Secular Trends in Cardiovascular Disease and Its Risk Factors in Japanese Half-Century Data From the Hisayama Study ( )

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1 Secular Treds i Cardiovascular Disease ad Its Risk Factors i Japaese Half-Cetury Data From the Hisayama Study ( ) Ju Hata, MD, PhD; Toshiharu Niomiya, MD, PhD; Yoichiro Hirakawa, MD, PhD; Masaharu Nagata, MD, PhD; Naoko Mukai, MD, PhD; Seiji Gotoh, MD, PhD; Masayo Fukuhara, MD, PhD; Fumie Ikeda, MD, PhD; Ketaro Shikata, MD, PhD; Daigo Yoshida, PhD; Koji Yoemoto, PhD; Masahiro Kamouchi, MD, PhD; Takaari Kitazoo, MD, PhD; Yutaka Kiyohara, MD, PhD Backgroud Chages i lifestyle ad advaces i medical techology durig the past half cetury are likely to have affected the icidece ad mortality of cardiovascular disease ad the prevalece of its risk factors i Japa. Methods ad Results We established 5 cohorts cosistig of residets aged 40 years i a Japaese commuity, i 1961 (=1618), 1974 (=2038), 1983 (=2459), 1993 (=1983), ad 2002 (=3108), ad followed up each cohort for 7 years. The age-adjusted icidece of stroke decreased greatly, by 51% i me ad by 43% i wome, from the 1960s to the 1970s, but this decreasig tred slowed from the 1970s to the 2000s. Amog the stroke subtypes, ischemic stroke i both sexes ad itracerebral hemorrhage i me showed a similar patter. Stroke mortality decreased as a result of the declie i icidece ad a sigificat improvemet i survival rate. Although the icidece of acute myocardial ifarctio did ot chage i either sex, disease mortality declied slightly i wome. From the 1960s to the 2000s, blood pressure cotrol amog hypertesive idividuals improved sigificatly ad the smokig rate decreased, but the prevalece of glucose itolerace, hypercholesterolemia, ad obesity icreased steeply. Coclusios Our fidigs suggest that i Japaese, the decreasig treds i the icidece of ischemic stroke have recetly slowed dow, ad there has bee o clear chage i the icidece of acute myocardial ifarctio, probably because the beefits of hypertesio cotrol ad smokig cessatio have bee egated by icreasig metabolic risk factors. (Circulatio. 2013;128: ) Key Words: coroary disease icidece mortality stroke treds Cardiovascular disease (CVD), icludig stroke ad coroary heart disease (CHD), is oe of the leadig causes of death worldwide. 1 Chages i lifestyle ad advaces i medical techology durig the past half cetury have likely affected the prevalece of cardiovascular risk factors ad thereby the icidece ad mortality of CVD. Accordig to vital statistics, Japaese populatios were characterized by higher stroke mortality ad lower CHD mortality tha Wester populatios i the 1960s, ad the stroke mortality i Japa bega to declie i the 1970s. 1 3 However, the vital statistics based o death certificates caot determie whether the secular chage i mortality reflected a chage i CVD icidece or the prevalece of its risk factors or a improvemet i case fatality. I additio, diagosis o death certificates is ot always accurate 4 ad is ot based o stadardized criteria. Therefore, populatio-based studies with stadardized diagostic criteria are eeded to examie accurate treds i the icidece, mortality, ad survival rate of CVD, as well as the prevalece of its risk factors. Cliical Perspective o p 1205 Several populatio-based observatioal studies have examied the secular treds i CVD i Wester 5 7 ad Japaese populatios 8 13 ; however, there have bee very few studies o CVD i Japa that have covered a period of multiple decades from the 1960s to the 2000s. 8 I our previous report from the Hisayama Study, 9 a log-term populatio-based prospective study i Japa, the icidece ad mortality of stroke decreased sigificatly, but those of CHD did ot show a clear secular chage i either sex durig the 40-year period from 1961 to For the preset Received November 6, 2012; accepted July 22, From the Departmet of Evirometal Medicie (J.H., T.N., Y.H., M.N., N.M., S.G., M.F., F.I., K.S., D.Y., Y.K.) ad Departmet of Medicie ad Cliical Sciece (J.H., T.N., Y.H., M.N., N.M., S.G., M.F., F.I., K.S., M.K., T.K.), Graduate School of Medical Scieces, Kyushu Uiversity, Fukuoka, Japa; ad Biostatistics Ceter, Kurume Uiversity, Kurume, Japa (K.Y.). The olie-oly Data Supplemet is available with this article at /-/DC1. Correspodece to Ju Hata, MD, PhD, Departmet of Evirometal Medicie, Graduate School of Medical Scieces, Kyushu Uiversity, Maidashi, Higashi-ku, Fukuoka City, Japa. juhata@evmed.med.kyushu-u.ac.jp 2013 America Heart Associatio, Ic. Circulatio is available at DOI: /CIRCULATIONAHA

2 Hata et al Cardiovascular Disease Treds i Japa 1199 study, we exteded the study period to 2009 ad examied 5 cohorts, which were established i differet years ad were used to represet each decade from the 1960s to the 2000s. The aims of the preset study were thus to provide a overview of the secular treds i the icidece, mortality, ad survival rates of stroke ad CHD alog with the prevalece of risk factors durig the past half cetury ad to cofirm whether or ot the previously reported secular chages i CVD had cotiued ito the most recet decade. Methods Study Cohorts The tow of Hisayama is located i a suburb of the Fukuoka metropolita area i Kyushu, Japa. Accordig to the atioal cesus, the populatio of the tow was approximately 6500 i 1960 ad 8400 i 2010, ad the age ad occupatioal distributios i the tow have bee very similar to those i the coutry of Japa as a whole (Figures I ad II i the olie-oly Data Supplemet). Sice 1961, aual health examiatios for residets of Hisayama aged 40 years have bee repeated by the tow govermet ad Kyushu Uiversity to determie their health status. We attempted to examie >80% of the residets i this age group i health examiatios every 2 to 5 years to establish ew cohorts. I the preset study, the examiatios i 1961, 1974, 1983, 1993, ad 2002 were used to establish 5 differet cohorts. I 1961, 1658 residets aged 40 years participated i the examiatio (90% of the total populatio i this age group). Similarly, the umber of participats was 2135 (participatio rate, 81%) i 1974, 2551 (81%) i 1983, 2111 (53%) i 1993, ad 3328 (78%) i After excludig those with a history of stroke or CHD, we established 5 cohorts cosistig of 1618 participats i 1961, 2038 i 1974, 2459 i 1983, 1983 i 1993, ad 3108 i 2002, ad each cohort was followed up for 7 years (Figure III i the olie-oly Data Supplemet). Cosequetly, these 5 cohorts roughly covered the decades of the 1960s, 1970s, 1980s, 1990s, ad 2000s, respectively. The study was approved by the Kyushu Uiversity Istitutioal Review Board for Cliical Research. Follow-Up Survey Each cohort was followed up for 7 years by the aual health examiatios or by mail or telephoe for ay participats who did ot udergo the examiatio or who moved out of the tow. The developmet of CVD was also checked by a daily moitorig system orgaized by the study team, local physicias, ad the tow govermet. All available iformatio about potetial CVD evets ad deaths amog the study participats was collected ad reviewed by physicia members of the study to determie the occurrece of CVD evets or cause of death uder the stadardized diagostic criteria throughout the study period. Whe a participat died, autopsy was performed at the Departmet of Pathology of Kyushu Uiversity, if coset for autopsy was obtaied. Our cohorts were characterized by extraordiarily high autopsy rates. Durig the 7-year follow-up period of each cohort, autopsy examiatio was performed for 181 (78%) of 232 deceased participats i the 1960s cohort, 165 (84%) of 196 i the 1970s cohort, 185 (84%) of 221 i the 1980s cohort, 156 (82%) of 190 i the 1990s cohort, ad 170 (64%) of 267 i the 2000s cohort (Figure III i the olie-oly Data Supplemet). The autopsy fidigs were used to adjudicate the uderlyig cause of death ad cofirm the existece of CVD (stroke lesios, myocardial ecrosis, ad atherosclerotic lesios i coroary, carotid, cerebral, ad other major arteries) ad to classify subtypes of stroke. Twety-four participats (1%) i the 1990s cohort were lost to follow-up, ad o participats i the other cohorts were lost to follow-up durig the follow-up periods (Figure III i the olie-oly Data Supplemet). Risk Factors Iformatio o medical history, treatmet of hypertesio ad diabetes mellitus, smokig habits, ad alcohol itake was obtaied by use of a stadardized questioaire. Smokig habits ad alcohol itake were categorized as curret use or ot. Curret smokig was defied as beig whe the participat smoked at least 1 cigarette per day. Curret drikig was defied as whe the participat drak at least 1 alcohol beverage per moth. Blood pressure was measured i a supie positio i 1961 ad i a seated positio i 1974, 1983, 1993, ad Hypertesio was defied as systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg (average of 3 measuremets) or the use of atihypertesive agets. Glucose itolerace was defied by a oral glucose tolerace test i participats with glycosuria i 1961, by fastig or postpradial plasma glucose cocetratios i 1974 ad 1983, ad by a 75-g oral glucose tolerace test i 1993 ad 2002, i additio to a medical history of or treatmet for diabetes mellitus (olie-oly Data Supplemet). 9,14 16 Serum total cholesterol cocetratios were measured by the modified Zak-Hely method i 1961, by the Zurkowski method i 1974, ad by the ezymatic method i 1983, 1993, ad ,14,17 Hypercholesterolemia was defied as serum total cholesterol levels 5.7 mmol/l (220 mg/dl). Body height ad weight were measured i light clothig without shoes, ad obesity was defied as body mass idex 25 kg/m 2. Diagostic Criteria for CVD Stroke was defied as a sudde oset of ocovulsive ad focal eurological deficit persistig for >24 hours ad was classified as ischemic stroke, itracerebral hemorrhage, subarachoid hemorrhage, or udetermied type. The diagosis of CHD icluded acute myocardial ifarctio, silet myocardial ifarctio, percutaeous coroary itervetio, coroary artery bypass graft surgery, ad sudde cardiac death withi 1 hour after the oset of acute illess. Acute myocardial ifarctio was diagosed whe a participat met at least 2 of the followig 4 criteria: (1) Typical symptoms, icludig prologed severe aterior chest pai; (2) evolvig diagostic ECG chages; (3) cardiac ezyme levels more tha twice the upper limit of the ormal rage; ad (4) morphological chages (local asyergy of cardiac wall motio o echocardiography, persistet perfusio defect o cardiac scitigraphy, or myocardial ecrosis or scars 1 cm log accompaied by coroary atherosclerosis at autopsy). Silet myocardial ifarctio was diagosed for participats without ay historical idicatio of cliical symptoms or abormal cardiac ezyme chages by either of the followig 2 criteria: (1) New oset of abormal Q waves o ECG plus morphological myocardium chages (local asyergy o echocardiography or persistet perfusio defect o scitigraphy), or (2) myocardial ecrosis or scars 1 cm log accompaied by coroary atherosclerosis at autopsy. For participats who died, the uderlyig causes of death were classified as stroke, CHD, or others, usig all available iformatio such as autopsy examiatio, medical records, ad death certificates. Deaths attributed to stroke ad CHD were further classified as to their subtypes. Durig the follow-up periods of the 5 cohorts, a total of 487 participats had first-ever stroke (344 ischemic stroke, 93 itracerebral hemorrhage, 45 subarachoid hemorrhage, ad 5 udetermied type) ad a total of 208 participats had first-ever CHD. Amog the 1106 deceased participats i total, 144 died of stroke (67 ischemic stroke, 48 itracerebral hemorrhage, 25 subarachoid hemorrhage, ad 4 udetermied type) ad 61 died of CHD (Figure III i the olie-oly Data Supplemet). Oly 4 participats had o iformatio for cause of death ad were diagosed as death of ukow cause. Statistical Aalysis The prevalece of each risk factor was adjusted for age by the direct method ad compared amog the cohorts by logistic regressio aalysis. The World Health Orgaizatio stadard populatio was used as a stadard populatio for the age adjustmet. The age-adjusted mea values of risk factors as cotiuous variables were calculated ad compared by the liear regressio model. Because the cohorts cotaied overlappig idividuals, the logistic ad liear regressio aalyses were fit by geeralized estimatig equatios to accout for idividuals cotributig to >1 examiatio. The icidece ad mortality rates of CVD were calculated by the perso-year method with adjustmet for age by the direct method ad compared by Poisso regressio. Because idividuals who developed CVD could ot cotribute to future cohorts, geeralized estimatig equatios were ot ecessary i the aalyses for icidece ad mortality. 18 Participats who developed stroke or acute myocardial ifarctio were also followed up for the subsequet 5 years or to the ed of the follow-up

3 1200 Circulatio September 10, 2013 period i each cohort, ad survival curves were draw with the Cox proportioal hazards model with adjustmet for age ad sex. I each of the above-metioed aalyses, pairwise comparisos versus the 1960s cohort were adjusted for multiple comparisos by Duett test (for logistic, liear, ad Poisso regressio) or Boferroi test (for the Cox model). All statistical aalyses were performed with SAS 9.3 (SAS Istitute, Cary, NC). Two-sided values of P<0.05 were cosidered statistically sigificat. Results Treds i Cardiovascular Risk Factors The age-adjusted prevalece or mea values of cardiovascular risk factors i the 5 baselie examiatios are summarized i Table 1. The populatio grew 5 years older i both sexes over the period from 1961 to The prevalece of hypertesio icreased durig the earlier period from 1961 to 1983 ad the decreased durig the subsequet period from 1983 to 2002, but these chages were ot dramatic. The proportio of participats receivig atihypertesive treatmet icreased steeply ad mea systolic blood pressure amog hypertesive me ad wome decreased sigificatly over the study period. Cosequetly, mea systolic blood pressure amog all participats decreased slightly i both sexes. I cotrast, the prevalece of metabolic risk factors (ie, glucose itolerace, hypercholesterolemia, ad obesity) icreased with time i both sexes. The smokig rate i me ad wome decreased sigificatly from 1961 to The alcohol drikig rate icreased slightly i me ad steeply i wome with time sice Treds i CVD Icidece The age-adjusted icidece rates of stroke ad CHD are compared amog the 5 cohorts i Table 2. Stroke icidece decreased greatly, by 51% i me ad by 43% i wome, i the earlier period from the 1960s to the 1970s, but this decreasig tred slowed dow i the subsequet period. A similar decreasig tred with a slowdow was observed i the icidece of ischemic stroke i both sexes. The icidece of itracerebral hemorrhage i me decreased cosistetly from the 1960s to the 1990s. The icideces of itracerebral hemorrhage i wome ad subarachoid hemorrhage i both sexes showed o clear secular chages over the study period. Although CHD icidece i me did ot show a sigificat secular chage over the period, CHD icidece i wome decreased sigificatly maily i the recet period from the 1980s to the 2000s. However, the icidece of acute myocardial ifarctio did ot decrease i either sex. Age-specific icidece rates of stroke ad acute myocardial ifarctio i the 5 cohorts are show i Figure 1. Stroke icidece cosistetly decreased maily i the aged group. I cotrast, the icidece of acute myocardial ifarctio showed o clear secular chages amog participats aged 79 years, whereas that i participats aged 80 years teded to icrease from the 1960s to the 1980s ad was uchaged thereafter. Treds i CVD Survival Participats who developed stroke or acute myocardial ifarctio durig the 7-year period were further followed up for the subsequet 5 years (or to the ed of the follow-up period) after the idex evets i each cohort. Figure 2 ad Table I i the olie-oly Data Supplemet demostrate the estimated survival rates ad hazard ratios for death over the 5 years after the oset of stroke or acute myocardial ifarctio, with adjustmet for age ad sex. The estimated 5-year survival rate of stroke improved greatly from the 1960s cohort (22.2%) to the 1980s cohort (55.3%) ad improved slightly thereafter (63.0% i the 2000s cohort). Although the 5-year survival rate of acute myocardial ifarctio did ot show a cotiuous improvemet, probably because of the limited sample size, the survival rate i the 2000s cohort (61.2%) was sigificatly higher tha that i the 1960s cohort (16.3%). Treds i CVD Age-adjusted mortality rates from stroke ad CHD are compared amog the 5 cohorts i Table 3. Stroke mortality i me ad wome decreased most i the earlier period from the 1960s to the 1970s, ad this decreasig tred slowed dow i the subsequet period. I regard to stroke subtypes, the mortality rate from ischemic stroke i both sexes decreased sigificatly over the study period, ad the same was true for the mortality rate from itracerebral hemorrhage i me ad that from subarachoid hemorrhage i wome. Although the mortality rates attributable to CHD ad acute myocardial ifarctio i me did ot show clear secular chages, i wome they showed decreasig treds over the study period. Discussio Usig the fidigs of 5 cohorts established i differet decades i a Japaese commuity, we demostrated that the decrease i stroke icidece ad mortality i this commuity was most proouced over the 1960s ad 1970s, ad the i the 3 more recet cohorts, the tred of decrease slowed. The icidece of acute myocardial ifarctio did ot show clear secular chages i either sex, but mortality from acute myocardial ifarctio teded to decrease i wome. From the 1960s to the 2000s cohort, blood pressure cotrol amog hypertesive idividuals improved sigificatly ad the prevalece of smokig decreased, whereas the prevalece of glucose itolerace, hypercholesterolemia, ad obesity icreased steeply. Chages i risk factors may have affected the treds i the risk of CVD durig the past half cetury i Japaese. Several populatio-based observatioal studies have examied secular treds i CVD i Japaese populatios 8 13 ; however, most of these studies have ot covered very log periods of time The Akita-Osaka Study 8 recetly reported secular treds i the icidece of stroke ad CHD amog middleaged (40 69 years) me ad wome who lived i urba ad rural commuities i Japa over a 40-year period from 1964 to I that study, stroke icidece decreased sigificatly i both commuities, which was i cocordace with the preset study. O the other had, CHD icidece icreased sigificatly amog me i the urba commuity over the 1980s util the ed of the study i 2003, which was differet from our fidig, probably because the Akita-Osaka Study did ot iclude elderly people, who have a higher risk of CVD. I the preset study populatio, the prevalece of hypertesio, oe of the most powerful risk factors for CVD, 14,19 did ot show a dramatic secular chage. I cotrast, average blood pressure levels i hypertesive idividuals decreased cotiuously ad greatly as a result of the spread of hypertesio treatmet. I additio, our

4 Hata et al Cardiovascular Disease Treds i Japa 1201 Table 1. Study Age-Adjusted Prevalece or Mea (SD) of Cardiovascular Risk Factors Amog 5 Baselie Examiatios of the Hisayama 1961 (=1618) 1974 (=2038) previous study reported that daily itake of salt amog Hisayama residets showed a large reductio, from 18.3 g/d i 1965 to 9.8 g/d i 2004, 20 which was also likely to cotribute to the reductio of blood pressure levels i the preset study populatio. The icidece of ischemic stroke decreased with time, probably because of the improvemet i hypertesio maagemet, the reductio i salt cosumptio, ad the decreasig smokig rate. The reductio i the icidece of stroke ad the improvemet i its survival rate cotributed to the decreasig tred i the stroke mortality. However, the decreasig treds i the icidece ad mortality of ischemic stroke slowed dow i recet years. Oe of the possible reasos for the slowdow is the icrease i the prevalece 1983 (=2459) 1993 (=1983) 2002 (=3108) P for Tred Me Number of participats Age, y 55 (11) 56 (11) 57 (11)* 61 (12)* 61 (12)* Hypertesio, % * 47.7* 43.7* Atihypertesive agets, % * 10.9* 14.7* 17.5* Systolic BP, mm Hg 136 (25) 139 (23)* 137 (19) 136 (18) 133 (20)* Diastolic BP, mm Hg 79 (14) 83 (12)* 84 (11)* 81 (10)* 81 (11)* 0.13 Systolic BP i hypertesive 161 (20) 157 (20)* 152 (16)* 152 (16)* 148 (18)* idividuals, mm Hg Diastolic BP i hypertesive 91 (13) 90 (11) 92 (9) 88 (10)* 89 (10) 0.01 idividuals, mm Hg Glucose itolerace, % * 29.9* 54.0* Hypercholesterolemia, % * 23.0* 25.2* 22.2* Total cholesterol, mmol/l 3.9 (0.9) 4.7 (0.8)* 5.0 (0.9)* 5.1 (0.8)* 5.1 (0.9)* Obesity, % * 20.2* 26.7* 29.2* Body mass idex, kg/m (2.3) 21.7 (2.3)* 22.3 (2.4)* 23.2 (2.1)* 23.4 (2.9)* Curret smoker, % * 47.0* 47.4* Curret driker, % Wome Number of participats Age, y 57 (12) 58 (12)* 58 (12) 61 (13)* 62 (13)* Hypertesio, % * 41.2* * Atihypertesive agets, % * 11.5* 15.2* 16.2* Systolic BP, mm Hg 137 (23) 139 (22) 136 (20) 135 (19)* 129 (20)* Diastolic BP, mm Hg 78 (12) 80 (11)* 80 (11)* 77 (10)* 76 (12)* Systolic BP i hypertesive 163 (20) 161 (20) 155 (17)* 155 (17)* 149 (19)* idividuals, mm Hg Diastolic BP i hypertesive 88 (11) 87 (11) 87 (9) 84 (10)* 86 (11)* idividuals, mm Hg Glucose itolerace, % * 7.0* 21.0* 35.1* Hypercholesterolemia, % * 33.5* 35.7* 35.3* Total cholesterol, mmol/l 4.2 (1.0) 5.0 (0.9)* 5.3 (1.0)* 5.5 (0.9)* 5.4 (0.9)* Obesity, % * 23.5* 26.2* 23.8* Body mass idex, kg/m (2.8) 22.4 (2.9)* 22.6 (2.7)* 23.0 (2.7)* 22.9 (3.5)* Curret smoker, % * 7.4* 4.6* 8.5* Curret driker, % * 29.3* BP idicates blood pressure. *P<0.05 compared with the examiatio i 1961 (after Duett test for multiple comparisos). of metabolic risk factors, which i tur is probably attributable to westerizatio of dietary habit ad physical iactivity as a result of motorizatio. For example, the daily itake of total (ad aimal) fat showed a cosiderable icrease, from 37.5 (11.4) g/d i 1965 to 52.3 (26.1) g/d i 2004, amog Hisayama residets, 20 which was likely to have bee the cause of the icreasig prevalece of hypercholesterolemia ad glucose itolerace. Glucose itolerace, 21 dyslipidemia, 17 obesity, 22 metabolic sydrome, 23 ad uderlyig isuli resistace 24 are importat risk factors for ischemic stroke i Japaese. Aother reaso may be that blood pressure cotrol i hypertesive idividuals was still ot sufficiet eve i the latest examiatio, whe the mea systolic

5 1202 Circulatio September 10, 2013 Table 2. Age-Adjusted Icidece (per 1000 Perso-Years) of Stroke ad Coroary Heart Disease Amog 5 Cohorts of the Hisayama Study 1960s Cohort ( ) Icidece Me Stroke ( ) Ischemic ( ) ICH ( ) SAH ( ) Udetermied ( ) CHD ( ) AMI ( ) Wome Stroke ( ) Ischemic ( ) ICH ( ) SAH ( ) Udetermied ( ) CHD ( ) AMI ( ) 1970s Cohort ( ) Icidece * ( ) * ( ) * ( ) blood pressure amog hypertesive idividuals was higher tha 140 mm Hg, which suggests that most hypertesive subjects did ot achieve the target blood pressure level recommeded by the cliical guidelies for hypertesio Although a decrease i the icidece ad mortality of itracerebral hemorrhage was see i me ad was likely attributable to the improvemet i hypertesio maagemet, a comparable tred of decrease was ot see i wome, probably because of the small umber of evets. I additio, our previous study suggested that alcohol cosumptio ad hypertesio syergistically icreased the risk of itracerebral hemorrhage. 28 Because the drikig rate i wome was much lower tha that i me over the study period, the impact of hypertesio o the developmet of itracerebral hemorrhage may be smaller i wome. The icidece of acute myocardial ifarctio did ot show a clear chage i either sex, probably because the icreasig prevalece of metabolic risk factors egated the beefit of improvemet i hypertesio cotrol. The icidece of total 1980s Cohort ( ) Icidece * ( ) * ( ) * ( ) ( ) 1990s Cohort ( ) Icidece * ( ) * ( ) * ( ) ( ) 2000s cohort ( ) Icidece P for Tred * ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) > ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) AMI idicates acute myocardial ifarctio; CHD, coroary heart disease; CI, cofidece iterval; ICH, itracerebral hemorrhage;, umber of evets; ad SAH, subarachoid hemorrhage. *P<0.05 compared with the 1960s cohort (after Duett test for multiple comparisos) CHD decreased recetly i wome, which suggests that the icidece of silet myocardial ifarctio showed a decreasig tred i wome. However, accurate diagosis of silet myocardial ifarctio is difficult because it depeds o the fidigs of autopsy ad cliical examiatios of cases without ay history of acute episodes. Therefore, the icidece of total CHD might have bee uderestimated, especially i the 2000s cohort. from acute myocardial ifarctio ad CHD i wome showed decreasig treds as a result of the improvemets i postevet survival rates. I cotrast, mortality from acute myocardial ifarctio ad CHD i me showed o clear secular chage. This sex differece may be explaied by the much higher smokig rate i me tha i wome. I the preset study populatio, the icidece of acute myocardial ifarctio i very elderly subjects (aged 80 years) icreased with time durig the earlier period from the 1960s to the 1980s. The decrease i stroke mortality, the most commo type of CVD i Japaese, might cotribute to the logevity of

6 Hata et al Cardiovascular Disease Treds i Japa 1203 Icidece per 1000 perso years Icidece per 1000 perso years Stroke 1960s cohort ( ) 1970s cohort ( ) 1980s cohort ( ) 1990s cohort ( ) 2000s cohort ( ) Age group (years) Acute myocardial ifarctio Age group (years) Figure 1. Age-specific icidece of stroke (top) ad acute myocardial ifarctio (bottom) with adjustmet for sex, amog 5 cohorts of the Hisayama Study. Bars idicate 95% cofidece itervals. people with atherosclerosis, ad these elderly subjects with relatively severe atherosclerosis might have a higher risk of other atherosclerotic disease, such as myocardial ifarctio. This icrease i the icidece of acute myocardial ifarctio i the elderly has come to a stop sice the 1980s, possibly i associatio with the slowdow of the decrease i the stroke mortality. The preset study was the first to examie the icidece, mortality, ad survival rates of stroke ad CHD over the past half cetury i a Japaese populatio that icluded both middle-aged ad elderly participats. The follow-up of each cohort was almost complete. The methods for case ascertaimet ad the diagostic criteria of CVD were cosistet throughout the study period. All CVD evets ad causes of death were adjudicated by a pael of study physicias, ad the presece of CVD lesios was morphologically cofirmed by autopsy i most of the deceased subjects. Although the remarkable improvemet i diagostic techiques over the past half cetury might have resulted i iformatio bias i diagosis, the possibility of misclassificatio i CVD diagosis was miimized by these study features. However, there are some issues to be discussed. First, because the diagostic methods for glucose itolerace were differet amog the cohorts, the prevalece of glucose itolerace might be uderestimated i the earlier cohorts. Secod, the methods for measuremet of serum total cholesterol were differet amog the cohorts, ad the cholesterol values were ot calibrated amog the differet methods. Third, socioecoomic iformatio such as educatio level ad occupatio, which might be associated with the icidece ad mortality of CVD, was ot available i the preset cohorts. Fially, it is geerally agreed that a acceptable participatio rate i a Survival rate (%) Survival rate (%) s cohort ( ) 1970s cohort ( ) 1980s cohort ( ) 1990s cohort ( ) 2000s cohort ( ) Stroke Follow-up period (moths) P for tred Acute myocardial ifarctio P for tred = Follow-up period (moths) Figure 2. Age- ad sex-adjusted 5-year survival curves after the oset of stroke (top) ad acute myocardial ifarctio (bottom) amog 5 cohorts of the Hisayama Study. *P<0.05 compared with 1960s cohort (after Boferroi correctio for multiple comparisos). populatio-based study (ie, a rate that practically elimiates the threat of selectio bias attributable to oparticipats) is >70% of the target populatio. 29,30 Therefore, we attempted to recruit >80% of residets to the tow s health examiatios. However, the participatio rate of the health examiatio i 1993 (53%) was lower tha that i the other 4 examiatios ( 78%), ad this might have icreased the risk of selectio bias i the 1990s cohort. As a possible reaso for this low participatio rate i 1993, every employee i Japa has bee required, startig i 1988 (Idustrial Safety ad Health Act), to have a medical examiatio at their place of employmet. Thus, employed residets teded ot to participate i the tow s health examiatio durig the 1990s. However, our mai coclusios did ot chage substatially whe we applied a cohort based o the health examiatio i 1988 (participatio rate, 81%) istead of the examiatios i 1983 ad 1993 (data ot show). I coclusio, the icidece ad mortality of ischemic stroke i both sexes ad itracerebral hemorrhage i me declied as a result of the improvemet of hypertesio maagemet or the reductio i the smokig rate. However, blood pressure cotrol i hypertesive participats is still isufficiet, ad the smokig rate i me is still much higher tha i Wester populatios. 31 I additio, the decreasig treds i the icidece of ischemic stroke slowed dow recetly, ad there was o clear chage i the icidece of acute myocardial ifarctio, probably because of the icreasig metabolic * * *

7 1204 Circulatio September 10, 2013 Table 3. Age-Adjusted (per 1000 Perso-Years) of Stroke ad Coroary Heart Disease Amog 5 Cohorts of the Hisayama Study 1960s Cohort ( ) 1970s Cohort ( ) 1980s Cohort ( ) 1990s Cohort ( ) 2000s Cohort ( ) P for Tred Me Stroke ( ) Ischemic ( ) ICH ( ) SAH ( ) Udetermied ( ) CHD ( ) AMI ( ) Wome Stroke ( ) Ischemic ( ) ICH ( ) SAH ( ) Udetermied ( ) CHD ( ) AMI ( ) * ( ) ( ) * ( ) risk factors. The itesive maagemet of metabolic risk factors ad best efforts to reduce the smokig rate ad to achieve strict blood pressure cotrol are eeded for further prevetio of CVD i Japaese. Sources of Fudig This study was supported i part by Grats-i-Aid for Scietific Research o Iovative Areas ( ) ad for Scietific Research (A, ad ; B, ; ad C, , , , , , ad ) from the Miistry of Educatio, Culture, Sports, Sciece ad Techology of Japa, ad by Health ad Labor Scieces Research Grats of the Miistry of Health, Labor ad Welfare of Japa (Comprehesive Research o Life-Style Related Diseases icludig Cardiovascular Diseases ad Diabetes Mellitus: H22-Jukakitou [Seishuu]- Ippa-005, H23-Jukakitou [Seishuu]-Ippa-005, H25-Jukakitou [Seishuu]-Ippa-005, H25-Jukakitou [Seishuu]-Ippa-009, ad H25-Jukakitou [Seishuu]-Sitei-022; ad Comprehesive Research o Demetia: H25-Nichisho-Ippa-004) * ( ) ( ) * ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Noe * ( ) * ( ) * ( ) ( ) Disclosures * ( ) * ( ) * ( ) ( ) * ( ) ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) ( ) ( ) * ( ) * ( ) ( ) ( ) > ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) AMI idicates acute myocardial ifarctio; CHD, coroary heart disease; CI, cofidece iterval; ICH, itracerebral hemorrhage;, umber of evets; ad SAH, subarachoid hemorrhage. *P<0.05 compared with the 1960s cohort (after Duett test for multiple comparisos) Refereces 1. World Health Orgaizatio. World Health Statistics Aual Geeva, Switzerlad: World Health Orgaizatio; Ueshima H. Explaatio for the Japaese paradox: prevetio of icrease i coroary heart disease ad reductio i stroke. J Atheroscler Thromb. 2007;14: Chalmers J, Arima H, Hata J. Cost-effective reductio i stroke: lessos from the Japaese hypertesio detectio ad cotrol program. J Hypertes. 2012;30: Hasuo Y, Ueda K, Kiyohara Y, Wada J, Kawao H, Kato I, Yaai T, Fujii I, Omae T, Fujishima M. Accuracy of diagosis o death certificates for uderlyig causes of death i a log-term autopsy-based populatio study i Hisayama, Japa; with special referece to cardiovascular diseases. J Cli Epidemiol. 1989;42: Sytkowski PA, D Agostio RB, Belager A, Kael WB. Sex ad time treds i cardiovascular disease icidece ad mortality: the Framigham Heart Study, Am J Epidemiol. 1996;143:

8 Hata et al Cardiovascular Disease Treds i Japa Kaga A, Popper J, Reed DM, MacLea CJ, Grove JS. Treds i stroke icidece ad mortality i Hawaiia Japaese me. Stroke. 1994;25: Tustall-Pedoe H, Vauzzo D, Hobbs M, Mähöe M, Cepaitis Z, Kuulasmaa K, Keil U. Estimatio of cotributio of chages i coroary care to improvig survival, evet rates, ad coroary heart disease mortality across the WHO MONICA Project populatios. Lacet. 2000;355: Kitamura A, Sato S, Kiyama M, Imao H, Iso H, Okada T, Ohira T, Taigawa T, Yamagishi K, Nakamura M, Koishi M, Shimamoto T, Iida M, Komachi Y. Treds i the icidece of coroary heart disease ad stroke ad their risk factors i Japa, 1964 to 2003: the Akita-Osaka study. J Am Coll Cardiol. 2008;52: Kubo M, Kiyohara Y, Kato I, Taizaki Y, Arima H, Taaka K, Nakamura H, Okubo K, Iida M. Treds i the icidece, mortality, ad survival rate of cardiovascular disease i a Japaese commuity: the Hisayama study. Stroke. 2003;34: Kodama K, Sasaki H, Shimizu Y. Tred of coroary heart disease ad its relatioship to risk factors i a Japaese populatio: a 26-year follow-up, Hiroshima/Nagasaki study. Jp Circ J. 1990;54: Morikawa Y, Nakagawa H, Naruse Y, Nishijo M, Miura K, Tabata M, Hirokawa W, Kagamimori S, Hoda M, Yoshita K, Hayashi K. Treds i stroke icidece ad acute case fatality i a Japaese rural area: the Oyabe study. Stroke. 2000;31: Kitamura A, Iso H, Iida M, Naito Y, Sato S, Jacobs DR, Nakamura M, Shimamoto T, Komachi Y. Treds i the icidece of coroary heart disease ad stroke ad the prevalece of cardiovascular risk factors amog Japaese me from 1963 to Am J Med. 2002;112: Kita Y, Turi TC, Ichikawa M, Sugihara H, Morita Y, Tomioka N, Rumaa N, Okayama A, Nakamura Y, Abbott RD, Ueshima H. Tred of stroke icidece i a Japaese populatio: Takashima stroke registry, It J Stroke. 2009;4: Taizaki Y, Kiyohara Y, Kato I, Iwamoto H, Nakayama K, Shiohara N, Arima H, Taaka K, Ibayashi S, Fujishima M. Icidece ad risk factors for subtypes of cerebral ifarctio i a geeral populatio: the Hisayama study. Stroke. 2000;31: Ohmura T, Ueda K, Hasuo Y, Kiyohara Y, Wada J, Kawao H, Shikawa A, Iwamoto H, Nakayama K, Nakamura Y, Fujishima M. Log-term progosis of diabetes i the geeral populatio of Hisayama (1): compariso of survival i subjects with ad without glucose itolerace observed i two cohorts 13 years apart [i Japaese]. J Jp Diab Soc. 1990;33: Alberti KG, Zimmet PZ. Defiitio, diagosis ad classificatio of diabetes mellitus ad its complicatios, part 1: diagosis ad classificatio of diabetes mellitus provisioal report of a WHO cosultatio. Diabet Med. 1998;15: Imamura T, Doi Y, Arima H, Yoemoto K, Hata J, Kubo M, Taizaki Y, Ibayashi S, Iida M, Kiyohara Y. LDL cholesterol ad the developmet of stroke subtypes ad coroary heart disease i a geeral Japaese populatio: the Hisayama study. Stroke. 2009;40: Parikh NI, Pecia MJ, Wag TJ, Laier KJ, Fox CS, D Agostio RB, Vasa RS. Icreasig treds i icidece of overweight ad obesity over 5 decades. Am J Med. 2007;120: Fukuhara M, Arima H, Niomiya T, Hata J, Yoemoto K, Doi Y, Hirakawa Y, Matsumura K, Kitazoo T, Kiyohara Y. Impact of lower rage of prehypertesio o cardiovascular evets i a geeral populatio: the Hisayama Study. J Hypertes. 2012;30: Tomoou M, Shirota T, Uchida K, Kiyohara Y. Chages of utritioal itakes ad food group itakes over a 40-year period i Hisayama [i Japaese]. Nakamura Gakue Daigaku Kekyu Kiyo. 2007;39: Doi Y, Niomiya T, Hata J, Fukuhara M, Yoemoto K, Iwase M, Iida M, Kiyohara Y. Impact of glucose tolerace status o developmet of ischemic stroke ad coroary heart disease i a geeral Japaese populatio: the Hisayama study. Stroke. 2010;41: Yoemoto K, Doi Y, Hata J, Niomiya T, Fukuhara M, Ikeda F, Mukai N, Iida M, Kiyohara Y. Body mass idex ad stroke icidece i a Japaese commuity: the Hisayama study. Hypertes Res. 2011;34: Hata J, Doi Y, Niomiya T, Taizaki Y, Yoemoto K, Fukuhara M, Kubo M, Kitazoo T, Iida M, Kiyohara Y. The effect of metabolic sydrome defied by various criteria o the developmet of ischemic stroke subtypes i a geeral Japaese populatio. Atherosclerosis. 2010;210: Gotoh S, Doi Y, Hata J, Niomiya T, Mukai N, Fukuhara M, Kamouchi M, Kitazoo T, Kiyohara Y. Isuli resistace ad the developmet of cardiovascular disease i a Japaese commuity: the Hisayama study. J Atheroscler Thromb. 2012;19: Chobaia AV, Bakris GL, Black HR, Cushma WC, Gree LA, Izzo JL Jr, Joes DW, Materso BJ, Oparil S, Wright JT Jr, Roccella EJ; Joit Natioal Committee o Prevetio, Detectio, Evaluatio, ad Treatmet of High Blood Pressure. Natioal Heart, Lug, ad Blood Istitute; Natioal High Blood Pressure Educatio Program Coordiatig Committee. Seveth report of the Joit Natioal Committee o Prevetio, Detectio, Evaluatio, ad Treatmet of High Blood Pressure. Hypertesio. 2003;42: Macia G, De Backer G, Domiiczak A, Cifkova R, Fagard R, Germao G, Grassi G, Heagerty AM, Kjeldse SE, Lauret S, Narkiewicz K, Ruilope L, Rykiewicz A, Schmieder RE, Boudier HA, Zachetti A Guidelies for the maagemet of arterial hypertesio: the Task Force for the Maagemet of Arterial Hypertesio of the Europea Society of Hypertesio (ESH) ad of the Europea Society of Cardiology (ESC). J Hypertes. 2007;25: Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, Imai Y, Imaizumi T, Ito S, Iwao H, Kario K, Kawao Y, Kim-Mitsuyama S, Kimura G, Matsubara H, Matsuura H, Naruse M, Saito I, Shimada K, Shimamoto K, Suzuki H, Takishita S, Taahashi N, Tsuchihashi T, Uchiyama M, Ueda S, Ueshima H, Umemura S, Ishimitsu T, Rakugi H; Japaese Society of Hypertesio Committee. The Japaese Society of Hypertesio Guidelies for the Maagemet of Hypertesio (JSH 2009). Hypertes Res. 2009;32: Kiyohara Y, Kato I, Iwamoto H, Nakayama K, Fujishima M. The impact of alcohol ad hypertesio o stroke icidece i a geeral Japaese populatio: the Hisayama Study. Stroke. 1995;26: Groves RM. Survey Errors ad Survey Costs. New York, NY: Wiley; Kasper JD, Shapiro S, Guralik JM, Badee-Roche KJ, Fried LP. Desigig a commuity study of moderately to severely disabled older wome: the Wome s Health ad Agig Study. A Epidemiol. 1999;9: Mackay J, Erikse M. The Tobacco Atlas. Geeva, Switzerlad: World Health Orgaizatio; Cliical Perspective The Japaese populatio has bee characterized by a higher icidece ad mortality of stroke ad a lower icidece ad mortality of coroary heart disease tha Wester populatios; however, the recet westerizatio of lifestyle ad advaces i medical techology are likely to have affected the icidece ad mortality of these diseases i Japa. Usig data from 5 cohorts established i differet decades over the past half cetury by the Hisayama Study, a prospective cohort study of cardiovascular disease i Japa, we showed that the icidece ad mortality of stroke decreased greatly from the 1960s to the 1970s, but this decreasig tred slowed dow recetly. I cotrast, the icidece of acute myocardial ifarctio did ot show a clear secular chage. These treds were likely to be associated with secular chages i cardiovascular risk factors. Although the improvemet i hypertesio maagemet ad the decrease i smokig rate cotributed to a declie i stroke icidece, most hypertesive subjects did ot achieve a guidelie-recommeded target blood pressure level of 140/90 mm Hg eve i the recet examiatio i 2002, ad smokig rates i me were still much higher tha i Wester populatios. I additio, the icreasig rates of metabolic risk factors, such as diabetes mellitus, dyslipidemia, ad obesity, are curretly the greatest cocer, because they may icrease the icidece of cardiovascular disease i the ear future. Our study suggests that strict blood pressure cotrol, smokig cessatio, ad itesive maagemet of metabolic risk factors are eeded for further prevetio of cardiovascular disease i Japa.