Chest
Volume 120, Issue 3, September 2001, Pages 900-908
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Clinical Investigations
Sleep and Breathing
Plasma Homocysteine Levels in Obstructive Sleep Apnea: Association With Cardiovascular Morbidity

https://doi.org/10.1378/chest.120.3.900Get rights and content

Abstract

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 ± 2.99μ mol/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.

Section snippets

Participants

We investigated fasting levels of homocysteine in a total of 345 male participants. These included three groups of OSA patients: (1) OSA patients with IHD (IHD-OSA; n = 49), of whom 21 patients had a history of myocardial infarction, 3 patients had a history of cerebrovascular accident, and 1 patient had a history of peripheral vascular disease); (2) OSA patients with hypertension only (HT-OSA; n = 61), defined as either having a history of antihypertensive treatment or BP > 140/90 mm Hg (1

Results

The demographic, clinical, and biochemical data of the five groups are presented in Table 1, Table 2. Overall, the three OSA groups were of similar severity, with mean AHI and minimum oxygen saturation varying from 33.74 to 30.1 and from 85.09 to 79.95%, respectively, with large variability within groups. The five groups were statistically significantly different in age and BMI and had a different prevalence of diabetes mellitus. In addition, they had statistically significant different

Discussion

The major finding of the present study is that the IHD-OSA group had significantly higher homocysteine levels than the IHD-only group after adjustment for major potential confounding factors. Homocysteine levels in the IHD-OSA group were also higher than those of the HT-OSA and OSA-only groups, as well as the CON group. Furthermore, the HT-OSA group had comparable levels of homocysteine to the IHD-only group.

In comparison with literature data on large-scale epidemiologic studies in nonselected

Acknowledgment

We are grateful to J. Selhub and M.R. Nadeau for performing the B6 determination and the HPLC determination for homocysteine quality control. We are grateful to the Technion Sleep Disorders Center staff for their help, and to Ms. Paula Herer who carried out the statistical analysis.

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    This study was supported in part by a grant from the Ministry of Health to Drs. L. Lavie and P. Lavie.

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