The effects of preventive
interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined
the effect of intensively treating traditional risk factors for CAN, including
hyperglycemia, hypertension, and dyslipidemia, in persons with type 2 diabetes
(T2D) and high cardiovascular risk participating in the Action to Control
Cardiovascular Risk in Diabetes (ACCORD) trial.
Research Design and Methods: CAN was defined as heart
rate variability indices below the 5th percentile of the normal
distribution. Of 10,250 ACCORD participants, 71% (n=7,275) had a CAN evaluation
at study entry and at least once after randomization. The effects of intensive
interventions on CAN were analyzed among these subjects through generalized
linear mixed models.
Results: As compared to standard intervention,
intensive glucose treatment reduced CAN risk by 16% (OR=0.84, 95%CI 0.75–0.94,
p=0.003) – an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR= 0.73, 95%CI
0.63–0.85, p<0.0001) rather than those with CVD (OR=1.10, 95%CI 0.91–1.34,
p=0.34) (p for interaction=0.001). Intensive blood pressure intervention
decreased CAN risk by 25% (OR=0.75, 95% CI 0.63–0.89, p=0.001), especially in
patients ≥65 years old (OR=0.66, 95% CI 0.49–0.88, p=0.005) (p for interaction
=0.05). Fenofibrate did not have a significant effect on CAN (OR=0.91, 95%CI 0.78–1.07,
Conclusions: These data confirm a beneficial effect of
intensive glycemic therapy and demonstrate, for the first time, a similar
benefit of intensive blood pressure control on CAN in T2D. A negative CVD
history identifies T2D patients who especially benefit from intensive glycemic
control for CAN prevention.
Y.T. was supported by a Mary K.Iacocca Fellowship from the Iacocca Foundation. R.P.B. was supported by NIH/NIDDK R01 DK107956-01, NIH U01 DK119083, and the JDRF Center of Excellence at the University of Michigan. The study was also supported by NIH grant DK36836 (Enrichment Core of the Diabetes Research Center at the Joslin Diabetes Center). The ACCORD clinical trial was funded by the National Heart, Lung, and Blood Institute (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010); by other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; and by General Clinical Research Centers. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.