Ioannis Liatakis

Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: a 6-year follow-up study

This study aimed to assess the predictive role of body mass index (BMI), waist circumference (WC) and the waist-to-hip ratio (WHR) for the incidence of coronary artery disease (CAD) in a cohort of essential hypertensive patients. We followed up 2266 essential hypertensive individuals (mean age, 57.8 years; males, 1083; office blood pressure (BP), 143/89 mm Hg) who were free of cardiovascular disease for a mean period of 6 years. All subjects had at least one annual visit and, at baseline, underwent blood sampling and a complete echocardiographic study to determine the left ventricular (LV) mass index. CAD was defined as a history of myocardial infarction or significant coronary artery stenosis that was revealed by angiography or a coronary revascularization procedure. The incidence of CAD throughout the follow-up period was 2.33%. Hypertensive individuals who developed CAD (n=53) had a greater baseline WC (101.1±11.7 vs. 96.4±12 cm, P=0.005), WHR (0.94±0.07 vs. 0.89±0.08 cm, P<0.0001) and LV mass index (117±26.8 vs. 103.3±27 g m−2, P<0.0001) compared with those without CAD at follow-up (n=2213), whereas no difference was observed compared with the baseline office BP and BMI values (P=NS for all). Using a multivariate Cox regression model, WC (hazard ratio (HR) 1.037, P=0.002) and LV mass index (HR 1.010, P=0.044) were found to be independent predictors of CAD. In essential hypertensive patients, WC could predict the future development of CAD, whereas BMI and WHR showed no independent prognostic value. These findings suggest that WC constitutes an easy clinical tool to assess risk in hypertension among individuals with obesity.

Effects of multielectrode renal denervation on elevated 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. Methods: Seventeen patients fulfilled at least four of five criteria for metabolic syndrome and under stable use of at least two antihypertensive drugs were randomized in 3 : 1 ratio to RDN (n = 13, 12 men, age: 58 ± 7 years) and control groups (n = 4, three men, age: 60 ± 5 years) and followed up for 3 months. Muscle sympathetic nerve activity (MSNA) at rest and during standard 75 g oral glucose tolerance test (OGTT) was assessed. Results: In the RDN group, office and average 24-h blood pressures reduced by 16 ± 21/10 ± 11 mmHg (P = 0.01/0.007) and 14 ± 16/5 ± 8 mmHg (P = 0.008/0.03) respectively; waist circumference reduced by 3.1 ± 3.6 cm (P = 0.008); and resting MSNA reduced from 55 ± 9 bursts per minute to 46 ± 8 bursts per minute (P = 0.0008) at month 3 post-RDN. During OGTT, although blunted MSNA responses were noted at baseline throughout the 120-min test, improved MSNA responses with burst frequency increased to 52 ± 8 bursts per minute (P < 0.001 vs. the resting MSNA, n = 13) at 30 min and to 54 ± 8 bursts per minute (P = 0.004 vs. the resting MSNA, n = 10) at 120 min and were observed at month 3 post-RDN. No such improvements were observed in the controls. No significant change was observed in the HOMA-IR in both groups at month 3. Conclusion: In this pilot study of patients with metabolic syndrome and associated hypertension, RDN reduced elevated sympathetic nerve activity and restored the normal neural response to oral glucose loading.

[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.

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.

Uric acid as an independent predictor of coronary artery disease in essential hypertension: Data from an 8-year-follow-up study

The role of serum uric acid (SUA) in cardiovascular risk prediction remains to be further determined. We assessed the predictive value of SUA for the incidence of coronary artery disease (CAD) in 2287 essential hypertensive patients who were followed up for a mean period of 8 years. The distribution of SUA levels at baseline was split by the median (5.2 mg/dL) and subjects were classified into those with high and low values. Hypertensives who developed CAD (n = 57) compared to those without CAD at follow‐up (n = 2230) had at baseline higher SUA. In multivariate Cox regression model, among established confounders, high SUA (hazard ratio = 1.216, P = .016) turned out to be independent predictor of CAD. In essential hypertensive patients SUA independently predicts CAD.

TCT-764 EFFECTS OF MULTIELECTRODE RENAL DENERVATION ON SYMPATHETIC NERVE ACTIVITY AND INSULIN RESISTANCE IN METABOLIC SYNDROME

BACKGROUND Clinical evaluation of renal denervation (RDN) as a therapy for uncontrolled hypertension continues. Current emphasis is on more rigorously controlled trials, including the controlling of technique variability and more efficient nerve inactivation. The Peregrine System Infusion Catheter is used to perform RDN via the delivery of alcohol into the perivascular space of the renal artery, directly targeting the sympathetic nerves. The technique and mode of action of denervation by alcohol may offer advantages over energybased approaches, and merit further assessment.

[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.