Iryna Dykun

Association of epicardial adipose tissue and left atrial size on non-contrast CT with atrial fibrillation: The Heinz Nixdorf Recall Study

AIMS Epicardial adipose tissue (EAT) is increased in subjects with atrial fibrillation (AF). Likewise, EAT is associated with left atrial (LA) size, as itself is a strong predictor of AF. We aimed to determine the association of EAT and LA size as computed tomography (CT)-derived measures with prevalent and incident AF and investigated whether both measures independently predict AF. METHODS AND RESULTS Participants from the Heinz Nixdorf Recall study without known cardiovascular disease were included. At baseline, EAT, defined as fat volume inside the pericardial sac, and LA size, defined as an axial area at the level of the mitral valve, were quantified from non-contrast enhanced cardiac CT. AF was determined from electrocardiogram at baseline and also at 5-year follow-up examination. Overall, 3467 participants (age: 58.9 ± 7.6 years, 47% male) were included. Ninety-six subjects had AF (46 prevalent and 50 incident). A 1-standard deviation (SD) change of EAT was associated with nearly two-fold increased prevalence of AF in univariate analysis, which persisted after adjustment for AF risk factors [odds ratio (OR) (95% confidence interval, 95% CI): 1.38 (1.11-1.72), P = 0.003]. Ancillary adjusting for LA reduced the effect [1.26 (0.996-1.60), P = 0.054]. For incident AF, no relevant effect was observed for EAT when adjusting for risk factors [1.19 (0.88-1.61), P = 0.26]. In contrast, a 1-SD chance of LA was strongly associated with AF independently of EAT and risk factors [2.70 (2.22-2.20), P < 0.0001]. LA but not EAT as non-contrast CT-derived measures improved the prediction of AF over risk factors (receiver operating characteristics: 0.810-0.845, P = 0.025). CONCLUSION LA size from non-contrast CT is strongly associated with prevalent and incident AF and ultimately diminishes the link of EAT with AF.

NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: The Heinz Nixdorf Recall Study☆ , ☆☆

BACKGROUND B-type natriuretic peptide (BNP) as well as N-terminal-proBNP (NT-proBNP) are associated with cardiac events in the general population. Yet, data from the general population comparing both peptides for their prognostic value is lacking. METHODS Participants from the population-based Heinz-Nixdorf-Recall-study without cardiovascular diseases were included. Associations of BNP and NT-proBNP with incident cardiovascular events (incident myocardial infarction, stroke, or cardiovascular death) were assessed using Cox regression; prognostic value was addressed using Harrells c statistic. RESULTS From overall 3589 subjects (mean age: 59.3 ± 7.7 yrs, 52.5% female), 235 subjects developed a cardiovascular event during 8.9 ± 2.2 yrs of follow-up. In regression analysis both natriuretic peptides were associated with incident cardiovascular events, independent of traditional risk factors (hazard ratio (HR) per unit increase on log-scale (95% CI): NT-proBNP: 1.60 (1.39; 1.84); BNP: 1.37 (1.19; 1.58), p<0.0001 respectively). Specifically looking at subjects <60 yrs only NT-proBNP, was linked with events (HR (95% CI): 1.59 (1.19; 2.13) for NT-proBNP, p=0.0019; HR: 1.25 (0.94; 1.65) for BNP, p=0.12, after adjustment for age and gender). Similar results were observed for females (HR (95% CI) 1.65 (1.28; 2.12), p=0.0001 for NT-proBNP, and 1.24 (0.96; 1.61), p=0.10 for BNP after adjustment for age). Adding NT-proBNP/BNP to traditional risk factors increased the prognostic value, with effects being stronger for NT-proBNP (Harrells c, 0.724 to 0.741, p=0.034) as compared to BNP (0.724 to 0.732, p=0.20). CONCLUSION Both, NT-proBNP and BNP are associated with future cardiovascular events in the general population. However, when both are available, NT-proBNP seems to be superior due to its higher prognostic value, especially in younger subjects and females.

Statin Medication Enhances Progression of Coronary Artery Calcification: The Heinz Nixdorf Recall Study

Statins are suggested to stabilize plaque by decreasing lipid-rich and necrotic plaque components and increasing plaque calcification [(1,2)][1]. However, to date the relationship between statin administration and progression of coronary artery calcification (CAC) is poorly understood, and existing

Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction

Background and objective Epicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction. Methods and results In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2–30.2] ml, p = 0.003), BMI (29.3 [18.4–40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7–72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08–4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10–2.94], p = 0.02 for volume, 2.04 [1.18–3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77–2.68], p = 0.26 for volume; 1.93 [1.11–3.39], p = 0.02 for attenuation). Conclusion CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.

Progression of coronary artery calcification by cardiac computed tomography.

The presence and extent of coronary artery calcification (CAC) is established in primary prevention since the CAC score is the single best predictor of future cardiovascular events. While CAC progresses with increasing age, individual CAC progression can be estimated based on the subject’s age, gender, and CAC percentile at first examination. To date, several algorithms and methods for the definition of CAC progression are available in the literature. Increased CAC progression is associated with traditional cardiovascular risk factors including hypertension, diabetes, and smoking status. Also, lipid-lowering therapy may influence the progression of CAC. Epicardial adipose tissue is a further cardiovascular risk marker that may lead to intensified CAC progression if its volume increases. In terms of clinical implications, initial data suggest that extensive CAC progression is linked to worse outcome; however, further studies are needed to establish this relationship and to define appropriate time intervals between repetitive examinations. This review article gives an overview of the existing literature with an emphasis on various definitions of CAC progression, predictors of increased CAC progression, as well as clinical implications.ZusammenfassungDas Vorhandensein und das Ausmaß der koronararteriellen Verkalkung (CAC) sind ein etablierter Risikofaktor in der Primärprävention als bester singulärer Prädiktor eines erhöhten kardiovaskulären Risikos. Während mit zunehmendem Alter auch der CAC-Score ansteigt, kann die individuelle Progression basierend auf Alter, Geschlecht und initialer CAC-Perzentile abgeschätzt werden. Bisher wurden zur Definition der CAC-Progression mehrere Algorithmen und Methoden in der Literatur beschrieben. Dabei ist die CAC-Progression mit traditionellen kardiovaskulären Risikofaktoren, einschließlich arterieller Hypertonie, Diabetes mellitus und Raucherstatus, assoziiert. Auch der Einfluss einer lipidsenkenden Therapie auf die Progression der CAC wird in der Literatur diskutiert. Zusätzlich konnte für das epikardiale Fettgewebe als Marker eines erhöhten kardiovaskulären Risikos ein Zusammenhang mit der CAC-Progression nachgewiesen werden. Bezüglich der klinischen Implikation konnten erste Daten eine Assoziation von vermehrter CAC-Progression mit zukünftigen Ereignissen nachweisen. Nicht zuletzt wegen der unterschiedlichen Definitionen sind jedoch weitere Daten notwendig, um den klinischen Nutzen einer repetitiven CAC-Score-Bestimmung sowie sinnvollen Zeitabständen zwischen zwei CT-Untersuchungen zu etablieren. Die vorliegende Übersichtsarbeit gibt einen Überblick über die aktuelle Literatur mit besonderem Augenmerk auf die verschiedenen Definitionen der CAC-Progression, Prädiktoren der CAC-Progression sowie klinischen Implikationen.

Left ventricle size quantification using non-contrast-enhanced cardiac computed tomography – association with cardiovascular risk factors and coronary artery calcium score in the general population: The Heinz Nixdorf Recall Study

Background Increased left ventricular (LV) size is associated with cardiovascular mortality and morbidity. Once non-contrast cardiac computed tomography (CT) is performed for other purposes, information of LV size is readily available. Purpose To determine the association of gated CT-derived LV size with cardiovascular risk factors and coronary artery calcification (CAC) and to describe age- and gender-specific normative values in a general population cohort. Material and Methods LV area was quantified from non-contrast-enhanced CT in axial, end-diastolic images at a mid-ventricular slice in participants of the population-based Heinz Nixdorf Recall Study, free of known cardiovascular disease. LV index (LVI) was calculated by the quotient of LV area and body surface area (BSA). Crude and adjusted regression analyses were used to determine the association of LVI with risk factors and CAC. Results Overall, 3926 subjects (age 59 ± 8 years, 53% women) were included in this analysis. From quantification in end-diastolic phase, men had larger LV index (2232 ± 296 mm2/m2 vs. 2088 ± 251 mm2/m2, both P < 0.0001). LVI was strongly correlated systolic blood pressure (men, PE [95% CI]: 22.8 [15.5–30.2] mm2/10 mmHg; women, 23.4 [18.1–28.6]), and antihypertensive medication (men, 45.2 [14.7–75.8] mm2; women: 46.5 [22.7–70.2], all P < 0.005). Cholesterol levels were associated with LVI in univariate analysis, however, correlations were low (R2 ≤ 0.04). In multivariable regression, blood pressure, antihypertensive medication and cholesterol levels, remained associated with LVI (P < 0.05). LVI was linked with CAC in unadjusted (men, increase of CAC + 1 by 13.0% [1.4–25.8] with increased LVI by 1 standard deviation of LVI, P = 0.03; women, 20.7% [10.0–32.3], P < 0.0001) and risk factor adjusted models (men, 14.6% [3.7–26.6], P = 0.007); women, 17.4% [7.8–27.8], P = 0.0002). Conclusion Non-contrast cardiac CT derived LV index is associated with body size and hypertension. LVI is weakly linked with CAC-score. Further studies need to evaluate whether assessment of LV dimensions from cardiac CT helps identifying subjects with increased cardiovascular risk.

Association of computed tomography-derived left ventricular size with major cardiovascular events in the general population: The Heinz Nixdorf recall study

OBJECTIVE To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease. METHODS LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models. RESULTS During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p<0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p<0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC<100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC<100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16). CONCLUSION CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores.

Comparison of Lipoprotein(a)-Levels in Patients ≥70 Years of Age With Versus Without Aortic Valve Stenosis

Although lipoprotein(a) (Lp[a]) is linked with aortic valve calcification and clinical aortic valve stenosis (AVS) in middle-aged cohorts, patients aged ≥70 years represent a majority of patients with AVS, in which mechanisms leading to AVS may differ. We sought to determine whether Lp(a) distinguishes patients ≥70 years with and without AVS. We matched 484 patients ≥70 years with AVS, scheduled for transcatheter aortic valve implantation with 484 patients without AVS by age group and gender. Lp(a) levels were compared in patients with and without AVS and stratified by presence and absence of clinical coronary artery disease (CAD) manifestation. A total of 968 patients (mean age 80 ± 5 years, 48% women) were included. When comparing patients with and without AVS, no difference in Lp(a) was observed (AVS: 17 [8; 56] mg/dl, no AVS: 18.5 [8.5; 57] mg/dl, p = 0.56). In contrast, patients with clinical CAD manifestation had higher Lp(a) levels than those without clinical CAD manifestation (coronary artery disease: 19 [9; 60] mg/dl, no coronary artery disease 15 [7; 44] mg/dl, p = 0.0006). In regression analysis, no significant association of Lp(a) with AVS was observed in unadjusted (OR [95% CI]: 0.98 [0.91 to 1.06], p = 0.59) and risk factor-adjusted models (0.98 [0.90 to 1.06], p = 0.57). However, Lp(a) was independently associated with clinical CAD manifestation (unadjusted: 1.14 [1.04 to 1.24], p = 0.003, risk factor adjusted: 1.17 [1.07 to 1.27], p = 0.0006). In conclusion, in a large cohort of patients ≥70 years, Lp(a) was associated with clinical CAD manifesation, but not with AVS. Our results suggest that in patients over 70 years, the development of AVS is not influenced by Lp(a).

CLINICAL RELEVANT EXTRACARDIAC FINDINGS ON NON-CONTRAST ENHANCED CARDIAC COMPUTED TOMOGRAPHY IN THE GENERAL POPULATION: THE HEINZ NIXDORF RECALL STUDY

The prevalence of clinical relevant extracardiac findings (ECF) on cardiac computed tomography (CT) scans in the general population is still not described. Participants aged 45-75yrs from the prospective population-based Heinz Nixdorf Recall Study were studied by non-contrast enhanced cardiac

Epicardial Adipose Tissue: New Kid on the Block

Over the last 2 decades, understanding of epicardial adipose tissue (EAT) significantly changed from an innocent bystander, protecting the coronary arteries from physical damage, to an inflammatory active endocrine organ that may influence development of atherosclerosis in the coronary arteries. EAT is a visceral adipose tissue, surrounding the heart and the coronary arteries. It is associated with cardiovascular risk factors and with coronary artery plaque burden. In addition, increasing evidence identifies a link of EAT with prevalent and incident coronary heart disease in patient cohorts as well as general population-based studies. This review article will give an overview over the existing literature on this emerging topic with special focus on the implications of EAT as a potential novel marker of cardiovascular risk burden.