Original Contributions. Secular Trends in Stroke Incidence and Mortality. The Framingham Study

Transcription

1 Origial Cotributios Secular Treds i Stroke Icidece ad Mortality The Framigham Study Philip A. Wolf, MD; Ralph B. D'Agostio, PhD; M. Agela O'Neal, MD; Pamela Sytkowski, PhD; Carlos S. Kase, MD; Albert J. Belager, MA; ad William B. Kael, MD Dowloaded from by o October, 0 Backgroud: The reductio i US stroke mortality has bee attributed to decliig stroke icidece. However, evidece is accumulatig of a tred i decliig stroke severity. Methods: We examied secular treds i stroke icidece, prevalece, ad fatality i Framigham Study subjects aged -6 years i three successive decades begiig i 9, 96, ad 97. Results: No sigificat declie i overall stroke ad trasiet ischemic attack icidece or prevalece occurred. I wome, but ot me, icidece of completed ischemic stroke declied sigificatly. Stroke severity, however, decreased sigificatly over time. Stroke with severe eurological deficit decreased i later decades, with a fall i rates of severe stroke cases i which patiets were ucoscious o admissio to the hospital. There was o substatial chage i the case mix of ifarcts ad hemorrhages ad o declie i hemorrhage to accout for the declie i severity. The proportio of isolated trasiet ischemic attacks icreased sigificatly over the 0 years studied, yieldig a apparet ad sigificat declie i case-fatality rates i me oly. Coclusios: Secular treds i stroke icidece ad fatality did ot follow a clear or defiite patter of declie. While a sigificat declie i stroke severity occurred over three decades, icidece of ifarctio fell oly i wome. The declie i total case fatality rates occurred oly i me ad resulted largely from a icreased icidece of isolated trasiet ischemic attacks. The severity of completed stroke was sigificatly lower i the later decades uder study. (Stroke 99;:-) KEYWORDS epidemiology icidece mortality Mortality rates for stroke i the Uited States have declied steadily sice 9, averagig per year util the mid-960s. I the 970s, the declie accelerated to approximately a 7 per year pace, but i recet years the pace of declie has slowed. - There is little doubt that this declie is real ad ot a artifact of reportig or death-certificate codig; the decrease i death from stroke has occurred i both sexes, i whites ad blacks, i all regios of the Uited States, ad over several revisios of the ICDA (Iteratioal Classificatio of Diseases Adapted for use i the Uited States). Furthermore, death from stroke has declied coicidet with dimiishig total death rates, led chiefly by fallig cardiovascular disease death rates. - From the Departmet of Neurology, Bosto Uiversity School of Medicie (P.A.W., M.A.O., C.S.K.); the Departmet of Mathematics, Bosto Uiversity (R.B.D., P.S., A.J.B.); ad the Sectio of Prevetive Medicie ad Epidemiology, Evas Memorial Departmet of Cliical Research ad Departmet of Medicie, Uiversity Hospital (P.A.W., C.S.K., W.B.K.), Bosto, Mass. Supported i part by grats -RO-NS (Natioal Istitute of Neurological Disorders ad Stroke), R0-HL0-0 (Natioal Heart, Lug, ad Blood Istitute) ad cotract NIH- NO-HC-0 (Natioal Heart, Lug, ad Blood Istitute). Address for reprits: Philip A. Wolf, MD, 0 East Cocord Street, Robiso Buildig B60, Bosto, MA 0. Received April 9, 99; fial revisio received Jue, 99; accepted July, 99. The key elemet i the declie is thought to be a fall i stroke icidece, a cosequece of the successful atiowide program to idetify ad treat hypertesio. ' However, there has bee a decrease i stroke case-fatality rates, resultig either from improved treatmet of stroke patiets or a decrease i stroke severity, - 7 although ot all studies have oted this decrease i case-fatality rates. To determie the basis of these treds i stroke deaths, icidece, ad severity, secular treds i stroke were examied i the geeral populatio sample i Framigham, Mass. Members of the Framigham cohort who were -6 years of age at the start of three successive decades begiig i 9 were studied. Subjects ad Methods The Framigham cohort of,070 me ad wome, aged -6 years ad free of cardiovascular disease at etry to the study i 9-9, has bee evaluated by meas of bieial examiatios. Surveillace has bee maitaied for the developmet of cardiovascular disease, icludig completed stroke ad trasiet ischemic attack (TIA). Methods of recruitmet, examiatio ad follow-up, ad criteria for diagosis have bee reported. 90 Sice 96, a study eurologist has evaluated the subjects i the hospital at the time of stroke to documet the evet ad to determie the specific stroke subtype. I recet years, at least oe computed tomo-

2 Stroke Vol, No November 99 TABLE. Secular Treds i Stroke ad Trasiet Ischemic Attack Over Three Decades Prevalece at start of decade 0-Year icidece rate -Year case-fatality rate KM rate () SE () Me -6 Decade Decade Decade /6 /6 /7... 9/7 /99 7/ /9 9/ 6/7 p=0.0 />=0. p=0.0 Wome -6 Decade Decade Decade /7 / /9...7 /7 /7 0/ / / 7/0 p=0. p=0j6 KM rate, Kapla-Meier estimate rate; SE, stadard error. Dowloaded from by o October, 0 graphic (CT) sca of the brai has bee obtaied i most stroke cases. Usig this detailed cliical ad CT sca iformatio, it has bee possible to classify stroke cases accordig to mechaism: atherosclerotic brai ifarctio (ABI), icludig large-vessel atherothrombotic ad lacuar ifarctio; solely TIA (isolated TLA); cerebral embolus from a documeted cardiac source (CE); itracerebral hemorrhage (ICH); subarachoid hemorrhage (SAH); ad other miscellaeous causes. I additio to this surveillace, TIAs were ascertaied prospectively by systematic questioig sice bieial exam i 97. The cliical records of each of the 6 icidet stroke ad TIA cases were reviewed by a eurologist ad classified accordig to two measures of stroke severity o admissio to the hospital: level of cosciousess ad severity of the eurologic deficits. Stroke severity at the time of hospitalizatio was graded as follows: oe, o deficit; mild, a deficit was preset i visual, commuicatio, motor ad/or sesory realms, but the patiet was idepedet i performace of the activities of daily livig; moderate, the deficit was severe eough that the patiet required assistace i ay oe of these spheres; ad severe, the patiet was fuctioally depedet o others i two or more spheres. Follow-up has bee good; oly 7 of the cohort has bee lost to follow-up or death after 6 years. Statistical Aalysis Three cohorts were examied. For computatio of icidece, the study group comprised,69 me ad,9 wome who were aged -6 years ad free of stroke at the begiig of bieial examiatios,, ad, correspodig to three decades begiig approximately i 9, 96, ad 97. Stroke icidece durig each period was computed as the Kapla-Meier estimate at 0 years, cosiderig deaths ad subjects lost to follow-up as cesored observatios. The log-rak test, usig decade umber as a ordered variable ad covaryig for age at the begiig of the decade, was used to test for treds i icidece rates across the decades. Stroke prevalece was computed as the percetage of all subjects alive at the begiig of each period who had previously experieced a stroke. The -year case-fatality rates were computed as the percetage of 0-yearicidece case patiets dyig withi the year after the evet. Treds i prevalece ad -year icidece casefatality rates were tested by logistic regressio, usig decade umber as a ordered variable ad covaryig for age at the begiig of the decade. The Matel-Haeszel X statistic was calculated to test the associatio betwee stroke severity ad decade umber. Results Fatality, Icidece, ad Prevalece Durig the three decades, 6 iitial strokes ad isolated TIAs occurred: i me ad i wome. Secular treds i -year case-fatality rates, icidece, ad prevalece were similar i the two sexes (Table ). I me, for all stroke types combied, -year casefatality rates fell substatially ad sigificatly from i decade to i decade to i decade (Table ). Prevalece rates rose sigificatly from. to. to. i successive decades. Icidece of iitial stroke evets did ot declie; i fact, 0-year icidece of stroke icreased steadily from.6 to 7. to.0, a tred that was ot statistically sigificat. I wome, the -year case-fatality rate rose the fell. Prevalece rose from. to. to.7 (Table ). Te-year icidece rates did ot chage appreciably; oe of the treds i wome were statistically sigificat (Table ). To assess the possibility that a chage i mechaisms of stroke might explai these patters, strokes were tabulated accordig to subtype by sex i each of the three decades (Table ). Stroke resultig from hemorrhage was relatively ifrequet, accoutig for 0 of the total. However, because case-fatality rates for stroke secodary to hemorrhage are substatially greater tha those for ifarctio, the proportio of stroke from itracraial hemorrhage was compared i the three decades. Durig the 0-year period, there

3 Wolfet al Secular Treds i Stroke Dowloaded from by o October, 0 TABLE. Cerebrovascular Disease i Three Successive Decades Accordig to Stroke Subtype Type Me -6 ABI CE ICH SAH Other Isolated TIA Total Wome -6 ABI CE ICH SAH Other Isolated TIA Decade Decade 9 Decade Total 0 ABI, atherosclerotic brai ifarctio; CE, cerebral embolus; ICH, itracerebral hemorrhage; SAH, subarachoid hemorrhage; TIA, trasiet ischemic attack were hemorrhages i all; seve ICHs ad four SAHs i me ad three ICHs ad ie SAHs i wome. Because the umbers were small, itraparechymatous ad subarachoid hemorrhages were combied. The proportio of stroke from hemorrhage did ot chage substatially i me ad was 0 i decade, i decade, ad 6 i decade. I wome, the proportio from hemorrhage followed the same tred: i decade, i decade, ad i decade. These chages were ot statistically sigificat i either sex. Trasiet ischemic attacks followed by stroke were classified accordig to completed stroke type, ot as TIAs. The proportio of cerebrovascular evets that were maifested solely as TIAs icreased substatially i the latter two decades. I me, oly occurred i decade ; i decades ad, isolated TIAs accouted for ad of all stroke evets, respectively (Table ). I wome, the tred was similar; isolated TIAs accouted for of stroke evets i decade, i decade, ad i decade (Table ). If isolated TIAs are removed, the proportio of completed strokes categorized as ABI was early the same i the three decades: 6, 6, ad 6 i me ad 6,, ad i wome. The tred toward a declie is o loger apparet. Furthermore, the proportio attributed to CE rose i decade i both sexes. Noe of these treds were sigificat; however, we may have lacked the power to detect a tred due to the limited umber of evets. After excludig these isolated TIA cases, secular treds i icidece ad case-fatality rates were ot sigificatly altered i wome. I me, the tred toward icreasig icidece is o loger see, icidece rates are flat across the three decades, ad the declie i TABLE. Secular Treds i Completed Stroke Over Three Decades (Isolated Trasiet Ischemic Attack Excluded) -Year case- 0-Year icidece fatality KMrate() SE () Me -6 Decade /7..0 0/ 6 Decade Decade 0/99 / /0 6/ 0 Wome -6 Decade 7/7 Decade 0/7 Decade 9/7 p= p=0. /7 /0 7/9 />=0.07 p= KM rate, Kapla-Meier estimate rate; SE, stadard error. case-fatality rates o loger reaches statistical sigificace (Tables ad ). Due to the limited umber of cases, aalysis of secular treds of specific stroke subtypes could be doe oly for brai ifarctio. While the overall patter was similar to that see for all completed stroke combied, i wome the declie i icidece became statistically sigificat (Table ). Stroke Severity To assess the possibility that secular treds i stroke severity were resposible for the treds i prevalece ad fatality, stroke severity ad level of cosciousess o admissio to the hospital of the 6 stroke icidece cases were compared over the three decades (Tables ad 6). Retrospective estimatio of stroke severity o admissio to the hospital could be made i all but seve stroke cases i me ad i wome ad was depe- TABLE. Secular Treds i Atherothrombotic Brai Ifarctio Over Three Decades -Year casefatality 0-Year icidece KM rate () SE () Me -6 Decade Decade Decade 9/7 9/99 / /9 /9 / Wome -6 Decade Decade Decade /7 6/7 /7 p= p=0. / 7 6/6 / 7 p=0.0 p=0. KM rate, Kapla-Meier estimate rate; SE, stadard error.

4 Stroke Vol, No November 99 Dowloaded from by o October, 0 TABLE. Stroke Severity o Admissio to Hospital for Completed Strokes (Isolated Trasiet Iscbemic Attack Excluded) Noe/mild Moderate Severe Ukow Decade Decade Decade Total over decades p<0.00 det o the iformatio available i the cliical record. Cases of isolated TIA were ot icluded i this severity aalysis. For me ad wome combied, there was a sigificat icrease i the frequecy of mild deficits ad a marked declie i severe deficits, particularly from decade to decade (Table ). The prevalece of stroke patiets ucoscious o admissio to the hospital rose slightly from decade to decade, the fell sigificatly from decade to decade i both me ad wome (p=0.0 for me ad wome combied) (Table 6). Discussio Over three successive decades, the prevalece of all stroke evets, icludig isolated TIA, rose, ad casefatality rates fell sigificatly i -6-year-old me; icidece rates rose, but this chage was ot statistically sigificat. I wome, icidece ad case-fatality rates were flat while prevalece rose, but oe of the treds were statistically sigificat. The proportio of cerebrovascular disease evets that were isolated TIAs chaged substatially over the three decades studied. I both me ad wome, isolated TIAs as a proportio of total cerebrovascular evets rose from i decade to i decade. This dramatic icrease is more likely to be apparet tha real ad is probably a cosequece of heighteed awareess of the importace of these trasiet evets as a harbiger of stroke. It is possible that treds i detectio ad treatmet of hypertesio ad other risk factors may have exerted a salutary impact o stroke severity, leadig to more TIAs tha completed strokes. Evidece to support this latter explaatio is ot available. However, whe treds i icidece of completed stroke ad brai ifarctio were examied, a defiite declie was see i wome, with rates geerally flat ad uchagig i me over three decades. There was a sigificat declie i the severity of the eurological deficit from stroke, icludig a reductio i TABLE 6. Percetage of Stroke Patiets Ucoscious o Admissio to Hospital for Completed Strokes (Isolated Trasiet Ischemic Attack Excluded) Decade Decade Decade Me Wome /6 / 9 7/9 6/6 /0 / 0 p=0.0 for decade versus decade (sexes combied) by x test. the prevalece of ucosciousess o admissio to the hospital i both sexes. The lesseig i the severity of the stroke was evidet oly i the most recet decade, from 97 to 9, ad resulted from a icrease i the proportio of cerebrovascular evets due to isolated TIAs ad to a real reductio i the severity of completed stroke. Because the umber of strokes due to itracerebral ad subarachoid hemorrhage was small, secular treds i stroke severity were largely due to a decrease i the severity of ischemic stroke. I Rochester, Mi., icidece of stroke declied steadily from 90 to 979 i wome; icidece rates remaied flat i me util the time period whe icidece fell i me as well. I Rochester, icidece rates have rise i the most recet quiqueium (90-9). Stroke severity has also falle dramatically i Rochester, where there was a sigificat (p< 0.00) reductio i the 0-day case-fatality rates (from durig 9-99 to 7 durig 90-9 ); the 90-9 quiqueium coicided with the availability of head CT sca. This tred of fallig stroke severity has also bee oted i other populatios. I a study of stroke outcome i Alleghey Couty, Pa., age-adjusted mortality rates declied sigificatly from 97 to 90 for four sex-race groups. I additio, hospital case-fatality rates also decreased sigificatly, from 9.6 to durig The declie i death rates correspoded to a reductio i the severity of stroke. Fewer stroke patiets were comatose, ad this reductio i the prevalece of coma was thought to reflect the decrease i stroke severity, which the authors foud was resposible for more tha 0 of the declie i case-fatality rates. Survival after stroke improved i a five-couty rural area of North Carolia, where two commuity-based stroke survey programs were i operatio. The authors compared survival of approximately 00 stroke patiets i each of two time periods, ad , ad foud improved survival (from 9 to 6 overall), with the most strikig improvemet i survival rate after cerebral hemorrhage (from to ). The sigificat declie i stroke severity ad i case-fatality rates accouted for a substatial portio of the improved survival rate after stroke. The declie i death rates, from 970 to 90, correspoded to US vital statistics ad cesus data reports for the same fivecouty area. The authors cocluded that the decrease i deaths from stroke mortality resulted ot solely from a decrease i icidece but i substatial measure from improved survival after stroke. A recet report of survival of a age- ad sexadjusted 0 sample of hospitalized stroke patiets i the Mieapolis-St. Paul, Mi., metropolita area i 970 was compared with that i 9. Hospitalized stroke -day case-fatality rates fell from 7.9 i 970 to. i 9 i me (p=0.0l) ad from.0 to.9 i wome (p<0.0). Thus, decreased death rates resulted ot from reduced icidece but from improved survival i this metropolita area betwee 970 ad 9, probably as a result of improved medical care of the acute stroke patiet. It seems likely that a umber of mechaisms have cotributed to the declie i stroke severity. First, icreased awareess ad recogitio of TIAs o the part of the geeral populatio ad physicias must

5 Dowloaded from by o October, 0 Wolfet al Secular Treds i Stroke explai some portio of the icrease i prevalece of these evets. This icreased recogitio would ted to icrease the icidece of total cerebrovascular evets while reducig the case-fatality rate. Secod, reductio i severity might result from a differetial declie i the icidece of specific stroke subtypes with high case-fatality rates, such as itracerebral ad subarachoid hemorrhage. I the Rochester, Mi., populatio, a declie i itracerebral hemorrhage icidece occurred over years, It was estimated that of hemorrhages i the years before the advet of the CT sca had icorrectly bee attributed to cerebral ifarctio ad that these hemorrhages teded to be smaller ad less severe. There has bee a clear declie i case-fatality rates for itracerebral hemorrhage i Hisayama, Japa, due i part to a decrease i the icidece of massive gaglioic hemorrhages from 96 to 9 i the two cohorts studied i that area of Japa. 7 I additio, decreased casefatality rates after subarachoid hemorrhage have bee reported i the period 97-9 i Rochester ad for white me ad wome i the Uited States. The third major factor resposible for the apparet reductio i case-fatality rates is the widespread availability of the head CT sca durig the latter half of the 970s. The resultat improvemet i diagostic sesitivity has probably icreased the apparet icidece of stroke by detectio of milder cases. Although case ascertaimet methods have ot chaged ad cliical criteria for the diagosis of stroke i Framigham have bee costat over more tha 0 years, the CT sca has udoubtedly had a impact. Improved diagostic sesitivity afforded by the routie availability of CT sca i Framigham sice 97 could have had a impact o the secod half of the third decade (97-9), ehacig detectio of milder stroke evets. This diagostic tool may also have cotributed to the icrease i icidece ad the commesurate declie i stroke severity over time. The icreased use of CT sca i the late 970s has bee related to a icrease i the rate of hospitalizatio atiowide, with a cocomitat declie of i-hospital case-fatality rates. 6 A similar patter has bee reported i Rochester, with a icrease i icidece ad a declie i- severity from stroke overall ad accordig to specific stroke subtype. However, i a study of secular treds i all cardiovascular disease (icludig coroary heart disease) i the Framigham cohort, the declie i mortality resulted primarily from improved case-fatality rates, with o substatial chage i disease icidece. 9 It has bee suggested that the improved survival of coroary heart disease patiets has resulted i a group at icreased risk for stroke, which might accout for the icrease i stroke icidece i Rochester i the years 9O-9. 0 Whether this explaatio applies i Framigham is uclear. The complete picture is udoubtedly related to the iterplay of a umber of factors, icludig the followig: a icrease i patiets susceptible to stroke, resultig from improved survival of coroary disease patiets; a declie i the icidece of severe stroke; decreased stroke case-fatality rates resultig from improvemets i medical care; icreased awareess of trasiet eurologic symptoms as harbigers of stroke; ad improved techology resultig i icreased diagostic sesitivity. Although there were clear improvemets i cotrol of hypertesio ad reductio of cigarette smokig ad serum total cholesterol levels i recet years, o covicig declie i stroke icidece was see i the Framigham cohort. 9 For the most part, the declie i stroke mortality i Framigham has resulted from a declie i stroke severity, ot icidece. Refereces. Klag MJ, Whelto PK, Seidler AJ: Declie i US stroke mortality: Demographic treds ad atihypertesive treatmet. Stroke 99; 0:-. Broderick JP, Phillips SJ, Whisat JP, O'Fallo WM, Bergstralh EJ: Icidece rates of stroke i the eighties: The ed of the declie i stroke? Stroke 99;0:77-. Cooper R, Sempos C, Hsieh S-C, Kovar MG: Slowdow i the declie of stroke mortality i the Uited States, Stroke 990;:7-79. Garraway WM, Whisat JP: The chagig patter of hypertesio ad the decliig icidece of stroke. JAMA 97;: -7. Howard G, Toole JF, Becker C, Lefkowitz DS, Truscott BL, Rose L, Evas GW: Chages i survival followig stroke i five North Carolia couties observed durig two differet periods. Stroke 99;0:-0 6. Alfredsso L, vo Arbi M, de Faire U: Mortality from ad icidece of stroke i Stockholm. Br Med J 96;9: Gillum RF: Cerebrovascular disease morbidity i the Uited States, 970-9: Age, sex, regio, ad vascular surgery. Stroke 96;7: Gillum RF, Gomez-Mari O, Kottke TE, Jacobs DR Jr, Prieas RJ, Folsom AR, Luepker RV, Blackbur H: Acute stroke i a metropolita area, 970 ad 90: The Miesota Heart Survey. J Chro Dis 9;ll: Shurtleff D: Some characteristics related to the icidece of cardiovascular disease ad death: The Framigham Study, -year follow-up. Sectio 0. Washigto, DC, 97, US Govermet Pritig Office. DHEW publicatio No. (NIH) Cupples LA, D'Agostio RB: Some risk factors related to the aual icidece of cardiovascular disease ad death usig pooled repeated bieial measuremets: Framigham Heart Study, 0-year follow-up, i Kael WB, Wolf PA, Garriso RJ (eds): The Framigham Study: A Epidemiological Ivestigatio of Cardiovascular Disease. Sectio. Bethesda, Md, Natioal Heart, Lug, ad Blood Istitute, 97. (NIH publicatio o ). Kalbfleisch JD, Pretice RL: The Statistical Aalysis of Failure Time Data. New York, Joh Wiley & Sos, 90, pp -7. Sedecor G, Cochra W: Statistical Methods, ed 7. Ames, Iowa, Iowa State Uiversity Press, 90. Kleibaum DG, Kupper LL, Morgester H: Epidemiologic Research. Bosto, Mass, Duxbury Press, 9, p 7. Ahmed OI, Orchard TJ, Sharma R, Mitchell H, Talbot E: Decliig mortality from stroke i Alleghey Couty, Pesylvaia: Treds i case fatality ad severity of disease, Stroke 9;9:-. McGover PG, Burke GL, Spraf ka JM, Xue S, Folsom AR, Blackbur H: Treds i mortality, morbidity, ad risk factor levels for stroke from 960 through 990: The Miesota Heart Survey. JAMA 99;6: Drury I, Whisat JP, Garraway WM: Primary itracerebral hemorrhage: Impact of CT o icidece. Neurology 9;: Ueda K, Hasuo Y, Kiyohara Y, Wada J, Kawao H, Kato I, Fuji I, Yaai T, Omae T, Fujishima M: Itracerebral hemorrhage i a Japaese commuity, Hisayama: Icidece, chagig patter durig log-term follow-up, ad related factors. Stroke 9;9:-. Igall TJ, Whisat JP, Wiebers DO, O'Fallo WM: Has there bee a declie i subarachoid hemorrhage mortality? Stroke 99;0: Sytkowski PA, Kael WB, D'Agostio RB: Chages i risk factors ad the declie i mortality from cardiovascular disease: The Framigham Heart Study. N Egl J Med 990;: Kuller LH: Icidece rates of stroke i the eighties: The ed of the declie i stroke? (editorial) Stroke 99;0:-