C. Mongiardi

Angiotensin II type 1 and type 2 receptor expression in circulating monocytes of diabetic and hypercholesterolemic patients over 3-month rosuvastatin treatment

BackgroundIn diabetes, a variety of pro-inflammatory cellular changes has been found in various cell types, including monocytes which are known to be involved in all the phases of atherogenesis. Angiotensin II (Ang II) type 1 receptor (AT1R) mediates the pro-atherogenic effects of Ang II whereas the type 2 receptor (AT2R) seems associated with atheroprotection. We sought to investigate the potential changes of AT1R-AT2R expression in human monocytes of type 2 diabetic- hypercholesterolemic patients and in hypercholesterolemic subjects, upon clinical treatment with rosuvastatin.MethodsThe AT1R membrane protein and mRNA AT1R and AT2R expression in monocytes were investigated in 10 type 2 diabetic-hypercholesterolemic patients and in 10 hypercholesterolemic subjects, before and after 3-month rosuvastatin treatment. Moreover, the serum cytokine levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected.ResultsAs expected, rosuvastatin was associated with a change in the lipid profile in the two groups. Both the membrane protein (P = 0.008) and the AT1R mRNA expression (P = 0.038) were significantly reduced during treatment in the absence of AT2R expression change in diabetic-hypercholesterolemic patients whereas no significant difference was observed in hypercholesterolemic subjects. The serum IL-4 levels were increased during treatment whereas no change was observed in IFN-γ in diabetic-hypercholesterolemic patients. No cytokine change was observed in hypercholesterolemic subjects.ConclusionsOur study on monocytes of diabetic-hypercholesterolemic patients, showing a reduced AT1R but not AT2R expression during rosuvastatin treatment, suggests that statin therapy may modulate favorably the AT1-AT2 receptor balance in subjects with coexistent type 2 diabetes.

CARDIOVASCULAR REMODELING IN MILD HYPERTENTION: ROLE OF SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS

Objective: To assess the correlation between soluble receptor for advanced glycation end products (sRAGE) and office, 24 hours and central blood pressure (BP) and heart morpho-functional parameters in untreated mild hypertensive patients. Design and method: We enrolled 74 patients, 35–55 years-old, with mild untreated hypertension, free from cardiovascular diseases or diabetes, not smokers. 52 normotensives age, sex and anthropometric parameters-matched were enrolled in the control group. Each subject underwent office and 24 hours BP measurement, arterial tonometry (central BP, Pulse Wave Velocity-PWV), echocardiography (left ventricular mass-LVM, atrial size), carotid ultrasonography (intima media thickness-IMT) and blood tests, with sRAGE dosage too. Results: sRAGE dosage was similar in hypertensives and normotensives (891 ± 697.9pg/ml vs. 900 ± 560.4pg/ml). There was no difference also between patients with normal glucose and with impaired fasting glucose, as well as between subjects with and without metabolic syndrome. In hypertensives, we found a negative correlation between sRAGE and LVM (r:−0.24,p:0.04), also confirmed by multivariate analysis (&bgr;:−0.223,p:0.04). A negative correlation was also observed between sRAGE and left atrial (LA) antero-posterior diameter (r:−0.37,p:0.002), LA volume (r:−0.34,p:0.004, confirmed by multivariate analysis &bgr;:−0.214,p:0.03) and BSA-indexed LA volume (r:−0.30,p:0.01). sRAGE correlated also with right atrial (RA) area (r:−0.38, p:0.001), but not with RA volume (r:−0.24, p:0.08). There was no correlation between sRAGE and office, 24 hours and central BP, PVW, carotid-IMT, glycemia, HOMA-index and uricaemia. Conclusions: Correlations between sRAGE and LVM, LA and RA dimensions suggest how advanced glycation end products could play a role in cardiovascular remodeling. Mild hypertension and young age of our population may explain lack of differences between sRAGE dosage in hypertensives and normotensives. Importantly, all the observed correlations were found in absence of drugs interference.

[LB.02.17]OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ARTERIAL HYPERTENSION: A ROLE IN IDENTIFYING EARLY VASCULAR DAMAGE?

Objective: Optical coherence tomography angiography (OCTA) is a novel, non-invasive OCT technique able to identify and characterize retinal vascular patterns. Aim of our cross-sectional study was to evaluate the correlation between retinal microvascular modifications detected with OCTA and arterial hypertension (AH). We also evaluated the role of OCTA as an useful tool for early diagnosis of subclinical organ damage in hypertensive patients. Design and method: We enrolled 70 subjects: 35 hypertensive and 35 normotensive (NT) patients matched for age, sex and BMI. Hypertensive patients was divided into two groups: mild (Blood Pressure-BP < 160/100 mmHg MH) and severe (BP >180/110 mmHg, SH). OCTA was performed applying different analysis protocols for macula and optic disk, using SD-OCTA Avanti Optovue by SSADA algorithm. OCT angiograms were studied with corresponding OCT B scans and retinal maps, to assess accuracy and clinical utility. Morphological data were correlated to office BP (OBP), central systolic blood pressure (c-SBP) and microalbuminuria (MI) to evaluate the predictive value of OCT analysis. Results: We observed a lower mean foveal choroidal thickness in hypertensive patients vs normotensive (NT 319,68 ± 61,72 mm, MH 251,04 ± 63,1 mm SH 262,65 ± 51,08 mm p = 0.003). Deep vascular layer resulted similar in the three groups (NT: 59,2 ± 1,5%; MH: 59,2 ± 2.2%; SH: 57,8 ± 2,6%) as well as deep foveal avascular zone area (NT: 0,34 ± 0,09 mm2; MH 0,36 ± 0,07 mm2; SH: 0,39 ± 0,1 mm2). Our preliminary data didn’t show a significant correlation between morphological retinal parameters and OBP, c-SBP and microalbuminuria. Conclusions: Our data show how OCTA could highlight some vascular modifications in hypertensive patients, suggesting a potential usefulness of OCTA to assess ocular damage. We need largest studies to estabilish a predictive role of this technique.

[PP.14.10] CARDIOVASCULAR REMODELING IN MILD HYPERTENSION: THE ROLE OF URIC ACID

Objective: It has been observed in animal models that uric acid can induce the growth of cardiomyocytes and the development of interstitial fibrosis. However, few clinical studies have shown conflicting results about the relationship between serum uric acid (SUA) and cardiovascular remodeling. Aim of this study was to evaluate the relationship between uric acid levels and cardiac, aortic and carotid morphofunctional parameters in a cohort of not treated mild hypertensive patients. Design and method: We enrolled 246 mild hypertensive patients (113 males and 133 females) without known cardiovascular disease, gout, diabetes mellitus and renal failure, matched for age and BMI. For each subject, we evaluated office and 24 h BP. Each patient underwent arterial tonometry (central blood pressure), echocardiography (left ventricular mass, thoracic aortic diameters), carotid (intima media thickness, IMT) and abdominal aortic ultrasonography and blood tests (SUA). Results: SUA levels were higher in men than women (5.3 ± 1.3 vs 4.8 ± 1.4 mg/dL p 0.04), but there was not a significant difference when hypertensive patients were compared to normotensive. Univariate analysis showed a significant correlation between serum uric acid levels and left ventricular mass (r = 0.24, p = 0.001) and relative wall thickness (r = 0.168, p = 0.01) suggesting a possible role of uric acid in the development of concentric geometry. We showed a significant correlation between 24 h SBP and 24 h DBP with SUA (p = 0.001 and p = 0.04). In a multivariate analysis we confirmed the correlation of left ventricular mass with 24 h SBP (beta = 0.169, p = 0.05) and SUA (beta = 0.240, p = 0.007). No correlation was found between SUA and carotid IMT, thoracic (root and ascending) and abdominal aortic diameters. Conclusions: In conclusion, our results may suggest a possible role of uric acid in the onset of structural and functional remodeling of left ventricle. Thoracic and abdominal aortic diameters and carotid IMT did not show any correlation with uric acid. These data need further confirmation in prospective studies.

[PP.37.23] CARDIOVASCULAR REMODELLING IN HYPERTENSIVE PATIENTS: DOES GENDER MATTER?

Objective: To investigate whether common cardiovascular risk factors act differently between genders in the development of organ damage in untreated mild hypertensive patients. To correlate also any differences in subclinical organ damage to office, 24 h and central blood pressure (BP). Design and method: We enrolled 60 women and 50 men (without cardiovascular disease or diabetes, non smokers) aged between 35 and 55 years old with mild hypertension. For the control group were enrolled 60 normotensive women and 50 normotensive men matched for age and BMI. For each subject, we evaluated office and 24 h BP. Each patient underwent arterial tonometry (central blood pressure), echocardiography (left ventricular mass, thoracic aortic diameters), carotid (intima media thickness, IMT) and abdominal aortic ultrasonography and blood tests. Results: Using a regression analysis we found an outstanding role of BMI (beta = 0.47, p = 0.0001) and central BP (beta = 0.26, p = 0.002) to predict left ventricular mass in women. In men, BMI (beta = 0.40, p = 0.001) age (beta = 0.21, p = 0.003) and 24 h SBP (beta = 0.34, p = 0.0001) seem to play a major role. Regarding thoracic aorta we found a significant correlation to central BP in both men and women (beta = 0.23, p = 0.01 and beta = 0.19, p = 0.03), whereas this association is detectable for abdominal aorta only in women (beta = 0.37, p = 0.01). Finally, in the prediction model of IMT, age and BMI were significant in both genders. In women we found a significant correlation with 24 h BP (beta = 0.20, p = 0.007), while in men with central BP (beta = 0.23, p = 0.007). Conclusions: In men target organ damage appears mainly related to age, BMI and 24 h BP. In women the role of age seems lower and CV remodelling appears also related to central BP.

GESTATIONAL DIABETES AND DEVELOPMENT OF HYPERTENSION: A STUDY USING AMBULATORY BLOOD PRESSURE MONITORING

Objective: To evaluate the incidence of arterial hypertension (AH) using ambulatory blood pressure monitoring (ABPM) after a long-term follow-up (average: 9 years) in women with pregnancy complicated by (gestational hypertension, GH) or (preclampsia, PE) or (gestational diabetes, GDM) versus women with uncomplicated pregnancies (UP). Design and method: We retrospectively selected, in the database of our city hospital, 200 women who delivered between 2002 and 2007: 50 with GH, 50 with PE, 50 with GDM, 50 with UP. Exclusion criteria were pre-existing AH and diabetes and previous cardiovascular events. For all women, we obtained family and personal medical history, obstetric and laboratory data both at baseline and at follow-up; ABPM was performed at follow-up in order to establish a possible diagnosis of AH. Results: At baseline and follow-up, groups were not different in age, family history of AH, smoking prevalence, BMI, renal function. GH, GDM and PE groups had higher values of mean 24 h SBP and 24 h DBP than UP group. The diagnosis of hypertension was made in 40% of women in GH group and in 32% of women in GDM group vs 14% in UP group (p = 0.005). Incidence of AH in PE group was higher than in UP group, but the difference did not reach statistical significance. Using a Kaplan-Meier analysis, no difference was found in the incidence of AH between GH, PE and GDM groups. No difference was found in the prevalence of masked hypertension and white coat hypertension in all groups. Conclusions: A pregnancy complicated by GDM gives a significantly higher risk of developing AH later in life, and this risk is not significantly different than that given by PE or GH.

[PP.11.17] CENTRAL BLOOD PRESSURE AND ABDOMINAL AORTIC DIAMETERS: ARE THERE ANY CORRELATIONS?

Objective: To assess the correlation between abdominal aortic diameters and office, 24-hour and central blood pressure (BP) in untreated hypertensive patients. Design and method: We enrolled 50 patients, 35–55 years old, with mild untreated hypertension, free from cardiovascular diseases or diabetes, not smokers. We also selected 50 subjects matched for age, sex and anthropometric parameters in the control group. Each subject underwent office and 24 hours BP measurement, arterial tonometry (central BP, Pulse Wave Velocity-PWV), abdominal aortic ultrasonography (iuxtarenal and infrarenal diameters; anteroposterior-AP, laterolateral-LL) and blood-tests. Results: Abdominal aortic measures were in physiological range for all the enrolled subjects, with significant higher diameters in males. Diameters were similar between normotensive and hypertensive patients both at iuxtarenal level (longitudinal AP: 15.7 ± 1.9 mm vs 16.3 ± 1.5 mm; transversal AP: 15.7 ± 1.8 mm vs 16.3 ± 1.5 mm; transversal LL: 15.8 ± 1.7 mm vs 16.6 ± 1.7 mm, p = ns) and at infrarenal one (longitudinal AP: 14.4 ± 1.6 mm vs 14.7 ± 1.5 mm, transversal AP: 14.3 ± 1.7 mm vs 14.6 ± 1.6 mm; transversal LL: 14.3 ± 1.7 mm vs 14.7 ± 1.7 mm, p = ns). Comparing the two groups by gender, these differences were still not significant in males. Conversely, the abdominal aortic diameters were higher in hypertensives women with significant difference at iuxtarenal (p = 0.005) and infrarenal level (p = 0.05). No significant correlations were found between office, central and 24-hour BP and aortic diameters for the whole popolation, whereas there was a mild correlation in females between iuxtarenal aortic diameters and systolic (r = 0.327, p = 0.019) and diastolic (r = 0.335, p = 0.016) central BP. Moreover, PWV correlated with iuxtarenal diameters in the whole population (r = 0.394, p < 0.001), in hypertensives (r = 0.403, p < 0.001) as well as in normotensives (r = 0.352, p < 0.001). Finally, both iuxtarenal and infrarenal aortic diameters correlated with age, abdominal circumference, BMI and serum uric acid. Conclusions: The hypertension contribution to abdominal aortic dilation appeared significant only in females, suggesting the role of a different hormonal pattern. We also found different iuxtarenal and infrarenal aortic remodelling, most likely due to different vascular wall structure.

[PP.23.02] RESISTANT HYPERTENSION AND RENAL RESISTIVE INDEX

Objective: Renal resistive index (RRI), assessed by Doppler sonography, has been classically considered as an expression of intrarenal vascular resistance. Recent studies, however, have showed that RRI is also influenced by arterial compliance, confirming its possible role as a marker of systemic vascular alterations. Our purpose was the evaluation of the renal resistive index in patients with uncontrolled hypertension with 3 or more antihypertensive drugs, including a diuretic (RH), in comparison with a group of patients with resistant drug hypertension controlled with 4 or more antihypertensive drugs (RH4) and patients with hypertension controlled with 3 antihypertensive agents (CH3). We also considered the correlation between renal resistive index and subclinical organ damage. Design and method: We enrolled 120 patients (40 RH, 40 RH4, 40 CH3) without renal arterial stenosis and known nephropathy from our outpatient clinic for hypertension. We matched patients for age, sex and BMI. Each patients performed a 24-hour blood pressure monitoring (ABPM), office blood pressure (OBP) measurement, Glomerular Filtration Rate (according to MDRD) assessment, echocardiography and carotid echo-color-Doppler ultrasonography. We also estimated renal resistive index by Doppler sonography. Results: OBP and ABP were higher in RH group in comparison with the RH4 and CH3 groups (OBP: 155 ± 7/88 ± 5 vs 130 ± 7/79 ± 9 vs 127 ± 7/76 ± 5 mmHg, p = 0.001; ABP: 141 ± 10/85 ± 6 vs 122 ± 8/73 ± 6 vs 121 ± 8/72 ± 6 mmHg, p = 0.001). Office pulse pressure was higher in RH than RH4 and CH3 groups (66 ± 12 vs 53 ± 10 vs 51 ± 6 mmHg, p = 0.001). Renal resistive index was similar in RH and RH4 (0.72 ± 0.08 vs 0.70 ± 0.07, p = n.s.) and higher than CH3 group (0.72 ± 0.08 vs 0.65 ± 0.06, p = 0.004; 0.70 ± 0.07 vs 0.65 ± 0.06, p = 0.019). We also found a significant correlation between renal resistive index and age (r = 0.421, p = 0.0001), GFR (r = −0.197, p = 0.036), office pulse pressure (r = 0.4 p = 0.0001). We did not observe significant correlation between renal resistive index and left ventricular mass index and carotid intima-media thickness. Conclusions: Renal resistive index is higher in patients with drug-resistant hypertension. The correlation between office pulse pressure and the renal resistive index confirms that the latter depends much more on systemic haemodynamics than on renal ones. These data need to be confirmed by larger and prospective studies.

Atypical case of acute coronary syndrome due to coronary-pulmonary steal syndrome secondary to pulmonary embolism

Case presentationDr. Mongiardi, Dr. Maresca: G.L. is a 64-year-old manon chronic oxygen therapy due to chronic obstructivepulmonary disease (COPD) in the setting of a bronchi-ectasic disease, referred to our hospital in September 2009because of a micturition-nocturnal-syncope preceded bydizziness. The patient had neither a personal history ofcoronary artery disease nor known cardiovascular riskfactors. In the emergency department (ED) the patientpresented preserved consciousness and mild dyspneadespite low flows of inhalatory O

ATHEROSCLEROTIC RENAL ARTERY STENOSIS: EFFECTS OF PERCUTANEOUS ANGIOPLASTY ON BLOOD PRESSURE AND RENAL FUNCTION: PP.30.185

Objective: Despite the large number of patients treated with percutaneous renal angioplasty (PTRA), it is still unclear whether hypertensive patients with atherosclerotic renovascular disease obtain a long term benefit on blood pressure (BP) control and renal function. This longitudinal study was aimed to evaluate the effects of renal angioplasty on BP and renal function, with a follow-up of at least 24 months. Design and Methods: Among 33 consecutive hypertensive patients with atherosclerotic renal artery stenosis (>70%), 21 patients underwent PTRA+stenting (PTRA group) and 12 patients were treated with medical therapy (control group). At baseline and after > 24 months, all the patients underwent 24 hour ambulatory BP monitoring (ABPM) and evaluation of creatinine clearance (MDRD formula). Results: At baseline PTRA group and control group were similar with regard to age, gender, BMI, BP values throughout the 24 hours and cardiovascular risk factors. Baseline creatinine clearance was significantly greater in the control group (72 ± 12 ml/min) than in PTRA group (51 ± 12 ml/min, p < 0.001). The use (number, type and dose) of antihypertensive drugs, statins and antiplatelet drugs was similar between PTRA and control groups. Mean length of follow-up was 32 ± 8 months in PTRA group and 34 ± 9 months in control group (ns). At the end of the follow-up, in PTRA group clinic systolic BP significantly decreased (from 158 ± 25 to 144 ± 16 mmHg, p < 0.01), whereas clinic diastolic BP and all BP parameters from ABPM were unchanged; in the control group all BP parameters (clinic and from ABPM) were unchanged. Compared to baseline the number of antihypertensive drugs was unchanged in PTRA group (from 3.2 ± 1.5 to 3.4 ± 1.3, ns), whereas in control group the number of drugs increased from 2 ± 1.7 to 3.7 ± 1.4 (p = 0.01). Creatinine clearance was unchanged in both groups. Conclusion: At >2 years PTRA seems not to improve BP control and renal function; however compared to patients treated with medical therapy, PTRA patients have not required an increase in antihypertensive drug treatment.