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Adjusted Drug Treatment Is Superior to Renal Sympathetic Denervation in Patients With True Treatment-Resistant Hypertension

&NA; We aimed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516

Autonomic Function in Hypertensive and Normotensive Subjects: The Importance of Gender

Abstract—Baroreceptor reflex sensitivity (BRS) has been found lower and heart rate variability (HRV) parasympathetic markers have been found higher in healthy women than in healthy men. Thus, in the present study we hypothesized gender differences in the autonomic function among hypertensive subjects. Forty-one hypertensive patients and 34 normotensive subjects, age 53±1 years, were examined. Four weeks after cessation of antihypertensive therapy, HRV was assessed in 24-hour Holter ECGs, and BRS was calculated with the transfer technique. A t test was performed after log transformation of spectral values. Resting blood pressure and heart rate in the hypertensive and the normotensive groups were 150±2/100±1 (mean±SEM) and 121±2/81±1 mm Hg, respectively, and 68±1 and 60±1 bpm, respectively (P <0.0005). Compared with normotensive controls, hypertensive patients had lower total power (1224±116 versus 1797±241 ms2;P =0.03), lower low frequency power (550±57 versus 813±115 ms2;P =0.04), lower high frequency power (141±23 versus 215±38 ms2;P =0.06), lower root mean square successive difference (28.7±2.7 versus 35.7±3.0 ms;P =0.03), and PNN50 (4.9±0.6% versus 9.8±1.5%;P =0.003). BRS was also lower in the hypertensive subjects (7.6±0.6 versus 10.4±0.8 ms/mm Hg;P =0.005). When comparing the same parameters between normotensive subjects and hypertensive subjects within the same gender group, we found significant reduction (P <0.05) only within the female group. The difference in BRS within the female group was twice that within the male group. Stepwise multiple regression analysis revealed gender, age, HDL cholesterol, and blood pressure as independent explanatory variables of BRS and HRV. Our results suggest that gender is an important determinant of BRS and HRV. Autonomic function parameters were especially impaired in hypertensive women compared with hypertensive men.

Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension After Witnessed Intake of Medication Before Qualifying Ambulatory Blood Pressure

&NA;It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatment-resistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treatment-resistant hypertension was defined as office systolic BP>140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs, including a diuretic. In addition, ambulatory daytime systolic BP>135 mm Hg was required after witnessed intake of antihypertensive drugs to qualify. RDN (n=6) was performed with Symplicity Catheter System. The mean office and ambulatory BPs remained unchanged at 1, 3, and 6 months in the 6 patients, whereas there was no known change in antihypertensive medication. Two patients, however, had a fall in both office and ambulatory BPs. Our findings question whether BP falls in response to RDN in patients with true treatment-resistant hypertension. Additional research must aim to verify potential BP lowering effect and identify a priori responders to RDN before this invasive method can routinely be applied to patients with drug-resistant hypertension. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Relationship between hemorrheologic factors and insulin sensitivity in healthy young men.

The present study aimed at testing a possible relationship between hemorrheologic factors, such as hematocrit, fibrinogen, and whole-blood viscosity, and insulin sensitivity in healthy humans. Twenty-one 21-year-old men were studied with the hyperinsulinemic euglycemic glucose clamp technique. We found statistically significant negative correlations between the glucose disposal rate (GDR) and calculated whole-blood viscosity at both high (r = -.55, P = .01) and low (r = -.51, P = .01) shear rates. We observed negative associations between GDR and fibrinogen (r = -.66, P = .002), GDR and hematocrit (r = -.63, P = .002), GDR and body mass index (r = -.51, P = .007), and GDR and resting heart rate (r = -.46, P = .04). Using stepwise multiple regression considering whole-blood viscosity, body mass index, mean arterial blood pressure, and heart rate as independent variables, we found that only whole-blood viscosity and body mass index were independent explanatory variables of the GDR. Together they accounted for 63% of the variability in the GDR in our subjects. These results suggest hemorrheologic, and therefore indirectly hemodynamic, factors as correlates to insulin sensitivity.

Hypertension in an urban HIV-positive population compared with the general population: influence of combination antiretroviral therapy.

Objectives Hypertension is a major risk factor for cardiovascular diseases and mortality. The introduction of combination antiretroviral therapy for HIV-infected patients has changed their prognosis substantially, but there is an additional cost from the increased risk of cardiovascular diseases. We aimed to assess the prevalence of hypertension in an HIV-infected population and to identify possible predictors. Methods A cohort of 542 unselected HIV-infected individuals had their blood pressure measured at three consecutive clinical visits. They were compared with an age-matched, sex-matched and body mass index-matched population-based control group (n = 24 968). Results The prevalence of hypertension among the white HIV-infected individuals was 36.5%, which was not significantly different from the general population. The mean diastolic blood pressure was higher in HIV-infected individuals. The highest prevalence of hypertension was found in those who had been treated by combination antiretroviral therapy for more than 5 years (44.4%). Patients with hypertension were characterized by older age, male sex, white ethnicity, higher body mass index, total cholesterol and low-density lipoprotein cholesterol, lower glomerular filtration rate, more frequent microalbuminuria, longer time with known HIV-positive status and longer combination antiretroviral therapy duration compared with normotensive individuals. Multivariate analysis revealed age, sex, body mass index, cholesterol, combination antiretroviral therapy duration and microalbuminuria as independent predictors of hypertension. Conclusion Diastolic blood pressure was increased in these white HIV-infected patients compared with the general population, but there was no difference in the prevalence of hypertension. However, the duration of combination antiretroviral therapy predicted hypertension independently.

The relationship between various measures of obesity and arterial stiffness in morbidly obese patients

BackgroundObesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness.MethodsThis is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar®, Sphygmocor®) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearmans correlation, independent samples t-test, chi-square tests, Fishers exact test and multiple linear regression analyses were used as statistical methods.ResultsA total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes.ConclusionMost measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients.Trial registrationClinicalTrials.gov Identifier NCT00626964

Reproducibility of blood pressure variability, white-coat effect and dipping pattern in untreated, uncomplicated and newly diagnosed essential hypertension.

Objective: To investigate the reproducibility of blood pressure (BP) variability, white‐coat effect (WCE) and nocturnal dipping pattern in untreated patients with uncomplicated essential hypertension using 24‐hour ambulatory BP monitoring (ABPM). Methods: Seventy‐five newly diagnosed, untreated essential hypertensive subjects (54 men, 21 women 47.6 ± 9.3 years) were recruited for the study based on conventional measured BP from a total of 180 patients referred for ABPM. Of these, 65 patients underwent repeated ABPM after 4 weeks observation without treatment. Reproducibility of BP, nocturnal dipping pattern, WCE and BP variability were assessed using different methods. Results: The average 24‐hour BP (140.8 ± 11.9/91.8 ± 6.4 vs. 140.5 ± 14.5/90.7 ± 7.6 mmHg, ns) or PP (49.6 ± 10.8 vs. 49.8 ± 9.8 mmHg, ns) did not change, nor did daytime BP or PP. The WCE diminished significantly during the observation period (reduction in SBP WCE Δ8.2 ± 12.5 mmHg, p < 0.0001, in DBP WCE, Δ3.3 ± 9.2 mmHg, p = 0.008 and in PP WCE Δ4.8 ± 11.2 mmHg, p = 0.002). Variability in SBP, DBP and PP decreased consistently and significantly during the observation period. The nocturnal dipping pattern was unchanged in 82% of the patients. In 12% non‐dipping pattern was converted to dipping pattern after repeated measurement. Conclusion: Average ABPs are highly reproducible in patients with uncomplicated essential hypertension of limited duration. Similarly, nocturnal dipping pattern reproduced satisfactorily. These measures have important clinical applicability. The white‐coat effect as well as variability are greatly attenuated during repeated measurements, and these measures may thus be of less utility in clinical practice.

Telomere length and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study

Short telomeres are associated with aging and age-related diseases. Our aim was to determine whether short leukocyte telomere length is associated with risk factors and cardiovascular diseases in a high-risk hypertensive population. We measured leukocyte telomere lengths at recruitment in 1271 subjects with hypertension and left ventricular hypertrophy (LVH) participating in the Lifestyle Interventions and Independence for Elders (LIFE) study. At baseline, short mean telomere length was associated with coronary artery disease in males (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.39–0.95), and transient ischemic attack in females (OR 0.62 95% CI 0.39–0.99). Proportion of short telomeres (shorter than 5 kb) was associated with Framingham risk score (r=0.07, P<0.05), cerebrovascular disease (OR 1.18, 95% CI 1.01–1.15) and type 2 diabetes in men (OR 1.07, 95% CI 1.02–1.11). During follow-up, proportion of short telomeres was associated with combined cardiovascular mortality, stroke or angina pectoris (hazard ratio 1.04, 95% CI 1.01–1.07). Telomere length was not associated with smoking, body mass index, pulse pressure or self-reported use of alcohol. Our data suggest that reduced leukocyte telomere length is associated with cardiovascular risk factors and diseases as well as type 2 diabetes, and is a predictor of cardiovascular disease in elderly patients with hypertension and LVH.

Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide.

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/ 10mm Hg above goal.

Increased plasma vasopressin in low renin essential hypertension

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)