title: Pulse pressure and stroke risk: development and validation of a new stroke risk model.
abstract: OBJECTIVE
  This study aims to develop and validate a stroke risk model incorporating pulse pressure (PP) as a potential risk factor. Recent evidence suggests that PP, defined as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), could be an incremental risk factor beyond SBP.
  
  
  METHODS
  Electronic health records (EHRs) of hypertensive patients from a US integrated health delivery system were analyzed (January 2004 to May 2012). Patients with ≥ 1 PP reading and ≥ 6 months of observation prior to the first diagnosis of hypertension were randomly split into development (two-thirds of sample) and validation (one-third of sample) datasets. Stroke events were identified using ICD-9-CM 433.xx-436.xx. Cox proportional hazards models assessed time to first stroke event within 3 years of first hypertension diagnosis based on baseline risk factors, including PP, age, gender, diabetes, and cardiac comorbidities. The optimal model was selected using the least absolute shrinkage and selection operator (LASSO); performance was evaluated by the c-statistic.
  
  
  RESULTS
  Among 34,797 patients selected (mean age 59.3 years, 48% male), 4272 patients (12.3%) had a stroke. PP was higher among patients who developed stroke (mean [SD] PP, stroke: 02.0 [15.3] mmHg; non-stroke: 58.1 [14.0] mmHg, p < 0.001). The best performing risk model (c-statistic, development: 0.730; validation: 0.729) included PP (hazard ratio per mmHg increase: 1.0037, p < 0.001) as a significant risk factor.
  
  
  CONCLUSIONS
  This study was subject to limitations similar to other studies using EHRs. Only patient encounters occurring within the single healthcare network were captured in the data source. Though the model was tested internally, external validation (using a separate data source) would help assess the model's generalizability and calibration.
  
  
  CONCLUSIONS
  This stroke risk model shows that greater PP is a significant predictive factor for increased stroke risk, even in the presence of known risk factors. PP should be considered by practitioners along with established risk factors in stroke treatment strategies.
authors.affiliation: Analysis Group Inc. , Boston, MA , USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ayyagari
authors.forename: Francis
authors.initials: F
authors.lastname: Vekeman
authors.forename: Patrick
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Siew Hwa
authors.initials: SH
authors.lastname: Ong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Faust
authors.forename: Alex
authors.initials: A
authors.lastname: Trahey
authors.forename: Gerardo
authors.initials: G
authors.lastname: Machnicki
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000502:physiology*; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology* / Q000503:physiopathology
keywords: Hypertension; Pulse pressure; Risk prediction; Stroke