It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and 65 not receiving ART) with no history of diabetes or hypertension. None of the renal markers, modeled as either continuous or categorical variables, correlated with FMD. Contrary to expectations, endothelial dysfunction may not be the link between nephropathy and CVD in HIV.

Unlike the general population, among hemodialysis patients body-mass index(BMI)is inversely related to blood pressure (BP) and mortality. To explore the reasons for this risk-factor paradox the cross-sectional association of obesity with the following factors was examined: the prevalence of hypertension, its control and echocardiographic left ventricular mass index (LVMI). Longitudinal follow-up explored the relationship of BMI with all-cause mortality. Further it explored whether poorer survival in leaner individuals was related to either high BP or greater LVMI. Among 368 hemodialysis patients both the prevalence of hypertension and its poor control were inversely related to BMI. BMI was also inversely associated with evidence of excess extracellular fluid volume but adjustment for this variable did not completely remove the inverse relationship between BP and BMI. Over 1122 patient-years of cumulative follow up (median 2.7 years) 119 (32%) patients died. In the first two years of follow up, the mortality hazard for the lowest BMI group was increased; thereafter, the survival curves were similar. Adjusting for several risk factors including BP and LVMI did not remove the inverse relationship of BMI with mortality. In conclusion, leaner patients on dialysis have a higher prevalence of hypertension, poorer control of hypertension, more LVMI, and greater evidence of extracellular fluid volume excess. However, volume only partially explains the greater prevalence or poorer control of hypertension. Leaner patients have an accelerated mortality rate in the first two years; this is not completely explained by BP, LVMI or other cardiovascular or dialysis-specific risk factors.

Background

The epidemiology of hypertension among hemodialysis (HD) patients is difficult to describe accurately because of difficulties in the assessment of blood pressure (BP).

Methods

Using 44-hour interdialytic ambulatory BP measurements, we describe the epidemiology of hypertension in a cohort of 369 patients. To seek correlates of hypertension control, antihypertensive agents were withdrawn among patients with controlled hypertension and ambulatory BP monitoring was repeated.

Results

Hypertension (defined as an average ambulatory systolic BP ≥135 mm Hg or diastolic BP ≥85 mm Hg, or the use of antihypertensive medications) was prevalent in 82% of the patients and independently associated with epoetin use, lower body mass index and fewer years on dialysis. Although 89% of the patients were being treated, hypertension was controlled adequately in only 38%. Poor control was independently associated with greater antihypertensive drug use. Inferior vena cava (IVC) diameter in expiration was associated with increased risk of poorly controlled hypertension both in cross-sectional analysis and after withdrawal of antihypertensive drugs.

Conclusions

Interdialytic hypertension is highly prevalent and difficult to control among HD patients. End-expiration IVC diameter is associated with poor control of hypertension in cross-sectional analyses as well as after washout of antihypertensive drugs. Among HD patients, an attractive target for improving hypertension control appears to be the reduction of extracellular fluid volume.

Most management decisions for the diagnosis and treatment of hypertension are made using blood pressure (BP) measurements made in the clinic. However, home BP recordings may be of superior prognostic value. In this review, we show that home BP recordings are generally superior to clinic BP measurements in predicting long-term prognosis. Home BP has been shown to significantly predict important end points including all-cause mortality, progression of chronic kidney disease, and functional decline in the elderly. In addition, home BP recordings significantly and strongly predict cardiovascular events. These findings are robust, as they concur despite having been studied in disparate populations, using heterogeneous methods of clinic and home BP measurement, and with varied methods of statistical analysis. The advantages of home BP recordings are not due solely to a larger number of measurements, and they extend to the elderly, patients with chronic kidney disease, and those on hemodialysis. Because home BP recordings combine improved accuracy with the advantages of low cost and easy implementation, most patients with known or suspected hypertension should have their BP assessed and managed by means of home BP recordings.

Background

Although probing dry-weight improves blood pressure control, its effect on echocardiographic left ventricular mass index (LVMI) is unknown.

Methods

Shortly following dialysis, 292 echocardiograms in 150 patients participating in the DRIP trial were obtained at baseline and longitudinally every 4 weeks on 2 occasions.

Results

At baseline, LVMI was 136.3 g/m2 in the control group and 138.7 g/m2 in the ultrafiltration group (p > 0.2 for difference). The change from baseline in LVMI in the control group was +3.5 g/m2 at 4 weeks and +0.3 g/m2 at 8 weeks (p > 0.2 for both changes). The change from baseline in LVMI in the ultrafiltration group was −7.4 g/m2 at 4 weeks (p = 0.005) and −6.3 g/m2 at 8 weeks (p = 0.045). With ultrafiltration, the change in LVMI diameter was −10.9 g/m2 more compared to the control group at 4 weeks (p = 0.012) and −6.6 g/m2 more compared to the control group at 8 weeks (p = 0.21). The reduction in interdialytic ambulatory blood pressure was also greater in response to probing dry-weight in those in the top half of LVMI at baseline (p = 0.02 for interaction effect at week 8).

Conclusion

LVMI, an important determinant of prognosis among long-term dialysis patients, is responsive to probing dry-weight.

The reference standard for making a diagnosis of hypertension among hemodialysis patients is 44-hour interdialytic ambulatory BP monitoring. However, a more practical way to diagnose and manage hypertension is to perform home BP monitoring that spans the interdialytic interval. In contrast to pre- and postdialysis BP recordings, measurements of BP made outside the dialysis unit correlate with the presence of left ventricular hypertrophy and directly and strongly with all-cause mortality. Hypervolemia that is not clinically obvious is the most common treatable cause of difficult to control hypertension; volume control should be the initial therapy to treat hypertension in most hemodialysis patients. To diagnose hypervolemia, continuous blood volume monitoring is emerging as an effective and simple technique. Reducing dietary and dialysate sodium is an often overlooked strategy to improve BP control. Although definitive randomized trials that demonstrate cardiovascular benefits of BP lowering among hypertensive hemodialysis have not been performed, emerging evidence suggests that lowering BP may reduce cardiovascular events. Since predialysis and post-dialysis BP are quite variable and agree poorly with measurements obtained outside the dialysis unit, treatment should be guided by BP obtained outside the dialysis unit. While the appropriate level to which BP should be lowered remains elusive, current data suggests that interdialytic ambulatory systolic BP should be lowered to <130 mmHg and averaged home systolic BP to <140 mmHg. Antihypertensive drugs will be required by most patients receiving 4 hour thrice weekly dialysis. Beta blockers, dihydropyridine calcium blockers and agents that block the renin-angiotensin system appear to be effective in lowering BP in these patients.

Background. Intradialytic blood pressure (BP) profiles have been associated with all-cause mortality, but its pathophysiology remains unknown. We tested the hypothesis that intradialytic changes in BP reflect excess volume.

Methods. The dry weight reduction in hypertensive haemodialysis patients (DRIP) trial probed dry weight in 100 prevalent haemodialysis patients; 50 patients who did not have their dry weight probed served as time controls. In this post hoc analysis, intradialytic BP was recorded at each of the 30 dialysis treatments during the trial. The slope of intradialytic BP over dialysis was calculated by the log of BP regressed over time. Using a linear mixed model, we compared these slopes between control and ultrafiltration groups at baseline and over time, tested the effect of dry weight reduction on these slopes and finally tested the ability of change in intradialytic slopes to predict change in interdialytic systolic BP.

Results. At baseline, intradialytic systolic and diastolic BP dropped at a rate of ~3%/h (P < 0.0001). Over the course of the trial, compared to the control group, the slopes steepened in the ultrafiltration group for systolic but not diastolic BP. Those who lost the most post-dialysis weight from baseline to 4 weeks and baseline to 8 weeks also experienced the greatest steepening of slopes. Each percent per hour steepening of the intradialytic systolic BP slope was associated with 0.71 mmHg [95% confidence interval (CI) 0.01–1.42, P = 0. 048] reduction in interdialytic ambulatory systolic pressure.

Conclusions. Intradialytic BP changes appear to be associated with change in dry weight among haemodialysis patients. Among long-term haemodialysis patients, intradialytic hypertension may, thus, be a sign of volume overload.

Among chronic hemodialysis patients, 217 hospitalizations/1000 patient-years are due to congestive heart failure; some are attributable to unrecognized hypervolemia. Hypervolemia can be detected by relative plasma volume (RPV) monitoring. The purpose of this study was to examine among 308 patients on long-term hemodialysis the value of slope of RPV compared to either ultrafiltration volume or ultrafiltration rate index in determining all-cause mortality. RPV slopes were calculated by least-squares regression. These slopes were related to all-cause mortality in unadjusted and adjusted Cox proportional hazards models. Over a median follow up of 30 months (IQR 14 – 54 months) 96 (31%) patients died yielding a crude mortality rate of 113/1000 patient years. We found that 1) RPV slope measurements were of prognostic significance (hazard ratio of flatter slopes (>1.39%/hour) 1.72, p = 0.01); 2) the ultrafiltration volume alone was not prognostically informative (hazard ratio of higher UF volume (>2.7 liter/dialysis) 0.78, p=0.23); 3) the ultrafiltration rate index alone was also not prognostically informative (hazard ratio of higher UF rate index (>8.4 mL/kg/hr) 0.89, p=0.6); and 4) the prognostic relationship of RPV slope to mortality was independent of conventional and unconventional cardiovascular risk factors including the ultrafiltration volume, ultrafiltration rate or ultrafiltration volume/kg post weight. RPV monitoring yields information that is prognostically important and independent of several risk factors including ultrafiltration volume, aggressiveness of ultrafiltration, and interdialytic ambulatory BP. Its use to assess excess volume among chronic hemodialysis patients should be tested in randomized controlled trials.

Blood pressure measured before and after dialysis does not agree well with those recorded outside the dialysis unit. Whether recordings obtained outside the dialysis unit are of greater prognostic value than blood pressure obtained just before and after dialysis remains incompletely understood. Among 326 patients on long-term hemodialysis, blood pressure was self-measured at home for one week, over an interdialytic interval by ambulatory recording and before and after dialysis over two weeks. Over a mean follow up of 32 (SD 20) months, 102 patients died (31%) yielding a crude mortality rate of 118/1000 patient years. Systolic but not diastolic blood pressure was found to be of prognostic importance. Multivariate-adjusted and unadjusted analyses showed increasing quartiles of ambulatory and home systolic blood pressure to be associated with all-cause mortality (adjusted hazard ratios for increasing quartiles of ambulatory: 2.51, 3.43, 2.62 and for home blood pressure: 2.15, 1.7, 1.44). Mortality was lowest when home systolic BP was between 120–130 mm Hg and ambulatory systolic blood pressure was between 110–120 mmHg. Blood pressure recorded before and after dialysis were not statistically significant (p=0.17 for predialysis and p=0.997 for postdialysis) in predicting mortality. Out-of-dialysis unit blood pressure measurement provided superior prognostic information compared to BP within the dialysis unit (likelihood ratio test, p<0.05).

Conclusions

Out-of-dialysis-unit blood pressure among hemodialysis patients is prognostically more informative than that recorded just before and after dialysis. Therefore the management of hypertension among these patients should focus on blood pressure recordings outside the dialysis unit.

Among hemodialysis patients the assessment of dry-weight remains a matter of clinical judgment because tests to assess dry-weight have not been validated. The objective of this study was to evaluate and validate relative plasma volume monitoring as a marker of dry-weight. We performed relative plasma volume monitoring using the Critline monitor at baseline and 8 weeks in 150 patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial. The intervention group of 100 patients had dry-weight probed whereas 50 patients served as time controls. Relative plasma volume slopes were defined as flat when they were less than the median (1.33%/hour) at the baseline visit. Among predominantly (87%) African-American hemodialysis patients, we found that flat relative plasma volume slopes suggest a volume overloaded state because of the following reasons: 1) probing dry-weight in these patients leads to steeper slopes; 2) those with flatter slopes at baseline had greater weight loss; 3) both baseline relative plasma volume slopes and the intensity of weight loss were found to be important for subsequent change in relative plasma volume slopes; and most importantly 4) relative plasma volume slopes predicted the subsequent reduction in interdialytic ambulatory systolic BP. Those with the flattest slopes had the greatest decline in BP upon probing dry-weight. Both baseline relative plasma volume slopes and the change in relative plasma volume slopes were important for subsequent changes in ambulatory systolic BP. We conclude that relative plasma volume slope monitoring is a valid method to assess dry-weight among hypertensive hemodialysis patients.

Purpose of Review

Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of BP has been shown to be associated with greater target organ damage and to be associated with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP

Recent findings

The time-keeper of the mammals resides centrally in the suprachiasmatic nucleus. Besides this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice to the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon 3 major factors: physical activity, autonomic function, and sodium sensitivity.

Summary

The integrated consideration of physical activity, autonomic function, and sodium sensitivity appear to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.

Background

Hemodialysis patients have a steady increase in blood pressure (BP) over the 44-hour interdialytic interval when ambulatory BP monitoring is used. Home BP recording allows for longer period of monitoring between dialysis and may better define the chronobiology of arterial hypertension. This study sought to determine the optimal time to perform home BP monitoring in hemodialysis patients to improve the strength of prediction of 44-hour interdialytic ambulatory BP.

Study Design

Diagnostic test study

Setting and Participants

This is an ancillary analysis of patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial.

Index test

Home BP measured three times a day for one week using a validated oscillometric monitor on 3 occasions at 4 week intervals after randomization. Home BP measured during the first third, second third and last third of time elapsed after dialysis as well as each third of dialysis was compared to the overall ambulatory BP.

Reference Tests

Interdialytic ambulatory BP measured on 3 occasions at 4 week intervals after randomization.

Results

Over the interdialytic interval, we found an increase in systolic ambulatory BP of 0.30 ± 0.36 mmHg/hr and an increase in systolic home BP of 0.40 ± 0.25 mmHg/hr. This relationship in home BP reached a plateau after approximately 48 hrs. A similar pattern was seen for diastolic home BP. Probing dry-weight steepened the slope of ambulatory BP but did not alter the time-dependent relationship of home BP. Home BP was on average higher (bias) by 14.1 (95% CI 12.0 to 16.2)/5.7 (95% CI 4.6 to 6.9) mmHg. The standard deviation of differences between methods (precision) was 4.6/2.8 mmHg. Measurement of BP during each third of the interdialytic interval gave the best precision as measured by model fit compared to ambulatory BP measurements.

Limitations

Our cohort was overrepresented by African American hemodialysis patients. Whether African American participants have a different pattern of BP response than non-African American participants in the interdialytic period is not known.

Conclusions

Our findings suggest that time elapsed after dialysis must to be considered in interpreting the home BP recordings in hemodialysis patients. Home BP measured in each third of the interdialytic interval is likely to yield the most reliable BP estimate.

Although volume excess causes hypertension whether it also affects circadian patterns of arterial pressures among hemodialysis patients remains unknown. To test the notion whether volume overload is associated with a unique BP “signature” a post-hoc analysis was performed among 145 patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) randomized controlled trial. Using 400 ambulatory BP recordings over 8 weeks comprising 35,302 measurements the trended cosinor model was found to be the best descriptor of BP chronobiology. The trended cosinor model may be described as a pattern of sinusoidal oscillation around a straight line with an upward trend during the interdialytic period and which has an intercept at the postdialysis time. Augmented volume removal therapy (AVRT) reduced the intercept systolic BP and increased the rate of rise in systolic BP over the interdialytic interval but had no effect on the systolic BP fluctuation (amplitude). Thus an elevated intercept and blunted slope pattern characterizes the “volume overload BP pattern” on ambulatory BP monitoring. Similar changes were seen for diastolic BP. AVRT neither restored dipping nor was associated with a lag-phenomenon for either the wake or sleep systolic BP. Lowering of systolic BP was greater than diastolic BP such that pulse pressure was reduced. An observational cohort of 37 patients followed for 6 months confirmed these findings. Randomized trials are now needed to evaluate the clinical impact of AVRT on hard outcomes since reduction of pulse pressure with this simple expedient has the potential to improve survival in hemodialysis patients.

Epidemiological studies demonstrate that a lower blood pressure and decline in blood pressure over months or years are associated with higher mortality in dialysis patients. In contrast, randomized controlled trials lack power to establish benefits of antihypertensive therapy. Patients on long-term dialysis participating in randomized controlled trials and receiving antihypertensive drug therapy were the subject of this meta-analysis. Outcomes assessed were the hazard ratio of cardiovascular events and all-cause mortality in treated group compared to controls. Among 1202 patients we identified in 5 studies, the overall benefit of antihypertensive therapy compared to control or placebo group had a combined hazard ratio for cardiovascular events of 0.69 (95% CI 0.56 to 0.84) using a fixed effects model and 0.62 (95% CI 0.44 to 0.88) using a random effects model. In a sensitivity analysis we found that the hypertensive group had a pooled hazard ratio of 0.49 (95% CI 0.35 to 0.67), but when normotensives were included in the trial lesser cardiovascular protection was seen (pooled hazard ratio of 0.86 (95% CI 0.67 to 1.12)). Test for herterogenity between hypertensive and “normotensive-included” groups was significant (p<0.006). Similar results were seen for risk ratio for death and cardiovascular events. There was evidence of publication bias based on Egger's test and funnel plot. Randomized trials suggest benefit of antihypertensive therapy among hemodialysis patients. Adequately powered randomized trials are required to confirm these observations especially among those with hypertension.

Volume excess is thought to be important in the pathogenesis of hypertension among hemodialysis patients. To determine whether additional volume reduction will result in improvement in blood pressure (BP) among hypertensive patients on hemodialysis and to evaluate the time-course of this response we randomized long-term hypertensive hemodialysis patients to ultrafiltration or control groups. In the additional ultrafiltration group (n=100) we probed the dry-weight without increasing time or duration of dialysis while the control group (n=50) only had physician visits. The primary outcome was change in systolic interdialytic ambulatory BP. Post-dialysis weight was reduced by 0.9 kg at 4 weeks and resulted in -6.9 mm Hg (95% CI -12.4, -1.3 mm Hg, p=0.016) change in systolic BP and -3.1 mm Hg (95% CI -6.2, -0.02 mm Hg, p=0.048) change in diastolic BP. At 8 weeks, dry-weight was reduced 1 kg, systolic BP changed -6.6 mm Hg (95% CI -12.2, -1.0 mm Hg, p=0.021) and diastolic BP -3.3 mm Hg (95% CI -6.4, -0.2 mm Hg, p=0.037) from baseline. The Mantel-Hanzel combined odds-ratio for systolic BP reduction of at least 10 mm Hg was 2.24 (95% CI 1.32, 3.81, p=0.003). There was no deterioration seen in any domain of the kidney disease quality of life health survey despite an increase in intradialytic signs and symptoms of hypotension. The reduction of dry-weight is a simple, efficacious and well tolerated maneuver to improve BP control in hypertensive hemodialysis patients. Long-term control of BP will depend on continued assessment and maintenance of dry-weight.

Dual blockade of the renin-angiotensin system (RAS) with a combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of hypertension and proteinuria has been tested in several randomized trials among patients with chronic kidney disease (CKD). Although combination therapy reduces proteinuria and blood pressure, adequately powered studies evaluating time to end-stage renal disease, death, or cardiovascular outcomes in patients with CKD have not been done. Dual blockade of RAS can cause hyperkalemia, renal failure, and orthostatic hypotension and potentially worsen outcomes; therefore, the risk-benefit ratio in patients with CKD remains unclear. A recent randomized trial in patients with cardiovascular disease or high-risk diabetes raises concerns about the safety of this combination therapy.

Home blood pressure (BP) monitoring serves as a practical method to detect changes in BP instead of ambulatory BP monitoring in hemodialysis patients. To evaluate the relationship of reduction in home BP compared to interdialytic ambulatory BP measurements we analyzed the data from the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial in which 100 patients had their dry weight probed based on clinical sign and symptoms and 50 patients served as controls. We measured home BP 3 times a day for 1 week using a validated oscillometric monitor on 3 occasions at 4-week intervals after randomization. Changes from baseline in home, predialysis BP and postdialysis BP were compared to interdialytic 44-hour ambulatory BP. Home and ambulatory BP monitoring was available in 141 of 150 (94%) patients. Predialysis systolic BP was not as sensitive as ambulatory BP in detecting change in BP with dry-weight reduction. Whereas postdialysis BP was capable of detecting an improvement in systolic BP in response to probing dry weight, by itself it does not provide evidence that change in postdialysis BP persists over the interdialytic period. Home BP reliably detected changes in ambulatory BP, albeit with less sensitivity at 4 weeks. However, at 4 and at 8 weeks, changes in home systolic BP were most strongly related to changes in interdialytic ambulatory systolic BP compared to predialysis and postdialysis BP. The reproducibility of BP measurements followed the order home > ambulatory >> predialysis > postdialysis. These data provide support for the use of home BP monitoring for the management of hypertension in hemodialysis patients.

The analysis of change is central to the study of kidney research. In the past 25 years, newer and more sophisticated methods for the analysis of change have been developed, however as of yet these newer methods are underutilized in the field of kidney research. Repeated measures ANOVA is the traditional model that is easy to understand and simpler to interpret, but it may not be valid in complex real-world situations. Problems with the assumption of sphericity, unit of analysis, lack of consideration for different types of change, and missing data, in the repeated measures ANOVA context are often encountered. Multilevel modeling, a newer and more sophisticated method for the analysis of change, overcomes these limitations and provides a better framework for understanding the true nature of change. The present article provides a primer on the use of multilevel modeling to study change. An example from a clinical study is detailed and the method for implementation in SAS is provided.

Purpose of review

Hypertension is an important risk factor for adverse cardiovascular and renal outcomes particularly in patients with chronic kidney disease. This review compares blood pressure measurements obtained in the clinic with those obtained outside the clinic to predict cardiovascular and renal injury and outcomes.

Recent findings

Data are accumulating that suggest that ambulatory blood pressure monitoring is a superior prognostic marker compared to blood pressures obtained in the clinic. Use of ambulatory blood pressure monitoring can detect white coat hypertension and masked hypertension which results in less misclassification of blood pressures. Ambulatory blood pressure monitoring is a marker of cardiovascular end points in CKD. Non dipping is associated with proteinuria and lower GFR. Although non-dipping is associated with more ESRD and cardiovascular events, adjustment for other risk factors removes the prognostic significance of non-dipping. For patients with CKD, not on dialysis, 24 hour ambulatory BP of <125/75 mm Hg, daytime ambulatory of <130/85 mm Hg and nighttime ambulatory BP of <110/70 mm Hg appear to be reasonable goal BP targets. In the management of hypertension in patients with CKD, control of hypertension is important. Ambulatory BP monitoring may be useful to assign more aggressive treatment to patients with masked hypertension and withdraw antihypertensive therapy in patients with white-coat hypertension.

Summary

Ambulatory blood pressure monitoring can refine cardiovascular and renal risk assessment in all stages of chronic kidney disease. The independent prognostic role of non-dipping is unclear.

Background:

Although the cardiac biomarker troponin T (cTnT) is strongly related to mortality in end-stage renal disease, the independent association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cTnT in predicting outcomes is unknown.

Objective:

To determine factors associated with NT-proBNP and cTnT, and to determine whether these levels are associated with mortality.

Study Design:

Cohort Study

Settings and Participants:

Asymptomatic hemodialysis patients (n=150) in 4 university-affiliated hemodialysis units.

Exposure and Outcomes:

For cross-sectional analysis, echocardiographic variables as exposures and N-terminal proBNP and cardiac troponin T as outcomes; for longitudinal analysis, association of N-terminal proBNP and cardiac troponin T as exposures to all-cause and cardiovascular disease mortality as outcomes.

Results:

In a multivariate regression analysis, low midwall fractional shortening a measure of poor systolic function was an independent correlate of log NT-proBNP (p<0.01), while left ventricular mass index was an independent correlate of cTnT (p<0.01). Over a median follow-up of 24 months, 46 patients died of which, 26 died due to cardiovascular causes. NT-ProBNP had a strong graded relationship with all-cause (Hazard Ratio (HR) 1.54, 4.78 and 4.03 for increasing quartiles, Chi2 32.2, p<0.001) and cardiovascular mortality (HR 2.99, 10.95, 8.54 Chi2 23.66, p<0.01), while cTnT had a weaker relationship with all-cause (HR 1.57, 2.32, 3.39, Chi2 23.09, p<0.01) and cardiovascular mortality (HR 1, 0.81, 2.12, 2.14, Chi2 15.05, p=0.1). The combination of the two biomarkers did not improve the association with all-cause or cardiovascular mortality compared to NT-proBNP alone. NT-proBNP was a marker of mortality even after adjusting for left ventricular mass index and midwall fractional shortening.

Limitations:

Our cohort was predominantly black and of limited sample size.

Conclusion:

NT-proBNP strongly correlates with left ventricular systolic dysfunction and is more strongly associated with mortality than cTnT in asymptomatic hemodialysis patients.