Rosa Maria Bruno

Sympathetic Nerve Traffic and Asymmetric Dimethylarginine in Chronic Kidney Disease

BACKGROUND AND OBJECTIVESnSympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD).nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnIn 48 stage 2 to 4 CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry.nnnRESULTSnCKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r = 0.32, P = 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P < 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P = 0.003) in a model including the same covariates.nnnCONCLUSIONSnSympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients.

[PP.28.20] DAPAGLIFLOZIN ACUTELY REDUCES AORTIC STIFFNESS, RESTORES ENDOTHELIAL DYSFUNCTION AND INDUCES RENAL VASODILATION IN TYPE 2 DIABETIC PATIENTS: A PILOT STUDY

Objective: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a novel drug class, able to reduce blood pressure (BP) values and cardiovascular events in type 2 diabetes (T2DM), Though BP and glucose control certainly contribute to the cardiovascular protection mediated by SGLT2-inhibitors, other mechanisms are plausible and not fully elucidated. Aim of this study is to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function in T2DM. Design and method: 16 T2DM patients, treatment-naïve for BP (age 57u200a±u200a9 years, 11 men, BMI 30.5u200a±u200a6.7, HbA1c 56.0u200a±u200a6.8u200ammol/mol) were enrolled. Neuro-hormonal and vascular variables were assessed before (V0) and after (V1) a 2-day treatment with dapagliflozin 10u200amg/die per os. 24h-urinary sodium and glucose, diuresis and free-water clearance were measured at V0 and V1. Brachial artery endothelium-dependent and independent vasodilation were assessed by flow-mediated dilation (FMD) and automated image analysis. Pulse wave velocity (PWV), central BP and its augmentation were assessed by applanation tonometry. Renal resistive index (RI) was assessed and renal vasodilating capacity evaluated by administration of low-dose glyceril trinitrate (GTN). Results: 2-day treatment with dapagliflozin induced a significant decrease in brachial systolic BP (130.7u200a±u200a12.8 to 125.4u200a±u200a11.2 mmHg, pu200a<u200a0.05), an increase in 24h-diuresis (1400[750] to 2000[750] ml, pu200a<u200a0.05), 24h-urinary glucose (406[3465] to 66239[43780] mg/24u200ah, pu200a<u200a0.05), while natriuresis and fasting blood glucose were unchanged. FMD was significantly increased (2.8u200a±u200a2.2 to 4.0u200a±u200a2.1%, pu200a<u200a0.05), in the presence of unchanged brachial artery diameter, shear rate and response to GTN. PWV was reduced (10.1u200a±u200a1.6 to 8.9u200a±u200a1.6u200am/s, pu200a<u200a0.05); a trend persisted even after correction for mean BP (pu200a=u200a0.053). RI was reduced (0.62u200a±u200a0.04 to 0.59u200a±u200a0.05, pu200a<u200a0.05), while RI response to GTN was unmodified. Changes in FMD, PWV and RI were not associated with changes in BP. Conclusions: 2-day treatment with dapagliflozin induce a significant improvement in systemic endothelial function, arterial stiffness and renal vasodilation; this effect is independent of changes in BP and occurrs in the presence of stable blood glucose and natriuresis. These preliminary data suggest that dapagliflozin has a direct beneficial effect on the vasculature, which might translate in reduced cardiovascular risk.

[PP.19.24] DETERMINANTS OF INAPPROPRIATELY HIGH PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS: A RETROSPECTIVE CROSS-SECTIONAL COHORT STUDY

Objective: Age and blood pressure (BP) are known to be the main determinants of large artery stiffness. However other factors may lead to an inappropriately high pulse wave velocity (PWV) on top of these two factors. We investigated the determinants of inappropriately high PWV in hypertensive patients, and their possible role in causing organ damage accrual. Design and method: Hypertensive patients were selected among those attending a visit in our Hypertension Outpatient Clinic and undergoing carotid-femoral PWV by applanation tonometry, and cardiac and carotid ultrasound during a 5-year period (2006–2011). Inappropriately high pulse wave velocity (PWV) was calculated as the ratio between the observed value and the values predicted according to the formula derived from international reference values stratified by age and mean BP (oPWV/pPWV). Results: 731 hypertensive patients were selected (age 30–88 years, 42% women, 57% taking BP-lowering drugs). Median oPWV/pPWV was 102% (range 61–196%). In a multiple linear regression model, independent determinants of oPWV/pPWV were: daylight hours (beta -1.72, pu200a<u200a0.001), age (beta -0.73, pu200a<u200a0.001), BMI (beta 0.49, pu200a=u200a0.01), blood glucose (beta 0.18, pu200a<u200a0.001), mean BP (betau200a=u200a-0.25, pu200a=u200a0.002) and heart rate (betau200a=u200a0.22, pu200a=u200a0.003). Though oPWV/pPWV was significantly higher in men and current smokers, the association disappeared in the multiple regression model. There was no association between oPWV/pPWV and any BP-lowering drug class. oPWV/pPWV was not associated with left ventricular mass. Conversely, oPWV/pPWV was an independent determinant of the presence of carotid plaques (beta 7.35, 5–95%CL 2.36–12.34). Conclusions: In hypertensive patients, inappropriately elevated PWV is associated more tightly than observed PWV to younger age and high blood glucose, thus it might help to better depict vascular aging in younger hypertensives and in those with metabolic alterations. A more advanced atherosclerotic process might also contribute to excess aortic stiffness. Whether an inappropriately high PWV translates into an increased cardiovascular risk should be determined in longitudinal studies.

[BP.01.05] IMPACT OF 24-H BLOOD PRESSURE MONITORING ON OBJECTIVE SLEEP DURATION AND FRAGMENTATION IN RESISTANT HYPERTENSIVE PATIENTS

Objective: 24-h ambulatory blood pressure monitoring (ABPM) is crucial for diagnosis of treatment-resistant hypertension (RH). However, repetitive cuff inflations during night might induce sleep deprivation and hamper physiological nocturnal BP fall. The study was aimed at investigating the impact of the ABPM on sleep duration and fragmentation in RH patients. Design and method: 20 RH patients and 13 healthy controls (HC) were recruited and underwent 7-day actigraphy and ABPM. The following parameters were calculated on the whole week and separately for the ABPM night: total sleep time (TSTtot and TSTABPM), wake after sleep onset (WASOtot and WASOABPM) and sleep efficiency (SEtot and SEABPM). Results: RH patients were older (63u200a±u200a11 vs 27u200a±u200a4 years, pu200a<u200a0.001), had higher 24-h (135u200a±u200a16/78u200a±u200a16 vs 122u200a±u200a11/74u200a±u200a5u200ammHg, pu200a=u200a0.01 and pu200a=u200a0.42) and nighttime BP (130u200a±u200a17/72u200a±u200a14 vs 106u200a±u200a11/62u200a±u200a7u200ammHg, pu200a<u200a0.001 for both) and a reduced dipping (6u200a±u200a6 vs 18u200a±u200a5%, pu200a<u200a0.001) than HC. RH had a lower TSTtot than HC (6.4u200a±u200a1.1 vs 7.5u200a±u200a0.9u200ah, pu200a<u200a0.01). TSTABPM was not reduced during the ABPM night in both groups (6.8u200a±u200a1.3 and 7.7u200a±u200a1.4, pu200a=u200ans vs TSTtot for both). However, WASOABPM tended to be longer than WASOtot in RH (RH: 73u200a±u200a34 vs 61u200a±u200a29u200amin, pu200a=u200a0.07; HC 30u200a±u200a24 vs 27u200a±u200a17u200amin, pu200a=u200ans), and SEABPM thus tended to be reduced in RH (84.4u200a±u200a7.2 vs 86.2u200a±u200a7.2%, pu200a=u200a0.09) but not in HC (93.7u200a±u200a3.2 vs 93.9u200a±u200a5.0 pu200a=u200a0.88). None of the considered sleep parameters were correlated with 24h-BP in HC and RH. Conclusions: ABPM did not significantly influence objective sleep duration and only marginally induce sleep fragmentation, thus can be safely used for diagnosis of resistant hypertension.

Relazione tra fattori psicosociali e malattia CV: l’ipertensione arteriosa come modello di approccio multidisciplinare alle differenze di genere

Ischemic heart disease represents a major cause of mortality both in men and in women. In addition to traditional cardiovascular risk factors, emerging evidence suggest that psychosocial factors, including depression, work- and marital-related stress, low socioeconomic status, are linked with cardiovascular disease and hypertension. This association seems to be tighter in women than in men, but more studies are required to demonstrate these findings, with potentially relevant clinical consequences. A multidisciplinary approach is warranted to firmly establish the role of gender as an effect modifier in the relationship between psychosocial factors and clinical outcomes such as blood pressure.

[PP.37.03] IMPACT OF SEASONALITY AND AIR POLLUTANTS ON WAVE REFLECTION IN HYPERTENSIVE PATIENTS

Objective: Important climate-related variations of clinic and ambulatory blood pressure (BP) have been repeatedly reported. However, the influence of seasonality and other environmental factors such as air pollutants and outdoor temperature on wave reflection, a parameter associated with increased risk of cardiovascular events, has never been investigated. The aim of the present study was to examine in a cross-sectional survey whether acute variations in these environmental factors may affect wave reflection, measured as augmentation pressure (AP) and augmentation index normalized at a heart rate of 75bpm (AIx75). Design and method: This survey included retrospectively 731 hypertensive patients (30–88 years, 417 drug-treated), referring to our Hypertension Center during a 5-year period (2006–2011). Radial arterial tonometry was performed to all participants in a quiet, temperature-controlled (22–24°C) room, with the calculation of central BP, Aix75 and AP. The data of the local office of the National Climatic Data Observatory were used to estimate meteorological conditions and air pollutants (PM10, O3, CO, N2O) exposure the same day of the vascular evaluation. Results: Aix75 (mean value 24.1u200a±u200a10.2%) was related to age (ru200a=u200a0.27, pu200a<u200a0.001), BMI (ru200a=u200a−0.12, pu200a=u200a0.002), central systolic BP (ru200a=u200a0.32, pu200a<u200a0.001), diastolic BP (ru200a=u200a0.14, pu200a<u200a0.001), total cholesterol (ru200a=u200a0.16, pu200a<u200a0.001), LDL (ru200a=u200a0.08, pu200a=u200a0.04), HDL (ru200a=u200a0.26, pu200a<u200a0.001),creatinine (ru200a=u200a−0.15, pu200a<u200a0.001). No significant correlation was found between AIx75 and environmental factors (daylightu200ahours, mean temperature and air pollutants). The multiple regression analysis including the above-mentioned variables confirmed an independent association of AIx75 only with age, central systolic BP, diastolic BP and female sex. This result was confirmed also in the untreated group. Furthermore, no significant correlation was found between AP (mean value 14.2u200a±u200a7.9 mmHg) and daylight hours, mean temperature and air pollutants, neither in the univariate analysis, nor in the multiple regression analysis adjusted for confounders. Conclusions: This cross-sectional analysis suggests that seasonality, expressed by the daily number of hours of light, and acute changes in environmental factors such as outdoor temperature and air pollutants concentration, do not influence either AP or AIx75.

[OP.8B.04] GENDER DIFFERENCES IN THE IMPACT OF DYSFUNCTIONAL COPING IN A HYPERTENSIVE POPULATION.

Objective: Chronic stress and coping strategies might influence cardiovascular health in a gender-dependent manner. Aim of this study is to investigate their impact on blood pressure control in men and women attending for the first time a visit in a Hypertension Outpatient Clinic. Design and method: Data from 330 patients were analyzed (males 51%, mean age 57u200a±u200a13 years, antihypertensive treatment 84%, previous CV events 9%, diabetes 7%, obesity 24%, smoking 13%, hypercholesterolemia 67%). Office blood pressure (BP) was measured, and medical history collected. Perceived Stress Scale (PSS), Brief-COPE, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAY-Y2) were administered. Results: Women were older and less obese, and showed lower office BP than men. Sleep quality was similar among men and women, while women showed higher STAI-Y2 and BDI values. Despite similar perceived stress, women showed higher emotion-focused and dysfunctional coping. In the overall population, univariate regression analysis showed that systolic BP was directly correlated with triglycerides and dysfunctional coping and inversely correlated with HDL. These correlations were confirmed in men, but not in women. In men, a multiple regression model, considering age, body mass index, diabetes, HDL, Triglycerides, number of antihypertensive drugs, STAI-Y2, BDI and dysfunctional coping, as independent variables, demonstrated that only diabetes (beta 12.9, pu200a=u200a0.04), number of antihypertensive drugs (beta -3.39, pu200a=u200a0.05) and dysfunctional coping (beta 0.91, pu200a=u200a0.03) were significantly associated with systolic BP. The model explained 23% of the variance of systolic BP, while dysfunctional coping 6%. Conversely in women only diabetes (pu200a=u200a0.049) was positively associated with systolic BP. Conclusions: Maladaptive coping strategies seems to translate into unfavorable cardiovascular outcome in men but not in women.