This study describes a significant association between post exercise slow HRR and increased levels of inflammatory markers in young PCOS women.
Post exercise HRR has been demonstrated as a risk factor for cardiovascular and all-cause mortality in healthy adults [10
], in individuals with CVD [30
] in individuals with risk factors for CVD [31
] and in men with diabetes [33
]. HRR is positively associated with insulin sensitivity as measured with a hyperinsulinemic-euglycemic clamp and metabolic syndrome in elderly men [34
] as well as in middle-aged men and women [35
HRR has also been found to be associated with individual components of the metabolic syndrome, such as blood glucose [36
] low HDL-C [34
] and resting systolic and diastolic blood pressure [35
]. Panzer et al.
] demonstrated a strong inverse relationship between fasting plasma glucose and HRR even at non-diabetic levels among middle-aged healthy men and women. Moreover, HRR has been shown to be inversely associated with triglyceride/HDL-C ratio in middle-aged healthy men and women [37
Although IR is not a key criterion to diagnose PCOS [26
], there is a wide consensus that subjects with PCOS are more insulin resistant than healthy women. IR has been found to be significantly associated with impaired cardiopulmonary functional capacity [6
]. Moreover, abnormal HRR was significantly associated to BMI and to AUCINS
(a powerful marker of IR), suggesting that impaired glucose metabolism in young overweight PCOS women might be a determinant of autonomic dysfunction [14
]. Unfortunately, the cross sectional nature of the present study does not allow the evaluation of a causal association between autonomic dysfunction and IR and the elucidation of the mechanisms involved in the pathogenesis of both conditions.
It is known that inflammation plays an important role in the development and progression of atherosclerosis [39
], and inflammatory markers such as CRP and WBCs count are strong predictors of cardiovascular events in healthy populations as well as patients with coronary heart disease [40
Higher CRP levels and WBCs count have been described [4
] in a wide PCOS women population suggesting an increased cardiovascular risk profile in these patients [2
]. Observational studies showed a decreased autonomic nervous system activity related to inflammatory markers [22
]. Recent experimental evidences suggest a role for the parasympathetic nervous system in the direct regulation of inflammation, pointing to the existence of a cholinergic anti-inflammatory reflex [24
]. Recently, Vieira et al.
] reported that post exercise HRR is independently associated with lower CRP in older sedentary individuals, suggesting an involvement of parasympathetic nervous system in regulating chronic inflammation in older adults. Moreover, it has been recently reported that the reduced cardiac adrenergic activity (evaluated by iodine-123-labeled metaiodobenzylguanidine uptake) observed in patients with glucose intolerance was associated to elevated pro-inflammatory cytokine levels [42
The association between autonomic nervous system and systemic inflammation in young PCOS women after adjustment for common cardiovascular and metabolic confounders shed light on the complex mechanisms and the possible therapeutic strategies related to this endocrine-cardiometabolic disease.
Experimental and clinical evidences suggest that exercise training is an effective therapeutic intervention aimed at improving autonomic function as well as cardiopulmonary functional capacity [43
]. In PCOS women, the exercise-induced improvement of cardiopulmonary and autonomic function should have been addressed to the improvement in insulin sensitivity, to the reduction in BMI, and to the powerful anti-inflammatory effect of training [46
]. However, exercise training should be continued regularly in order to maintain the described beneficial effects [48
Our previous prospective controlled data [46
], in fact, confirmed that exercise training is effective in reducing BMI and improving insulin sensitivity markers in PCOS women, even thought no significant changes in sex hormones were observed. At this regard, it could be possible to hypothesize that the exercise induced improvement of autonomic function is mediated by BMI reduction and insulin sensitivity improvement.
Recently, Thompson et al.
] studied the effect of weight loss on HRR in overweight and obese PCOS patients. After 10 weeks of diet, a significant improvement in HRR was observed in concert with a reduction in body weight, waist circumference, blood pressure, fasting insulin and glucose levels, HOMA score, T, FAI, and with an increase in SHBG [49
]. In addition, HRR was significantly related to the reduction in body weight and waist circumference [49
]. These findings demonstrated that weight loss can exert a beneficial role in reducing the cardiovascular risk in PCOS patients also improving the autonomic function [49
Given the cross-sectional nature of the present study, it cannot be determined whether impaired autonomic function is the cause or effect of systemic inflammation. A potential limitation of our data is that we did not control for diet status, which may potentially confound the relation between HRR and inflammation markers. Because of the relation between cardiopulmonary functional capacity and HRR, strength of this study is the use of directly measured peak oxygen uptake as a covariate.