Short- and Long-Term Neuroadrenergic Effects of Moderate Dietary Sodium Restriction in Essential Hypertension

Background— In essential hypertension, marked restrictions in dietary sodium intake cause in the short-term period an increase in muscle sympathetic nerve traffic (MSNA) and a baroreflex impairment. The present study was set out to assess on a long-term basis the neuroadrenergic and reflex effects of moderate sodium restriction. Methods and Results— In 11 untreated mild to moderate essential hypertensive patients (age 42.0±2.6 years, mean±SEM), we measured beat-to-beat blood pressure (Finapres), heart rate (ECG), and MSNA (microneurography) at rest and during stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were performed at regular sodium intake, after 1 and 8 weeks of low-sodium diet (80 mmol NaCl/d), and repeated again at regular sodium intake. After 1 week, urinary sodium excretion was markedly reduced. This was accompanied by a slight blood pressure reduction, no heart rate change, and a significant increase in plasma renin activity, aldosterone, and MSNA (+23.0±4.6% P <0.05). Whereas baroreflex heart-rate control was unchanged, baroreflex modulation of MSNA was reduced by 46.8±5.1% ( P <0.01). At the end of the 8-week low-sodium diet, the neurohumoral and baroreflex responses were similar to the ones observed after 1 week of the dietary intervention. All changes disappeared when regular sodium diet was restored. Conclusions— Thus, a moderate dietary sodium restriction triggers a sympathetic activation and a baroreflex impairment. Maintenance of low-sodium diet for several weeks does not attenuate these adverse adrenergic and reflex effects

Effects of long-term lercanidipine or hydrochlorothiazide administration on hypertension-related vascular structural changes.

Vascular remodelling and hypertrophy represent early therapeutic targets of antihypertensive treatment. The present study was aimed at assessing the effects of 1-year administration of the highly vasoselective calcium-channel blocker lercanidipine (10 mg/day) or the diuretic compound hydrochlorothiazide (25 mg/day) on hypertension-related vascular alterations. The study was also aimed at assessing whether and to what extent: (i) pharmacological regression of vascular hypertrophy is related only to the blood pressure (BP) reduction "per se" or also to the specific ancillary properties of a given drug and (ii) treatment provides restoration of vascular function indicative of normal vascular structure.In 26 untreated patients with mild-to-moderate essential hypertension sphygmomanometric and finger BP, heart rate, forearm and calf blood flow (venous occlusion plethysmography) and corresponding vascular resistance (forearm and calf vascular resistance: FVR and CVR) were assessed before and following 6 and 12 months of either lercanidipine or hydrochlorothiazide administration. Vascular resistance was also evaluated following a local ischaemic stimulus (FVR(min) and CVR(min)) in order to assess the effects of treatment on arteriolar structural alterations.For superimposable BP reductions, lercanidipine caused FVR and CVR to decrease significantly more than hydrochlorothiazide. Similarly, the FVR(min) and CVR(min) reductions induced by lercanidipine were markedly and significantly greater than those caused by hydrochlorothiazide (-46.1% and -40.9% vs -22.5% and -19.9%, p0.01 for both). FVR(min), and CVR(min), however, remained higher than those found in 10 age-matched normotensive individuals.These data provide evidence that, compared to hydrochlorothiazide, lercanidipine favours a greater regression of the vascular structural changes associated with hypertension, probably through its "ancillary" properties. Lercanidipine, however, does not allow restoration of a "normal" vascular structure, thereby suggesting that vascular hypertrophy is only in part a reversible phenomenon

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases

Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project

A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women

Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan-Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (&gt;= 4.7 mg/dL) and CVM (&gt;= 5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12-1.40], p &lt; 0.001) and CVM (1.31 [1.11-1.74], p &lt; 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12-1.43], p &lt; 0.001) and hypertriglyceridemia (1.31 [1.02-1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23-1.73], p &lt; 0.001) and hypertriglyceridemia (HR 1.31 [0.99-1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels

Clinical Relevance of the Sympathetic–Vascular Interactions in Health and Disease

The sympathetic nervous system is known to play a pivotal role in the short- and long-term regulation of different cardiovascular functions. In recent decades, increasing evidence has demonstrated that sympathetic neural influences are involved not only in the vasomotor modulation of small resistance arteries but also in the control of large arteries. Sympathetic activity and vascular function, which are key factors in the pathophysiology and prognosis of cardiovascular disease, are linked by a close relationship. Evidence from experimental studies indicates that the sympathetic nervous system is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, namely nitric oxide, reactive oxygen species and endothelin. Additionally, there is evidence of a reciprocal influence between endothelial function and sympathetic mechanisms. This paper will provide an overview of the relationships between endothelial function and the sympathetic nervous system characterizing physiological states. It will also briefly mention the alterations described in cardiovascular disease, with particular emphasis on essential hypertension and congestive heart failure, i.e., the two pathological states in which endothelial dysfunction and neuroadrenergic activation appear to be relevant factors for determining cardiovascular prognosis

Sustained sympathoinhibitory effects of cardiac resynchronization therapy in severe heart failure

Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure-dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean+/-SEM age, 68.4+/-1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration > or =130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and approximately 10 weeks after successful resynchronization therapy. Ten age- and NYHA class-matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1+/-3.6 vs 30.7+/-3.0 bs/min, -30.5%, P<0.02) and as burst frequency corrected for heart rate (68.3+/-5.9 vs 47.3+/-4.3 bs/100 beats, -32.1%, P<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications

The "J curve" problem revisited: Old and new findings

This paper critically addresses the issue of the "J-curve" paradox-the finding described in studies performed about 30 years ago indicating that treatment-induced systolic blood pressure values below 120 or 125 mm Hg and diastolic blood pressure values below 75 mm Hg are characterized by an increase, rather than a reduction, in the incidence of coronary events. This paper focuses on four major subjects: 1) the benefits of a lower blood pressure target during treatment; 2) the historical background of the "J-curve" phenomenon; 3) the evidence collected in recent clinical trials regarding the existence of a "J-curve" in treated hypertensive patients; and 4) the recent recommendations by the Task Force Committee of the European Society of Hypertension on blood pressure goals to be achieved during treatment. © 2010 Springer Science+Business Media, LLC

Transient effects of carotid baroreflex stimulation via the neck chamber device on central venous pressure

Abstract We examined in 11 young subjects (age 29.7±3.6 years, mean±SEM) whether carotid baroreceptor stimulation via the neck chamber device may affect central venous pressure (CVP), thus potentially involving other reflexogenic areas in the examined responses. Application of progressively greater neck chamber subatmospheric pressures caused a progressive lengthening in RR interval, which reached a peak at the maximal value of negative neck chamber pressure applied. This was accompanied by significant and progressively greater reduction in CVP values when the data were calculated considering the early changes occurring within the first 2 seconds of the stimulus. There was a weak correlation between the early changes in CVP and the RR interval responses when all stimuli were pooled together (r = 0.32, P < .05). The results of the present study suggest that the neck chamber technique employed to assess carotid baroreceptor‐heart rate sensitivity can transiently affect via the CVP reduction cardiopulmonary receptors activity, which may participate at the integrated reflex responses