See related article, p Cardiovascular disease (CVD) and cerebrovascular disease

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1 Guidelie-Directed Low-Desity Lipoprotei Maagemet i High-Risk Patiets With Ischemic Stroke Fidigs From Get With The Guidelies-Stroke 2003 to 2012 Gustavo Saposik, MD, MSc, FRCPC; Gregg C. Foarow, MD; Wequi Pa, PhD*; Li Liag, PhD*; Adria F. Heradez, MD; Lee H. Schwamm, MD; Eric E. Smith, MD, MPH, FRCPC; o behalf of the AHA Get-with-the-Guidelies Stroke Backgroud ad Purpose Limited iformatio is available o stroke prevetio i high-risk patiets with preexistig cardiovascular disease. Our aim was to use admissio low-desity lipoprotei (LDL) values to evaluate differeces i the attaimet of Natioal Cholesterol Educatio Program-Adult Treatmet Pael III guidelies goals at the time of the idex evet i high-risk patiets with stroke ad preexistig cardio- or cerebrovascular disease. Methods Observatioal study, usig data from the Get-With-The-Guidelies-Stroke Registry icludig patiets with a acute ischemic stroke or trasiet ischemic attack from April 2003 to September Participats were classified as high risk if they had history of trasiet ischemic attack (TIA), stroke (cardiovascular disease), ad coroary artery disease (CAD). Results Of the patiets admitted with a acute stroke or TIA, (21.3%) had previous stroke/tia, (16.3%) had previous CAD, ad (9.7%) had cocomitat CAD ad cardiovascular disease. Overall, oly 68% of patiets with stroke were at their preadmissio Natioal Cholesterol Educatio Program III guidelie-recommeded LDL target; 51.3% had LDL <100 mg/dl; ad oly 19.8% had LDL<70 mg/dl. Amog those presetig with a recurret stroke, >45% had LDL>100 mg/dl. Whe compared with patiets with CAD, patiets with previous TIA/stroke were less likely to have LDL<100 or <70 mg/dl. I multivariable aalysis, older age, me, white race, lack of major vascular risk factors, previous use of cholesterol-lowerig therapy, ad care provided i larger hospitals were associated with meetig LDL targets o admissio testig. Coclusios Maagemet of dyslipidemia i high-risk patiets with preexistet CAD or stroke cotiues to be suboptimal. Oly 1 i 5 patiets with prior TIA/stroke had LDL levels <70 mg/dl. (Stroke. 2014;45: ) Key Words: cardiovascular diseases cholesterol diabetes mellitus dyslipidemias LDL cholesterol prevetio & cotrol stadards stroke therapeutics See related article, p Cardiovascular disease (CVD) ad cerebrovascular disease are a major cause of death ad disability worldwide. 1,2 Because of a agig populatio ad decreasig case fatality rate from improved medical care, there will be icreasig umbers of survivors of stroke ad myocardial ifarctio. 3 As a result, cliicias will be exposed to more high-risk patiets with CVD ad cerebrovascular disease. Aggressive maagemet of risk factors (icludig lifestyle modificatios, atihypertesives, atithrombotics, ad lipid-lowerig therapy) is regarded as oe of the most effective strategies to decrease the burde of CVD ad cerebrovascular diseases. 4 Differet scietific associatios icludig the America Heart Associatio (AHA), ad the America College of Cardiology, have established guidelies to stress the importace of risk-factor assessmet ad maagemet. 5,6 Durig the past 2 decades, covicig evidece from cliical trials revealed the importace of low-desity lipoprotei (LDL) cholesterol lowerig therapies i the reductio of cardiovascular morbidity ad mortality. 7 9 Furthermore, the beefits of treatmet seem more proouced amog patiets with established Received July 14, 2014; fial revisio received August 25, 2014; accepted September 11, From the Divisio of Neurology, Departmet of Medicie, Stroke Outcomes Research Ceter, St. Michael s Hospital, Uiversity of Toroto, Toroto, Otario, Caada (G.S.); Divisio of Cardiology, Uiversity of Califoria, Los Ageles (G.C.F.); Duke Cliical Research Istitute, Durham, NC (W.P., L.L., A.F.H.); Stroke Service ad Istitute for Heart, Vascular ad Stroke Care, Massachusetts Geeral Hospital, Bosto (L.H.S.); ad Calgary Stroke Program, Hotchkiss Brai Istitute, Uiversity of Calgary, Calgary, Alberta, Caada (E.E.S.). All authors have approved the fial versio of the article. *Drs Pa ad Liag had full access to the data. Guest Editor for this article was Athoy J. Furla, MD. The olie-oly Data Supplemet is available with this article at /-/DC1. Correspodece to Gustavo Saposik, MD, MSc, FRCPC, Divisio of Neurology, Stroke Outcomes Research Ceter, St. Michael s Hospital, 55 Quee St E, Room 93, Toroto, Otario, Caada M5C 1R6. saposikg@smh.ca 2014 America Heart Associatio, Ic. Stroke is available at DOI: /STROKEAHA

2 3344 Stroke November 2014 or at high risk of developig CVD. 4,5 Durig the study period, most guidelies (eg, the Natioal Cholesterol Educatio Program [NCEP] Adult Treatmet Pael III [ATP III], the AHA, ad the Caadia Guidelies for the Maagemet of Dyslipidemia ad Hypertesio) focused o LDL-cholesterol as the primary therapeutic target ad recommed idividualized treatmet goals tailored to the estimated cardiovascular risk. 5,10 13 The AHA guidelies for secodary prevetio of ischemic stroke recommed that patiets with ischemic stroke or trasiet ischemic attack (TIA) with elevated cholesterol or comorbid coroary artery disease (CAD) should be otherwise maaged accordig to NCEP III guidelies (class IA), for those with atherosclerotic TIA/stroke a target of 70 mg/dl is suggested to obtai maximum beefit (class IIa; level of evidece B). 5 Most recetly, the AHA ad America College of Cardiology recommeded i 2013 that cholesterol therapy be switched from LDL target-based therapy to therapy based o provisio to patiet groups cosidered most likely to beefit. 14 However, despite the well-established efficacy of lipid-lowerig therapy, limited data are available o guidelie attaimet amog high-risk patiets with ad without preexistig CVD, particularly amog patiets with stroke ad TIA. Our goal was to evaluate ad compare differeces i the attaimet to the cotemporary lipid guidelies, based o admissio LDL testig, amog uselected patiets with history of TIA, stroke, diabetes mellitus, ad, CAD admitted with acute ischemic stroke or TIA to participatig istitutios i the Get With The Guidelies (GWTG)-Stroke Program. Methods Populatio Target ad Data Collectio We evaluated all patiets with a TIA or stroke erolled i the GWTG- Stroke from April 2003 to September Details of the GWTG-Stroke Program have bee published elsewhere. 15,16 I brief, participatig hospitals eter cliical iformatio i a Web-based maagemet tool (Outcome Scieces Ic, Cambridge, MA). They also receive decisio support ad obtai feedback reports of their performace o quality measures. Hospitals were istructed to record data from cosecutive stroke ad TIA admissios. Case ascertaimet was through cliical idetificatio durig hospitalizatio, retrospective idetificatio by Iteratioal Classificatio of Diseases-Nith Revisio codes, or both. The eligibility of each case was cofirmed at chart review before abstractio. The Web-based system checks for data quality to esure that the reported data are complete ad iterally cosistet. LDL cholesterol is oe of the 7 core key performace measures of the GWTG-Stroke program 17 based o existig AHA/America Stroke Associatio ad NCEP-ATP III guidelies ad edorsed by the Natioal Quality Forum. 5,10 Traied persoel at each istitutio abstracted LDL ad other lipid levels if measured usig the iteret-based tool usig stadardized data defiitios ad detailed codig istructios. We used a previously published algorithm to determie the prestroke NCEP-ATP III goal (Table I i the olie-oly Data Supplemet). 18 Participats with missig LDL, high-desity lipoprotei, or total cholesterol (=10336; 1.1%) ad those with missig relevat cliical iformatio (=170169; 15.7%) were excluded (Figure I i the olie-oly Data Supplemet) because these elemets were ecessary to determie the NCEP-ATP III goals. 10 We also excluded patiets with high levels of triglycerides (>400 mg/dl) for prevetig idirect calculatio of LDL levels. Exposure All erolled patiets with a case idex TIA/stroke were classified i the followig groups: (1) preexistig TIA/stroke (group CVD), (2) preexistig CAD, (3) preexistig cocomitat CVD ad CAD, ad (4) o preexistig CAD/CVD group icludig patiets with o kow history of TIA, stroke, or CAD. The latest group was stratified by diabetes mellitus. Outcome Measures The AHA ad NCEP-ATP III guidelies i place at the time of the registries recommeded the same target LDL for patiets (<100 mg/ dl) for ischemic stroke or patiets with TIA who have evidece of atherosclerosis. 10,19 A lower target (<70 mg/dl) is recommeded for high-risk patiets to achieve a maximal beefit. 5 Adherece to NCEP- ATP III guidelies was recommeded i the 2011 update of the AHA guidelies. 5 I this study, the primary outcome measure was attaimet of the recommeded LDL<100 mg/dl. Secodary outcomes icluded a LDL<70 mg/dl ad meetig the NCEP III goals. Statistical Aalysis The study populatio was stratified ito 4 groups: (1) patiets with preexistig cerebrovascular disease (TIA/stroke); (2) patiets with preexistig CAD; (3) patiets with cocomitat preexistig CAD ad CVD, ad (4) patiets with o history of CVD or CAD (o preexistig CAD/CVD group). Percetages ad mea (SD) were reported to describe distributio of categorical ad cotiuous patiet characteristics variables with ormal distributio. For the cotiuous variables with skewed distributio, media (25th, 75th percetiles) were reported. Pearso χ 2 test ad Kruskal Wallis test were used to test differece across the patiet groups for categorical ad cotiuous variables, respectively. The tred i the use of lipid testig over time were tested usig the Cochra Matel Haeszel row-mea score test. Multivariable logistic regressio models were performed to determie the idepedet predictors of meetig LDL targets. The geeralized estimatig equatios approach was used to accout for withi-hospital clusterig. The covariates i the multivariable aalysis icluded baselie patiet characteristics age (as a cotiuous variable), sex, race/ethicity (categorized as white, black, Hispaic, or other), comorbid coditios (atrial fibrillatio, prosthetic heart valve, carotid steosis, diabetes, peripheral vascular disease, hypertesio, dyslipidemia, ad smokig), year of erollmet, ad hospital characteristics (bed size, aual umber of stroke discharges, academic teachig status, ad geographical regio). Hospital bed size was etered as a cotiuous variable, whereas aual umber of stroke discharges were categorized as 0 to 100, 101 to 300, or >300. Hospital teachig status ad hospital regio (defied as Northeast, Midwest, South, or West) were determied usig statistics published by the America Hospital Associatio. 20 All P values were 2-sided, with P value <0.05 cosidered statistically sigificat. Aalyses were performed usig SAS versio 9.2 software (SAS Istitute, Cary, NC). Each participatig hospital received istitutioal review board approval to eroll participats without idividual patiet coset uder the commo rule or a waiver of authorizatio ad exemptio. Outcome Scieces, Ic, serves as the data collectio ad coordiatio ceter for GWTG. The Duke Cliical Research Istitute was resposible for data aalysis. Results Of the patiets presetig with a acute stroke to ay of the 1246 participatig istitutios betwee 2003 ad 2012, (21.3%) had a preexistig stroke/tia, had preexistig CAD (16.3%), (9.7%) had cocomitat preexistig CAD ad CVD, ad (52.7%) had o kow or documeted history of CVD or CAD. Mea age (±SD) was 69.9±14 years, 48.1% were me. The case idex evet was a TIA i (26.6%) of patiets, whereas the remaiig 73.4% correspoded to stroke. Overall, 57.7% (= ) patiets received care i academic istitutios.

3 Saposik et al LDL Targets i High-Risk Patiets From GWTG-Stroke 3345 Table 1. Baselie Characteristics Overall (Without CAD) CAD/MI (Without CVD) Cocomitat CAD/MI ad Diabetes No History of Stroke/TIA/CAD/MI No Diabetes Variable Level N (%) (%) (%) (%) (%) (%) Demographic Age, y Mea±SD 69.9± ± ± ± ± ±15.5 Sex Wome (51.9) (57.0) (42.3) (45.0) (53.8) (54.2) Race/ethicity White (73.8) (81.3) (77.9) (61.8) (75.9) Hispaic (6.4) (6.5) 7853 (5.3) 4981 (5.6) (9.9) (5.7) Black (16.7) (20.4) (11.1) (14.3) (23.6) (15.1) Other (3.2) 5965 (3.1) 3426 (2.3) 1894 (2.1) 6093 (4.8) (3.3) Medical history Atrial fibrillatio/flutter (15.2) (15.1) (21.3) (22.1) (10.3) (12.8) Prosthetic heart valve (1.4) 2258 (1.2) 3623 (2.4) 2357 (2.7) 818 (0.6) 3418 (1.0) Hypertesio (76.6) (79.0) (82.5) (83.6) (84.7) (68.2) Peripheral vascular (4.4) 7523 (3.9) (7.8) 9085 (10.3) 4207 (3.3) 7508 (2.1) disease Curret smoker (19.5) (17.4) (16.1) (15.7) (16.8) (24.1) Dyslipidemia (42.9) (44.3) (56.4) (56.6) (46.7) (31.8) Heart failure (5.2) 7890 (4.1) (10.0) 9702 (11.0) 5394 (4.3) 9566 (2.7) Qualifyig evet Stroke type Ischemic (73.4) (70.2) (74.8) (70.9) (76.7) (74.1) stroke TIA (26.6) (29.8) (25.2) (29.1) (23.3) (25.9) Previous medicatio Previous cholesterol (41.8) (47.6) (59.7) (64.5) (44.3) (24.5) lowerig therapy Period (caledar year) (0.5) 955 (0.5) 645 (0.4) 356 (0.4) 635 (0.5) 1536 (0.4) (1.5) 3126 (1.6) 2444 (1.6) 1313 (1.5) 1882 (1.5) 5006 (1.4) (4.1) 8016 (4.1) 6740 (4.5) 3746 (4.2) 5272 (4.2) (3.8) (8.1) (8.2) (9.1) 7782 (8.8) (8.1) (7.6) (11.5) (11.8) (12.7) (12.4) (11.5) (10.6) (13.2) (14.0) (13.7) (13.3) (13.2) (12.5) (16.6) (16.2) (16.0) (16.2) (16.1) (17.4) (17.2) (16.8) (16.2) (16.8) (16.9) (18.0) (16.9) (16.5) (15.7) (16.5) (17.1) (17.6) (10.5) (10.3) (9.9) 8857 (10.0) (10.9) (10.9) Years i GWTG (18.4) (18.7) (18.2) (18.5) (18.2) (18.3) (9.1) (9.1) (9.5) 8390 (9.5) (9.5) (8.7) (11.5) (11.6) (12.2) (11.7) (11.8) (11) (12.3) (12.5) (12.7) (12.3) (12.6) (12) (12.3) (12.4) (12.4) (12.2) (12.3) (12.3) (11.5) (11.3) (11.3) (11.4) (11.3) (11.7) (10.1) (9.8) (9.7) 8720 (9.8) (9.8) (10.5) (7.5) (7.3) (7.2) 6340 (7.2) 9399 (7.4) (8.0) (4.4) 8490 (4.4) 6067 (4.1) 3914 (4.4) 5356 (4.2) (4.7) (Cotiued )

4 3346 Stroke November 2014 Table 1. Cotiued Overall (Without CAD) (%) CAD/MI (Without CVD) (%) Cocomitat CAD/MI ad (%) Diabetes (%) No History of Stroke/TIA/CAD/MI No Diabetes (%) Variable Level N (%) (2.4) 4748 (2.4) 3415 (2.3) 2208 (2.5) 3046 (2.4) 8654 (2.4) (0.5) 1019 (0.5) 693 (0.5) 440 (0.5) 595 (0.5) 1934 (0.6) Hospital characteristics No. of stroke (4.5) 8696 (4.5) 6261 (4.2) 3853 (4.4) 5983 (4.7) (4.6) discharges (48.7) (48.1) (48.9) (47.7) (49.3) (48.9) (46.8) (47.4) (46.9) (48.0) (46.0) (46.5) No. of beds Media (25th 75th) 361 (250, 540) 360 (252, 537) 358 (250, 533) 359 (250, 530) 366 (257, 547) 360 (249, 540) Regio Northeast (29.8) (28.3) (30.9) (28.8) (29.1) (30.6) Midwest (18.4) (17.8) (19.5) (19.9) (17.3) (18.2) South (37.0) (37.9) (37.0) (38.2) (39.2) (35.6) West (14.8) (16.0) (12.7) (13.2) (14.5) (15.6) Hospital type Academic (57.7) (57.4) (56.7) (56.0) (58.6) (58.5) CAD idicates coroary artery disease; CVD, cardiovascular disease; GWTG, Get With The Guidelies; MI, myocardial ifarctio; ad TIA, trasiet ischemic attack. Dyslipidemia was observed i 42.9% of patiets ad 41.8% were receivig lipid-lowerig therapy before the idex evet. Table 1 summarizes other demographic ad baselie characteristics. The mea (±SD) LDL was (±38), (±38), 95.1 (±39), ad 93.5 (±39) mg/dl i o patiets with preexistig CAD/CVD (without history of CAD, CVD, or diabetes mellitus) ad those with preexistig CVD, CAD, ad both, respectively. Outcome Measures Although 47.6% of patiets with preexistig TIA/stroke were receivig cholesterol-lowerig agets, oly 54.5% met the LDL<100 mg/dl target ad oly 21.4% met the LDL<70 mg/ dl target (Table 2). Similarly, although 59.7% of patiets with stroke ad preexistig CAD were receivig cholesterol-lowerig Table 2. Variable Outcome Measures by Patiet Risk-Group Overall N (%) (Without CAD) (%) CAD/MI (Without CVD) (%) agets, oly 62.3% ad 28.5% met the LDL<100 ad the LDL<70 mg/dl targets, respectively (Table 2; Figure). Amog patiets with o preexistig CVD or CAD, eve fewer had LDL<100 or <70 mg/dl (P<0.001; Table 2). Similarly, oly approximately half of patiets without preexistig vascular disease, but with diabetes mellitus, meet the NCEP-ATP III guidelies or meet a LDL<100 mg/dl. The use of statis was commo after their ew (idex) ischemic stroke. Overall, 81% of patiets were discharged o statis after their idex hospitalizatio captured by GWTG-Stroke. Me were more likely to meet the LDL targets compared with wome. For example, 54.2% of me versus 48.6% of wome met the LDL<100 mg/dl target (P<0.0001). Similarly, 22.1% of me versus 17.7% of wome met the LDL<70 mg/dl target. Cocomitat CAD/MI ad (%) Diabetes (%) No History of Stroke/TIA/CAD/MI No Diabetes (%) LDL outcomes NCEP III (68.0) NA* NA* (62.3) (64.1) (51.5) (74.6) < <100 mg/dl (51.3) (54.5) (62.3) (64.1) (51.5) (41.6) < LDL <70 mg/dl (19.8) (21.4) (28.5) (30.0) (20.9) (12.4) < Cholesterol-lowerig therapy Discharged o statis (81.1) (80.8) (84.3) (84.8) (82.9) (78.1) < CAD idicates coroary artery disease; CVD, cardiovascular disease; LDL, low-desity lipoprotei; MI, myocardial ifarctio; NA, ot applicable; NCEP, Natioal Cholesterol Educatio Program; ad TIA, trasiet ischemic attack. *We could ot distiguish previous stroke/tia of carotid origi from hemorrhagic/other origi for adequate NCEP goal classificatio. P Value

5 Saposik et al LDL Targets i High-Risk Patiets From GWTG-Stroke 3347 LDL (mg/dl) o admissio Figure. Box-plot represetig low-desity lipoprotei (LDL) values o admissio for each risk group. Values represets media LDL i mg/dl o admissio. CAD idicates coroary artery disease; DM, diabetes mellitus; ad TIA, trasiet ischemic attack. Temporal Treds Overall, there was a gradual icrease i the use of preadmissio cholesterol-lowerig treatmet from 39.5% (before 2006) to 53.1% (2012) i patiets with preexistig CVD (P<0.0001) ad from 51.8% (before 2006) to 64.0% (2012) amog those with preexistig CAD (P<0.0001), ad from 56.0% (before 2006) to 69.0% (2012) for patiets with cocomitat preexistig CAD ad CVD durig the study period (Table 3). We also observed better LDL cotrol (LDL<100 mg/dl) over time ragig from 48.2% i 2006 to 59.3% i 2012 (P<0.0001) i patiets with CVD (23.0% improvemet) ad from 57.4% to 65.9% (P<0.0001) for patiets with preexistig CAD (14.8% improvemet; Table 3). Despite the lower proportio of high-risk patiets meetig LDL targets, greater improvemets were observed durig the study period. For example, there was a 58% relative improvemet i the proportio of patiets with preexistig TIA/stroke meetig LDL<70 mg/dl target i 2012 compared with 2006 (Table 3). Similar treds were observed i me, but cotrol rates for LDL<100 mg/dl icreased oly i me, from 55.7% to 65.3% (P<0.0001; Table II i the olie-oly Data Supplemet). White patiets were more likely to meet LDL targets compared with black, Hispaic, ad other race/ethic group patiets (Table 4). There was a sex by race iteractio (P<0.0001) for all outcomes (Tables III ad IV i the olieoly Data Supplemet). Multivariable Aalysis Multivariable aalysis usig geeralized estimatig equatios to accout for clusterig revealed that older age, male sex, white race, presece of vascular risk factors (eg, history of atrial fibrillatio, heart failure, carotid steosis, ad peripheral vascular disease), takig cholesterol-lowerig agets before idex evet, later year erollmet, erollmet i larger Table 3. Temporal Treds i the Attaimet to Guidelie-Recommeded LDL Targets Amog Differet Risk Groups Risk Group 2006 ad Prior P Value* Patiets with preexistig TIA/stroke Dyslipidemia (37.4) 9534 (41.5) (41.8) (44.4) (46.9) (48.1) (50.0) < Receivig treatmet at (39.5) (44.2) (45.4) (47.8) (50.7) (52.0) (53.1) < the time of admissio LDL<100 mg/dl (48.2) (51.8) (52.8) (54.6) (56.3) (58.5) (59.3) < LDL<70 mg/dl 4552 (16.3) 4404 (19.2) 5298 (19.5) 6721 (21.3) 7417 (22.7) 8025 (25.0) 5178 (25.7) < Patiets with preexistig CAD Dyslipidemia, (%) (49.4) (53.4) (54.5) (56.9) (59.1) (60.5) 9186 (62.1) < Receivig treatmet at (51.8) (56.7) (59.8) (60.8) (62.6) (63.2) 9472 (64.0) < the time of admissio LDL<100 mg/dl (57.4) (60.8) (61.5) (62.7) (63.7) (65.0) 9751 (65.9) < LDL<70 mg/dl 5388 (23.0) 5013 (26.5) 5632 (27.6) 6904 (29.0) 7237 (29.9) 7444 (31.9) 4753 (32.1) < Patiets with cocomitat preexistig CAD ad CVD Dyslipidemia 6467 (49.0) 5764 (52.6) 6394 (54.2) 8181 (57.1) 8823 (59.3) 8989 (61.7) 5569 (62.9) < Receivig treatmet at 7396 (56.0) 6633 (60.5) 7499 (63.6) 9346 (65.2) (68.1) (69.0) 6110 (69.0) < the time of admissio LDL<100 mg/dl 7792 (59.0) 6799 (62.1) 7464 (63.3) 9183 (64.0) 9708 (65.2) 9852 (67.6) 6008 (67.8) < LDL<70 mg/dl 3124 (23.7) 3016 (27.5) 3380 (28.7) 4323 (30.1) 4700 (31.6) 4946 (33.9) 3070 (34.7) < Patiets with o Hx of stroke/tia/cad/mi/dm Dyslipidemia, (%) (34.4) (36.5) (34.2) (29.0) (29.7) (30.6) (31.1) < Receivig treatmet at (24.1) 9854 (26.3) (26.5) (23.0) (23.6) (24.7) 9561 (24.8) < the time of admissio LDL<100 mg/dl (37.7) (40.1) (41.6) (40.7) (41.8) (44.1) (44.6) < LDL<70 mg/dl 4971 (10.7) 4393 (11.7) 5467 (12.4) 7054 (11.5) 7993 (12.6) 8467 (13.6) 5493 (14.3) < CAD idicates coroary artery disease; CVD, cardiovascular disease; DM, diabetes mellitus; Hx, history; LDL, low-desity lipoprotei; MI, myocardial ifarctio; ad TIA, trasiet ischemic attack. *P value for tred test usig Cochra Matel Haeszel row-mea scores statistic.

6 3348 Stroke November 2014 Table 4. ad CVD Race/Ethic Differeces i the Attaimet to Guidelie-Recommeded LDL Targets i Patiets With CAD Overall, (%) White, (%) Black, (%) Hispaic, (%) Overall LDL<100 mg/dl (51.3) (53.2) (44.4) (48.8) (46.8) < LDL<70 mg/dl (19.8) (20.9) (15.6) (19.0) 5267 (18.1) < Patiets with preexistig TIA/stroke LDL<100 mg/dl (54.5) (56.4) (48.4) 6842 (53.9) 3187 (53.4) < LDL<70 mg/dl (21.4) (22.4) 7070 (17.8) 2809 (22.1) 1244 (20.9) < Patiets with preexistig CAD/MI LDL<100 mg/dl (62.3) (64.0) 8519 (51.4) 4608 (58.7) 2107 (61.5) < LDL<70 mg/dl (28.5) (29.7) 3358 (20.3) 2094 (26.7) 986 (28.8) < Patiets with cocomitat preexistig CAD ad CVD LDL<100 mg/dl (64.1) (65.9) 6959 (54.8) 3095 (62.1) 1233 (65.1) < LDL<70 mg/dl (30.0) (31.4) 2836 (22.3) 1442 (29.0) 608 (32.1) < No Hx of stroke/ TIA/CAD/MI/DM LDL<100 mg/dl (41.6) (42.9) (37.2) 7867 (39.3) 4228 (35.8) < LDL<70 mg/dl (12.4) (12.8) 5768 (10.8) 2291 (11.4) 1237 (10.5) < Numbers betwee brackets represet colum percetages. CAD idicates coroary artery disease; CVD, cardiovascular disease; DM, diabetes mellitus; Hx, history; LDL, low-desity lipoprotei; MI, myocardial ifarctio; ad TIA, trasiet ischemic attack. Other, (%) P Value hospitals or hospitals located i the West or Midwest were all idepedetly associated with a higher odds of meetig the LDL goals. The directios of the associatios were cosistet across all risk groups (data ot show). Multivariable-adjusted predictors of meetig LDL goals for patiets with preexistig CVD ad CAD are show i Table 5. Discussio I the preset study, icludig > patiets with a acute ischemic stroke admitted to participatig istitutios i the GWTG-Stroke, we evaluated attaimet to the recommeded LDL targets i 4 differet groups: patiets with stroke ad previous TIA/stroke, patiets with stroke ad previous CAD/ myocardial ifarctio, patiets with stroke ad cocomitat preexistig CAD ad CVD, ad patiets without history of cardio- or cerebrovascular evets. We foud that oly 21.4% of high-risk patiets with preexistig TIA/stroke ad 28.5% of patiets with stroke ad preexistig CAD, ad 30.0% of patiets with stroke ad cocomitat previous CVD ad CAD met the curret LDL recommeded targets. Oly half of patiets with stroke with diabetes mellitus met the NCEP III guidelies, ad 44% were takig cholesterol-lowerig agets. Wome ad black patiets presetig with a acute stroke ad preexistig CAD or CVD were less likely to achieve the LDL targets whe compared with me ad white patiets, respectively. High-risk patiets with preexistig CAD compared with CVD aloe were more likely to attai the LDL targets. We were also able to idetify idepedet factors associated with attaimet to the LDL guidelies amog high-risk patiets with preexistig TIA/ stroke ad CAD, icludig older age, male sex, whites or white race, lack of vascular risk factors (except for atrial fibrillatio), beig o lipid-lowerig agets before idex evet, erollmet i the latest years, ad admissios to hospitals located i the West or Midwest or larger istitutios. Large epidemiological studies showed a icreased risk of ischemic stroke amog patiets with dyslipidemia. Accordig to several meta-aalyses, icludig > patiets icluded i stati trials, the larger the reductio i LDL, the greater the reductio i stroke risk. 7,21 Most guidelies i place durig the study period (eg, NCEP, AHA, ad Caadia guidelies for the maagemet of dyslipidemia) recommeded LDL-cholesterol lowerig as the primary lipid target. 5,10,12 The cardiovascular risk reductio is more oticeable for high-risk patiets, usually defied as those with preexistig CVD or coroary heart equivalets (NCEP). 10 Our study occurs i the cotext of a ew revisio to the guidelie-recommeded approach to lipid maagemet. The AHA ad America College of Cardiology, carryig o the work of ATP IV, has recetly issued its recommedatios that icludes chages to the priciples of lipid maagemet. 14 The ew guidelies abado LDL-targeted treatmet i favor of directig fixed dose high- or moderate itesity stati therapy to patiet groups cosidered likely to beefit based o radomized cotrolled trial evidece: (1) history of symptomatic CVD iclude stroke or TIA of atherosclerotic origi, (2) LDL 190 mg/dl, (3) diabetes mellitus age 40 to 75 years with LDL 70 mg/dl, or (4) estimated 10-year risk of myocardial ifarctio or stroke 7.5% based o ew Pooled Cohort Equatios. Although the ew guidelies 14 base treatmet eligibility o predicted future risk from the pooled cohort equatios, rather tha LDL cutoffs, cholesterol levels still figure i the pooled cohort calculatios. We may see a wideig of the gap betwee guidelie-recommeded ad actual practice, depedig o the degree to which the cotroversy surroudig the ew guidelies is resolved. I additio, there are large-scale cliical trials i progress evaluatig ew LDL-lowerig agets that have erollmet criteria based o LDL levels achieved or ot achieved with stati therapy. Should oe or more of these trials prove to be positive, revisios to the guidelies would be expected.

7 Saposik et al LDL Targets i High-Risk Patiets From GWTG-Stroke 3349 Table 5. Multivariable Aalysis: Factors Associated With Meetig LDL Targets i Patiets With History of TIA/stroke ad CAD/MI Variables/Outcome Thus, our study provides a assessmet of the real-world success of guidelie-based cholesterol maagemet i high-risk patiets those hospitalized with a ew ischemic stroke i the time period whe recommedatios were based o LDL goal achievemet based o risk group. We are ot able to determie retroactively how may patiets were treated accordig to ew guidelie specificatios because the GWTG-Stroke database did ot previously collect iformatio o cholesterol-lowerig drug class ad dose itesity ad cotais isufficiet iformatio to calculate the predicted risk accordig to the Pooled Cohort Equatio. However, it is clear that may patiets with ew ischemic stroke or TIA would have bee cosidered isufficietly treated accordig to the ew guidelies as well for example, i 2011 to 2012 oly 58% of patiets with preexistig TIA or stroke ad oly 64% of patiets with preexistig CAD were takig cholesterol-lowerig drugs of ay kid. LDL<100 mg/dl, OR (95% CI) LDL<70 mg/dl, OR (95% CI) Prior Stroke/TIA Previous CAD/MI Previous Stroke/TIA Previous CAD/MI Age, per 10 y 1.14 ( ) 1.24 ( ) 1.12 ( ) 1.17 ( ) Wome (vs me) 0.72 ( ) 0.67 ( ) 0.72 ( ) 0.72 ( ) Race/ethicity, white as referet Black 0.83 ( ) 0.81 ( ) 0.81 ( ) 0.76 ( ) Hispaic 0.96 ( ) 0.94 ( ) 0.99 ( ) 0.97 ( ) Other 0.91 ( ) 0.96 ( ) 0.94 ( ) 1.01 ( ) Vascular risk factors Atrial fibrillatio/flutter 1.38 ( ) 1.34 ( ) 1.30 ( ) 1.22 ( ) Prosthetic heart valve 1.08 ( ) 1.03 ( ) 1.01 ( ) 0.95 ( ) Carotid steosis 1.03 ( ) 1.00 ( ) 1.05 ( ) 1.00 ( ) PVD 1.11 ( ) 1.03 ( ) 1.17 ( ) 1.10 ( ) Hypertesio 1.01 ( ) 1.05 ( ) 1.07 ( ) 1.04 ( ) Smoker 0.89 ( ) 0.86 ( ) 0.88 ( ) 0.85 ( ) Dyslipidemia 0.83 ( ) 0.88 ( ) 0.92 ( ) 0.94 ( ) Heart failure 1.20 ( ) 1.15 ( ) 1.26 ( ) 1.19 ( ) Previous ischemic stroke vs TIA 0.83 ( ) 0.82 ( ) 0.88 ( ) 0.86 ( ) Previous cholesterol-lowerig therapy 3.23 ( ) 3.53 ( ) 3.19 ( ) 3.12 ( ) Caledar time (per y) 1.05 ( ) 1.04 ( ) 1.07 ( ) 1.06 ( ) Stroke volume, year as referet ( ) 0.92 ( ) 0.96 ( ) 0.95 ( ) ( ) 0.97 ( ) 0.97 ( ) 0.97 ( ) No. of beds (per 100 beds) 1.00 ( ) 1.00 ( ) 1.01 ( ) 1.00 ( ) Regio, West as referet Northeast 0.94 ( ) 0.95 ( ) 0.96 ( ) 0.95 ( ) Midwest 1.01 ( ) 1.01 ( ) 1.03 ( ) 1.05 ( ) South 0.94 ( ) 0.94 ( ) 0.97 ( ) 0.95 ( ) Academic ceter 1.00 ( ) 0.98 ( ) 1.02 ( ) 1.00 ( ) Multivariable aalysis adjusted for age (as a cotiuous variable), sex, race (categorized as white, black, Hispaic, or other), comorbid coditios (atrial fibrillatio, prosthetic heart valve, carotid steosis, diabetes, peripheral vascular disease, hypertesio, dyslipidemia, ad smokig), year of erollmet ad hospital characteristics (bed size, aual umber of stroke discharges, academic teachig status, ad geographical regio). CAD idicates cardiovascular disease; CI, cofidece iterval; CVD, cerebrovascular disease; LDL, low-desity lipoprotei; MI, myocardial ifarctio; OR, odds ratio; PVD, peripheral vascular disease; ad TIA, trasiet ischemic attack. Previous studies coducted i differet coutries i the 1990s have also documeted sigificat gaps betwee evidece-based medicie ad real-world cliical practice For example, amog 4888 outpatiets erolled i the Lipid Treatmet Assessmet Project, overall oly 38% attaied the LDL-cholesterol goal recommeded by NCEP-ATP II. A Caadia study icludig 5000 high-risk ambulatory patiets with CAD, CVD, or both foud that <25% met LDL-guidelie recommeded targets. 26 A sigle-ceter study of hospitalized patiets with ischemic stroke ot oly foud higher attaimet of prestroke LDL targets based o admissio lipid testig (73%) but also foud that higher risk patiets, who had more striget prestroke LDL targets, had the highest likelihood of ot beig at goal. 18,27 The calculated cumulative risk reductio for implemetig lifestyle modificatios, atithrombotics, atihypertesive, ad lipid-lowerig therapy (all guidelie-recommeded strategies

8 3350 Stroke November 2014 i secodary stroke prevetio) is 80%. 4 The results of this study highlight the substatial gap betwee curret guidelies ad target achievemet i a outpatiet settig. A few studies showed the importace of optimizig discharge plaig for future adherece to the guidelies, 28,29 but most of the studies were coducted i ipatiet settigs. For example, both The Reductio of Atherothrombosis for Cotiued Health (REACH) Registry ad results from the GWTG revealed improvemets i cholesterol testig over time ad reducig ethic ad racial disparities. 18 A recet study icludig 1154 stroke survivors participatig i The Natioal Health ad Nutritio Examiatio Surveys ( ) revealed that cholesterol treatmet rates icreased from 30% to 40% i me (P=0.02) ad from 28% to 36% (P<0.01) i wome, but cotrol rates icreased oly i me, from 62% to 87% (P<0.01). It is importat to bear i mid that total cholesterol (defied as >5.2 mmol/l [>200 mg/dl]) was the therapeutic target. 30 Our study icludig > patiets for a 9-year period revealed similar treds for each high-risk group. The fidig that oly 40% to 50% of high-risk patiets were already o lipid-lowerig agets at the time of the idex evet is cocerig. However, most patiets (80%) were discharged o statis after their ew (idex) ischemic stroke (Table 2). The observed gap i LDL levels betwee patiets with either preexistig stroke/tia or o CVD ad those with preexistig CAD could be explaied by differeces i the emphasis of recommeded targets betwee cardiovascular ad stroke prevetio guidelies. 5,6,12 I additio, stadard of care procedures more widely implemeted for patiets with CAD (ie, coroary revascularizatio) could improve patiets awareess ad cosequetly treatmet success. Together, these results suggest that cliicias may be more aggressive whe facig older me with preexistig CVD or CAD with o vascular risk factors. Alteratively, socioecoomic, lifestyle behavior, ad geetic factors may explai why ethic groups other tha whites, patiets livig i the ortheast or south regios, or patiets cared for i smaller hospitals were less likely to meet the LDL targets. Ecoomic factors have also bee documeted i previous studies usig hierarchical models. 31 The results of our study have practical cliical ad policy implicatios. Several studies evaluatig key process measures revealed that a high proportio of patiets are discharged o lipid-lowerig agets after a TIA/stroke. 18,32,33 The lower attaimet to the LDL guidelies at the time of the idex evet for patiets with preexistig CAD or CVD may suggest lower access or less aggressive ambulatory care i stroke prevetio. New strategies may be eeded to facilitate equal access to stroke prevetio cliics, especially for high-risk groups. Outpatiet adherece to evidece-based therapies should also be carefully ad regularly assessed with close follow-up by the family physicia, geeral practitioer, or specialists. Several limitatios deserve commet. We oly icluded participatig istitutios i GWTG-Stroke, ad our results may represet a uderestimatio of the low attaimet to the lipid guidelies. Secod, data were collected based o the medical record ad may ot be completely accurate if cliical documetatio was icomplete. Third, LDL-measuremets were ot performed i a cetral core laboratory. However, this reflects real-world practice where physicias iitiate or titrate therapy based o available test results. Fourth, we were uable to distiguish the subtype of a history of stroke (eg, betwee preexistig hemorrhagic stroke versus stroke because of carotid steosis), to allow us estimate the NCEP goals for CVD patiets (olie-oly Data Supplemet). Fifth, the database does ot cotai iformatio o prestroke cholesterol drug class or dose. Fially, cholesterol levels were obtaied after oset of stroke ad TIA, which may lower levels because of acute phase respose. However, this ulikely to have chaged the results because blood samples were likely obtaied i first 24 hours. I additio, we ote that our fidigs are relevat oly to stroke ad patiets with TIA ad are probably ot represetative of cholesterol levels i the geeral populatio. Despite these limitatios, our study costitutes the first step i uderstadig the differetial gaps i ambulatory maagemet of high-risk patiets with preexistig cerebrovascular disease. This large study is uique i providig evidece those high-risk patiets with preexistig CVD aloe or cocomitat CVD ad CAD received suboptimal therapy. Oly 1 i 4 of those patiets met the LDL<70 mg/dl. Oly half of patiets with stroke ad diabetes mellitus met LDL<100 mg/dl at the time of admissio. I additio, wome with CVD are less likely to achieve the lipid targets. Curret maagemet of dyslipidemia after a TIA/stroke remais suboptimal, despite a high proportio of idividuals beig discharged o lipid-lowerig agets after their acute hospitalizatio for ischemic stroke. Quality improvemet strategies should be directed to facilitate access to ambulatory care for high-risk patiets with preexistig CVD, i particular, for those who are less likely to achieve the recommeded targets. Ackowledgmets We thak Cassadra Ottawa for her help i orgaizig tables ad ivestigators participatig i the America Heart Associatio Get With The Guidelies-Stroke. Sources of Fudig The Get-with-the-Guidelies is fuded by the America Heart Associatio ad the America Stroke Associatio. The program is also supported i part by urestricted educatioal grats to the America Heart Associatio by Pfizer, Ic, New York, NY, ad the Merck-Scherig Plough Partership (North Wales, PA), who did ot participate i the desig, aalysis, article preparatio, or approval. Disclosures Dr Saposik is supported by the Distiguished Cliicia Scietist Award from Heart ad Stroke Foudatio of Caada after a ope peer-review competitio. Dr Foarow receives research support from Patiet-cetered Outcomes Research Istitute ad Amge. Dr Schwamm serves as the Chair of the AHA GWTG Stroke Cliical Work Group (o compesatio). The other authors report o coflicts. Refereces 1. Kim AS, Johsto SC. Global variatio i the relative burde of stroke ad ischemic heart disease. Circulatio. 2011;124: Beaglehole R, Boita R, Horto R, Adams C, Alleye G, Asaria P, et al. Priority actios for the o-commuicable disease crisis. Lacet. 2011;377: Goldstei LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushell CD, et al; America Heart Associatio; America Stroke Associatio Stroke Coucil. Primary prevetio of ischemic stroke: a guidelie from the America Heart Associatio/America Stroke Associatio Stroke Coucil: cosposored by the Atherosclerotic Peripheral Vascular

9 Saposik et al LDL Targets i High-Risk Patiets From GWTG-Stroke 3351 Disease Iterdiscipliary Workig Group; Cardiovascular Nursig Coucil; Cliical Cardiology Coucil; Nutritio, Physical Activity, ad Metabolism Coucil; ad the Quality of Care ad Outcomes Research Iterdiscipliary Workig Group. Circulatio. 2006;113:e873 e Hackam DG, Spece JD. Combiig multiple approaches for the secodary prevetio of vascular evets after stroke: a quatitative modelig study. Stroke. 2007;38: Furie KL, Kaser SE, Adams RJ, Albers GW, Bush RL, Faga SC, et al. Guidelies for the prevetio of stroke i patiets with stroke or trasiet ischemic attack: a guidelie for healthcare professioals from the America Heart Associatio/America Stroke Associatio. Stroke. 2011;42: O Gara PT, Kusher FG, Ascheim DD, Casey DE Jr, Chug MK, de Lemos JA, et al; CF/AHA Task Force ACCF/AHA guidelie for the maagemet of ST-elevatio myocardial ifarctio: executive summary: a report of the America College of Cardiology Foudatio/ America Heart Associatio Task Force o Practice Guidelies. Circulatio. 2013;127: Amareco P, Lavallée P, Touboul PJ. Stroke prevetio, blood cholesterol, ad statis. Lacet Neurol. 2004;3: Gorelick PB, Sacco RL, Smith DB, Alberts M, Mustoe-Alexader L, Rader D, et al. Prevetio of a first stroke: a review of guidelies ad a multidiscipliary cosesus statemet from the Natioal Stroke Associatio. JAMA. 1999;281: McAlister FA, Zarke KB, Campbell NR, Feldma RD, Levie M, Maho J, et al. The 2001 caadia recommedatios for the maagemet of hypertesio: Part two--therapy. Ca J Cardiol. 2002;18: Natioal Cholesterol Educatio Program (NCEP) Expert Pael o Detectio, Evaluatio, ad Treatmet of High Blood Cholesterol i Adults (Adult Treatmet Pael III). Third report of the Natioal Cholesterol Educatio Program (NCEP) Expert Pael o Detectio, Evaluatio, ad Treatmet of High Blood Cholesterol i Adults (Adult Treatmet Pael III) fial report. Circulatio. 2002;106: De Backer G, Ambrosioi E, Borch-Johse K, Brotos C, Cifkova R, Dallogeville J, et al. Europea guidelies o cardiovascular disease prevetio i cliical practice. Third joit task force of europea ad other societies o cardiovascular disease prevetio i cliical practice. Eur Heart J. 2003;24: Aderso TJ, Grégoire J, Hegele RA, Couture P, Macii GB, McPherso R, et al update of the Caadia Cardiovascular Society guidelies for the diagosis ad treatmet of dyslipidemia for the prevetio of cardiovascular disease i the adult. Ca J Cardiol. 2013;29: Goldstei LB, Bushell CD, Adams RJ, Appel LJ, Brau LT, Chaturvedi S, et al. Guidelies for the primary prevetio of stroke: a guidelie for healthcare professioals from the america heart associatio/america stroke associatio. Stroke. 2011;42: Stoe NJ, Robiso JG, Lichtestei AH, Bairey Merz CN, Blum CB, Eckel RH, et al ACC/AHA guidelie o the treatmet of blood cholesterol to reduce atherosclerotic cardiovascular risk i adults: a report of the America College of Cardiology/America Heart Associatio Task Force o Practice Guidelies. Circulatio. 2014;129(25 suppl 2):S1 S Schwamm LH, Foarow GC, Reeves MJ, Pa W, Frakel MR, Smith EE, et al. Get With the Guidelies-Stroke is associated with sustaied improvemet i care for patiets hospitalized with acute stroke or trasiet ischemic attack. Circulatio. 2009;119: LaBresh KA, Reeves MJ, Frakel MR, Albright D, Schwamm LH. Hospital treatmet of patiets with ischemic stroke or trasiet ischemic attack usig the Get With The Guidelies program. Arch Iter Med. 2008;168: Foarow GC, Reeves MJ, Smith EE, Saver JL, Zhao X, Olso DW, et al. Characteristics, performace measures, ad i-hospital outcomes of the first oe millio stroke ad trasiet ischemic attack admissios i get with the guidelies-stroke. Circ Cardiovasc Qual Outcomes. 2010;3: Smith EE, Pa W, Olso D, Reeves MJ, Ovbiagele B, Peterso ED, et al. Frequecy ad determiats of lipid testig i ischemic stroke ad trasiet ischemic attack: fidigs from get with the guidelies-stroke. Stroke. 2010;41: Sacco RL, Adams R, Albers G, Alberts MJ, Beavete O, Furie K, et al; America Heart Associatio; America Stroke Associatio Coucil o Stroke; Coucil o Cardiovascular Radiology ad Itervetio; America Academy of Neurology. Guidelies for prevetio of stroke i patiets with ischemic stroke or trasiet ischemic attack: a statemet for healthcare professioals from the America Heart Associatio/America Stroke Associatio Coucil o Stroke: co-sposored by the Coucil o Cardiovascular Radiology ad Itervetio: the America Academy of Neurology affirms the value of this guidelie. Stroke. 2006;37: America Hospital Associatio. America Hospital Associatio Guide Book. Chicago: America Hospital Associatio; Baiget C, Keech A, Kearey PM, Blackwell L, Buck G, Pollicio C, et al. Efficacy ad safety of cholesterol-lowerig treatmet: prospective meta-aalysis of data from 90,056 participats i 14 radomised trials of statis. Lacet. 2005;366: EUROASPIRE I ad II Group; Europea Actio o Secodary Prevetio by Itervetio to Reduce Evets. Cliical reality of coroary prevetio guidelies: a compariso of EUROASPIRE I ad II i ie coutries. EUROASPIRE I ad II Group. Europea Actio o Secodary Prevetio by Itervetio to Reduce Evets. Lacet. 2001;357: Pearso TA, Laurora I, Chu H, Kafoek S. The lipid treatmet assessmet project (L-TAP): a multiceter survey to evaluate the percetages of dyslipidemic patiets receivig lipid-lowerig therapy ad achievig low-desity lipoprotei cholesterol goals. Arch Iter Med. 2000;160: Ovbiagele B, Saver JL, Bag H, Chambless LE, Nassief A, Miuk J, et al. Stati treatmet ad adherece to atioal cholesterol guidelies after ischemic stroke. Neurology. 2006;66: Davidso MH, Maki KC, Pearso TA, Pasterak RC, Deedwaia PC, McKeey JM, et al. Results of the Natioal Cholesterol Educatio (NCEP) Program Evaluatio ProjecT Utilizig Novel E-Techology (NEPTUNE) II survey ad implicatios for treatmet uder the recet NCEP Writig Group recommedatios. Am J Cardiol. 2005;96: Saposik G, Goodma SG, Leiter LA, Ya RT, Fitchett DH, Bayer NH, et al. Applyig the evidece: Do patiets with stroke, coroary artery disease, or both achieve similar treatmet goals? Stroke. 2009;40: Smith EE, Abdullah AR, Amirfarza H, Schwamm LH. Serum lipid profile o admissio for ischemic stroke: failure to meet Natioal Cholesterol Educatio Program Adult Treatmet Pael (NCEP-ATPIII) guidelies. Neurology. 2007;68: Hayes SM, Dupuis M, Murray S. Issues ad challeges i the assessmet, diagosis ad treatmet of cardiovascular risk factors: assessig the eeds of cardiologists. BMC Med Educ. 2008;8: Ovbiagele B, Saver JL, Fredieu A, Suzuki S, Selco S, Rajajee V, et al. I-hospital iitiatio of secodary stroke prevetio therapies yields high rates of adherece at follow-up. Stroke. 2004;35: Shah NS, Huffma MD, Nig H, Lloyd-Joes DM. Treds i vascular risk factor treatmet ad cotrol i US stroke survivors: the Natioal Health ad Nutritio Examiatio Surveys ( ). Circ Cardiovasc Qual Outcomes. 2013;6: Vekitachalam L, Wag K, Porath A, Corbala R, Hirsch AT, Cohe DJ, et al; REACH Registry Ivestigators. Global variatio i the prevalece of elevated cholesterol i outpatiets with established vascular disease or 3 cardiovascular risk factors accordig to atioal idices of ecoomic developmet ad health system performace. Circulatio. 2012;125: Foarow GC, Reeves MJ, Zhao X, Olso DM, Smith EE, Saver JL, et al. Age-related differeces i characteristics, performace measures, treatmet treds, ad outcomes i patiets with ischemic stroke. Circulatio. 2010;121: Saposik G, Black SE, Hakim A, Fag J, Tu JV, Kapral MK. Age disparities i stroke quality of care ad delivery of health services. Stroke. 2009;40: