title: Serum angiotensin-converting enzyme and recurrent vascular events. The SMART-MR study.
abstract: OBJECTIVE
  Chronic exposure to high levels of angiotensin-converting enzyme (ACE) might increase the risk of hypertensive cardiovascular events. However, little data are available on the association of direct measures of ACE activity with vascular risk and disease. We examined whether serum ACE levels were associated with the risk of recurrent vascular events.
  
  
  METHODS
  Within the SMART-MR study, a prospective cohort study among patients with symptomatic atherosclerotic disease, analyses were performed in 950 patients (mean age 58 ± 10 years) without use of ACE-inhibitors or angiotensin II receptor blockers. At baseline, participants underwent a vascular screening and serum ACE levels (U/L) were measured. Patients were followed for recurrent vascular events, including vascular death, ischemic stroke, and ischemic coronary heart disease (CHD).
  
  
  RESULTS
  After a mean follow up of 7.2 years (range 0.2-10.1 years), we documented 55 cases of vascular death, 33 cases of ischemic stroke, and 77 cases of ischemic CHD. Multivariable Cox-regression models showed that higher baseline ACE levels were associated with an increased risk of ischemic stroke and CHD; HR's (95%CI) were 1.7 (1.0-2.7) and 1.8 (1.2-2.9). High ACE particularly increased risk of stroke in patients with high blood pressure (defined as >140/90 mmHg) (HR = 4.8; 95%CI 1.0-19.4). This relation was independent of several confounders including use of antihypertensive medication. Serum ACE was not significantly associated with risk of vascular death.
  
  
  CONCLUSIONS
  Our results suggest that in a population with high vascular risk, higher serum ACE levels contribute to an increased risk of ischemic stroke and CHD events.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
authors.forename: Hadassa M
authors.initials: HM
authors.lastname: Jochemsen
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Geerlings
authors.forename: Frank L
authors.initials: FL
authors.lastname: Visseren
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Majon
authors.initials: M
authors.lastname: Muller
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A