RESUMO
BACKGROUND AND AIMS: Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms. APPROACH AND RESULTS: To identify the predominant suppressors of NASH in the setting of hyperlipidemia, we collected liver biopsy samples from patients with hyperlipidemia, with or without NASH, and performed RNA-sequencing analysis. Notably, decreased Lineage specific Interacting Motif domain only 7 (LMO7) expression robustly correlated with the occurrence and severity of NASH. Although overexpression of LMO7 effectively blocked hepatic lipid accumulation and inflammation, LMO7 deficiency in hepatocytes greatly exacerbated diet-induced NASH progression. Mechanistically, lysine 48 (K48)-linked ubiquitin-mediated proteasomal degradation of tripartite motif-containing 47 (TRIM47) and subsequent inactivation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) cascade are required for the protective function of LMO7 in NASH. CONCLUSIONS: These findings provide proof-of-concept evidence supporting LMO7 as a robust suppressor of NASH in the context of hyperlipidemia, indicating that targeting the LMO7-TRIM47 axis is a promising therapeutic strategy for NASH.
Assuntos
Hiperlipidemias , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Hiperlipidemias/complicações , Fígado/patologia , Inflamação/metabolismo , Hepatócitos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Proteínas com Motivo Tripartido/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismoRESUMO
BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.
Assuntos
Doenças Cardiovasculares , Diabetes Gestacional , Hiperlipidemias , Hipertensão Induzida pela Gravidez , Nascimento Prematuro , Gravidez , Adulto , Feminino , Recém-Nascido , Humanos , Estados Unidos , Adulto Jovem , Resultado da Gravidez , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Nascimento Prematuro/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Índice de Massa Corporal , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/complicações , Fatores de Risco , Hiperlipidemias/complicaçõesRESUMO
Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared to patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case by case basis. Randomized controlled trial evidence in cancer patients is very limited and there is urgent need for more data to inform clinical practice. Therefore, coexistence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.
Assuntos
Doença da Artéria Coronariana , Hiperlipidemias , Isquemia Miocárdica , Neoplasias , Humanos , Isquemia Miocárdica/etiologia , Doença da Artéria Coronariana/complicações , Obesidade/complicações , Hiperlipidemias/complicações , Neoplasias/complicações , Neoplasias/epidemiologia , Fatores de RiscoRESUMO
Akt3 is one of the three members of the serine/threonine protein kinase B (AKT) family, which regulates multiple cellular processes. We have previously demonstrated that global knockout of Akt3 in mice promotes atherogenesis in a macrophage-dependent manner. Whether enhanced Akt3 kinase activity affects atherogenesis is not known. In this study, we crossed atherosclerosis-prone ApoE-/- mice with a mouse strain that has enhanced Akt3 kinase activity (Akt3nmf350) and assessed atherosclerotic lesion formation and the role of macrophages in atherogenesis. Significant reduction in atherosclerotic lesion area and macrophage accumulation in lesions were observed in ApoE-/-/Akt3nmf350 mice fed a Western-type diet. Experiments using chimeric ApoE-/- mice with either ApoE-/-/Akt3nmf350 bone marrow or ApoE-/- bone marrow cells showed that enhanced Akt3 activity specifically in bone marrow-derived cells is atheroprotective. The atheroprotective effect of Akt3nmf350 was more pronounced in male mice. In line with this result, the release of the pro-inflammatory cytokines IL-6, MCP1, TNF-α, and MIP-1α was reduced by macrophages from male but not female ApoE-/-/Akt3nmf350 mice. Levels of IL-6 and TNF-α were also reduced in atherosclerotic lesions of ApoE-/-/Akt3nmf350 male mice compared to ApoE-/- mice. Macrophages from male ApoE-/-/Akt3nmf350 mice were also more resistant to apoptosis in vitro and in vivo and tended to have more pronounced M2 polarization in vitro. These findings demonstrated that enhanced Akt3 kinase activity in macrophages protects mice from atherosclerosis in hyperlipidemic mice in a gender-dependent manner.
Assuntos
Aterosclerose , Hiperlipidemias , Animais , Masculino , Camundongos , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Hiperlipidemias/complicações , Hiperlipidemias/genética , Interleucina-6 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Peripheral serotonin levels are associated with cardiovascular disease risk. We previously found that serum serotonin levels are higher in hyperlipidemic mice than wild-type mice. Evidence also suggests that serotonin regulates biomineralization, in that serotonin treatment augments TNF-a-induced matrix calcification of aortic valve interstitial cells and that a selective inhibitor of peripheral serotonin, LP533401, rescues bone loss induced by ovariectomy in mice. Thus, in the present study, we examined the effects of LP533401 on both skeletal bone mineral density (BMD) and aortic calcification in both young and older hyperlipidemic mice susceptible to calcific atherosclerosis and bone loss. By serial in vivo microCT imaging, we assessed BMD and aortic calcification of Apoe-/- mice fed an atherogenic (high cholesterol) diet alone or mixed with LP533401. Results show that in the young mice, LP533401 blunted skeletal bone loss in lumbar vertebrae but not in femurs. LP533401 also blunted the initial development of aortic calcification but not its progression. Echocardiographic analysis showed that LP533401 blunted both hyperlipidemia-induced cardiac hypertrophy and left ventricular dysfunction. In the older mice, LP533401 increased the BMD of lumbar vertebrae but not of femurs. The aortic calcification progressed in both controls and LP533401-treated mice, but, at post-treatment, LP533401-treated mice had significantly less aortic calcification than the controls. These findings suggest that LP533401 mitigates adverse effects of hyperlipidemia on skeletal and vascular tissues in site- and stage-dependent manners.
Assuntos
Aterosclerose , Calcinose , Hiperlipidemias , Pirimidinas , Calcificação Vascular , Feminino , Camundongos , Animais , Serotonina , Calcificação Fisiológica , Valva Aórtica/diagnóstico por imagem , Hiperlipidemias/complicações , Calcificação Vascular/etiologiaRESUMO
OBJECTIVE: The United States Preventative Services Task Force guidelines for screening for abdominal aortic aneurysms (AAA) are broad and exclude many at risk groups. We analyzed a large AAA screening database to examine the utility of a novel machine learning (ML) model for predicting individual risk of AAA. METHODS: We created a ML model to predict the presence of AAAs (>3 cm) from the database of a national nonprofit screening organization (AAAneurysm Outreach). Participants self-reported demographics and comorbidities. The model is a two-layered feed-forward shallow network. The ML model then generated AAA probability based on patient characteristics. We evaluated graphs to determine significant factors, and then compared those graphs with a traditional logistic regression model. RESULTS: We analyzed a cohort of 10,033 patients with an AAA prevalence of 2.74%. Consistent with logistic regression analysis, the ML model identified the following predictors of AAA: Caucasian race, male gender, advancing age, and recent or past smoker with recent smoker having a more profound affect (P < .05). Interestingly, the ML model showed body mass index (BMI) was associated with likelihood of AAAs, especially for younger females. The ML model also identified a higher than predicted risk of AAA in several groups, including female nonsmokers with cardiac disease, female diabetics, those with a family history of AAA, and those with hypertension or hyperlipidemia at older ages. An elevated BMI conveyed a higher than expected risk in male smokers and all females. The ML model also identified a complex relationship of both diabetes mellitus and hyperlipidemia with gender. Family history of AAA was a more important risk factor in the ML model for both men and women too. CONCLUSIONS: We successfully developed an ML model based on an AAA screening database that unveils a complex relationship between AAA prevalence and many risk factors, including BMI. The model also highlights the need to expand AAA screening efforts in women. Using ML models in the clinical setting has the potential to deliver precise, individualized screening recommendations.
Assuntos
Aneurisma da Aorta Abdominal , Hiperlipidemias , Humanos , Masculino , Feminino , Estados Unidos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/epidemiologia , Fatores de Risco , Prevalência , Aprendizado de Máquina , Assistência ao Paciente , Hiperlipidemias/complicações , Programas de Rastreamento , Ultrassonografia/efeitos adversosRESUMO
In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE-/- mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE-/- mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.
Assuntos
Hiperlipidemias , MicroRNAs , Osteoporose , Ubiquinona/análogos & derivados , Camundongos , Animais , Hiperlipidemias/complicações , Osteogênese , Espécies Reativas de Oxigênio/metabolismo , Osteoporose/prevenção & controle , Osteoporose/tratamento farmacológico , Diferenciação Celular , Mitocôndrias/metabolismo , Apolipoproteínas E/farmacologia , Apolipoproteínas E/uso terapêuticoRESUMO
BACKGROUND: Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. METHODS: A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. RESULTS: A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG â§11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups. CONCLUSIONS: TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.
Assuntos
Hiperlipidemias , Pancreatite , Feminino , Gravidez , Humanos , Troca Plasmática , Estudos Retrospectivos , Estudos de Coortes , Doença Aguda , Pontuação de Propensão , Pancreatite/complicações , Pancreatite/terapia , Hiperlipidemias/complicações , Hiperlipidemias/terapia , TriglicerídeosRESUMO
BACKGROUND: The incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing annually. However, population-based morbidity assessments need to be updated. Early, rapid, and effective lipid-lowering may minimize pancreatic injury and improve clinical prognosis. It is essential to choose the proper treatment. However, treatment options for HLAP are controversial, and there is no uniform treatment protocol. METHODS: In this retrospective study, 127 patients with hyperlipidemic severe acute pancreatitis (HL-SAP) were registered from January 2018 to December 2022 at the General Hospital of Ningxia Medical University. Medical and radiological records of hospitalized patients were collected to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Risk factors for HL-SAP were analyzed using multifactorial logistic regression. A propensity score matching method was used to compare the clinical outcomes of standard and plasma exchange therapies. RESULTS: In this research, the prevalence of HLAP increased about 1.6 times, and the prevalence of HL-SAP was 50.60%. HL-SAP occurs most often in people between the ages of 30 and 39. Amylase exceeded 110 U/L in 84.3% of patients and 330 U/L in only 47.2%. 83.5% of HL-SAP patients had fatty livers and high body mass index (BMI). A total of 48.0% of patients experienced organ failure, ICU treatment (55.1%), recurrence (33.1%), and death (21.3%). Between the hyperlipidemic group and the biliary group in terms of age, gender, BMI, fatty liver, pleural effusion, abdominal constriction syndrome (ACS), multiple organ dysfunction syndrome (MODS), length of hospital, medical costs, morbidity and mortality, triglyceride, cholesterol, creatinine, blood glucose, D-dimer, amylase, albumin, lactate dehydrogenase, serum phosphorus, serum calcium, oxygenation index, and recurrence rate were statistically significant (P < 0.05). High BMI (P = 0.0038, odds ratio (OR) = 1.336, 95%CI: 0.99-1.804), high C-reactive protein (CRP) (P = 0.022, OR = 1.011, 95%CI: 1.003-1.019), low calcium (P = 0.003, OR = 0.016, 95%CI. 0.001-0.239), low albumin (P = 0.012, OR = 0.045, 95%CI: -0.062-0.192), and high D-dimer (P = 0.041, OR = 0.619, 95%CI: 0.053-2.510) were risk factors for HL-SAP, according to multifactorial logistic regression analysis. Adjusted for propensity score matching (PSM), Serum triglyceride (TG) was significantly lower in both the standard treatment (P < 0.001) and plasma exchange (P < 0.001) groups at 48 h compared with the initial test after the attack. Clearance (83.20% ± 0.0% vs. 84.4% ± 0.0%, P = 0.531), length of hospital stay (19.9 ± 4.9 vs. 19.8 ± 11.1, P = 0.092), and death (26.3% vs. 23.6%, P = 0.791) showed no difference between the two groups. However, the difference in medical costs(P = 0.039)between the two groups was statistically significant. CONCLUSION: The incidence of HLAP exhibited a significant increase, remarkable severity, recurrent trend, and mortality. High BMI, high CRP, low calcium, low albumin, and high D-dimer are risk factors for HL-SAP. Compared with standardized treatment, plasma exchange does not improve the prognosis of HL-SAP patients, and standardized treatment is equally effective, safe, and low-cost in early treatment.
Assuntos
Hiperlipidemias , Pancreatite , Humanos , Adulto , Pancreatite/complicações , Pancreatite/terapia , Estudos Retrospectivos , Doença Aguda , Cálcio , Prognóstico , Hiperlipidemias/complicações , Hiperlipidemias/terapia , Proteína C-Reativa , Triglicerídeos , AmilasesRESUMO
BACKGROUND: Diabetes is an important factor in the development of penile inflammation. We studied whether type 2 diabetes (DM), with/without hypertension and hyperlipidemia increased the risk of circumcision among men aged between 30 and 69 using a population-based dataset in Taiwan during a 5-year follow-up period. METHODS: The research data in this study were obtained from Taiwan's National Health Insurance Research Database between 1997 and 2010. We identified 23,197 patients who had a new diagnosis of DM and randomly matched 115,985 subjects as controls. We observed whether circumcision was the treatment after a new DM diagnosis. The initial step involved analyzing the data using Poisson regression analysis. To address potential confounding factors, this study employed propensity score matching based on three variables. Additionally, a Cox regression with a Gamma frailty was utilized to compare outcomes between different groups. RESULTS: Poisson regression analysis showed that DM (RR = 1.75, 95CI = 0.10 ~ 1.22), but not hypertension (RR = 1.14, 95CI=-0.44 ~ 0.70), hyperlipidemia (RR = 0.94, 95CI=-0.66 ~ 0.53), or age (RR = 0.83, 95CI=-0.43 ~ 0.62), had an impact on circumcision treatment. Cox regression with a frailty model found that DM was a risk factor associated with circumcision (HR = 2.31, 95% CI = 1.74 ~ 3.06, p-value < 0.01), whereas no significant difference was noted between circumcision and hypertension (HR = 1.10, 95% CI = 0.80 ~ 1.51), hyperlipidemia (HR = 1.05, 95% CI = 0.79 ~ 1.40), or age (HR = 1.00, 95% CI = 0.99 ~ 1.02). CONCLUSIONS: Type 2 diabetes mellitus, but not hypertension, hyperlipidemia or age increases the risk of circumcision in men aged between 30 and 69 years.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Fragilidade , Hiperlipidemias , Hipertensão , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Seguimentos , Taiwan/epidemiologia , Fragilidade/complicações , Fatores de Risco , Hipertensão/complicações , Hiperlipidemias/epidemiologia , Hiperlipidemias/complicações , Incidência , Estudos RetrospectivosRESUMO
BACKGROUND: Malnutrition is linked to a higher risk of unfavorable outcomes in various illnesses. The present investigation explored the correlation between inadequate nutritional condition and outcomes in older individuals diagnosed with hyperlipidemia. METHODS: The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status. All patients were divided into two groups according to GNRI. A Kaplan-Meier analysis was used to assess the survival rates of different groups at risk of malnutrition. In addition, GNRI was used in COX proportional risk regression models to evaluate its predictive effect on both overall mortality and cardiovascular mortality among patients with hyperlipidemia. Furthermore, the study employed restricted cubic splines (RCS) to examine the nonlinear correlation between GNRI and mortality. RESULTS: The study included 4,532 elderly individuals diagnosed with hyperlipidemia. During a median follow-up duration of 139 months, a total of 1498 deaths from all causes and 410 deaths from cardiovascular causes occurred. The Kaplan-Meier analysis demonstrated significantly poorer survival among individuals at risk of malnutrition, as indicated by the GNRI. In the malnutrition risk group, the modified COX proportional hazards model revealed that a decrease in GNRI was associated with a higher risk of all-cause mortality (HR=1.686, 95% CI 1.212-2.347) and cardiovascular mortality (HR=3.041, 95% CI 1.797-5.147). Furthermore, the restricted cubic splines revealed a non-linear association between GNRI and both all-cause mortality and cardiovascular mortality (p-value for non-linearity = 0.0039, p-value for non-linearity=0.0386). CONCLUSIONS: In older patients with hyperlipidemia, lower levels of GNRI are associated with mortality. The GNRI could potentially be used to predict all-cause mortality and cardiovascular mortality.
Assuntos
Doenças Cardiovasculares , Hiperlipidemias , Desnutrição , Humanos , Feminino , Idoso , Masculino , Doenças Cardiovasculares/mortalidade , Hiperlipidemias/mortalidade , Hiperlipidemias/epidemiologia , Hiperlipidemias/complicações , Desnutrição/mortalidade , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/tendências , Causas de Morte/tendências , Avaliação Nutricional , Estado Nutricional , Medição de Risco/métodos , Fatores de Risco , Estimativa de Kaplan-Meier , Modelos de Riscos ProporcionaisRESUMO
ABSTRACT: A 38-year-old man presented with fever, cough, and jaundice. Four days before, he had started taking amoxicillin/clavulanic acid. He subsequently developed a morbilliform rash, and, according to clinical features and blood analyses, a diagnosis of mononucleosis with Epstein-Barr virus-associated antibiotic-induced exanthema and secondary hemophagocytic lymphohistiocytosis was made. A skin biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with interface dermatitis and many foamy macrophages in the papillary dermis and around the vessels of the superficial dermal plexus. A blood lipid test uncovered marked hypercholesterolemia and hypertriglyceridemia. After treatment with dexamethasone and immunoglobulin, the skin rash, liver function, and lipid profile progressively improved. Xanthomatous cells have been observed in skin biopsies of acute graft-versus-host disease with liver involvement, and these cells have been suggested to represent a clue to the presence of hepatic disease. In our case, underlying cholestatic hepatopathy with hyperlipidemia was present. We believe that the incidental finding of foamy cells in graft-versus-host disease cases and in our case are likely related to the presence of severe liver disease with cholestatic hepatopathy and secondary hyperlipidemia in different background conditions.
Assuntos
Infecções por Vírus Epstein-Barr , Exantema , Doença Enxerto-Hospedeiro , Hiperlipidemias , Linfo-Histiocitose Hemofagocítica , Masculino , Humanos , Adulto , Linfo-Histiocitose Hemofagocítica/patologia , Infecções por Vírus Epstein-Barr/complicações , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/complicações , Herpesvirus Humano 4 , Amoxicilina , Exantema/induzido quimicamente , Exantema/complicações , Lipídeos , Macrófagos/patologiaRESUMO
BACKGROUND: Hyperlipidemia is a risk factor for stroke, and worsens neurological outcome after stroke. Endothelial progenitor cells (EPCs), which become dysfunctional in cerebral ischemia, hold capacity to promote revascularization. OBJECTIVE: We investigated the role of dyslipidemia in impairment of EPC-mediated angiogenesis in cerebral ischemic mice. METHODS AND RESULTS: The high fat diet (HFD)-fed mice following by ischemic stroke exhibited increased infarct volumes and neurological severity scores, and poorer angiogenesis. Bone marrow-EPCs treated with palmitic acid (PA) showed impaired functions and inhibited activity of AMP-activated protein kinase (AMPK). Notably, AMPK deficiency aggravated EPC dysfunction, further decreased mitochondrial membrane potential, and increased reactive oxygen species level in EPCs with PA treatment. Furthermore, the expression of fatty acid oxidation (FAO)-related genes was remarkably reduced, and carnitine palmitoyltransferase 1A (CPT1A) protein expression was downregulated in AMPK-deficient EPCs. AMPK deficiency aggravated neurological severity scores and angiogenesis in ischemic brain of HFD-fed mice, accompanied by suppressed protein level of CPT1A. EPC transplantation corrected impaired neurological severity scores and angiogenesis in AMPK-deficient mice. CONCLUSION: Our findings suggest that AMPK deficiency aggravates poor angiogenesis in ischemic brain by mediating FAO and oxidative stress thereby inducing EPC dysfunction in hyperlipidemic mice.
Assuntos
Células Progenitoras Endoteliais , Ácidos Graxos , Hiperlipidemias , AVC Isquêmico , Camundongos Endogâmicos C57BL , Animais , Células Progenitoras Endoteliais/metabolismo , Hiperlipidemias/metabolismo , Hiperlipidemias/complicações , Camundongos , Masculino , Ácidos Graxos/metabolismo , AVC Isquêmico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas Quinases Ativadas por AMP/metabolismo , Modelos Animais de Doenças , Oxirredução , Carnitina O-Palmitoiltransferase/metabolismo , Neovascularização Fisiológica/fisiologia , Camundongos Knockout , AngiogêneseRESUMO
OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is considered a rare inflammatory rheumatologic disorder that is seen primarily in older adult men. Patients present with arthralgias of large joints accompanied by painful pitting edema of the hands and feet. Few studies have reported the prevalence of metabolic syndromes, including diabetes mellitus and hyperlipidemia in these patients. METHODS: This case series reviewed 25 patients who were diagnosed as having RS3PE in a private outpatient clinic. RESULTS: Nearly half of the patients (48%) had diabetes mellitus, predominantly type 2, and more than half of the patients (60%) had hyperlipidemia. CONCLUSIONS: We believe that future case studies on RS3PE should include an assessment of various comorbidities that can be seen in patients with this autoinflammatory disorder. The increased availability of musculoskeletal ultrasound provides a potential area of study to differentiate this disorder from other inflammatory arthritis and improve reaching the correct diagnosis.
Assuntos
Edema , Sinovite , Humanos , Masculino , Sinovite/diagnóstico , Sinovite/epidemiologia , Sinovite/complicações , Edema/epidemiologia , Edema/diagnóstico , Edema/etiologia , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Hiperlipidemias/epidemiologia , Hiperlipidemias/complicações , Comorbidade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
AIMS: The variant p.Arg149Cys in ACTA2, which encodes smooth muscle cell (SMC)-specific α-actin, predisposes to thoracic aortic disease and early onset coronary artery disease in individuals without cardiovascular risk factors. This study investigated how this variant drives increased atherosclerosis. METHODS AND RESULTS: Apoe-/- mice with and without the variant were fed a high-fat diet for 12 weeks, followed by evaluation of atherosclerotic plaque formation and single-cell transcriptomics analysis. SMCs explanted from Acta2R149C/+ and wildtype (WT) ascending aortas were used to investigate atherosclerosis-associated SMC phenotypic modulation. Hyperlipidemic Acta2R149C/+Apoe-/- mice have a 2.5-fold increase in atherosclerotic plaque burden compared to Apoe-/- mice with no differences in serum lipid levels. At the cellular level, misfolding of the R149C α-actin activates heat shock factor 1, which increases endogenous cholesterol biosynthesis and intracellular cholesterol levels through increased HMG-CoA reductase (HMG-CoAR) expression and activity. The increased cellular cholesterol in Acta2R149C/+ SMCs induces endoplasmic reticulum stress and activates PERK-ATF4-KLF4 signaling to drive atherosclerosis-associated phenotypic modulation in the absence of exogenous cholesterol, while WT cells require higher levels of exogenous cholesterol to drive phenotypic modulation. Treatment with the HMG-CoAR inhibitor pravastatin successfully reverses the increased atherosclerotic plaque burden in Acta2R149C/+Apoe-/- mice. CONCLUSION: These data establish a novel mechanism by which a pathogenic missense variant in a smooth muscle-specific contractile protein predisposes to atherosclerosis in individuals without hypercholesterolemia or other risk factors. The results emphasize the role of increased intracellular cholesterol levels in driving SMC phenotypic modulation and atherosclerotic plaque burden.
Assuntos
Aterosclerose , Hiperlipidemias , Placa Aterosclerótica , Camundongos , Animais , Placa Aterosclerótica/complicações , Actinas/metabolismo , Camundongos Knockout para ApoE , Aterosclerose/etiologia , Colesterol/metabolismo , Hiperlipidemias/complicações , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Músculo Liso/metabolismo , Músculo Liso/patologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND AND PURPOSE: The effectiveness of hyperlipidemia treatment in strokes secondary prevention has been established. However, whether pretreatment with statins could confer protective effects when a patient's baseline low-density lipoprotein cholesterol (LDL-C) level is <70 mg/dL remains uncertain. Additionally, the ability of statin treatment to reduce poststroke complications, mortality, and recurrence in this patient group is unclear. METHODS AND RESULTS: In this retrospective observational study, we enrolled patients who had experienced an ischemic stroke with LDL-C levels <70 mg/dL. We analyzed the association of statin use with baseline characteristics, stroke severity, in-hospital complications, mortality rates, stroke recurrence rate, and mortality rate. Patients who used and patients who did not use statins were similar in terms of age and sex. Patients using statins had higher rates of diabetes mellitus, hypertension, prior stroke, and coronary artery disease but a lower incidence of atrial fibrillation. Stroke severity was less pronounced in those using statins. We also evaluated the relationship between in-hospital statin use and complications. We noted that in-hospital statin use was associated with lower rates of infection, hemorrhagic transformation, gastrointestinal hemorrhage, and mortality, as well as higher rates of positive functional outcomes. The 1-year recurrence rate was similar in both groups. CONCLUSIONS: Statin use is associated with milder strokes and improved poststroke outcomes, even in patients with well-controlled LDL levels. Neurologists may consider prescribing statins for patients with ischemic stroke who do not overt hyperlipidemia. Further research into potential underlying mechanisms is warranted.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico , Hiperlipidemias/tratamento farmacológico , AVC Isquêmico/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Masculino , FemininoRESUMO
PURPOSE: Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. MATERIALS AND METHODS: In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18â-â87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). RESULTS: DES occurred with significantly (p < 0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidaemia, hyperuricaemia, osteoporosis, and nephrolithiasis. CONCLUSION: Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.
Assuntos
Síndromes do Olho Seco , Hiperlipidemias , Hiperuricemia , Nefrolitíase , Osteoporose , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Hiperuricemia/complicações , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Fatores de Risco , Hiperlipidemias/complicações , Osteoporose/complicações , Nefrolitíase/complicaçõesRESUMO
OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.
Assuntos
Apolipoproteínas E , Biomarcadores , Modelos Animais de Doenças , Hiperlipidemias , Restrição Física , Animais , Hiperlipidemias/metabolismo , Hiperlipidemias/complicações , Camundongos , Biomarcadores/metabolismo , Apolipoproteínas E/genética , Proteômica/métodos , Estresse Psicológico/complicações , MicroRNAs/metabolismo , MicroRNAs/genética , Ferroptose , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Camundongos Knockout , Proteína Desacopladora 1/metabolismo , Biologia ComputacionalRESUMO
PURPOSE OF REVIEW: Inflammation is gaining attention as a target for prevention of atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to compare the evidence for inflammation with the evidence for low-density lipoprotein (LDL) cholesterol in ASCVD. RECENT FINDINGS: Evidence from human genetic studies and randomized controlled trials implicate the inflammatory pathway from the inflammasome through interleukin (IL)-1 to IL-6 as a cause of ASCVD. Higher levels of IL-6 may lead to proportionally increased risk of ASCVD, and randomized controlled trials of IL-6 inhibitors are underway. The causal evidence for LDL cholesterol in ASCVD is overwhelming and recent important findings instead revolve around development of improved LDL cholesterol lowering therapy through RNA and DNA based therapeutics. Even though some lipid-lowering therapies lower IL-6, the IL-6 inflammatory pathway and LDL cholesterol are two separate causes of ASCVD. SUMMARY: IL-6 mediated inflammation most likely causes ASCVD, in parallel with LDL cholesterol. However, fewer individuals in the general population are exposed to high IL-6 than high LDL cholesterol. For inflammation, future research should focus on improving efficacy and safety of anti-inflammatory therapy, and for LDL cholesterol, future research should focus on wider and more effective implementation of LDL cholesterol lowering therapy.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipidemias , Humanos , LDL-Colesterol , Doenças Cardiovasculares/epidemiologia , Interleucina-6 , Colesterol , Aterosclerose/epidemiologia , Hipercolesterolemia/complicações , Hiperlipidemias/complicações , Inflamação/complicaçõesRESUMO
PURPOSE OF REVIEW: Combined hyperlipidemia is the most common lipid disorder and is strongly polygenic. Given its prevalence and associated risk for atherosclerotic cardiovascular disease, this review describes the potential for utilizing polygenic risk scores for risk prediction and management of combined hyperlipidemia. RECENT FINDINGS: Different diagnostic criteria have led to inconsistent prevalence estimates and missed diagnoses. Given that individuals with combined hyperlipidemia have risk estimates for incident coronary artery disease similar to individuals with familial hypercholesterolemia, early identification and therapeutic management of those affected is crucial. With diagnostic criteria including traits such apolipoprotein B, low-density lipoprotein cholesterol, and triglyceride, polygenic risk scores for these traits strongly associate with combined hyperlipidemia and could be used in combination for clinical risk prediction models and developing specific treatment plans for patients. SUMMARY: Polygenic risk scores are effective tools in risk prediction of combined hyperlipidemia, can provide insight into disease pathophysiology, and may be useful in managing and guiding treatment plans for patients. However, efforts to ensure equitable polygenic risk score performance across different genetic ancestry groups is necessary before clinical implementation in order to prevent the exacerbation of racial disparities in the clinic.