[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects.
Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9 pm), after 5 hrs of untreated OSA ( 2am) and in the morning after awakening (6 am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 +/- 9 vs 56.0 +/- 9 pg/mL; PRA: 0.99 +/- 0.15 vs. 1.15 +/- 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep.
Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels.
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) and obesity have been linked to systolic and diastolic dysfunction of the left ventricle. Right ventricular function is poorly understood in the 2 clinical conditions. Data from this study show that otherwise healthy obese patients with OSA had increased an left atrial volume index compared with similarly obese patients without OSA (16.3 +/- 1.2 ml/m in obese patients without OSA vs 20.2 +/- 1.0 ml/m in those with OSA, p = 0.02) and altered diastolic function reflected by changes in mitral annular late diastolic velocity (-5.7 +/- 0.7 cm/s in obese patients without OSA vs -7.3 +/- 0.7 cm/s in those with OSA, p = 0.007), mitral annular early diastolic velocity (-7.9 +/- 0.6 cm/s in obese patients without OSA vs -6.4 +/- 0.3 cm/s in those with OSA, p = 0.05), and early to late diastolic annular ratio >1 (82% of obese patients without OSA vs 26% of those with OSA, p = 0.001), which may be signs of early subclinical impairment of cardiac function. Importantly, healthy obese subjects had similarly increased left ventricular mass compared with obese patients with OSA but normal diastolic function and left atrial size. There was a trend toward abnormal right ventricular filling in patients with OSA, measured by altered superior vena cava diastolic velocity during expiration (-15 +/- 2 cm/s in obese patients without OSA vs -10 +/- 3 cm/s in those with OSA, p = 0.2) and a tendency toward diastolic dysfunction reflected by decreased lateral tricuspid annular early diastolic velocity (-7.2 +/- 0.5 cm/s in obese patients without OSA vs -6.1 +/- 0.5 cm/s in those with OSA, p = 0.1) beyond that seen in obesity alone. In conclusion, OSA independent of obesity may induce cardiac changes that could predispose to atrial fibrillation and heart failure.
The American Journal of Cardiology 06/2007; 99(9):1298-302. · 3.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is linked to both coronary artery disease (CAD) and sudden death, but any causal role remains unclear. A family history of premature CAD and related mortality is an independent risk factor for the development of CAD. We hypothesized that OSA is associated with a family history of premature mortality from ischemic heart disease.
We prospectively studied 588 subjects who underwent polysomnography from May 2000 to June 2004. Demographics, comorbidities, family history of cardiovascular disease, and the ages and causes of death for 10 strata of family members were recorded for all subjects. We excluded those subjects with known causes of premature cardiac death, such as hypertrophic cardiomyopathy and long-QT syndrome. OSA was defined by American Academy of Sleep Medicine criteria (ie, apnea-hypopnea index >or= 5). Premature CAD mortality was defined as death due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women).
Polysomnography confirmed OSA in 316 subjects and excluded it in 202 subjects. The unadjusted odds ratio (OR) for OSA and a family history of premature CAD mortality was 2.11 (95% confidence interval [CI], 1.10 to 4.31; p = 0.031). After adjusting for each subject's sex, body mass index, and history of CAD, there was a significant and independent association between OSA and family history of premature CAD mortality (OR, 2.13; 95% CI, 1.04 to 4.66; p = 0.046).
Regardless of their own CAD status, people with OSA are more likely than those without OSA to have a family history of premature CAD mortality.
[show abstract][hide abstract] ABSTRACT: Any sustained elevation of oxidative stress in patients with obstructive sleep apnoea (OSA) might help explain their increased risk for cardiovascular diseases. We tested the hypothesis that measures of oxidative stress are increased in otherwise healthy subjects with OSA when compared to closely matched OSA-free control subjects.
Plasma indices of oxidative stress and lipid peroxidation [thiobarbituric acid-reactive substances (TBARS), oxidized LDL (oxLDL), isoprostanes] were measured in 41 moderate-severe OSA males without other diseases and in 35 matched controls first before sleep, then after 4 h of untreated OSA, and again in the morning after 4 h of effective treatment with continuous positive airway pressure (CPAP). Plasma levels of oxLDL, TBARS, and isoprostanes in OSA patients (n=34, 26, 17, respectively) were comparable to the controls (n=28, 27, 15 for the three markers, respectively). Neither untreated OSA nor CPAP treatment nor normal sleep affected levels of any of the three measures of oxidative stress. There was no association between the severity of sleep apnoea and any measure of oxidative stress.
Otherwise healthy OSA patients, without any other co-morbidities, do not manifest evidence for higher oxidative stress and lipid peroxidation. Thus, oxidative stress and lipid peroxidation do not appear to be key mediators of increased cardiovascular disease in OSA patients.
European Heart Journal 12/2005; 26(22):2435-9. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the acute hemodynamic and autonomic effects of smokeless tobacco.
Smokeless tobacco use is increasing. Its cardiovascular effects are not well understood.
Sixteen healthy, male, habitual snuff tobacco users (aged 22 +/- 1 year) were studied, using a randomized, double-blind, placebo-controlled, crossover design with two separate experimental sessions: placebo and tobacco. Muscle sympathetic nerve activity (MSNA), electrocardiogram, blood pressure, calf blood flow, nicotine, and catecholamines were measured.
Snuff tobacco increased plasma nicotine from 2.8 +/- 0.5 ng/ml to 10.4 +/- 1.1 ng/ml. Mean blood pressure increased by 10 +/- 1 mm Hg, and heart rate increased by 16 +/- 2 beats/min. Peripheral vascular resistance, MSNA, and norepinephrine concentration did not change with tobacco, but epinephrine increased by approximately 50%.
Oral snuff tobacco increases heart rate, blood pressure, and epinephrine. Despite the increase in blood pressure, there is no decrease in either MSNA or peripheral vascular resistance. Smokeless tobacco is a powerful autonomic and hemodynamic stimulus. Catecholamine release from the adrenal medulla likely contributes to this response.
Journal of the American College of Cardiology 04/2005; 45(6):910-4. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The metabolic syndrome, an emerging public health problem, represents a constellation of cardiovascular risk factors. It has been suggested that the presence of obstructive sleep apnea (OSA) may increase the risk of developing some of the features of the metabolic syndrome, including hypertension, insulin resistance, and type 2 diabetes. In this article, we discuss the parallels between the metabolic syndrome and obstructive sleep apnea and describe possible OSA-related factors that may contribute to the metabolic syndrome, specifically the roles of obesity, hypertension, dyslipidemia, sex hormones, inflammation, vascular dysfunction, leptin, insulin resistance, and sleep deprivation.
Current Diabetes Reports 03/2005; 5(1):53-8. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is associated with obesity, sympathetic activation, systemic inflammation, and cardiovascular morbidity. Obesity, beta-adrenergic agonists, and inflammation are linked to decreased expression and/or secretion of an adipose tissue-derived antiatherogenic hormone, adiponectin. The purpose of the study was to investigate whether OSA affected plasma levels of adiponectin, which might help explain OSA-associated cardiovascular morbidity.
We randomly selected 68 otherwise healthy male subjects, either with moderate/severe OSA [apnea-hypopnea index (AHI)>or=20; n=35] or without OSA (AHI<or=5; n=33). The diagnosis of OSA was made based on prospective full polysomnography. Adiponectin was measured before polysomnography between 8 and 10 pm.
AHI was higher in the OSA group (49.5+/-4.4 vs. 2.9+/-0.4 events/h; p<0.001). OSA subjects were also more obese, with greater BMI (33+/-1 vs. 30+/-1; p=0.016) and percentage body fat (29+/-1% vs. 26+/-1%; p=0.030). Adiponectin levels were 7.67+/-0.73 and 6.33+/-0.51 microg/mL in the OSA and non-OSA groups, respectively, and this difference was significant in covariate analysis (taking into account age, hemodynamic characteristics, measures of body fat, and OSA severity) (p=0.009). After excluding from both groups the subjects with extreme BMI, such that the OSA and non-OSA study cohorts had similar BMI and percentage body fat, subjects with OSA had significantly higher plasma adiponectin (8.49+/-0.92 vs. 6.32+/-0.55 microg/mL; p=0.042), differences also evident in covariate analysis (p=0.017).
Plasma adiponectin levels are elevated in otherwise healthy subjects with OSA. Therefore, low adiponectin is unlikely to explain the association between OSA and cardiovascular disease.
Obesity research 01/2005; 13(1):186-90. · 4.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular disease, endothelial dysfunction, and oxidative stress, generated by repetitive nocturnal hypoxemia and reperfusion. Circulating free nitrotyrosine has been reported as a novel biomarker of nitric oxide (NO)-induced oxidative/nitrosative stress. Nitrosative stress has been implicated as a possible mechanism for development of cardiovascular diseases. We tested the hypothesis that repetitive severe hypoxemia resulting from OSA would increase NO-mediated oxidative stress. We studied 10 men with newly diagnosed moderate to severe OSA who were free of other diseases, had never been treated for OSA, and were taking no medications. Nitrotyrosine measurements, performed by liquid chromatography-tandem mass spectrometry, were made before and after untreated apneic sleep. We compared free nitrotyrosine levels in these patients with those obtained at similar times in 10 healthy male control subjects without OSA, with similar age and body mass index. Evening baseline nitrotyrosine levels were similar before sleep in the control and OSA groups [0.16 +/- 0.01 and 0.15 +/- 0.01 ng/ml, respectively, P = not significant (NS)]. Neither normal nor disturbed apneic sleep led to significant changes of plasma nitrotyrosine (morning levels: control group 0.14 +/- 0.01 ng/ml; OSA group 0.15 +/- 0.01 ng/ml, P = NS). OSA was not accompanied by increased circulating free nitrotyrosine either at baseline or after sleep. This observation suggests that repetitive hypoxemia during OSA does not result in increased NO-mediated oxidative/nitrosative stress in otherwise healthy subjects with OSA.
[show abstract][hide abstract] ABSTRACT: Whether increased homocysteine is one mechanism linking obstructive sleep apnoea (OSA) to cardiovascular abnormalities is unclear. We hypothesised that plasma homocysteine would be higher in OSA patients than in control subjects, would increase further during sleep, and decrease after treatment with continuous positive airway pressure (CPAP).
For study A, homocysteine was measured in 22 OSA patients and 20 controls first before sleep, then after 5 h of untreated OSA, and then in the morning after CPAP treatment. Homocysteine was similar in the OSA and control subjects at all three time points, and declined overnight in both groups (P=0.0017, P=0.036, respectively). To further assess this diurnal variation, we studied plasma homocysteine under a full-night protocol in 10 OSA patients and 12 controls (study B). Homocysteine was measured before sleep, in the morning after sleep, and at noon. Results in both OSA and control groups showed an overnight decline in homocysteine which was reversed by noon (repeated measures ANOVA: OSA, P=0.04; controls, P=0.02). Study C showed that disturbed sleep did not affect homocysteine levels in normal subjects.
There is a significant diurnal variation in plasma homocysteine, so that homocysteine is lower in the morning after waking. Neither OSA nor disturbed sleep elicit acute or chronic changes in homocysteine.
European Heart Journal 09/2004; 25(15):1325-9. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: We compared brain natriuretic peptide (BNP) levels in patients with obstructive sleep apnea (OSA) with and without cardiovascular disease to BNP in healthy control subjects. OSA was not associated with increased plasma BNP or atrial natriuretic peptide (ANP) in otherwise healthy subjects during wakefulness. Untreated OSA increased ANP overnight, and ANP levels decreased with treatment of OSA. However, OSA did not elicit acute overnight changes in BNP, either in normal subjects or in patients with coexisting cardiovascular disease (including chronic heart failure).
The American Journal of Cardiology 09/2004; 94(4):529-32. · 3.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: We studied systolic and diastolic function of the left and right ventricles in obese male subjects. Obese subjects had increased left ventricular mass and normal left ventricular systolic and diastolic function. They also had impaired right ventricular relaxation and right ventricular filling.
The American Journal of Cardiology 07/2004; 93(12):1569-72. · 3.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cardiovascular events such as myocardial infarction, sudden death, and stroke have a peak incidence in the early hours after waking. The mechanisms involved in this circadian variation are not clear. Endothelial dysfunction is associated with increased risk for cardiovascular events. We tested the hypothesis that endothelial function is reduced in the early morning, around the time of waking, compared with measurements obtained both before sleep and later in the day in healthy humans.
We studied 30 subjects (19 men, 11 women; mean age, 41.6 years). All participants underwent polysomnography to exclude obstructive sleep apnea or other sleep disorders. Brachial artery flow-mediated endothelium-dependent vasodilation (FMD) and endothelium-independent dilation (non-FMD) were measured on 3 different occasions: before subjects went to sleep (9 PM), the next morning immediately after waking (6 AM), and during the late morning 5 hours after waking (11 AM). All subjects had normal sleep with good sleep efficiency of 84+/-2%. Compared with before sleep, FMD decreased markedly in the early morning after waking and recovered by late morning (9 pm, 7.5+/-1%; 6 am, 4.4+/-0.7%; 11 am, 7.7+/-1%; P=0.02). Non-FMD was similar for the 3 periods of observation (9 pm, 17.3+/-1.6%; 6 am, 17.2+/-1.3%; 11 am, 18.5+/-1.7%).
FMD is blunted in the early morning in healthy subjects. Decreased endothelial function in the early morning may have implications for our understanding of the morning peak in cardiac and vascular events.
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is associated with nocturnal angina and ST-segment depression, which are relieved by treatment with continuous positive airway pressure (CPAP). We tested the hypothesis that severe nocturnal hypoxia in patients with OSA causes myocyte necrosis as evidenced by increases in cardiac troponin T.
Prospective cohort study.
Cardiovascular physiology and sleep research laboratory.
Fifteen male volunteers with coronary artery disease (CAD) and moderate or severe OSA (apnea-hypopnea index [AHI] > 15).
Polysomnography and measurement of serum cardiac troponin T before sleep, after 4 h of untreated OSA, and in the morning after 4 h of treatment with CPAP. The mean AHI for the group was 41 (SD 16), and the mean oxygen saturation nadir during sleep was 83% (SD 8%). All measurements of cardiac troponin T were < 0.010 ng/mL.
Despite the fact that some patients with OSA may experience nocturnal ischemia, this study shows that patients with severe OSA and coexisting CAD do not have nightly episodes of myocardial injury detectable by the current-generation cardiac troponin T assay.
[show abstract][hide abstract] ABSTRACT: C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related to amount of body fat. The long form of the leptin receptor resembles cytokine receptors, which include the interleukin-6 receptor. Both leptin and CRP may be increased in women, in obesity, and in inflammation, and both have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk. We tested the hypothesis that leptin is associated with CRP levels independently of the influences of gender, body mass index (BMI), waist-to-hip ratio, and other variables.
We studied 100 healthy volunteers (48 men, and 52 women). For all subjects, leptin was independently associated with CRP after adjustment for age, gender, BMI, waist-to-hip ratio, smoking, and alcohol consumption (F=12.39, P=0.0007). There was a strong and significant positive relationship between leptin and CRP in both women (R=0.61, P<0.0001) and men (R=0.55, P<0.0001) considered separately. The association between leptin and CRP was significant even after adjustment for age, BMI, waist-to-hip ratio, smoking, and alcohol consumption in women (F=7.13, P=0.01) and men (F=5.69, P=0.02). When only subjects with BMI <25 kg/m2 were considered (n=47), CRP was not linked to BMI (R=0.02, P=0.96), but a significant association between leptin and CRP was still evident (R=0.55, P<0.0001).
Leptin and CRP levels are independently associated in normal humans, providing further evidence linking metabolic and inflammatory cardiovascular disease mechanisms.
[show abstract][hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is associated with hypertension. The vasorelaxing peptide adrenomedullin (ADM) may counteract effects of OSA-induced release of vasopressor substances.
Plasma ADM levels were measured at 9:30 PM, 2:00 AM (after 4 to 5 h of untreated OSA), and 6:00 AM (after 4 h of continuous positive airway pressure treatment) in 15 OSA patients and in 10 controls.
Baseline ADM levels were similar in the OSA and control groups (28.7 +/- 6.7 v 27.7 +/- 6.4 pg/mL, respectively), did not change overnight in either group, and were not affected by continuous positive airway pressure.
OSA does not exert any significant acute or chronic effects on plasma ADM levels.
American Journal of Hypertension 02/2004; 17(1):74-6. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with severe obstructive sleep apnea (OSA) may have increased risk for cardiovascular and cerebrovascular diseases. Serum amyloid A (SAA) protein has recently been linked to the development of atherosclerosis, stroke, diabetes, and dementia. We tested the hypothesis that plasma SAA levels are increased in otherwise healthy subjects with OSA.
Plasma SAA levels were measured in 10 male patients with moderate to severe OSA before sleep, after 5 hours of untreated OSA, and in the morning after effective continuous positive airway pressure treatment. SAA levels were also measured in 10 closely matched control subjects at similar time points. Baseline plasma SAA levels before sleep were strikingly higher in patients with moderate to severe OSA than in controls (18.8+/-2.6 versus 7.2+/-2.6 microg/mL, respectively; P=0.005) and remained unchanged in both groups throughout the night. SAA levels in 10 male patients with mild OSA were comparable with controls (P=0.46). Plasma SAA in 7 female patients with moderate to severe OSA was also markedly higher compared with matched control female subjects (24.1+/-2.4 versus 10.2+/-2.4 microg/mL, respectively; P=0.0013) but was not different from male patients with moderate to severe OSA (P=0.3). There was a significant positive correlation between SAA and apnea-hypopnea index (r=0.40, P=0.03).
Plasma SAA levels are more than 2-fold greater in patients with moderate to severe OSA compared with subjects with mild OSA or healthy controls regardless of gender. Elevated SAA may contribute to any increased risk for cardiovascular and neuronal dysfunction in patients with OSA.