was addressed to citizens to rate their neighbourhood environment across the 14 PST items (1: large to 7: little room for improvement). Exploratory factor, cluster and regression analyses were used to explore the dimensionality of the scale, depict neighbourhood profiles and explore differences in ratings according to socio-demographic characteristics, area-level census indicators and residents' assessment of neighbourhood social position (10-step ladder). RESULTS: With the exception of safety (M = 4.4, SD = 1.7), 492 participants (mean age 42, 50% residents for > 10 years) from 254 postcodes (21.7% islandwide) did not rate other features favourably, with lowest scores for "influence and sense of control" and "public transport". A stepwise pattern of dissatisfaction was observed along the social position continuum both for features rated less as well as more favourably (e.g. social contact). For instance, among participants who placed their neighbourhood at the three top steps of the ladder, 48.8% gave a low rating for "influence and sense of control", while the equivalent figure was 81.0% at the bottom three steps (OR = 4.5, 95% CI 2.3, 8.6). A clear dimensionality of Built (6 items, Cronbach's α = 0.798), Physical (3 items, α = 0.765), Social (2 items, α = 0.749) and Service (3 items, α = 0.58) environment was identified. A social gradient was evident according to census measures of socio-economic disadvantage (e.g. pre-1980 housing, single-parent households) with larger differences in terms of the built than the social environment. CONCLUSIONS: The study profiled the variability and documented the inequity in the health-related neighbourhood environment across Cypriot communities. The readily interpretable dimensionality of the scale supports its construct validity, allowing calculation of composite scores. The PST can be used as measurement tool in research as well as public health practice to advocate for neighbourhood initiatives which support and enhance citizens' participation.
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Características de la Residencia , Medio Social , Adulto , Estudios Transversales , Chipre , Humanos , Internet , Encuestas y CuestionariosRESUMEN
BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Inhibidores de PCSK9 , Polimorfismo de Nucleótido Simple , Proproteína Convertasa 9/genética , Inhibidores de Serina Proteinasa/uso terapéutico , Anticolesterolemiantes/efectos adversos , Biomarcadores/sangre , Isquemia Encefálica/epidemiología , Isquemia Encefálica/prevención & control , Regulación hacia Abajo , Dislipidemias/sangre , Dislipidemias/epidemiología , Estudio de Asociación del Genoma Completo , Humanos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Inhibidores de Serina Proteinasa/efectos adversos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with kidney dysfunction are at risk of developing ischaemic heart disease. We investigated the association between eGFR and early-, mid- and long-term clinical outcome in patients undergoing coronary angiography and intervention. METHODS: Retrospective study on 4968 patients with complete data on eGFR, 65% male and aged 32-80 years, admitted to Danderyd University Hospital, Stockholm, Sweden for coronary angiography and intervention from 2006 to 2008. Data were censored at 0-30 days, 31-365 days and 366-1825 days of follow-up. RESULTS: Baseline eGFR was strongly associated with all-cause mortality at all three time periods studied with each 10 ml/min per 1.73 m2 increase in eGFR being associated with a â¼30% (p < .001), 25% (p = .002) and 20% (p < .001) decrease in all-cause mortality at 30, 365 and 1825 days respectively. Each 10 ml/min per 1.73 m2 increase in eGFR was associated with a â¼21% (p < .001) decrease in re-hospitalisation for MI at 365 days and a 6% decrease (p = .03) at day 30 for re-vascularisation. CONCLUSIONS: We report a strong association between kidney function and all-cause mortality at both early, mid- and long-term follow-up in patients undergoing coronary angiography and intervention, with eGFR significantly associated with MI-related mortality after one month of follow-up. Kidney function was also shown to be associated with risk for re-vascularisation at one month, indicating mostly procedural-related risk and with new MI at mid-term follow-up. Further research is warranted to explore the mechanisms linking kidney function and cardiovascular disease to improve both the short- and long-term care of these patients.
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Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/etiología , Tasa de Filtración Glomerular/fisiología , Riñón/fisiopatología , Revascularización Miocárdica/métodos , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Suecia/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Media messages have been used in Ghana to promote insecticide-treated net (ITN)/bed net usage in an effort to impact on malaria prevention. The aim of this study was to assess the effect of such malaria-related messages delivered through electronic/print media and by volunteers/health workers on the use of ITNs by children living in a household. METHODS: Data was collected from September to November of 2008 using a structured, interviewer-administered questionnaire by the Ghana Statistical Service as part of a national demographic and health survey (DHS). Secondary data analysis was performed on the collected data using multivariate logistic regression for both individual messages and a composite (any of) message variable. RESULTS: From the 11,788 households surveyed, 45% had at least one net. Households with male heads were more likely to have a child sleeping under a bed net the previous night (p = 0.0001). Individual Messages delivered by a health worker or a dedicated radio programme, had the highest effect for one or more children sleeping under a net the night before (OR(adjusted) = 1.65; 95% CI = 1.44 to 1.88 and OR(adjusted) = 1.26; 95% CI =1.12 to 1.42 respectively) while hearing any of the eight messages (composite score) resulted in the highest odds for one or more children (OR(adjusted) = 3.06; 95% CI = 2.27 to 4.12) sleeping under a bed net. CONCLUSION: Efforts to relate ITN messages to the public are very useful in increasing use of bed nets and having multiple ways of reaching the public increases their effect, with the biggest effect seen when health workers and volunteers were used to deliver malaria-related messages to the public.
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Comunicación , Conocimientos, Actitudes y Práctica en Salud , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Malaria/prevención & control , Adulto , Niño , Preescolar , Femenino , Ghana , Personal de Salud , Encuestas Epidemiológicas , Humanos , Insecticidas/farmacología , Masculino , Medios de Comunicación de Masas , Persona de Mediana Edad , Control de Mosquitos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field. RESEARCH DESIGN AND METHODS: A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform. RESULTS: Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department). CONCLUSIONS: Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.
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We aimed to test the association between matrix metalloproteinase (MMP) genetic polymorphisms and (a) intima-media thickness in the common carotid (IMTcc) and (b) the presence of plaques in the carotid and femoral bifurcations. Carotid and femoral bifurcations were scanned with ultrasound in 762 Cypriot community dwellers (46% men) over the age of 40 years. IMTcc and the presence of plaques were recorded. The MMP1 1G/2G, MMP3 5A/6A, MMP7 -181A>G, MMP9 R279Q, and MMP12 -82A>G polymorphisms were determined with the TaqMan method. In men, the presence of plaques in any bifurcation was associated with the MMP9 279Q allele (OR adjusted=4.50; 95% CI=2.0 to 10.1; p<0.001) and the MMP7 -181A allele was associated with the presence of femoral plaques (OR adjusted=2.61; 95% CI=1.36 to 4.99; p=0.004). In women, the presence of femoral plaques was associated with the MMP12 -82G allele (OR adjusted=1.9; 95% CI=1.14 to 3.16; p=0.014). Our results suggest that the effect of common MMP genotypes on plaque presence may be site- and sex-dependent.
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Grosor Intima-Media Carotídeo , Metaloproteinasas de la Matriz/genética , Placa Aterosclerótica/enzimología , Placa Aterosclerótica/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/genética , Chipre , Femenino , Arteria Femoral/diagnóstico por imagen , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 7 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagenRESUMEN
OBJECTIVES: Reported reductions in emergency department visits and hospitalizations for asthma in previous studies have suggested a beneficial effect of the coronavirus disease of 2019 (COVID-19) lockdown measures on asthma morbidity. Nevertheless, studies relying on administrative data may overestimate the true impact of lockdowns due to changes in health-seeking behavior and reduced availability of pediatric asthma services during the pandemic. In this study, we systematically reviewed the literature and identified observational cohort studies that focused on nonadministrative data to assess the true impact of COVID-19 lockdowns on symptom control in children with asthma. METHODS: A systematic literature search was conducted between January 2020 and August 2022 (International Prospective Register of Systematic Reviews ID: CRD42022354369). The impact of COVID-19 lockdowns across studies was expressed as a standardized mean difference (SMD) for continuous outcomes and as a summary relative risk (RR) for binary outcomes. RESULTS: During the lockdown periods, the pooled asthma symptoms control test score (SMD: 1.99, 95% confidence interval [CI]: 0.75, 3.24, I2 : 98.4%) and the proportion of children with well-controlled asthma (RR: 1.35, 95% CI: 1.06, 1.71, I2 : 77.6%) were significantly increased. On the other hand, the pooled proportion of children with poorly controlled asthma (RR: 0.47, 95% CI: 0.38, 0.57, I2 : 0.0%) was significantly decreased. CONCLUSIONS: During COVID-19 lockdowns, asthma symptoms and breakthrough disease exacerbations were significantly reduced in children with asthma. Further research is warranted on potential interventions aiming to enhance asthma control after the pandemic while taking into consideration their acceptability and potential tradeoffs.
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Asma , COVID-19 , Niño , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Asma/epidemiología , Progresión de la Enfermedad , Hospitalización , Estudios Observacionales como AsuntoRESUMEN
The Consequentialist Scale (Robinson, 2012) [89] assesses the endorsement of consequentialist and deontological moral beliefs. This study empirically investigated the application of the Greek translation of the Consequentialist Scale in a sample of native Greek speakers. Specifically, 415 native Greek speakers completed the questionnaire. To uncover the underlying structure of the 10 items in the Consequentialist Scale, an Exploratory Factor Analysis (EFA) was conducted. The results revealed a three-factor solution, where the deontology factor exhibited the same structure as the original work by Robinson (2012) [89], while the original consequentialism factor split into two separate factors. Significant Pearson's r correlations were observed between age and responses to the Consequentialist Scale. Separate EFAs were conducted for two age groups based on a medial split: younger (36 years old or less) and older (more than 36 years old). Interestingly, the younger group exhibited a two-factor solution with the same structure as the original work, while the older group showed a three-factor solution. A hierarchical k-means cluster analysis revealed that the cluster of participants who scored higher in deontology compared to consequentialism primarily consisted of older participants, whereas the two other clusters comprised of younger participants exhibited the reverse pattern. Neither gender nor previous experience with philosophy significantly affected scores on the Consequentialist Scale. Overall, our study provides evidence that the Consequentialist Scale is suitable for use in the Greek population.
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BACKGROUND: Vascular age (VA) is independent and chronological age for assessing cardiovascular disease (CVD) risk. However, tools for the implementation of VA are currently lacking. We aimed to develop a questionnaire to assess the current knowledge gaps related to VA and barriers to its implementation in routine practice. METHODS: Using a stepwise mixed-method approach, a quantitative questionnaire was constructed in four phases: (1) basic item generation and the development of a semi-qualitative questionnaire (SQQ); (2) dissemination to the VascAgeNet extended network and an analysis of the semi-qualitative questionnaire responses; (3) the development of a quantitative questionnaire (QQ); and (4) an assessment of the content and face validity and internal reliability in an additional sample. RESULTS: Based on six main topics initially identified through an expert panel, a SQQ was developed and disseminated. Finally, a 22-item QQ was developed, with questions grouped around three main themes: knowledge of VA and its risk factors; perceptions and beliefs regarding the importance and contribution of VA to risk classification; and the application of VA measurements in clinical and research practice and its potential limitations (Cronbach's alpha between 0.920 and 0.982 for all three categories). CONCLUSION: We report the development of a QQ on VA addressed to both clinicians and non-clinicians aiming to assess their knowledge, perceptions and application of VA measurements.
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Desert dust storms (DDS) are natural events that impact not only populations close to the emission sources but also populations many kilometers away. Countries located across the main dust sources, including countries in the Eastern Mediterranean, are highly affected by DDS. In addition, climate change is expanding arid areas exacerbating DDS events. Currently, there are no intervention measures with proven, quantified exposure reduction to desert dust particles. As part of the wider "MEDEA" project, co-funded by LIFE 2016 Programme, we examined the effectiveness of an indoor exposure-reduction intervention (i.e., decrease home ventilation during DDS events and continuous use of air purifier during DDS and non-DDS days) across homes and/or classrooms of schoolchildren with asthma and adults with atrial fibrillation in Cyprus and Crete-Greece. Participants were randomized to a control or intervention groups, including an indoor intervention group with exposure reduction measures and the use of air purifiers. Particle sampling, PM10 and PM2.5, was conducted in participants' homes and/or classrooms, between 2019 and 2022, during DDS-free weeks and during DDS days for as long as the event lasted. In indoor and outdoor PM10 and PM2.5 samples, mass and content in main and trace elements was determined. Indoor PM2.5 and PM10 mass concentrations, adjusting for premise type and dust conditions, were significantly lower in the indoor intervention group compared to the control group (PM2.5-intervention/PM2.5-control = 0.57, 95% CI: 0.47, 0.70; PM10-intervention/PM10-control = 0.59, 95% CI: 0.49, 0.71). In addition, the PM2.5 and PM10 particles of outdoor origin were significantly lower in the intervention vs. the control group (PM2.5 infiltration intervention-to-control ratio: 0.49, 95% CI: 0.42, 0.58; PM10 infiltration intervention-to-control ratio: 0.68, 95% CI: 0.52, 0.89). Our findings suggest that the use of air purifiers alongside decreased ventilation measures is an effective protective measure that reduces significantly indoor exposure to particles during DDS and non-DDS in high-risk population groups.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Oligoelementos , Adulto , Humanos , Niño , Contaminación del Aire Interior/prevención & control , Contaminación del Aire Interior/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Polvo/prevención & control , Polvo/análisis , Material Particulado/análisis , Tamaño de la PartículaRESUMEN
AIM: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. METHODS AND RESULTS: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD -1.99; 95% CI (-3.49 to -0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). CONCLUSIONS: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study.
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BACKGROUND: SCORE2 and SCORE2-OP algorithms and associated online calculators provide a new and easy method of estimating the 10-year cardiovascular risk in apparently healthy Europeans. The aim of the study was to determine the performance of these algorithms in terms of discrimination and calibration in the cohort of the Cyprus Epidemiological Study on Atherosclerosis (CESA), not only for the 10-year risk for myocardial infarction (MI), stroke and cardiovascular death, but also for all types of atherosclerotic cardiovascular events (ASCVE). METHODS: SCORE2 and SCORE2-OP for low-risk regions were calculated in a non-diabetic subset of CESA consisting of 908 people (mean age±SD: 57.8±10.5; range 40-89; 58.8% female) using baseline risk factors. Mean follow-up was 13.2±3.7 years (range 1-17) with 89 primary endpoints (MI, stroke and cardiovascular death) and 136 secondary endpoints (primary endpoints, angina, cardiac failure, coronary revascularization, transient ischemic attack, claudication and critical limb ischemia). RESULTS: The C-statistic for the prediction of the primary endpoint for all ages was 0.76 (95% CI 0.70 to 0.81) and the observed 10-year event rate was similar to the predicted one. However, the observed 10-year rate for secondary events was similar to the estimated one only when the algorithm for high-risk regions was used. CONCLUSIONS: SCORE2 and SCORE2-OP moderate risk algorithms perform well in the Cypriot population for predicting the 10-year risk for MI, stroke and fatal cardiovascular disease. However, an estimate of the 10-year risk for all ASCVD events is best calculated from the high-risk algorithm.
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Aterosclerosis , Enfermedades Cardiovasculares , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Medición de Riesgo/métodos , Infarto del Miocardio/epidemiología , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , AlgoritmosRESUMEN
BACKGROUND: Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown. OBJECTIVES: Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction. METHODS: We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE. RESULTS: Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively. CONCLUSIONS: NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort.
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Aterosclerosis , Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Adulto , Anciano , Aterosclerosis/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Humanos , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Factores de Riesgo , UltrasonografíaRESUMEN
After publishing an in-depth study that analyzed the ability of computerized methods to assist or replace human experts in obtaining carotid intima-media thickness (CIMT) measurements leading to correct therapeutic decisions, here the same consortium joined to present technical outlooks on computerized CIMT measurement systems and provide considerations for the community regarding the development and comparison of these methods, including considerations to encourage the standardization of computerized CIMT measurements and results presentation. A multi-center database of 500 images was collected, upon which three manual segmentations and seven computerized methods were employed to measure the CIMT, including traditional methods based on dynamic programming, deformable models, the first order absolute moment, anisotropic Gaussian derivative filters and deep learning-based image processing approaches based on U-Net convolutional neural networks. An inter- and intra-analyst variability analysis was conducted and segmentation results were analyzed by dividing the database based on carotid morphology, image signal-to-noise ratio, and research center. The computerized methods obtained CIMT absolute bias results that were comparable with studies in literature and they generally were similar and often better than the observed inter- and intra-analyst variability. Several computerized methods showed promising segmentation results, including one deep learning method (CIMT absolute bias = 106 ± 89 µm vs. 160 ± 140 µm intra-analyst variability) and three other traditional image processing methods (CIMT absolute bias = 139 ± 119 µm, 143 ± 118 µm and 139 ± 136 µm). The entire database used has been made publicly available for the community to facilitate future studies and to encourage an open comparison and technical analysis (https://doi.org/10.17632/m7ndn58sv6.1).
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Arterias Carótidas , Grosor Intima-Media Carotídeo , Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Común/diagnóstico por imagen , Humanos , Ultrasonografía/métodos , Ultrasonografía DopplerRESUMEN
BACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Enfermedad Coronaria/epidemiología , Fosfolipasas A2/genética , Estudios de Casos y Controles , Enfermedad Coronaria/enzimología , Enfermedad Coronaria/genética , Estudios Transversales , Europa (Continente) , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Estudios Prospectivos , Factores de RiesgoRESUMEN
Common carotid intima-media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts' manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan-Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.1.
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Algoritmos , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Anciano , Sistemas de Computación , Femenino , Humanos , Masculino , Persona de Mediana Edad , UltrasonografíaRESUMEN
PURPOSE OF THE REVIEW: Validated tools to improve cardiovascular disease (CVD) risk assessment and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. Noninvasive measures of arteriosclerosis and subclinical atherosclerosis such as pulse wave velocity (PWV) and carotid intima-media thickness (cIMT), respectively, have emerged as promising risk stratification tools and potential modifiable biomarkers. Their wide use as surrogate markers in clinical research studies is based on the strong pathophysiological links with CVD. However, whether their effect as risk stratification or intervention targets is superior to established clinical approaches is uncertain. In this review, we examine the evidence on the utility of PWV, cIMT, and plaque assessment in routine practice and highlight unanswered questions from the clinician's perspective. SOURCES OF INFORMATION: Electronic databases PubMed and Google Scholar were searched until February 2020. METHODS: This narrative review is based on peer-reviewed meta-analyses, national and international societies' guidelines, and on focused critical review of recent original studies and landmark studies in the field. KEY FINDINGS: Although patients with CKD are considered in the high-risk CVD groups, there is still need for tools to improve risk stratification and individualized management strategies within this group of patients. Carotid intima-media thickness is associated with all-cause mortality, CVD mortality, and events in CKD and hemodialysis cohorts. However, the evidence that measurement of cIMT has a clinically meaningful role over and above existing risk scores and management strategies is limited. Plaque assessment is a better predictor than cIMT in non-CKD populations and it has been incorporated in recent nonrenal-specific guidelines. In the CKD population, one large observational study provided evidence for a potential role of plaque assessment in CKD similar to the non-CKD studies; however, whether it improves prediction and outcomes in CKD is largely understudied. Pulse wave velocity as a marker of arterial stiffness has a strong pathophysiological link with CVD in CKD and numerous observational studies demonstrated associations with increased cardiovascular risk. However, PWV did not improve CVD reclassification of dialysis patients when added to common risk factors in a reanalysis of ESRD cohorts with available PWV data. Therapeutic strategies to regress PWV, independently from blood pressure reduction, have not been studied in well-conducted randomized trials. LIMITATIONS: This study provides a comprehensive review based on extensive literature search and critical appraisal of included studies. Nevertheless, formal systematic literature review and quality assessment were not performed and the possibility of selection bias cannot be excluded. IMPLICATIONS: Larger, prospective, randomized studies with homogeneous approach, designed to answer specific clinical questions and taking into consideration special characteristics of CKD and dialysis, are needed to study the potentially beneficial role of cIMT/plaque assessment and PWV in routine practice.
JUSTIFICATION: Les outils validés pour faciliter l'évaluation des risques de maladies cardiovasculaires (MCV) et de mortalité chez les patients atteints d'insuffisance rénale terminale (IRT) sont insuffisants. Les mesures non invasives de l'artériosclérose et de l'artériosclérose infraclinique, respectivement la vitesse de l'onde de pouls (VOP) et la mesure de l'épaisseur intima-média de la carotide (EIMc), sont apparues comme des outils prometteurs de stratification des risques et des biomarqueurs potentiellement modifiables. L'usage répandu de la VOP et de l'EIMc comme marqueurs de substitution dans les études cliniques est fondé sur leurs liens physiopathologiques étroits avec les MCV. On ignore toutefois si leur effet pour la stratification des risques ou comme cibles d'intervention est supérieur aux approches cliniques établies. Cette revue examine les données probantes sur la pertinence des mesures de VOP et d'EIMc et de l'analyse plaquettaire dans les pratiques courantes et met en lumière les questions sans réponses du point de vue du clinicien. SOURCES: Les bases de données PubMed et Google Scholar ont été consultées jusqu'en février 2020. MÉTHODOLOGIE: Cette revue narrative est fondée sur des méta-analyses révisées par les pairs, sur les lignes directrices de sociétés nationales et internationales et sur un examen critique et ciblé des études originales récentes et d'études phares dans le domaine. PRINCIPAUX RÉSULTATS: Bien que les patients atteints d'IRT fassent déjà partie des groupes présentant un risque élevé de MCV, l'ajout d'outils pour améliorer la stratification des risques et de stratégies de gestion individualisées est toujours nécessaire pour ce groupe de patients. L'EIMc est associée à la mortalité toutes causes, ainsi qu'aux risques d'événements cardiovasculaires et de mortalité liée aux MCV dans les cohortes de patients atteints d'IRT et hémodialysés. Les preuves soutenant un rôle cliniquement significatif de la mesure de l'EMIc au-delà des scores de risque et des stratégies de gestion existantes sont toutefois limitées. L'analyse plaquettaire s'avère un meilleur prédicteur que l'EIMc dans les populations non atteintes d'IRT et a récemment été intégrée aux lignes directrices non liées aux maladies rénales. Dans les populations atteintes d'IRT, une vaste étude observationnelle a fourni des preuves quant à un possible rôle de l'analyse plaquettaire similaire à celui rapporté dans les études ne portant pas sur des patients atteints d'IRT. Cependant, la question de savoir si cette mesure améliore la prédiction et les résultats des patients atteints d'IRT demeure largement sous-étudiée. La VOP, à titre de marqueur de la rigidité artérielle, a un lien physiopathologique fort avec les MCV en contexte d'IRT, plusieurs études observationnelles ayant démontré des associations avec un risque accru d'événements cardiovasculaires. Par contre, la VOP n'a pas amélioré le reclassement cardiovasculaire des patients dialysés lorsqu'on l'a ajoutée aux facteurs de risques communs dans une nouvelle analyse des cohortes de patients atteints d'IRT disposant de données de VOP. Les stratégies thérapeutiques pour réduire la VOP, indépendamment de la pression artérielle, n'ont pas été étudiées dans le cadre d'essais à répartition aléatoire bien menés. LIMITES: Cette étude fournit une revue complète fondée sur une recherche documentaire approfondie et une évaluation critique des études incluses. Cependant, aucune analyse documentaire systématique formelle ou d'évaluation de la qualité n'ont été effectuées et un biais de sélection ne peut être exclu. CONCLUSION: L'étude d'un rôle potentiellement bénéfique des mesures de VOP et d'EIMc et de l'analyse plaquettaire dans la pratique courante en contexte d'IRT requiert des essais prospectifs de grande envergure avec répartition aléatoire. Ces essais devraient s'articuler autour d'une approche homogène, être conçus pour répondre à des questions cliniques spécifiques et tenir compte des caractéristiques propres aux patients atteints d'IRT et dialysés.
RESUMEN
BACKGROUND: Non-invasive cardiovascular disease (CVD) risk prediction, in subclinical stages, aiming to stratify patients and tailor interventions remains an unmet need in chronic kidney disease (CKD). In this meta-analysis, we summarize the association of carotid intima-media thickness (cIMT), coronary artery calcium score (CACS) and pulse wave velocity (PWV) with all-cause mortality, cardiovascular (CV) mortality and CV events in non-dialysis CKD and patients on haemodialysis. METHODS: Systematic review and meta-analysis of prospective cohort studies. RESULTS: Out of 27 984 records, a total of 45 studies were eligible for quantitative synthesis; 11 for cIMT, 18 for CACS and 16 for PWV involving 2235, 4904 and 5717 patients, respectively. Meta-analysis was possible from pooled data of five cIMT studies (708 subjects), eight CACS studies (862 subjects) and nine PWV studies (1508 subjects). In dialysis patients, cIMT was associated with all-cause mortality [relative risk (RR) per unit increase: 1.08, 95% confidence interval (CI) 1.00-1.17, I 2: 68%] and CV mortality (RR: 1.29, 95% CI 1.14-1.47, I 2: 0%). High versus low CACS was associated with all-cause mortality (RR: 2.51, 95% CI 1.66-3.79, I 2: 5.7%) and CV events (RR: 3.77 95% CI 2.16-6.58, I 2: 20.2%). High versus low PWV was associated with all-cause (RR: 5.34, 95% CI 3.01-9.47, I 2: 0%) and CV mortality (RR: 8.55, 95% CI 4.37-16.73, I 2: 0%). The combined estimated for all-cause mortality per 1 m/s increment unit in PWV was 1.25 (95% CI 1.17-1.34, I 2: 0%) and for CV mortality was 1.24 (95% CI 1.16-1.34, I 2: 15.5%). In non-dialysis patients, CACS was associated with CV events (RR: 4.02, 95% CI 1.57-10.29, I 2: 63.4%). High versus low PWV was associated with all-cause mortality (RR: 2.52, 95% CI 1.40-4.55, I 2: 62.6%). CONCLUSIONS: Non-invasive measures of atherosclerosis and arterial stiffening are associated with all-cause and CV mortality as well as CV events among patients with all stages of CKD. These markers could be considered for the evaluation of CV morbidity and mortality risks. Moreover, the results of this meta-analysis support the study of interventions, with effect on these markers of vascular disease, on long-term CVD outcomes.
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The characteristics of desert dust storms (DDS) have been shown to change in response to climate change and land use. There is limited information on the frequency and intensity of DDS over the last decade at a regional scale in the Eastern Mediterranean. An algorithm based on daily ground measurements (PM10, particulate matter ≤10 µm), satellite products (dust aerosol optical depth) and meteorological parameters, was used to identify dust intrusions for three Eastern Mediterranean locations (Crete-Greece, Cyprus, and Israel) between 2006 and 2017. Days with 24-hr average PM10 concentration above ~30 µg/m3 were found to be a significant indicator of DDS for the background sites of Cyprus and Crete. Higher thresholds were found for Israel depending on the season (fall and spring: PM10 > 70 µg/m3, winter and summer: PM10 > 90 µg/m3). We observed a high variability in the frequency and intensity of DDS during the last decade, characterized by a steady trend with sporadic peaks. The years with the highest DDS frequency were not necessarily the years with the most intense episodes. Specifically, the highest dust frequency was observed in 2010 at all three locations, but the highest annual median dust-PM10 level was observed in 2012 in Crete (55.8 µg/m3) and Israel (137.4 µg/m3), and in 2010 in Cyprus (45.3 µg/m3). Crete and Cyprus experienced the same most intense event in 2006, with 24 h-PM10 average of 705.7 µg/m3 and 1254.6 µg/m3, respectively, which originated from Sahara desert. The highest 24 h-PM10 average concentration for Israel was observed in 2010 (3210.9 µg/m3) during a three-day Saharan dust episode. However, a sub-analysis for Cyprus (years 2000-2017) suggests a change in DDS seasonality pattern, intensity, and desert of origin. For more robust conclusions on DDS trends in relation to climate change, future work needs to study data over several decades from different locations.