To the editor
We have read with great interest the study by Gabryelska et al,1 suggesting that serum hypoxia-inducible factor-1α (HIF-1α) protein might serve as a promising diagnostic marker in obstructive sleep apnea (OSA), after exclusion of some chronic hypoxia disorders. The marker showed an area under the curve (AUC) of 0.841 for a cutoff value of 1055.6 pg/ml, with high sensitivity, specificity, and positive predictive value. In addition, no circadian fluctuation was demonstrated.1
A previous meta-analysis of prospective studies showed that moderate and severe OSA is associated with a significant increase in the risk of major adverse cardiovascular events, irrespective of the presence of comorbidities, as well as coronary artery disease, while severe OSA also increases the risk of stroke and cardiovascular and all-cause mortality.2
Serum HIF-1α levels have been previously shown to correlate with the coronary artery calcification (CAC) score in a cohort of 405 asymptomatic patients with type 2 diabetes (r = 0.36, P <0.001), with an AUC of 0.775, a sensitivity of 61.1%, and a specificity of 87.6% for predicting the extent of CAC (cutoff value, 236.5 pg/ml).3 These findings might imply that the serum HIF-1α level is an independent risk factor for CAC in patients with type 2 diabetes, a frequent comorbidity in OSA.3
Another observational study including 296 patients with acute decompensated heart failure demonstrated that serum HIF-1α levels were higher in these patients compared with healthy controls (P <0.001), while they were also significantly higher in patients with heart failure with reduced ejection fraction, compared with patients with heart failure with preserved ejection fraction.4 Of note, serum HIF-1α levels were higher in patients who died during follow-up as compared with survivors (P <0.001).4 In addition, investigators documented that serum HIF-1α levels positively correlated with the concentrations of N-terminal fragment of the prohormone brain natriuretic peptide (r = 0.337, P <0.001) and cardiac troponin T (r = 0.357, P <0.001), while they negatively correlated with left ventricular ejection fraction (r = −0.332, P <0.001) and systolic blood pressure (r = −0.145, P = 0.013). However, no association between serum HIF-1α levels and in-hospital mortality was observed in the fully adjusted Cox regression model. Finally, the AUC of serum HIF-1α in predicting the type of acute decompensated heart failure was shown to be 0.73, with a sensitivity of 35.2% and a specificity of 90%, for the cutoff value of 3.62 ng/ml.4
To sum up, serum HIF-1α levels might have significant diagnostic and even prognostic value in patients with either asymptomatic or symptomatic cardiovascular disease (CVD). It would be interesting if Gabryelska et al1 could perform a subgroup analysis assessing whether there is a difference in serum HIF-1α levels among enrolled patients with OSA according to the CVD status at baseline. Of course, large-scale prospective studies are required to investigate whether this biomarker could provide prognostic information on the development of CVD and its manifestation in patients with OSA.
Patoulias Dimitrios, MD, MSc, PhD (c), 2nd Propedeutic Department of Internal Medicine, General Hospital “Hippokration,” Konstantinoupoleos 49, 54 642 Thessaloniki, Greece, phone: +30 2310892354, email: dipatoulias@gmail.com
February 27, 2020.
Dimitrios Patoulias, Alexandra Katsimardou, Maria-Styliani Kalogirou, Maria Toumpourleka, Michael Doumas (DP, AK, MSK, MT, MD: 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, General Hospital “Hippokration,” Thessaloniki, Greece; MD: Veterans Affairs Medical Center, George Washington University, Washington, District of Columbia, United States)
Patoulias Dimitrios, MD, MSc, PhD (c), 2nd Propedeutic Department of Internal Medicine, General Hospital “Hippokration,” Konstantinoupoleos 49, 54 642 Thessaloniki, Greece, phone: +30 2310892354, email: dipatoulias@gmail.com
None declared.
Patoulias D, Katsimardou A, Kalogirou MS, et al. Hitting two birds with one stone: the potential role of serum hypoxia-inducible factor-1α protein levels in obstructive sleep apnea–related cardiovascular disease. Pol Arch Intern Med. 2020; 130: 161-162. doi:10.20452/pamw.15219
- 1.
- Gabryelska A, Szmyd B, Panek M, et al. Serum hypoxia-inducible factor-1α protein level as a diagnostic marker of obstructive sleep apnea. Pol Arch Intern Med. 2020; 130: 158-160.Crossref
- 2.
- Xie C, Zhu R, Tian Y, Wang K. Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis. BMJ Open. 2017; 7: e013983.
- 3.
- Li G, Lu WH, Ai R, et al. The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients. Cardiovasc Diabetol. 2014; 13: 52.
- 4.
- Li G, Lu WH, Wu XW, et al. Admission hypoxia-inducible factor 1α levels and in-hospital mortality in patients with acute decompensated heart failure. BMC Cardiovasc Disord. 2015; 15: 79.