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Impaired Baroreflex Function and Arterial Compliance in Primary Journal of Human Hypertension (1999) 13, 29–36 1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 http://www.stockton-press.co.uk/jhh ORIGINAL ARTICLE Impaired baroreflex function and arterial compliance in primary aldosteronism F Veglio, P Molino, G Cat Genova, R Melchio, F Rabbia, T Grosso, G Martini and L Chiandussi Department of Medicine and Experimental Oncology, University of Turin, Italy The purpose of this study was to evaluate if changes in mary aldosteronism patients in the supine position (P vascular properties were related to baroreflex function = 0.002 and P Ͻ 0.05 respectively). Aldosterone in patients with primary aldosteronism. Twenty-three plasma levels (R2 = 0.31, P = 0.01),age,systolicand patients with primary aldosteronism, 22 essential hyper- diastolic BP, high and low frequency components of tensive patients and 16 normal controls were studied. diastolic BP variability were independently related to Continuous finger blood pressure (BP) was recorded by compliance in primary aldosteronism. In conclusion Portapres device during supine rest and active stand primary aldosteronism is associated with an impaired up. Compliance was estimated from the time constant baroreflex function related in part to a reduced arterial of pressure decay during diastole. Baroreflex sensitivity compliance. Despite a reduction of BP values and was calculated by autoregressive cross-spectral analy- aldosterone levels, surgical or pharmacological treat- sis of systolic BP and interbeat interval. The result was ment did not significantly change compliance values. that baroreflex gain and compliance were lower in pri- Keywords: baroreflex; compliance; primary aldosteronism Introduction of arterial pressure decay during the diastolic por- tion of the arterial pressure wave. During the development and progression of hyper- The aim of the present study was to evaluate if tension, the vascular structural changes may have the arterial compliance was reduced in patients with substantial effects on baroreflex activity. In patients primary aldosteronism and if the impaired spon- with essential hypertension, a reduced compliance taneous baroreflex gain was related to a reduced of carotid artery is partially related to baroreflex dis- 1 arterial compliance, analysing finger arterial press- function. ure waves recorded non-invasively by the Port- Abnormal circulatory reflexes have also been apres device. reported in hypertensive patients with primary aldo- steronism.2 Recently, using the spectral analysis of blood pressure (BP) and heart rate variability, we Materials and methods found an impaired spontaneous baroreflex control of Subjects the heart rate in such patients.3 Several studies have shown that a chronic mineralocorticoid excess leads We studied 23 hypertensive patients with primary ± to an increased collagen production inducing a peri- aldosteronism (PA: age 47.8 2.3 years, 12M/11F), 22 BP-matched essential hypertensives (EH: age 47.5 vascular fibrosis and heart remodelling in rats and ± humans.4–6 Hence these vascular changes could 2.3 years, 13M/9F) and 16 normal controls (N: age ± reduce arterial compliance and impair the barore- 45.7 2.3 years, 8M/8F). The diagnosis of primary aldosteronism was established by standard endo- flex sensitivity. 11 Spectral analysis of BP and heart rate variability crine tests. The differential diagnosis between has become a useful tool to assess the spontaneous aldosterone producing adenoma (APA) and idio- baroreflex gain by means of cross-spectrum analysis pathic aldosteronism (IHA) was performed by a 6- and calculation of the alpha index.7,8 (131-I)-iodo-methylnorcholesterol adrenal scan and Furthermore, various methods have been pro- adrenal computed tomography; when the TC scan posed to calculate the parameters of the Windkessel was negative or inconclusive adrenal vein sampling model (including total arterial compliance) from was performed. Six patients had adrenal adenoma analysis of the peripheral arterial pressure wave.9,10 and 17 bilateral adrenal hyperplasia. In the conventional time-domain approach, com- There was no evidence of renal injury or cardiac pliance values are estimated from the time constant failure in any patient. The study was performed at our Clinical Division after informed consent had been obtained and patients were asked not to take Correspondence: Dr Franco Veglio, Cattedra di Medicina Interna, any antihypertensive drugs or other medication and Ospedale S. Vito, Strada S. Vito 34, 10133 Torino, Italy to follow a diet with a normal sodium content for Received 7 August 1998; revised and accepted 20 September 1998 almost 4 weeks before the test. Participants were Baroreflex in primary aldosteronism F Veglio et al 30 asked to refrain from smoking, drinking coffee and taking sedatives for at least 24 h before test onset. Ten PA patients (7M/3F: two APA/eight IHA) were also studied after 1 year after the treatment: two patients were treated with surgical therapy while eight subjects received pharmacological ther- apy (high dose of spironolactone). Two males dis- continued spironolactone because of side effects (gynaecomastia, and reduction of libido); at the time of the study they were treated with Ca-antagonists and/or alpha-blockers. Protocol Study was performed in a quiet room between 9 am and 1 pm. After 30 min of supine rest, continuous finger BP was recorded by Portapres Model-2 device (TNO, Amsterdam, NL) at 200 Hz sampling fre- quency in the supine position for 15 min. The same procedure was repeated during 15 min of active stand up. Portapres provides an indirect measure- ment of BP in a finger based on the arterial volume- clamp method of Penaz and the physiocal (physiological calibration) criteria for the full unloading of the arteries in a manner identical to Figure 1 Top: Finger blood pressure record in a normal subject. Finapres.12,13 The same finger was used both in the Bottom: Diastolic portion of the blood pressure curve, used to supine and upright position. calculate compliance values. Data analysis Spectral analysis and baroreflex gain Data were then downloaded on a PC and analysed For each period (supine and upright), a sequence of by the Beatfast program (TNO) to identify systolic 400 to 600 data points (5–10 min) was analysed. The (SBP) and diastolic (DBP) blood pressure values and stationary point of BP and interbeat interval data interbeat intervals (IBI) for each cardiac cycle: after was checked by visual inspection. Mean values of digital low pass filtering at 17 Hz, SBP is stored as SBP, DBP, IBI were calculated. In the frequency the highest pressure level during the ejection. DBP domain, power spectral analysis of SBP, DBP and is arterial end diastolic pressure just before the next IBI was performed by the autoregressive method upstroke begins. IBI is the time difference between (Burg method) using custom software implemented two following systolic pressures. on MATLAB program, after linear interpolation of data at 1 Hz frequency (to obtain equispaced data) Windkessel parameters and demeaning. The order of the autoregressive model was 13 ± 2. Compliance (C) was estimated from the time con- The total power was then divided into low fre- stant (␶) of arterial pressure decay during diastole quency (0.025 − 0.14 Hz, LF) and high frequency (Figure 1): ␶ = R*C, where R are peripheral resist- (0.14 − 0.4 Hz, HF) components. Spectral compo- ances. This method requires the computation of car- nents of IBI variability were expressed in normalised diac output (CO) and peripheral resistances (R): CO units (by dividing the power of a given component was estimated from the algorithm proposed and by the total variance from which the direct current validated with invasive studies by Cohn et al14 as a component had been subtracted, and multiplying by multivariate function of ejection time, heart rate, 100). The baroreflex gain was computed as alpha body surface area and age: stroke volume =−6.6 + index, ie, the square root of the ratio of the powers (0.25 ET) − (0.62 HR) + (40.4 BSA) − 0.51 (Age), of IBI in the LF range to corresponding SBP spec- where ET is the ejection time in milliseconds, HR is tral components: heart rate in beats per minute and BSA is body sur- ␣ =√ face area in squared meters. Peripheral resistances LFIBI / LFSBP were then calculated as mean arterial pressure/CO. For each period (supine and upright), a sequence Hormonal measurements of 150 to 250 arterial pressure waves were analysed. An automatic procedure implemented on MATLAB At the end of the supine period and after 1 h of software provides the computation of compliance, upright position, blood samples (7 ml) were with- CO and R for each wave, excluding artifacts and drawn from the antecubital vein into K2-EDTA abnormal waveforms: a minimum of 100 valid tubes placed on ice. Plasma was immediately separ- waves was required for further evaluations. Mean ated and stored at −40°C until assayed. Plasma renin values of Windkessel parameters were calculated for activity was assayed by radioimmunoassay (RIA) each period. measuring the quantity of generated angiotensin I Baroreflex in primary aldosteronism F Veglio et al 31 (Incstar Corp, Stillwater, MN, USA). Plasma aldos- and EH patients at rest, compared to N controls (P terone was measured by RIA (Sorin, Saluggia, Italy). = 0.004). In the upright position PA patients showed Plasma adrenaline and noradrenaline levels were higher total peripheral resistances than the other assayed by high performance liquid chromatography two groups. This parameter increased significantly with an electrochemical detector. in PA and EH patients after tilt. CO did not differ between all groups at rest and during tilt, and it decreased significantly during tilt Statistical evaluation in PA and N subjects. Statistical evaluation was performed by the Statisti- Spectral components of BP and HR variability are cal Analysis System (SAS Institute Inc, Cary, NC, shown in Table 3. Low frequency component of SBP USA) using ANOVA or t-test for paired data where and DBP variability at rest was significantly higher appropriate.
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