Response to Statin Therapy in Obstructive Sleep Apnea Syndrome: A Multicenter Randomized Controlled Trial

Abstract

Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m2. In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (−0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: −6.34 mmHg (−12.68; −0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.

Effect of 12-month intervention with low-dose atorvastatin on pulse wave velocity in subjects with type 2 diabetes and dyslipidaemia

“…The impact of statin administration on arterial stiffness has been examined in healthy individuals and in subjects with either hypertension, hypercholesterolaemia, chronic obstructive pulmonary disease, obstructive sleep apnoea, chronic kidney disease or obesity. [17][18][19][20][21][22][23][24][25][26][27] The results of these studies were either negative [25][26][27] or they showed a non-significant trend for reduction of PWV. 17,18,21 The study with the longest duration was performed by Fassett et al 18 in 37 patients with chronic kidney disease who were randomly assigned to receive either 10 mg of atorvastatin or placebo for 3 years.…”

“…In addition, several studies in non-diabetic population reported conflicted results. [17][18][19][20][21][22][23][24][25][26][27] Two recent meta-analyses, examined the impact of statin treatment on PWV and concluded that statin treatment reduced PWV; however, these meta-analyses did not include studies in people with T2DM, and there was significant heterogeneity in the studies analysed. 28,29 The main aim of this prospective non-randomized observational study was to examine the impact of treatment with either 10 mg atorvastatin plus diet or diet alone for 12 months on cf-PWV in subjects with T2DM and dyslipidaemia, who were free of clinically apparent macrovascular disease.…”

Beneficial effect of continuous positive airway pressure on lipid profiles in obstructive sleep apnea: a meta-analysis

“…The correlation between change in inflammatory parameters and the effect of CPAP on lipid profiles could not be concluded because only a few of recruited studies provided such information. However, one recent study by Joyeux-Faure showed that the statin therapy known for anti-inflammatory effect had no effect on inflammatory or autonomic activity markers despite its lipid-lowering effect [ 48 ].…”

Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets

“…Among patients undergoing percutaneous coronary intervention, OSA was an independent predictor of lower effectiveness of antiplatelet therapy ( 120 ). Statin treatment in OSA patients lowered blood pressure and corrected lipid panel, but did not affect early atherosclerosis ( 121 ). This observation leads to questioning whether platelets should be considered a therapeutic target in OSA or rather a component of pathogenetic pathways.…”