a Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism A 25-Year Population-Based Study Mare D. Silverstein, MD; John A. Heit, MD; David N. Mok, MD; Tanya M. Petterson, MS: W. Michael O'Fallon, PhD: L. Joseph Melton I, MD Backgrounds The incidence of venous thromboembo- lism has not been well described, and there are no stud- {esof long-term trends in the incidence of venous throm- boembolism Objectives: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe tends in incidence. Methods: We performed a retrospective review of the complete medical records from @ popullation-based in- ception cohort of 2218 patients who resided within Olm- sted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. Results: The overall average age- and sex-adjusted an- ‘nual incidence of venous thromboembolism was 117 per 100 000 (deep vein thrombosis, 48 per 100 000: pulmo- nary embolism, 69 per 100000), with higher age- adjusted rates among males than females (130 vs 110 per 100.000, respectively). The incidence of venous throm- boembolism rose markedly with increasing age for both, sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the inc dence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than $5 years, and increased for women older than 60 « tional health problem, especially among the elderly. Whil the incidence of pulmonary embolisin has decreased over yelustons: Venous thromboembolism is a major na- lime, the incidence of deep vein thrombosis remains un- changed for men and is increasing for older women. These lindings emphasize the need for more accurate identili- cation of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis, Arch Intern Med. 1998;158:585-593 HE REPORTED annual inci dence of venous thrombo- embolism varies widely, ranging from 43.7 to 145.0 per 100000 (published {dentified cases solely by review of inpa- sat medical records may have uunderes- timated the true incidence since cases not occurring in an acute-care hospital (eg, cases from nursing homes or other From the Department of Medicine, the Divisions of Arca General internal Medicine (Drs Silverstein and Mohr) and Cardiovascular Diseases and Section of Hematology Research (Dr Hei); the Department of Health Sciences Research, and the Sections of Clinical Epidemiology (Drs Silverstein and Melton) and Biostatistics (Qs Peterson and Dr OFallon), Mayo Clinic and Mayo Foundation, Rochester, Minn Dr Silverstein {snow a the Medical University of Sou Carolina Charleston, Downloaded From: on 06/04/2018. rales were age- and sex-adjusted to the 1080 US white population) for deep vein thrombosis and 20.8 to 65.8 per 100000 for pulmonary embolism. A number of study design factors may have contrib- ‘uted tothe wide variation in reported rates, For example, different studies identified cases using data froma variety of sources, ‘including patient questionnaires, the US National Hospital Discharge Survey.* or Medicare elaims.* Because of diagnostic uncertainty oF misclassification, data from these sources may have underesti- mated or overestimated the actual inc dence rate. Moreover, none of these stu dies accurately separated initial from recurrent events oF included events dis- covered during autopsy. Studies that long-term care facilities and those in which death occurred suddenly within the community) could be missed.* Some studies report data from only selected populations, such as patients aged 65 years or alder.” patients referred to ter- ary care centers for diagnostic evalua tion and treatment,’ oF patients from different geographic districts.” Further- rmore, there are no studies of tends in the incidence of venous thromboembo- lism over time. Due to these limitations fn existing data, we performed a study to estimate the incidence of deep vein thrombosis and pulmonary embolism within a well-defined geographic populs- tion and describe trends in incidence (©1998 American Medical Association. Al rights reserved,PATIENTS, MATERIALS, AND METHODS MATERIALS AND METHODS Using the data resources of the Rochester Epidemiology Project’ we dented the inception cohor of resident of Olmsted County, Minnesota, with afst-Metime episode of deep vein thrombosis or pulmonary embolism during the 25-year petiod Irom 1960 through 1990, Olimsted {County (1990 population, 106470) sloested 144k south cast of Minneapolis, Minn, Population-based epidemio~ Toga studies are possible inthis sting because medial cares largely self-contained within the community. Most the cares provided by the Mayo Clink, Rochester, Minn, ‘wth approximately 1000 staf physicians and 2 lrg a Tlisted hospitals, andthe Olimsted Medical Center, with approximately 75 staff physicians and he afiised Olm- Hd Communlty Hosta Rochester. The Mayo Clinic and its affliated hospitals (Saint Marys and Rochester Meth- cut Hospi Rochester) have maintained common med Cal record system since 1907, The Mayo Clinic unit medi Calrecord contains both inpaient and outpatient data that Seca rettievabl or review. The medial diagnoses and sugicl procedures entered into these medical records have ibe indexed in an atomated form since 1935. The index Includes diagnoses made during outpatient office visits and cline contin meron department cae nig death ceruicaton® The medical records of the Olmsted Medical Center andthe other medial cae providers who terve the resident of Olnsied County are ls indexed and Tetrevable. Thus details ofthe medical care provided to the residents of Olmsted County are svallable for sy. IDENTIFICATION OF THE PATIENT COHORT ‘We conducted a retrospective, population-based sty to ‘ental Olmsted County residents with rst-fetime on set of deep vein thrombossor pulmonary embolism from January 1, 1966, through December 1, 1990, A master ist, ‘of potental sted County residents with deep vin throm tows, pulmonary emboli, pulmonary infarction, or si lar diagnoses or who had any diagnos test or procedure ted ithe diagnosis of deep veln thrombosis or pulmo- nary embolus, was consructed by searching the compu rized Indexes of medical dagnoses and surgical prce- lures ae well aval valable databases for dlagore tess, bling data, death cetlicates and autopey diagnoses for Olmsted County residents. The fellowing datasources were Included: First, the Medical Diagnostic Index wa searched todentify all patients wth daghones of dep vein hrom- tosis phlcbls,rombophlcbus,phegmasi alba lens Plepinasia cerules dolens and similar terms for venous thrombosis: (6) pulmonary embolism, pulmonary infarc tion, or similar diagnoses; snd (0) varicose veins, varicose tlcer, sass ulcer, venous insullictency postphebite syn roe speci eon snd i lar dagnoses; and (A) patients undergoing «radionuclide study for venous thromboembolism, ncding perfusion or venilation-perfusion lung scans, radiolabeled brino~ gemleg scanning or radionuclide venography Second, the Sera recede nds wa searched ely al thromboss or pulmonary emboli, including ve liga tion inferior vena cava ligation or inerruptin,place- tment ofan inferior vena cava filer or similar device, and ‘enous or pulmonary thrombectomy. Third, multiple ra Aiology databases ofthe Mayo Clinic were searched for pa tents who underwent venography, pulmonary anglogr phy, duplex ulrmonography, computed tomography, or fagneti resonance imaging to Went any adil pa tients with diagnoses of deep vein thromaboss pulmonary ebollsm, or pulmonary tnarction, (During te study pe- tod all computed tomography and magneticresonance n- aging studies for Olmsted County residents were er- formed the Mayo Clini and their diagnoses were included inthe radiology databases) Fourth, the echocardiogr- phy computer database ofthe Mayo Clinic was searched to dently patients with diagnoses of pulmonary embo- lem, pulinonary bypertension, orsiiar diagnoses Filth data om the Mayo Cine vacUlar laboratory logbook were entered intoacomputer database forth study, andl pa- tents undergoing impedance plethysmograpky, Doppler tltaconography, or duplex llrsonographiy for venous di fase were identified, Finally, computerized billing data Bases ofthe Mayo Clinic were searched to dential pa dent with charges for noninvasive vascular laboratory tet, including impedance plethysmography and Doppler ultra: sonography. The final maser list of potential cases con- tained 9646 individuals whose complete (inpatient and ot patient) medical record fom al roviders of health care th Olmsted County were reviewed | for the study DEFINITION OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM, Each pisode of deep vein thrombosis or pulmonary embo- lism was categorized int the highest of Teel of dagnos- tccertainty (finite, probable, or posible) based om the fol lowing eiera. A deep vein thrombosis was categorized xs follows: definite when confirmed by venography. computed tomography, magnetic resonance imaging or pathologic ex- mination of thrombus removed during sper or autopsy. probable if testing forthe definite level of diagnostic cer thnty was ether nt performed or results were indetern tates the recltsofat leat 1 of the following noninvasive Ie were pote ipeance nog con fous wave Doppler ultrasonographic examination per- formed inthe Mayo linc vsctlar laboratory, compression dluplexulssonography, radionuclide venogrphy, or radio- labeled fibrinogen leg scanning, and possible i confirma tory tests were not done or rests were indeterminate and (@) the medial record indiated thats physician made ade gos of dep ven thrombi (or posible deep vein thon tens) () sigs and sympioms consistent with deep vein thrombosis were present and (©) the patent underwent therapy with anticoagulants (heparin sodium, arfarnso- dum orasinilr agent) or asurgial procedurfor deep vin thrombosis A pulmonar embolism was categorized a ol- low: define when conlirmed by pulmonary angiography, computed tomography, magnele resonance imaging, of pathologic examination of thrombus removed during ur ry oF auopey proeble lf testing forthe defint level of {iggnontc certainty wascither not performed or results were (©1998 American Medical Association. Al rights reserved, Downloaded From: on 06/04/2018.indeterminate and perfusion or ventilation perfusion hing scan was interpreted as high probably fr pulmonary em bolism, and possible if confirmatory tests Were ether not dlone or results were indeterminate and (a) the medical re- ‘ord indicated that a physician made a dagnost of pul- tionary embolism, () signs and sympioms consistent with pulmonary embolism were preset, and (the patent un- crwent therapy with anticoagulant (heparin, warfarin, or simular agent) or surgical procedure or pulmonary em bolism suchas placement of inferior vena cava ites. A short period of anticoagulation therapy while awaiting completion of dagnosticevalstion fr eliter suspected deep ‘ein thrombosis r pulmonary embolism was ineuficint {grounds for inclusion as posible venous thromboerbo- im. An episode of ven thromboembolism consisting ofboth des vein rombosis snd pulmonary emboli a ‘aegorized into the highest evel of diagnostic estan rex tent for either manifestation. Because pulmonary emo lem sa complication of deep vein thrombosis, the resus ate presented as deep vein thrombosis alone or pulmo nary embolism with or without deep vein thrombosis ‘Venous thromboembolism evens that were fist den ted during the patent Hfetime and met our criteria, and events confirmed during autopsy that had een objec tively verified by an invasive ornorivaive testo the date of death were classild as evens discovered before death Events confirmed during autopsy meting only our dag” nose criteria fora possible deep vein thrombosis r pul tnonary embolism on the date of death, or events discov ted during autopsy for which medial ecord review could notestablsh the date ofonset, were clase as events dis- covered after death, ‘Mayo Clinic pathologists performed ll autopsy ex- aminations and completed the respective death ceri ‘les of persons dying within Olmsted County during the Study period, For purposes of analysis, pulmonary embo- ilmerentsdiscovered afer death were csi sa ease of death” if the pathologist labeled it ay sch in the au topsy report oie death cerfcate Usted pulmonary em bolism as an immediate or underlying cause of death orn- cluded pulmonary embolism in pat ofthe death erica Pulmonary embolism events discovered afer death were classified asa contributory cause of death i the patholo fst completing the death certifeate included pulmonary mbolis asa contributing cause or othe significant con Alton on part 2 ofthe death certlicate. Pulmonary embo- ile events fist identified on postmortem examination but sot specifically Labeled as «cause of death in the atopy report or listed on the death cerificate were categorized snot aeaise of death INCIDENCE CRITERIA Eligibility for this analysis required that patients have a firs-time episode of deep vein thrombosis or pulmonary ‘embolism while residents of Olmsted County during the study period from January 1, 1966, through December 31, 1900. Resideney in Olmsted County at the time of first, diagnosis of venous thromboembolism was confirmed by review of each patient’s medical record to verily the patient’ address on the date of diagnosis. In making these determinations, we had access to a mean (45D) of 30.5 + 19.2 years (median, 30 years) of documented medical history prior to the first diagnosis of venous {thromboembolism in these patients. DATA COLLECTION sc cy ei Pi seers ee Sr Ca) siesta rs, ss cg nn saa SUSE ant ore li steal ag DATA ANALYSIS son in p98 ppl we i cs ee tad te oa pba mse mae Se eee Se (ele tic re atl nate pleas cc ooh ah Es a scpriniimkee wheal spied inten tsps lt ast Sop tpt me SRE URC et ale To-year intervals for the analysis ofthe subgroups. The mid roc sid Sp ima Ne sips estes cei a alana he (©1998 American Medical Association. Al rights reserved, Downloaded From: on 06/04/2018.