1 / 52

EUROECHO 2007 Lisbon, Portugal, December 5 – 8, 2007 Carotid scanning:

EUROECHO 2007 Lisbon, Portugal, December 5 – 8, 2007 Carotid scanning: an extension of the routine echocardiography study?. INTIMA-MEDIA THICKNESS AND ATHEROSCLEROSIS. Damiano Baldassarre Enrica Grossi Paoletti Centre Department of Pharmacological Sciences, University of Milan and

jbrake
Download Presentation

EUROECHO 2007 Lisbon, Portugal, December 5 – 8, 2007 Carotid scanning:

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. EUROECHO 2007 Lisbon, Portugal, December 5 – 8, 2007 Carotid scanning: an extension of the routine echocardiography study? INTIMA-MEDIA THICKNESS AND ATHEROSCLEROSIS Damiano Baldassarre Enrica Grossi Paoletti Centre Department of Pharmacological Sciences, University of Milan and Cardiologico Monzino Centre IRCCS

  2. INTIMA MEDIA THICKNESS (IMT) Near wall ICA BULB IMT COMMON CAROTID ECA Far wall Non-invasive marker of early arterial wall alteration. Easily assessed by B-mode ultrasound.

  3. Blood intima interface Media Adventitia interface Intimal plus media thickness of the arterial wall: a direct measurement with ultrasound imaging. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R.Circulation1986;74:1399-1406 Lumen { Echogenic lines Ultrasound Adventitia { Histology Intima Media Thickness (IMT)

  4. the interest increases exponentially with the time (about a 1000 papers published in the last 3 years ) Methodology for IMT measurement (widely used in clinical research) 400 PUBMED KEYWORDS: “Carotid IMT” OR "intima media thickness" OR "intimal medial thickness" OR "intima-media thickness" OR "intimal plus medial complex“. Pubmed limits: Humans and English 300 starting from 1986, when the study of Pignoli was published N° of studies published per year(as an index of interest of the scientific community for this methodology) 200 100 0 1995 1999 2002 1991 1993 1997 1998 2000 2001 2003 1992 1994 1996 2004 2005 2006 1986-1990 Year of publication

  5. What have we learned from this big amount of information?

  6. CAROTID IMT is associated: • with the same vascular risk factors known to affect atherosclerosis at coronary level IMT is now widely used in clinical trials as a marker of atherosclerosis to evaluate the effects of pharmacological agents • with the presence of clinical signs of coronary disease (i.e. AMI, angina etc.) • with the extent of coronary disease as assessed by angiography • with the incidence of previous vascular events

  7. Despite this big amount of information, little is known about the usefulness of IMT as an additive marker of cardiovascular risk to be used in clinical practice on an individual basis.

  8. Carotid IMT, measured with an electronic caliper (a method feasible in routine clinical practice) provides suitable information to associate carotid IMT • with atherosclerosis in other vascular districts • with the risk profile of the patient.

  9. In a first series of cross-sectional studies, mainly performed in patients attending our Lipid Clinic, we have shown that carotid IMT, as measured in clinical practice, correlates well with coronary VRFs CAROTID ARTERY INTIMA-MEDIA THICKNESS MEASURED BY ULTRASONOGRAPHY IN NORMAL CLINICAL PRACTICE CORRELATES WELL WITH ATHEROSCLEROSIS RISK FACTORS. Baldassarre D, Amato M, Bondioli A, Sirtori CR, Tremoli E. Stroke 2000;31: 2426-2430. INCREASED CAROTID ARTERY INTIMA-MEDIA THICKNESS IN SUBJECTS WITH PRIMARY HYPOALPHALIPOPROTEINEMIA. Baldassarre D, Amato M, Pustina L, Tremoli E, Sirtori CR, Calabresi L, Franceschini G. Arterioscler, Thromb Vasc Biol 2002;22:317-322. CORRELATION OF PARENTS’ LONGEVITY WITH CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS ATTENDING A LIPID CLINIC. Baldassarre D, Amato M, Veglia F, Pustina L, Castelnuovo S, Sirtori CR, and Tremoli E. Atherosclerosis 2005;179:111-117.

  10. Characteristics of subjects with and without Coronary Heart Disease (CHD) Baldassarre et al., Stroke 2000;31: 2426-2430.

  11. These results support very well the concept that: even when measured in the routine clinical practice, carotid IMT is a suitable marker: they do not provide any information concerning the potential role of IMT as a test for predictive purposes on individual basis • to investigate the effect of vascular risk factors • to identify groups of patients with and without a history of vascular events

  12. PREVENTIVE MEDICINE Before a new test can be used for predictive purposes Essential to establish its performance in the recognition of those individuals who effectively had had not experienced the target end point.

  13. Thus, we have performed a study aimed at investigating on an individual basis whether IMT measurements can be added to, or used instead of, vascular risk factors in the recognition of patients with and without a history of vascular events

  14. RECOGNITION OF PATIENTS WITH AND WITHOUT VASCULAR EVENTS BY ARTIFICIAL NEURAL NETWORK ANALYSES Patients without events (specificity) 91% Patients with events (sensitivity) 95% Weighted Mean (Prediction accuracy) 92% Thus, also the results of this study supported a potential role of carotid IMT to be used for predictive purposes • Combining some ultrasonic variables with a set of clinical variables, it was possible to reach an accuracy of prediction of about 92%, with • 95% of correct classification of patients with a history of vascular events • 91% of correct classification of those without Baldassarre et al., Ann Med. 2004;36(8):630-40.

  15. Before trying to use carotid IMT for predictive purposes three further questions had to be answered: 1. Is there a direct correlation between carotid and coronary atherosclerosis? 2. In what kind of patients IMT measurement may actually have the highest clinical usefulness? 3. what threshold value has to be adopted to obtain the maximal IMT predictive capacity?

  16. Before trying to use carotid IMT for predictive purposes three questions had to be answered: 1. Is there a direct correlation between carotid and coronary disease? 2. In what kind of patients IMT measurement may actually have the highest clinical usefulness? 3. what threshold value has to be adopted to obtain the maximal IMT predictive capacity?

  17. IN VIVO STUDIES Carotid Atherosclerosis Coronary Atherosclerosis VS ICA weaker correlations (r ≈ 0.3) Bif CC ECA (B-mode Ultrasound) (Quantitative angiography) Adams Circulation 1995 - Balbarini Angiology 2000 - Holaj Can J Cardiovasc 2003 CAROTID AND CORONARY ATHEROSCLEROSIS AUTOPSY STUDIES Significant correlation between carotid and coronary atherosclerosis (correlation coefficient = 0.5-0.6) Young et al., Am J Cardiol 1960;6:300-308. Holme et al. Arteriosclerosis 1981 Mitchell et al. BMJ 1962;5288:1293-301

  18. External carotid ultrasound (ECU) is focused on arterial wall Quantitative coronary angiography (QCA) provides information on arterial lumen diameter HYPOTHESIS This lower correlation was just due to methodological problems

  19. INTRAVASCULAR ULTRASOUND (IVUS) The miniaturisation of high-frequency intravascular ultrasound transducers has allowed the direct examination, in living humans, of the thickening of vessel walls of coronary arteries

  20. AIM OF THE STUDY To evaluate whether a correlation closer to the one obtained in autopsy studies can be obtained by measuring carotid and coronary atherosclerosis by using more homogeneous arterial wall parameters, i.e. IMT, in both vascular districts

  21. Carotid wall B-Mode ultrasound More homogeneous parameters from both vascular districts Classical approach VS VS Coronary wall Coronary lumen Angiography Intravascular ultrasound APPROACH

  22. C-IMTMean C-IMTMax 0.55 0.52 0.51 %DS 0.36 0.35 Autopsy Studies (mean of 3 studies) Carotid IMT Vs Angiography (mean of 6 studies) Carotid IMT Vs IVUS (Present study) Correlation coefficients between Carotid and Coronary atherosclerosis Correlation coefficients between carotid IMT and coronary lumen were much lower than those observed in autopsy studies those obtained evaluating IMT in both arterial districts were much higher and reach values very similar to the ones observed in studies post-mortem 0.60 PRESENT STUDY Thus, carotid IMT correlates very well with coronary atherosclerosis 0.55 DATA REPORTED IN LITERATURE 0.50 Correlation coefficient (r) 0.45 0.40 0.35 0.30

  23. Before trying to use carotid IMT for predictive purposes three questions had to be answered: 1. Is there a direct correlation between carotid and coronary disease? 2. In what kind of patients IMT measurement may actually have the highest clinical usefulness? 3. what threshold value has to be adopted to obtain the maximal IMT predictive capacity?

  24. Is the population with FRS≥20% (high risk) a good target for IMT measurements? Patients at high risk (e.g. those with a Framingham Risk Score >20%) are already qualified for aggressive treatment Thus, in this kind of patients, no further risk stratification tools are needed.

  25. Patients at intermediate-risk (FRS: 10-20%) represent for many clinicians a gray decision area In fact, although these patients do not currently qualify for aggressive treatment, epidemiological and clinical evidences show that cardiac events occur in many of these individuals The number of patients at intermediate-risk is high (for instance, they constitute 40% of the US population) Thus, tools to further stratify the risk in patients at intermediate-risk are actually needed

  26. Before trying to use carotid IMT for predictive purposes three questions had to be answered: 1. Is there a direct correlation between carotid and coronary disease? 2. In what kind of patients IMT measurement may actually have the highest clinical usefulness? 3. what threshold value has to be adopted to obtain the maximal IMT predictive capacity?

  27. Epidemiologic data currently available indicate that a value of IMT equal or greater than 1 mm at any age is associated with a significantly increased risk of myocardial infarction or cerebrovascular disease. 400 GENERAL POPULATION IMT ≥ 1 mm 300 Folsom et al. Diabetes Care 2003;26:2777-84. Chambless et al. Clin Epidemiol 2003;56:880. Salonen et al. Arterioscler Thromb 1991;11:1245-9. Chambless et al. Am J Epidemiol 1997;146:483. Frequency 200 100 0 0,38 0,88 1,38 1,88 2,38 MEAN MAX IMT Low High Risk of CAD and CVD

  28. AIM OF THE STUDY A longitudinal observational study aimed at investigating whether the measurement, in clinical practice, of carotid Max-IMT could be combined with the FRS to improve the predictability of cardiovascular events in patients who are at low or intermediate risk Baldassarre et al., Atherosclerosis 2006 May 6 [Epub ahed of print]

  29. Thus, can we say that IMT has not predictive capacity? NO ! The addition to the FRS of the “plaque status”, expressed in terms of presence or absence of a Max-IMT value ≥1 mm (or even ≥ 1.3 mm), did not significantly improve the predictive power of the FRS.

  30. Effect of age on carotid IMT Effect of gender on carotid IMT P<0.0001 8 2.0 r =0.43 p<0.0001 6 1.5 4 Age adjusted Max-IMT (mm) Max-IMT (mm) 1.0 2 0 0.5 0 20 40 60 80 Women Men Age (years) Age and sex known to have a major impact on IMT measurements have not been taken into account. Baldassarre et al., STROKE 2000;31: 2426-2430

  31. Deciles of Max-IMT distribution in men and women calculated in a group of about 2000 Italian dyslipidemic patients, plotted for 10-years age intervals. MEN WOMEN 90th 4.0 4.0 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  32. In selected populations affected by major risk factors like patients with dyslipidemia, hypertension, or diabetes, an IMT greater than 1 mm is present in almost every patient above 50 years of age MEN WOMEN 90th 4.0 4.0 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  33. In addition, if age and sex are not taken into account, each patient with an IMT ≥1 mm is classified as having the same risk either if man or women, and either if young or old; 90th 4.0 4.0 MEN WOMEN 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  34. In addition, if age and sex are not taken into account, each patient with an IMT ≥1 mm is classified as having the same risk either if man or women and either if young or old; but , if we consider for example an IMT value of 1.3 mm, this may be the highest value within the IMT distribution of young patients but even the lowest one when the IMT distribution of patients older 50 are considered MEN WOMEN 90th 4.0 4.0 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  35. In addition, by using this approach, each patient with an IMT value greater than 1 mm is classified as having the same risk either if he has an IMT of 1.1 mm or if he has an IMT of 2.5 mm or greater: this is out of any biological plausibility. MEN WOMEN 90th 4.0 4.0 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  36. To overcome this problem in our study the “best threshold values” (BTVs), above which to consider Max-IMT as abnormally high, were calculated for each 10-years age interval in men and women. MEN WOMEN 90th 4.0 4.0 90th 80th 70th 60th 80th 3.0 3.0 70th 50th 60th 40th Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 2.0 2.0 30th 30th 20th 20th 10th 10th 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  37. To overcome this problem in our study the “best threshold values” (BTVs), above which to consider Max-IMT as abnormally high, were calculated for each 10-years age interval in men and women. These were found to be the 60th and 80th percentiles of Max-IMT distribution for men and women, respectively, for each decade of age. MEN WOMEN By using these new IMT threshold values the results of the analyses completely changed 90th 4.0 4.0 90th 80th 3.0 3.0 70th 60th 80th 3.0 3.0 2.5 2.5 70th 50th 2.1 60th 40th 2.0 Deciles of Max-IMT distribution Deciles of Max-IMT distribution Max-IMT (mm) Max-IMT (mm) 50th 40th 1.7 2.0 2.0 30th 30th 1.4 20th 1.3 20th 10th 10th 0.9 0.8 0.7 1.0 1.0 0.0 0.0 20-29 30-39 40-49 50-59 60-69 70-79 20-29 30-39 40-49 50-59 60-69 70-79 DECADES OF AGE (years) DECADES OF AGE (years) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  38. Repeating the Cox analysis, using these BTVs as stratification tools: a FRS above 10% was associated with an HR of 2.60; p = 0.03 (95% CI 1.07 - 6.3) a Max-IMT above BTV gave a HR of 2.42; p = 0.04 (95% CI 1.04 - 5.66) FRS Max-IMT independent predictors of new cardiovascular events. Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  39. Stratifying the study population according to the presence of a FRS above or below 10% and Max-IMT above or below BTV Max-IMT best threshold value (BTV): men = 60th percentile women = 80th percentile 7 6 5 4 3 Hazard ratio 2 1 Max-IMT ≥ BTV 0 Max-IMT < BTV 10<FRS<20% FRS < 10% Values are adjusted for pharmacological treatments Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  40. 7 6 5 4 3 2 1 0 Stratifying the study population according to the presence of a FRS above or below 10% and Max-IMT above or below BTV the concomitant presence of FRS ≥10% and Max-IMT above the BTV yielded a marked increase in the HR. 6.7 (p=0.01) Max-IMT best threshold value (BTV): men = 60th percentile women = 80th percentile the strength of the associations between Max-IMT and outcome was at least as strong as the associations seen with FRS 4.2 P<0.05 4.1 P<0.05 Hazard ratio Max-IMT ≥ BTV Max-IMT < BTV 10<FRS<20% FRS < 10% Values are adjusted for pharmacological treatments Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  41. p=0.67 Max-MT≥BTV Max-MT<BTV HR FOR HAVING A NEW CARDIOVASCULAR EVENT IN LOW, INTERMEDIATE AND HIGH RISK GROUPS Max-IMT best threshold value (BTV): men = 60th percentile women = 80th percentile 3 2 In addition, compared to low-risk patients Log Hazard Ratio 1 0 Low risk FRS<10% Intermediate risk 10≤FRS<20% High risk 20<FRS<30% Values are adjusted for pharmacological treatments Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  42. Predicted incidence by the Framingham Risk Score Observed incidence incidence of new cardiovascular events predicted on the basis of FRS vs. incidence actually observed (estimated by the Kaplan-Meyer method) 50 40 30 Incidence of cardiovascular events (%) Threshold for drug therapy 20 10 0 Max-MT< BTV Max-MT ≥ BTV Max-MT< BTV Max-MT ≥ BTV Intermediate risk patients (10%<FRS<20%) Low risk patients (FRS<10%) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  43. Max-MT< BTV Max-MT ≥ BTV Max-MT< BTV Max-MT ≥ BTV Intermediate risk patients (10%<FRS<20%) Low risk patients (FRS<10%) incidence of new cardiovascular events predicted on the basis of FRS vs. actually observed incidence (estimated by the Kaplan-Meyer method) 50 Predicted incidence by the Framingham Risk Score Observed incidence 40 30 Incidence of cardiovascular events (%) Threshold for drug therapy 20 10 0 Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  44. incidence of new cardiovascular events predicted on the basis of FRS vs. actually observed incidence (estimated by the Kaplan-Meyer method) Ratio = 3.11 50 Predicted incidence by the Framingham Risk Score Observed incidence 40 On the basis of the two last histograms it can be calculated that the “actually observed incidence of new cardiovascular events” can be better predicted by FRS if this is multiplied for 3.11 . 30 Incidence of cardiovascular events (%) Threshold for drug therapy 20 10 0 Max-MT ≥ BTV Intermediate risk patients (10%<FRS<20%) Low risk patients (FRS<10%) Baldassarre et al., Atherosclerosis. 2007;191(2):403-408.

  45. IMT as predictor of vascular events

  46. One American study provides convincing evidences that carotid artery IMT is a good predictor of new vascular events. about the 95% of the subjects with an IMT classifiable in the first quintile were free of vascular events. Thus suggesting that carotid IMT may be effectively considered as a good marker of evolutive atherosclerotic disease. In contrast, the percentage of subjects free of vascular events in the group with the highest quintile of IMT was less than 75% Follow up: about 7 years 4500 patients 65 years or older O’Leary et al. New Eng J Med 1999

  47. THE IMPROVE STUDY THE IMPROVE STUDY Carotid Intima Media Thickness (IMT) and IMT-Progression as Predictors of Vascular Events in a High Risk European Population

  48. DESIGN The IMPROVE Study is a multicenter, longitudinal, observational study carried out in an Pan-European population of 3732 patients at high risk of cardiovascular disease for the presence of at least three vascular risk factors. Vascular risk factors: Male or Female at least 5 years after menopause Hypercholesterolemia Hypertriglyceridemia Hypo-alpha-lipoproteinemia Hypertension Diabetes Smoking habits Family history of cardiovascular diseases FINLAND n=1050 (2 clinical centers) SWEDEN n=533 THE NETHERLANDs n=553 FRANCE n=501 ITALY n=1095 (2 clinical centers)

  49. OBJECTIVE To evaluate the association between Carotid IMT-progression within 15 months Cross-sectional carotid IMT the rate of subsequent vascular events

  50. < 1.04 1.04 - 1.20 1.22 - 1.41 1.42 - 1.70 >1.70 Baseline carotid IMTMean-Max as predictor of new cardiovascular events 1.00 1st quintile Thus, also in an European population carotid IMT is a very good predictor of new vascular events 2nd quintile 0.98 3rd quintile 0.95 % event free 4th quintile IMTMean-Max 0.92 5th quintile 0.89 0 1 2 3 follow-up (years)

More Related