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Gert-Jan R Ten Kate,
Lisan A Neefjes,
Admir Dedic,
Koen Nieman,
Janneke G Langendonk,
Annette J Galema-Boers,
Jeanine Roeters van Lennep,
Adriaan Moelker,
Gabriel P Krestin, Eric J Sijbrands,
Pim J de Feyter
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ABSTRACT: OBJECTIVE: To evaluate the influence of LDL receptor (LDLR) -negative mutational status on CT coronary atherosclerosis in asymptomatic statin treated patients with heterozygous familial hypercholesterolemia (FH). METHODS: Coronary CT angiography (CCTA) was performed in 145 FH patients (93 men; mean age 52 ± 8) screened for LDLR and apolipoprotein B (APOB) mutations. The extent of coronary plaque was compared between two groups: 1) 59 patients (41%) heterozygous for LDLR-negative mutations (LDLR-negative) and 2) 86 patients (59%) with reduced or normal LDLR function (LDLR-positive) consisting of 32 LDLR-defective mutations, 8 APOB mutations and 46 patients in whom no mutation could be identified. The diseased segments score (DSS) was the primary study endpoint defined as the number of coronary artery segments (0-17) with >20% luminal diameter narrowing. We compared the DSS between LDLR-negative and LDLR-positive patients. Within the LDLR-positive group a secondary analysis was performed between identified (LDLR-defective, APOB) and unidentified mutational status. RESULTS: The median DSS was higher in LDLR-negative than in LDLR-positive patients (4 (1-7) and 2 (0-5); P = 0.017). After adjustment for risk factors, LDLR-negative mutational status remained an independent predictor of the DSS (B = 1.09; P = 0.047). The DSS in the LDLR-positive group was similar for patients with identified and patients with unidentified mutational status. CONCLUSION: In asymptomatic statin treated patients with a clinical diagnosis of FH, LDLR-negative mutational status is associated with a higher extent of subclinical CT coronary atherosclerosis.
Atherosclerosis 01/2013; · 3.79 Impact Factor
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Lisan A Neefjes,
Gert-Jan R Ten Kate,
Rossi Alexia,
Koen Nieman,
Annette J Galema-Boers,
Janneke G Langendonk,
Annick C Weustink,
Nico R Mollet, Eric J Sijbrands,
Gabriel P Krestin,
Pim J de Feyter
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ABSTRACT: We determined the extent, severity, distribution and type of coronary plaques in cardiac asymptomatic patients with familial hypercholesterolemia (FH) using computed tomography (CT).
FH patients have accelerated progression of coronary artery disease (CAD) with earlier major adverse cardiac events. Non-invasive CT coronary angiography (CTCA) allows assessing the coronary plaque burden in asymptomatic patients with FH.
A total of 140 asymptomatic statin treated FH patients (90 men; mean age 52 ± 8 years) underwent CT calcium scoring (Agatston) and CTCA using a Dual Source CT scanner with a clinical follow-up of 29 ± 8 months. The extent, severity (obstructive or non-obstructive plaque based on >50% or <50% lumen diameter reduction), distribution and type (calcified, non-calcified, or mixed) of coronary plaque were evaluated.
The calcium score was 0 in 28 (21%) of the patients. In 16% of the patients there was no CT-evidence of any CAD while 24% had obstructive disease. In total 775 plaques were detected with CT coronary angiography, of which 11% were obstructive. Fifty four percent of all plaques were calcified, 25% non-calcified and 21% mixed. The CAD extent was related to gender, treated HDL-cholesterol and treated LDL-cholesterol levels. There was a low incidence of cardiac events and no cardiac death occurred during follow-up.
Development of CAD is accelerated in intensively treated male and female FH patients. The extent of CAD is related to gender and cholesterol levels and ranges from absence of plaque in one out of 6 patients to extensive CAD with plaque causing >50% lumen obstruction in almost a quarter of patients with FH.
Atherosclerosis 12/2011; 219(2):721-7. · 3.79 Impact Factor
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Lisan A Neefjes,
Gert-Jan R Ten Kate,
Alexia Rossi,
Annette J Galema-Boers,
Janneke G Langendonk,
Annick C Weustink,
Adriaan Moelker,
Koen Nieman,
Nico R Mollet,
Gabriel P Krestin, Eric J Sijbrands,
Pim J de Feyter
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ABSTRACT: To determine the calcium score and coronary plaque burden in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH) compared with a control group of patients with low probability of coronary artery disease, having non-anginal chest pain, using CT.
101 asymptomatic patients with FH (mean age 53 ± 7 years; 62 men) and 126 patients with non-anginal chest pain (mean age 56 ± 7 years; 80 men) underwent CT calcium scoring and CT coronary angiography. All patients with FH were treated with statins during a period of 10 ± 8 years before CT. The coronary calcium score and plaque burden were determined and compared between the two patient groups.
The median total calcium score was significantly higher in patients with FH (Agatston score = 87, IQR 5-367) than in patients with non-anginal chest pain (Agatston score = 7, IQR 0-125; p < 0.001). The overall coronary plaque burden was significantly higher in patients with FH (p < 0.01). Male patients with FH, whose low-density lipoprotein cholesterol levels were reduced by statins below 3.0 mmol/l, had significantly less coronary calcium (p < 0.01) and plaque burden (p = 0.02).
The coronary plaque burden is high in asymptomatic middle-aged patients with FH despite intense statin treatment.
Heart (British Cardiac Society) 07/2011; 97(14):1151-7. · 4.22 Impact Factor
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European Heart Journal 11/2010; 31(21):2565-6a. · 10.48 Impact Factor
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ABSTRACT: Atherosclerosis is an inflammatory disease, complicated by progressively increasing atherosclerotic plaques that eventually may rupture. Plaque rupture is a major cause of cardiovascular events, such as unstable angina, myocardial infarction, and stroke. A number of noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify so-called vulnerable atherosclerotic plaques that are prone to rupture. The purpose of the present review is to systematically investigate the accuracy of noninvasive imaging techniques in the identification of plaque components and morphologic characteristics associated with plaque vulnerability, assessing their clinical and diagnostic value.
Current problems in cardiology 11/2010; 35(11):556-91. · 3.96 Impact Factor
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Daniel Staub,
Arend F L Schinkel,
Blai Coll,
Stefano Coli,
Antonius F W van der Steen,
Jess D Reed,
Christian Krueger,
Kai E Thomenius,
Dan Adam, Eric J Sijbrands,
Folkert J ten Cate,
Steven B Feinstein
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ABSTRACT: Proliferation of the adventitial vasa vasorum (VV) is inherently linked with early atherosclerotic plaque development and vulnerability. Recently, direct visualization of arterial VV and intraplaque neovascularization has emerged as a new surrogate marker for the early detection of atherosclerotic disease. This clinical review focuses on contrast-enhanced ultrasound (CEUS) as a noninvasive application for identifying and quantifying carotid and coronary artery VV and intraplaque neovascularization. These novel approaches could potentially impact the clinician's ability to identify individuals with premature cardiovascular disease who are at high risk. Once clinically validated, the uses of CEUS may provide a method to noninvasively monitor therapeutic interventions. In the future, the therapeutic use of CEUS may include ultrasound-directed, site-specific therapies using microbubbles as vehicles for drug and gene delivery systems. The combined applications for diagnosis and therapy provide unique opportunities for clinicians to image and direct therapy for individuals with vulnerable lesions.
JACC. Cardiovascular imaging 07/2010; 3(7):761-71. · 14.29 Impact Factor
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ABSTRACT: Left ventricular dysfunction in patients with chronic coronary artery disease may be a result of dysfunctional but viable myocardium due to myocardial hibernation. Coronary revascularisation may substantially improve regional and global left ventricular dysfunction and long-term survival if a substantial amount of dysfunctional but viable myocardium is present. Because coronary revascularisation, by percutaneous coronary intervention or coronary bypass surgery, is associated with an increased periprocedural risk in patients with severe left ventricular dysfunction, careful preprocedural selection is needed. Assessment of myocardial viability with SPECT may facilitate clinical decision making and should be considered in patients with ischaemic left ventricular dysfunction who are eligible for coronary revascularisation. The most frequently used SPECT protocols use thallium-201 (201Tl) rest-redistribution, technetium-99m (99mTc) labelled viability tracers, or 18F-fluorodeoxyglucose (FDG) for assessment of myocardial glucose metabolism. Approximately 50% of the patients with ischaemic left ventricular dysfunction have a substantial amount of dysfunctional but viable myocardium on SPECT and should be considered for coronary revascularisation. The absence of myocardial viability can help to identify patients who will not benefit from high-risk percutaneous coronary interventions or surgery.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 05/2010; 6 Suppl G:G115-22. · 3.29 Impact Factor
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Arend F L Schinkel,
Abdou Elhendy,
Ron T van Domburg,
Elena Biagini,
Vittoria Rizzello,
Caroline E Veltman,
Gerrit L Ten Kate, Eric J Sijbrands,
K Martijn Akkerhuis,
Marcel L Geleijnse,
Folkert J Ten Cate,
Maarten L Simoons,
Jeroen J Bax,
Don Poldermans
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ABSTRACT: The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration >or=120 ms, respectively (p <0.0001). Annualized event rates for cardiac death/nonfatal infarction were 2.8% in patients with QRS duration <120 ms and 4.8% in patients with QRS duration >or=120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >or=120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia.
The American journal of cardiology 12/2009; 104(11):1490-3. · 3.58 Impact Factor
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ABSTRACT: The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men. The pathogenesis for this risk difference has not been fully elucidated. We investigated whether female sex was associated with macrovascular disease and death, independently of known risk factors related to type 2 diabetes, nephropathy, or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria.
We conducted a prospective, prolonged follow-up study of a subgroup of 67 diabetic patients (46 men and 21 women) without established cardiovascular disease who participated in a larger clinical trial. Data were collected on current and past health, medication use, blood pressure, renal function, and HbA(1c) during the follow-up period of 4.7 +/- 0.8 (means +/- SE) years. The end point was a composite of death, cardiovascular disease, cerebrovascular events, and peripheral artery disease.
Of the women, eight (38.1%) met the end point compared with six (13.4%) of the men (P = 0.02 for difference in event-free survival). The hazard ratio of women relative to men was 3.19 (95% CI 1.11-9.21), which further increased after adjusting for age, systolic blood pressure, BMI, smoking, total-to-HDL cholesterol ratio, urinary albumin excretion, and retinopathy.
In our study population of normotensive patients with type 2 diabetes and microalbuminuria, female sex was associated with increased risk of fatal and nonfatal cardiovascular disease, independent of the classical cardiovascular risk factors, the severity of nephropathy or presence of retinopathy, or health care utilization.
Diabetes Care 09/2006; 29(8):1851-5. · 8.09 Impact Factor
