Kaffer Kara

Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study.

OBJECTIVES This study sought to determine whether epicardial fat volume predicts coronary events in the general population. BACKGROUND Epicardial adipose tissue (EAT) is suggested to promote plaque development in the coronary artery tree. METHODS We quantified EAT volume in participants from the prospective population-based Heinz Nixdorf Recall cohort study free of cardiovascular disease. Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years. Multivariable association of EAT with cardiovascular risk factors, coronary artery calcification (CAC), and coronary events was assessed using regression analysis. RESULTS From the overall 4,093 participants (age 59.4 years, 47% male), 130 subjects developed a fatal or nonfatal coronary event. Incidence of coronary events increased by quartile of EAT (0.9% vs. 4.7% for 1(st) and 4th quartile, respectively, p < 0.001). Doubling of EAT was associated with a 1.5-fold risk of coronary events when adjusting for cardiovascular risk factors (hazard ratio [HR] [95% confidence interval (CI)]: 1.54 [1.09 to 2.19]), which remained unaltered after further adjustment for CAC score (HR [95% CI]: 1.50 [1.07 to 2.11]). For discrimination of subjects with events from those without, we observed a trend for improvement of Harrells C and explained variance by EAT over traditional cardiovascular risk factors, which, however, did not reach statistical significance (0.720 to 0.730 for risk factors alone and with EAT added, respectively, p = 0.10, R(2) = 2.73% to R(2) = 2.92%, time-dependent integrated discrimination improvement = 0.196%). CONCLUSIONS Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score.

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.

Coronary artery calcification outperforms thoracic aortic calcification for the prediction of myocardial infarction and all-cause mortality: the Heinz Nixdorf Recall Study.

Background Thoracic aortic calcification (TAC) is associated with cardiovascular (CV) risk factors and prevalent coronary artery disease. We aimed to investigate whether TAC burden is associated with incident myocardial infarction (MI) and all-cause mortality in subjects without known coronary artery disease and to determine its predictive value for these endpoints. Methods We used longitudinal data from the population-based prospective Heinz Nixdorf Recall Study. TAC and coronary artery calcification (CAC) scores were quantified from non-contrast enhanced electron beam computed tomography. Cox regression analysis was used to determine the association of TAC with incident MI or all-cause mortality, adjusting for CV risk factors and additionally for CAC-score in a separate step. Predictive value of TAC was assessed using Harrells C index. Results Overall, 4040 participants without known coronary artery disease (59.4 years, 47% male) were included in this analysis. During a mean follow-up of 8.0 ± 1.5 years, we observed 136 coronary events and 304 deaths. In subjects with TAC>0 vs TAC = 0, the incidence of nonfatal MI was 4.2% vs 2.0% (p < 0.001), and all-cause mortality was 8.9% vs 5.2% (p < 0.001). Risks for coronary events and for all-cause mortality increased significantly with increasing TAC-scores (p < 0.001). After adjustment for CV risk factors, body mass index (BMI) and CV medication, a unit increase of TAC on a logarithmic scale (log(TAC + 1)) remained independently associated with coronary events (hazard ratio (HR) (95% confidence interval (CI)): 1.06 (1.00–1.14), p = 0.03) and all-cause mortality (HR 1.06 (1.01–1.12), p < 0.01). After further adjustment for CAC-score (log(CAC + 1)), hazard ratios were attenuated for both endpoints (coronary events: 0.98 (0.91–1.05), p = 0.56, all-cause mortality: 1.03 (0.98–1.08), p = 0.33). When adding log(TAC + 1) to the model containing traditional risk factors and CAC, Harrells C indices did not increase for coronary events (0.773–0.772, p = 0.66) or for all-cause mortality (0.741–0.743, p = 0.49). Conclusion TAC is associated with incident coronary events and all-cause mortality independent of traditional CV risk factors in the general population. TAC fails to improve event prediction over CAC in both coronary events and all-cause mortality.

Predicting risk of coronary events and all-cause mortality: role of B-type natriuretic peptide above traditional risk factors and coronary artery calcium scoring in the general population: the Heinz Nixdorf Recall Study.

Aims Several biomarkers including B-type natriuretic peptide (BNP) have been suggested to improve prediction of coronary events and all-cause mortality. Moreover, coronary artery calcium (CAC) as marker of subclinical atherosclerosis is a strong predictor for cardiovascular mortality and morbidity. We aimed to evaluate the predictive ability of BNP and CAC for all-cause mortality and coronary events above traditional cardiovascular risk factors (TRF) in the general population. Methods We followed 3782 participants of the population-based Heinz Nixdorf Recall cohort study without coronary artery disease at baseline for 7.3 ± 1.3 years. Associations of BNP and CAC with incident coronary events and all-cause mortality were assessed using Cox regression, Harrell’s c, and time-dependent integrated discrimination improvement (IDI(t), increase in explained variance). Results Subjects with high BNP levels had increased frequency of coronary events and death (coronary events/mortality: 14.1/28.2% for BNP ≥100 pg/ml vs. 2.7/5.5% for BNP < 100 pg/ml, respectively). Subjects with a BNP ≥100 pg/ml had increased incidence of hard endpoints sustaining adjustment for CAC and TRF (for coronary events: hazard ratio (HR) (95% confidence interval (CI)) 3.41(1.78–6.53); for all-cause mortality: HR 3.35(2.15–5.23)). Adding BNP to TRF and CAC increased measures of predictive ability: coronary events (Harrell’s c, for coronary events, 0.775–0.784, p = 0.09; for all-cause mortality 0.733–0.740, p = 0.04; and IDI(t) (95% CI), for coronary events: 2.79% (0.33–5.65%) and for all-cause mortality 1.78% (0.73–3.10%). Conclusions Elevated levels of BNP are associated with excess incident coronary events and all-cause mortality rates, with BNP and CAC significantly and complementary improving prediction of risk in the general population above TRF.

Beyond Framingham risk factors and coronary calcification: does aortic valve calcification improve risk prediction? The Heinz Nixdorf Recall Study

Background Aortic valve calcification (AVC) is considered a manifestation of atherosclerosis. In this study, we investigated whether AVC adds to cardiovascular risk prediction beyond Framingham risk factors and coronary artery calcification (CAC). Methods A total of 3944 subjects from the population based Heinz Nixdorf Recall Study (59.3±7.7 years; 53% females) were evaluated for coronary events, stroke, and cardiovascular disease (CVD) events (including all plus CV death) over 9.1±1.9 years. CT scans were performed to quantify AVC. Cox proportional hazards regressions and Harrell’s C were used to examine AVC as event predictor in addition to risk factors and CAC. Results During follow-up, 138 (3.5%) subjects experienced coronary events, 101 (2.6%) had a stroke, and 257 (6.5%) experienced CVD events. In subjects with AVC>0 versus AVC=0 the incidence of coronary events was 8.0% versus 3.0% (p<0.001) and the incidence of CVD events was 13.0% versus 5.7% (p<0.001). The frequency of events increased significantly with increasing AVC scores (p<0.001). After adjustment for Framingham risk factors, high AVC scores (3rd tertile) remained independently associated with coronary events (HR 2.21, 95% CI 1.28 to 3.81) and CVD events (HR 1.67, 95% CI 1.08 to 2.58). After further adjustment for CAC score, HRs were attenuated (coronary events 1.55, 95% CI 0.89 to 2.69; CVD events 1.29, 95% CI 0.83 to 2.00). When adding AVC to the model containing traditional risk factors and CAC, Harrells C indices did not increase for coronary events (from 0.744 to 0.744) or CVD events (from 0.759 to 0.759). Conclusions AVC is associated with incident coronary and CVD events independent of Framingham risk factors. However, AVC fails to improve cardiovascular event prediction over Framingham risk factors and CAC.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification

B‐type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP‐associated risk results from coronary atherosclerosis or atrial fibrillation.

Comparison of coronary artery calcification, carotid intima-media thickness and ankle-brachial index for predicting 10-year incident cardiovascular events in the general population

Aims To compare the predictive value of coronary artery calcification (CAC), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) in a primary prevention cohort depending on risk factor profile to determine which of the three markers improves cardiovascular (CV) risk discrimination best in which risk group. Methods and Results We quantified CAC, CIMT, and ABI in 3108 subjects (mean age 59.2 ± 7.7, 47.1% male) without prevalent CV diseases from the population-based Heinz Nixdorf Recall study. Associations with incident major CV events (coronary event, stroke, CV death; n = 223) were assessed during a follow-up period of 10.3 ± 2.8 years with Cox proportional regressions in the total cohort and stratified by Framingham risk score (FRS) groups. Discrimination ability was evaluated with Harrell’s C. All three markers were associated with CV events (hazard ratio [95% confidence interval (CI)]: CAC: 1.31 (1.23–1.39) per 1-unit increase in log(CAC + 1) vs. CIMT: 1.27 (1.13–1.43) per 1 SD vs. ABI: 1.30 (1.14–1.49) per 1 SD, in FRS adjusted models). Considering reclassification, CAC lead to highest reclassification in the total cohort, while also for CIMT and ABI significant improvement in net-reclassification was observed [NRI (95% CI): CAC: 0.55 (0.42–0.69); CIMT: 0.32 (0.19–0.45); ABI: 0.19 (0.10–0.28)]. Conclusion Coronary artery calcification provides the best discrimination of risk compared with CIMT and ABI, particularly in the intermediate risk group, whereas CIMT may be an alternative measure for reassurance in the low risk group.

B-type natriuretic peptide for incident atrial fibrillation—The Heinz Nixdorf Recall Study

BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Thus, identifying subjects with unknown AF or at higher risk for future AF in the general population is of importance. B-type natriuretic peptide (BNP) is linked with silent cardiac diseases. We evaluated the association of BNP with incident AF in a large population-based cohort study. METHODS We included subjects from the population-based Heinz Nixdorf Recall study without known coronary heart disease, prior stroke, history of open heart surgery, heart-device therapy, or prevalent AF at baseline. Association of continuous and binary (≥31pg/ml for male, ≥45pg/ml for female) BNP with incident AF after 5 years was assessed using logistic regression analysis. RESULTS A total of 3067 subjects (mean age 58.9 years, 47.9% male) were included in this analysis. Subjects with incident AF (n=42) had higher levels of BNP (median (Q1; Q3): 33.2pg/ml (19.4; 50.5) vs. 16.9pg/ml (9.2; 30.2)). Likewise, BNP was associated with incidence of AF both in univariate model and when adjusting for AF risk factors (odds ratio (OR) (95% confidence interval (CI)): BNP as continuous variable: 1.27 (1.09; 1.47), p=0.002; BNP as binary variable: 2.68 (1.41; 5.11) with AF risk factor adjustment). Notably, especially younger subjects (<60 years) showed stronger association with incident AF than older ones (OR (95%CI) for dichotomized BNP: 7.20 (1.60; 32.49), p=0.01 for <60 years, vs. 2.13 (0.89; 5.09), p=0.09 for 60-70 years, and 4.40 (1.29; 14.97), p=0.02 for >70 years). CONCLUSIONS Elevated levels of BNP are associated with significant excess of incident AF, independent of traditional AF risk factors in the general population. Gender-specific BNP thresholds may help in prevention by detecting unknown or future AF, which carries a high risk of stroke events.

Safety and Effectiveness of a Novel Vascular Closure Device: A Prospective Study of the ExoSeal Compared to the Angio-Seal and ProGlide

Purpose: To prospectively assess the safety and efficacy of a novel absorbable vascular closure device (ExoSeal) in patients undergoing cardiac catheterization with femoral access compared to the established collagen-based (Angio-Seal) and suture-mediated (ProGlide) closure devices. Methods: This prospective, observational, dual-center, non-randomized, non-blinded study enrolled 1013 patients (65.1±11.8 years) undergoing cardiac catheterization via a common femoral artery access in which hemostasis was achieved using a vascular closure device (255 Angio-Seal, 258 ProGlide, and 500 ExoSeal). In hospital complications (bleeding, hematoma, pseudoaneurysm, vessel occlusion, dissection, and arteriovenous fistula) of the puncture site and device failures (persistent bleeding) were recorded and compared for ExoSeal vs. the established devices (Angio-Seal + ProGlide). Results: There were more complications after utilization of ExoSeal compared to established devices (3.6% vs. 1.2%, p=0.012). No significant difference was observed in the device success rate between the established vascular closure devices (96.3%) and the novel device (94.8%, p=0.28). Considering each closure system, Angio-Seal had the lowest complication rate (0.4%) and the highest efficacy (99.2%); the latter differed significantly from ExoSeal (94.8%, p=0.001). Logistic regression analysis revealed a >3-fold odds of complications when using ExoSeal, which remained unchanged in multivariate analysis. Conclusion: Utilization of the novel vascular closure device is associated with a higher complication rate and a similar device failure rate compared to collagen-based and suture-mediated devices, with Angio-Seal having the lowest complication and device failure rates.