Richard H. White
The Epidemiology of Venous Thromboembolism
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The Epidemiology of Venous Thromboembolism
Richard H.White,MD
Abstract—Venous thromboembolism(VTE)occurs for the first time inϷ100persons per100,000each year in the United
States,and ris exponentially fromϽ5cas per100,000personsϽ15years old toϷ500cas(0.5%)per100,000
persons at age80years.Approximately one third of patients with symptomatic VTE manifest pulmonary embolism
(PE),whereas two thirds manifest deep vein thrombosis(DVT)alone.Despite anticoagulant therapy,VTE recurs
frequently in the first few months after the initial event,with a recurrence rate ofϷ7%at6months.Death occurs in Ϸ6%of DVT cas and12%of PE cas within1month of diagnosis.The time of year may affect the occurrence of VTE,with a higher incidence in the winter than in the summer.One major risk factor for VTE is ethnicity,with a
significantly higher incidence among Caucasians and African Americans than among Hispanic persons and Asian-
Pacific Islanders.Overall,Ϸ25%to50%of patient with first-time VTE have an idiopathic condition,without a readily平和
identifiable risk factor.Early mortality after VTE is strongly associated with prentation as PE,advanced age,cancer,
and underlying cardiovascular dia.(Circulation.2003;107:I-4–I-8.)
Key Words:venous thromboembolismⅢpulmonary embolismⅢepidemiologyⅢprognosisⅢthrombosisⅢveins
Incidence of VTE
A number of studies have focud specifically on the epide-miology of VTE.Anderson et al determined the incidence of VTE in Worcester,Massachutts,over an18-month period in the mid1980s by reviewing the hospital discharge records of all patients coded as having VTE,including both recurrent and first-time episodes.The number of cas(nϭ405)was small,and97%were Caucasian.1In Minnesota,Silverstein et al analyzed the medical records of all residents of Olmsted County who were diagnod with VTE between1966and 1990(nϭ2218).They categorized cas of VTE as definite, probable,or possible bad on the level of objective confir-mation.Importantly,a large number of cas of PE diagnod at autopsy were categorized as definite VTE whether or not it was clinically symptomatic.2Becau the autopsy rate in Olmsted County is at least three times greater than the United States average,and becau PE is reported in7%to30%of all autopsy ries(median15%),3this type of VTE may have been overreprented.
Kniffen et al ud Medicare hospital discharge data from1986 to1989to estimate the incidence of DVT and PE among individuals in the United StatesϾ65years of age.4The study included recurrent VTE and categorized cas as PE when this diagnosis was listed with a diagnosis of DVT.The Longitudinal Investigation of Thromboembolism Etiology study by Cushman et al combined2prospective cohort studies of individualsϾ45 years of age:the Cardiovascular Health Stud
y and the Athero-sclerotic Risk in Communities Study.5Cas with confirmed VTE were identified,and all death records between enrollment (1987to1989)and1997were reviewed.Hansson et al followed a cross-ctional sample of men in Go¨teborg,Sweden,born in 1913,and analyzed the incidence of VTE bad on hospital discharge diagnosis or autopsy records.6In Malmo¨,Sweden, Nordstro¨m et al identified all patients with a venographic diagnosis of DVT during1987and reviewed the associated medical records to determine their demographic and clinical features.Cas of both initial and recurrent VTE were included.7 White et al have reported veral studies using linked(1990to prent)hospital discharge records of California residents with a social curity number(Ͼ95%of the population)who were hospitalized in any nonfederal hospital in California(Ϸ95%of the population)with DVT or PE.8–10In the studies,race/ ethnicity was defined bad on coding by the hospital admis-sions office,but no laboratory or physiological data is included in this administrative data t.Although linked to a death registry,the cau of death among patients who died out of the hospital can not be accurately determined.9
In the studies,involving predominantly Caucasian pop-ulations,the incidence of first-time symptomatic VTE di-rectly standardized for age and x to the United States population ranged from71to117cas per100,000popula-tion.1,2,11–14The higher incidence,reported by Silverstein et a
l,likely reflects the large number of cas of PE detected at autopsy.2As summarized below,the effects of race/ethnicity are so dominating that this incidence rate should not be extrapolated to non-Caucasians.Table1summarizes the major factors that affect the incidence of VTE.
Relative Incidence of DVT and PE
The most important methodological factor affecting the reported relative incidences of DVT and PE is reliance on
From the University of California,Davis,Sacramento,California.
Correspondence to Richard H.White,M.D.,Suite2400,PSSB,4150V Street,Sacramento,California95817.Phone:916-734-7005,Fax: 916-734-2732,E-mail:rhwhite@ucdavis.edu
©2003American Heart Association,Inc.
Circulation is available at DOI:10.1161/01.CIR.0000078468.11849.66
autopsy data.Most clinical studies that do not include autopsy data have reported the incidence of cli
nically diagnod DVT to be approximately twice that of PE.Anderson et al reported an incidence of first-time DVT of48per100,000,compared with23per100,000for PE(32%of VTE cas).1Murin et al found that51,233cas were admitted to California hospitals with VTE had DVT alone,whereas21,625(30%)had PE during the same period.10In a study of postoperative patients, 41%of VTE cas were PE.15In the Longitudinal Investiga-tion of Thromboembolism Etiology study,28%of VTE cas were PE.5
Studies that include a large number of VTE cas diag-nod by autopsy generally report a higher proportion of cas with PE than DVT.The yearly incidence of PE and DVT was205and182per100,000,respectively,among men over age50as reported by Hansson et al,6and69and48per 100,000,respectively,as reported by Silverstein et al.2It is probable that autopsy data overestimate the incidence of PE by detecting asymptomatic cas,whereas reliance on clinical diagnosis probably underestimates the incidence.
Effect of Race/Ethnicity
Gore et al compared the prevalence of VTE at autopsy among 600cas over age40years in Boston and an equal number in Kyushu,Japan.There was a strikingly higher prevalence of PE in North Americans(15%)than in Japane(0.7%).15
In California,which has an ethnically diver population including a large number of African Americans,Hispanics, and Asian-Pacific Islanders,White et al reported an annual incidence of idiopathic VTE in personsՆ18years of23per 100,000among Caucasians;29per100,000among African Americans;14per100,000among Hispanics;and6per 100,000among Asian-Pacific Islanders.9During1996,the standardized incidence of first-time VTE was86per100,000 among Caucasians;93per100,000among African-Americans;37per100,000among Latinos;and19per 100,000among Asian-Pacific Islanders.The findings sup-port the obrvations by Klatsky et al of a lower adjusted risk of VTE among Hispanics[risk ratio(RR)ϭ0.7,95%confi-dence interval(CI)0.3–1.5]and Asians(RRϭ0.2,95%CI 0.1–0.5)than in Caucasians in a large cohort followed prospectively in the Kair Health System in Northern California.16
The relatively low incidence of VTE in Asians and Hispanics has not been explained,but may relate to a lower prevalence of genetic factors predisposing to VTE,such as factor V Leiden in Asian populations(0.5%)compared with Caucasians(5%).17–19In venographic studies of patients recovering from hip replacement surgery,the incidence of asymptomatic VTE in Asians appears comparable with that in North America,20–22suggesting that the difference in VTE incidence may be related to less efficient inactivation of coagulation by activated protein C or less fibrinolytic activity a
mong Caucasians.The lower incidence of VTE in Hispanics than in African Americans cannot be explained by a lower prevalence of factor V Leiden,as this genetic condition is prent inϷ2%of Hispanic andϽ1%of African Americans.17,23
Effect of Age
A number of published studies have shown that the incidence of first-time VTE ris exponentially with age,from a negligible rate(Ͻ5per100,000per year)among children Ͻ15years of age to values in the range of450to600per 100,000per year(Ϸ0.5%/year)among individuals over the age of80years.1,2As shown in Figure1,the incidence increas dramatically after age60.1
Among individuals50to59years old,Anderson et al obrved an incidence of first-time plus recurrent VTE of62 per100,000,whereas for patients in this same age range, Silverstein et al obrved a much higher incidence of122per 100,000among women and147per100,000among men.In the study reported by Hansson et al,the obrved incidence was132per100,000population age50–59.6Among indi-
Summary of the Epidemiology of First-Time VTE
Variable Finding
Incidence in Total Population(AssumingϾ95%Caucasian)Ϸ70–113cas/100,000/year1,2,11–14
Age Exponential increa in VTE with age,particularly after age40years1,2,4,7
25–35years oldϷ30cas/100,000persons
70–79years oldϷ300–500cas/100,000persons
Gender No convincing difference between men and women1,2
Race/Ethnicity 2.5–4-fold lower risk of VTE in Asian-Pacific Islanders and Hispanics9
Relative Incidence of PE vs DVT Abnt autopsy diagnosis:Ϸ33%PE;66%DVT1,10
中级职称英语考试>靠边停车技巧With autopsy:Ϸ55%PE,45%DVT2,6
Seasonal Variation Possibly more common in winter and less common in summer24–26
Risk FactorsϷ25%to50%“idiopathic”depending on exact definition
Ϸ15%–25%associated with cancer;Ϸ20%following surgery(3mo.)2,5,27 Recurrent VTE6-month incidence:Ϸ7%;higher rate in patients with cancer5,28–30
Recurrent PE more likely after PE than after DVT4,10,31
Death After Treated VTE30day incidenceϷ6%after incident DVT,2,5,10
30day incidenceϷ12%after PE1,32,33
Death strongly associated with cancer,age,and cardiovascular dia
White Epidemiology of VTE I-5
viduals 70to 79years old,Hansson et al reported 522VTE cas per 100,000per year;1,6Anderson et al reported 316cas per 100,000per year (35%recurrent);Silverstein et al reported 440cas per 100,000per year;2Nordstro ¨m et al reported that the incidence of DVT alone was 765cas per 100,000population during a single year (unknown proportion with recurrent DVT);7and Kniffin et al reported an annual incidence of 442cas per 100,000population (includes individuals with recurrent VTE).4Overall,Nordstro ¨m et al estimated that the cumulative probability of developing VTE between ages 50and 80was 10.7%for Swedish men.
Effect of Sex
Although u of oral contraceptives and postmenopausal hormone replacement have been associated with VTE in women,published data suggest no consistent differences in the incidence of VTE among men and women.
Anderson et al found a similar incidence in both xes (Figure 1).1Silverstein et al noted a slightly higher incidence rate among younger women,2and a modest predilection among older men.Cushman et al reported similar incidences among men and women except for a 2-fold higher rate in men over age 75.5Among patients Ͼ65years,Kniffin et al reported that women had a slightly higher relative risk of DVT (RR ϭ1.05,95%CI 1.0–1.1)and a lower risk of PE (RR ϭ0.86,95%CI 0.82–0.90).4Nordstro ¨m et al reported no significant difference in the incidence of DVT between men and women.7Using the California Discharge Data t we noted a slightly higher incidence of first-time VTE in women (78per 100,000adults over age 18)than in men (63per 100,000);the difference was due largely to a higher incidence in women Ͼ80years old.In the abnce of a consistent difference among studies,therefore,the incidence of VTE is probably approximately equal in men and women.
Seasonal Variation
Although some reports have described a higher incidence of fatal PE during the winter months,24,25
Bounameaux et al obrved no such asonal variation in the incidence of DVT.11Using a large French discharge data t (n ϭ127,318),Boulay et al found 10%to 15%more admissions during
小学新标准英语birthdaywinter months and 10%to 15%fewer admission during the summer.26Additional studies are needed to confirm this finding.Assuming the amount of physical activity in a population decreas in the winter,it is possible that this finding demonstrates an inver relationship between physi-cal activity and development of VTE.
Incidence of Idiopathic Versus Secondary VTE
Although Anderson et al did not classify VTE cas as idiopathic or condary,they did note that 15%of the patients in their study had cancer.In the study by Cushman et al,47%of 304cas had idiopathic VTE,defined as no associated cancer,antecedent trauma,or recent surgery or immobiliza-tion.5Twenty-five percent of their cas had undergone antecedent surgery,and 25%had cancer.In a recent analysis of the data from Silverstein et al,Heit et al reported that only 26%of cas were idiopathic,and attributed 59%to immo-bilization or nursing home residence,18%to cancer,12%to trauma,and the remainder to medical illness,stroke,or central venous lines or pacemakers.27In our analysis of patients in California hospitalized with first-time VTE,18%had malignancy,23%had under
gone surgery within 2months,15%developed VTE during a hospitalization for medical illness,2%had major trauma,and a 41%were idiopathic.Thus,the proportion of patients with VTE cate-gorized as idiopathic falls in the range of 26%to 47%of first-time cas;the exact figure depends partly on the definitions of idiopathic and condary VTE.
Recurrent VTE
Cushman et al found the first-year incidence of recurrent VTE was 7.7%overall and 7.8%among patients with idiopathic VTE;patients with cancer had a higher rate of recurrence (14.0%per year).5In a prospective cohort study of 355patients with DVT,Prandoni et al reported recurrent VTE in 8.6%after 6months and 30.3%after 8years.28Hansson et al reported rates of recurrent VTE of 7.0%at 1year and 22.0%at 5years.29In the Olmsted county study,Heit et al found the incidence of recurrent VTE was 10.1%at 6months,12.9%after 1year,and 30.4%after 10years.30This relatively high recurrence rate may reflect changes in methods of diagnosis and treatment of VTE over the 25-year period during which the data were collected.
Using the California Patients Discharge Data Set,the 6-month recurrence rate of VTE was 6.4%in the cohort of patients hospitalized for DVT (n ϭ51,233)and 5.8%in the cohort initially hospitalized for
PE (n ϭ21,625).10When deaths were censored according to the Kaplan –Meier tech-nique,VTE recurrence rates were identical in the 2cohorts.Figure 2shows that recurrent VTE is most likely in the weeks after initial hospitalization for DVT.Heit et al also reported a higher incidence of recurrent VTE in the period immediately after diagnosis with a gradual reduction in the recurrence rate over time.30
In the study by Murin et al,1086%of recurrent events after DVT were DVT,whereas 66%of recurrent events after PE were PE.Kniffen et al reported similar relationships,which have also been obrved in randomized clinical studies.
31
Figure 1.Annual incidence of VTE among residents of Worces-ter MA 1986,by age and x.(Reproduced by permission from Anderson FA,et al.Arch Intern Med .1991;151:933–938.)
I-6Circulation June 17,2003
Finally,in the study by Hansson et al of 591patients with DVT,77%of recurrent events were DVT.29
Mortality after Initial VTE
Ca fatality rates are difficult to interpret using data col-lected retrospectively,particularly when autopsy data are ud to identify patients with PE.Prospective data also may be difficult to interpret when autopsies are not performed on patients who die of unexplained caus.Cushman et al noted a 28-day ca-fatality rate of 9.4%after first-time DVT and 15.1%after first-time PE.5Among patients with idiopathic VTE,the 28-day rate was 5.2%compared with 7.3%after condary VTE and 25.4%among patients with cancer.In our study,the 6-month fatality rate was 10.5%among patients with DVT and 14.7%among tho with PE.10The cohort of Silverstein et al had 30-day ca fatality rates of 5.5%for patients with DVT and 8.0%for tho with PE not diagnod at autopsy.2The ca-f
atality rate of recurrent VTE may differ from that of initial VTE.31In the study by Prandoni et al,of 355patients with first-time DVT,16.7%of patients had died at 1year,with cancer the most frequent cau.28Siddique et al recently analyzed the 30-day ca-fatality rate after primary diagnosis of PE among individuals Ͼ65years of age and reported a rate of 16.1%in African Americans and 12.9%in Caucasians.32Patients diagnod with PE during hospitalization for another condition had a higher ca-fatality rate (32.5%)than tho admitted for PE.In the study by Anderson et al,11.6%of patients died during the index hospitalization,5%of tho with DVT and 23%of tho with PE.1During long-term (2to 3.5years)follow-up,however,the mortality rate was 25%for patients with PE and 32%for patients with DVT.Mortality was strongly associ-ated with age,and PE was listed on the death certificate as contributory in only 4of the 108deaths.Finally,the Inter-national Cooperative Pulmonary Embolism Registry was established to determine mortality rates of PE and to identify baline factors associated with death.The 3-month overall crude mortality rate was 17.4%;45.1%of deaths were
ascribed to PE.33After excluding patients in whom PE was first discovered at autopsy,the 3-month overall mortality rate was 15.3%.Systolic arterial hypotension,congestive heart failure,cancer,tachypnea,right-ventricular hypokinesis on echocardiography,chronic obstructive pulm
corgi
onary dia,and age Ͼ70years were significantly associated with in-cread mortality risk in patients with PE.
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Figure 2.Time cour of rehospitalization for recurrent DVT or PE among patients initially hospitalized for DVT without prior hospitalization for VTE.(Modified from White et al.Arch Int Med 2000;160:2038.)
White Epidemiology of VTE I-7
