Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Effect of continuous positive airway pressure on ambulatory blood pressure in patients with obstructive sleep apnoea

OBJECTIVES: Previous reports on the effects of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) on blood pressure has shown contradictory results. Accordingly, we have investigated the effects of CPAP on blood pressure and on the potential reversal of the diagnosis of hypertension in patients with OSA evaluated repeatedly by ambulatory blood pressure monitoring. METHODS: We studied 122 patients (104 men and 18 women), 55.1+/-10.5 years of age, with diagnosis of OSA corroborated by overnight polysomnography at the clinic. Among those patients, 83 were treated with CPAP after their first evaluation, while 39 remained without CPAP for the duration of the trial. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, at baseline and after 2 and 4 months of intervention. RESULTS: There was a small, but not statistically significant, reduction in ambulatory blood pressure in patients treated with CPAP (0.7 and 1.5 mmHg in 24-h mean of systolic and diastolic blood pressure after 2 months of therapy; 2.0 and 2.3 mmHg after 4 months; P>0.239). The blood pressure reduction was very similar in patients with OSA followed for 4 months without CPAP (1.9 and 2.2 mmHg in 24-h mean of systolic and diastolic blood pressure, respectively; P=0.543). We found a high (77%) prevalence of hypertension among the patients participating in this study, although only 37% were receiving antihypertensive medication at the time of recruitment. The prevalence of hypertension was slightly but not significantly reduced to just 74% after 4 months of treatment with CPAP. CONCLUSIONS: The small reduction in blood pressure for consecutive profiles of ambulatory monitoring can probably be explained by the documented 'ABPM pressor effect' on patients using the ambulatory device for the first time. The high prevalence of hypertension among patients with OSA is not significantly reduced by treatment with CPAP. These results suggest that patients with OSA should always be properly evaluated for diagnosis of hypertension, and provided, if needed, with antihypertensive treatment apart from the recommended CPAP.     

Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea.

Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index [AHI] 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.     

Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome.

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.     

Long-term effect of continuous positive airway pressure on BP in patients with hypertension and sleep apnea

OBJECTIVE: To analyze the long-term effect of continuous positive airway pressure (CPAP) on ambulatory BP in patients with obstructive sleep apnea (OSA) and hypertension, and to identify subgroups of patients for whom CPAP could be more effective. METHODS: We conducted a prospective, long-term follow-up trial (24 months) in 55 patients with OSA and hypertension (mean CPAP use, 5.3 +/- 1.9 h/d [+/- SD]). Twenty-four-hour ambulatory BP monitoring (ABPM) was measured at baseline and after intervention with CPAP on an intention-to-treat basis. In addition, the correlation between the changes in 24-h mean arterial pressure (24hMAP) and CPAP compliance, OSA severity, and baseline ABPM was assessed. RESULTS: At the end of follow-up, a significant decrease was shown only in diastolic BP (- 2.2 mm Hg; 95% confidence interval [CI], - 4.2 to - 0.1; p = 0.03) but not in 24hMAP or other ABPM parameters. However, a correlation between changes in 24hMAP and baseline systolic BP (r = - 0.43, p = 0.001), diastolic BP (r = - 0.38, p = 0.004), and hours of use of CPAP (r = - 0.30, p = 0.02) was observed. A significant decrease in the 24hMAP was achieved in a subgroup of patients with incompletely controlled hypertension at entry (- 4.4 mm Hg; 95% CI, - 7.9 to - 0.9 mm Hg; p = 0.01), as well as in those with CPAP compliance > 5.3 h/d (- 5.3 mm Hg; 95% CI, - 9.5 to - 1.2 mm Hg; p = 0.01). Linear regression analysis showed that baseline systolic BP and hours of CPAP were independent predictors of reductions in BP with CPAP. CONCLUSION: Long-term CPAP reduced BP modestly in the whole sample. However, patients with higher BP at entry and good CPAP compliance achieved significant reductions in BP.     

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.     

Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure

Obstructive sleep apnea (OSA) is highly prevalent among patients with congestive heart failure (CHF) and may contribute to progression of cardiac dysfunction via hypoxia, elevated sympathetic nervous system activity, and systemic hypertension. Our aim was to assess the long-term effect of OSA treatment with nocturnal continuous positive airway pressure (CPAP) on systolic heart function, sympathetic activity, blood pressure, and quality of life in patients with CHF. Fifty-five patients with CHF and OSA were randomized to 3 months of CPAP or control groups. End points were changes in left ventricular ejection fraction, overnight urinary norepinephrine excretion, blood pressure, and quality of life. Nineteen patients in the CPAP group and 21 control subjects completed the study. Compared with the control group, CPAP treatment was associated with significant improvements in left ventricular ejection fraction (delta 1.5 +/- 1.4% vs. 5.0 +/- 1.0%, respectively, p = 0.04), reductions in overnight urinary norepinephrine excretion (delta 1.6 +/- 3.7 vs. -9.9 +/- 3.6 nmol/mmol creatinine, p = 0.036), and improvements in quality of life. There were no significant changes in systemic blood pressure. In conclusion, treatment of OSA among patients with CHF leads to improvement in cardiac function, sympathetic activity, and quality of life.     

Decreased exercise capacity in mild essential hypertension: non-invasive indicators of limiting factors.

Available data suggest that exercise capacity is limited in hypertension. The mechanism of this reduced maximal exercise capacity has not been fully elucidated. In this study 22 patients with mild essential hypertension (162 +/- 22 mmHg systolic and 95 +/- 8 mmHg diastolic) and 36 normotensive control subjects (128 +/- 13 mmHg systolic and 80 +/- 7 mmHg diastolic) (P less than 0.01) performed an ergometer test till exhaustion. Body mass index in the two groups did not differ. The maximal oxygen consumption VO2 was lower in the hypertensive group (18 +/- 7 versus 23 +/- 8 ml/kg/min; P less than 0.02) as was the maximal workload (141 +/- 52 vs. 185 +/- 70 Watt; P less than 0.01). Rate pressure product rose only 2.7 fold in hypertensive patients versus 3.5 fold in the control group (P less than 0.001). In hypertensive patients maximal workload decreased with increasing resting systolic blood pressure (P less than 0.05) while in the normotensive subjects maximal workload rose with increasing resting systolic blood pressure (P less than 0.05). In conclusion both high and low blood pressure was associated with a decreased maximal voluntary exercise capacity. Even mild hypertension was accompanied by lower maximal exercise capacity. Hypertensive patients also had a lower maximal VO2 and lower maximal rate pressure product than did normotensive subjects.     

Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea

BACKGROUND: Patients with obstructive sleep apnea (OSA) are at increased risk for hypertension. The mechanisms responsible for the development of hypertension are controversial. We hypothesized that patients with OSA had an abnormal 24-h blood pressure (BP) and an abnormal activity in vasoactive hormones, and that both BP and hormones were normalized during treatment with long-term nasal continuous positive airway pressure (CPAP). METHODS: The 24-h BP and plasma levels of the vasoactive hormones (renin, angiotensin II, aldosterone, atrial natriuretic peptide, brain natriuretic peptide, vasopressin, and endothelin-1) were measured in 24 patients with OSA and in 18 control subjects. Thirteen patients with OSA were reexamined after 14 months of CPAP therapy. RESULTS: Patients with OSA had significantly increased BP and heart rate and a reduced nocturnal BP drop. Both angiotensin II (13.3 +/- 1.6 v 7.8 +/- 1.0 pmol/L) and aldosterone (94.0 +/- 9.4 v 62.2 +/- 4.5 pmol/L) were significantly higher in OSA than in control subjects. Positive correlations were found between angiotensin II and daytime BP (systolic: r = 0.49, P <.01; diastolic: r = 0.52, P <.01). The CPAP therapy resulted in a decrease in BP, and this CPAP-induced reduction in BP was correlated with a decrease in both plasma renin (r = 0.76 to 0.92, all P <.01) and plasma angiotensin II concentration (r = 0.58 to 0.81, all P <.05). CONCLUSIONS: Plasma angiotensin II and aldosterone were elevated in OSA, and plasma angiotensin II was correlated with BP. Long-term CPAP reduced BP, and this decrease in BP was correlated with the reductions in plasma renin and angiotensin II levels. We suggest that OSA mediates hypertension, at least in part, via a stimulation of angiotensin II production.     

Impact of obstructive sleep apnea on right ventricular global function: sleep apnea and myocardial performance index

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstructions during sleep, and it might cause cardiovascular complications such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary hypertension. OBJECTIVES: To determine right ventricular diameters and myocardial performance index (MPI) reflecting ventricular global function in uncomplicated OSA patients. METHODS: 49 subjects without hypertension, diabetes mellitus, or any cardiac or pulmonary disease referred for evaluation of OSA had overnight polysomnography and complete echocardiographic assessment. According to the apnea-hypopnea index (AHI), subjects were divided into three groups: group 1: control subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5-14, n = 11), and group 3: moderate-severe OSA (AHI > or = 15, n = 18). Right ventricular free wall diameter was measured by M mode, and right ventricular MPI was calculated as (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection time. RESULTS: There were no differences of age, body mass index, heart rates, systolic and diastolic blood pressures among the groups (p > 0.05). Right ventricular end-diastolic and end-systolic diameters were not statistically different between the groups, and were within normal limits. Also, right ventricular free wall diameter was not significantly different between the groups of control, mild OSA and moderate-severe OSA (6.7 +/- 0.9, 6.9 +/- 1.0, 7.1 +/- 1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62 +/- 0.18) than in group 2 patients (0.50 +/- 0.10), and group 1 patients (0.48 +/- 0.08, p < 0.001). CONCLUSIONS: It was suggested that patients with moderate-severe OSA had a right ventricular global dysfunction, in addition to the presence of a diastolic dysfunction.     

Effect of continuous positive airway pressure treatment on pulmonary artery pressure in patients with isolated obstructive sleep apnea: a meta-analysis

Pulmonary hypertension (PH) can occur in patients with obstructive sleep apnea (OSA) in the absence of cardiac or lung disease. Data on the development and severity of PH, and the effect of continuous positive airway pressure (CPAP) therapy on pulmonary artery (PA) pressures in these patients have been inconsistent in the literature. We sought to determine whether CPAP therapy affects PA pressures in patients with isolated OSA in this meta-analysis. We searched PubMed, Medline, EMBASE and other databases from January 1980 to August 2015. Studies of patients with OSA, defined as an apnea–hypopnea index >10 events/h, and PH, defined as PA pressure >25 mmHg were included. Two reviewers independently extracted data and assessed risk of bias. A total of 222 patients from seven studies (341.53 person-years) had reported PA pressures before and after treatment with CPAP therapy. 77 % of participants were men, with a mean age of 52.5 years, a mean apnea–hypopnea index of 58 events/h, and mean PA pressure of 39.3 ± 6.3 mmHg. CPAP treatment duration ranged from 3 to 70 months. Using fixed effects meta-analysis, CPAP therapy was associated with a decrease in PA pressure of 13.3 mmHg (95 % CI 12.7–14.0) in our study population. This meta-analysis found that CPAP therapy is associated with a significantly lower PA pressure in patients with isolated OSA and PH.     

Predictive value of clinic blood pressure variability for pressure changes during placebo in elderly hypertensives

OBJECTIVES: Syst-China is the ongoing placebo-controlled double-blind outcome trial in older (aged 60 years or more) Chinese patients with isolated systolic hypertension (systolic blood pressure 160-219 mmHg and diastolic blood pressure < 95 mmHg). This article is based on the data accumulated until 31 August 1992. Its purpose is to investigate the extent to which the variability in the clinic blood pressure readings at baseline could predict the blood pressure changes observed in the placebo arm of the trial. METHODS: From 2379 patients recruited into the trial, 728 [455 men and 273 women, aged 66.7+/-5.5 years (mean +/- SD)] were selected, because their blood pressure readings for the three run-in visits as well as 3, 6 and 12 months after random allocation were available. Overall and between-visit blood pressure variabilities at baseline were estimated from the two readings obtained with the subject seated during the first and second run-in visits. The baseline blood pressure used to calculate the blood pressure changes during follow-up was the average of the two readings during the third run-in visit. RESULTS: The blood pressure variability at baseline was larger for women than it was for men. For all of the subjects combined, the blood pressure had decreased by 4.1+/-14.4 mmHg (P < 0.001) systolic and 0.5+/-6.7 mmHg (P < 0.06) diastolic by the 3-month follow-up visit, by 8.5+/- 15.2 and 1.4+/-7.5 mmHg, respectively, after 6 months and by 10.3+/-15.7 and 1.9+/-7.9 mmHg, respectively, after 1 year (p < 0.001 for all). Stepwise multiple regression analysis showed that sex, age, alcohol intake and the blood pressure at baseline were significant determinants of the long-term (1 year) blood pressure changes. Aftger adjustment for the aforementioned covariates, the between-visit variability was a significant predictor of the changes in the diastolic blood pressure after 1 year of placebo treatment for the men (partial r+/-SEM -0.36+/-0.12, P < 0.01) and for all of the subjects (-0.19+/-0.09, P < 0.05). For men, the partial regression coefficient between the overall variability and the changes in the diastolic blood pressure also attained statistical significance (-0.39+/- 0.14, P < 0.01). CONCLUSION: For older Chinese patients with isolated systolic hypertension, in particular for men, a higher blood pressure variability at baseline was associated with a larger decrease in diastolic blood pressure during 1-year follow-up on placebo, explaining up to 2% of the variance of the observed changes. Similar associations were not observed for systolic blood pressure.     

Haemodynamic effects of short-term nasal continuous positive airway pressure therapy in sleep apnoea syndrome: monitoring by a finger arterial pressure device.

We have evaluated the effects of short-term nasal continuous positive airway pressure (nCPAP) therapy on systemic blood pressure and heart rate in patients with obstructive sleep apnoea syndrome. Twenty five consecutive patients were examined during baseline conditions (No-CPAP) and during one night of nCPAP treatment (CPAP). The mean value and the variation coefficient of cardiovascular variables, examined by a finger arterial pressure device (Finapres), were determined in wakefulness and sleep. Without nCPAP an increase in blood pressure from wakefulness to sleep was observed in all patients from 138 +/- 3 mmHg to 146 +/- 3 and 155 +/- 4 mmHg, and from 80 +/- 1 mmHg to 82 +/- 2 and 84 +/- 2 mmHg, respectively, for systolic and diastolic values in non rapid eye movement (NREM) and rapid eye movement (REM) sleep. Conversely, heart rate decreased from 75 +/- 2 beats.min-1 to 70 +/- 2 and 69 +/- 2 beats.min-1. In addition, variability of heart rate and blood pressure was greatly increased compared with the awake state. Short-term nCPAP therapy significantly reduced systolic pressure from 144 +/- 3 mmHg to 137 +/- 3 and 143 +/- 4 mmHg during NREM and REM sleep, respectively, associated with a decrease in heart rate (from 69 +/- 2 to 65 +/- 2 beat.min-1). In total sleep and in all sleep stages a significantly reduced variability (p less than 0.001) was found. No changes were observed for diastolic pressure during CPAP night compared with baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.

OBJECTIVES: We studied structural and functional cardiac alterations in obstructive sleep apnea (OSA), their relationship to the severity of OSA, and the effects of treatment with continuous positive airway pressure (CPAP). BACKGROUND: Obstructive sleep apnea may influence the cardiac function by several mechanisms in the awake patient. METHODS: Left and right ventricular morphology and function were studied using echocardiography before and after treatment with CPAP in symptomatic patients (Epworth sleepiness score, 10 +/- 4.8) with severe OSA (apnea-hypopnea index [AHI], 42 +/- 24). The patients (n = 43, 32 men) had no known cardiac disease and were obese (body mass index, 31.6 +/- 5.4 kg/m2). The same echocardiographic parameters were studied in age-matched overweight patients (n = 40; body mass index, 26.4 +/- 2.3 kg/m2). RESULTS: The patients were hypertensive (systolic blood pressure, 153 +/- 25 mm Hg), with a higher resting heart rate (77 +/- 10 beats/min, p = 0.008) compared with age-matched control patients (n = 40). There was right ventricular dilatation, hypertrophic interventricular septum, reduced left ventricular stroke volume, tissue Doppler-determined systolic and diastolic velocities of the left and right ventricle, and normal pulmonary artery pressure. The structural and functional parameters were significantly associated with AHI (p < 0.004). Multiple stepwise regression showed the interventricular septum thickness, right ventricular free wall, and mitral annulus tissue Doppler systolic velocities to be predictive of a higher AHI (p < 0.001). Six months after treatment with CPAP, significant improvements were observed in the symptoms and hemodynamics, as well as left and right ventricular morphology and function. CONCLUSIONS: The structural and functional consequences of OSA on the heart are influenced by the severity of AHI. These effects are reversible if the apneic episodes are abolished.     

Ambulatory blood pressure is still elevated in treated hypertensive diabetic subjects compared with untreated diabetic subjects with the same office blood pressure.

Ambulatory blood pressure, ABP, was determined every 15 min for 24 h (Spacelabs 5200 system) in 16 hypertensive diabetic subjects treated for high blood pressure. Office blood pressure (OBP) in these subjects (systolic BP greater than 160 mmHg and diastolic BP greater than 95 mmHg before treatment) had been reduced by treatment to the borderline range (systolic less than or equal to 160 mmHg and/or diastolic less than or equal to 95 mmHg). Sixty-five diabetic subjects with normal or borderline OBP were included as controls. The two groups had the same age (58 +/- 10 yrs in both groups), duration of diabetes (15 +/- 9 yrs), 24 hr microalbumin, and included the same percentage of subjects with moderate neuropathy (36% and 29%, NS). The two groups had the same OBP (138 +/- 16 mmHg and 140 +/- 16 mmHg systolic, NS, 84 +/- 9 mmHg and 84 +/- 13 mmHg diastolic, NS). In contrast, ambulatory BP was significantly higher in the treated group, when compared with the controls (123 +/- 13 mmHg and 133 +/- 23 mmHg systolic, P less than 0.025, 77 +/- 7 mmHg and 84 +/- 16 mmHg diastolic, P less than 0.015). The difference was significant both in daytime and in nighttime, and was more significant in nighttime (11 mmHg systolic, P less than 0.02, 9 mmHg diastolic, P less than 0.004) than in daytime (9 mmHg systolic, P less than 0.05 and 5 mmHg diastolic, P less than 0.05). Ambulatory heart rate was also significantly higher in the treated group, but only in daytime (7 b/min difference, P less than 0.02). The study demonstrated the need to survey and investigate ABP in treated hypertensive diabetic subjects.     

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Hemodynamic and antianginal effects during rest and exercise of intravenous isradipine, a new dihydropyridine calcium antagonist

In an open randomized study, hemodynamic and antianginal effects of nifedipine and the new dihydropyridine derivative isradipine were compared in patients with stable, angiographically confirmed coronary heart disease. Right heart hemodynamics, systemic arterial blood pressure, ECG, and drug plasma concentrations were measured before medication at rest and exercise, after infusions of increasing doses at rest, and again after treatment at rest and exercise. A linear relationship between serum concentrations and cumulated dosages was obtained for both drugs. At rest, both drugs significantly increased cardiac output and heart rate. The reduction of arterial blood pressure was significantly greater after isradipine (systolic from 148 +/- 3 to 104 +/- 3 mmHg; diastolic from 90 +/- 4 to 58 +/- 2 mmHg) than after nifedipine (systolic 149 +/- 6 to 125 +/- 4 mmHg; diastolic 92 +/- 4 to 76 +/- 3 mmHg). The minimal effective plasma level of isradipine regarding blood pressure reduction was estimated at 5 ng/ml (nifedipine: 10-25 ng/ml). During exercise both medications significantly reduced mean pulmonary artery pressure (isradipine: 40 +/- 3 to 20 +/- 1 mmHg, nifedipine: 37 +/- 4 to 22 +/- 1 mmHg), pulmonary artery wedge pressure (isradipine: 23 +/- 3 to 10 +/- 1 mmHg, nifedipine 24 +/- 3 to 14 +/- 1 mmHg), and diastolic arterial pressure (isradipine: 103 +/- 3 to 73 +/- 4 mmHg, nifedipine: 99 +/- 3 to 91 +/- 2 mmHg), whereas systolic pressure was reduced by only isradipine (189 +/- 4 to 147 +/- 5 mmHg). Neither medication significantly changed electrocardiographic ST depression during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute and chronic effects of continuous positive airway pressure therapy on left ventricular systolic and diastolic function in patients with obstructive sleep apnea and congestive heart failure

BACKGROUND:

Obstructive sleep apnea (OSA) may contribute to the pathogenesis of congestive heart failure (CHF). Nocturnal continuous positive airway pressure (CPAP) therapy can alleviate OSA and may have a role in the treatment of CHF patients.

OBJECTIVES:

To investigate the acute and chronic effects of CPAP therapy on left ventricular systolic function, diastolic function and filling pressures in CHF patients with OSA.

METHODS:

Twelve patients with stable CHF (New York Heart Association II or III, radionuclide ejection fraction lower than 40%) underwent overnight polysomnography to detect OSA. In patients with OSA (n=7), echocardiography was performed at baseline (awake, before and during acute CPAP administration) and after 6.9±3.3 weeks of nocturnal CPAP therapy. Patients without OSA (n=5) did not receive CPAP therapy, but underwent a baseline and follow-up echocardiogram.

RESULTS:

In CHF patients with OSA, acute CPAP administration resulted in a decrease in stroke volume (44±15 mL versus 50±14 mL, P=0.002) and left ventricular ejection fraction ([LVEF] 34.8±5.0% versus 38.4±3.3%, P=0.006) compared with baseline, but no change in diastolic function or filling pressures (peak early diastolic mitral annular velocity [Ea]: 6.0±1.6 cm/s versus 6.3±1.6 cm/s, P not significant; peak early filling velocity to peak late filling velocity [E/A] ratio: 1.05±0.74 versus 1.00±0.67, P not significant; E/Ea ratio: 10.9±4.1 versus 11.3±4.1, P not significant). In contrast, chronic CPAP therapy resulted in a trend to an increase in stroke volume (59±19 mL versus 50±14 mL, P=0.07) and a significant increase in LVEF (43.4±4.8% versus 38.4±3.3%, P=0.01) compared with baseline, but no change in diastolic function or filling pressures (Ea: 6.2±1.2 cm/s versus 6.3±1.6 cm/s, P not significant; E/A ratio: 1.13±0.61 versus 1.00±0.67, P not significant; E/Ea ratio: 12.1±2.7 versus 11.3±4.1, P not significant). There was no change in left ventricular systolic function, diastolic function or filling pressures at follow-up in CHF patients without OSA.

CONCLUSIONS:

Acute CPAP administration decreased stroke volume and LVEF in stable CHF patients with OSA. In contrast, chronic CPAP therapy for seven weeks improved left ventricular systolic function, but did not affect diastolic function or filling pressures. The potential clinical implications of the discrepant effects of CPAP therapy on left ventricular systolic and diastolic function in CHF patients with OSA warrant further study.