Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome

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Abstract

Purpose

Polycystic ovary syndrome (PCOS) is frequently accompanied by the presence of cardiovascular risk factors. It has also been recognized that there is a significant relationship between the autonomic nervous system and adverse cardiac events. Heart rate recovery (HRR) after exercise is a marker of parasympathetic activity and attenuation of this parameter has been shown to be associated with increased cardiac mortality. A delayed recovery of systolic blood pressure (SBP) after peak exercise has been found to have diagnostic value and might reflect sympathetic hyperactivity. The analysis of variations in heart rate has also been used to determine the balance between sympathetic and vagal nerve activities in the heart. Our objective was to determine HRR, the SBP response to exercise and heart rate variability (HRV) in patients with PCOS.

Methods

The study population consisted of 26 untreated patients with PCOS and 24 healthy controls who were matched with respect to age, body mass index and physical activity. All subjects underwent symptom-limited exercise tolerance test according to a modified Bruce protocol. Following peak exercise, subjects walked a 2-min cool-down period. Heart rate recovery was calculated as the difference between heart rate at peak exercise and heart rate at the relevant minute of recovery. Blood pressure recovery indexes were determined by dividing the systolic blood pressure at 1, 2 and 3 min in recovery to the systolic blood pressure at peak exercise.

Results

HRR at 1 min (HRR1) of the patients with PCOS were significantly lower than that of controls (20 ± 4 vs 28 ± 8 bpm, p < 0.0001). Although, resting SBP of the two groups were similar (117 ± 7 vs 117 ± 10 mmHg, p = 0.663), the SBP of the patients with PCOS at peak exercise were significantly higher when compared to controls (172 ± 12 vs 156 ± 14 mmHg, p < 0.0001). In addition, the SBP of the patients with PCOS remained significantly elevated when compared to controls at the first, second and third minute of recovery (168 ± 13 vs 148 ±15 mmHg, 162 ± 13 vs 136 ± 16 mmHg, 152 ± 17 vs 127 ± 15 mmHg, respectively, p < 0.0001 for all three). The SBP recovery index at 2 and 3 min of the patients with PCOS were significantly higher than that of controls (0.93 ± 0.04 vs 0.87 ± 0.07, p < 0.0001 and 0.87 ± 0.07 vs 0.82 ±0.09, p = 0.017, respectively). Both time domain and frequency domain parameters of patients with PCOS were significantly lower than that of controls.

Conclusion

This study shows that the patients with PCOS have attenuated HRR1, exaggerated SBP response to exercise which is delayed to recover and a depressed HRV. These findings might also suggest alterations in autonomic neurol control of the cardiovascular system in this disorder.

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women in their reproductive years, with a prevalence of up to 10% [1]. It is characterized by chronic anovulation and hyperandrogenism, and is frequently accompanied by the presence of cardiovascular risk factors. Specific risk factors that have been reported include hyperlipidemia [2], obesity [3], insulin resistance [4] and elevations in C-reactive protein [5]. That, in turn, has led to concern about the effect of PCOS on long-term health, particularly with regard to diabetes, hypertension and coronary heart disease. In addition, women with PCOS have been found to exhibit endothelial dysfunction [6] and increased atherosclerosis in cross-sectional studies involving angiography [7], increased coronary calcium by computed tomography [8] and increased carotid intima-media thickness by ultrasound [6], [9]. Yet, it is not clear that these findings translates into increased cardiovascular mortality [10].

It has been also recognized that there is a significant relationship between the autonomic nervous system and cardiovascular mortality [11]. Heart rate recovery (HRR) after exercise is a marker of parasympathetic activity [12], [13], and attenuation of this parameter has been shown to be associated with increased long-term mortality [14], [15]. A delayed recovery of systolic blood pressure (SBP) after peak exercise has been found to have diagnostic value [16] and might reflect sympathetic hyperactivity [17], [18]. In addition, the analysis of variations in heart rate has also been used to determine the balance between sympathetic and vagal nerve activities in the heart [19]. Although activation of the sympathetic neurons innervating the ovary might precede the development of cystic ovaries [20], there is limited data on sympathetic and parasympathetic activity in women with PCOS [21]. Therefore, in the present study, we sought to determine the autonomic activity in patients with PCOS utilizing the parameters derived from a treadmill exercise test and a 24 h-Holter recording.

Section snippets

Study population

Study population consisted of 26 untreated patients with PCOS and 24 healthy controls. PCOS is defined as the presence of all of following three criteria: (i) polycystic ovaries; (ii) oligo-/anovulation; and (iii) clinical or biochemical evidence of hyperandrogenism after the exclusion of adrenal enzymatic deficiencies, Cushing's syndrome and tumors. Anovulation was defined as serum progesterone < 3 ng/ml. Clinical hyperandrogenism was defined by the presence of hirsutism, acne, or androgenic

Results

The baseline clinical characteristics of patients with PCOS and controls are given in Table 1. Both groups included young subjects with a mean age of around 26 years. The groups were well matched with respect to age, body mass index and physical activity. The biochemical parameters of patients with PCOS were comparable with those of control subjects. However, patients with PCOS had nonsignificantly higher levels of triglycerides, testosterone, insulin and LH than that of controls.

Exercise test

Discussion

The major findings of this study are that the patients with PCOS have an attenuted HRR1, an exaggerated SBP response to exercise which is delayed to recover and a depressed HRV.

The increase in heart rate that accompanies exercise is due in part to a reduction in vagal tone. Recovery of the heart rate immediately after exercise, especially during the first minute, is a function of vagal reactivation [12], [13]. Thus, HRR1 after treadmill exercise has been widely accepted as an indicator of

References (47)

  • A.J. van Boven et al.

    Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preserved left ventricular function. REGRESS Study Group

    Am Heart J

    (1998)
  • J.T. Bigger et al.

    Frequency domain measures of heart period variability to assess risk late after myocardial infarction

    J Am Coll Cardiol

    (1993)
  • G.R. Sandercock et al.

    The reliability of short-term measurements of heart rate variability

    Int J Cardiol

    (2005)
  • R.E. Kleiger et al.

    Time domain measurements of heart rate variability

    Cardiol Clin

    (1992)
  • U. Heider et al.

    Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries

    Fertil Steril

    (2001)
  • R.A. Lobo et al.

    Psychological stress and increases in urinary norepinephrine metabolites, platelet serotonin, and adrenal androgens in women with polycystic ovary syndrome

    Am J Obstet Gynecol

    (1983)
  • L. Lind et al.

    Heart rate recovery after exercise is related to the insulin resistance syndrome and heart rate variability in elderly men

    Am Heart J.

    (2002)
  • E. Carmina et al.

    Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women

    J Clin Endocrinol Metab

    (1999)
  • R.A. Wild et al.

    Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome

    J Clin Endocrinol Metab

    (1985)
  • R. Azziz et al.

    PCOS/Troglitazone Study Group. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial

    J Clin Endocrinol Metab

    (2001)
  • A. Dunaif et al.

    Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome

    Diabetes

    (1989)
  • N. Boulman et al.

    Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease

    J Clin Endocrinol Metab

    (2004)
  • M.A. Birdsall et al.

    Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization

    Ann Intern Med

    (1997)
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