Response to Sympathetic Activity, Heart Failure, Obesity, and Metabolic Syndrome: Is There Any Role for Sleep Apnea?
We appreciate the interest expressed by Drager et al1 for our recent article on the sympathoexcitatory effects of metabolic syndrome (MS) in heart failure patients.2 In brief, in our study we found that sympathetic nerve traffic was markedly increased in heart failure and more so in patients combining this disease with MS. It should be worthy of mention that in our study the additive sympathoexcitation was evident for a similar impairment in left ventricular ejection fraction in the 2 groups, and the major determinants of this exceedingly high adrenergic drive were waist circumference and body mass index.
In their letter, Drager et al1 underline the importance of obstructive sleep apnea (OSA) as a crucial variable to be taken into account when dealing with MS. They also suggest that a large part of the sympathetic overdrive that we observed depends on OSA-related mechanisms rather than on the clustering of metabolic, as well as blood pressure, abnormalities characterizing this condition.
We agree that OSA may not participate as an “innocent bystander” in the neurogenic abnormalities characterizing MS. It is likely, however, that the sympathetic overdrive is not exclusively an OSA-dependent phenomenon. At least 4 good reasons support this hypothesis. First, a number of studies has shown that >50% of heart failure patients who do not have MS display at the polysomnographic evaluation OSA, which is, thus, an important contributor to sympathetic activation regardless of the presence or absence of this condition. Second, we previously observed a clear-cut increase in muscle sympathetic nerve traffic in obese subjects (ie, in subjects with an important MS component) without any evidence of OSA.3 Third, similar findings have been reported recently in heart failure patients, in which sympathetic activation was detectable even when the apnea/hypopnea index was within the reference range.4 Fourth, in a recent study we examined the relative contribution of OSA to the MS-related sympathetic activation.5 To this aim we evaluated MS patients without and with polysomnographic evidence of OSA matched for other confounders. The results show that OSA explains no more than one third of the adrenergic overdrive seen in MS, thus again stressing the relevance of extra-OSA mechanisms in the phenomenon.
Finally, Drager et al1 highlight the favorable effects of continuous positive airway pressure in OSA. It is worthy of mention, however, that a recent study performed in heart failure correction of OSA by this procedure did not improve survival.6 Because sympathetic activation has unequivocal prognostic importance in heart failure, this may, albeit very indirectly, support the hypothesis that in this condition OSA does not play a majorsympathoexcitatory role. The data may also suggest, however, that on clinical grounds, OSA may not represent a major cause of death in these patients.
Drager LF, Krieger EM, Lorenzi-Filho G. Sympathetic activity, heart failure, obesity, and metabolic syndrome: is there any role for obstructive sleep apnea? Hypertension. 2007 ;49: e38.
Grassi G, Seravalle G, Quarti Trevano F, Scopelliti F, Dell’Oro R, Bolla G, Mancia G. Excessive sympathetic activation in heart failure with obesity and metabolic syndrome: characteristics and mechanisms. Hypertension. 2007; 49: 535–541.
Grassi G, Facchini A, Quarti Trevano F, Dell’Oro R, Arenare F, Tana F, Bolla G, Monzani A, Robuschi M, Mancia G. Obstructive sleep apnea-dependent and -independent adrenergic activation in obesity. Hypertension. 2005; 46: 321–325.
Spaak J, Egri ZJ, Kubo T, Yu E, Ando S, Kaneko Y, Usui K, Bradley TD, Floras JS. Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea. Hypertension. 2005; 46: 1327–1332.
Scopelliti F, Seravalle G, Quarti Trevano F, Facchini A, Arenare F, Rozzoni A, Tana F, Robuschi M, Bolla GB, Grassi G, Mancia G. Sleep apnoea syndrome potentiates the neuroadrenergic and metabolic alterations characterizing patients with metabolic syndrome. J Hypertens. 2006; 24 (suppl 4): S145. Abstract.