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Cardiovascular autonomic neuropathy (CAN)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Cardiac autonomic neuropathy (CAN) is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes.

  • there have been recommended five simple tests, the cardiac autonomic reflex tests, to establish the diagnosis (1):
    • 1) heart rate variability (HRV) with deep breathing
    • 2) HRV lying to standing
    • 3) the Valsalva manoeuvre;
    • 4) postural fall in blood pressure; and
    • 5) blood pressure response to sustained handgrip

    • a single abnormal test may indicate early CAN, and three positive tests are recommended for a definitive diagnosis (1,2)

  • prevalence data are highly dependent on the diagnostic criteria, type of tests and normative data sets used, age, and gender
    • rates are reported as high as 35% in type 1 DM and 44% in type 2 DM, with a prevalence rate of up to 60% in longstanding diabetics (3)

  • association with increased mortality risk
    • older studies have shown 5-year mortality rates as high as 16-50 % in T1DM and T2DM, with a high proportion attributed to sudden cardiac death (4,5)
    • more recently published meta-analysis included 2,900 subjects with diabetes reported a pooled relative risk of mortality of 3.45 (95 % CI, 2.66-4.47) in patients with CAN (6)

  • progression of CAN usually begins with parasympathetic denervation, followed by sympathetic tone enhancement and eventually sympathetic denervation
    • resting tachycardia is often the presenting sign (ranging from 100 to 130 bpm)
      • as CAN progresses in severity then there is a decrease in heart rate
    • baroreflex sensitivity
      • in subclinical CAN will initially have abnormalities in HRV - this is then followed by changes in baroreflex sensitivity (1)
      • in advanced CAN, orthostasis will result secondary to sympathetic denervation along with impaired baroreflex sensitivity and decreased noradrenaline response to change in posture

Management:

  • seek expert advice
    • weight loss in obese diabeticss and aerobic exercise for patients with both type 1 and type 2 DM has been shown to improve HRV and cardiac autonomic functionality (1,2)
    • early and comprehensive glycaemic control is believed to help prevent diabetic complications and potentially reverse CAN symptoms (1,2)
    • pharmaceutical management of HRV is controversial - there is no definitive treatment - agents considered include beta blockers, digoxin, verapamil and ACE inhibitors
      • treatment of orthostatic hypotension is required in general only when patients are symptomatic

Reference:

  • Ewing DJ et al. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8 (5):491-498.
  • Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014; 5 (1):17-39.
  • Pop-Busui R. What do we know and we do not know about cardiovascular autonomic neuropathy in diabetes? J Cardiovasc Transl Res 2012; 5: 463-468.
  • Navarro X, Kennedy WR, Sutherland DE. Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation. Diabetologia. 1991; 34(Suppl 1):S108-S112.
  • Ewing DJ, Campbell IW, Clarke BF. Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. Annals of Internal Medicine. 1980; 92:308-311.
  • Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care. 2003; 26:1895-1901

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