T. Kalos

[OP.7B.02] METABOLIC SYNDROME IS ASSOCIATED WITH INCREASED SYMPATHETIC NERVOUS SYSTEM ACTIVITY AND ARTERIAL STIFFNESS IN RESISTANT HYPERTENSIVE PATIENTS.

Objective: Resistant hypertension is related to sympathetic overdrive and arterial stiffening, while there are scarce data whether metabolic syndrome further potentiates sympathetic activity and vascular abnormalities in this setting. The aim of this study was to assess the effect of the metabolic syndrome on muscle sympathetic nerve activity (MSNA) and arterial stiffness in resistant hypertensive patients. Design and method: We studied 36 patients with resistant hypertension [age: 59 ± 10 years, 24 males, office blood pressure (BP): 178/93 ± 14/11 mmHg, 24-hour BP: 146/84 ± 13/11 mmHg, under 4.3 ± 0.6 drugs] that underwent transthoracic echocardiographic study and blood sampling for assessment of the metabolic profile. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria and arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV). In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results: Resistant hypertensive patients with metabolic syndrome (n = 16) compared to those without (n = 20) exhibited higher waist circumference (109.2 ± 5.3 vs 94.8 ± 9.1 cm, p = 0.001), fasting glucose (130.9 ± 2.2 vs 94.3 ± 2.2 mg/dl, p < 0.05), office systolic BP (185 ± 16 vs 170 ± 13 mmHg, p < 0.001) and left ventricular mass index (132.2 ± 17.1 vs 123.6 ± 16.2 g/m2, p = 0.001). Moreover, metabolic syndrome2patients compared to those without were characterized by greater levels of carotid to femoral PWV (11.8 ± 0.7 vs 9.2 ± 0.9 m/sec, p < 0.001) and sympathetic nerve traffic as reflected by MSNA levels (82.1 ± 2.5 vs 73.3 ± 2.1 bursts per 100 heart beats, p < 0.001). In all participants MSNA was related to waist circumference (r = 0.36, p = 0.004) and office systolic BP levels (r = 0.36, p < 0.05) but there was no association with PWV values (p = NS). Conclusions: In resistant hypertensive patients, metabolic syndrome is associated with high MSNA and PWV levels. These findings support that metabolic syndrome further deteriorates sympathetic activity and arterial stiffening characterizing resistant hypertension.

7A.10: METABOLIC SYNDROME PREDICTS INDEPENDENTLY FROM ITS COMPONENTS ADVERSE EVENTS IN ESSENTIAL HYPERTENSIVE SUBJECTS.

Objective: Metabolic syndrome (MS) is associated with increased risk for atherosclerotic cardiovascular disease, whereas its prognostic role in hypertension remains controversial. The aim of the present study was to assess the relevant impact of each component of MS on the risk for the incidence of adverse events in a cohort of essential hypertensives. Design and method: We followed up for a median period of 40 months (IQR 28–60 months) 2176 essential hypertensives free of cardiovascular disease (mean age 57.6 years, 1010 males, office blood pressure (BP) = 143.4/89.2 mmHg). All subjects had at least one annual visit and at baseline underwent complete echocardiographic study for estimation of left ventricular mass index and blood sampling for assessment of metabolic profile and glomerular filtration rate. MS was defined according to the updated NCEP III criteria. Endpoint of interest was the incidence of stroke, coronary artery disease (CAD) and their composite. Results: MS was present at baseline in 819 hypertensives (37.6%) and DM in 305 (14%). The incidence of the composite end-point was 3.1% (20 patients with stroke, 50 with CAD, 2 with both) over the whole follow-up period. Patients with DM were more likely to experience the composite event in comparison to reference category (5.9% versus 1.9%, log rank p < 0.001) or MS (5.9% versus 3.7%, log rank p = 0.018). Patients with MS were more likely to experience the event of interest in comparison to reference category (3.7% versus 1.9%, log rank p = 0.024). When Cox regression models were implemented, MS predicted the composite end-point (HR = 1.94, 95% CIs 1.42–2.67, p < 0.001). MS remained a significant independent predictor after multivariable adjustment for age, gender, left ventricular hypertrophy, glomerular filtration rate and hypertension pattern. When individual components of MS were consecutively inserted into the final multivariable model instead of MS per se, none of them predicted independently the endpoint. Increased triglycerides were associated with increased incidence of composite endpoint but when adjustment for additional confounders was performed this association rendered not significant. Conclusions: Metabolic syndrome predicts independently from its components adverse events in essential hypertensive subjects.

ACUTE DETRIMENTAL EFFECTS OF E-CIGARETTE AND TOBACCO CIGARETTE SMOKING ON BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY IN HEALTHY SUBJECTS

Objective: This study aimed to assess the acute effects of tobacco cigarettes, e-cigarettes and sham smoking on blood pressure and sympathetic nervous system in healthy subjects. Design and method: We studied 10 normotensive male habitual smokers (mean age 33 years, body mass index: 24.1 kg/m2, office blood pressure = 117/72 mmHg) free of cardiovascular disease. The study design was randomized and placebo controlled with 3 experimental sessions. Subjects smoked 2 tobacco cigarettes containing 1.1 mg nicotine or simulate smoking (sham smoking) with the 2 cigarettes separated by 5 minutes, while 45 minutes after finishing the second cigarette, subjects smoked a third cigarette or sham cigarette. Additionally, participants smoked e-cigarettes for a period of 5 and 30 minutes. Sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) (baroreflex-dependent) and skin sympathetic nerve activity (SSNA) (baroreflex-independent). Results: After the first, second and third tobacco cigarette smoking there was an increase in mean arterial pressure (by 11.2 ± 1.4%, 12.3 ± 1.3% and 13.1 ± 1.4%, respectively, p < 0.05 for all) and heart rate (by 25.1 ± 3.7%, 26.3 ± 2.7% and 25.9 ± 3.7%, respectively, p < 0.05 for all). Similarly e-cigarette smoking at 5 and 30 minutes was accompanied by augmentation of mean arterial pressure (by 10.9 ± 1.2% and 12.8 ± 1.4%, respectively, p < 0.05 for both) and heart rate (by 22.5 ± 3.3% and 23.9 ± 3.8%, respectively, p < 0.05 for both). The first, second and third tobacco cigarette smoking was accompanied by lower MSNA (by 28.1 ± 4.4%, 29.6 ± 5.3% and 30.1 ± 5.2%, respectively, p < 0.05 for all), whereas SSNA was increased (by 98.2 ± 19.4%, 100.2 ± 22.7% and 101.5 ± 21.6%, respectively, p < 0.05 for all). Additionally, e-cigarette smoking at 5 and 30 minutes caused a decrease in MSNA (by 26.9 ± 3.6%, and 28.3 ± 5.1%, respectively, p < 0.05 for both), and an augmentation in SSNA (by 97.9 ± 20.1% and 100.9 ± 20.6%, respectively, p < 0.05 for both). Sham smoking was devoid of any effects on blood pressure, MSNA and SSNA. Conclusions: E-cigarette smoking acutely increases blood pressure and has a detrimental effect on sympathetic nerve activity regulation similar to tobacco smoking in healthy subjects.

EXAGGERATED EXERCISE BLOOD PRESSURE RESPONSE IS ACCOMPANIED BY SYMPATHETIC OVERDRIVE AND ARTERIAL STIFFNESS IN SUBJECTS WITH HIGH NORMAL BLOOD PRESSURE

Objective: The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis. The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP. Design and method: 42 subjects with high normal office BP [defined as office systolic BP = 130–139 mmHg and office diastolic BP = 85–89 mmHg (age: 53 ± 9 years, 29 males, office BP: 134/84 mmHg, 24-hour BP: 114/72 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n = 12) (peak exercise systolic BP > or = 210mmHg in men and > or = 190 mmHg in women) and those without HRE (n = 30). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results: Subjects with a HRE compared to those without exhibited higher waist circumference (108.2 ± 5.3 vs 94.7 ± 9.2 cm, p = 0.001) and were characterized by greater levels of carotid to femoral PWV (8.5 ± 0.8 vs 7.0 ± 0.9 m/sec, p < 0.001) and sympathetic nerve traffic as reflected by MSNA levels (41.1 ± 1.5 vs 32.1 ± 1.9 bursts per 100 heart beats, p < 0.001), while did not differ regarding metabolic profile and left ventricular mass index (p = NS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (r = 0.229, p < 0.05), PWV (r = 0.218, p = 0.002), and MSNA (r = 0.214, p < 0.05). Moreover, MSNA was related to waist circumference (r = 0.33, p = 0.004) and office systolic BP levels (r = 0.31, p < 0.05) but there was no association with PWV values (p = NS). Conclusions: In subjects with high normal BP, a HRE identifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.

ISOLATED SYSTOLIC HYPERTENSION VERSUS COMBINED SYSTOLIC-DIASTOLIC HYPERTENSION AS PREDICTORS OF NEW-ONSET DIABETES MELLITUS: DATA FROM A GREEK 8-YEARS-FOLLOW-UP STUDY

Objective: The aim of the study was to compare the predictive role of isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension for the incidence of new-onset diabetes mellitus (NOD) in essential hypertensive patients. Design and method: We followed up 1435 non-diabetic essential hypertensives with office systolic blood pressure (BP)>or = 140 mmHg [mean age 57 years, 730 males, office BP = 153/92 mmHg] for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent echocardiographic study and blood sampling for estimation of metabolic profile. Patients with baseline ISH exhibited office systolic BP >or = 140 mmHg and office diastolic BP < 90 mmHg, while those with systolic-diastolic hypertension had office systolic BP >or = 140 mmHg and office diastolic BP >or = 90 mmHg. Moreover, NOD was defined if at one or more of the follow-up visits a previously non-diabetic patient reported being on insulin or an oral hypoglycemic drug or if casual plasma glucose concentration >or = 200 mg/dl or fasting glucose concentration >or = 126 mg/dl or 2-h post load glucose >or = 200 mg/dl during an oral glucose tolerance test. Results: The incidence of NOD over the follow-up period was 4.2% (n = 60). Patients with ISH (n = 460) compared to those with systolic-diastolic hypertension (n = 975) were older (65 ± 11 vs 54 ± 10 years, p < 0.0001), had at baseline lower waist circumference (94.5 ± 11 vs 99 ± 13 cm, p < 0.0001), office systolic BP (149 ± 12 vs 155 ± 13 mmHg, p < 0.0001), office diastolic BP (80 ± 8 vs 98 ± 6 mmHg, p < 0.0001), while did not differ regarding left ventricular mass index, glucose and lipid levels (p = NS for all). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio = 2.143, p = 0.016) and systolic-diastolic hypertension (hazard ratio = 1.272, p = 0.029) predicted NOD. However, in multivariate Cox regression model, age (hazard ratio = 1.039, p < 0.001), baseline glucose levels (hazard ratio 1.011, p = 0.016), waist circumference (hazard ratio=1.067, p < 0.001) and ISH (hazard ratio=1.651, p = 0.029) but not systolic-diastolic hypertension were be independent predictors of NOD. Conclusions: ISH but not systolic-diastolic hypertension exhibits independent prognostic value for NOD. These findings support that ISH constitutes a hypertensive phenotype of increased metabolic risk needing careful evaluation and treatment.

ISOLATED SYSTOLIC HYPERTENSION VERSUS COMBINED SYSTOLIC-DIASTOLIC HYPERTENSION AS PREDICTORS OF ATRIAL FIBRILLATION: DATA FROM A GREEK 8-YEAR-FOLLOW-UP STUDY

Objective: The aim of the present study was to compare the predictive role of isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension for the incidence of atrial fibrillation (AF) in essential hypertension. Design and method: We followed up 1605 essential hypertensives with office systolic blood pressure (BP) > or =140 mmHg [mean age 58.1 years, 842 males, office BP = 153/92 mmHg] for a mean period of 8 years. Patients with baseline ISH exhibited office systolic BP >or =140 mmHg and office diastolic BP <90 mmHg, while those with systolic-diastolic hypertension had office systolic BP > or =140 mmHg and office diastolic BP > or = 90 mmHg. Moreover, new-onset AF was defined as hospitalization for AF or compatible electrocardiographic tracings. Results: The incidence of new-onset AF over the follow-up period was 3.4% (n = 55). Patients with ISH (n = 510) compared to those with systolic-diastolic hypertension (n = 1095) were older (65 ± 10 vs 55 ± 11 years, p < 0.0001), had at baseline lower office systolic BP (149 ± 10 vs 155 ± 13 mmHg, p < 0.0001) and office diastolic BP (80 ± 5 vs 98 ± 7 mmHg, p < 0.0001), while did not differ regarding left ventricular mass index (p = NS). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio = 4.612, p = 0.013) and systolic-diastolic hypertension (hazard ratio = 1.794, p = 0.036) predicted new-onset AF. However, in multivariate Cox regression model, age (hazard ratio = 1.078, p < 0.001), left atrium diameter (hazard ratio = 1.102, p < 0.001) and ISH (hazard ratio = 1.551, p = 0.035) but not systolic-diastolic hypertension turned out to be independent predictors of new-onset AF episodes. Conclusions: In hypertensive patients, ISH but not systolic-diastolic hypertension exhibits independent prognostic value for AF. These findings support that ISH constitutes a hypertensive phenotype of increased risk for AF needing careful management.

EXERCISE HEART RATE DURING TREADMILL TEST IS RELATED TO RENAL FUNCTIONAL RESERVE IN ESSENTIAL HYPERTENSIVE PATIENTS: A NOVEL LINK BETWEEN THE HEART AND THE KIDNEYS

Objective: Renal functional reserve (RFR) refers to the capacity of the kidney to augment its level of function under the influence of certain stimuli and it constitutes a valuable diagnostic tool for recognizing high risk patients for acute kidney injury and chronic kidney disease. The aim of our study was to assess the relation of RFR with diverse clinical parameters in patients with essential hypertension and glomerular filtration rate (GFR) > 60 ml/min/1.73m2. Design and method: 15 hypertensive subjects [mean age = 57 years, body mass index = 28.5 kg/m2, office systolic/diastolic blood pressure (BP) = 148/90 mmHg] were included and underwent exercise treadmill stress test, 24-hour ambulatory BP and echocardiographic examination. All subjects were fasted for 8 hours and then baseline hydration status was recorded using bioimpedance analysis. Basal GFR was measured after hydration and stress GFR was achieved after ingestion of oral protein 1 g/kg as cooked meal. Basal and Stress GFR were determined by Creatinine Clearance = Urine Creatinine/Serum Creatinine x Urine Volume/time x 1.73/body surface area. RFR was calculated as Stress GFR – Basal GFR. Results: Patients with a history of hypertension greater than 10 years, had lower RFR values (-14.59 ± 43.26vs 21.35 ± 28.19 ml/min/1.73m2, p < 0.001). There was no correlation of RFR values with respect to age, family history, smoking, dipping status and office BP. In contrast, a statistically significant positive correlation was found between RFR and maximum heart rate during treadmill test (r = 0.880, p = 0.009). Hypertensives with high RFR were also characterized by higher maximum HR during treadmill test (157 ± 22 vs 142 ± 20 bpm, p < 0.05). Conclusions: RFR is related to treadmill exercise heart rate in essential hypertension, suggesting a link between the dynamic regulation of renal function and sympathetic overdrives influence on the heart rate. These findings suggest that treadmill test may be used to identify hypertensive patients with unfavorable RFR, thus more susceptible to kidney damage.

[BP.07.03] EXAGGERATED EXERCISE BLOOD PRESSURE RESPONSE IS ACCOMPANIED BY INCREASED SYMPATHETIC ACTIVITY AND ARTERIAL STIFFNESS IN SUBJECTS WITH HIGH NORMAL BLOOD PRESSURE

Objective: The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis. The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP. Design and method: 20 subjects with high normal office BP [defined as office systolic BP=130–139 mmHg and office diastolic BP=85–89 mmHg (age: 52 ± 9 years, 12 males, office BP: 135/85 mmHg, 24-hour BP: 115/73 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n=6) (peak exercise systolic BP > =210mmHg in men and >=190 mmHg in women) and those without HRE (n = 14). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results: Subjects with a HRE compared to those without exhibited higher waist circumference (109.2 ± 5.3 vs 94.8 ± 9.1 cm, p = 0.001) and were characterized by greater levels of carotid to femoral PWV (8.5 ± 0.7 vs 7.1 ± 0.9 m/sec, p < 0.001) and sympathetic nerve traffic as reflected by MSNA levels (42.1 ± 1.5 vs 33.1 ± 1.9 bursts per 100 heart beats, p < 0.001), while did not differ regarding metabolic profile and left ventricular mass index (p = NS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (r = 0.229, p < 0.05), PWV (r = 0.218, p = 0.002), and MSNA (r = 0.214, p < 0.05). Moreover, MSNA was related to waist circumference (r = 0.33, p = 0.004) and office systolic BP levels (r = 0.31, p < 0.05) but there was no association with PWV values (p = NS). Conclusions: In subjects with high normal BP, a HRE indentifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.

[OP.1B.03] ARTERIAL STIFFNESS INDEPENDENTLY PREDICTS STROKE IN PATIENTS WITH ESSENTIAL HYPERTENSION: DATA FROM A GREEK 8-YEAR-FOLLOW-UP STUDY

Objective: Although arterial stiffening is related to atherosclerosis progression, its prognostic role in cerebrovascular events in hypertension is not fully elucidated. The aim of the present study was to assess the predictive role of arterial stiffness for the incidence of stroke in a cohort of essential hypertensive patients. Design and method: We followed up 1079 essential hypertensives (mean age 55.8 years, 572 males, office blood pressure (BP) = 144/91 mmHg) for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent blood sampling for assessment of metabolic profile and arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method. The distribution of PWV was split by the median (8.1 m/sec) and accordingly subjects were classified into those with high (n = 546) and low values (n = 533). Stroke was defined as rapid onset of a new neurological deficit persisting at least 24 hours unless death supervened confirmed by computed tomography and magnetic resonance angiography and/or cerebrovascular angiography findings. Results: The incidence of stroke over the follow-up period was 2.03%. Hypertensives who had stroke (n = 25) compared to those without stroke at follow-up (n = 1054) were older at baseline (63 ± 8 vs 55 ± 10 years, p = 0.012), had higher office BP levels (155 ± 13 vs 144 ± 16 mmHg, p = 0.022) and prevalence of high PWV levels (68% vs 42%, p = 0.019). No difference was observed between hypertensives with stroke and those without stroke with respect to baseline renal function and lipid levels (p = NS for all). By univariate Cox regression analysis it was revealed that high baseline PWV levels predicted stroke (hazard ratio = 1.314, p = 0.0034). Moreover, in multivariate Cox regression model, baseline age (hazard ratio = 1.098, p = 0.04) and PWV (hazard ratio = 1.105, p = 0.015) but not baseline office BP levels turned out to be independent predictors of stroke. Conclusions: In essential hypertensive patients, PWV predicts future development of stroke, independently of established confounders, including BP. These findings support that PWV constitutes a potent prognosticator of cerebrovascular events and its estimation is essential in order to improve risk stratification in hypertension.

[OP.LB.02.03] EFFECTS OF MULTIELECTRODE RENAL DENERVATION ON SYMPATHETIC NERVE ACTIVITY AND INSULIN RESISTANCE IN METABOLIC SYNDROME

Objective: This study aimed to investigate the effects of renal denervation (RDN) on sympathetic nerve activity and insulin resistance in patients with metabolic syndrome at 3 months post-RDN. Design and method: Seventeen patients fulfilled 4/5 criteria for metabolic syndrome and under stable use of at least two anti-hypertensive drugs at maximum tolerated doses for at least 4 weeks were enrolled and randomized in 3:1 ratio to RDN [n = 13, 12 males, age: 58 ± 7 years] and Control groups [n = 4, 3 males, age: 60 ± 5 years]. Both groups were followed up for 3 months. Muscle sympathetic nerve activity (MSNA) measurements were performed to assess sympathetic nerve activity at fasting state and during standard 75 g oral glucose tolerance test (OGTT). Blood sampling was also performed to assess insulin resistance (HOMA-IR). Results: In the RDN group, office BP reduced by 16 ± 21/10 ± 11 mmHg (P = 0.01/0.007); average 24-hour BP reduced by 14 ± 16/5 ± 8 mmHg (P = 0.008/0.03); waist circumference reduced by 3.1 ± 3.6 cm (P = 0.008); and MSNA at fasting state reduced from 55 ± 10 bursts per minute/82 ± 15 bursts per 100 heart beats to 46 ± 8 bursts per minute/71 ± 15 bursts per 100 heart beats (P = 0.0008/0.006) at 3 months post-RDN. During OGTT, while blunted MSNA responses were noted at baseline throughout the 120-minute test (P > 0.05/0.05 vs. MSNA at fasting state), improved MSNA responses with burst frequency/burst incidence increased to 52 ± 8 bursts per minute/76 ± 12 bursts per 100 heart beats (P < 0.001/0.04 vs. the MSNA at fasting state, n = 13) at 30 minutes and to 58 ± 16 bursts per minute/80 ± 14 bursts per 100 heart beats (P = 0.04/0.008 vs. the MSNA at fasting state, n = 10) at 120 minutes were observed at 3 months post- RDN. No such improvements were observed in the 4 control group subjects at 3 months follow-up. No statistical significant change was observed in the HOMA-IR in both groups at 3 months. Conclusions: Strategies to target specifically the elevated sympathetic nerve activity may provide substantial clinical benefits to patients with metabolic syndrome and associated hypertension.