Importance of 24 Hours Ambulatory Blood Pressure Monitoring in Patients With Acromegaly and Correlation With Cardiac Magnetic Resonance Findings

doi:10.21203/rs.3.rs-2491932/v1

Arterial hypertension (AH) is prevalent in acromegaly, but few studies using 24-hour ambulatory blood pressure monitoring (24h-ABPM) suggest that its frequency may be different from office blood pressure (OBP). Left ventricular hypertrophy (LVH) is one of the most frequent cardiac abnormalities. Cardiac magnetic resonance (CMR) is considered the gold standard to evaluate the heart.

OBJECTIVES: To compare the frequency of AH when measured by 24h-ABPM and by OBP and to correlate BP with cardiac mass.

METHODS: Patients over 18 years of age with acromegaly underwent OBP evaluation and were later referred to the 24h-ABPM. Treatment-naïve patients were submitted to CMR.

RESULTS: We evaluated 96 patients. From 29 non hypertensive patients by OBP, 9 had AH on 24h-ABPM. In the group of patients with a previous diagnosis of AH by OBP, 25 had controlled BP and 42 had abnormal BP on 24h-ABPM when analyzed by OBP there were 28 with controlled BP. We observed a positive correlation between diastolic BP measured in 24h-ABPM and IGF-I levels, but we do not observe the same correlation with age, sex, body mass index and GH levels. The CMR was performed in 11 patients. We found a positive correlation of left ventricular mass (LVM) and BP of 24h-ABPM. In contrast, there was no correlation of OBP with CMR parameters.

CONCLUSIONS: We observed, that 24h-ABPM in acromegaly allows the diagnosis of AH in some patients with normal BP in OBP and also to allow a better treatment. 24h-ABPM shows a better correlation with VM by CMR.

We observed that 24h-ABPM in acromegaly is important because it allows the diagnosis of arterial hypertension in some patients with normal blood pressure in OBP and also to allow a better management of drug treatment in patients previously diagnosed with AH. Also, it shows a better correlation with ventricular mass when assessed by the gold-standard method CMR. Therefore, we think our study can contribute to the management of patients with acromegaly, highlighting the importance of using 24h-ABPM and not only OBP in these patients.

Acromegaly

Hypertension

Cardiac Magnetic Resonance

24h-24-hour ambulatory blood pressure monitoring

Acromegaly is a rare multisystem disease caused by hypersecretion of growth hormone (GH) and consequently excess of insulin-like growth factor-I (IGF-I) that leads to multiple comorbidities and premature mortality (1). Arterial hypertension (AH) is historically mentioned as significantly more prevalent among patients with acromegaly than in general population (2), although few studies with small series (the biggest with 40 patients) using 24-hour ambulatory blood pressure monitoring (24h-ABPM) suggest that it is overestimated by clinical measurements (3, 4). Cardiac involvement can be an early event in acromegaly and its progression is related to the time of disease activity (5). The most frequent cardiac abnormality is left ventricular hypertrophy (LVH), that is found regardless of the presence of other cardiovascular risk factors (5). However, several studies have documented the coexistence of AH, diabetes and dyslipidemia as accelerators of cardiac complications in patients with acromegaly (5).

Cardiac magnetic resonance (CMR) imaging with gadolinium is considered the gold standard method to evaluate the heart anatomy and function (6, 7). CMR has been used to evaluate cardiac involvement and the efficacy of acromegaly control over cardiomyopathy (6, 8). An independent relation of cardiac morphological changes in echocardiography [increases in left ventricular mass (LVM), posterior wall thickness, interventricular septum thickness, relative thickness of left ventricular wall, and left atrial end-systolic diameter] and AH has been demonstrated (9). However, no previous study has correlated blood pressure (BP) levels measured by 24h-ABPM and cardiac mass measured by CMR.

The aims of this study were to compare the frequency of AH when measured by 24h-ABPM and by office measurement in a cohort of patients with acromegaly, and to analyze the usefulness of 24h-ABPM to evaluate the efficacy of AH treatment in patients with a previous diagnosis of AH. Furthermore, to correlate systolic blood pressure (SBP) and diastolic blood pressure (DBP) with cardiac mass in patients with acromegaly.

Study population

Consecutive > 18 years-old patients with acromegaly were recruited from the outpatient endocrinology clinic of the Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ) from August 2018 until March 2021. Diagnosis of acromegaly was made according to current criteria (10). This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of HUCFF/UFRJ (3. 858. 071) and Faculdade de Medicina da UFRJ and all patients signed written informed consent forms.

Study Design

This was a transversal, single-center study. This study was conducted in accordance with the Declaration of Helsinki and ap

Clinical And Biochemical Variables

The following clinical and biochemical variables were evaluated before 24h-ABMP: body mass index (BMI), calculated using the formula weight (kg) divided by height squared (m²) (11) and systolic and diastolic blood pressures (BP), measured in millimeters of mercury (mmHg).

The cardiovascular risk factors investigated were smoking (at least 1 cigarette/day), diabetes mellitus [fasting glucose ≥ 126 mg/dL and/or glycated hemoglobin (HbA1c) at least 6.5% in two separate samples and/or current use of antidiabetic treatment] (12), dyslipidemia [total cholesterol > 200 mg/dL, low-density lipoprotein cholesterol (LDL-c), calculated using the Friedewald formula (total cholesterol minus HDL-c minus triglycerides/5 in mg/dL), > 130 mg/dL and/or triglycerides > 150 mg/dL or statin use], overweight correspond to a BMI ≥ 25Kg/m² and obesity (BMI ≥ 30 kg/m²) (13, 14).

Office Bp (Obp) Measurements

Patients were submitted twice to BP measurement by aneroid sphygmomanometer during the physical examination at neuroendocrinology outpatient clinic of HUCFF-UFRJ with the patient seated (at least 1 min apart), on the right arm supported at the level of the heart, with a cuff appropriate to the size of the arm. We used the average of both measurements in accordance with the usual recommendations of American Heart Association and European Society of Cardiology (13, 14). The usual antihypertensive medication was checked. Arterial hypertension was defined as SBP higher than 140 mmHg and/or DBP higher than 90 mmHg following repeated examination or as treatment of previously diagnosed AH (15).

Hormone Assays

Plasma GH levels were measured with chemiluminescent immunoassay (HGH kit IMMULITE 2000 XPi; Siemens, Erlangen, Germany). GH detection had an analytical sensitivity of 0.05 ng/mL with intra-assay and interassay coefficients of variation of 3.5% and 6.5%, respectively. The International Reference Preparation (IRP) for GH was the 98/574. Plasma IGF-I level was assessed based on upper limit of normal range (ULNR) and measured with chemiluminescent immunoassay (IGF-I kit IMMULITE 2000 XPi; Siemens, Erlangen, Germany). IGF-I detection had an analytical sensitivity of 20–25 ng/mL with intra-assay and interassay coefficients of variation of 3.9% and 8.1%, respectively. The IRP for IGF-I was the 87/518. All plasma samples were collected in the early morning after an 8h fasting period.

Twenty-four Hours Abpm

Patients underwent 24h-ABPM at ProHart outpatient clinic at HUCFF-UFRJ using a validated DynaMAPA AOP (Cardios, São Paulo, SP, Brazil) (16). All patients, who used antihypertensive drugs, were instructed to take their usual medication. The protocol consisted of measurements every 15 min during the daytime and every 30 min during sleep. The night time measurement was individually adjusted according to the patient’s record. Mean SBP and DPB of 24 h, and of daytime and night time were evaluated. Sleep time relative SBP or DBP decline or “dipping” was calculated as 100% (mean daytime SBP or DBP – mean night-time SBP or DBP)/ mean day-time SBP or DBP. A nondipper profile was considered when this ratio was less than 10% for SBP or DBP and the patients classified as dipping or non dipping patterns. The usual 24h-ABPM normality values considered were SBP daytime ≤ 135mmHg and DBP daytime ≤ 85mmHg and SBP night time ≤ 120mmHg and DBP night time ≤ 70mmHg (17).

Cardiac Evaluation

CMR acquisition and interpretation

Treatment-naïve patients underwent CMR study before the 24h-ABPM measurement.

A whole-body 3.0-T scanner was used (MAGNETOM Trio, Siemens AG) with an eight-element body coil and fast parallel acquisition. The CMR was performed at baseline by only one investigator blinded to the clinical data. The following measures were analyzed: left atrium volume, interventricular septum and posterior wall thickness, left ventricular ejection fraction (LVEF), LV end-diastolic volume, LV end-systolic volume (VDFVE and VSFVE) and LV mass. We used a cut-off point for LVEF of 57%.

Cine imaging using retrospective electrocardiography gating with segmented steady-state free precession (SSFP) readout during a breath hold was done. Standard imaging included a short axis stack of cine SSFP images from cardiac base to apex. Typical scan variables included field of view = 32–38 cm, matrix of 256 x 208, slice thickness = 8 mm, gap = 2 mm, GRAPPA acceleration factor of 2, with 12 segments per RR interval (temporal resolution of 38 msec), resulting in approximately 8 − 10 heart beats per breath-hold. All analyses were blindly performed in a dedicated offline workstation (CMR42, Circle Cardiovascular Imaging). The LVM, left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LVEF (stroke volume divided by end-diastolic volume), and interventricular septum thickness (IVST) were determined. All CMR data except LVEF and IVST were indexed (i) to body surface area (BSA). The normal values (18) are as follows: LVMi, men 49–85; women, 41–81; LVEDVi, men 57–105, women 56–96; LVESVi, men 14–38, women 14–34; LVEF 57–77.

Delayed Myocardial Enhancement

Late gadolinium enhancement (LGE) was performed approximately 7–10 minutes after an IV injection of 0.15 mmol/kg of a gadolinium chelate infusion (gadoteric acid), using a standard segmented inversion-recovery spoiled gradient echo sequence with careful inversion time (TI) adjustment for null the myocardium. Typical acquisition variables were as follows: matrix 240 x 192; slice thickness, 8 mm; gap, 2 mm; 14 segment views; and TI, 280–320 msec with phase-sensitive reconstruction images on short and long axis of the left ventricle. LGE was considered positive when hyperenhancement was observed in at least two different views, was confirmed by phase-sensitive reconstruction images, and was considered not an artifact by the reader (19).

Statistical analysis

Statistical analyses were performed using SPSS 20.0 for Mac (IBM, Chicago, IL, USA). The Kolmogorov–Smirnov test was performed to analyze the distribution pattern of numerical variables. Categorical variables were expressed as percentage and frequency, and numerical variables were expressed as mean ± SD or median (min – max). Student’s t test or the Mann-Whitney U test was performed to compare numerical variables between the two groups. Correlations between numerical variables were analyzed using Pearson’s correlation test or Spearman test, as appropriate. P value < 0.05 was considered significant.

We evaluated 96 patients with acromegaly (55 females) of whom 63 had controlled disease and 67 had a previous diagnosis of AH and were in use of medications to control BP. Clinical and laboratory characteristics of the entire cohort are described in Table 1.

Table 1: Clinical and laboratorial characteristics of the patients

Characteristics	Value
Age (years)	56 (21-88)
Women (%)	55 (57.3)
BMI (kg/m²)	32.8 (31.1-34.6)
Overweight (%)	29 (30.2)
Obesity (%)	34 (35.4)
Hypertension (%)	67 (69.8)
Diabetes mellitus (%)	37 (40.2)
Glucose (mg/dL)	105 (70-437)
HbA1c (%)	6.2 (4.8-13.1)
Total cholesterol (mg/dL)	173 (112-307)
HDL cholesterol (mg/dL)	47.5 (24-117)
LDL cholesterol (mg/dL)	101.5 (44-219)
Triglycerides (mg/dL)	129 (35-645)
Family hypertension (%)	46 (48.4)
Active smoker/previous smoker (%)	30 (32.6)
Pharmacological control n (%)	63 (68.4)
Active acromegaly, n (%)	29 (31.5)
IGF-I (% ULNR)	0.88 (0.16-4.81)
GH (mcg/L)	0.8 (0-119)
Acromegaly diagnosis (years)	12 (1-38)
Office SBP (mmHg)	130 (92-180)
Office DBP (mmHg)	80 (60-113)
Hypertension diagnosis (years)	14 (1-45)
Hypertensive by 24h-ABPM n (%)	53 (55.2)
Hypertensive by office BP n (%)	75 (78.1)
Night hypertension n (%)	52 (54.1)
Nondipper SBP (%)	56 (58.3)
Nondipper DBP (%)	51 (53.1)

Values are expressed as absolute values, median + range or frequency. BMI, body mass index; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; IGF-I, insulin-like growth factor-I; ULNR, upper limit of normal range; GH, growth hormone; SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure; n, number of patients.

From the patients with a previous diagnosis of AH (n=67), most of them were using multiple antihypertensive drugs to control AH (Table 2) and underwent the following acromegaly treatments (most of them underwent surgery and subsequent adjuvant drug treatment): 37 were submitted to transsphenoidal surgery (nine patients had two or more surgeries), 10 patients underwent radiotherapy and twenty were only treated with medical therapy. From the patients under medical therapy, 25 were using cabergoline, 41 octreotide LAR, seven pasireotide LAR and three pegvisomant. Most of hypertensive patients had macroadenoma and the median duration of acromegaly was 12 years (1-38). Fifty-one of these patients had controlled acromegaly.

Table 2- Description of antihypertensive treatment in patients with acromegaly

Numbers of antihypertensive drugs	Number of patients (total=67)
Three or more drugs	25
Two drugs (diuretic + ACE-i/ARB or DHP-CCB)	21
One drug (diuretic or ACE-i or ARB)	19
Not reported	2

ACE-i, angiotensin converting enzyme-inhibitor; ARB, angiotensin AT-1 receptor blocker;
DHP-CCB, dihydropyridine calcium channel blocker.

From the patients without previous AH (n=29), most of them harbored macroadenomas (19/29) and underwent surgery subsequently followed by drug treatment: 16 had been submitted to transsphenoidal surgery, three had a history of two or more surgeries, three underwent radiotherapy and eight were only treated with medical therapy. From the patients under medical treatment, 25 were in use of cabergoline, 41 of octreotide LAR and seven of pasireotide LAR. From this group twelve patients had controlled acromegaly, and the median duration of acromegaly was 5 years (1-27).

No difference of age, GH and IGF-I levels, total cholesterol, HDL-cholesterol and LDL-cholesterol levels or glucose level, family history of AH and smoke history was observed between the groups with or without a previous diagnosis of AH.

From 29 non hypertensive acromegaly patients by OBP, nine (31%) had AH on 24h-ABPM (Table 3). In the group of patients with a previous diagnosis of AH, 25 had controlled BP and 42 had abnormal BP on 24h-ABPM (17 had abnormal BP, one only abnormal DBP, 20 nocturnal abnormal BP, three resistant BP and one isolated SBP on 24h-ABPM) (Table 4). When comparing the BP of patients with a previous diagnosis of AH analyzed by OBP with that of 24h-ABPM, we observed nine patients with uncontrolled BP in the 24h-ABPM that had a controlled BP in OBP measure (Table 5), in addition 4 patients presented high BP in OBP but had a controlled BP in 24h-ABPM.

Table 3: Report of 24h-ABPM in patients without diagnosis of previous hypertension

Report of ABPM-24h:	Patients without the diagnosis of previous arterial hypertension (n= 29)
Normal BP behavior in the 24 hours	20
Abnormal BP behavior in the 24 hours	5
Nocturnal arterial hypertension alone	3
Higher 24h-DBP	1
ABPM-24h, 24-hour ambulatory blood pressure monitoring; BP, Blood pressure; DBP, Diastolic blood pressure; SBP, Systolic blood pressure.

Table 4: Report of 24h-ABPM in patients with diagnosis of previous hypertension

Report of ABPM-24h:	Patients with previous diagnosis of arterial hypertension (n= 67)
Normal BP behavior in the 24 hours	23
Abnormal BP behavior in the 24 hours	17
Resistant high BP from white coat	2
Abnormal DBP in the 24hours	1
Nocturnal arterial hypertension	20
Resistant BP	3
Isolated SBP in the 24-hours	1

ABPM-24h, 24-hour ambulatory blood pressure monitoring; BP, blood pressure; DBP,
diastolic blood pressure; SBP, systolic blood pressure.

Table 5- BP analyses in patients with previous AH (n=67) by OBP and 24h-ABMP

	OBP	24h-ABMP
Controlled BP	29	25
Not controlled BP	38	42

BP, blood pressure; AH, arterial hypertension; OBP, office blood pressure; 24h-ABMP, 24-
hour ambulatory blood pressure monitoring.

We observed a high prevalence of systolic and diastolic non-dipper patients [16 (69.6%) in the office non-hypertension group and 56 (83.6%) in the office hypertension group] and a positive correlation between maximum and minimum DBP measured in 24h-ABPM and IGF-I levels (r=0.215, p=0.044 and r=0.246, p=0.021, respectively), but we did not observe the same correlation with age, sex, BMI and GH levels.

Patients with controlled BP at 24h-ABPM were younger than those with high BP at 24h-ABPM [53 (21 – 82) vs 59 (23 – 88), respectively, p=0.001], but no difference of GH and IGF-I levels, total cholesterol, HDL-cholesterol and LDL-cholesterol or glucose level, family history of AH and smoke history were found between these groups. We also did not find any difference in the number of patients with controlled acromegaly between these two groups (Table 6).

Table 6: Main characteristics of the sample with and without controlled BP on 24h-ABPM

Value	Controlled 24h- ABPM (n=45)	Not controlled 24h-ABPM (n=51)	p value
Age (years)	53 (21-82)	59 (23-88)	001
Women (%)	55.5 (25)	58.8 (30)	979
Overweight (%)	82.2 (37)	76.5 (39)	232
Diabetes mellitus (%)	42.2 (19)	35.3 (18)	319
Glucose (mg/dL)	105 (73-437)	109.5 (70-339)	926
Total colesterol (mg/dL)	166.5 (117-278)	182 (112-307)	091
HDL cholesterol (mg/dL)	47.5 (26-77)	48 (24-117)	931
LDL cholesterol (mg/dL)	95.5 (48-196)	103.5 (44-219)	136
Triglycerides (mg/dL)	123 (35-645)	147 (57-281)	161
Family hypertension (%)	53.3	66.7	0. 173
Active smoker/previous smoker (%)	8.9 (4)	31.4 (16)	131
Active acromegaly, n (%)	40 (18)	29.4 (15)	992
GH (mcg/L)	4 (<0.05-119)	2.5 (0.08-37.4)	0. 751
IGF-I (% ULNR)	0.87 (0.31-3.83)	0.88 (0.16-4.81)	0.773
Values are expressed as absolute values, median + range or frequency. BP, blood pressure; ABPM, ambulatory blood pressure measurements; HDL, high-density lipoprotein; LDL, low-density lipoprotein; GH, growth hormone; n, number of patients; IGF-I, insulin-like growth factor-I; ULNR, upper limit of normal range

The CMR was performed in 11 treatment-naive patients (4 had previous AH diagnosis). We found a positive correlation of left ventricular mass (LVM) with several parameters of 24h-ABPM: night time DBP (p=0.004 r=0.788), max. night time DBP (p=0.001 r=0.855), min night time DBP (p=0.036 r=0.633), min night time mean BP (p=0.029 r=0.655), max night time mean BP (p=0.037 r=0.633), max SBP daytime (p=0.013 r=0.745), min daytime DBP (p=0.004 r=0.791), min mean daytime BP (p=0.004 r=0.845), max SBP night time (p=0.007 r=0.761). In contrast, there was no correlation of DBP and SBP measured by OBP with CMR parameters.

The LVM was significantly higher in the abnormal 24h-ABMP group than in the normal 24h-ABPM group [230 (189-277) vs 113 (96-188), respectively, p= 0.004), but no difference in the ejection fraction or left atrial volume between the groups was found (p=0.662 and p=0.429, respectively). LVH (Figure 1) was observed in 63.6% of the patients submitted to CMR. Two patients had fibrosis without ischemic etiology at CMR, but one had a previous myocarditis history. The other nine patients didn’t have myocardial fibrosis. Systolic function was normal in all patients.

We found, in the largest series of the literature to date, that the frequency of AH is higher in patients with acromegaly when analyzed by 24h-ABPM than with OBP. We observed a positive correlation of maximal DBP and night time minimal DBP with IGF-I levels. We also correlated for the first time CMR parameters with BP parameters measured in 24h-ABPM and found a positive correlation of several parameters of 24h-ABPM and LVM.

Cardiovascular disease is one of the most prevalent comorbidities in acromegaly, with AH being the most common disorder with prevalence of 18 to 60% (1, 20). Studies with 24h-ABPM in acromegaly have elicited conflicting results whether the frequency is higher than when analyzed by OBP or not (1). Minniti et al (4) were the first to report the BP profile on ABPM-24h in patients with acromegaly and observed a lower frequency than in clinical measurement (17.5% vs 42.5%, respectively). Costenaro et al (3) confirmed the initial findings, with a frequency of elevated BP of 32.4% by clinical measurement and of 22.9% by 24h-ABPM. However, Terzolo et al (21) showed a higher mean 24h-DBP in patients with acromegaly in 24h-ABPM. In our study, some patients with a previous diagnosis of AH and normal BP on OBP had high BP on 24h-ABPM and, therefore, adjustment of anti-hypertensive treatment was performed.

We observed a high frequency of systolic and diastolic non-dipper patients, similar to two previous studies (3, 21). It is known that target organ injury occurs more severely in non-dipper patients with AH than dipper patients (22), so this find in our cohort can be associated with a higher incidence of cardiac involvement in patients with acromegaly that present this non-dipper pattern, highlighting the importance of 24h-ABPM in these patients.

The prevalence of obstructive sleep apnea syndrome (OSA) in patients with acromegaly is very high according to several studies (60–95.3%) (20, 23–25). The gold standard method for diagnosing OSA is polysomnography (26), but it has a high cost and its access is limited (27), which makes it not widely available. Some questionnaires are used to identify OSA, but their specificity is low (28). Patients with OSA often have disrupted sleep, and the prevalence of AH and diurnal hypertension in this group is high, being another common cause of secondary hypertension that overlaps in acromegaly patients (29). When submitted to 24h-ABPM evaluation patients with OSA commonly have a non-dipping profile and a higher variation on BP (30, 31). As our patients probably have a high frequency of non diagnosed OSA, as a previous study of our center showed a prevalence of 87.5% (24), we hypothesize that this is one of the reasons for the greater number of nocturnal hypertensive patients by 24h-ABPM.

Another important finding is that 31% of the patients that would be considered normotensive by OBP, actually had a diagnosis of AH when analyzed by 24h-ABPM. Considering this, it is important that 24h-ABPM be preconized for all patients with acromegaly, even if they have normal BP values in the clinical examination. To reinforce this finding, in a previous study, three patients with uncontrolled BP by 24h-ABPM also had normal OBP (3).

Most clinical guidelines (13, 14, 32) recommend that 24h-ABPM be applied to adult patients to confirm the OBP diagnosis of AH based on the high prevalence of masked hypertension. Masked hypertension is defined as a normal OBP and an elevated BP on out-of‐office readings (33) and must be investigated in patient groups more likely to have masked hypertension, including males, older individuals, smokers, and those with a high body mass index (BMI), diabetes mellitus, or high serum cholesterol levels (34) or adults with untreated OBP values consistently between 120/75 and 129/79 mm Hg (13). This is probably the case also of patients with acromegaly, as shown in our study.

The 24h-ABPM provides a more comprehensive assessment of BP over the course of a day and have been reported to better predict health outcomes than OBP (17), but there are few studies with acromegaly patients. Two studies in acromegaly patients (3, 4) had proposed the use of 24h-ABPM-24h as a routine to correctly recognized the truly hypertensive individuals, independently of previous diagnosis of AH and to identify elevations in night-time BP. Our study reinforces the importance of this recommendation.

We observed a positive correlation of IGF-I levels with maximum and minimum DBP measured by 24h-ABPM, similar to a previous study (3). Nevertheless, we did not find any correlation with daytime–DBP and night time DBP or with GH- levels. The OBP was not correlated with GH or IGF-I levels. The correlation between severity of hypertension and GH or IGF-I levels has been investigated in several studies, but findings are discordant (35–37). Schutte et al (38) showed a positive correlation between BP levels and higher IGF-I concentrations, with an inverse relationship when IGF-I levels were within the normal range.

CMR T1 mapping studies in patients from general population with isolated AH showed little expansion in extracellular volume and that was proportional to the development of LVH (39). The LV mass was higher when compared to that of normotensive subjects and the myocardial fibrosis (both focal and diffuse) was not common in the groups, except when LVH were present (39).

Few studies in the literature have used CMR to evaluate cardiac abnormalities in acromegaly patients (40, 41). The reported frequencies of LVH, myocardial fibrosis, and LV systolic dysfunction in patients with acromegaly evaluated by CMR ranged from 5–72%, 0–13.5%, and 0–12.5%, respectively. The patient sample sizes included in previous studies have been relatively small (three of the five articles had a sample size of 15 or fewer patients). In the present study, we analyzed both OBP and 24h-ABMP and tried to relate both with abnormalities in CMR. Our resultsrevealed a high proportion of LVH in patients with not controlled BP in the 24h-ABPM, but we did not find any difference when BP was measured by OBP. We found a positive correlation of LVM and several parameters of 24h-ABPM, but the same correlation was not observed between BP measured by OBP and CMR parameters, again highlighting that 24h-ABPM is a more precise methodology in these patients and probably has a better correlation with cardiac endpoints.

The main limitation of this study was related to the difficulty of finding naïve-treatment patients with acromegaly who agreed to perform CMR, which made the number of patients small (eleven patients) and thus, the analyses could not be reliable and often significant in some parameters. Also, patients with acromegaly have some confounding bias for AH as age, BMI, family history of AH that were difficult to eliminate to analyzed isolately the impact of acromegaly in this population. Specially, the impact of OSA in our patients cannot be estimated as polysomnography was not performed. In addition, more studies have to be done to clarify the relation of high levels of GH and IGF-I with cardiac abnormalities in CMR.

We observed that 24h-ABPM in acromegaly is important because it allows the diagnosis of AH in some patients with normal BP in OBP and also to allow a better management of drug treatment in patients previously diagnosed with AH. Also, it shows a better correlation than OBP with ventricular mass when assessed by the gold-standard method CMR.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Conflicts of Interest: M.R.G. has served as an advisory board member for Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Re-cordati Rare Diseases and Crinetics Pharmaceuticals; as a research investigator for Crinetics Pharmaceuticals, Recordati Rare Diseases and Novartis Pharmaceuticals; and as a speaker for Crinetics Pharmaceuticals, Novartis Pharmaceuticals, Ipsen, Novo Nordisk and Recordati Rare Diseases. L.K. has received speaker fees from Novartis and Ipsen.

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No competing interests reported.

Importance of 24 Hours Ambulatory Blood Pressure Monitoring in Patients With Acromegaly and Correlation With Cardiac Magnetic Resonance Findings

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Patients And Methods

Study population

Study Design

Clinical And Biochemical Variables

Office Bp (Obp) Measurements

Hormone Assays

Twenty-four Hours Abpm

Cardiac Evaluation

CMR acquisition and interpretation

Delayed Myocardial Enhancement

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1