The relationship between sleep deprivation and the nocturnal decline of blood pressure.

Blood pressure (BP) has a circadian pattern with a 10% to 15% drop in systolic and diastolic BP comparing nighttime and daytime averages. The mechanism and the "reason" for the decline of nocturnal blood pressure has not been described. If the nocturnal decline is a restorative physiologic process we reasoned that sleep deprivation would increase the nocturnal drop. Thus, we tested the hypothesis that there is a compensatory decline in nocturnal sleep blood pressure after a period of nocturnal sleep deprivation. Twenty-four house staff personnel (normotensive and not taking any BP medications) with a mean age of 29.3 years were recruited for this study (13 men and 11 women). Subjects were randomly assigned to have 24-h BP monitoring after being sleep deprived (on call with 3 +/- 1.3 h of sleep) or after a normal night's sleep (7.3 +/- 0.8 h). There was no significant difference in hours asleep or time to bed or time awake for both 24-h studies. Subjects had similar activities for both monitoring intervals. The percent change in day awake versus night asleep mean values for systolic BP, diastolic BP, and mean arterial pressure for sleep deprived and normal night's sleep intervals were compared using paired t tests. None of these paired parameters were significantly different despite a subjectively "deeper" sleep postcall. In conclusion, sleep deprivation does not appear to result in a compensatory decline in nocturnal blood pressure. Thus, the "reason" for the normal nocturnal decline in blood pressure remains to be explored.

Treatment of hypertension in renal failure patients: when do we overtreat? When do we undertreat?

Despite the commonplace nature of hypertension in chronic dialysis patients, many issues remain unresolved. According to current JNC/V (see text) recommendation, a systolic blood pressure of < 120 mm Hg is optimal, 120-129 mm Hg is normal, and one of 130-139 mm Hg is high-normal. The majority of dialysis patients receiving treatment in the United States is probably not maintained in the optimal blood pressure range. However, if the J curve hypothesis has credence, many of our dialysis patients may be susceptible to overtreatment, especially of their diastolic blood pressure. In patients with ischemic cardiovascular disease, several studies show a decrease in survival with diastolic blood pressures < 85 mm Hg. This J curve phenomenon is seen predominantly in patients with ischemic heart disease. Since many, and possibly most, of the currently treated end-stage renal disease patients in the United States have existing atherosclerotic cardiovascular disease when they start chronic dialysis therapy, lowering of the diastolic blood pressure below a J threshold may be dangerous. This problem may be especially prevalent in diabetics with diabetic cardiomyopathy. Diabetics and other end-stage renal disease patients may be started on hemodialysis with glomerular filtration rates in the 10- to 15-cm2/min range. Patients with high residual renal function may have small intradialytic weight gains and frequent intradialytic hypotension. This 'overtreatment' may lead to postdialysis arrhythmias and sudden death in chronic dialysis patients. As in the nonrenal failure population, end-stage renal disease patients with left ventricular hypertrophy have a 2- to 3-fold increased risk of death from cardiovascular diseases, and all cause mortality. In contrast to nonrenal failure patients, normotensive ESRD patients may show an increase of left ventricular mass over time. Although left ventricular hypertrophy can be reversed with good blood pressure control, patients are often undertreated based on analysis of dialysis clinic blood pressures. Even if clinic systolic blood pressure levels are optimal, chronic dialysis patients may still have unacceptably high ambulatory blood pressure levels due to a rise in nocturnal blood pressure with sleep.

Circadian blood pressure variation versus renal function.

Several published reports describe an abnormal circadian blood pressure profile in chronic renal failure subjects. Factors other than renal failure, including age, diagnosis of diabetes mellitus, autonomic dysfunction, and race, also may affect circadian blood pressure profiles. To further elucidate the relationship between renal function and circadian blood pressure variation, we compared day/night circadian blood pressure changes in three groups of male veteran hypertensive patients: group A, creatinine clearance (CC) > 80 mL/min, n = 20; group B, CC 20 to 80 mL/min, n = 19; and group C, CC < 20 mL/min, n = 14. We use postural changes in catecholamines, renin, and aldosterone as a measure of autonomic function. No significant difference in day/night percent change in systolic, diastolic, mean arterial pressure (MAP), or heart rate was seen by renal function group. Regression analysis using age, diagnosis of diabetes mellitus, postural hormonal changes, and creatinine clearance found race to be the only significant predictor of the day/night percent change in MAP (P < 0.05). Compared with whites, black subjects had higher nocturnal heart rates (P = 0.01); smaller day/night heart rate changes (P = 0.03); significantly higher diastolic blood pressure (P = 0.01); and a trend toward smaller day/night change in diastolic blood pressure (P = 0.06). In conclusion, renal function level does not influence day/night blood pressure changes. The blunting or reversal of the normal circadian blood pressure pattern seen in some chronic renal failure hypertensive subjects may be attributable to the association between chronic renal failure and cofactors associated with abnormal circadian blood pressure, including black race and possibly severity of atherosclerosis.

The effect of sleep intervals on analysis of 24-h ambulatory blood pressure data.

Twenty-four hour blood pressure exposure and circadian blood pressure variability may be important predictors of hypertensive end-organ damage. Since sleep is a major determinant of circadian blood pressure decline, day/night blood pressure changes may be affected by sleep intervals. The current study compares 24-h blood pressure results with and without adjustment for patient-specific sleep intervals. Forty male hypertensive patients (22 with renal insufficiency and 18 with normal renal function) underwent 24-h blood pressure study with SpaceLabs 90207 monitors. They also filled out sleep questionnaires to evaluate time awake and asleep during the day and night intervals. Data was analyzed with and without adjustment for daytime asleep and nighttime awake intervals. The percent change in systolic, diastolic, and mean arterial pressure as well as heart rate was not different statistically or clinically with or without adjustment for sleep intervals. Nevertheless, there was a progressive increase in the day versus night percent change in these hemodynamic parameters with adjustment for sleep intervals. When we used arbitrary cut-offs to define "non-dipper", ie, less than 10% drop in a given hemodynamic parameter, and used patient-specific sleep intervals, clinically and statistically different numbers of "non-dippers" were seen versus sleep unadjusted data (19 v 12, using diastolic BP, P < .01). In conclusion, it may not be necessary to adjust for sleep intervals when relating 24-h blood pressure and day/night blood pressure variability to hypertensive end-organ damage. However, arbitrary cut-offs to define "non-dippers" may be greatly and capriciously affected by sleep/awake intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of autonomic function using Valsalva ratio and 30:15 postural ratio prior to and after haemodialysis treatment.

In published studies of chronic haemodialysis patients, the frequency of autonomic dysfunction varies widely. One reason for the variation may be the time of testing with respect to time of dialysis. The current study tests the hypothesis that autonomic function--as measured by heart rate responses to the Valsalva manoeuvre (Valsalva ratio) and 30:15 electrocardiogram (ECG) R-R interval to upright posture (postural ratio)--is different when patients are above 'dry weight' (predialysis) than when they are at or below dry weight (postdialysis). The study also reviews available literature to analyze other factors that may affect the results of autonomic testing in this population. A total of 25 chronic haemodialysis patients underwent standard Valsalva and 30:15 R-R interval postural autonomic testing prior to and after haemodialysis. In addition, pre- and postdialysis orthostatic responses were measured and compared with a control population. The 30:15 ratio increased after dialysis (p = 0.001). The Valsalva ratio did not change with dialysis. Out of 25 subjects, seven had an abnormal 30:15 ratio prior to dialysis decreasing to two out of 25 patients postdialysis (p < 0.03). Orthostatic responses predialysis did not differ from those in the control group. Review of the literature shows great variability in definition of normal Valsalva and postural (30:15 R-R interval) ratios. Diabetic patients in the current and prior studies were more likely to have abnormal responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal blood pressure measurement: can it be predicted by self-monitoring and is 24-hr BP monitoring clinically important in the treatment of hypertension.

We predict that 24-hour blood pressure data will be required prior to starting treatment in order to receive third-party payment. We are currently performing a cost benefit analysis in patients with mild to moderate hypertension to see the prevalence of inappropriate treatment of hypertension (diagnosed by normal 24-hour BP results) in an outpatient clinic population. We will compare the cost of treating that segment of the population that is inappropriately on treatment to the cost of 24-hour BP monitoring for the entire study population. As a result of this type of analysis, health care payors may require 24-hour BP documentation prior to hypertension treatment for all cases of mild to moderate hypertension.

Refractory hypotension associated with hypocalcemia and renal disease.

A 35-year-old hypertensive man presented with chronic renal insufficiency, congestive heart failure, and refractory hypotension. He had metabolic acidosis and profound hypocalcemia. Left ventricular function and blood pressure worsened after intravenous infusion of saline and bicarbonate, but improved dramatically after intravenous calcium administration. This case illustrates that hypocalcemia is a cause of refractory hypotension and heart failure.

Blood pressure changes during daytime sleep and comparison of daytime and nighttime sleep-related blood pressure changes in patients with chronic renal failure.

Blood pressure has a diurnal pattern primarily related to activity and sleep. Chronic renal failure patients may lack the normal nocturnal decline in blood pressure during sleep. In 33 subjects (14 with normal renal function and 19 with renal dysfunction), the relationship between depth of daytime sleep, as determined by electroencephalographic sleep phase, and change in mean arterial blood pressure (MAP) and heart rate measured oscillometrically, was correlated. In 15 chronic renal failure patients, the effect of daytime and nighttime sleep on MAP and heart rate was compared. The percent change in night asleep versus day awake MAP and heart rate was measured (with Space Labs ambulatory blood pressure monitors) and compared with the percent change in daytime sleep-related MAP and heart rate measured during a daytime sleep electroencephalographic study. During daytime sleep, MAP changes are not significantly different in the normal versus renal dysfunction groups. In the 33 study subjects, MAP declines progressively from the upright position to Phase 3/4 sleep (118 +/- 3.6 to 106 +/- 3.6 mm Hg). The largest decline occurs between the upright to recumbent position, before sleep. Heart rate declines moving from the upright to recumbent position, 76 +/- 2.3 to 70 +/- 2.1 beats/min, but does not decline further with sleep. In 15 chronic renal failure patients, heart rate (10.8 +/- 2.8%; P < 0.05), but not MAP, declines during nighttime sleep. Both MAP (7.7 +/- 3.3%) and heart rate (5.4 +/- 1.9%) decline significantly during daytime sleep. The responses of MAP and heart rate to daytime and nighttime sleep were in opposite directions in 3 of 15 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of transdermal clonidine in chronic hemodialysis patients.

Large fluctuations of blood pressure are commonly experienced by hypertensive, chronic hemodialysis patients. Many patients hold anti-hypertensive medication immediately prior to dialysis to prevent intradialytic hypotension. Weekly dosing of continuously released antihypertensive agents may result in better blood pressure control than conventional daily dosing. To evaluate the effect of weekly transdermal clonidine on this problem, we compared intra- and interdialytic blood pressure control and side effects during six weeks of transdermal clonidine monotherapy and six weeks of conventional oral antihypertensive treatment in nine stable chronic hemodialysis patients. Since transdermal clonidine is recommended for mild to moderately severe hypertension and since clonidine is excreted by the kidneys and removed by hemodialysis, we also evaluated blood pressure control and clonidine levels while utilizing high-dose transdermal clonidine, up to 0.12 mg per week. Intradialytic blood pressure was monitored twice weekly during the weeks 3-6 of transdermal clonidine and conventional therapy. Twenty-four hour blood pressure was monitored weeks 3 and 6 of each study phase. Plasma clonidine levels were measured by HPLC in 11 patients. Transdermal clonidine monotherapy failed to adequately control blood pressure in 6 of 21 chronic dialysis patients with moderate to severe hypertension. No significant difference in intra- or interdialytic blood pressure control or side effects (including dry mouth or thirst) was found comparing conventional to transdermal clonidine therapy. While not statistically different, heart rate was lower during transdermal clonidine therapy compared to conventional therapy, especially at very high doses. Despite a mean hemodialysis clearance of clonidine of 59.2 +/- 7.8 ml/min, clonidine levels remained therapeutic beyond one week.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate of change of end-stage renal disease treatment incidence 1978-1987--has there been selection?

End-stage renal disease (ESRD) treatment rates in the United States have increased steadily since 1973. Decreasing selection against elderly patients with a poor prognostic primary cause of ESRD (i.e., diabetic nephropathy) may partly account for this increase in rates. To test this hypothesis, we calculated log ESRD treatment incidence (ESRDI) rates by four major primary causes of ESRD (diabetic nephropathy (DN), hypertensive nephropathy (HN), glomerulonephritis (GN), and cystic kidney disease (PC); two age groups (old (O), greater than 65 and young (Y), 15 to 44 yr of age) for black and white, male and female, new ESRD patients from 1978 to 1987. As predicted, summary log ESRDI slopes (produced by analysis of covariance) occurred in the following decreasing order, ODN (0.19), OGN = OHN = YDN (0.134). YHN = YPC = YGN (in white patients) = slope not significantly different from 0. Log ESRDI slopes for young black males and females with GN increased significantly between 1978 and 1987, possibly as a result of an increased incidence of GN. In conclusion, decreasing selection may be a factor in the continuing increase in the U.S. ESRD population.

Effect of osmolar changes on plasma arginine vasopressin (PAVP) in dialysis patients.

The effect of changes in plasma osmolality and changes in plasma arginine vasopressin (PAVP) were analyzed in 10 stable chronic hemodialysis patients utilizing four protocols. During regular hemodialysis opposing influences on PAVP (decrease in blood pressure and intravascular volume and increase in serum calcium) resulted in no significant change in PAVP (by analysis of variance). In the second protocol low dialysate calcium (2.5 meq/l) isovolemic hemodialysis was used. PAVP and serum osmolality levels declined from 2.0 +/- 0.4 to 1.4 +/- 0.2 microU/ml (p less than 0.05), and 285 +/- 2.5 mOsm/l to 275 +/- 3.2 mOsm/l respectively. Removal of PAVP by hemodialysis did not occur as evidenced by no difference in arterial-venous PAVP levels and no "rebound" of PAVP for three hours after completion of dialysis (second protocol). Isovolemic low calcium high dialysate sodium (145 meq/l) hemodialysis was utilized in the third protocol. Serum osmolality and PAVP did not change. Addition of a very high dialysate sodium (155 meq/l) to isovolemic low calcium hemodialysis resulted in an increase in plasma sodium, osmolality and AVP (139.7 +/- 0.62 to 144 +/- 0.67 meq/l, 294 +/- 2.79 to 304.3 +/- 2.4 mOsm/l and 1.8 +/- 0.3 to 2.7 +/- 0.5 microU/ml (p less than 0.05 for each) respectively. In conclusion, PAVP responds to changes in plasma osmolality in chronic hemodialysis patients.

The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects.

We compared the changes in serum creatinine levels over time after a mean follow-up of 9.8 years in essential hypertensive (EH, n = 56) and control (n = 59) male veteran subjects. All subjects had normal serum creatinine levels (62 to 124 mumol/L) and "normal" urinalysis results on entry into the study. Subjects with comorbid renal diagnoses and diabetes mellitus were eliminated from the analysis. Although not statistically significant, the rate of change in the serum creatinine concentration over time was greater in the EH cohort compared with the control cohort (1.08 +/- 4.8 vs 0.027 +/- 3.5 mumol/L per year). The difference was especially marked in black EH subjects vs black control subjects (1.60 +/- 6.2 mumol/L per year vs -0.21 +/- 3.3 mumol/L per year). When age, race, body mass index, and a diagnosis of EH were entered into a logistic regression analysis, EH subjects had a statistically significantly greater rate of decline in renal function than did control subjects (1.5 +/- 8.3 mumol/L per year). When mean time-averaged systolic blood pressure for each subject was also included in the logistic regression analysis, only systolic time-averaged blood pressure was statistically significant (0.063 +/- 0.029 mumol/L per year). We conclude that in the absence of clinically detected parenchymal renal disease, EH subjects have a greater rate of decline in renal function than do nonhypertensive subjects. Time-averaged blood pressure is predictive of the change in serum creatinine concentration not only in EH subjects but also in nonhypertensive subjects. Thus, preservation of renal function may require a blood pressure lower than the currently accepted normotensive range.

Comparative incidence rates of end-stage renal disease treatment by state.

End-stage renal disease (ESRD) treatment rates vary significantly between states in the United States. Much of this variation relates to the much higher rate of ESRD in blacks and the differences in race, age, and sex composition of various states. Even after adjusting for race, age, and sex differences utilizing data from new patients reported to Medicare with ESRD between 1980 and 1983, marked variation in treatment incidence rates per million population were still present. Overall rates varied from 45 in North Dakota to 99 in New Jersey. Regional rate patterns were demonstrated with very high rates in southwestern states (Texas, New Mexico, Arizona, and California: 87-91/million). In contrast, several south-central states had lower rates (Arkansas, Louisiana, Mississippi, Alabama, and Tennessee: 66-75/million). By state the rates for blacks were consistently higher than for whites. After adjustment for sex and age differences, the rates for blacks varied from 125 in Arkansas to 242 in New Jersey. Several north-eastern states (Massachusetts, Connecticut, Rhode Island, New Jersey) had higher rates of ESRD in blacks (197-242 million) as compared with several south-central states (Arkansas, Louisiana, Mississippi, Tennessee, Alabama) where rates varied from 125 to 180 million. ESRD rates by primary etiologies by state showed marked variation of the major primary etiologies of ESRD: diabetic nephropathy rates were most predictive of overall ESRD rates, with much higher rates in the southwestern states (28.1-33.2) as compared with the south-central states (12.8-16.3).(ABSTRACT TRUNCATED AT 250 WORDS)