《外科护理学》课程阅读资料（英文）周围血管疾病 venous thrombosis

Th NEW ENGLAND JOURNAL MEDICINE ORIGINAL ARTICLE An Association between Atherosclerosis and Venous Thrombosis Paolo Prandoni,M.D.,Ph.D.Franca Bilora,M.D.,Antonio Marchiori,M.D. Enrico Bernardi MD Francesco Petrobelli M D Anthonie W.A Lensing,M.D.,Ph.D.Martin H.Prins,M.D.,Ph.D. and Antonio Girolami,M.D. ABSTRACT BACKGROUND n abou lism,the caus are detectabl complications.Whether atherosclerosis is associated with an increased risk ofvenous th thrombosis is unknown. the Depa were62neditmsonogrptyoftecaoidaneisn29umeierndpeicaswho ts to at the dep had deep venous thrombosis of the legs without symptomatic atherosclerosis and in neous thrombosis,patents wit control subjects were assessed for plaques. paop RESULTS NEngl]Med203,3481435-4L eous (47 pe percent cor ence interva 1 1to55.00934 and 48 ofthe 150 control sub 320 ,05 nte l 24 5to 39.5).The odds ratios for carotid plaque s in patients with spontaneous thrombosis.as ry thrombosis and wit controls,were 2.3 (95 per va,1.4o3 1.1t02.9 the strength of this association did not change CONCLUSIONS bosis.Athe common risk factors. N ENGL J MED 348:15 WWW.NEJM.ORG APRIL 10,2003 1435 d Journal of Medici Downloaded from nejm 1820 use only.No

n engl j med 348;15 www.nejm.org april 10, 2003 The new england journal of medicine 1435 original article An Association between Atherosclerosis and Venous Thrombosis Paolo Prandoni, M.D., Ph.D., Franca Bilora, M.D., Antonio Marchiori, M.D., Enrico Bernardi, M.D., Francesco Petrobelli, M.D., Anthonie W.A. Lensing, M.D., Ph.D., Martin H. Prins, M.D., Ph.D., and Antonio Girolami, M.D. From the Department of Medical and Surgi￾cal Sciences, Second Chair of Internal Med￾icine, University of Padua Medical School, Padua, Italy (P.P., F.B., A.M., E.B., F.P., A.G.); the Center for Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (A.W.A.L.); and the Department of Clinical Epidemiology, University of Maastricht, Maastricht, the Netherlands (M.H.P.). Address reprint re￾quests to Dr. Prandoni at the Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy, or at paoprand@tin.it. N Engl J Med 2003;348:1435-41. Copyright © 2003 Massachusetts Medical Society. background In about a third of patients with venous thromboembolism, the cause of the disorder is unexplained. In patients with atherosclerosis, activation of both platelets and blood co￾agulation and an increase in fibrin turnover are detectable, which may lead to thrombotic complications. Whether atherosclerosis is associated with an increased risk of venous thrombosis is unknown. methods We performed ultrasonography of the carotid arteries in 299 unselected patients who had deep venous thrombosis of the legs without symptomatic atherosclerosis and in 150 control subjects. Patients with spontaneous thrombosis, patients with secondary thrombosis from acquired risk factors, and control subjects were assessed for plaques. results At least one carotid plaque was detected in 72 of the 153 patients with spontaneous thrombosis (47.1 percent; 95 percent confidence interval, 39.1 to 55.0), 40 of the 146 with secondary thrombosis (27.4 percent; 95 percent confidence interval, 20.2 to 34.6), and 48 of the 150 control subjects (32.0 percent; 95 percent confidence interval, 24.5 to 39.5). The odds ratios for carotid plaques in patients with spontaneous thrombosis, as compared with patients with secondary thrombosis and with controls, were 2.3 (95 per￾cent confidence interval, 1.4 to 3.7) and 1.8 (95 percent confidence interval, 1.1 to 2.9), respectively. In a multivariate analysis that accounted for risk factors for atherosclerosis, the strength of this association did not change. conclusions There is an association between atherosclerotic disease and spontaneous venous throm￾bosis. Atherosclerosis may induce venous thrombosis, or the two conditions may share common risk factors. abstract The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved

Th NEW ENGLAND IOURNAL MEDICINE THROMBOEMBOLISM IS and tially fatal diseas osis.Th e spontaneous dee fecting approximately 2 p All subjects provided written informed consent erable progr cutive outpatients admitted to our insti 三三 tution between March 1996 and April 2001 with ,child mal-vein thrombosis, h。 Datie f eithe ger episodes in na thromboembolism or symptomatic atherosclero tients with prothrombotic tendencies.Although sis (ischemic stroke,transient ischemic attack emyocardial infarct on,angina,or intermitte tients.the disease still remains unexplained in up tients and those who declined to to30 percent ofpatients. recruited patients were hospitalized and received We hypothesized tha conventional treatr nent (i.e or low or veno lant thewe atherosclerosis)has long been identified as anin Patients were classified as having secondan contro nd prospective studi ha到 i the pre three mor legs hyperlipidemia.or hypertension 13-16 Further sified as having spontancous thrombosis.Screen more,atherosclerosis is associate d with act ation ing for mutations and conditions associated with of both pln and b protein h plications. G20210A mutation :and lupus-like anticoagulants)was left to the discretion rmed accord case elsewhere in th 0. to p ea me asvmptomatic atherosclerotic disease and the risk of venous thromboembolism,we assessed wheth clinical presentation. -w plaques e pr ent and, so,quan study period,150 subject ere a for c ents w. ith lated to nous thrombosis and in a control group ofsub- embolism or atherosclerosis and who had no clini ects without thrombosis.We compared t e fre cal evidence or history of such dis As each ncy cha cteristics of caroti plaque patient spontaneous venous thr mbo wa room in the ward who was frea age (in five-year age groups)and sex to the qualify ing patient was se ted s the control.If that the part apate,the n METHoDS control STUDY DESIGN AND OBJECTIVE Before unde rgoing carotid-artery ultrasor 8 ontr study to alua e the po phy,patients wit thrombosis an 1436 N ENGL J MED 348;15 WWW.NEJM.ORG APRIL 10.200 Downloaded from r No without permission

n engl j med 348;15 www.nejm.org april 10, 2003 The new england journal of medicine 1436 enous thromboembolism is a serious and potentially fatal disease af￾fecting approximately 2 persons per 1000 each year in Western countries.1-5 Although consid￾erable progress has been made in the diagnosis and treatment of this disorder, many questions remain concerning its pathogenesis. Classic risk factors for venous thrombosis include cancer, surgery, immo￾bilization, fractures, paralysis, pregnancy, child￾birth, and use of estrogens.6-8 These conditions not only predispose apparently normal people to throm￾bosis but also are likely to trigger episodes in pa￾tients with prothrombotic tendencies.9 Although acquired or inherited risk factors potentially respon￾sible for this disorder are identifiable in most pa￾tients, the disease still remains unexplained in up to 30 percent of patients.6-12 We hypothesized that patients with atheroscle￾rosis may be at increased risk for venous thrombo￾sis. Indeed, older age (a well-known risk factor for atherosclerosis) has long been identified as an in￾dependent risk factor for venous thrombosis.1,2,6-8 A few case–control and prospective studies have found an association between venous thromboem￾bolic disorders and chronic arterial disease of the legs, hyperlipidemia, or hypertension.13-16 Further￾more, atherosclerosis is associated with activation of both platelets and blood coagulation as well as an increase in fibrin turnover, which can lead to throm￾botic complications.17-23 In subjects without symptomatic atherosclero￾sis, carotid plaques are considered a reliable marker of arterial disease elsewhere in the circulation.24-28 To determine whether an association exists between asymptomatic atherosclerotic disease and the risk of venous thromboembolism, we assessed wheth￾er vessel-wall plaques were present and, if so, quan￾tified them by means of carotid-artery ultrasonog￾raphy in a consecutive series of patients with acute venous thrombosis and in a control group of sub￾jects without thrombosis. We compared the fre￾quency and characteristics of carotid plaques among patients with spontaneous thrombosis, pa￾tients with secondary thrombosis as a result of ac￾quired risk factors, and control subjects without thrombosis. study design and objective This was a case–control study to evaluate the po￾tential relation between asymptomatic carotid-wall plaques and acute spontaneous deep venous throm￾bosis. The protocol was approved by the institution￾al review board of Padua University, in Padua, Italy. All subjects provided written informed consent. patients All consecutive outpatients admitted to our insti￾tution between March 1996 and April 2001 with symptomatic proximal-vein thrombosis, as assessed by compression ultrasonography, were eligible for the study. Patients with a history of either venous thromboembolism or symptomatic atherosclero￾sis (ischemic stroke, transient ischemic attack, acute myocardial infarction, angina, or intermittent claudication) were excluded, as were pregnant pa￾tients and those who declined to participate. All recruited patients were hospitalized and received conventional treatment (i.e., unfractionated or low￾molecular-weight heparin followed by oral antico￾agulant therapy).10 Patients were classified as having secondary thrombosis if they had cancer, had given birth with￾in the previous three months, had had leg trauma or fracture, had been immobilized for more than one week, or took estrogens; all other patients were clas￾sified as having spontaneous thrombosis. Screen￾ing for mutations and conditions associated with thrombophilia (antithrombin, protein C, or pro￾tein S deficiency; factor V Leiden; prothrombin G20210A mutation; hyperhomocysteinemia; and lupus-like anticoagulants) was left to the discretion of treating physicians and was performed accord￾ing to previously described methods.29-33 Carriers of thrombophilia were classified as having sponta￾neous or secondary thrombosis according to their clinical presentation. During the study period, 150 control subjects were randomly selected from patients who were ad￾mitted for conditions unrelated to venous thrombo￾embolism or atherosclerosis and who had no clini￾cal evidence or history of such diseases. As each patient with spontaneous venous thrombosis was recruited, the first patient admitted to the same room in the ward who was frequency-matched for age (in five-year age groups) and sex to the qualify￾ing patient was selected as the control. If that pa￾tient declined to participate, the next patient admit￾ted who met the requirements was selected as the control. Before undergoing carotid-artery ultrasonogra￾phy, patients with thrombosis and control subjects were evaluated for the presence of risk factors for v methods The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved

ATHEROSCLEROSIS AND VENOUS THROMBOSIS atherosclerosis ion the basis ofaclinical evami corded as well as the number and site ofassociated nation,biochemical tests,or both,data on the fol- ipsilateral and contralateral smaller lesions.In ad- dia thicknes with smoking wa ofless than one month:hvpertension.defined ba cation and expre ssed in millimeters.The higher of systolic blood pressure of more than 160 mm Hg the two values was recorded s or 100 of the height in meters)of more than 30:diabetes first examination. ions or a level of at least 200 mg per deciliter(11.1 mmol per liter)bosis and control subjects werecompared with use e at le nd 2 ho s or D defined bva fasting venous cholesterol was assessed with logis s Re. ing 240 mg per deciliter(6.2 mmol per liter),ora el exce ding 250 mg ce intervals Initially,the three groups were or by the g drugs Th smoking status,hyperlipidemia,hypertension,obe ULTRASONOGRAPHY OF CAROTI ARTERIES sity,and diabetes) nt of the car d arteries was per hich the th d h oupswereinc the patie dd with an Apogee 800 Plus device (Advanced Tech- eg with an 8.5-MHz probe for MHz probe tn secondary sis,was risk factors of athero clerosis finally the relation between spontaneous thrombosis and the presence d tion opp I plaque was a as ide with andorbeaopsoefp The dia thi raphy.and the following segments were examined the common carotid arteries was expressed in each roup as the mean±S and he analysisofva used to com groups. dinal and ing a ment ofcar Plaque was defined as a protrusion into the Statistical analyses were performed with SpSS sta- e lumen of at l mn tistical software (version 9.0). measured alon ReSuLts as stenosis ofup to 30percent,stenosis of31to50 STUDY POPULATION s or to 70 pe cent,or se℃u ients ad th prox d 3 found the greatest ous thromboembolism and 43 he N ENGL J MED 348:15 WWW.NEJM.ORC APRIL 10.200 1437 Downloaded from n use only.N other us moupemison ety

n engl j med 348;15 www.nejm.org april 10, 2003 atherosclerosis and venous thrombosis 1437 atherosclerosis.34 On the basis of a clinical exami￾nation, biochemical tests, or both, data on the fol￾lowing variables were recorded on a standard form: smoking status, with smoking defined as habitual, daily use of 10 or more cigarettes, with interruptions of less than one month; hypertension, defined by a systolic blood pressure of more than 160 mm Hg or a diastolic blood pressure of more than 90 mm Hg (or both) on at least two occasions or by the use of hypotensive drugs; obesity, defined by a body-mass index (the weight in kilograms divided by the square of the height in meters) of more than 30; diabetes mellitus, defined by a plasma glucose level of at least 126 mg per deciliter (7.0 mmol per liter) after an overnight fast on at least two occasions or a level of at least 200 mg per deciliter (11.1 mmol per liter) 2 hours after the administration of 75 g of oral glu￾cose and at least once between 0 and 2 hours or by the use of antidiabetic drugs; and hyperlipidemia, defined by a fasting venous cholesterol level exceed￾ing 240 mg per deciliter (6.2 mmol per liter), or a fasting venous triglyceride level exceeding 250 mg per deciliter (2.8 mmol per liter) on at least two oc￾casions, or by the use of lipid-lowering drugs. ultrasonography of carotid arteries Bilateral assessment of the carotid arteries was per￾formed by a trained operator who was unaware of the patients’ clinical status. The test was carried out with an Apogee 800 Plus device (Advanced Tech￾nology Laboratories), with an 8.5-MHz probe for B-mode imaging and a 6-MHz probe for pulsed￾wave color Doppler imaging according to standard￾ized methods.35,36 Patients were examined in the supine position with their neck rotated 45 degrees in the direction opposite the site being examined. The carotid trunk was identified with the use of both B-mode and pulsed-wave color Doppler ultrasonog￾raphy, and the following segments were examined: common carotid artery, carotid bifurcation, and in￾ternal and external carotid arteries. All arteries un￾derwent longitudinal and transverse scanning as well as a flow analysis. Plaque was defined as a protrusion into the vessel lumen of at least 2 mm, as measured from the border between the adventitial and medial lay￾ers.35,36 The percentage of vessel obstruction was measured along the longitudinal axis and classified as stenosis of up to 30 percent, stenosis of 31 to 50 percent, stenosis of 51 to 70 percent, or stenosis of 71 to 100 percent. When more than one plaque was found, the greatest degree of obstruction was re￾corded, as well as the number and site of associated ipsilateral and contralateral smaller lesions. In ad￾dition, the measure of the intima–media thickness of the right and left common carotid arteries was obtained 1 to 3 cm proximally to the carotid bifur￾cation and expressed in millimeters. The higher of the two values was recorded. The reproducibility of the ultrasonographic as￾sessment of carotid atherosclerosis was evaluated in 100 consecutive patients by having the test repeat￾ed by another operator within one hour after the first examination. statistical analysis The clinical characteristics of patients with throm￾bosis and control subjects were compared with use of the Kruskal–Wallis test for continuous variables and the chi-square test for dichotomous variables. The presence of carotid plaques in the three groups was assessed with logistic-regression analyses. Re￾sults were expressed as odds ratios with 95 percent confidence intervals. Initially, the three groups were assessed with use of a pairwise univariate compar￾ison. Then, risk factors for atherosclerosis (age, sex, smoking status, hyperlipidemia, hypertension, obe￾sity, and diabetes) were introduced in a multivariate model in which the three groups were included with the use of dummy variables. In analyses taking into account only the patients with thrombosis, the odds ratio for carotid atherosclerosis in patients with spontaneous thrombosis, as compared with those with secondary venous thrombosis, was adjusted for the presence or absence of thrombophilia and risk factors of atherosclerosis. Finally, the relation between spontaneous thrombosis and the presence of carotid plaques was assessed in subgroups of pa￾tients older than 60 years and older than 70 years. The measure of the intima–media thickness of the common carotid arteries was expressed in each group as the mean ±SD, and the analysis of variance was used to compare the study groups. Kappa sta￾tistics were used to assess interobserver variability of the ultrasonographic assessment of carotid plaques. Statistical analyses were performed with SPSS sta￾tistical software (version 9.0). study population Of 378 consecutive outpatients admitted with prox￾imal-vein thrombosis, 76 were excluded, 33 because of previous venous thromboembolism and 43 be￾results The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved

Th NEW ENGLAND IOURNAL MEDICINE omatic atherosclerosis of the re ent in 32 p s20.9p formed inuded in the study and in 33 patients with secondary thrombosis (22.6 Onthe basis of the 533 bophilic ties we re iden tients ar spon ane 25 swith sponta fo cancerin65 recent traumaot fracture in dd recen thrombophilia and in 15 ofthe 64 patients with se surgery in16,prolongedimmobilizationin10,use ondary thrombosis(23.4percent)inwhom this de- 3).During termination was made(Table 1). and w dy The had been admitted to the hospital for the following at least one carotid plaque was detected in 72 of reasons:infectious diseases in 20,cardiac causes in ory condition 18 nce interval,39 17 55040 ic conditions in 15.hematologic conditions in 15. 074n cent:95 pe 2l,20.2 neurologicconditions in11,hepaticdiseasein8,re- to 34.6),and 48 of the 150 control subjects (32.0 nal di ease in7,and endocrin ogic diseases in ence interval,24. e m n char te log tc-reg n analys tors for atherosclerosis.The three study groups likely to have carotid plagues than those with sec were similar with regard to these features.Sympto- ondary thrombosis (odds ratio,2.3:95 perc ent con interval,1.4 to 3.7)or con .q ent co ith s erosclerotic lesions similar to that of control sub jects(odds ratio,0.895percentconfidence interval Control ount risk fctors for atherd sis.the odds ratio Age-y 67.0416.7 65.8+174 65.4415.7 for carotid plaques in patients with spontaneous 65(4 6845.3 rombosis as compared wit bosis and w (95 pero Smoker-no.(% 40(26.1 4933.6 45(30.0 -no.% 4630.1） 3725.3 46(30.刀 with secondary thrombosis did 2516,3 171 25(16,7 ntly from those in control subjects (odds ratio. Obesity一no.(3 0.895 ent con 117.2 12(倍.2) 16(10.7 05o1.5 Diabetes-no.(%) 1610.5 128.21 18(12.0 68(4.4 64(43 the association between spontar ous thrombosis bophilia no 25t 15对 lar 14+ ciation did not cha nge after adius g the g ment for risk factors for atheroscle is and throm bophilic ab d od ，2.3:9 ce I erval,1. 03 resence of carotid plaques grew stronger with age,with an adjusted odds ratio of 3.0(95 perce maincomSinaSnithSaoVeidcnononc 4)ar 1438 N ENGL J MED 348:15 WWW.NEJM.ORG APRIL 10,2003 urnal of Mec without permission Medical Society.All rights reserved

n engl j med 348;15 www.nejm.org april 10, 2003 The new england journal of medicine 1438 cause of symptomatic atherosclerosis. Of the re￾maining 302 patients, 299 provided written in￾formed consent and were included in the study. On the basis of the clinical presentation, 153 pa￾tients had spontaneous thrombosis and 146 had secondary thrombosis (cases associated with active cancer in 65, recent trauma or fracture in 44, recent surgery in 16, prolonged immobilization in 10, use of estrogens in 8, and recent childbirth in 3). During the study period, 150 eligible control subjects gave their consent and were enrolled in the study. They had been admitted to the hospital for the following reasons: infectious diseases in 20, cardiac causes in 18, respiratory conditions in 18, neoplastic condi￾tions in 17, gastrointestinal causes in 16, rheumat￾ic conditions in 15, hematologic conditions in 15, neurologic conditions in 11, hepatic disease in 8, re￾nal disease in 7, and endocrinologic diseases in 5. Table 1 shows the main characteristics of the study subjects as well as the prevalence of risk fac￾tors for atherosclerosis. The three study groups were similar with regard to these features. Sympto￾matic pulmonary embolism was present in 32 pa￾tients with spontaneous thrombosis (20.9 percent) and in 33 patients with secondary thrombosis (22.6 percent). Thrombophilic abnormalities were iden￾tified in 25 of the 68 patients with spontaneous thrombosis (36.8 percent) who were screened for thrombophilia and in 15 of the 64 patients with sec￾ondary thrombosis (23.4 percent) in whom this de￾termination was made (Table 1). carotid plaques At least one carotid plaque was detected in 72 of the 153 patients with spontaneous thrombosis (47.1 percent; 95 percent confidence interval, 39.1 to 55.0), 40 of the 146 with secondary thrombosis (27.4 percent; 95 percent confidence interval, 20.2 to 34.6), and 48 of the 150 control subjects (32.0 percent; 95 percent confidence interval, 24.5 to 39.5). In the univariate logistic-regression analysis, patients with spontaneous thrombosis were more likely to have carotid plaques than those with sec￾ondary thrombosis (odds ratio, 2.3; 95 percent con￾fidence interval, 1.4 to 3.7) or controls (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 2.9). Pa￾tients with secondary thrombosis had a risk of ath￾erosclerotic lesions similar to that of control sub￾jects (odds ratio, 0.8; 95 percent confidence interval, 0.5 to 1.3). In the multivariate analysis, after taking into ac￾count risk factors for atherosclerosis, the odds ratio for carotid plaques in patients with spontaneous thrombosis as compared with those with secondary thrombosis and with controls was 2.4 (95 percent confidence interval, 1.4 to 4.0). The odds in patients with secondary thrombosis did not differ signifi￾cantly from those in control subjects (odds ratio, 0.8; 95 percent confidence interval, 0.5 to 1.5). In logistic-regression models that included only patients with venous thrombosis, the strength of the association between spontaneous thrombosis and the presence of any carotid lesions remained significant and of similar magnitude (odds ratio, 2.3; 95 percent confidence interval, 1.4 to 3.7). The value of this association did not change after adjust￾ment for risk factors for atherosclerosis and throm￾bophilic abnormalities (adjusted odds ratio, 2.3; 95 percent confidence interval, 1.3 to 3.9). The asso￾ciation between spontaneous thrombosis and the presence of carotid plaques grew stronger with age, with an adjusted odds ratio of 3.0 (95 percent confidence interval, 1.7 to 5.4) among patients old￾er than 60 years and an adjusted odds ratio of 3.9 * Plus–minus values are means ±SD. There were no significant differences among the groups. † The causes of thrombophilia were as follows: antithrombin deficiency in 2, protein C deficiency in 1, protein S deficiency in 3, factor V Leiden alone in 10, prothrombin mutation alone in 2, hyperhomocysteinemia (homocysteine, >15 µmol per liter) alone in 4, and hyperhomocysteinemia in combination with factor V Leiden and prothrombin mutation in 2 and 1, respectively. ‡ The causes of thrombophilia were as follows: protein C deficiency in two, fac￾tor V Leiden alone in three, prothrombin mutation in one, lupus-like anticoag￾ulants in five, hyperhomocysteinemia alone in three, and hyperhomocysteine￾mia in combination with factor V Leiden in one. Table 1. Main Characteristics of the Study Population.* Characteristic Patients with Spontaneous Thrombosis (N=153) Patients with Secondary Thrombosis (N=146) Control Subjects (N=150) Age — yr 67.0±16.7 65.8±17.4 65.4±15.7 Male sex — no. (%) 71 (46.4) 65 (44.5) 68 (45.3) Smoker — no. (%) 40 (26.1) 49 (33.6) 45 (30.0) Hypertension — no. (%) 46 (30.1) 37 (25.3) 46 (30.7) Hyperlipidemia — no. (%) 25 (16.3) 17 (11.6) 25 (16.7) Obesity — no. (%) 11 (7.2) 12 (8.2) 16 (10.7) Diabetes — no. (%) 16 (10.5) 12 (8.2) 18 (12.0) Screened for thrombophilia — no. (%) 68 (44.4) 64 (43.8) — Thrombophilia — no. 25† 15‡ — The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved

ATHEROSCLEROSIS AND VENOUS THROMBOSIS (95 percent confidence interval,1.8 to 8.4)among patients older than70 years. The interobserver variability of the ultrasonograph Char ic assessment of carotid atherosclerosis was high N-72 00 ≤309% 45162.51 25162.53 29160.4 31-509 2230.61 13325) 14129.2 ADDITIONAL OBSERVATIONS Thererisisofthecrotidplaqueprod 51-709 56.9 1(2.5 504 re shown in >70% 0 12.5) 0 ipsilateral and contralateral plaques ocation Common carotid artery 5(6.9 25.0 36.2 Carotid bifurcation 14(19.4) 14(35.0) 15(31.2 was sis,0. Intemal carotid artery 4461.1) 2255.01 2654.2) with secondary thrombosis.and 0.880.32 in the 925) 25.0 control subjects.Asignificant difference was found between pati ts with spont neo sis an d as the ble 3.Number and Location of Ipsilateral and Contralateral Minor Carotid cant difference between patients with secondary thrombosis and control subjects(P=0.80). ontaneo DISCUSSION Site of Minor Lesior (N=45 (N= Our study demonstrates a relation between asymp carotid artery 3(6. 26.刀 26.1 prevalence Carotid bifurcation 75.6 6(20.0 7212 with unexplained thrombotic eve emal carotid artery 28(62.2) 15(50.0 18(54.5) s(47 1 percent than in those with secondary ones(27.4per External carotid artery 715.6 7233) 618.2) cent)or witho t).This th rosclerosis is associated with activation of and thrombophilic conditions.When the analysis platelets and blood coagulation,as well as increased came even str onger.In ad ngvenous the the de the number ofplaques,the number of carotid seg- flowing venous system.High D dimer levels have been found to be 30 th an increased ris ng were more amon other two gr ouns since carotid plaques rep ent arterial occlusive disease ofthe legs hyperlinide. marker of arterial disease else here in the circu- on our suggest eithe athe k of venous thror wo conditions share common risk factors shown that,surprisingly enough,the use of statins N ENGLJ MED 348:15 WWW.NEJM.ORC APRIL 10.200 1439 Downloaded from r 18.2011. y.N other us mhoupemison

n engl j med 348;15 www.nejm.org april 10, 2003 atherosclerosis and venous thrombosis 1439 (95 percent confidence interval, 1.8 to 8.4) among patients older than 70 years. reproducibility of ultrasonographic assessments of carotid plaques The interobserver variability of the ultrasonograph￾ic assessment of carotid atherosclerosis was high (kappa=0.86; 95 percent confidence interval, 0.75 to 0.97). additional observations The characteristics of the carotid plaque producing the greatest degree of obstruction are shown in Ta￾ble 2. The number and location of associated small￾er ipsilateral and contralateral plaques are given in Table 3. The mean intima–media thickness of the com￾mon carotid arteries was 1.06±0.46 mm in patients with spontaneous thrombosis, 0.83±0.32 in those with secondary thrombosis, and 0.88±0.32 in the control subjects. A significant difference was found between patients with spontaneous thrombosis and both those with secondary thrombosis and control subjects (P<0.001), whereas there was no signifi￾cant difference between patients with secondary thrombosis and control subjects (P=0.80). Our study demonstrates a relation between asymp￾tomatic atherosclerotic lesions and spontaneous venous thrombosis of the legs. The prevalence of carotid plaques was significantly higher in patients with unexplained thrombotic events (47.1 percent) than in those with secondary ones (27.4 percent) or in age- and sex-matched subjects without thrombo￾sis (32.0 percent). This association was still present after adjustment for risk factors for atherosclerosis and thrombophilic conditions. When the analysis was confined to elderly patients, the association be￾came even stronger. In addition, other features of atherosclerosis (such as intima–media thickness of the carotid arteries, the degree of carotid stenosis, the number of plaques, the number of carotid seg￾ments involved, and the extent of contralateral ca￾rotid involvement) were far more frequent among subjects with spontaneous thrombosis than in the other two groups. Since carotid plaques represent a marker of arterial disease elsewhere in the circu￾lation,24-28 our results suggest either that athero￾sclerosis can induce venous thrombosis or that the two conditions share common risk factors. Atherosclerosis is associated with activation of platelets and blood coagulation, as well as increased fibrin turnover.17-23 A role of this prothrombotic state in promoting venous thrombosis is plausible, on the basis of the assumption that activated plate￾lets and coagulation factors appear in the slow￾flowing venous system. High d-dimer levels have been found to be associated with an increased risk of venous thromboembolism37,38 and recurrent venous thromboembolism.39 In addition, old age, arterial occlusive disease of the legs, hyperlipide￾mia, and hypertension have been reported to be as￾sociated with an increased risk of venous throm￾boembolism.1,2,13-16 Finally, two recent studies have shown that, surprisingly enough, the use of statins discussion Table 2. Characteristics of the Plaque Producing the Largest Degree of Obstruction in Subjects with at Least One Plaque. Characteristic Patients with Spontaneous Thrombosis (N=72) Patients with Secondary Thrombosis (N=40) Control Subjects (N=48) Stenosis ≤30% 45 (62.5) 25 (62.5) 29 (60.4) 31–50% 22 (30.6) 13 (32.5) 14 (29.2) 51–70% 5 (6.9) 1 (2.5) 5 (10.4) >70% 0 1 (2.5) 0 Location Common carotid artery 5 (6.9) 2 (5.0) 3 (6.2) Carotid bifurcation 14 (19.4) 14 (35.0) 15 (31.2) Internal carotid artery 44 (61.1) 22 (55.0) 26 (54.2) External carotid artery 9 (12.5) 2 (5.0) 4 (8.3) Table 3. Number and Location of Ipsilateral and Contralateral Minor Carotid Lesions. Site of Minor Lesion Patients with Spontaneous Thrombosis (N=45) Patients with Secondary Thrombosis (N=30) Control Subjects (N=33) Common carotid artery 3 (6.7) 2 (6.7) 2 (6.1) Carotid bifurcation 7 (15.6) 6 (20.0) 7 (21.2) Internal carotid artery 28 (62.2) 15 (50.0) 18 (54.5) External carotid artery 7 (15.6) 7 (23.3) 6 (18.2) The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved