Coronary Artery Disease: Hillege HL

Daemen J, Simoons ML, Wijns W, Bagust A, Bos G, Bowen JM, Braunwald E, Camenzind E, Chevaliers B, DiMario C, Fajadeto J, Gitt A, Guagliumi G, Hillege HL, James S, Jüni P, Kastrati A, Kloth S, Kristensen SD, Krucoff M, Legrand V, Pfisterer M, Rothman M, Serruys PW, Silber S, Steg PG, Tariah I, Wallentin L, Windecker SW, Aimonetti A, Allocco D, Berenger M, Boam A, Calle JP, Campo G, Carlier S, de Schepper J, Di Bisceglie G, Dobbels H, Farb A, Ghislain JC, Hellbardt S, ten Hoedt R, Isaia C, de Jong P, Lekehal M, LeNarz L, Mhullain FN, Nagai H, Patteet A, Paunovic D, Potgieter A, Purdy I, Raveau-Landon C, Ternstrom S, Van Wuytswinkel J, Waliszewski M, Anonymous00071. · Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands. · EuroIntervention. · Pubmed #19284063 No free full text.

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Tio RA, Dabeshlim A, Siebelink HM, de Sutter J, Hillege HL, Zeebregts CJ, Dierckx RA, van Veldhuisen DJ, Zijlstra F, Slart RH. · Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. · J Nucl Med. · Pubmed #19164219 No free full text.

Abstract: The purpose of this study was to compare the prognostic value of left ventricular ejection fraction (LVEF) and myocardial perfusion reserve (MPR) assessed with PET in patients with ischemic heart disease (IHD). Myocardial perfusion is the main determinant of left ventricular function in patients with IHD. The prognostic value of LVEF has been widely established. In addition, MPR determines survival in patients with hypertrophic and dilated cardiomyopathies. In the present study, we evaluated whether MPR also determines survival in patients with IHD. METHODS: Between 1995 and 2003, 480 consecutive patients with chronic IHD underwent dipyridamole stress and rest 13N-ammonia PET to determine MPR. Additionally, 18F-FDG PET was performed for viability (mismatching defects), infarction (matching defects), and left ventricular function assessment. Patients were followed for all causes of mortality and major cardiovascular events. RESULTS: In 463 of the 480 patients, valid MPR could be measured (368 men; mean age, 66+/-11 y; LVEF, 35%+/-15%). One hundred nineteen patients underwent a PET-driven revascularization (67 through percutaneous coronary intervention and 52 through coronary artery bypass grafting). The remaining 344 patients were the subject of this study. The overall MPR was 1.71+/-0.50 (intertertile boundaries, 1.49 and 1.84). After adjustment for age and sex, MPR was associated with a hazard ratio for cardiac death of 4.11 (95% confidence interval, 2.98-5.67) per SD decrease, whereas the risk for LVEF was 2.76 (2.00-3.82) per SD decrease. CONCLUSION: Patients with IHD with a low MPR are at high risk of cardiac death. MPR is a more sensitive predictor for cardiac death than is LVEF.

Geluk CA, Dikkers R, Perik PJ, Tio RA, Götte MJ, Hillege HL, Vliegenthart R, Houwers JB, Willems TP, Oudkerk M, Zijlstra F. · Thoraxcenter, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, PB 30001, 9700 RB, Groningen, The Netherlands. · Eur Radiol. · Pubmed #17901959 links to  free full text

Abstract: We determined the efficiency of a screening protocol based on coronary calcium scores (CCS) compared with exercise testing in patients with suspected coronary artery disease (CAD), a normal ECG and troponin levels. Three-hundred-and-four patients were enrolled in a screening protocol including CCS by electron beam computed tomography (Agatston score), and exercise testing. Decision-making was based on CCS. When CCS>or=400, coronary angiography (CAG) was recommended. When CCS<10, patients were discharged. Exercise tests were graded as positive, negative or nondiagnostic. The combined endpoint was defined as coronary event or obstructive CAD at CAG. During 12+/-4 months, CCS>or=400, 10-399 and <10 were found in 42, 103 and 159 patients and the combined endpoint occurred in 24 (57%), 14 (14%) and 0 patients (0%), respectively. In 22 patients (7%), myocardial perfusion scintigraphy was performed instead of exercise testing due to the inability to perform an exercise test. A positive, nondiagnostic and negative exercise test result was found in 37, 76 and 191 patients, and the combined endpoint occurred in 11 (30%), 15 (20%) and 12 patients (6%), respectively. Receiver-operator characteristics analysis showed that the area under the curve of 0.89 (95% CI: 0.85-0.93) for CCS was superior to 0.69 (95% CI: 0.61-0.78) for exercise testing (P<0.0001). In conclusion, measurement of CCS is an appropriate initial screening test in a well-defined low-risk population with suspected CAD.

Geluk CA, Dikkers R, Kors JA, Tio RA, Slart RH, Vliegenthart R, Hillege HL, Willems TP, de Jong PE, van Gilst WH, Oudkerk M, Zijlstra F. · Department of Cardiology, Thoraxcenter, University Medical Center Groningen, University of Groningen, The Netherlands. · BMC Cardiovasc Disord. · Pubmed #17629903 links to  free full text

Abstract: BACKGROUND: Asymptomatic subjects at intermediate coronary risk may need diagnostic testing for risk stratification. Both measurement of coronary calcium scores and exercise testing are well established tests for this purpose. However, it is not clear which test should be preferred as initial diagnostic test. We evaluated the prevalence of documented coronary artery disease (CAD) according to calcium scores and exercise test results. METHODS: Asymptomatic subjects with ST-T changes on a rest ECG were selected from the population based PREVEND cohort study and underwent measurement of calcium scores by electron beam tomography and exercise testing. With calcium scores > or =10 or a positive exercise test, myocardial perfusion imaging (MPS) or coronary angiography (CAG) was recommended. The primary endpoint was documented obstructive CAD (>/=50% stenosis). RESULTS: Of 153 subjects included, 149 subjects completed the study protocol. Calcium scores > or =400, 100-399, 10-99 and <10 were found in 16, 29, 18 and 86 subjects and the primary endpoint was present in 11 (69%), 12 (41%), 0 (0%) and 1 (1%) subjects, respectively. A positive, nondiagnostic and negative exercise test was present in 33, 27 and 89 subjects and the primary endpoint was present in 13 (39%), 5 (19%) and 6 (7%) subjects, respectively. Receiver operator characteristics analysis showed that the area under the curve, as measure of diagnostic yield, of 0.91 (95% CI 0.84-0.97) for calcium scores was superior to 0.74 (95% CI 0.64-0.83) for exercise testing (p = 0.004). CONCLUSION: Measurement of coronary calcium scores is an appropriate initial non-invasive test in asymptomatic subjects at increased coronary risk.

Geluk CA, Tio RA, Tijssen JG, van Dijk RB, Dijk WA, Hillege HL, de Jong PE, van Gilst WH, Zijlstra F. · Department of Cardiology, Thoraxcentre, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. · Neth Heart J. · Pubmed #17612673 links to  free full text

Abstract: BACKGROUND: The use of invasive procedures has mostly been studied in retrospective (multi)- national registries. Limited evidence exists on the association between microalbuminuria and coronary artery disease (CAD). METHODS: The incidence of major adverse cardiac events (MACE) and invasive cardiac procedures was registered between 1997 and 2003 in 8139 subjects, without prior documented CAD, in the PREVEND cohort study (the Netherlands), in which the focus is on microalbuminuria and cardiovascular risk. Qualitative coronary angiographic analysis was performed. RESULTS: During 5.5 years of follow-up, a first MACE occurred in 271 (3.3%) and a first coronary angiography (CAG) was performed in 264 (3.2%) subjects. Of these, 216 CAGs were available for qualitative angiographic analysis. Indications for CAG were stable angina in 129, acute coronary syndrome (ACS) in 55 and ST-elevation myocardial infarction (STEMI) in 32 subjects. Obstructive coronary artery disease was present in 61, 53 and 30 subjects, respectively. A revascularisation was performed in 50 (39%), 50 (91%) and 25 (78%) subjects, respectively. Microalbuminuria was associated with a first MACE, after adjustment for established risk factors. Microalbuminuria was present at baseline in 9% of subjects with normal coronary arteries, in 21% of subjects with one- and two-vessel CAD and in 39% of subjects with threevessel or left main CAD at CAG during follow-up (Ptrend=0.005). CONCLUSION: This large cohort study shows that two-thirds of diagnostic CAGs for stable angina were not followed by a revascularisation, in contrast to CAGs for STEMI or ACS. Furthermore, this study shows that microalbuminuria is associated with CAD. (Neth Heart J 2007;15:133-41.).

Geluk CA, Post WJ, Hillege HL, Tio RA, Tijssen JG, van Dijk RB, Dijk WA, Bakker SJ, de Jong PE, van Gilst WH, Zijlstra F. · Department of Cardiology, Thoraxcenter, University Medical Center Groningen, University of Groningen, The Netherlands. · Atherosclerosis. · Pubmed #17157301 No free full text.

Abstract: AIMS: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population. METHODS AND RESULTS: Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37+/-19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1-3 and >3mg/L of, respectively, 1.26 (95% CI 0.67-2.40) and 3.16 (95% CI 1.26-3.16), relative to hs-CRP <1mg/L. CONCLUSION: In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis.

Smilde TD, Hillege HL, Navis G, Voors AA, Brouwer J, van Veldhuisen DJ. · Department of Cardiology, Thoraxcenter, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands. · Int J Cardiol. · Pubmed #16337501 No free full text.

Abstract: INTRODUCTION: Renal function is one of the strongest prognostic markers in patients with chronic heart failure, but it has been suggested that this might be due to (local, i.e. renal) vascular atherosclerosis. The aim of the present study is to evaluate the prognostic value of renal function in both ischemic and non-ischemic mild chronic heart failure. METHODS: From 161 patients with early chronic heart failure and NYHA class II, who had been enrolled in a multicenter trial, ischemic chronic heart failure was present in 120 patients and non-ischemic chronic heart failure in 41 patients. Estimated glomerular filtration rate was calculated by the Cockcroft-Gault equation (GFRc). RESULTS: Follow-up duration was 13 years (mean 11.7 years). Mean age was 60.5+/-8.0 years, 86% was male and mean left ventricular ejection fraction was 0.29+/-0.08. Baseline characteristics were not statistically different between the groups. Multivariate Cox regression analysis revealed that in non-ischemic chronic heart failure, renal function was an important predictor of all-cause mortality (Relative Risk; 1.65 (1.05-2.58); p=0.029). In contrast, in ischemic chronic heart failure, renal function was not related to all-cause mortality (Relative Risk; 1.07 (0.92-1.23); p=0.40). CONCLUSION: In mild chronic heart failure, renal function is a prognostic risk marker for long-term mortality in non-ischemic chronic heart failure, but not in patients with coronary artery disease. These data suggest that renal vascular abnormalities are not primarily responsible for the prognostic value of renal function in patients with mild chronic heart failure.

Smilde TD, Hillege HL, Navis G, Boomsma F, de Zeeuw D, van Veldhuisen DJ. · Department of Cardiology, Thoraxcenter, University Hospital, Groningen, The Netherlands. · Am Heart J. · Pubmed #15215807 No free full text.

Abstract: BACKGROUND: Renal dysfunction is a strong predictor of mortality in chronic heart failure (CHF). Most patients with CHF have atherosclerotic vascular disease, and several authors have suggested that impaired renal function is only a marker of advanced atherosclerosis. We compared renal function in patients with ischemic and nonischemic CHF and examined associations with prognosis and extent of neurohormonal activation. METHODS: In a large survival study (1906 patients), patients with documented coronary artery disease (CAD, n = 995), were compared with patients with idiopathic dilated cardiomyopathy (IDC, n = 429). In a smaller substudy, plasma neurohormones were determined in 270 patients and 37 patients (CAD and IDC, respectively). All patients had advanced CHF (New York Heart Association functional class III-IV). At baseline, the mean patient age was 64 +/- 10 years, and the mean left ventricular ejection fraction was 0.26 +/- 0.08. The baseline glomerular filtration rate was calculated with the Cockcroft-Gault equation (GFRc). RESULTS: GFRc was a strong predictor for mortality in both groups on multivariate analysis. The relative risk was 3.04 for patients with IDC (P < or =.01, for the lowest quartile < or =53 mL/min), and the relative risk for patients with CAD was 1.81 (P =.01 for the lowest quartile < or =42 mL/min). Plasma neurohormones showed a relation with GFRc in both groups. CONCLUSIONS: GFRc is related to survival and plasma neurohormones in both patient groups. In patients with IDC, this association appears to be at least as strong as in patients with CAD.

Stuveling EM, Hillege HL, Bakker SJ, Asselbergs FW, de Jong PE, Gans RO, de Zeeuw D, Anonymous00203. · Department of Internal Medicine, University Medical Centre Groningen, Groningen, The Netherlands. · Atherosclerosis. · Pubmed #14709363 No free full text.

Abstract: C-reactive protein (CRP) and microalbuminuria (MA) have been identified as risk markers for cardiovascular disease (CVD). We questioned whether CRP and MA are similar markers of vascular disease in different regions of the vascular tree like the heart, kidneys and extremities or if they differ in their relationships with these vascular beds. Baseline levels of CRP and urinary albumin were measured in 6669 non-diabetic participants in the Prevention of Renal and Vascular ENdstage Disease (PREVEND) study, a Dutch cohort derived from the general population. We defined three domains of vascular disease; coronary heart disease (myocardial infarction or infarct pattern on the ECG), renal insufficiency (creatinine clearance <60 ml min(-1)) and peripheral artery disease (ankle brachial index <0.9 or lower limb revascularisation). The prevalence of an elevated CRP (27.7 vs. 17.9%) and MA (17.5 vs. 10.4%) were increased in subjects with vascular disease as compared with subjects without CVD. The prevalence of an elevated CRP was equal in subjects with either coronary heart disease, renal insufficiency or peripheral artery disease (28.4 vs. 29.5 vs. 26.0%, NS), whereas MA was most prevalent in subjects with coronary heart disease (22.5 vs. 12.8 vs. 14.9%, P<0.05). Using multivariate analyses, CRP was independently associated with all three domains of vascular disease, whereas MA was independently associated with coronary heart disease only. In addition, we found synergistic contributions of an elevated CRP and older age to the risk of vascular disease in all three domains. Thus, CRP and MA are risk markers for vascular disease, each showing a different risk profiling for different vascular beds.