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Plasma Homocysteine Levels in Obstructive Sleep Apnea^*

Association With Cardiovascular Morbidity

^* From the Unit of Anatomy and Cell Biology (Dr. L. Lavie and Ms. Perelman), and Sleep Laboratory (Dr. P. Lavie), Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Correspondence to: Lena Lavie, DSc, Unit of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; e-mail: lenal{at}tx.technion.ac.il

Objectives: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality. Plasma levels of homocysteine are also associated with cardiovascular morbidity and mortality. We therefore investigated homocysteine and conventional cardiovascular risk factors in OSA patients with and without cardiovascular morbidity in comparison with normal control subjects and ischemic heart disease (IHD) patients without OSA.

Setting: Technion Sleep Medicine Center, Haifa, Israel.

Methods and participants: Levels of homocysteine, cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, creatinine, vitamins B₁₂ and B₆, and folic acid were determined in 345 participants after overnight fasting. These included OSA patients with IHD (n = 49), with hypertension (n = 61), or without any cardiovascular disease (n = 127). Two control groups were employed: IHD patients without or with low likelihood for sleep apnea (n = 35), and healthy control subjects (n = 73).

Results: After adjustment for age, body mass index, creatinine, and existence of diabetes mellitus, OSA patients with IHD had significantly higher homocysteine levels (14.6 ± 6.77 µmol/L) than all other groups including the IHD-only patients. Hypertensive OSA patients had comparable homocysteine levels to IHD patients (11.80 ± 5.28 µmol/L and 11.92 ± 5.7 µmol/L, respectively), while patients with OSA only had comparable levels to normal control subjects (9.85 ± 2.99 µmol/L and 9.78 ± 3.49 µmol/L, respectively). No differences in conventional cardiovascular risk factors or in vitamin levels were found between groups.

Conclusions: Patients with the combination of IHD and OSA have elevated homocysteine levels. We hypothesize that these results may be explained by endothelial dysfunction combined with excess free-radical formation in OSA patients.

Key Words: homocysteine • hypertension • ischemic heart disease • obstructive sleep apnea

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