PDF herunterladen
Ultraschall Med 2003; 24(3): 162-174
DOI: 10.1055/s-2003-40058
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Intima-Media-Dicke der Karotisarterien: Früher Indikator für Arteriosklerose und therapeutischer Endpunkt

Intima Media Thickness of the Carotid Arteries: Early Pointer to Arteriosclerosis and Therapeutic EndpointM.  Ludwig1 , A.  v. Petzinger-Kruthoff1 , M.  v. Buquoy1 , K.  O.  Stumpe1
  • 1Medizinische Universitäts-Poliklinik Bonn
Weitere Informationen

Publikationsverlauf

eingereicht: 4. Oktober 2002

angenommen: 19. Februar 2003

Publikationsdatum:
20. Juni 2003 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Frühe arteriosklerotische Gefäßwandprozesse sind erkennbar an einer Zunahme der arteriellen Wanddicke. Die Verdickung des Intima-Media-Komplexes stellt einen nicht-invasiven und gut reproduzierbaren Messparameter für Arterienwandumbauprozesse dar, der im Bereich der Karotiden mithilfe hochauflösender Ultraschallmethoden einfach bestimmt werden kann. Bezogen auf Messungen der Intima-Media-Dicke (IMD) der Karotisarterien kommen aber verschiedene Arbeitsgruppen zu unterschiedlichen Ergebnissen. Die Ursache hierfür könnte in der Auswahl der Messregionen (unterschiedliche Segmente und Gefäßabschnitte der Karotisarterie, sondennahe/sondenferne Gefäßwand), in der unterschiedlichen Interpretation der Grenzflächenechos des Intima-Madia-Komplexes oder in der unterschiedlichen Beziehung zwischen sonographischen und anatomischen Gefäßwandstrukturen der sondennahen und -fernen Arterienwand begründet sein. Messungen der IMD an der sondennahen Karotiswand erfassen nur Teile der Media zusammen mit einer von Ultraschallartefakten beeinflussten Intimaschicht und nicht den totalen Intima-Media-Komplex. Es gibt zwei verschiedene Verfahren zur IMD-Messung: 1) mehrfache manuelle Messungen in unterschiedlichen Segmenten der Karotisarterien an der sondennahen und der sondenfernen Gefäßwand und 2) automatische, computerunterstützte Messungen, welche an der sondenfernen Gefäßwand der distalen Arteria carotis communis vorgenommen werden. Bei der manuellen Messtechnik liegen die Intra- und Interbeobachtervariabilitäten bei 0,09 bis 0,13 mm und 0,12 und 0,18 mm (absolute Differenzen zwischen den Messwerten). Die Reproduzierbarkeit ist am besten, wenn die manuellen IMD-Messungen an der sondenfernen Wand der A. carotis communis in einer Entfernung von 1 cm vom Bulbus und an geraden parallelen Wandechos, die keine lokale Verdickung aufweisen, durchgeführt wird. Die Variabilität ist außerdem bei der automatischen Methode geringer als beim manuellen Ausmessen der IMD. IMD-Werte der A. carotis communis sind altersabhängig. Im jüngeren Lebensalter (20- bis 30-jährige Personen) liegt die IMD im Durchschnitt bei 0,5 mm, während sie bei älteren Personen (60- bis 70-jährige) durchschnittlich 0,9 mm beträgt. Darüber hinaus korreliert die IMD der Karotiden mit anderen Risikofaktoren wie z. B. dem systolischen Blutdruck, den Serumlipiden und dem Rauchen. Außerdem besteht bei Männern und Frauen eine positive Beziehung zwischen IMD der Karotiden und der Existenz sowie dem Ausmaß der koronaren Herzkrankheit. Aufgrund der Tatsache, dass in großen klinischen Studien eine Korrelation zwischen IMD und kardiovaskulären Ereignissen wie z. B. Herzinfarkt und Schlaganfall gefunden wurde, hat die FDA den zweidimensionalen Ultraschall als valide Technik in klinischen Arteriosklerosestudien anerkannt. Es konnte gezeigt werden, dass sich durch die Verabreichung verschiedener blutdruck- und lipidsenkender Medikamente die Regression oder eine verlangsamte Progression von Verdickungen der Intima-Media-Schicht der Karotiden erzielen lässt. In Ergänzung zu IMD-Messungen der Karotiden als prädiktiver Faktor zukünftiger kardiovaskulärer Ereignisse steigt dieses Risiko drastisch im Falle der Existenz von Plaques im Bereich der Karotiden an. Im klinischen Alltag sollte daher aus Sicht der Autoren dieser Arbeit die hochauflösende Duplexsonographie sowohl zur Untersuchung der IMD der A. carotis communis als auch zur Erfassung von Plaques und Stenosen eingesetzt werden. Zusammenfassend kann gesagt werden, dass sich die hochauflösende Duplexsonographie zur Erfassung, Quantifizierung und Verlaufsbeobachtung von strukturellen Veränderungen der Arterienwand eignet. Die Empfindlichkeit dieser Methode ist ausreichend für den Einsatz in klinischen Studien, die sich mit der Progression und der Regression früher arteriosklerotischer Veränderungen in den extrakraniellen Karotisarterien befassen. Darüber hinaus kann die IMD der A. carotis als therapeutischer Endpunkt verwandt werden.

Abstract

An early sign of atherosclerosis is hypertrophy of the arterial wall. Increased intima-media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. There are important differences in B-mode measurements of carotid IMT between laboratories. These might concern on IMT image acquisition (in relation to the segment and/or the wall of measure) as well as determination of the echo boundary defining the IMT interfaces and the difference in relationship between anatomic and sonographic structures of the near and far arterial wall. Measurements derived from the near wall reflect thickness of a part of media and intima influenced by sonographic artefacts, rather than that of the total intima-media complex. Two main approaches are used for measuring IMT: 1) manual measurement at multiple extracranial carotid sites in near and far walls, and 2) automated computerized measurement, restricted to the far wall of the distal common carotid artery. Intra- and inter-observer variabilities have been found to vary in manual measurements between 0.09 to 0.13 mm and 0.12 to 0.18 mm (absolute differences). The best reproducibility of manual IMT-measurements is found at the far wall of the common carotid artery 1 cm from the bulb in the site of two parallel wall contures without local thickening. For automated measurements lower intra- and inter-observer variabilities have been reported. IMT of the common carotid artery is strongly influenced by age. For younger age groups (20 to 30 years) mean IMT values of 0.5 mm have been reported, while IMT values of 0.9 mm have been found for older subjects (60 to 70 years). Carotid IMT correlates with other risk factors such as systolic blood pressure, serum lipids and smoking, as well as being positively linked to the presence and extend of coronary artery disease in both women and men. The demonstration of a correlation between IMT and cardiovascular events such as stroke and myocardal infarction in clinical studies of atherosclerosis progression and cardiovascular outcomes have led to FDA accepting 2D ultrasound as a valid technique in clinical studies of atherosclerosis. Regression or slowing of progression of increased carotid IMT by various antihypertensive and lipid-lowering drugs agents have been reported. In addition to carotid IMT measurement as a predictive value of future vascular events the presence of plaques or stenosis in the carotid artery tree increases drastically the risk for cardiovascular events. Therefore the authors of this article propose the use of high resolution Duplex-Sonography for the assessment IMT of the common carotid artery as well as the detection of plaques and stenosis in clinical practice. In conclusion, high-resolution Duplex-sonography seems promising for the detection, quantification and serial investigations of structural alterations of the arterial wall. The method is sensitive enough to be applied in clinical studies of the progression and regression of early preintrusive atherosclerotic lesions in extracranial carotid arteries. Moreover IMT of the common carotid artery can be used as a therapeutic endpoint.

Schlüsselwörter

Intima-Media-Dicke - Nicht-invasive Techniken - B-mode - Arterienwand - Arteriosklerose

Key words

Intima-media thickness - non-invasive techniques - B-mode imaging - arterial wall - atherosclerosis

Literatur

  • 1 Statistisches Bundesamt .Informationelle Gesundheitsversorgung. Wiesbaden; 2002
    Google Scholar
  • 2 Marosi L, Ehringer H. The extracranial carotid artery in a high-resolution real-time ultrasonic imaging system: the morphological findings in healthy young adults.  Ultraschall Med. 1984;  5 174-181
    PubMedGoogle Scholar
  • 3 Terwey B, Gahbauer H, Montemayor M, Proussalis A, Zollner G. B-image sonography of carotid bifurcation.  Ultraschall Med. 1984;  5 190-201
    PubMedGoogle Scholar
  • 4 Ludwig M. Untersuchungen zur Arterioskleroseentwicklung in großen Arterien: Quantitative Analyse der arteriellen Gefäßwandstruktur mit einem neu entwickelten hochauflösenden Sonographie-Verfahren. Habilitationsschrift Bonn; 1994
    Google Scholar
  • 5 Pignoli P, Tremoli E, Poli A, Oreste P L, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.  Circulation. 1986;  74 1399-1406
    CrossrefPubMedGoogle Scholar
  • 6 Simon A, Megnien J L, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia.  Circulation. 1997;  96 2449-2452
    PubMedGoogle Scholar
  • 7 Tang R, Henning M, Tomasson B, Scherz R, Ravinetto R, Catalini R, Rubva R, Zanchetti A, Bond M G. For the ELSA-investigators: Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: The European Lacidipine Study on Atherosclerosis (ELSA).  J Hypertens. 2000;  18 97-201
    PubMedGoogle Scholar
  • 8 Salonen J T, Salonen R. Ultrasonographically Assessed Carotid Morphology and the Risk of Coronary Heart Disease.  Arterioscl Thromb. 1991;  11 1245-1249
    CrossrefPubMedGoogle Scholar
  • 9 Salonen R, Salonen J T. Intima-media changes in a population study: KIHD. I: Boccalon H, ed. Vascular Medicine New York, NY. Elsevier Science Publishers BV; 1993
    Google Scholar
  • 10 Graf S, Gariepy J, Massonneau M, Armentano R L, Mansour S, Barra J G. Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing.  Ultrasound Med Biol. 1999;  9 1353-1363
    PubMedGoogle Scholar
  • 11 Pignoli P. Ultrasonic Evaluation of Arterial Intima and Media Thickness: Development and Validation of Methodology. Pathobiology of the Human Atherosclerotic Plaque (Glagov S, Newman WP, Schaffer SA). Springer Verlag. New York/Berlin/Heidelberg/London/Paris/Tokyo/Hongkong 1990: 705-729
    Google Scholar
  • 12 Wikstrand J, Wiklund O. Frontiers in cardiovascular science - quantitative measurements of atherosclerotic manifestations in humans.  Atherosclerosis and Thrombosis. 1992;  12 114-118
    PubMedGoogle Scholar
  • 13 Barnes R W, Bond M G, Riley W A, Wilmoth S K. Atherosclerosis risk in communities - Ultrasound Reading Center: quantitative B-mode scanning protocol in (S. Glagov, W.P. Newman, S.A. Schaffer) Pathobiology of the human atherosclerotic plaque. Springer Verlag. New York/ Berlin/Heidelberg/London/Paris/Tokyo/Hongkong 1990: 889-998
    Google Scholar
  • 14 Mercuri M, Bond M G, Nichols F T, Carr A A, Flack J M, Byington R, Raines J. For the MIDAS group: Baseline reproducibility of B-mode ultrasound imaging measurements of carotid intima-media thickness: The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS).  J Cardiovascular Diagnosis and Procedures. 1993;  11 241-255
    PubMedGoogle Scholar
  • 15 Lonn E. Modifying the natural history of atherosclerosis: The Secure Trial.  IJCP. 2001;  117 13-18
    PubMedGoogle Scholar
  • 16 Kanters S DJM, Algra A, van Leeuwen M S, Banga J D. Reproducibility of In Vivo Carotid Intima-Media Thickness Measurements.  Stroke. 1997;  28 665-671
    CrossrefPubMedGoogle Scholar
  • 17 Borhani N O, Mercuri M, Borhani P A, Buckalew V M, Canossa-Terris M, Carr A A, Kappagoda T, Rocco M V, Schnaper H W, JR S owers, Bond M G. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS).  JAMA. 1996;  276 785-830
    CrossrefPubMedGoogle Scholar
  • 18 Bots M L, Hofman A, Grobbee D E. Increased common carorid intima-media thickness - adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study.  Stroke. 1997;  28 2442-2446
    PubMedGoogle Scholar
  • 19 de Groot E, Jukima J W, Montauban van Swinjdregt AD, Zwinderman A H, Ackerstaff R GA, van der Steen A FW, Bom N, Lie K I, Bruschke A VG. on behalf of the Regress Study Group . B-Mode ultrasound assessment of pravastatine treatment effect on carotid and femoral artery walls and its correlation with coronary arteriographic findings: A report of the Regression Growth Evaluation Statine Study (REGRESS).  ACC. 1998;  31 1561-1567
    PubMedGoogle Scholar
  • 20 Touboul P J, Prati P, Scarabin P Y, Adrai V, Thibout E, Ducimetiere P. Use of monitoring software to improve measurement of carotid wall thickness by B-mode imaging.  J Hypertens. 1992;  10 (suppl 5) S37-S41
    PubMedGoogle Scholar
  • 21 Frost D, Friedl A, Beischer W. Determination of intima-media thickness of carotid artery: influences of methods, probands and examination variables.  Ultraschall Med. 1998;  19 168-173
    PubMedGoogle Scholar
  • 22 Schmidt-Trucksäss A, Cheng D, Sandrock M, Schulte-Mönting J, Rauramaa R, Huonker M, Burkhardt H. Computerised analysing system using the active contour in ultrasound measurement of carotid artery intima-media thickness.  Clinical Physiology. 2001;  21 561-569
    CrossrefPubMedGoogle Scholar
  • 23 Cheng D, Schmidt-Trucksäss A, Cheng K, Burkhardt H. Using snakes to detect the intimal and adventitial layers of the common carotid artery wall in sonographic images.  Computer methods and programs in biomedicine. 2002;  67 27-37
    CrossrefPubMedGoogle Scholar
  • 24 Pauciullo B, Iannuzzi A, Sartorio R, Irace C, Covetti G, di Constanzo A, Rubba B. Increased intimal-medial thickness of common carotid artery in hypercholesterolemic children.  Arterioscler Thromb. 1994;  14 1075-1079
    PubMedGoogle Scholar
  • 25 Wendelhag I, Wiklung O, Wikstrand J. Arterial wall thickness in familial hypercholesterolemia - ultrasound measurement of intima-media thickness in common carotid artery.  Atherosclerosis and Thrombosis. 1992;  12 70-77
    PubMedGoogle Scholar
  • 26 Salonen R, Haapanen A, Salonen J T. Measurement of intima-media thickness of common carotid arteries with high-resolution B-mode ultrasonography: inter- and intra-observer-variability.  Ultrasound Med Biol. 1991;  17 225-230
    CrossrefPubMedGoogle Scholar
  • 27 Baldassarre D, Werba J B, Tremoli E, Poli A, Pazzuccuni F, Sirtori C R. Common carotid intima-media thickness measurement: a method to improve accuracy and precision.  Stroke. 1994;  25 1588-1592
    PubMedGoogle Scholar
  • 28 Persson J, Stavenow L, Wikstrand J, Israelsson B, Formgren J, Berglund G. Non-invasive quantification of atherosclerotic lesions: reproducibility of ultrasonographic measurement of arterial wall thickness and plaque size.  Arterioscler Thromb. 1992;  12 261-266
    PubMedGoogle Scholar
  • 29 Blankenhorn D H, Selzer R H, Crawford D W, Barth J D, Liu C R, Liu C H, Mack W J, Alaupovic P. Beneficial effects of colestipol-niacine therapy of the common carotid artery: 2- and 4-year reduction of intima-media thickness measured by ultrasound.  Circulation. 1993;  88 20-28
    PubMedGoogle Scholar
  • 30 Riley W A, Barns R W, Bond M G, Evans G, Chambless L E, Heiss G. High-resolution B-mode ultrasound reading methods in the atherosclerotic risk in communities (ARIC) cohort.  J Neuroimaging. 1991;  1 168-172
    CrossrefPubMedGoogle Scholar
  • 31 Salonen R, Tervahauta M, Salonen J T, Pekkanen J, Nissinen A, Karvonen M J. Ultrasonographic manifestations of common carotid atherosclerosis in elderly Eastern Finish men: prevalence and associations with cardiovascular diseases and risk factors.  Arterioscler Thromb. 1994;  14 1631-1640
    PubMedGoogle Scholar
  • 32 O'Leary D H, Polak J F, Wolfson S K, Bond M G, Bommer W, Sheth S, Psaty B M, Sharret A R, Manolio T A. on behalf of the CHS collaborative research group . Use of sonography to evaluate carotid atherosclerosis in the elderly.  Stroke. 1991;  22 1155-1163
    PubMedGoogle Scholar
  • 33 Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients. A new model for the quantification and follow-up of preclinical atherosclerosis in living human subjects.  Atherosclerosis. 1988;  3 253-261
    PubMedGoogle Scholar
  • 34 Ferrara L A, Mancini M, Celentano A, Galderisi M, Iannuzzi R, Marotta T, Gaeta I. Early Changes of the Arterial Carotid Wall in Uncomplicated Primary Hypertensive Patients.  Arterioscler Thromb. 1994;  14 1290-1296
    PubMedGoogle Scholar
  • 35 Suurküla M, Agewall S, Fagerberg B, Wendelhag I, Widgren B, Wikstrand J. on behalf of the Risk Intervention Study (RIS) Group . Ultrasound Evaluation of Atherosclerotic Manifestations in the Carotid Artery in High-Risk Hypertensive Patients.  Arterioscler Thromb.. 1994;  14 1297-1304
    PubMedGoogle Scholar
  • 36 Howard G, Sharett A R, Heiss G, Evans G W, Chambless L E, Riley W A. Carotid intimal medial thickness distribution in general populations as evaluated by B-mode ultrasound.  Stroke. 1993;  24 1297-1304
    PubMedGoogle Scholar
  • 37 Gariepy J, Denarie N, Cjironi G, Salomon J, Levenson J, Simon A. Gender difference in the influence of smoking on arterial wall thickness.  Atherosclerosis. 2000;  153 139-145
    CrossrefPubMedGoogle Scholar
  • 38 Willinek W A, Ludwig M, Lennarz M, Höller T, Stumpe K O. High-normal serum homocysteine concentrations are associated with an increased risk of early atherosclerotic carotid artery wall lesions in healthy subjects.  J Hypertension. 2000;  18 425-430
    PubMedGoogle Scholar
  • 39 Iribarren C, Folsom A R, Jacobs D R, Gross M D, Belcher J D, Eckfeldt J H. for the ARIC Study Investigators . Association of Serum Vitamin Levels, LDL Susceptibility to Oxidation, and Autoantibodies Against MDA-LDL With Carotid Atherosclerosis.  Arterioscler Thromb Vasc Biol. 1997;  17 1171-1177
    PubMedGoogle Scholar
  • 40 O’Leary DH, Polak J F, Kronmal R A, Kittner S J, Bond G, Wolfson S K, Brommer W, Price T R, Gardin J M, Savage P J. on behalf of the CHS Collaborative Research Group . Distribution and Correlates of Sonographically Detected Carotid Artery Disease in the Cardiovascular Health Study.  Stroke. 1992;  23 1752-1760
    CrossrefPubMedGoogle Scholar
  • 41 Gariepy J, Salomon J, Denarie N, Laskri F, Megnien J L, Levenson J, Simon A. Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA-Study.  Atheroscler Thromb Vasc Biol. 1998;  4 584-590
    PubMedGoogle Scholar
  • 42 Zanchetti A. on behalf of the ELSA investigators . Prevalence of Carotid Atherosclerosis in Hypertension: Preliminary Baseline Data from the European Lacipidine Study on Atherosclerosis (ELSA).  Blood Pressure. 1996;  5(Suppl 4) 30-35
    PubMedGoogle Scholar
  • 43 Wiklund O, Hulthe J, Wikstrand J, Schmidt C, Olofsson SO, Bondjers G. Effect of Controlled Release/Extended Release Metoprolol on Carotid Intima-Media Thickness in Patients With Hypercholesterolemia.  Stroke. 2002;  33 572-577
    CrossrefPubMedGoogle Scholar
  • 44 Smilde T J, van Wissen S, Wollersheim H, Kastelein J JP, Stalenhoef A FH. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.  Lancet. 2001;  357 577-581
    CrossrefPubMedGoogle Scholar
  • 45 Schreiner P J, Heiss G, Tyroler H A, Morrisett J D, Davis C E, Smith R. Race and gender differences in the association of Lp (a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study.  Arterioscler Thromb Vasc Biol. 1996;  16 471-478
    PubMedGoogle Scholar
  • 46 Skoglund-Andersson C, Tang R, Bond M G, de Faire U, Hamstein A, Karpe F. LDL particle size distribution is associated with esgment-specific extracranial carotid intima-media thickening in healthy 50-year-old men.  Arterioscler Thromb Vasc Biol. 1999;  10 2422-2430
    PubMedGoogle Scholar
  • 47 Enderle M D, Balletshofer B M, Schmulling R M, Haring H U, Pfohl M. Early detection of atherosclerosis with high resolution ultrasound exemplified by type II diabetic patients.  Ultraschall Med. 1998;  19 16-21
    PubMedGoogle Scholar
  • 48 Shinozaki K, Hattori Y, Suzuki M, Hara Y, Kanazawa A, Takaki H. Insulin resistance as an independent risk factor for carotid artery wall intima media thickening in vasospastic angina.  Arterioscler Thromb Vasc Biol. 1997;  17 3302-3310
    PubMedGoogle Scholar
  • 49 Salonen R, Salonen J T. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study.  Atherosclerosis. 1990;  81 33-40
    PubMedGoogle Scholar
  • 50 Markus R A, Mack W J, Azen S P, Hodis H N. Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness.  Am J Clin Nutr. 1997;  65 1000-1004
    PubMedGoogle Scholar
  • 51 Hedblad B, Wikstrand M D, Janzon L, Wedel H, Berglund G. Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness.  Circulation. 2001;  103 1721-1726
    CrossrefPubMedGoogle Scholar
  • 52 Furberg C D, Adams H P, Applegate W B, Byington R P, Espeland M A, Hartwell T, Hunninghake D B, Lefkowitz D S, Probstfield J, Riley W A, Young B. for the Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group . Effect of Lovastatin on Early Carotid Atherosclerosis and Cardiovascular Events.  Circulation. 1994;  90 1679-1687
    PubMedGoogle Scholar
  • 53 Salonen R, Nyyssönen K, Porkkala E, Rummukainen J, Belder R, Park J S, Salonen J T. Kuopio Atherosclerosis Prevention Study (KAPS).  Circulation. 1995;  92 1758-1764
    PubMedGoogle Scholar
  • 54 Hodis H N, Mack W J, LaBree L, Selzer R H, Liu C R, Azen S P. The role of carotid intima-media thickness in predicting clinical coronary events.  Ann Intern Med. 1998;  128 262-269
    CrossrefPubMedGoogle Scholar
  • 55 Bots M L, Hoes A W, Koudstaal P J, Hofman A, Grobee D E. Common carotid intima-media-thickness and risk of stroke and myocardial infarction.  Circulation. 1997;  96 1432-1437
    CrossrefPubMedGoogle Scholar
  • 56 Simons P CG, Alegra A, Bots M L, Grobbee D E, van der Graaf Y. for the SMART Study Group . Common Carotid Intima-Media Thickness and Arterial Stiffness.  Circulation. 1999;  100 951-957
    CrossrefPubMedGoogle Scholar
  • 57 Simon A, Gariepy J, Chironi G, Megnien J L, Levenson J. Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk.  J Hypertens. 2002;  20 159-169
    CrossrefPubMedGoogle Scholar
  • 58 O'Leary D H, Polack J F, Kronmal R A, Manolio T A, Gregory L B, Wolfson S K. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults.  N Engl J Med. 1999;  340 14-22
    CrossrefPubMedGoogle Scholar
  • 59 Pitt B, Byington R P, Furberg C D, Hunninghake D B, Mancini G BJ, Miller M E, Riley W. for the PREVENT Investigators . Effect of Amlodipine on the Progression of Atherosclerosis and the Occurrence of Clinical Events.  Circulation. 2000;  102 1503-1510
    CrossrefPubMedGoogle Scholar
  • 60 Lonn E M, Yusuf S, Dzvik V, Doris C I, Yi Q, Smith S. for the SECURE investigators . Effects of Ramipril and vitamin E on Atherosclerosis. The study to evaluate ultrasound changes in patients treated with Ramipril and vitamin E (SECURE).  Circulation. 2001;  103 919-925
    PubMedGoogle Scholar
  • 61 Ludwig M, Stapff M, Ribeiro A, Fritschka E, Tholl U, Smith R D, Stumpe K O. Comparison of the effects of losartan and atenolol on common carotid artery initima-media thickness in patients with hypertension: results of a 2-year, double-blind, randomised, controlled study.  Clin Ther. 2002;  24 1175-1193
    CrossrefPubMedGoogle Scholar
  • 62 Stumpe K, Fritschka E, Jörger U, von Buquoy M, Schremmer D, Ludwig M. Superiority of amlodipine over enalapril in reversing carotid artery intima-media thickening in hypertensive patients.  European Heart Journal. 2002;  23 417 (P2183, Abstr.)
    PubMedGoogle Scholar
  • 63 Crouse III JR, Byington R P, Bond M G, Espeland M A, Craven T E, Sprinkle J W, McGovern M E, Furberg C D. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC II).  Am J Cardiol. 1995;  75 455-459
    CrossrefPubMedGoogle Scholar
  • 64 Simon A, Gariepy J, Moyse D, Levenson J. Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes.  Circulation. 2001;  103 2949-2954
    PubMedGoogle Scholar
  • 65 Orloff D G. Use of surrogate endpoints: a practical necessity in lipid-altering and antiatherosclerosis drug development.  Am J Cardiol. 2001;  87(4A) 35A-41A
    CrossrefPubMedGoogle Scholar
  • 66 Spence J D. Ultrasound measurement of carotid plaque as a surrogate autcome for coronary artery disease.  Am J Cardiol. 2002;  89(4A) 10B-15B
    PubMedGoogle Scholar
  • 67 Schminke U, Hilker L, Mosch L. Volumetric assessment of plaque progression with 3-dimensional ultrasonography under statin therapy.  J Neuroimaging. 2002;  12 245-251
    CrossrefPubMedGoogle Scholar

Prof. Dr. M. Ludwig

Medizinische Universitäts-Poliklinik Bonn

Wilhelmstr. 35 - 37 · 53111 Bonn