Sympathoadrenal mechanisms in the pathogenesis of sleep apnea-related hypertension.

Obstructive sleep apnea-hypopnea (OSAH) is regarded as an increasingly common cause of sustained hypertension. The vast majority of mechanistic studies linking these entities have focused on the role of sympathoactivation. This review therefore addresses this purported mechanism by highlighting studies conducted in the past 5 years that speak to OSAH-related changes in sympathoregulation, independent of obesity, as well as the intervening players and pathways that may be relevant to such changes. Finally, studies with a focus on changes in sympathoregulation induced by continuous positive airway pressure (CPAP) therapy are discussed. Taken together, these findings strengthen the claim that the sympathoadrenal pressor system is essential for the development of the hypertensive state in individuals with OSAH.

The impact of prior multidisciplinary predialysis care on mineral metabolic control among chronic hemodialysis patients.

BACKGROUND/AIMS: Disordered mineral metabolism is independently associated with mortality among chronic dialysis patients. We hypothesized that, upon dialysis start, biochemical markers of mineral metabolism would be better controlled among patients who had received multidisciplinary predialysis care (MDC). METHODS: We conducted a retrospective cohort study of incident hemodialysis patients between 2002 and 2005. Corrected calcium (Ca), phosphate (P), calcium-phosphate product (CaxP), and intact parathyroid hormone (iPTH) at the time of dialysis initiation and over the first year thereafter were compared based on prior MDC receipt. Furthermore, we examined the relationship between the duration of MDC and mineral metabolic parameters. RESULTS: 67 patients received MDC and 84 patients received conventional or no nephrologist-based care. Patients who received MDC had a higher iPTH (p = 0.03) both at dialysis initiation and over the subsequent year while Ca, P, and CaxP were not significantly impacted. Among patients who received MDC, mineral metabolic values at dialysis initiation did not differ by duration of predialysis care. CONCLUSIONS: The receipt of MDC had a limited effect on mineral metabolic profiles at the time of and over the first year following chronic hemodialysis initiation. The survival benefits associated with the receipt of MDC may be mediated by mechanisms other than improved mineral metabolic control.

Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension.

OBJECTIVES: Fluid displacement from the lower extremities to the upper body during sleep is strongly associated with obstructive sleep apnoea in hypertensive patients. The present pathophysiological study tests the hypothesis that intensified diuretic therapy will reduce the apnoea-hypopnoea index and blood pressure of uncontrolled hypertensive patients with obstructive sleep apnoea in proportion to the reduction in overnight change in leg fluid volume. METHODS: Uncontrolled treated hypertensive patients underwent overnight polysomnography and measurement of overnight changes in leg fluid volume and neck circumference. Those with an apnoea-hypopnoea index at least 20 events per hour (n=16) received metolazone 2.5 mg and spironolactone 25 mg daily for 7 days after which the daily dose was doubled for 7 additional days. Baseline testing was again repeated. RESULTS: Intensified diuretic therapy reduced the apnoea-hypopnoea index from 57.7 ± 33.0 to 48.5 ± 28.2 events per hour (P=0.005), overnight change in leg fluid volume from -418.1 ± 177.5 to -307.5 ± 161.9 ml (P<0.001) and overnight change in neck circumference from 1.2 ± 0.6 to 0.7 ± 0.4 cm (P<0.001). There was an inverse correlation between the reduction in overnight change in leg fluid volume and decrease in apnoea-hypopnoea index (r=-0.734, P=0.001). The reduction in overnight change in leg fluid volume was also significantly correlated with the change in morning blood pressure (r=0.708, P=0.002 for SBP; r=0.512, P=0.043 for DBP). CONCLUSION: The findings provide further evidence that fluid redistribution from the legs to the neck during sleep contributes to the severity of obstructive sleep apnoea in hypertension and may be an important link between these two conditions.

Influence of lower body positive pressure on upper airway cross-sectional area in drug-resistant hypertension.

We previously showed that in hypertensive patients the amount of fluid displaced from the legs overnight is directly related to the severity of obstructive sleep apnea and that the rostral fluid shift was greater in drug-resistant hypertensive patients. The findings suggested that this fluid redistribution increases upper airway collapsibility, yet more direct evidence is lacking. The present study examines the effects of graded lower body positive pressure on leg fluid volume, upper airway cross-sectional area, and neck circumference in patients with drug-resistant hypertension (n=25) and controlled hypertension (n=15). In both groups, the reduction in mean upper airway cross-sectional area and oropharyngeal junction area, assessed by acoustic pharyngometry, and the increase in neck circumference, determined by mercury strain gauge plethysmography, were related to the amount of fluid displaced from the legs (R(2)=0.41, P<0.0001; R(2)=0.42, P<0.0001; and R(2)=0.47, P<0.0001, respectively). Displacement of leg fluid volume was significantly greater in patients with drug-resistant hypertension than in controlled hypertension (P<0.0001), and as a consequence, the former experienced greater reductions in mean upper airway cross-sectional area and oropharyngeal junction area (P=0.001 and P<0.0001, respectively). The findings support the concept that in hypertensive subjects, rostral fluid displacement may participate in the pathogenesis of obstructive sleep apnea by narrowing the upper airway and making it more susceptible to collapse during sleep. The exaggerated fluid volume displacement from the legs and upper airway response to lower body positive pressure in patients with drug-resistant hypertension provide additional evidence of an important link between drug-resistant hypertension and obstructive sleep apnea.

Independent association of drug-resistant hypertension to reduced sleep duration and efficiency.

BACKGROUND: Experimentally induced sleep deprivation can raise blood pressure (BP) and worsen hypertension. We recently reported a significantly higher prevalence of obstructive sleep apnea (OSA) and reduced rapid eye movement (REM) sleep time in drug-resistant hypertensives compared to controlled hypertensives. The objective of this study was to test the hypothesis that short sleep duration is associated with resistant hypertension (RH) independently of OSA, which can itself disrupt and shorten sleep. METHODS: In a case-control study, overnight polysomnographic results of subjects with OSA and RH (n = 62) were compared to those with OSA of equal severity and either controlled hypertension (CH) (n = 49) or normotension (n = 40). RESULTS: Subjects with RH slept 33.8 min (P = 0.02) and 37.2 min (P = 0.02) less than those with CH and normotension, respectively. Consequently, sleep efficiency was reduced by 7.9% (P = 0.007) and 10.2% (P = 0.002), respectively. They also spent 9.7 min (P = 0.06) and 11.6 min (P = 0.04) less time in REM sleep compared to those with CH and normotension, respectively. Older age, greater body mass index (BMI) and greater apnea-hypopnea index (AHI) were also associated with shorter sleep time (P = 0.02, P = 0.001, and P = 0.03, respectively) and reduced sleep efficiency (P = 0.0003, P = 0.03, and P = 0.01, respectively). CONCLUSIONS: Our study demonstrates that, compared to subjects with CH or normotension, those with RH have shorter total and REM sleep times and lower sleep efficiency independently of OSA. These data suggest that reduced sleep time may contribute to the severity of hypertension.

Antihypertensive drug persistence and compliance among newly treated elderly hypertensives in ontario.

BACKGROUND: Poor medication-taking behaviors are important considerations in the management of hypertension. METHODS: We conducted a retrospective cohort study addressing antihypertensive drug persistence and compliance by linking 4 administrative databases and a province-wide clinical database in Ontario, Canada, to derive a cohort of elderly hypertensive patients, aged 66 years or more, who had received a new prescription for an antihypertensive agent between 1997 and 2005 to determine trends across years and associations with drug class and sociodemographic and other factors. RESULTS: Our cohort consisted of 207,473 patients (58.4% were women, mean age 74.2 years, 73.1% were comorbid-free), 41,236 of whom had diabetes. Persistence and compliance increased between 1997 and 2005 (all P<.02) and were greater in those of higher socioeconomic status but lesser in urban residents (all P<.0001). Persistence was lower in comorbid-free patients and greater in older patients, whereas compliance was lower in older patients and greater in women and comorbid-free patients (all P<.0001). Significant differences between the drug classes emerged with initial prescriptions for all drug classes showing greater therapy and class persistence compared with diuretics (all P<.0001). Angiotensin-converting enzyme inhibitors showed the best therapy persistence and compliance, and beta-blockers showed the worst compliance (all P<.0001). CONCLUSION: Our data provide evidence of an overall improvement in antihypertensive drug compliance and persistence across years, as well as significant differences across drug classes and other patient-level factors. Awareness of such factors could translate into concerted efforts at optimizing medication-taking behaviors among newly diagnosed elderly hypertensive patients.

Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension.

Obstructive sleep apnea occurs frequently in patients with drug-resistant hypertension. The factors accounting for this observation, however, are unclear. Both conditions demonstrate clinical features suggestive of extracellular fluid volume overload. The aims of this study were to examine whether the spontaneous overnight fluid shift from the legs to the upper body is associated with obstructive sleep apnea in hypertensive subjects and whether its magnitude is greater in drug-resistant hypertension. Leg fluid volume and the circumference of the calf and neck were measured before and after sleep in drug-resistant hypertensive (n = 25) and controlled hypertensive (n=15) subjects undergoing overnight polysomnography. The severity of obstructive sleep apnea was greater in the drug-resistant hypertensive group than in the controlled hypertensive group (apnea-hypopnea index: 43.0 ± 5.4 versus 18.1 ± 4.2 events per hour of sleep; P = 0.02, case-mix adjusted). In both groups, the apnea-hypopnea index strongly related to the amount of leg fluid volume displaced (R² = 0.56; P < 0.0001), although the magnitude of change was greater in the drug-resistant hypertensive group (346.7 ± 24.1 versus 175.8 ± 31.3 mL; P = 0.01, propensity-score adjusted). The overnight reduction in calf circumference and increase in neck circumference were also greater in drug-resistant hypertension (both P ≤ 0.02). In hypertensive subjects, rostral fluid displacement strongly relates to the severity of obstructive sleep apnea with its magnitude being greater in drug-resistant hypertension. Our findings support the concept that fluid redistribution centrally during sleep accounts for the high prevalence of obstructive sleep apnea in drug-resistant hypertension.

The price of obstructive sleep apnea-hypopnea: hypertension and other ill effects.

This review addresses the cardiovascular, cerebrovascular, and metabolic consequences that accompany obstructive sleep apnea-hypopnea (OSAH) in conjunction with the mechanistic pathways implicated in mediating these effects. Particular emphasis is placed on the association with hypertension (HTN). Varying levels of evidence support a role of OSAH in perpetuating sustained HTN, nocturnal HTN, and difficult to control HTN as well as in contributing to the occurrences of nondipping of blood pressure (BP) and increased BP variability. In this context, the emergence of matched designs, adjusted analyses, meta-analyses as well as longitudinal and interventional studies strengthens causal inferences drawn from older observational studies, which suffered from such limitations as confounding.

Can nocturnal hypertension predict cardiovascular risk?

Nocturnal hypertension and non-dipping of blood pressure during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis. This review addresses several aspects related to these blood pressure abnormalities including definitions, diagnostic limitations, pathogenesis and associated patient profiles, prognostic significance, and therapeutic strategies. Taken together, persistent nocturnal hypertension and non-dipping blood pressure pattern, perhaps secondary to abnormal renal sodium handling and/or altered nocturnal sympathovagal balance, are strongly associated with deaths, cardiovascular events, and progressive loss of renal function, independent of daytime and 24-hour blood pressure. Several pharmacological and non-pharmacological approaches may restore nocturnal blood pressure and circadian blood pressure rhythm to normal; however, whether this translates to a clinically meaningful reduction in unfavorable cardiovascular and renal consequences remains to be seen.

Nocturnal blood pressure profiles among normotensive, controlled hypertensive and refractory hypertensive subjects.

BACKGROUND: Nocturnal blood pressure abnormalities are independently associated with an increased risk of death and cardiovascular disease. It is unclear, however, whether they are related to the presence or severity of hypertension. OBJECTIVES: To determine and compare the prevalence of sleep pattern disturbances in normotensive (NT) and hypertensive patients. METHODS: The present cross-sectional study assessed the nocturnal blood pressure profiles from 24 h ambulatory blood pressure monitoring of refractory hypertensive (RH) (n=26), controlled hypertensive (CH) (n=52) and NT (n=52) subjects who were matched for age, sex and body mass index. Results are expressed as mean +/- SD or proportion, as appropriate. RESULTS: During sleep, the percentage fall in mean arterial pressure was 15.1+/-6.1% in the NT group, 11.5+/-7.0% in the CH group and 7.7+/-7.7% in the RH group (P<0.0001). The corresponding proportions of nondipping were 25.0%, 42.3% and 61.5%, respectively (P=0.006), and those of nocturnal hypertension were 9.6%, 23.1% and 84.6%, respectively (P<0.0001). All pairwise comparisons of nocturnal blood pressure fall were significant. The proportion of subjects in the RH group who experienced a rise in nocturnal blood pressure (19.2%) was significantly greater than the proportions in the NT and CH groups (P=0.001), as was the proportion of subjects with nocturnal hypertension (P<0.0001). There was less extreme dipping in RH, although the difference was not statistically significant (P=0.08). CONCLUSIONS: A significantly higher prevalence of nondipping, nocturnal hypertension and nocturnal blood pressure rising in RH was demonstrated. These sleep disturbances or independently, their cause, may account for the difficulties in attaining blood pressure control.

Relationship between self-reported sleep duration and changes in circadian blood pressure.

BACKGROUND: Abnormalities in sleep duration and circadian blood pressure (BP) rhythm are both independently associated with increased risk of death and cardiovascular disease. The relationship, however, between these two entities remains unclear. This study was undertaken to determine whether abnormal sleep duration is associated with nondipping status and elevated morning surge. METHODS: In a cross-sectional study, we assessed the relationship between self-reported sleep duration and circadian BP profiles from 24-h ambulatory BP monitoring (ABPM) in 108 normotensive and 417 hypertensive subjects, independent of relevant sociodemographic, anthropometric, and medical factors. RESULTS: On average, subjects reported sleeping 6.5 +/- 1.7 h with 18.5% sleeping < or =5 h and 7.6%, > or =9 h. There were 199 (37.9%) nondippers in our cohort and the mean morning surge was 18.7 +/- 1.7 mm Hg. The adjusted odds ratio for nondipping (<10% nocturnal systolic BP fall) associated with a 1-h decrement in sleep duration was 1.12 (P = 0.04) and with age per 5-year increment, 1.15 (P = 0.0003). The adjusted odds ratio for an elevated morning surge (> or =18.0 mm Hg) associated with a 1-h increment in sleep duration was 1.13 (P = 0.02). CONCLUSIONS: Our study indicates that a sleep deficit is associated with nondipping and a decreased morning surge, whereas a sleep surfeit is associated with less nondipping and an increased morning surge. These findings provide a possible link for the heightened risk of cardiovascular disease associated with disturbances in circadian BP rhythm and the extremes of sleep quantity.