Correlation of Quantitated Intravascular Volume with Blood Pressure in Patients with Systemic Hypertension

Abstract

Introduction:

Volume management is an essential component of anti-hypertensive therapy. Different volume phenotypes have been proposed. We sought to study the total blood volume (TBV), plasma volume (PV) and red blood cell volume (RBV) in hypertensive patients.

Methods:

We included patients followed in an outpatient cardiology clinic from 1998–2003. Blood volume (BV) parameters were measured using radioisotope iodine-131-labeled albumin dilution technique. Values were expressed as percentage (%) deviation from ideal volumes.

Results:

A total of 95 patients were included. The intravascular volume distribution as percent deviation from normal volume ranged from −23% to +28% for TBV, −22% to +36% for PV and −29% to +37% for RBV. There was no significant correlation between systolic BP and any of the BV parameters (TBV and SBP, r=−0.03; PV and SBP, r=−0.12; RBV and SBP, r=−0.08).

Discussion:

Patients with hypertension have a wide variation in BV parameters. BV does not correlate with SBP.

INTRODUCTION

Uncontrolled blood pressure (BP) is a leading cause for cardiac and renal-related morbidity and mortality. Evidence-based guidelines focus on the simplification of hypertension management, moving away from personalized treatment approaches. Blood volume (BV) and vascular tone are well-established determinants of BP (1–3), making them central targets in the management of hypertension. The presence of several hypertension phenotypes based on the combination of volume status and vascular tone have been reported (4) but findings have been inconsistent. Studies investigating the significance of volume phenotypes in hypertension date back to the 1970’s and were mostly performed in experimental settings. The present study was undertaken to provide a contemporary analysis of the three main components of total BV in adults with hypertension [total blood volume (TBV), plasma volume (PV) and red blood cell volume (RBV)], and determine whether there is a relationship between BV parameters and systemic BP in hypertensive patients encountered in clinical practice.

METHODS

Retrospective analysis of patients with chronic stable hypertension followed in an U.S. urban cardiology outpatient clinic from 1998–2003. BV was measured during early evaluation of hypertension using the indicator-dilution-technique of radio-labelled iodine-131 albumin. The clinic used an FDA approved and commercially marketed technology indicated for blood volume determinations (Daxor Volumex HSA I-131, N.Y). There was no specific timing as to when a BV was obtained in the course of an evaluation of HTN. The science behind blood volume analysis is based upon the indicator dilution technique. A known amount of tracer is introduced into an unknown volume, and after it has fully mixed within that volume, the dilution of the tracer is measured. The lower the concentration of tracer, the larger the volume of the substance the tracer was introduced into. Labelled albumin was injected over 1 minute with serial blood draws at 12, 18, 24, 30 and 36 minutes post-injection. Activity values were extrapolated back to time zero to provide a measure of PV (BVA- 100, Daxor, N.Y). Values are expressed as percentage (%) deviation (+/−) from normal expected volumes. Normal reference values were determined from previously established gender-adjusted reference curves using the deviation from ideal body weight method (2,5). BP was obtained in a seated position with single time-point measurements. The deidentified dataset was obtained from Daxor, NY for all patients with available BV analysis and clinical data. Analysis was performed using the student t-test and interaction testing. A p-value <0.05 was considered statistically significant.

RESULTS

A total of 95 consecutive patients were included in our analysis. The mean office systolic BP (standard deviation [±SD]) was 148 (±48) mmHg and mean diastolic pressure (±SD) was 91 (±7) mmHg. There was a predominance of women (56.8%), with an overall mean age of 60 years. The self-identified racial background of our patients varied, with 40% White, 35.8% Black, 8.4% Hispanic, and 2.1% Asian. Twenty-nine patients (30.5%) had diabetes, 5 (5.3%) had diagnosed renal disease (eGFR <60mg/dl/min), and 11 (11.6%) had heart failure. The majority of the patients were receiving at least one anti-hypertensive medication (70.6%); 21.2% were on a beta-blocker, 27.1% on ACE-inhibitor or ARB, 22.3% were on a diuretic, 17.6% received calcium channel blockers, and 8.2% alpha-blockers. Diuretic therapy was equally distributed between blacks and non-blacks (15% vs 17%).

The intravascular volume distribution as percent deviation from normal volume ranged from −23% to +28% for TBV, −22% to +36% for PV and −29% to +37% for RBCV (Figure 1A). There was no significant correlation between systolic BP and any of the BV parameters (TBV and systolic BP, r=−0.03; PV and systolic BP, r=−0.12; TBV and systolic BP, r=−0.08) (Figure 1B). There was a significant interaction for gender and the relationship between gender and systolic BP (women: coefficient 0.35 vs. men: coefficient −0.65; p=0.022). Blacks had significantly lower BV compared to non-blacks (p<0.001), despite comparable SBP [152± 25 mm Hg vs. 145±20 mm Hg, (mean ± SD), p>0.05] (Figure 1C–E). There was no difference in TBV, PV or RBV when comparing patients with or without anti-hypertensive treatment (p>0.05); patients on diuretics had overall lower BV parameters, but this difference was not statistically significant.

Figure 1:

Blood volume analysis in patients with hypertension. A- Deviation of total blood volume from ideal. B- Correlation between blood volume and systolic blood pressure. Race based blood volume analysis. Deviation from ideal C- Total blood volume, D- Plasma Volume, and E- Red Blood Cell Volume, stratified by race (Blacks vs. White/Hispanic/Asian).

DISCUSSION

Our findings reveal a large variability in measured BV among patients with chronic stable hypertension. There does not appear to be a significant association between volume status and BP regardless of treatment, gender or race. The present findings are unique as we report from a contemporary clinical cohort and the results suggest the presence of diverse volume phenotypes amongst patients with hypertension. The findings highlight that hypervolemia should not be regarded as ubiquitous in hypertension or necessarily the prime target in the management of hypertension for every patient.

While the relationship between BV and plasma renin-activity was reported to differ among racial subgroups (6), it has been suggested that blacks with hypertension are likely to be in the low-renin profile and hence the BP lowering efficacy of Renin-Angiotensin-Aldosterone-System (RAAS) inhibitors to be attenuated in this patient population. Although limited by the lack of RAAS measurements in our study, BV parameters shown to be lower in blacks despite similar BP. This provides uncertainty toward any long-held conclusion of predominant volume expansion as a sole basis for hypertension in black patients.

Some limitations are worth mentioning. The clinical diagnostic use of BV analysis using radiolabeled dilution technique was not protocolized/standardized. Thus, it is likely that not all patients with the diagnosis of hypertension underwent this test which introduced an unmeasured bias. Further, the therapeutic actions by the clinician and the outcomes of the patients were not measured and included in the analysis.

Volume management is essential to anti-hypertensive therapy as described in current guidelines. Our findings suggest that volume assessment could provide unique insight during the workup of hypertension. Thus future work needs to determine whether quantitated volume analysis might help guide the most appropriate therapy in hypertensive adults.