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1.
Circulation ; 150(9): 687-705, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-38881440

RESUMEN

BACKGROUND: Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke. METHODS: We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with Ldlr knockout (designated SR-BI∆CT/∆CT/Ldlr-/-). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI∆CT/∆CT/Ldlr-/- mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions. RESULTS: SR-BI∆CT/∆CT/Ldlr-/- mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions. CONCLUSIONS: WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.


Asunto(s)
Infarto del Miocardio , Peroxidasa , Placa Aterosclerótica , Accidente Cerebrovascular , Animales , Masculino , Ratones , Dieta Occidental/efectos adversos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/patología , Infarto del Miocardio/tratamiento farmacológico , Peroxidasa/metabolismo , Placa Aterosclerótica/tratamiento farmacológico , Receptores de LDL/genética , Receptores de LDL/deficiencia , Rotura Espontánea , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control
2.
Circulation ; 150(10): 758-769, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39087344

RESUMEN

BACKGROUND: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis). METHODS: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net. RESULTS: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality. CONCLUSIONS: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Metales , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aterosclerosis/orina , Aterosclerosis/mortalidad , Cadmio/orina , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/orina , Cobalto/orina , Cobre/orina , Etnicidad , Incidencia , Metales/orina , Estudios Prospectivos , Factores de Riesgo , Tungsteno/orina , Estados Unidos/epidemiología , Uranio/orina , Zinc/orina
3.
Circulation ; 149(7): 521-528, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38235551

RESUMEN

BACKGROUND: Racism is highly prevalent in the United States. Few data exist about whether perceived interpersonal racism is associated with risk of coronary heart disease (CHD). METHODS: We followed 48 305 participants in the Black Women's Health Study through biennial mailed and Internet-based health questionnaires from 1997, when they provided information on perceived interpersonal racism and were free of cardiovascular disease and cancer, until the end of 2019. We averaged participant responses to 5 validated questions about perceived interpersonal racism in everyday activities, such as "people act as if they think you are dishonest." We summed the positive responses to 3 questions about perceived racism in interactions that involved jobs, housing, and police; scores ranged from 0 (no to all) to 3 (yes to all). CHD cases were defined as nonfatal myocardial infarctions confirmed through medical records, fatal cases identified through the National Death Index, and self-reported revascularization events. We used Cox proportional hazard models adjusting for major confounders to estimate hazard ratios (HRs). RESULTS: During 22 years of follow-up, we identified 1947 incident CHD cases. For women who reported experiences of racism in employment, housing, or involving the police relative to women who reported no such experiences, the age-adjusted HR for CHD was 1.35 (95% CI, 1.13-1.61; Ptrend=0.006), and the multivariable HR for CHD was 1.26 (95% CI, 1.05-1.51; Ptrend=0.05). For women in the highest quartile of perceived interpersonal racism in daily life relative to women in the lowest quartile, the age-adjusted HR for CHD was 1.25 (95% CI, 1.07-1.46; Ptrend=0.006). After multivariable adjustment, the HR was attenuated and no longer statistically significant. CONCLUSIONS: Perceived experiences of interpersonal racism in employment, in housing, and with the police were associated with higher incidence of CHD among Black women, whereas perceived racism in everyday life was not associated with higher risk.


Asunto(s)
Enfermedad Coronaria , Infarto del Miocardio , Racismo , Humanos , Femenino , Estados Unidos/epidemiología , Enfermedad Coronaria/epidemiología , Población Negra , Salud de la Mujer , Infarto del Miocardio/epidemiología , Incidencia , Factores de Riesgo , Negro o Afroamericano
4.
Circ Res ; 132(4): 452-464, 2023 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-36691918

RESUMEN

BACKGROUND: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). METHODS: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). RESULTS: Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.


Asunto(s)
Enfermedad Coronaria , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Estudios Prospectivos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios de Casos y Controles , Proteómica , Apolipoproteínas , Factores de Riesgo , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , Triglicéridos , HDL-Colesterol , Lipoproteína(a) , Apolipoproteínas B/uso terapéutico , Apolipoproteína A-I
5.
Circ Res ; 132(12): 1692-1706, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289902

RESUMEN

Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic disease. Food insecurity is an example of a powerful social determinant of health that impacts health outcomes. Nutrition insecurity, a distinct but related concept to food insecurity, is a direct determinant of health. In this article, we provide an overview of how diet in early life relates to cardiometabolic disease and then continue to focus on the concepts of food insecurity and nutrition insecurity. In the discussions herein we make important distinctions between the concepts of food insecurity and nutrition insecurity and provide a review of their concepts, histories, measurement and assessment devices, trends and prevalence, and links to health and health disparities. The discussions here set the stage for future research and practice to directly address the negative consequences of food and nutrition insecurity.


Asunto(s)
Enfermedades Cardiovasculares , Desnutrición , Humanos , Estados Unidos/epidemiología , Dieta , Estado Nutricional , Alimentos , Enfermedades Cardiovasculares/epidemiología
6.
Artículo en Inglés | MEDLINE | ID: mdl-39445427

RESUMEN

BACKGROUND: Chronic kidney disease confers a high risk of atherosclerotic cardiovascular disease (ASCVD), partly due to hyperlipidemia. Although statins reduce the risk of ASCVD in chronic kidney disease, residual risk persists. We investigated whether higher remnant cholesterol is associated with an increased risk of ASCVD in statin users and nonusers with impaired renal function. METHODS: We included 107 925 individuals from CGPS (Copenhagen General Population Study) initiated in 2003 to 2015, of whom 10 427 had impaired renal function (estimated glomerular filtration rate, <60 mL/min per 1.73 m2). Remnant cholesterol was calculated from a standard lipid profile. ASCVD was myocardial infarction, coronary heart disease death, ischemic stroke, coronary artery bypass graft, or percutaneous coronary intervention extracted from Danish nationwide health registries from baseline through 2018; individuals with events before the start of follow-up were excluded from relevant analysis. RESULTS: In individuals with impaired renal function during up to 15 years of follow-up, 597 were diagnosed with myocardial infarction, 618 with ischemic stroke, and 1182 with ASCVD. In these individuals, a 1-mmol/L (39 mg/dL) higher remnant cholesterol level was associated with multivariable-adjusted hazard ratios of 1.21 (95% CI, 1.03-1.43) for myocardial infarction, 1.12 (95% CI, 0.93-1.34) for ischemic stroke, and 1.19 (95% CI, 1.05-1.35) for ASCVD. Corresponding hazard ratios for ASCVD were 1.36 (95% CI, 1.01-1.81) in statin users and 1.16 (95% CI, 1.01-1.33) in nonusers. Of the 1.36-fold excess risk of ASCVD in impaired versus normal renal function, elevated remnant cholesterol and elevated LDL (low-density lipoprotein) cholesterol explained 25% (95% CI, 2.5%-47%) and 0% in statin users and 8.3% (95% CI, 2.4%-14%) and 14% (95% CI, 6.4%-22%) in nonusers, respectively. CONCLUSIONS: Our results suggest that higher remnant cholesterol is a good marker of increased risk of ASCVD in individuals with impaired renal function, while higher LDL cholesterol may not be. Patients with chronic kidney disease who have high levels of remnant cholesterol are identifiable through higher non-HDL (high-density lipoprotein) cholesterol or apoB levels.

7.
Arterioscler Thromb Vasc Biol ; 44(1): 314-321, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37970719

RESUMEN

BACKGROUND: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied. METHODS: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively). RESULTS: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg. CONCLUSIONS: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.


Asunto(s)
Enfermedad Coronaria , Sobrepeso , Masculino , Humanos , Adulto Joven , Adulto , Sobrepeso/epidemiología , Sobrepeso/complicaciones , Peso al Nacer , Índice de Masa Corporal , Factores de Riesgo , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/complicaciones
8.
Circulation ; 147(3): 254-266, 2023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-36649394

RESUMEN

Cardiac rehabilitation (CR) is a guideline-recommended, multidisciplinary program of exercise training, risk factor management, and psychosocial counseling for people with cardiovascular disease (CVD) that is beneficial but underused and with substantial disparities in referral, access, and participation. The emergence of new virtual and remote delivery models has the potential to improve access to and participation in CR and ultimately improve outcomes for people with CVD. Although data suggest that new delivery models for CR have safety and efficacy similar to traditional in-person CR, questions remain regarding which participants are most likely to benefit from these models, how and where such programs should be delivered, and their effect on outcomes in diverse populations. In this review, we describe important gaps in evidence, identify relevant research questions, and propose strategies for addressing them. We highlight 4 research priorities: (1) including diverse populations in all CR research; (2) leveraging implementation methodologies to enhance equitable delivery of CR; (3) clarifying which populations are most likely to benefit from virtual and remote CR; and (4) comparing traditional in-person CR with virtual and remote CR in diverse populations using multicenter studies of important clinical, psychosocial, and cost-effectiveness outcomes that are relevant to patients, caregivers, providers, health systems, and payors. By framing these important questions, we hope to advance toward a goal of delivering high-quality CR to as many people as possible to improve outcomes in those with CVD.


Asunto(s)
Rehabilitación Cardiaca , Enfermedades Cardiovasculares , Humanos , Rehabilitación Cardiaca/métodos , Lagunas en las Evidencias , Enfermedades Cardiovasculares/terapia , Cuidadores
9.
Circulation ; 148(9): e9-e119, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37471501

RESUMEN

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.


Asunto(s)
Cardiología , Enfermedad Coronaria , Isquemia Miocárdica , Humanos , American Heart Association , Isquemia Miocárdica/diagnóstico , Antígeno Nuclear de Célula en Proliferación , Estados Unidos
10.
Stroke ; 55(1): 40-49, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38018831

RESUMEN

BACKGROUND: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death. METHODS: The dental cohort (n=6351) of the ARIC study (Atherosclerosis Risk in Communities) was followed for incident ischemic stroke, CHD event, and all-cause mortality. Of all the participants at visit 4 (n=11 656), those who were unable to go through dental examination, or with prevalent ischemic stroke and CHD events, were excluded. The full-mouth dental examination was conducted at visit 4 (1996-1998), assessing dental caries. The dose response of decayed, missing, and filled surfaces due to caries was assessed and related to the outcome. Outcomes were assessed through the end of 2019. Additionally, the effect of regular dental care utilization on dental caries was evaluated. RESULTS: Participants with ≥1 dental caries had an increased risk of stroke (adjusted hazard ratio [HR], 1.40 [95% CI, 1.10-1.79]) and death (adjusted HR, 1.13 [95% CI, 1.01-1.26]) but not for CHD events (adjusted HR, 1.13 [95% CI, 0.93-1.37]). The association of dental caries and ischemic incident stroke was significantly higher in the African American population compared with the White subgroup (interaction term P=0.0001). Increasing decayed, missing, and filled surfaces were significantly associated with stroke (adjusted HR, 1.006 [95% CI, 1.001-1.011]) and death (adjusted HR, 1.003 [95% CI, 1.001-1.005]) but not CHD (adjusted HR, 1.002 [95% CI, 1.000-1.005]). Regular dental care utilization lowered (adjusted odds ratio, 0.19 [95% CI, 0.16-0.22]; P<0.001) the chance of caries. CONCLUSIONS: Among the cohort, dental caries was independently associated with the risk of ischemic stroke and death, with the effect higher in African American participants. Regular dental care utilization was associated with a lower chance of caries, emphasizing its relevance in the prevention of these events.


Asunto(s)
Enfermedad Coronaria , Caries Dental , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Humanos , Estados Unidos/epidemiología , Caries Dental/epidemiología , Factores de Riesgo , Incidencia , Enfermedad Coronaria/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/diagnóstico
11.
Am Heart J ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39442855

RESUMEN

Colchicine has emerged as an effective agent for reducing ASCVD based on recent large cardiovascular outcome trials and exerts its benefit through targeting inflammation. In light of the robust body of data and FDA approval of low-dose colchicine for ASCVD prevention, this paper aimed to use the National Prescription Audie to quantify the volume and trends of colchicine prescriptions dispensed rough U.S. retail pharmacies between March 2018 and February 2024. Despite a 6% increase in total monthly prescriptions since 2020, driven primarily by cardiologists, this specialty still represents only 2.8-4% of the national monthly totals with small absolute numbers (i.e. estimated ∼4000 incremental prescriptions/month since 2020), suggesting limited cardiologist adoption of colchicine for ASCVD prevention despite favorable clinical trial data.

12.
Cytometry A ; 105(8): 639-652, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38867433

RESUMEN

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis. To this end, we have developed a 7-marker flow cytometry panel for analyzing NETosis on human peripheral neutrophils following in vitro stimulation, and in fresh circulating neutrophils under inflammatory conditions. This panel was optimized on neutrophils isolated from whole blood and analyzed fresh or in vitro stimulated with phorbol 12-myristate 13-acetate (PMA) or ionomycin, two known NET-inducing agonists. Neutrophils were identified as SSChighFSChighCD15+CD66b+. Neutrophils positive for amine residues and 7-Aminoactinomycin D (7-AAD), our DNA dye of choice, were deemed necrotic (Zombie-NIR+7-AAD+) and were removed from downstream analysis. Exclusion of Zombie-NIR and positivity for 7-AAD (Zombie-NIRdim7-AAD+) was used here as a marker of neutrophil-appendant DNA, a key feature of NETs. The presence of two NET-associated proteins - myeloperoxidase (MPO) and neutrophil elastase (NE) - were utilized to identify neutrophil-appendant NET events (SSChighFSChighCD15+CD66b+Zombie NIRdim7-AAD+MPO+NE+). We also demonstrate that NETotic neutrophils express citrullinated histone H3 (H3cit), are concentration-dependently induced by in vitro PMA and ionomycin stimulation but are disassembled with DNase treatment, and are present in both chronic and acute inflammation. This 7-color flow cytometry panel provides a novel tool for examining NETosis in humans.


Asunto(s)
Trampas Extracelulares , Citometría de Flujo , Neutrófilos , Acetato de Tetradecanoilforbol , Humanos , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Citometría de Flujo/métodos , Acetato de Tetradecanoilforbol/farmacología , Ionomicina/farmacología , Fenotipo , Peroxidasa/metabolismo , Inflamación/inmunología , Biomarcadores/metabolismo , Elastasa de Leucocito/metabolismo
13.
Curr Atheroscler Rep ; 26(11): 649-658, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39243345

RESUMEN

PURPOSE OF REVIEW: To summarize the recent evidence and guideline recommendations on aspirin or P2Y12 inhibitor monotherapy in patients with stable ischemic heart disease and provide insights into future directions on this topic, which involves transition to a personalized assessment of bleeding and thrombotic risks. RECENT FINDINGS: It has been questioned whether the evidence for aspirin as the foundational component of secondary prevention in patients with coronary artery disease aligns with contemporary pharmaco-invasive strategies. The recent HOST-EXAM study randomized patients who had received dual antiplatelet therapy for 6 to 18 months without ischemic or major bleeding events to either clopidogrel or aspirin for a further 24 months, and demonstrated that the patients in the clopidogrel arm had significantly lower rates of both thrombotic and bleeding complications compared to those in the aspirin arm. The patient-level PANTHER meta-analysis showed that in patients with established coronary artery disease, P2Y12 inhibitor monotherapy was associated with lower rates of myocardial infarction, stent thrombosis as well as gastrointestinal bleeding and hemorrhagic stroke compared to aspirin monotherapy, albeit with similar rates of all-cause mortality, cardiovascular mortality and major bleeding. Long-term low-dose aspirin is recommended for secondary prevention in patients with stable ischemic heart disease, with clopidogrel monotherapy being acknowledged as a feasible alternative. Dual antiplatelet therapy for six months after percutaneous coronary intervention remains the standard recommendation for patients with stable ischemic heart disease. However, the duration of dual antiplatelet therapy may be shortened and followed by P2Y12 inhibitor monotherapy or prolonged based on individualized evaluation of the patient's risk profile.


Asunto(s)
Aspirina , Isquemia Miocárdica , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Humanos , Aspirina/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Isquemia Miocárdica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria/métodos , Hemorragia/inducido químicamente , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Terapia Antiplaquetaria Doble/métodos
14.
Circ Res ; 130(4): 529-551, 2022 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-35175840

RESUMEN

Ischemic heart disease (IHD) is the leading cause of mortality in women. While traditional cardiovascular risk factors play an important role in the development of IHD in women, women may experience sex-specific IHD risk factors and pathophysiology, and thus female-specific risk stratification is needed for IHD prevention, diagnosis, and treatment. Emerging data from the past 2 decades have significantly improved the understanding of IHD in women, including mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries. Despite this progress, sex differences in IHD outcomes persist, particularly in young women. This review highlights the contemporary understanding of coronary arterial function and disease in women with no obstructive coronary arteries, including coronary anatomy and physiology, mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries, noninvasive and invasive diagnostic strategies, and management of IHD.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Circulación Coronaria/fisiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiología , Antagonistas Adrenérgicos beta/uso terapéutico , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Conducta de Reducción del Riesgo
15.
Eur Radiol ; 34(10): 6568-6577, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38676731

RESUMEN

OBJECTIVES: This study aimed to compare the image quality and diagnostic performance of standard-resolution (SR) and ultra-high-resolution (UHR) coronary CT angiography (CCTA) based on photon-counting detector CT (PCD-CT) of coronary stents and explore the best reconstruction kernel for stent imaging. METHODS: From July 2023 to September 2023, patients were enrolled to undergo CCTA using a dual-source PCD-CT system after coronary angioplasty with stent placement. SR images with a slice thickness/increment of 0.6/0.4 mm were reconstructed using a vascular kernel (Bv48), while UHR images with a slice thickness/increment of 0.2/0.2 mm were reconstructed using vascular kernels of six sharpness levels (Bv48, Bv56, Bv60, Bv64, Bv72, and Bv76). The in-stent lumen diameters were evaluated. Subjective image quality was also evaluated by a 5-point Likert scale. Invasive coronary angiography was conducted in 12 patients (25 stents). RESULTS: Sixty-nine patients (68.0 [61.0, 73.0] years, 46 males) with 131 stents were included. All UHR images had significantly larger in-stent lumen diameter than SR images (p < 0.001). Specifically, UHR-Bv72 and UHR-Bv76 for in-stent lumen diameter (2.17 [1.93, 2.63] mm versus 2.20 [1.93, 2.59] mm) ranked the two best kernels. The subjective analysis demonstrated that UHR-Bv72 images had the most pronounced effect on reducing blooming artifacts, showcasing in-stent lumen and stent demonstration, and diagnostic confidence (p < 0.001). Furthermore, SR and UHR-Bv72 images showed a diagnostic accuracy of 78.3% (95% confidence interval [CI]: 56.3%-92.5%) and 88.0% (95%CI: 68.8%-97.5%), respectively. CONCLUSION: UHR CCTA by PCD-CT leads to significantly improved visualization and diagnostic performance of coronary stents, and Bv72 is the optimal reconstruction kernel showing the stent struts and in-stent lumen. CLINICAL RELEVANCE STATEMENT: The significantly improved visualization of coronary stents using ultra-high resolution CCTA could increase the diagnostic accuracy for in-stent restenosis and avoid unnecessary invasive quantitative coronary angiography, thus changing the clinical management for patients after percutaneous coronary intervention. KEY POINTS: Coronary stent imaging is challenging with energy-integrating detector CT due to "blooming artifacts." UHR images using a PCD-CT enhanced coronary stent visualization. UHR coronary stent imaging demonstrated improved diagnostic accuracy in clinical settings.


Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía Coronaria , Stents , Humanos , Femenino , Masculino , Anciano , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Persona de Mediana Edad , Fotones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía
16.
Arterioscler Thromb Vasc Biol ; 43(7): 1324-1333, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37199161

RESUMEN

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between levels of LE8 and the risk of cardiovascular disease (CVD) outcomes is not known from a large prospective cohort. We aim to analyze the relationship between CVH, indicated by LE8, and risks of coronary heart disease (CHD), stroke, and CVD. Moreover, we sought to test whether the genetic susceptibility to CHD or stroke could be modified by LE8. METHODS: A total of 137 794 participants free of CVD from the UK Biobank were included. CVH was scored using LE8 and categorized as low, moderate, and high. RESULTS: During a median of 10 years, 8595 CVD cases (6968 CHDs and 1948 strokes) were documented. A higher LE8 score was associated with remarkably lower risks of CHD, stroke, and CVD (P<0.001 for all). Comparing the high CVH to the low CVH, the hazard ratios (95% CI) were 0.34 (0.30-0.38) for CHD, 0.45 (0.37-0.54) for stroke, and 0.36 (0.33-0.40) for CVD. Moreover, the model with LE8 achieved higher accuracy and outperformed the model with Life's Simple 7 for CHD, stroke, and CVD (P<0.001 for all). The protective associations of the LE8 score with CVD outcomes were more pronounced among women (P interaction, <0.001 for CHD and 0.0013 for CVD, respectively) and among younger adults (P interaction, <0.001, 0.007, and <0.001 for CHD, stroke, and CVD, respectively). In addition, a significant interaction was found between the genetic risk of CHD and the LE8 score (P interaction, <0.001). The inverse association was stronger among those with a lower genetic risk of CHD. CONCLUSIONS: High level of CVH, defined by LE8, was associated with significantly lower risks of CHD, stroke, and CVD.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad Coronaria , Accidente Cerebrovascular , Adulto , Estados Unidos/epidemiología , Humanos , Femenino , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética
17.
Lipids Health Dis ; 23(1): 238, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095825

RESUMEN

Multi-vessel coronary disease (MVCD) is a severe form of coronary artery disease (CAD) that significantly increases the risk of acute coronary syndrome (ACS) and heart attacks. The triglyceride glucose (TyG) index is a reliable and convenient marker for insulin resistance (IR). Recent studies have demonstrated its predictive value for CAD in patients with MVCD. This review aims to explore the application of the TyG index in managing MVCD and its underlying pathogenesis to enhance risk stratification and improve therapeutic decision-making.


Asunto(s)
Glucemia , Enfermedad de la Arteria Coronaria , Resistencia a la Insulina , Triglicéridos , Humanos , Triglicéridos/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Glucemia/metabolismo , Biomarcadores/sangre , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico
18.
Clin Rehabil ; 38(2): 184-201, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37731365

RESUMEN

OBJECTIVE: To explore the extent and type of evidence in relation to group-based cardiac telerehabilitation interventions and health outcomes in coronary artery disease patients. DATA SOURCES: A literature search was conducted in August 2022 and July 2023 in databases including PubMed, CINAHL, Scopus and PsycINFO. The search process followed the scoping review methodology guided by the Joanna Briggs Institute for scoping reviews. METHODS: The inclusion criteria were a peer-reviewed journal article published in English between 1 January 2017 and 15 August 2022 and updated to cover until 15 July 2023 concerning group-based cardiac telerehabilitation in adult coronary artery disease patients. All group-based cardiac telerehabilitation interventions and health outcome types were charted and summarized. RESULTS: The researcher screened a total of 2089 articles, of which 22 were retained with a total of 1596 participants. Group-based cardiac telerehabilitation interventions were particularly useful for patients with multi-faceted technological applications and social support. The patients received guidance regarding cardiovascular disease risk factors. Physical fitness, psychological complaints and quality of life were often measured outcomes in the included studies. CONCLUSIONS: This scoping review indicates the success of various rehabilitation interventions utilizing different technologies for coronary patients. Coronary patients were guided in making lifestyle changes, and positive findings were observed in the health outcomes measured after the telerehabilitation intervention. The findings of this review can provide valuable guidance for developing and evaluating sustainable group-based cardiac telerehabilitation programs that aim to benefit coronary patients.


Asunto(s)
Enfermedad de la Arteria Coronaria , Telerrehabilitación , Adulto , Humanos , Enfermedad de la Arteria Coronaria/rehabilitación , Telerrehabilitación/métodos , Calidad de Vida , Aptitud Física , Evaluación de Resultado en la Atención de Salud
19.
Nurs Health Sci ; 26(1): e13109, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38467127

RESUMEN

Postmenopausal women with negative personality characteristics are at an increased risk of psychological disorders, yet little is known about the mechanism underlying the relationship between type D personality and psychological distress in postmenopausal women with coronary disease. This study assessed the mediating roles of perceived social support and self-perceived burden in the relationship between type D and psychological distress based on the equity theory and stress-buffering model. Demographic characteristics, type D, psychological distress, perceived social support, and self-perceived burden were completed by 335 participants with self-reported questionnaires using a cross-sectional design in Southeast China. The results revealed that perceived social support and self-perceived burden both separately and serially mediated the relationship between type D personality and psychological distress. Effective intervention strategies aimed at improving perceived social support or reducing self-perceived burden may be beneficial in reducing psychological distress.


Asunto(s)
Enfermedad de la Arteria Coronaria , Distrés Psicológico , Humanos , Femenino , Estudios Transversales , Análisis de Mediación , Posmenopausia , Personalidad , Estrés Psicológico/complicaciones , Estrés Psicológico/psicología , Apoyo Social
20.
Medicina (Kaunas) ; 60(9)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39336544

RESUMEN

Background and Objectives: The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods: This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results: A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm2/m2. The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment (p = 0.004), age (p = 0.003), diabetes mellitus (p = 0.016) and STS score (p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis (p ≤ 0.001). Conclusions: Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.


Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedad de la Arteria Coronaria , Humanos , Masculino , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/mortalidad , Femenino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Pronóstico , Incidencia , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Serbia/epidemiología , Enfermedades Asintomáticas/epidemiología , Índice de Severidad de la Enfermedad , Factores de Riesgo
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