RESUMEN
BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.
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Aterosclerosis , LDL-Colesterol , Humanos , Adulto , Masculino , Femenino , Adulto Joven , Adolescente , LDL-Colesterol/sangre , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Valor Predictivo de las Pruebas , Medición de Riesgo/métodos , Factores de Riesgo , HDL-Colesterol/sangreRESUMEN
Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.
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Biomarcadores , Enfermedad de la Arteria Coronaria , Proteínas de la Membrana , Análisis de la Aleatorización Mendeliana , Proteómica , Humanos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Ratones , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/sangre , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , LDL-Colesterol/sangre , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Estudios de Casos y Controles , Aterosclerosis/sangre , Aterosclerosis/genéticaRESUMEN
BACKGROUND: Atherogenic index of plasma (AIP) index is an important marker of insulin resistance and a significant risk factor for cardiovascular disease. Abdominal aortic calcification (AAC) is significantly associated with subclinical atherosclerotic disease. However, there are no studies that have examined the relationship between AIP index and AAC, so we investigated the potential association between them in the general population. METHODS: This was a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES, 2013-2014). The association of AIP with AAC was estimated by multivariable regression analysis. RESULTS: After adjusting for confounders, the odds of extensive AAC doubled per unit increase in the AIP index (OR = 2.00, 95% CI: 1.05, 3.83; P = 0.035). The multivariable OR and 95% CI of the highest AIP index tertile compared with the lowest tertile was significantly different. (OR = 1.73, 95% CI: 1.05, 2.83; P = 0.031). The subgroup analyses indicated that the association was consistent irrespective of age, sex, hypertension, diabetes, smoking status, eGFR and hypercholesteremia. CONCLUSIONS: The AIP index was independently associated with the presence of extensive AAC in the study population. Further studies are required to confirm this relationship.
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Aorta Abdominal , Aterosclerosis , Encuestas Nutricionales , Calcificación Vascular , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/patología , Calcificación Vascular/epidemiología , Calcificación Vascular/sangre , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Adulto , Factores de Riesgo , Biomarcadores/sangre , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/sangre , AncianoRESUMEN
Background: The relationship between atherogenic index of plasma (AIP) and triglyceride glucose-body mass index (TyG-BMI) and sarcopenia has not been studied in the United States (US) population. Methods: This research included 4,835 people from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The relationship between sarcopenia and TyG-BMI, as well as the AIP index, was examined through the utilization of restricted cubic spline (RCS) analysis, subgroup analysis, and multivariate logistic regression analysis. Diagnostic value of AIP and TyG-BMI for sarcopenia was compared by receiver operating characteristic (ROC) curves. Results: In this research, 428 people with sarcopenia were identified among the 4,835 subjects that were included in the experiment. AIP and sarcopenia were positively associated with an odds ratio (OR) of 1.58 and a 95% confidence interval (CI) of (1.07, 2.34) on fully adjusted multivariate logistic regression analysis. Similarly, TyG-BMI and sarcopenia were positively associated with an OR of 8.83 and a 95% CI of (5.46, 14.26). AIP and sarcopenia had a non-linear positive connection (P-value<0.001, P-Nonlinear=0.010), while TyG-BMI and sarcopenia had a linear positive correlation (P-value<0.001, P-Nonlinear=0.064), according to RCS analysis. Subgroup analyses showed a significant interaction between TyG-BMI and sarcopenia due to gender (P = 0.023). ROC curves showed that TyG-BMI (AUC:0.738, 95% CI: 0.714 - 0.761) was more useful than AIP (AUC:0.648, 95% CI: 0.622 - 0.673) in diagnosing sarcopenia. Conclusion: In US adults aged 20-59 years, our study revealed a correlation between elevated AIP and TyG-BMI levels and heightened sarcopenia risk. Moreover, TyG-BMI has better diagnostic validity than AIP.
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Aterosclerosis , Glucemia , Índice de Masa Corporal , Sarcopenia , Triglicéridos , Humanos , Sarcopenia/sangre , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Adulto , Triglicéridos/sangre , Glucemia/análisis , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Adulto Joven , Encuestas NutricionalesRESUMEN
BACKGROUND: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. CONTENT: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. SUMMARY: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.
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Lípidos , Lipoproteínas , Humanos , Lipoproteínas/sangre , Lipoproteínas/análisis , Lípidos/sangre , Lípidos/análisis , LDL-Colesterol/sangre , Apolipoproteínas B/sangre , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Lipoproteína(a)/sangreRESUMEN
Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.
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Aorta , Apolipoproteína A-I , Aterosclerosis , Coffea , Modelos Animales de Enfermedad , Selectina-P , Extractos Vegetales , Animales , Selectina-P/sangre , Selectina-P/metabolismo , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Masculino , Ratas , Coffea/química , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Apolipoproteína A-I/sangre , Aorta/metabolismo , Aorta/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence. RESULTS: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence (p-overall = 0.006, p-nonlinear = 0.689) and recurrence (p-overall = 0.001, p-nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results. CONCLUSION: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.
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Aterosclerosis , Cálculos Renales , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Cálculos Renales/epidemiología , Cálculos Renales/sangre , Persona de Mediana Edad , Prevalencia , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/etiología , Triglicéridos/sangre , Factores de Riesgo , Recurrencia , HDL-Colesterol/sangre , Estados Unidos/epidemiología , Modelos LogísticosRESUMEN
BACKGROUND: The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. METHODS AND RESULTS: We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. CONCLUSIONS: Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.
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Adipoquinas , Adiponectina , Aterosclerosis , Colesterol , Leptina , Resistina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Aterosclerosis/sangre , Aterosclerosis/etnología , Aterosclerosis/epidemiología , Leptina/sangre , Adipoquinas/sangre , Adiponectina/sangre , Colesterol/sangre , Resistina/sangre , Estados Unidos/epidemiología , Biomarcadores/sangre , Estudios Transversales , Anciano de 80 o más Años , Triglicéridos/sangre , Obesidad/sangre , Obesidad/etnología , Obesidad/epidemiología , Estudios Longitudinales , Factores de Riesgo , Estudios ProspectivosRESUMEN
BACKGROUND: Oral isotretinoin causes changes in serum lipid values. These changes are not seen in every patient, regardless of dose. It is unclear what causes these changes and how often serum lipid values should be followed up. AIMS: We aimed to evaluate the relationship between the change in serum lipid values and personal and familial risk factors. METHODS: Serum lipid values at baseline (0th), 1st, 3rd, and 6th months of isotretinoin treatment of acne patients aged 16 years and over using oral isotretinoin at a dose of 0.5-1 mg/kg/day between January 2017 and December 2019 were recorded retrospectively. The relationship between personal and familial risk factors and changes in serum lipid values were evaluated statistically. RESULTS: In pairwise comparison, a significant difference was detected between the 0th and 1st month, 0th and 3rd month, 0th and 6th month, and 1st and 6th month in the average serum lipid (Low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), total cholesterol, triglyceride) levels. However, no significant difference was detected between 3rd and 6th month. The change in LDL levels between the 0th and the 3rd month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.034). The change in VLDL levels between the 0th and 6th month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.022). It was observed that the changes in total cholesterol and VLDL levels between the 0th and 3rd month increased as body mass index (BMI) increased (p = 0.03, p = 0.014, respectively). Similarly, the changes in triglyceride and VLDL levels between 0th and 6th month and between 1st and 6th month increased by an increase in BMI (respectively; p = 0.006, p = 0.019; p = 0.016, p = 0.022). The increase in the levels of VLDL between the 1st and the 6th month was found to be significantly higher in smokers than in non-smokers (p = 0,032). CONCLUSION: We recommend evaluation of serum lipids values in the 0th, 1st, and 3rd month in all acne patients using oral isotretinoin and that these values have to be checked monthly in the following months for smokers, those with a history of atherosclerosis, and those with a BMI above normal.
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Acné Vulgar , Isotretinoína , Lípidos , Humanos , Isotretinoína/efectos adversos , Isotretinoína/uso terapéutico , Isotretinoína/administración & dosificación , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/sangre , Masculino , Femenino , Estudios Retrospectivos , Adolescente , Factores de Riesgo , Adulto Joven , Adulto , Lípidos/sangre , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/administración & dosificación , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Triglicéridos/sangre , Administración OralRESUMEN
OBJECTIVE: This study aims to evaluate the role of elevated lipoprotein (a) [Lp(a)] levels as a potential contributor to residual risk in individuals with atherosclerotic cardiovascular disease (ASCVD). Considering that approximately 90% of Lp(a) levels are genetically determined and can vary regionally, we assessed Lp(a) levels in a cohort of ASCVD patients from the Turkish population, where data is currently limited. METHODS: We conducted a retrospective analysis of data and Lp(a) measurements collected from individuals diagnosed with ASCVD at a single center. RESULTS: The analysis included Lp(a) levels of 1193 consecutive individuals. The mean Lp(a) level was 28.2 mg/dL, with a median of 16 mg/dL and an interquartile range (IQR) from the 25th to the 75th percentile, 7 mg/dL to 39 mg/dL. The highest recorded Lp(a) level was 326 mg/dL. Among the cases, 18.7% exhibited Lp(a) levels ≥ 50 mg/dL, 10.8% had levels ≥ 70 mg/dL, and 5.8% had levels ≥ 90 mg/dL. The mean levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were 132 ± 47 mg/dL and 212 ± 54 mg/dL, respectively. Lp(a) levels were significantly higher in females compared to males. Furthermore, the proportion of females with Lp(a) levels ≥ 90 mg/dL was higher than in males (11.4% vs. 1.4%; P < 0.01). Additionally, a modest but significant correlation was observed between Lp(a) levels and TC (r = 0.075, P = 0.01) as well as LDL-C (r = 0.106, P < 0.01). CONCLUSION: This study revealed that Lp(a) concentrations were higher in women and statin users among ASCVD patients and identified a weak but significant correlation between Lp(a) levels and both TC and LDL-C.
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Aterosclerosis , Lipoproteína(a) , Humanos , Masculino , Femenino , Lipoproteína(a)/sangre , Estudios Retrospectivos , Turquía/epidemiología , Persona de Mediana Edad , Aterosclerosis/sangre , Anciano , AdultoRESUMEN
OBJECTIVES: In childhood-onset SLE (cSLE), patients have an increased risk of premature atherosclerosis. The pathophysiological mechanisms for this premature atherosclerosis are not yet completely understood, but besides traditional risk factors, the endothelium plays a major role. The first aim of this study was to measure levels of SLE-associated markers involved in endothelial cell (EC) function and lipids in a cSLE cohort longitudinally in comparison with healthy controls (HC). Next aim was to correlate these levels with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and nailfold capillaroscopic patterns. METHODS: Blood serum samples, videocapillaroscopy images and patient characteristics were collected in a multicentre longitudinal cSLE cohort and from age and sex comparable HC. Disease activity was evaluated by SLEDAI. A total of 15 EC markers and six lipids were measured in two longitudinal cSLE samples (minimum interval of 6 months) and in HC. Nailfold videocapillaroscopy images were scored according to the guidelines from the EULAR Study Group on Microcirculation in Rheumatic Diseases. RESULTS: In total, 47 patients with cSLE and 42 HCs were analysed. Median age at diagnosis was 15 years (IQR 12-16 years). Median time between t=1 and t=2 was 14.5 months (IQR 9-24 months). Median SLEDAI was 12 (IQR 6-18) at t=1 and 2 (IQR 1-4) at t=2. Serum levels of angiopoietin-2, CCL2, CXCL10, GAS6, pentraxin-3, thrombomodulin, VCAM-1 and vWF-A2 were elevated in cSLE compared with HC at t=1. While many elevated EC markers at t=1 normalised over time after treatment, several markers remained significantly increased compared with HC (angiopoietin-2, CCL2, CXCL10, GAS6, thrombomodulin and VCAM-1). CONCLUSION: In serum from patients with cSLE different markers of endothelial activation were dysregulated. While most markers normalised during treatment, others remained elevated in a subset of patients, even during low disease activity. These results suggest a role for the dysregulated endothelium in early and later phases of cSLE, possibly also during lower disease activity. TRIAL REGISTRATION NUMBER: NL60885.018.17.
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Biomarcadores , Lupus Eritematoso Sistémico , Angioscopía Microscópica , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Femenino , Masculino , Niño , Adolescente , Biomarcadores/sangre , Estudios Longitudinales , Angioscopía Microscópica/métodos , Endotelio Vascular/fisiopatología , Edad de Inicio , Células Endoteliales , Índice de Severidad de la Enfermedad , Estudios de Casos y Controles , Trombomodulina/sangre , Lípidos/sangre , Aterosclerosis/sangre , Aterosclerosis/fisiopatologíaRESUMEN
AIM: To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). METHODS: The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. RESULTS: The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. CONCLUSION: Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.
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Aterosclerosis , Biomarcadores , Grosor Intima-Media Carotídeo , Senescencia Celular , Inmunosenescencia , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Adulto , Adulto Joven , Persona de Mediana Edad , Aterosclerosis/sangre , Aterosclerosis/inmunología , Aterosclerosis/etiología , Aterosclerosis/diagnóstico , Aterosclerosis/diagnóstico por imagen , Biomarcadores/sangre , Estudios de Casos y Controles , Adolescente , Molécula 1 de Adhesión Intercelular/sangre , Linfocitos T/inmunología , Molécula 1 de Adhesión Celular Vascular/sangre , Senescencia de Células TRESUMEN
Sepsis and atherosclerotic cardiovascular disease (ASCVD) are major health challenges involving complex processes like inflammation, renin-angiotensin system (RAS) dysregulation, and thrombosis. Despite distinct clinical symptoms, both conditions share mechanisms mediated by bradykinin. This review explores bradykinin's role in inflammation, RAS modulation, and thrombosis in sepsis and ASCVD. In sepsis, variable kininogen-bradykinin levels may correlate with disease severity and progression, though the effect of bradykinin receptor modulation on inflammation remains uncertain. RAS activation is present in both diseases, with sepsis showing variable or low levels of Ang II, ACE, and ACE2, while ASCVD consistently exhibits elevated levels. Bradykinin may act as a mediator for ACE2 and AT2 receptor effects in RAS regulation. It may influence clotting and fibrinolysis in sepsis-associated coagulopathy, but evidence for an antithrombotic effect in ASCVD is insufficient. Understanding bradykinin's role in these shared pathologies could guide therapeutic and monitoring strategies and inform future research.
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Aterosclerosis , Coagulación Sanguínea , Bradiquinina , Sistema Renina-Angiotensina , Sepsis , Transducción de Señal , Humanos , Bradiquinina/metabolismo , Sepsis/fisiopatología , Sepsis/metabolismo , Sepsis/sangre , Aterosclerosis/fisiopatología , Aterosclerosis/metabolismo , Aterosclerosis/sangre , Animales , Coagulación Sanguínea/efectos de los fármacos , Receptores de Bradiquinina/metabolismo , Trombosis/fisiopatología , Trombosis/sangre , Trombosis/metabolismoRESUMEN
The evaluation of serum Lp(a) values in childhood and adolescence has been widely debated, and in the last few years, many authors have tried to better define Lp(a) role in atherosclerosis pathogenesis, starting from childhood. In our narrative review, we have evaluated the main historical stages of Lp(a) studies in childhood, trying to focus on pathogenic mechanisms linked to elevated serum Lp(a) values, starting from ischemic stroke and vascular damage, and to its possible direct involvement in premature atherosclerosis from childhood onwards. Historic manuscripts on Lp(a) in pediatric patients have mainly focused on serum Lp(a) values and increased stroke risk. More recently, many studies have evaluated Lp(a) as a coronary vascular disease (CVD) risk factor starting from childhood, especially related to a positive family history of premature CVD. Finally, only a few studies evaluated the role of Lp(a) in premature atherosclerotic processes and endothelial and vascular damage in pediatric patients. Lastly, we have hypothesized a future perspective, with the hope that plasma Lp(a) levels will be treated with a tailored pharmacologic approach, and Lp(a) will become a precocious therapeutic target to control the atherosclerotic pathways from the first years of life.
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Enfermedades Cardiovasculares , Lipoproteína(a) , Humanos , Lipoproteína(a)/sangre , Lipoproteína(a)/metabolismo , Niño , Adolescente , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/metabolismo , Factores de Riesgo , Aterosclerosis/sangreRESUMEN
Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE-/- mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3-7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3-7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function.
Asunto(s)
Aterosclerosis , ARN Circular , Infarto del Miocardio con Elevación del ST , ARN Circular/genética , Humanos , Animales , Infarto del Miocardio con Elevación del ST/genética , Infarto del Miocardio con Elevación del ST/sangre , Aterosclerosis/genética , Aterosclerosis/sangre , Aterosclerosis/metabolismo , Ratones , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Persona de Mediana Edad , Femenino , Regulación de la Expresión Génica , Ratones Endogámicos C57BL , Anciano , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismoRESUMEN
BACKGROUND: This study evaluates the association between vitamin A levels, AIP (the atherogenic index of plasma), and subclinical hypothyroidism. METHODS: A cross-sectional analysis was conducted involving a representative sample of 3530 Chinese adults. Linear and logistic regression models were utilized to evaluate the associations between AIP and subclinical hypothyroidism, stratified by vitamin A levels. These analyses were further differentiated by sex and age groups to identify any demographic-specific associations. RESULTS: In the vitamin A-sufficient group, an increase in AIP was associated with elevated total triiodothyronine (TT3) levels (ß = 0.26, 95%CI: 0.09, 0.41, p = 0.003). Conversely, in the group with severe vitamin A deficiency, higher AIP levels were linked to increased free triiodothyronine (fT3) and TT3 levels and decreased free thyroxine (fT4) levels (ß = 0.12, 0.03, and -0.29, respectively). Additionally, severe vitamin A deficiency increased the risk associated with AIP and subclinical hypothyroidism (OR = 1.66, 95%CI: 1.07, 2.58, p = 0.025). This risk was notably more pronounced in women and older adults, with odds ratios of 2.44 (95%CI: 1.55, 3.86, p < 0.001) and 2.14 (95%CI: 1.36, 3.38, p = 0.001), respectively. CONCLUSIONS: Vitamin A deficiency may increase the risk of the association between AIP and subclinical hypothyroidism, particularly among women and the elderly.
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Hipotiroidismo , Deficiencia de Vitamina A , Vitamina A , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Femenino , Masculino , Estudios Transversales , China/epidemiología , Persona de Mediana Edad , Adulto , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , Vitamina A/sangre , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Anciano , Triyodotironina/sangre , Factores de Riesgo , Tiroxina/sangre , Enfermedades AsintomáticasRESUMEN
BACKGROUND: Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples. METHODS: Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics. RESULTS: External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients. CONCLUSIONS: The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.
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Plaquetas , Enfermedad de la Arteria Coronaria , Vesículas Extracelulares , Leucocitos , Trombina , Humanos , Trombina/metabolismo , Vesículas Extracelulares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Plaquetas/metabolismo , Leucocitos/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Estudios de Casos y Controles , Aterosclerosis/sangre , Lípidos de la Membrana/sangre , Lípidos de la Membrana/metabolismo , Fosfatidilserinas/sangre , Síndrome Coronario Agudo/sangre , Coagulación Sanguínea , LipidómicaRESUMEN
PURPOSE: The atherogenic index of plasma (AIP) is a novel comprehensive lipid index. We aimed to investigate a possible relationship between AIP index and kidney stones in US adults. METHODS: This cross-sectional study was conducted among adults with complete AIP index and questionnaire records on kidney stones from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. The AIP index served as the exposure variable, defined as the logarithm of the ratio between triglycerides (TG, mmol/L) and high-density lipoprotein cholesterol (HDL-c, mmol/L). Self-reported history of kidney stones was utilized as the outcome variable. The independent relationship between AIP index and the risk of kidney stones was fully assessed. RESULTS: A total of 14,833 participants were included in this study, with an average AIP index of -0.07 ± 0.01. The proportion of kidney stones progressively increased with higher AIP index tertile intervals (7.33% vs. 9.97% vs. 12.57%, P < 0.001). Furthermore, AIP index was found to be independently associated with the risk of kidney stones after adjusting for confounding factors (OR = 1.32, 95% CI 1.08-1.61, P = 0.006). Restricted cubic spline (RCS) analysis confirmed the robustness of our results. There was no significant interaction observed based on subgroup analysis stratified by age, gender, race, body mass index (BMI, kg/m2), smokers, diabetes, hypertension, and cardiovascular disease (P for interaction > 0.05). CONCLUSIONS: The AIP index may be a potential epidemiological tool to quantify the role of dyslipidemia in the risk of kidney stones in US adults.
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Aterosclerosis , Cálculos Renales , Humanos , Cálculos Renales/sangre , Cálculos Renales/epidemiología , Cálculos Renales/etiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/etiología , Encuestas Nutricionales , Triglicéridos/sangre , Estados Unidos/epidemiología , HDL-Colesterol/sangre , AncianoRESUMEN
Evidence of the associations between long-term exposure to PM2.5 and O3 and human blood lipid concentrations is abundant yet inconclusive. Whether clean air policies could improve lipid profiles remains unclear. In total, 2979312 participants from a Chinese nationwide prospective study were included. For cross-sectional analyses, linear mixed-effects models were utilized to assess the associations of pollutants with lipid profiles (TC, LDL-C, TG, HDL-C). For longitudinal analyses, a quasi-experimental design and difference-in-differences models were employed to investigate the impact of China's Clean Air Act. In the cross-sectional analyses, each IQR increase in PM2.5 was associated with 2.49 % (95 % CI: 2.36 %, 2.62 %), 2.51 % (95 % CI: 2.26 %, 2.75 %), 3.94 % (95 % CI: 3.65 %, 4.23 %), and 1.54 % (95 % CI: 1.38 %, 1.70 %) increases in TC, LDL-C, TG, and HDL-C, respectively. For each IQR increase in O3, TC, LDL-C, TG, and HDL-C changed by 1.06 % (95 % CI: 0.95 %, 1.17 %), 1.21 % (95 % CI: 1.01 %, 1.42 %), 1.78 % (95 % CI: 1.54 %, 2.02 %), and -0.63 % (95 % CI: -0.76 %, -0.49 %), respectively. Longitudinal analyses showed that the intervention group experienced greater TC, LDL-C, and HDL-C reductions (1.77 %, 4.26 %, and 7.70 %, respectively). Our findings suggest that clean air policies could improve lipid metabolism and should be implemented in countries with heavy air pollution burdens.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Lípidos , Material Particulado , Humanos , China , Masculino , Femenino , Persona de Mediana Edad , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Adulto , Lípidos/sangre , Estudios Transversales , Ozono/análisis , Estudios Prospectivos , Aterosclerosis/prevención & control , Aterosclerosis/sangre , Anciano , Estudios Longitudinales , Exposición a Riesgos AmbientalesRESUMEN
SOURCE CITATION: Koren MJ, Rodriguez F, East C, et al. An "inclisiran first" strategy vs usual care in patients with atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2024;83:1939-1952. 38593947.