title: Abnormal indices of autonomic function are no longer predictors of poor outcome in diabetic patients without neuropathy but with coexisting coronary artery disease who receive optimal pharmacological therapy.
abstract: BACKGROUND
  Cardiovascular autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) and has been regarded as a parameter associated with a poor outcome.
  
  
  OBJECTIVE
  We investigated whether indices of cardiovascular autonomic function have prognostic value in the current era of pharmacological therapy recommended for DM patients with coexisting coronary artery disease (CAD), which consists of drugs that affect autonomic balance, i.e. angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and statins.
  
  
  METHODS
  We studied 127 consecutive patients with type 2 DM and angiographically documented stable CAD (age: 64 years, women: 28%, treatment: ACEI/ARBs: 100%, statins: 98%, beta-blockers: 88%, insulin therapy: 46%). The assessment of autonomic balance within the cardiovascular system included heart rate variability (HRV) (time and spectral-domain analyses) and non-invasive evaluation of baroreflex sensitivity (sequence and controlled breathing methods). Primary end-points were cardiovascular mortality and urgent hospital admissions due to cardiovascular symptoms.
  
  
  RESULTS
  During the mean follow-up of 502 +/- 161 days, 28 patients (22%) experienced a cardiovascular event: 7 died and 21 were admitted to hospital. We found the following predictors of an increased risk of the combined end point (cardiovascular death and hospitalisation): elevated level of N-terminal BNP (for log NT-proBNP - HR = 2.6, p = 0.004), severe CAD (3-vessel disease - HR = 2.4, p = 0.02), renal insufficiency (eGFR < 60 ml/min/1.73 m2 - HR = 2.7, p = 0.008), and female gender (HR = 3.2, p = 0.002). None of the indices of autonomic balance had prognostic value (p > 0.2 for all).
  
  
  CONCLUSIONS
  In the population of diabetic patients with stable CAD who receive optimal pharmacological therapy, indices of impaired autonomic function are no longer predictors of poor outcome.
authors.affiliation: Department of Physiology, Medical University, Wroclaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Ponikowska
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Reczuch
authors.forename: Kinga
authors.initials: K
authors.lastname: Wegrzynowska-Teodorczyk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Witkowski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rydlewska
authors.forename: Ludmiła
authors.initials: L
authors.lastname: Borodulin-Nadzieja
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.forename: Darrel
authors.initials: D
authors.lastname: Francis
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D000787:Angina Pectoris / Q000453:epidemiology; D001341:Autonomic Nervous System / Q000503:physiopathology*; D017704:Baroreflex; D002318:Cardiovascular Diseases / Q000401:mortality; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000453:epidemiology; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain