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Risk factors for hypertensive crisis: importance of out-patient blood pressure control

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Fmily Prctice Vol. 21, No. 4 Oxford University Press 2004, ll rights reserved. Doi: /fmpr/cmh412, vilble online t Printed in Gret Britin Risk fctors for hypertensive crisis:
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Fmily Prctice Vol. 21, No. 4 Oxford University Press 2004, ll rights reserved. Doi: /fmpr/cmh412, vilble online t Printed in Gret Britin Risk fctors for hypertensive crisis: importnce of out-ptient blood pressure control Jmes E Tisdle,b,d, Mike B Hung b,e nd Steven Borzk c,f Tisdle JE, Hung MB nd Borzk S. Risk fctors for hypertensive crisis: importnce of outptient blood pressure control. Fmily Prctice 2004; 21: Objectives. The purpose of this study ws to identify independent risk fctors for development of hypertensive crisis. Methods. This ws retrospective, cse-controlled study. Cses were 143 ptients who presented during 3-yer period to the Emergency Deprtment with the dignosis of hypertensive crisis, defined s systolic pressure 180 mmhg nd/or distolic pressure 110 mmhg nd symptoms of hypertensive emergency during the Emergency Deprtment presenttion. Controls were 485 ptients with hypertension, mtched to cses on the bsis of ge, sex nd rce, who were not dmitted to the Emergency Deprtment with n episode of hypertensive crisis during the study period. Co-morbid conditions were identified from computerized helth system dtbses nd medicl records. Out-ptient blood pressures were obtined from medicl records from rndomly selected out-ptient clinic visits. Results. The verge blood pressure during Emergency Deprtment presenttion in ptients with hypertensive crisis ws 197 ± 21/108 ± 14 mmhg. Less successful out-ptient systolic blood pressure control ws n independent risk fctor for hypertensive crisis [odds rtio (OR) 1.30 ( ), per 10 mmhg, P 0.001]. Higher out-ptient distolic blood pressures [OR 1.21 ( per 10 mmhg, P = 0.07] nd history of hert filure [OR 3.48 ( ), P = 0.06] trended towrds independence s risk fctors. Conclusion. Less effective blood pressure control, bsed on out-ptient systolic blood pressure mesurements, is n independent risk fctor for n Emergency Deprtment presenttion due to hypertensive crisis. Keywords. Blood pressure, hypertension, risk fctors. Introduction Hypertensive crises re common cuse of medicl urgencies or emergencies dignosed in emergency rooms. 1 Identifiction of risk fctors for development of Received 7 My 2003; Revised 22 October 2003; Accepted 10 Mrch Deprtment of Phrmcy Prctice, Eugene Applebum College of Phrmcy nd Helth Sciences, Wyne Stte University, b Deprtment of Phrmcy Services, nd c Henry Ford Hert nd Vsculr Institute, Henry Ford Hospitl, Detroit, MI, USA. Correspondence to Jmes E Tisdle, Phrm D, Associte Professor, Deprtment of Phrmcy Prctice, School of Phrmcy nd Phrmcl Sciences, Purdue University, W7555 Myers Building, WHS, 1001 West 10th Street Indinpolis, IN 46202, USA; E-mil: d Present ddress: Deprtment of Phrmcy Prctice, School of Phrmcy nd Phrmcl Sciences, Purdue University, Indinpolis, IN, USA; e Present ddress: Deprtment of Phrmcy Services, Select Specilty Hospitl, Detroit, MI, USA; f Present ddress: Florid Crdiology Group, P.A., Atlntis, FL, USA. hypertensive crisis is importnt, so tht specific ptients t incresed risk cn be trgeted for more ggressive therpy nd/or risk fctor intervention for the prevention of morbidity ssocited with cute severe blood pressure elevtions. However, risk fctors for the development of hypertensive crisis hve not been studied extensively. A hypertensive crisis is known to occur more commonly in mles nd in Africn- Americns. 2 In ddition, hypertensive crises re known to occur with pek incidence between the ges of 40 nd 50 yers. 3 Other risk fctors tht predispose ptients with hypertension to hypertensive crisis hve not been determined. Intuitively, it my be expected tht ptients with less effective out-ptient blood pressure control re t higher risk of experiencing n episode of hypertensive crisis, but this hs never been reported in published tril. Existing dt hve shown tht non-dherence with ntihypertensive medictions independently increses the odds of severe, uncontrolled hypertension, 2 suggesting tht poorer blood pressure control my indeed be risk fctor for hypertensive crisis. The influence of co-morbid conditions such s hert filure or renl filure on the risk of hypertensive crisis is lso 420 Risk fctors for hypertensive crisis 421 unknown. Hert filure is ssocited with elevted plsm concentrtions of vsoconstricting substnces such s norepinephrine, ngiotensin II, endothelin, ldosterone nd vsopressin, 4,5 nd hert filure nd renl dysfunction re ssocited with fluid retention, ll of which my be expected to predispose ptients with chronic hypertension to hypertensive crisis. The purpose of this study ws to identify risk fctors for development of hypertensive crisis in ptients with chronic hypertension. We hypothesized tht the risk of hypertensive crisis is incresed in ptients with: (i) poorly controlled out-ptient blood pressure; (ii) hert filure; nd/or (iii) chronic renl dysfunction. Methods This ws retrospective, cse-controlled study. Sources of dt were the Henry Ford Helth System dtbse, 6 the Helth Allince Pln dtbse nd review of medicl records. The Henry Ford Helth System dtbse mintins informtion on ll in-ptients nd mbultory ptients treted within the helth system. Informtion mintined in this dtbse includes demogrphics, inptient nd mbultory clinic dignoses ccording to the Interntionl Clssifiction of Diseses, Ninth Revision, Clinicl Modifiction (ICD-9) 7 codes, procedures, emergency room visits, billing codes, nd other clinicl nd finncil informtion. 6 The Helth Allince Pln is helth mintennce orgniztion owned nd operted by Henry Ford Hospitl, nd its dtbse provides informtion regrding prescribed drug therpy for enrolled ptients. Cses Cses were ptients who presented to the Emergency Deprtment t Henry Ford Hospitl with the dignosis of hypertensive crisis during 3-yer period. Hypertensive crisis ws defined s systolic blood pressure 180 mghg nd/or distolic blood pressure 110 mmhg, 8 in the presence of symptoms known to be ssocited with hypertensive emergency, bsed on ICD-9 codes ssigned in the Emergency Deprtment. 7 Ptients were initilly included in the cse group if the primry or secondry Emergency Deprtment dignosis ws hypertension or clinicl mnifesttion of hypertensive crisis (Tble 1). The following ICD codes were used to estblish initilly the Emergency Deprtment dignosis of hypertensive crisis: hypertension (401); hypertension, benign or mlignnt (401.0); hypertension, benign or mlignnt with congestive hert filure (402.01); hypertension, unspecified (401.9); hypertension, unspecified with congestive hert filure (402.91); hypertensive encephlopthy (437.2); ortic dissection (441.0); cute renl filure (584); unstble ngin (411.1); nd cute coronry insufficiency (411.89). Ptients were excluded if the primry reson for dmission ws hed injury or cerebrovsculr ccident. A totl of 305 Emergency Deprtment ptients were ssigned one of these ICD-9 codes. Medicl records of these ptients were reviewed to determine blood pressures during the Emergency Deprtment presenttion. Ptients were included in the finl cse group only if the Emergency Deprtment blood pressure ws 180 mmhg systolic nd/or 110 mmhg distolic. 8 Of the 305 ptients who were ssigned to one of the bove ICD-9 codes, 143 ptients met the inclusion criteri, nd were included s cses of hypertensive crisis. Controls A totl of ptients were identified in the Henry Ford Helth System dtbse with the ICD-9 code for hypertension (401). Controls were defined s ptients with hypertension who were not dmitted to the Emergency Deprtment with n episode of hypertensive TABLE 1 Clinicl mnifesttions/symptoms nd physicin-ssigned dignoses used to clssify ptients presenting to the Emergency Deprtment with severely elevted blood pressure into the hypertensive crisis cse group Signs/symptoms Acute hert filure Shortness of breth; crckles/rles suggestive of pulmonry oedem on chest usculttion; jugulr venous distension; chest X-ry suggestive of pulmonry oedem; physicin-ssigned dignosis of hert filure Unstble ngin or cute coronry Crushing, squeezing chest pin, chest tightness, chest pressure, with or without rdition to insufficiency rms or jw; physicin-ssigned dignosis of unstble ngin or cute coronry syndrome Aortic dissection Bck or chest pin rditing to the rms; widening of the medistinum on chest X- ry; echocrdiogrm, CT scn or MRI indicting ortic dissection; physicin-ssigned dignosis of ortic dissection Hypertensive encephlopthy Acute renl filure Mentl sttus chnges; physicin-ssigned dignosis of hypertensive encephlopthy Elevted serum cretinine; diminished urine output; physicin-ssigned dignosis of cute renl filure CT = computed tomogrphy; MRI = mgnetic resonnce imging. 422 Fmily Prctice n interntionl journl TABLE 2 Results of the univrite nlysis of risk fctors for Emergency Deprtment presenttion with hypertensive crisis Cses (n = 143) Controls b (n = 485) P Age (yers) 52 ± ± Mle 38% 41% 0.51 Africn-Americn 79% 81% 0.59 History of dibetes mellitus 18.9% 18.1% 0.84 History of chronic renl insufficiency 4.9% 2.3% 0.10 History of coronry rtery disese 7.0% 6.2% 0.73 History of hert filure 4.2% 1.4% 0.04 History of cerebrovsculr ccident 0 2.3% 0.08 History of cocine buse 2.8% No. of ntihypertensive drugs being tken 1.2 ± ± Cses = ptients with hypertension who presented to the Emergency Deprtment with hypertensive crisis during 3-yer period. b Controls = ptients with hypertension who did not present to the Emergency Deprtment with hypertensive crisis during the sme 3-yer period. crisis during the 3-yer study period. Control ptients were mtched to the cse popultion on the bsis of ge (±5 yers), sex nd rce. Mtching for ge, sex nd rce ws performed becuse these fctors hd been identified previously s risk fctors for hypertensive crisis, nd mtching for these vribles therefore llowed us to evlute other risk fctors in mtched popultion. Of the ptients identified s hving received the dignosis of hypertension, 485 were mtched to the cse group for ge (±5 yers), sex nd rce, nd on this bsis were selected s the control group. This smple size in the control group ws selected becuse it llowed clcultion of sttisticlly significnt odds rtio (OR) of 2.0. Rndomiztion ws performed using rndom number genertor feture vilble in Microsoft Excel version 7.0. Dt collection Co-morbid conditions were identified from the computerized dtbses nd medicl records. To ssess the degree of blood pressure control during tretment, blood pressures were obtined from medicl records documented during rndomly selected out-ptient clinic visits. Sttisticl nlysis Univrite nlysis of risk fctors for n Emergency Deprtment visit due to hypertensive crisis ws performed. Student s unpired t-test ws used for prmetric dt, wheres chi-squre or Fisher s exct test ws used for non-prmetric dt s pproprite. To identify independent risk fctors for n Emergency Deprtment visit due to hypertensive crisis, fctors with univrite P-vlue 0.30 were incorported into multivrite logistic regression nlysis. Multivrite ORs for Emergency Deprtment visits due to hypertensive crisis were clculted. Results Ptient chrcteristics Chrcteristics of ptients included re presented in Tble 2. By design, there were no significnt differences between the groups in ge, sex or rce. The verge blood pressure during Emergency Deprtment presenttion in the cse group of ptients with hypertensive crisis ws 197 ± 21/108 ± 14 mmhg. Univrite nlysis The prevlence of specific co-morbid conditions in the hypertensive crisis versus the control groups is presented in Tble 2. A significntly higher proportion of hypertensive crisis ptients hd history of hert filure thn in the control group. There ws non-significnt trend towrds higher frequency of chronic renl insufficiency in the hypertensive crisis group. Of interest, the number of ntihypertensive drugs tken ws significntly higher in the control group thn in the hypertensive crisis group. A significntly higher proportion of ptients in the cse group were receiving no ntihypertensive drug therpy compred with tht in the control group (29.5 versus 6.0%, P 0.001). The degree of successful out-ptient blood pressure control in the two groups is presented in Figure 1. Outptient control of blood pressure ws significntly better in the control group compred with tht in the ptients who subsequently presented to the Emergency Deprtment with n episode of hypertensive crisis. Multivrite nlysis Independent co-morbid risk fctors for n Emergency Deprtment visit due to hypertensive crisis re presented in Tble 3. Less successful out-ptient blood pressure control, mesured in terms of systolic blood Risk fctors for hypertensive crisis 423 TABLE 3 Results of the multivrite nlysis to determine independent co-morbid risk fctors for n Emergency Deprtment visit due to hypertensive crisis Co-morbid condition Odds rtio (95% CI) P Chronic renl filure 1.48 ( ) 0.54 History of hert filure 3.48 ( ) 0.06 Out-ptient systolic blood pressure 1.30 ( ) Out-ptient distolic blood pressure 1.21 ( ) 0.07 No. of ntihypertensive drugs being tken 0.89 ( ) 0.63 Odds rtio bsed on ech 10 mmhg increse in blood pressure. FIGURE 1 Blood pressures during rndomly selected outptient clinic visits. Difference in systolic blood pressure: 13.8 mmhg (95% CI mmhg); difference in distolic blood pressure: 6.7 mmhg (95% CI mmhg). = cses; = controls pressure, ws significnt independent risk fctor. The odds of n Emergency Deprtment presenttion due to hypertensive crisis were incresed by 30% for every 10 mm increse in out-ptient systolic blood pressure. There were non-significnt trends towrds history of hert filure nd less well-controlled out-ptient distolic blood pressure s independent risk fctors. The number of ntihypertensive drugs tken ws not significnt independent risk fctor for hypertensive crisis. ORs for n Emergency Deprtment presenttion due to hypertensive crisis bsed on vrying increments of systolic nd distolic blood pressure re presented in Tble 4. Discussion The results of this study demonstrte tht less effective control of systolic blood pressure on n out-ptient bsis is n independent risk fctor for hypertensive crisis leding to n Emergency Deprtment presenttion. In the present study, verge out-ptient systolic blood pressures were ~14 mmhg lower in the group of ptients who did not present with hypertensive crisis compred with the cse group. Averge out-ptient distolic blood pressures were 7 mmhg lower in the control group. The odds of n Emergency Deprtment presenttion due to hypertensive crisis were incresed by 30% for every 10 mmhg increse in out-ptient systolic blood pressure, nd by 21% for every 10 mmhg increse in out-ptient distolic blood pressure. These dt underscore the importnce of dequte blood pressure control for reduction in morbidity ssocited with hypertension. The number of ntihypertensive drugs tken ws not n independent risk fctor for hypertensive crisis, nd therefore cnnot necessrily be used s n indictor of more refrctory (or better controlled) hypertension. Reltively few studies hve been performed to determine risk fctors for hypertensive crisis in ptients with chronic hypertension. Hypertensive crises occur most commonly in individuls between the ges of 40 nd 50 yers. 3 Africn-Americn rce nd mle sex re lso known to be risk fctors. 2 In ddition, socioeconomic nd ptient fctors including lck of primry cre physicin, lck of medicl insurnce nd non-dherence to ntihypertensive regimens were found independently to increse the odds of severe, uncontrolled hypertension (men blood pressure 222 ± 28/141 ± 15 mmhg) in n urbn popultion of Africn- Americn nd Hispnic ptients. 2 Illicit drug use or one or more lcohol-relted problems were not found to be independent risk fctors for severe, uncontrolled hypertension. In the present study of hypertensive individuls, in which ptients were mtched for the previously known hypertensive crisis risk fctors of ge, sex nd rce, less effective control of out-ptient systolic blood pressure ws found to be n independent risk fctor for hypertensive crisis. Although intuitively expected to be risk fctor, less well-controlled out-ptient blood pressure hs not been reported previously s risk fctor for hypertensive crisis. However, in study of 189 ptients who underwent digestive trct surgery, men pre-opertive systolic blood pressure ws n independent risk fctor for development of postopertive hypertensive urgency. 9 In tht study, for every 1 mmhg increse in pre-opertive systolic blood pressure, the odds rtio for development of postopertive hypertensive urgency ws 1.16, representing 16% increse in risk for every 1 mmhg increse in systolic pressure. 9 Therefore, in the post-surgicl setting, higher pre-opertive blood pressure is ssocited with n incresed risk of post-opertive hypertensive crisis. 424 Fmily Prctice n interntionl journl TABLE 4 Odds rtios for n Emergency Deprtment visit due to hypertensive crisis bsed on vrying increments of out-ptient systolic nd distolic blood pressure Odds rtio (95% CI) Increse in systolic blood pressure 10 mmhg 1.30 ( ) 5 mmhg 1.14 ( ) 1 mmhg 1.03 ( ) Increse in distolic blood pressure 10 mmhg 1.21 ( ) b 5 mmhg 1.10 ( ) b 1 mmhg 1.02 ( ) b P 0.001; b P = In ddition, s mentioned bove, non-dherence with ntihypertensive mediction hs been shown to be risk fctor for hypertensive crisis, 2 presumbly s result of less effective blood pressure control. The design of the present study precluded n nlysis of ptient complince with ntihypertensive mediction, nd therefore it is unknown whether the poorer control of out-ptient blood pressure in the hypertensive crisis group ws result of mediction non-dherence, indequte response to specific ntihypertensive medictions or both. In ny event, the results of the present study further underscore the importnce of dequte blood pressure control for voidnce of episodes of hypertensive crisis. We hypothesized tht history of hert filure or renl dysfunction is lso n independent risk fctor for hypertensive crisis. Neither of these conditions independently incresed the odds of hospitl presenttion with hypertensive crisis. However, trend towrds sttisticl significnce ws present for history of hert filure, with n OR of Hert filure is ssocited with well-known elevtions in plsm norepinephrine, ngiotensin II, endothelin, ldosterone nd vsopressin concentrtions, 4,5 ll of which re vsoconstricting nd/or sodium-retining substnces tht my contribute to elevtion of blood pressure. Further study is necessry to determine whether hert filure is indeed n independent risk fctor for hypertensive crisis, nd lso to estblish whether control of hert filure symptoms or slowing of the progression of hert filure my reduce the risk of hypertensive crisis. Limittions of this investigtion should be cknowledged. This ws retrospective cohort tril, subject to the potentil bises of such studies. As mentioned previously, informtion regrding ptient dherence with ntihypertensive medictions ws not vilble. Therefore, the impct of mediction nondherence s risk fctor for hypertensive crisis could not be evluted in this study. Additionl study is required to define the reltive impct of mediction non-dherence on the risk of hypertensive crisis. The blood pressure definition of hypertensive crisis used in this study ( 180/110 mmhg) ws lower thn tht used in some previous studies. 2 However, our definition of hypertensive crisis ws bsed both on clinicl signs/symptoms of hypertensive crisis tht resulted in ptient presenttion to the Emergency Deprtment nd on presenting blood pressure in the stge 3 rnge s defined by the sixth report of the Joint Ntionl Committee on Prevention, Detection, Evlution, nd Tretment of High Blood Pressure (JNC-VI) guidelines. 8 The definition of hypertensive crisis used in this study is therefore cliniclly relevnt, nd is consistent with the definition of hypertensive crisis s defined in JNC-VI 8 s well s other published definitions Clinicl implictions Less effective out-ptient blood pressure control, s represented by out-ptient systolic blood pressure mesurements, is n independent risk fctor for hypertensive
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