Lipids are biological compounds that play multiple roles in human disease. Thus, neutral lipids, such as TG are critical in energy storage and have been involved in the pathogenesis of cardiovascular diseases, metabolic syndrome, and T2DM . Lipid signaling pathways in patients with HS are poorly understood as well as the cellular mechanisms of lipid-mediated HS-induced pathogenesis. Gene expression of certain sphingolipids such as ceramide and sphingosine-1, that act as biologically active signaling molecules, have been implicated in the pathogenesis of the disease . In a recent report, Fincher et al. , showed an increased localized accumulation of neutral lipids in HS-infected tissue as a result of a great bacterial load in these lesions. Moreover, recurrence of the disease has been linked to the development of dermic and subcutaneous sinus tracts, and lipids rafts in plasma membranes of keratinocytes also play a role in the regulation of metabolic and proliferative activity of these cells in HS patients . Local steroidogenic activities in the skin have been implicated in the regulation of immune responses at local or systemic levels, and impaired of this cutaneous steroidogenesis has been linked to inflammatory skin disorders . Finally, recent studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of lipid metabolism, may have pro-inflammatory activity on macrophages and has been linked to some markers of systemic inflammation, such as hs-CRP . Nevertheless, there is no evidence to date, on its involvement in HS pathogenesis.
In clinical studies, HS patients often have higher serum TG and lower HDL-C levels than controls. The present study confirms a significant decrease in HDL-C in patients with HS compared with healthy controls. In this sense, Tsaousi et al. , found that matrix metalloproteinase 8, a collagen cleaving enzyme involved in the breakdown of extracellular matrix in normal and pathological processes, and in the degradation of ApoA1, a component of HDL particles, is one of the most highly upregulated molecules in HS lesions.
More recently, the AIP value, a logarithmically transformed ratio of molar concentrations of TG to HDL-Cholesterol, has been reported as a good marker for the risk of atherosclerosis and cardiovascular disease . AIP is an easily calculated parameter from the standard lipid profile that adds predictive value beyond that of the individual lipids and/or TC/HDL-C ratio. Furthermore, it is considered a subrogate of small LDL-C particle size distribution, with a better correlation than the LDL-C/ApoB ratio . AIP provides additional information in predicting short- and long-term outcomes in patients with acute coronary syndrome but also it may be an independent factor for the risk of type 2 diabetes mellitus and metabolic syndrome [31,32].
Interestingly, in HS patients (even after excluding the few participants on lipid-lowering agents) serum LDL-C, the traditional marker of the atherosclerotic burden was similar to controls. Nevertheless, AIP was higher in patients with HS than controls. In this sense, since HS is associated with high cardiovascular morbidity, AIP could be used as a good predictor of cardiovascular risk in these patients even in the presence of a normal lipid profile. Further studies on this matter would be interesting to perform.
In this study, AIP is related to BMI, waist circumference, blood pressure, lipid parameters, hs-CRP, and insulin resistance. Nevertheless, in the present study, AIP is an independent factor for the risk of a more severe HS, measured by the PGA. Besides, this association seems to be independent of hs-CRP, a well-known marker of inflammation. Besides, a cut-off point of 0.11 for this index has demonstrated to have a 4-fold increased risk for a PGA score ≥3. This index could be useful not only to detect patients at high risk for metabolic (obesity, diabetes, or metabolic syndrome) or cardiovascular complications (high blood pressure, cardiovascular events) but also to alert the clinician to the presence of a more severe HS.
Study strength and limitations
This is the first study assessing the role of AIP in patients with HS. Nevertheless, it has the inherent limitations of a case-control study regarding causality. Besides, as an observational study, it may be subject to some bias due to the possible existence of confounders. However, to try to avoid this issue, adjustment for multiple potential confounding factors has been carried out.