title: The natural history of asymptomatic severe carotid artery stenosis.
abstract: BACKGROUND
  Although level 1 evidence supports carotid endarterectomy (CEA) for stroke prevention in patients with asymptomatic severe carotid artery stenosis (ASCAS; >70%), medical therapy alone has been promulgated by some as equally effective. The goal of this study was to determine the natural history of medically treated patients with ASCAS.
  
  
  METHODS
  Patients with ASCAS from 2005 to 2006 were identified in a health network database. Patients were included if the initial therapeutic plan involved medical therapy alone (usually because of comorbidities or patient preference). Study end points included: ipsilateral neurologic symptoms (INS) of transient ischemic attack and/or stroke, death, and INS and/or death.
  
  
  RESULTS
  There were 126 carotid arteries identified in 115 patients. Using standard duplex velocity criteria, 88 (70%) had severe (70%-89%) and 38 (30%) had very severe stenoses (VSS; 90%-99%). The average age was 73.5 years, demographic characteristics included: 66% hypertension, 64% coronary artery disease, 30% diabetes, 5% chronic kidney disease (CKD), and 86% were taking a statin drug (28% had a low-density lipoprotein level <100 mg/dL). There were 31 patients (24.6%) who developed INS during a mean follow-up of 27 months; most (23 of 31; 74%) occurred within 12 months of the initial duplex ultrasound examination; 14 (45%) were strokes. The 5-year actuarial freedom from INS was 70.1 ± 5%. Multivariate predictors of INS included: VSS (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.56-6.76; P = .002), CKD (HR, 6.25; 95% CI, 2.05-19.2; P = .001), and age (HR, 0.94; 95% CI, 0.91-0.98; P = .001). There were 41 patients (33%) who underwent eventual carotid revascularization (32 CEA, nine stent); 23 of 41 (56%) were performed for INS and 18 (44%) for plaque progression. Overall 5-year actuarial survival was 69.8% ± 4.1%. Multivariate predictors of death included: age (HR, 1.06; 95% CI, 1.03-1.1; P = .0001), chronic obstructive pulmonary disease (HR, 1.92; 95% CI, 1.08-3.41; P = .03), and diabetes (HR, 5.08; 95% CI, 2.86-9.01; P < .0001). The 5-year actuarial freedom from INS and/or death was 54 ± 4.4%. Multivariate predictors of INS and/or death were: VSS (HR, 1.98; 95% CI, 1.22-3.23; P = .006), CKD (HR, 5.46; 95% CI, 2.12-14.08; P = .0004), and diabetes (HR, 2.6; 95% CI, 1.59-4.24; P = .0001). Statin use was not protective against INS or death in this cohort.
  
  
  CONCLUSIONS
  Medically managed patients with ASCAS develop INS early, especially in patients with VSS. Medical therapy with aspirin and statins failed to control ASCAS, thus validating the role of CEA in these patients as promulgated in multiple current treatment guidelines.
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass. Electronic address: mconrad@partners.org.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Conrad
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Michalczyk
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Arissa
authors.initials: A
authors.lastname: Opalacz
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Virendra I
authors.initials: VI
authors.lastname: Patel
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: LaMuraglia
authors.affiliation: Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Cambria
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D001783:Blood Flow Velocity; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D016893:Carotid Stenosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D015897:Comorbidity; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D002317:Cardiovascular Agents; D005343:Fibrinolytic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001241:Aspirin