Alterations in heart rate variability in patients with peripheral arterial disease requiring surgical revascularization have limited association with postoperative major adverse cardiovascular and cerebrovascular events.

OBJECTIVE: Obstructive sleep apnea (OSA) is common in peripheral arterial disease (PAD) and associates with high mortality after surgery. Since abnormal heart rate variability (HRV) is predictive of postoperative complications, we investigated the relations of HRV with PAD, OSA and major adverse cardiovascular and cerebrovascular events (MACCE). MATERIALS AND METHODS: Seventy-five patients (67±9 years) scheduled for sub-inguinal revascularization and 15 controls (63±6 years) underwent polysomnography and HRV analyses. OSA with an apnea-hypopnea index (AHI) ≥20/hour was considered significant. HRV was measured during wakefulness, S2, S3-4 and rapid eye movement (REM) sleep with time and frequency domain methods including beat-to-beat variability, low frequency (LF) and high frequency (HF) power, and detrended fluctuation analysis (DFA). MACCE was defined as cardiac death, myocardial infarction, coronary revascularization, hospitalized angina pectoris and stroke. RESULTS: Thirty-six patients (48%) had AHI≥20/hour. During follow-up (median 52 months), 22 patients (29%) suffered a MACCE. Compared to controls, fractal correlation of HRV (scaling exponent alpha 1 measured with DFA) was weaker during S2 and evening wakefulness in all subgroups (+/-AHI≥20/hour, +/-MACCE) but only in patients with AHI≥20/hour during morning wakefulness. The LF/HF ratio was lower in all subgroups during S2 but only in patients with AHI ≥20/hour during evening or morning wake. In the covariance analysis adjusted for age, body mass index, coronary artery disease and PAD duration, the alpha 1 during morning wakefulness remained significantly lower in patients with AHI≥20/hour than in those without (1.12 vs. 1.45; p = 0.03). Decreased HF during REM (p = 0.04) and S3-4 sleep (p = 0.03) were predictive of MACCE. In analyses with all sleep stages combined, mean heart rate as well as very low frequency, LF, HF and total power were associated with OSA of mild-to-moderate severity (AHI 10-20/hour). CONCLUSIONS: HRV is altered in patients with PAD. These alterations have a limited association with OSA and MACCE.

The Leu7Pro polymorphism of preproNPY is associated with decreased insulin secretion, delayed ghrelin suppression, and increased cardiovascular responsiveness to norepinephrine during oral glucose tolerance test.

CONTEXT: Neuropeptide Y (NPY) plays a role in angiogenesis, cardiovascular regulation, and hormone secretion. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY is associated with vascular diseases and has an impact on hormone levels in healthy subjects. OBJECTIVE: The current study investigated the role of the Leu7Pro polymorphism in metabolic and cardiovascular autonomic regulation. DESIGN AND SUBJECTS: A 5-h oral glucose tolerance test was performed on 27 healthy volunteers representing two preproNPY genotypes (Leu7/Pro7 and Leu7/Leu7) matched for age, sex, body mass index and physical activity. MAIN OUTCOME MEASURES: Simultaneously we performed cardiovascular autonomic function tests and plasma measurements of sympathetic transmitters, glucose, insulin, and ghrelin. RESULTS: The subjects with Leu7/Pro7 genotype had decreased plasma NPY, norepinephrine (NE), and insulin concentrations and insulin to glucose ratios. The suppression of ghrelin concentrations after glucose ingestion was delayed in these subjects. They also had increased heart rate variability indices and baroreflex sensitivity. However, they displayed significant negative association of NE concentration with variability of low-frequency R-R-intervals and with baroreflex sensitivity. CONCLUSIONS: The Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test. The increased responsiveness of autonomic functions to NE associated with the polymorphism may be connected to increased cardiovascular vulnerability.

Beat-to-beat oscillations in pulse pressure.

We compared 5-min standard deviations (SD) and frequency domain measures of beat-to-beat pulse pressure (PP) variability with those of RR-interval, systolic (SBP) and diastolic (DBP) blood pressure variabilities, and with cross-spectral baroreflex sensitivity (BRS) in a population-based sample of 150 healthy individuals, aged 35-64 years. Beat-to-beat variability of PP was composed of similar frequency components as the other spectral variabilities, and was closely related to SBP variability. The proportion of high frequency (HF) component from overall variability was higher in PP variability than in SBP and DBP variabilities. The low frequency (LF) component and the SD of beat-to-beat PP correlated inversely with BRS (-0.48 and -0.32, respectively; P<0.001 for both). To test a hypothesis that arterial stiffening is associated with increased beat-to-beat oscillation in PP, we examined associations of beat-to-beat PP variability with risk factors of atherosclerosis, i.e. with age, gender, smoking, blood pressure, body mass index, serum lipids, glucose, insulin and homeostasis model assessment of insulin resistance. The SD of beat-to-beat PP variability correlated with age (0.21, P = 0.010), PP (0.31, P<0.001) and body mass index (0.22, P = 0.008). The LF component of PP variability correlated not only with age (0.17, P = 0.041), PP (0.27, P = 0.001) and body mass index (0.22, P = 0.007), but also with serum insulin (0.17, P = 0.042), homeostasis model assessment of insulin resistance (0.18, P = 0.031) and serum triglycerides (0.16, P = 0.048). Our findings suggest that increased beat-to-beat oscillation of PP reflects arterial stiffening and impaired baroreflex function.