Peretz Lavie

Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study.

Abstract Objective: To assess whether sleep apnoea syndrome is an independent risk factor for hypertension. Design: Population study. Setting: Sleep clinic in Toronto. Participants: 2677 adults, aged 20-85 years, referred to the sleep clinic with suspected sleep apnoea syndrome. Outcome measures: Medical history, demographic data, morning and evening blood pressure, and whole night polysomnography. Results: Blood pressure and number of patients with hypertension increased linearly with severity of sleep apnoea, as shown by the apnoea-hypopnoea index. Multiple regression analysis of blood pressure levels of all patients not taking antihypertensives showed that apnoea was a significant predictor of both systolic and diastolic blood pressure after adjustment for age, body mass index, and sex. Multiple logistic regression showed that each additional apnoeic event per hour of sleep increased the odds of hypertension by about 1%, whereas each 10% decrease in nocturnal oxygen saturation increased the odds by 13%. Conclusion: Sleep apnoea syndrome is profoundly associated with hypertension independent of all relevant risk factors.

Sleep disorders and melatonin rhythms in elderly people.

Biological aging is often associated with problems with sleep and daytime napping.1 There is considerable evidence linking melatonin, produced by the pineal gland, with the sleep-wake cycle. When administered orally to humans or animals it enhances sleep2 and has a synchronising effect on circadian rhythms. Circulating melatonin concentrations decrease in old age, and its time of secretion is delayed.3 We examined whether sleep disorders in old age were associated with changes in concentration of 6-sulphatoxymelatonin, the major urinary measure of melatonin. The study population comprised four groups: (a) eight independently living patients with insomnia (four men, four women, mean age 73.1 (SD 3.9)); (b) 15 patients with insomnia (five men, 10 women, mean age 82.1 (8.8)) who had lived a minimum of six months in a nursing home; (c) 25 elderly patients without sleep disorders (19 …

Prevalence of sleep apnea syndrome among patients with essential hypertension

The purpose of this study was to investigate the prevalence of sleep apnea syndrome (SAS) among patients with essential hypertension. Sixteen of 50 patients with essential hypertension were suspected of having SAS based on their responses to a sleep questionnaire. Whole-night polysomnographic recordings revealed that 11 of the 16 patients, which is 22% of the initial sample, had SAS as defined by the occurrence of at least 10 apneas lasting 10 seconds each per hour of polygraphically defined sleep. The preponderant finding of SAS in this group indicates that the possibility of the syndrome should be taken into consideration in the clinical evaluation of these patients.

Interindividual Heterogeneity in the Hypoxic Regulation of VEGF Significance for the Development of the Coronary Artery Collateral Circulation

BACKGROUND The coronary artery collateral circulation may be beneficial in protecting against myocardial ischemia and necrosis. However, there is a tremendous interindividual variability in the degree of new collateral formation in patients with coronary artery disease. The basis for this interindividual heterogeneity is not understood. In this study we test the hypothesis that failure to generate collateral vessels is associated with a failure to appropriately induce with hypoxia or ischemia the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS AND RESULTS We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography. We found that there was a highly significant difference in the hypoxic induction of VEGF in patients with no collaterals compared with patients with some collaterals (mean fold induction 1.9+/-0.2 versus 3.2+/-0.3, P<0.0001). After subjecting the data to ANCOVA, using as covariates a number of factors that might influence the amount of collateral formation (ie, age, sex, diabetes, smoking, hypercholesterolemia), patients with no collaterals still have a significantly lower hypoxic induction of VEGF than patients with collaterals. CONCLUSIONS This study provides evidence in support of the hypothesis that the ability to respond to progressive coronary artery stenosis is strongly associated with the ability to induce VEGF in response to hypoxia. The observed interindividual heterogeneity in this response may be due to environmental, epigenetic, or genetic causes. This interindividual heterogeneity may also help to explain the variable angiogenic responses seen in other conditions such as diabetic retinopathy and solid tumors.

All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age

The objective of this study was to assess whether an increasing severity of sleep apnoea is associated with increased all-cause mortality hazards and to assess whether the syndrome is associated with excess mortality, in comparison with the general population. Participants included 14,589 adult males, aged 20–93 yrs, referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep apnoea. Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs. The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with apnoea severity. Cox proportional analysis revealed that both respiratory disturbance index (RDI) and body mass index significantly influenced all-cause mortality hazard but there was no interaction between them. Males with respiratory disturbance index >30 had a significantly higher mortality hazard rate than the reference group of males with RDI ≤10. Comparing mortality rates of males with moderate/severe sleep apnoea to the general population revealed that only males aged <50 yrs showed an excess mortality rate. The hazard of mortality in sleep apnoea increases with apnoea severity as indexed by respiratory disturbance index. Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged <50 yrs. The lack of information about possible confounders and treatment effects should be taken into consideration in the interpretation of these results.

Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a highly prevalent breathing disorder in sleep that is an independent risk factor for cardiovascular morbidity and mortality. A large body of evidence, including clinical studies and cell culture and animal models utilising intermittent hypoxia, delineates the central role of oxidative stress in OSAHS as well as in conditions and comorbidities that aggregate with it. Intermittent hypoxia, the hallmark of OSAHS, is implicated in promoting the formation of reactive oxygen species (ROS) and inducing oxidative stress. The ramifications of increased ROS formation are pivotal. ROS can damage biomolecules, alter cellular functions and function as signalling molecules in physiological as well as in pathophysiological conditions. Consequently, they promote inflammation, endothelial dysfunction and cardiovascular morbidity. Oxidative stress is also a crucial component in obesity, sympathetic activation and metabolic disorders such as hypertension, dyslipidaemia and type 2 diabetes/insulin resistance, which aggregate with OSAHS. These conditions and comorbidities could result directly from the oxidative stress that is characteristic of OSAHS or could develop independently. Hence, oxidative stress represents the common underlying link in OSAHS and the conditions and comorbidities that aggregate with it.

Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment.

OBJECTIVES To investigate the occurrence of nocturnal ischemic events in patients with obstructive sleep apnea syndrome (OSAS) and ischemic heart disease (IHD). BACKGROUND Although previous reports documented nocturnal cardiac ischemic events among OSAS patients, the exact association between obstructive apneas and ischemia is not yet clear. It is also not known what differentiates between patients showing nocturnal ischemia and those that do not. METHODS Fifty-one sleep apnea patients (age 61.3+/-8.3) with IHD participated in the study (after withdrawal of beta-adrenergic blocking agents and anti-anginotic treatment). All patients underwent whole-night polysomnography including ambulatory blood pressure recordings (30 min interval) and continuous Holter monitoring during sleep. A control group of 17 OSAS patients free from IHD were also similarly studied. Fifteen of the 51 patients were also recorded under continuous positive airway pressure (CPAP). RESULTS Nocturnal ST segment depression occurred in 10 patients (a total of 15 events, 182 min), of whom six also had morning ischemia (06-08 am). Five additional patients had only morning ischemia. No ischemic events occurred in the control group. Age, sleep efficiency, oxygen desaturation, IHD severity and nocturnal-double product (DP) values were the main variables that significantly differentiated between patients who had ischemic events during sleep and those who did not. Nocturnal ischemia predominantly occurred during the rebreathing phase of the obstructive apneas, and it is characterized by increased heart rate (HR) and DP values. Treatment with continuous positive airway pressure significantly ameliorated the nocturnal ST depression time from 78 min to 33 min (p<0.001) as well as the maximal DP values (14,137+/-2,827 vs. 12,083+/-2,933, p<0.001). CONCLUSIONS Exacerbation of ischemic events during sleep in OSAS may be explained by the combination of increased myocardial oxygen consumption as indicated by increased DP values and decreased oxygen supply due to oxygen desaturation with peak hemodynamic changes during the rebreathing phase of the obstructive apnea. Treatment with CPAP ameliorated the nocturnal ischemia.

Melatonin: role in gating nocturnal rise in sleep propensity.

The present article reviews the evidence that melatonin possesses sleep-inducing effects and that it gates the increase in nocturnal sleepiness. It is shown that, without exception, all the studies that have investigated daytime administrations of melatonin reported increased sleepiness, even at doses that do not increase plasma levels of melatonin beyond its physiological levels. By contrast, nighttime increase in sleepiness was achieved only after administration of high doses. Based on these findings and on the precise coupling between the endogenous nocturnal increase in melatonin secretion and the opening of the sleep gate, it is suggested that melatonin participates in the regulation of the sleep-wake cycle by inhibiting the central nervous system wakefulness generating system. This inhibition allows a smooth transition from wakefulness to sleep. Clinical findings on decreased levels of nocturnal melatonin in chronic insomniacs, and on the efficacy of exogenous melatonin in improving sleep in melatonin-deficient insomniacs, are congruent with this hypothesis.

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function.

BACKGROUND Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.

Bariatric surgery In morbidly obese sleep-apnea patients: short- and long-term follow-up

Forty-seven obese sleep-apnea patients were investigated in the sleep laboratory before and after a massive weight reduction achieved by bariatric surgery. The first postoperative sleep investigations were performed approximately 1 y after surgery and revealed a highly significant decrease in the number of apneic episodes per hour of sleep and a significant improvement in all sleep-quality-related measures. A second postoperative sleep study was performed approximately 7 y postoperatively and revealed that regaining of weight was associated with the reappearance of sleep apnea syndrome, although the great majority of the patients still felt, subjectively, that they were well and did not suffer from recurrence of the sleep apnea syndrome.