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2.
Int J Cardiol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32360645

RESUMO

BACKGROUND: Although percutaneous coronary intervention (PCI) has been the mainstay of revascularization strategy for significant coronary artery disease, future cancer risk after PCI has never been explored. We aimed to investigate the risk of incident cancer in patients undergoing PCI for the first time. METHODS: We studied 125,613 patients who underwent the first PCI between 2010 and 2015 without a prior history of cancer. For comparison, we selected 628,065 age- and sex-matched controls without any history of cancer or PCI who completed the assigned national health examination during the same period. RESULTS: During a median 4.56 years (interquartile range, 3.06-6.13 years), 8528 patients from the PCI group and 40,166 controls were newly diagnosed with cancer (incidence rate, 15.1 vs. 13.9 per 1000 person-years, p < 0.0001). Patients undergoing PCI presented a higher risk for cancer development than the controls in multivariable Cox analysis (adjusted HR [aHR] 1.06, 95% CI 1.04-1.09, p < 0.0001). To minimize potential surveillance bias, we performed 1-year lag analysis by eliminating participants who developed cancer within 1 year from the PCI. In this analysis, the increased risk of overall cancer in the PCI group became insignificant (aHR 1.02, 95% CI 0.99-1.05, p = 0.2017). Regarding site-specific cancers, however, the risk of lung and hematologic malignancies remained higher and the risk of gastrointestinal, liver/biliary/pancreas, thyroid, and breast cancers remained lower in the PCI group. CONCLUSIONS: Differential future cancer risks were observed in patients undergoing PCI. The results suggest that specialized surveillance strategy might be warranted for this expanding population.

3.
PLoS One ; 15(5): e0232573, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374784

RESUMO

OBJECTIVES: To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND: Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS: Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS: The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS: An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level.

4.
Fetal Pediatr Pathol ; : 1-8, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400248

RESUMO

Introduction: We studied the association between Henoch-Schönlein purpura nephritis (HSPN) and complement system activation. Methods: We retrospectively reviewed the pathologic findings and medical records of 35 children and 12 adults with HSPN and compared the differences according to C4d positivity in three groups consisting of total 47 patients, 35 pediatric and 12 adult patients, respectively. C4d staining of renal biopsy was additionally performed at the time of diagnosis or retrospectively using archival biopsy material. Results: The overall rate of C4d positivity was 53.2%: 20 (57.1%) of the 35 children and five (41.7%) of the 12 adults. Among the groups there was no significant difference in the severity of proteinuria, renal function, presence of crescents or mesangial proliferation stratified by C4d positivity, unlike IgA nephropathy. Conclusions: We suggest that the activation of complement system is not correlated with the clinical or pathological severity of HSPN.

5.
Circ Cardiovasc Imaging ; 13(5): e009707, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32418453

RESUMO

BACKGROUND: There is a lack of studies investigating the heterogeneity of patients with aortic stenosis (AS). We explored whether cluster analysis identifies distinct subgroups with different prognostic significances in AS. METHODS: Newly diagnosed patients with moderate or severe AS were prospectively enrolled between 2013 and 2016 (n=398, mean 71 years, 55% male). Among demographics, laboratory, and echocardiography parameters (n=32), 11 variables were selected through dimension reduction and used for unsupervised clustering. Phenotypes and causes of mortality were compared between the clusters. RESULTS: Three clusters with markedly different features were identified. Cluster 1 (n=60) was predominantly associated with cardiac dysfunction, cluster 2 (n=86) consisted of elderly with comorbidities, especially end-stage renal disease, whereas cluster 3 (n=252) demonstrated neither cardiac dysfunction nor comorbidities. Although AS severity did not differ, there was a significant difference in adverse outcomes between the clusters during a median 2.4 years follow-up (mortality rate, 13.3% versus 19.8% versus 6.0% for cluster 1, 2, and 3, P<0.001). Particularly, compared with cluster 3, cluster 1 was associated with only cardiac mortality (adjusted hazard ratio, 7.37 [95% CI, 2.00-27.13]; P=0.003), whereas cluster 2 was associated with higher noncardiac mortality (adjusted hazard ratio, 3.35 [95% CI, 1.26-8.90]; P=0.015). Phenotypes and association of clusters with specific outcomes were reproduced in an independent validation cohort (n=262). CONCLUSIONS: Unsupervised cluster analysis of patients with AS revealed 3 distinct groups with different causes of death. This provides a new perspective in the categorization of patients with AS that takes into account comorbidities and extravalvular cardiac dysfunction.

6.
J Microbiol ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323196

RESUMO

Multiple transcriptional regulators play important roles in the coordination of developmental processes, including asexual and sexual development, and secondary metabolism in the filamentous fungus Aspergillus nidulans. In the present study, we characterized a novel putative C2H2-type transcription factor (TF), RocA, in relation to development and secondary metabolism. Deletion of rocA increased conidiation and caused defective sexual development. In contrast, the overexpression of rocA exerted opposite effects on both phenotypes. Additionally, nullifying rocA resulted in enhanced brlA expression and reduced nsdC expression, whereas its overexpression exerted the opposite effects. These results suggest that RocA functions as a negative regulator of asexual development by repressing the expression of brlA encoding a key asexual development activator, but as a positive regulator of sexual development by enhancing the expression of nsdC encoding a pivotal sexual development activator. Deletion of rocA increased the production of sterigmatocystin (ST), as well as the expression of its biosynthetic genes, aflR and stcU. Additionally, the expression of the biosynthetic genes for penicillin (PN), ipnA and acvA, and for terrequinone (TQ), tdiB and tdiE, was increased by rocA deletion. Thus, it appears that RocA functions as a negative transcriptional modulator of the secondary metabolic genes involved in ST, PN, and TQ biosynthesis. Taken together, we propose that RocA is a novel transcriptional regulator that may act either positively or negatively at multiple target genes necessary for asexual and sexual development and secondary metabolism.

7.
Int J Stem Cells ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32323512

RESUMO

Cell labeling technologies are required to monitor the fate of transplanted cells in vivo and to select target cells for the observation of certain changes in vitro. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been transplanted for the treatment of heart injuries or used in vitro for preclinical cardiac safety assessments. Cardiomyocyte (CM) labeling has been used in these processes to facilitate target cell monitoring. However, the functional effect of the labeling agent on hiPSC-CMs has not been studied. Therefore, we investigated the effects of labeling agents on CM cellular functions. 3'-Dioctadecyloxacarbocyanine perchlorate (DiO), quantum dots (QDs), and a DNA plasmid expressing EGFP using Lipo2K were used to label hiPSC-CMs. We conclude that the hiPSC-CM labeling with DiO and QDs does not induce arrhythmogenic effects but rather improves the mRNA expression of cardiac ion channels and Ca2+ influx by L-type Ca2+ channels. Thus, DiO and QD labeling agents may be useful tools to monitor transplanted CMs, and further in vivo influences of the labeling agents should be investigated in the future.

8.
J Cardiovasc Magn Reson ; 22(1): 25, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32321533

RESUMO

BACKGROUND: Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. METHODS: This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). RESULTS: CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: - 24.2 ± 2.7% in cirrhosis vs - 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from - 24.9 ± 2.4% to - 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). CONCLUSIONS: Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

10.
Biomolecules ; 10(2)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033247

RESUMO

Cytokines and chemokines are transcriptionally regulated by inflammatory transcription factors such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor (IRF)-3. A daidzein derivative compound, 8-hydroxydaidzein (8-HD), isolated from soy products, has recently gained attention due to various pharmacological benefits, including anti-inflammatory activities. However, regulation of the inflammatory signaling mechanism for 8-HD is still poorly understood, particularly with respect to the IRF-3 signaling pathway. In this study, we explored the molecular mechanism of 8-HD in regulating inflammatory processes, with a focus on the IRF-3 signaling pathway using a lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid [Poly (I:C)] stimulated murine macrophage cell line (RAW264.7). The 8-HD downregulated the mRNA expression level of IRF-3-dependent genes by inhibiting phosphorylation of the IRF-3 transcription factor. The inhibitory mechanism of 8-HD in the IRF-3 signaling pathway was shown to inhibit the kinase activity of IKKε to phosphorylate IRF-3. This compound can also interfere with the TRIF-mediated complex formation composed of TRAF3, TANK, and IKKε leading to downregulation of AKT phosphorylation and reduction of IRF-3 activation, resulted in inhibition of IRF-3-dependent expression of genes including IFN-ß, C-X-C motif chemokine 10 (CXCL10), and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). Therefore, these results strongly suggest that 8-HD can act as a promising compound with the regulatory function of IRF-3-mediated inflammatory responses.

11.
Eur J Prev Cardiol ; 27(8): 870-881, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32013600

RESUMO

AIMS: Dyslipidaemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We investigated the risks of death and cardiovascular disease in relation to each lipid component to establish evidence for primary prevention in young adults. METHODS: In this nationwide population-based cohort study, we analysed 5,688,055 statin-naïve subjects, aged 20-39 years, undergoing general health check-ups between 2009 and 2014. The endpoint was a composite of clinical events including death, myocardial infarction (MI), and stroke. We compared the incidence and risk of clinical events according to each lipid variable. RESULTS: During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%): 16,262 deaths (0.29%), 8578 MIs (0.15%), and 5967 strokes (0.10%). The risk of clinical events gradually increased with increasing total cholesterol (TC) and triglycerides and decreasing high-density lipoprotein cholesterol (HDL-C), largely driven by MI. Low-density lipoprotein cholesterol (LDL-C) had a J-shaped association with clinical events, showing the lowest risk for LDL-C of 84-101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted hazard ratio, 1.20; p < 0.001) after adjusting for conventional risk factors. CONCLUSIONS: For statin-naïve young adults, the risk of clinical events was proportional to lipid levels, positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had an independent and the strongest association with the clinical events. Screening and intervention for abnormal lipid levels, particularly triglycerides, from an early age might be of clinical value.

12.
Eur Heart J Cardiovasc Imaging ; 21(5): 479-488, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32065624

RESUMO

AIMS: In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. METHODS AND RESULTS: Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004). CONCLUSION: Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.

13.
J Am Coll Cardiol ; 75(4): 380-390, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32000949

RESUMO

BACKGROUND: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis. OBJECTIVES: The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition. METHODS: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure. RESULTS: The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005). CONCLUSIONS: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.

14.
J Am Heart Assoc ; 9(5): e013958, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32089046

RESUMO

Background Rapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography-determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP. Methods and Results Qualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher-ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78-0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52-0.67]; Duke coronary artery disease score, 0.74 [0.68-0.79]; ML model 1, 0.62 [0.55-0.69]; ML model 2, 0.73 [0.67-0.80]; all P<0.001; statistical model, 0.81 [0.75-0.87], P=0.128). Conclusions Based on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP.

15.
J Clin Hypertens (Greenwich) ; 22(2): 261-269, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32003938

RESUMO

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

16.
J Med Internet Res ; 22(1): e15057, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32012053

RESUMO

BACKGROUND: In addition to medication, health behavior management is crucial in patients with multiple risks of cardiovascular mortality. OBJECTIVE: This study aimed to examine the efficacy of a 3-month Smart Management Strategy for Health-based electronic program (Smart Healthing). METHODS: A 2-arm randomized controlled trial was conducted to assess the efficacy of Smart Healthing in 106 patients with at least one indicator of poor disease control and who had hypertension, diabetes, or hypercholesterolemia. The intervention group (n=53) took part in the electronic program, which was available in the form of a mobile app and a Web-based PC application. The program covered 4 areas: self-assessment, self-planning, self-learning, and self-monitoring by automatic feedback. The control group (n=53) received basic educational material concerning disease control. The primary outcome was the percentage of participants who achieved their clinical indicator goal after 12 weeks into the program: glycated hemoglobin (HbA1c) <7.0%, systolic blood pressure (SBP) <140 mmHg, or low-density lipoprotein cholesterol <130 mg/dL. RESULTS: The intervention group showed a significantly higher success rate (in comparison with the control group) for achieving each of 3 clinical indicators at the targeted goal levels (P<.05). Only the patients with hypertension showed a significant improvement in SBP from the baseline as compared with the control group (72.7% vs 35.7%; P<.05). There was a significant reduction in HbA1c in the intervention group compared with the control group (difference=0.54%; P≤.05). In the intervention group, 20% of patients with diabetes exhibited a ≥1% decrease in HbA1c (vs 0% among controls; P≤.05). CONCLUSIONS: A short-term self-management strategy-based electronic program intervention may improve clinical outcomes among patients with cardiovascular risks. TRIAL REGISTRATION: ClinicalTrials.gov NCT03294044; https://clinicaltrials.gov/ct2/show/NCT03294044.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32063545

RESUMO

BACKGROUND AND AIMS: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex. METHODS: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed. RESULTS: The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. CONCLUSIONS: PAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden.

18.
Eur Heart J Cardiovasc Imaging ; 21(4): 363-374, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31985803

RESUMO

AIMS: There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. METHODS AND RESULTS: A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55-65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41-0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). CONCLUSION: Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01443637.

19.
Circ Res ; 126(7): 824-835, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31978313

RESUMO

RATIONALE: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. OBJECTIVE: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. METHODS AND RESULTS: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20-1.53) for total cholesterol, 1.41 (1.25-1.60) for LDL-C, 1.28 (1.11-1.47) for triglycerides, and 0.82 (0.72-0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. CONCLUSIONS: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.

20.
JAMA Cardiol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31968065

RESUMO

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

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