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AIMS: Thoracic aortic diameter is modulated by various factors including both physiological and pathological mechanisms. The aim of this study was to explore the determinants of thoracic aortic size focusing on arterial blood pressure and physical activity in normotensive and hypertensive individuals. METHODS: Ascending and descending aortic diameters were measured in participants of the Copenhagen General Population Study using thoracic CT angiography. To assess the relation between arterial blood pressure and thoracic aortic diameters, individuals with diabetes, hypercholesterolemia, smoking, and prescribed antihypertensive medication were excluded. Intensity of physical activity was recorded based on self-reported questionnaire data. RESULTS: A total of 1214 normotensive and 284 hypertensive individuals were examined. In all individuals, male sex, older age, and body surface area were associated with higher diameters of the ascending and descending aorta ( P â<â0.01). In normotensive individuals, hard physical activity >â4âh/week was independently associated with higher thoracic aortic diameters (ascending ß:1.09[0.52;1.66] and descending ß : 0.47[0.14;0.80], both P â<â0.01), whereas higher systolic blood pressure was not associated with thoracic aortic diameters (ascending P â=â0.12 and descending p â=â0.33). In hypertensive individuals, higher systolic blood pressure (per 10âmmHg) was independently associated with higher thoracic aortic diameters (ascending ß : 0.55[0.17;0.94] and descending ß : 0.23[0.10;0.37] mm/10âmmHg, both P â<â0.01), whereas hard physical activity was not associated with higher aortic diameters (ascending P â=â0.11 and descending P â=â0.51). CONCLUSION: In normotensive individuals hard physical activity, and in hypertensive individuals increasing systolic blood pressure are factors each independently associated with larger thoracic aortic size. These findings suggest a context sensitive mode of aortic vascular response to size modulating adaptation.
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Aorta Torácica , Presión Sanguínea , Hipertensión , Humanos , Masculino , Hipertensión/fisiopatología , Femenino , Persona de Mediana Edad , Aorta Torácica/fisiopatología , Aorta Torácica/diagnóstico por imagen , Anciano , Presión Sanguínea/fisiología , Ejercicio Físico , AdultoRESUMEN
BACKGROUND: Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women. METHODS: The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta. RESULTS: 1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p â< â0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p â= â0.12). CONCLUSIONS: Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter.
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Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required-moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health.
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Aterosclerosis , Diagnóstico Precoz , Medicina de Precisión , Humanos , Aterosclerosis/diagnóstico , Medicina de Precisión/métodos , Biomarcadores/sangreRESUMEN
BACKGROUND: Younger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. OBJECTIVE: This study aimed to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia, independent of other perinatal risk factors. STUDY DESIGN: A total of 911 women with previous preeclampsia aged 35 to 55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range, 0-28) after index pregnancy. Early- and late-onset preeclampsia were defined as gestational age at delivery of <34+0 and ≥34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors, and the primary outcome. RESULTS: Women with early-onset preeclampsia (N=139) were older (46.2±5.7 vs 44.4±5.5 years; P<.001), more likely to have hypertension (51.1% vs 35.1%; P≤.001), and had a higher body mass index (27.9±6.3 vs 26.9±5.5 kg/m2; P=.051) compared with women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome (coronary atherosclerosis) on the cardiac computed tomography among women with early- and late-onset preeclampsia was 28.8% vs 22.2%, respectively (P=.088; adjusted odds ratio, 1.74; 95% confidence interval, 1.01-3.01; P=.045 after adjustment for maternal age at index pregnancy, prepregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birthweight and sex, and follow-up length). CONCLUSION: Women with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia. However, according to the current evidence, it does not seem indicated to limit screening, diagnostic, and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.
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Enfermedad de la Arteria Coronaria , Preeclampsia , Humanos , Femenino , Embarazo , Preeclampsia/epidemiología , Preeclampsia/diagnóstico , Adulto , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios de Seguimiento , Persona de Mediana Edad , Factores de Riesgo , Índice de Masa Corporal , Edad Gestacional , Tomografía Computarizada por Rayos X/métodos , Modelos LogísticosRESUMEN
Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Adulto , Humanos , Femenino , Persona de Mediana Edad , Calcio , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Dolor en el Pecho/diagnóstico por imagenRESUMEN
AIMS: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. CONCLUSION: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Circulación Coronaria , Imagen de Perfusión Miocárdica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Valores de Referencia , Imagen de Perfusión Miocárdica/métodos , Angiografía Coronaria/métodos , Circulación Coronaria/fisiología , Angiografía por Tomografía Computarizada/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Factores de Edad , Factores Sexuales , Tomografía Computarizada por Rayos X/métodos , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.
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Enfermedad de la Arteria Coronaria , Adulto , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Índice de Masa Corporal , Angiografía Coronaria , Alta del Paciente , Estudios Prospectivos , Dolor en el Pecho/diagnóstico por imagenRESUMEN
Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.
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Enfermedad de la Arteria Coronaria , Femenino , Humanos , Persona de Mediana Edad , Dolor en el Pecho/etiología , Dolor en el Pecho/diagnóstico , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Masculino , AncianoRESUMEN
BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Calcio , Valor Predictivo de las Pruebas , Dolor en el Pecho , Necrosis , Angiografía Coronaria/métodosRESUMEN
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH). METHODS: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55âyears of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis. RESULTS: In the entire population (median age 66âyears, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A , TET2 , and ASXL1 , accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1ß, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. CONCLUSION: In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Infecciones por VIH , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Femenino , Hematopoyesis Clonal , Infecciones por VIH/complicaciones , Constricción Patológica , Hematopoyesis/genética , Evolución Clonal , Enfermedad de la Arteria Coronaria/genética , Mutación , InflamaciónRESUMEN
Background: Plasma (p-)activin A is elevated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients. Methods: The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results: P-activin A was increased by CKD stage 3 (124-225 pg/mL, P < .001) and correlated inversely with eGFR (r = -0.53, P < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64-4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion: P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated.
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OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: ⢠No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. ⢠A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. ⢠A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.
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OBJECTIVE: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications). RESULTS: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63]). CONCLUSIONS: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X , Dolor en el Pecho , Diabetes Mellitus/epidemiología , Angiografía por Tomografía Computarizada , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: The coronary atheroma burden drives major adverse cardiovascular events (MACE) in patients with suspected coronary heart disease (CHD). However, a consensus on how to grade disease burden for effective risk stratification is lacking. The purpose of this study was to compare the effectiveness of common CHD grading tools to risk stratify symptomatic patients. METHODS: We analyzed the 5-year outcome of 381 prospectively enrolled patients in the CORE320 international, multicenter study using baseline clinical and cardiac computer-tomography (CT) imaging characteristics, including coronary artery calcium score (CACS), percent atheroma volume, "high-risk" plaque, disease severity grading using the CAD-RADS, and two simplified CAD staging systems. We applied Cox proportional hazard models and area under the curve (AUC) analysis to predict MACE or hard MACE, defined as death, myocardial infarction, or stroke. Analyses were stratified by a history of CHD. Additional forward selection analysis was performed to evaluate incremental value of metrics. RESULTS: Clinical characteristics were the strongest predictors of MACE in the overall cohort. In patients without history of CHD, CACS remained the only independent predictor of MACE yielding an AUC of 73 (CI 67-79) vs. 64 (CI 57-70) for clinical characteristics. Noncalcified plaque volume did not add prognostic value. Simple CHD grading schemes yielded similar risk stratification as the CAD-RADS classification. Forward selection analysis confirmed prominent role of CACS and revealed usefulness of functional testing in subgroup with known CHD. CONCLUSION: In patients referred for invasive angiography, a history of CHD was the strongest predictor of MACE. In patients without history of CHD, a coronary calcium score yielded at least equal risk stratification vs. more complex CHD grading.
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Angina Estable , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Angina Estable/diagnóstico por imagen , Angina Estable/terapia , Calcio , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Tomografía Computarizada Multidetector , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
Background: We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1ß, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD. Methods: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Results: Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2â mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1ß was not associated with CAD. Conclusions: In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD.
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BACKGROUND & AIMS: Fatty liver disease has been associated with higher all-cause as well as liver-related, ischemic heart disease (IHD)-related and extrahepatic cancer-related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality. METHODS: We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver-related mortality. RESULTS: During a median follow-up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all-cause (1.26-fold), liver-related (9-fold), and extrahepatic cancer-related (1.25-fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver-related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3-fold and 6-fold, respectively, higher liver-related mortality than non-carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all-cause, IHD-related, or extrahepatic cancer-related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver-related mortality. CONCLUSIONS: Human genetic data support that fatty liver disease is a causal driver of liver-related mortality.
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Neoplasias , Enfermedad del Hígado Graso no Alcohólico , Humanos , Análisis de la Aleatorización Mendeliana , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de Riesgo , Hígado , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Humanos , Terapia de Resincronización Cardíaca/métodos , Dispositivos de Terapia de Resincronización Cardíaca , Incidencia , Resultado del Tratamiento , Ventrículos Cardíacos/diagnóstico por imagen , HospitalizaciónRESUMEN
PURPOSE: Absolute measures of myocardial blood flow (MBF) obtained with dynamic myocardial CT perfusion (DM-CTP) are underestimated when compared with reference standards. This is to some extent explained by incomplete extraction of iodinated contrast agent (iCA) to the myocardial tissue. We aimed to establish an extraction function for iCA, use the function to calculate MBFCT and to compare this with MBF measured with 82Rb positron emission tomography (PET). MATERIALS AND METHODS: Healthy individuals without coronary artery disease (CAD) were examined with 82Rb PET and DM-CTP. The factors a and ß of the generalized Renkin-Crone model were estimated using a non-linear least squares model. The factors providing the best fit for the data were subsequently used to calculate MBFCT. RESULTS: Of consecutive 91 individuals examined, 79 were eligible for analysis. The factors a and ß providing the best fit of the nonlinear least-squares model to the data were a â= â0.614 and ß â= â0.218 (R-squared â= â0.81). Conversion of the CT inflow parameter (K1) values using the derived extraction function resulted in a significant correlation between MBF measured during stress using CT and PET (P â= â0.039). CONCLUSION: In healthy individuals, flow estimates obtained with dynamic myocardial CT perfusion during stress were, after conversion to MBF using the extraction of iodinated CT contrast agent, correlated with absolute MBF quantified with 82Rb PET.