Papers by Mamad Trihatmowidjoyo
The Lancet, Jan 1, 1992
Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding for... more Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.
European Journal of Nuclear Medicine and Molecular Imaging, Jan 1, 2010
Atherosclerosis is the major cause of cardiovascular disease, which still has the leading positio... more Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat cardiovascular disease.
European heart …, Jan 1, 1996
Background A substantial proportion of patients undergoing heart catheterization for suspected co... more Background A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time.
American heart …, Jan 1, 1996
The objective of this study was to clarify whether morphologic evaluation of the in vivo artery w... more The objective of this study was to clarify whether morphologic evaluation of the in vivo artery with intravascular ultrasound provides as sensitive a marker as endothelial dysfunction or microscopic histologic assessment. Endothelial dysfunction assessed with the changes in the vessel diameter during acetylcholine infusion has been used as a more sensitive marker of atherosclerosis than the angiographic estimates of morphologic structure of the vessel. Recent advent of intravascular ultrasound has provided such highresolution images of the vessels that morphologic changes in the vessel structure are sensitively and accurately detected. Twenty-two rabbits were divided into three groups: six rabbits fed a cholesterol-rich diet for 2 weeks as the hypercholesterolemia group, eight rabbits fed with the diet for 8 weeks as the atherosclerosis group, and eight rabbits fed a normal diet as the normal group. After evaluating the atherosclerotic lesions by intravascular ultrasound, the crosssectional area was measured in the baseline and during the infusion of acetylcholine (0.05, 0.5, and 5 pg/kg/min) and nitroglycerin (5 pg/kg/min). No atherosclerotic lesions were detectable with intravascular ultrasound in any rabbit despite the presence of microscopic intimal lesions in the vessels in the rabbits of the atherosclerosis group. The crosssectional area increased during acetylcholine infusion in the rabbits of the normal and the hypercholesterolemia groups. In contrast, in the rabbits of the atherosclerosis group, the cross-sectional area did not significantly increase during acetylcholine infusion at the rate of 0.5 pg/kg/min and even tended to decrease at the rate of 5 pg/kg/min (-3.8% ± 3.7%, P< 0.05 vs the normal group). Dilating responses to nitroglycerin infusion were similar among all three groups. In conclusion, impairment of the endotheliumodependent vasodilating response assessed with intravascular ultrasound in the in vivo vessel precedes the appearance of echographic atherosclerotic findings. Thus intravascular ultrasound, if used in combination with drug intervention to assess endothelial function, would provide even more accu-
Circulation, Jan 1, 2001
Background-Most of our knowledge about atherosclerosis at young ages is derived from necropsy stu... more Background-Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. Methods and Results-Intravascular ultrasound was performed in 262 heart transplant recipients 30.9Ϯ13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4Ϯ13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness Ն0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals Ͻ20 years old to 85% in subjects Ն50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08Ϯ0.48 mm and 32.7Ϯ15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). Conclusions-This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.
Atherosclerosis, Jan 1, 2000
American journal of …, Jan 1, 1991
To assess whether carotid atherosclerosis measured by B-mode ultrasound is related to cardiovascu... more To assess whether carotid atherosclerosis measured by B-mode ultrasound is related to cardiovascular risk factors, 386 cases with carotid artery wall thickening and an equal number of controls free of arterial intima-media thickening were drawn from the cohort of the Atherosclerosis Risk in Communities (ARIC) Study examined in four communities in the United States between 1988 and 1990. Cases and controls were individually matched on sex, race, age group, study center, and date of examination. The mean values of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglyceride, blood pressure, and pack-years of cigarette smoking were higher in cases than controls. Mean high density lipoprotein (HDL) cholesterol was lower in cases than controls. Case-control differences were all statistically significant. Multivariable-adjusted odds ratios point to differences of considerable magnitude in the risk of carotid atherosclerosis between groups defined by clinical and public health-oriented risk factor cut-points.
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Papers by Mamad Trihatmowidjoyo