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1.
Colomb Med (Cali) ; 51(2): e4320, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33012891

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19) has resulted in a global health crisis. Prior to the arrival of this viral pandemic, the world was already plagued with a significant burden of cardiovascular disease. With the introduction of the novel virus, the world now faces a double jeapordy. Early reports have suggested an increased risk of death in individuals with underlying cardio-metabolic disorders. The exact effects of COVID-19 on the cardiovascular system are not well determined, however lessons from prior viral epidemics suggest that such infections can trigger acute coronary syndromes, arrhythmias and heart failure via direct and indirect mechanisms. In this article, we aimed to discuss the effects and potential underlying mechanisms of COVID -19 as well as potential implications of treatments targeted against this virus on the cardiovascular system.


Assuntos
Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus/isolamento & purificação , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Fatores de Risco
2.
Medicine (Baltimore) ; 99(39): e22219, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991415

RESUMO

Short stature is reportedly associated with cardiovascular disease (CVD). However, the mechanism underlying this intriguing epidemiological finding is unclear. Pulse wave velocity (PWV), a marker of vascular stiffness, is a predictor of future CVD. Therefore, PWV may be affected by height even before overt CVD occurs. Here, we investigated the association between adult height and PWV in subjects without overt CVD.A total of 1019 subjects (48 ±â€Š12 years old; 509 men, 21 with diabetes mellitus, 209 with hypertension) without overt CVD were enrolled, all of whom underwent brachial-ankle PWV (baPWV) measurements. The subjects were divided into 3 groups by height. A multiple regression model was used to estimate baPWV values among heights after the adjustment for confounders.Mean baPWV value was highest in the group with the shortest height for both sexes (both P < .001). Bivariate correlation analysis between height and baPWV showed significant correlations in men (r = -0.131, P = .003) and women (r = -0.180, P < .001). In the multiple regression analysis with adjustment for identified confounders, group height was a predictor of baPWV (P for trend = .003) in younger men (<50 years old) but not in older men, while group height was correlated with baPWV in older women (≥50 years old, P for trend = .014) but not in younger women.Height is inversely correlated with baPWV in subjects without overt CVD, especially in younger men and older women. This may explain the historical epidemiological observation of an inverse relationship between height and CVD.


Assuntos
Estatura/fisiologia , Doenças Cardiovasculares/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Fatores Etários , Índice Tornozelo-Braço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso/estatística & dados numéricos , Fatores Sexuais
3.
Geriatr Gerontol Int ; 20(10): 980-987, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32886834

RESUMO

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Extremidade Inferior/fisiopatologia , Força Muscular/fisiologia , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Fragilidade , Força da Mão , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Estudos de Tempo e Movimento , Velocidade de Caminhada/fisiologia
4.
Fluids Barriers CNS ; 17(1): 55, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912226

RESUMO

Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).


Assuntos
Barreira Hematoencefálica/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Microvasos/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Diabetes Mellitus/fisiopatologia , Encefalite/imunologia , Encefalite/fisiopatologia , Humanos , Inflamação/imunologia , Microvasos/imunologia , Doenças do Sistema Nervoso/imunologia , Pandemias , Pneumonia Viral/imunologia , Convulsões/imunologia , Convulsões/fisiopatologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologia
5.
Vasc Health Risk Manag ; 16: 307-316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764951

RESUMO

Purpose: This study was conducted to investigate the relationships between arterial stiffness, frailty and fall-related injuries among community-dwelling older adults. Materials and Methods: A cross-sectional study of a random sample of older adults aged 60 years and older was conducted. Main study parameters: arterial stiffness was measured by the determining the cardio-ankle vascular index (CAVI); Frailty status was defined using a 7-item frailty screening scale, developed in Russia. This questionnaire included question about falls and fall-related injuries. Orthostatic test and anthropometric tests were done. Medical history (comorbidity, medications), the Osteoporosis Self-assessment Tool (OST), nutritional, physical, cognitive and functional status were evaluated. Results: The study population included 163 people aged 60-89 years. The average predicted value of CAVI in women aged 60-69 was 9.13 ± 0.13, in men, 9.49 ± 0.05; in women aged 70-79, it was 9.49 ± 0.16, in men, 9.73 ±0.11; in women aged 80 and older it was 10.04 ±0.18, in men, 10.24 ±0.10 units. The CAVI above the predicted value was associated with fall-related injuries even after adjustment for age, sex, use of ß-blockers (BBs), history of stroke, and region of residence with the odds ratio 3.52 (95% CI: 1.03 -12.04). Conclusion: Our study revealed an independent association between arterial stiffness and fall-related injuries in older adults over 60 years. The findings suggest that clinicians, especially geriatricians, should pay attention to arterial stiffness of patients with fall-related injuries. Similarly, the patients with CAVI above age-predicted value should be evaluated for risk of falls for prevention of fall-related injuries.


Assuntos
Acidentes por Quedas , Doenças Cardiovasculares/complicações , Idoso Fragilizado , Fragilidade/complicações , Rigidez Vascular , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Fragilidade/diagnóstico , Fragilidade/fisiopatologia , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
6.
PLoS One ; 15(8): e0236667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756570

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular co-morbidities and mortality. Arterial stiffness is an independent predictor of cardiovascular risk and mortality, and is influenced by the presence of OSA and related comorbidities. There is a paucity of data regarding long-term evolution of arterial stiffness in CPAP-treated OSA patients. We aimed to prospectively study long term PWV variations and determinants of PWV deterioration. METHODS: In a prospective obese OSA cohort, at time of diagnosis and after several years of follow-up we collected arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), clinical and metabolic parameters, and CPAP adherence. Univariate and multivariate analyses were performed in order to determine contributing factors. RESULTS: Seventy two OSA patients (men: 52.8%, median age: 55.8 years and median BMI of 38.5 kg/m2) with a prevalence of hypertension: 58.3%, type 2 diabetes: 20.8%, hypercholesterolemia: 33.3%, current or past smoking: 59.7%, were evaluated after a median follow-up of 7.4 [5.8; 8.3] years. Over the period of follow-up, the median increase in PWV was 1.34 [0.10; 2.37] m/s. In multivariate analysis, the increase in PWV was associated with older age (10 extra years was associated with a 5.24 [1.35; 9.12] % increase in PWV) and hypertension (a significant increase in PWV of 8.24 [1.02; 15.57] %). No impact of CPAP adherence on PWV evolution was found. CONCLUSION: PWV progression in CPAP-treated OSA patients is mainly related to pre-existing cardio-metabolic comorbidities and not influenced by CPAP adherence. In this high cardiovascular risk population, it is crucial to associated weight management and exercise with CPAP treatment.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Obesidade/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Rigidez Vascular/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Pressão Positiva Contínua nas Vias Aéreas/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/fisiopatologia
7.
PLoS One ; 15(8): e0237601, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817643

RESUMO

BACKGROUND: Plasma volume status (PVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular disease because of its role in the prevention and of the management of heart failure. However, it remains undetermined whether an abnormal PVS is a risk for all-cause and cardiovascular mortality in the general population. METHODS AND RESULTS: We used a nationwide database of 230,882 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up between 2008 and 2011. There were 586 cardiovascular deaths, 2,552 non-cardiovascular deaths, and 3,138 all-cause deaths during the follow-up period of four years. Abnormally high and low PVS were identified from the results of 80% of all subjects (high and low PVS ≥ 7 and < -13.3, respectively). Multivariate Cox proportional hazard regression analysis demonstrated that high PVS was an independent risk factor for all-cause, cardiovascular and non-cardiovascular deaths. Although low PVS was a positive risk factor for cardiovascular deaths as well, it was a negative risk factor for non-cardiovascular deaths. The addition of PVS to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes. CONCLUSIONS: This is the first prospective report to reveal the impact of PVS on all-cause and cardiovascular mortality. PVS could be an additional risk factor for all-cause and cardiovascular mortality in the general population.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Mortalidade/tendências , Volume Plasmático , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Bases de Dados Factuais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo
8.
PLoS One ; 15(8): e0237072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745151

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased cardiovascular disease (CVD) risk which may start even before diagnosis. To explore this CVD risk prior to RA, we determined multiple risk factors and two 10-year clinical risk scores in a cohort of individuals at-risk of RA. We also analyzed associations with arthritis development and autoantibody status and compared a subset of at-risk individuals to an age and sex matched seronegative control group. METHODS: In a cohort of 555 consecutive arthralgia patients positive for rheumatoid factor (RF) and / or anti-citrullinated protein antibody (ACPA) we retrospectively identified patients with preclinical arthritis (i.e. those who developed arthritis), and non-arthritis patients (those without arthritis development during maximum 5 years follow up). Demographics, CVD risk factors and the 10-year cardiovascular risk according to the SCORE and QRISK3 system were determined at baseline. RESULTS: Preclinical arthritis patients (n = 188) had a higher heart rate (68 vs 63 bpm, p = 0.048) and lower cholesterol (5.2 mmol/l vs 5.5, p = 0.006), HDL (1.0 mmol/l vs 1.1, p0.003) and ApoB (0.85 g/l vs 0.91, p = 0.011) compared to non-arthritis patients (n = 367). Lipid levels were associated with ACPA status in both the preclinical arthritis and non-arthritis group. Ten-year CVD risk scores did not differ between preclinical arthritis and non-arthritis patients, in total, 7% (SCORE) and 8% (QRISK3) of seropositive arthralgia patients were classified as high risk. Seropositive at-risk patients (n = 71) had higher total cholesterol (5.4 vs 4.9, p<0.001), TC/HDL ratio (4.0 vs 3.0, p<0.001), triglycerides (1.4 vs 1.0, p = 0.001), ApoB (1.0 vs 0.9, p = 0.019) and 10-year risk scores (median SCORE 1.0 vs 0.0, p = 0.030 and median QRISK3 4.4 vs 3.1, p<0.001) compared to seronegative controls. CONCLUSION: Our results suggest that lipid changes commence prior to RA diagnosis and that ACPAs might play a role.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/etiologia , Adulto , Anticorpos Anti-Proteína Citrulinada , Artralgia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/imunologia , Fatores de Risco
9.
Nature ; 584(7822): 589-594, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32814899

RESUMO

The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development1,2. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization3,4. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease.


Assuntos
Doenças Cardiovasculares/genética , Fractais , Predisposição Genética para Doença , Coração/anatomia & histologia , Coração/fisiologia , Miocárdio/metabolismo , Adulto , Idoso , Animais , Doenças Cardiovasculares/fisiopatologia , Citoesqueleto/genética , Citoesqueleto/fisiologia , Técnicas de Inativação de Genes , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Coração/embriologia , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Miocárdio/citologia , Oryzias/embriologia , Oryzias/genética , Fenótipo
11.
Rev Cardiovasc Med ; 21(2): 225-240, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706211

RESUMO

In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Dieta , Hidroxibenzoatos/administração & dosagem , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Transdução de Sinais
12.
Rev Cardiovasc Med ; 21(2): 253-261, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706213

RESUMO

It is known that functional defects of GATA binding protein 5 (GATA5), an important member of GATA transcription factor family, could cause multiple congenital defects. However, the mechanisms of this transcription factor in cardiovascular diseases are still little known. Finding a genetic approach should help with understanding the possible roles of GATA5 in different cardiovascular diseases and purpose it as a possible therapeutic agent. Hence, this review is divided into three chapters to summarize the roles and main regulatory mechanisms of GATA5 in hypertension, arrhythmia and congenital heart disease, respectively. In each chapter, this review firstly introduces the roles of GATA5 mutations, and then discusses the main regulatory mechanisms of GATA5 in the corresponding diseases (Such as the endothelial dysfunction signaling pathway in the chapter of hypertension, GATA5-NaV1.5 signaling pathway in the chapter of arrhythmia, GATA5-HEY2 and GATA5-Nodal signaling pathway in the chapter of congenital heart disease). Additionally, based on these regulatory networks, it is also speculated that abnormal methylation of the GATA5 gene promoter may lead to cardiovascular diseases such as congenital heart disease. This conjecture is proposed to enrich the regulatory networks of GATA5 and provide a theoretical basis for diagnosis and treatment of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Fator de Transcrição GATA5/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Fator de Transcrição GATA5/genética , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais
14.
Ther Adv Cardiovasc Dis ; 14: 1753944720934937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32611276

RESUMO

Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction and in symptomatic patiens with inappropriate sinus tachycardia. Moreover, interesting effect of ivabradine on endothelial and myocardial function and on oxidative stress and inflamation pathways are progressively emerging. The aim of this paper is to highlight newer evidences about ivabradine effect (and consequently possible future application of the drug) in pathological settings different from guidelines-based clinical practice.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Ivabradina/uso terapêutico , Animais , Função Atrial/efeitos dos fármacos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Ivabradina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
15.
PLoS Med ; 17(7): e1003163, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32658890

RESUMO

BACKGROUND: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3. METHODS AND FINDINGS: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification. CONCLUSIONS: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Produtos Finais de Glicação Avançada/metabolismo , Insuficiência Renal Crônica/mortalidade , Pele/química , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluorescência , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco
16.
J Cardiovasc Magn Reson ; 22(1): 53, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32684167

RESUMO

BACKGROUND: Conventional 2D inversion recovery (IR) and phase sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) have been widely incorporated into routine CMR for the assessment of myocardial viability. However, reliable suppression of fat signal, and increased isotropic spatial resolution and volumetric coverage within a clinically feasible scan time remain a challenge. In order to address these challenges, this work proposes a highly efficient respiratory motion-corrected 3D whole-heart water/fat LGE imaging framework. METHODS: An accelerated IR-prepared 3D dual-echo acquisition and motion-corrected reconstruction framework for whole-heart water/fat LGE imaging was developed. The acquisition sequence includes 2D image navigators (iNAV), which are used to track the respiratory motion of the heart and enable 100% scan efficiency. Non-rigid motion information estimated from the 2D iNAVs and from the data itself is integrated into a high-dimensional patch-based undersampled reconstruction technique (HD-PROST), to produce high-resolution water/fat 3D LGE images. A cohort of 20 patients with known or suspected cardiovascular disease was scanned with the proposed 3D water/fat LGE approach. 3D water LGE images were compared to conventional breath-held 2D LGE images (2-chamber, 4-chamber and stack of short-axis views) in terms of image quality (1: full diagnostic to 4: non-diagnostic) and presence of LGE findings. RESULTS: Image quality was considered diagnostic in 18/20 datasets for both 2D and 3D LGE magnitude images, with comparable image quality scores (2D: 2.05 ± 0.72, 3D: 1.88 ± 0.90, p-value = 0.62) and overall agreement in LGE findings. Acquisition time for isotropic high-resolution (1.3mm3) water/fat LGE images was 8.0 ± 1.4 min (3-fold acceleration, 60-88 slices covering the whole heart), while 2D LGE images were acquired in 5.6 ± 2.2 min (12-18 slices, including pauses between breath-holds) albeit with a lower spatial resolution (1.40-1.75 mm in-plane × 8 mm slice thickness). CONCLUSION: A novel framework for motion-corrected whole-heart 3D water/fat LGE imaging has been introduced. The method was validated in patients with known or suspected cardiovascular disease, showing good agreement with conventional breath-held 2D LGE imaging, but offering higher spatial resolution, improved volumetric coverage and good image quality from a free-breathing acquisition with 100% scan efficiency and predictable scan time.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Adiposidade , Água Corporal/química , Doenças Cardiovasculares/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Coração/diagnóstico por imagem , Imageamento Tridimensional , Imagem por Ressonância Magnética , Compostos Organometálicos/administração & dosagem , Tecido Adiposo/fisiopatologia , Adulto , Idoso , Suspensão da Respiração , Técnicas de Imagem de Sincronização Cardíaca , Doenças Cardiovasculares/fisiopatologia , Eletrocardiografia , Feminino , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
18.
Am J Physiol Heart Circ Physiol ; 319(2): H488-H506, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618516

RESUMO

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiological complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. Therefore, this review article explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion, 2) discussing mechanistic links between chronic stress and endothelial dysfunction, and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward, and we propose that further efforts should be made to 1) more clearly define the concept of stress and 2) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated.


Assuntos
Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Estresse Psicológico/complicações , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/psicologia , Catecolaminas/metabolismo , Doença Crônica , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Fatores de Risco , Transdução de Sinais , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia
19.
PLoS One ; 15(7): e0236193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692755

RESUMO

BACKGROUND: Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints. METHODS: We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes. RESULTS: Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61). CONCLUSION: Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.


Assuntos
Ivabradina/farmacologia , Modelos Genéticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Alelos , Doenças Cardiovasculares/fisiopatologia , Determinação de Ponto Final , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/genética , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Proteínas Musculares/genética , Canais de Potássio/genética , Fatores de Risco
20.
Cardiovasc Ther ; 2020: 1321782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695226

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.


Assuntos
Doenças Cardiovasculares/etiologia , Frequência Cardíaca , Coração/inervação , Hidradenite Supurativa/complicações , Sistema Nervoso Parassimpático/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adolescente , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Feminino , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Adulto Jovem
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