Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Associations between symptoms and functional capacity in patients after COVID-19 infection and community controls.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC or 'long COVID') reflect ongoing symptoms, but these are non-specific and common in the wider community. Few reports of PASC have been compared with a control group. AIMS: To compare symptoms and objective impairment of functional capacity in patients with previous COVID-19 infection with uninfected community controls. METHODS: In this community-based, cross-sectional study of functional capacity, 562 patients from Western Melbourne who had recovered from COVID-19 infections in 2021 and 2022 were compared with controls from the same community and tested for functional capacity pre-COVID-19. Functional impairment (<85% of the predicted response) was assessed using the Duke Activity Status Index (DASI) and 6-min walk distance (6MWD) test. A subgroup underwent cardiopulmonary exercise testing before and after exercise training. RESULTS: Of 562 respondents (age 54 ± 12 years, 69% women), 389 were symptomatic. Functional impairment (<85% predicted metabolic equivalent of tasks) was documented by DASI in 149 participants (27%), and abnormal 6MWD (<85% predicted) was observed in 14% of the symptomatic participants. Despite fewer risk factors and younger age, patients with COVID-19 had lower functional capacity by 6MWD (P < 0.001) and more depression (P < 0.001) than controls. In a pilot group of seven participants (age 58 ± 12 years, two women, VO2 18.9 ± 5.7 mL/kg/min), repeat testing after exercise training showed a 20% increase in peak workload. CONCLUSIONS: Although most participants (69%) had symptoms consistent with long COVID, significant subjective functional impairment was documented in 27% and objective functional impairment in 14%. An exercise training programme might be beneficial for appropriately selected patients.

Catheter-Based Renal Denervation: 9-Year Follow-Up Data on Safety and Blood Pressure Reduction in Patients With Resistant Hypertension.

BACKGROUND: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU). METHODS: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU. RESULTS: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (P<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (P<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (P=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m2. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (P<0.0001). CONCLUSIONS: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

Association Between the Gut Microbiome and Their Metabolites With Human Blood Pressure Variability.

BACKGROUND: Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability. METHODS: Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean±SD, 59.8±7.26 years; body mass index, 25.2±2.83 kg/m2). These data were used to determine nighttime dipping, morning BP surge (MBPS) and BP variability as SD. The gut microbiome was determined by 16S ribosomal RNA (rRNA) sequencing and metabolite levels by gas chromatography. RESULTS: We identified specific taxa associated with systolic BP variability, nighttime dipping, and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while Prevotella spp. and Clostridium spp., were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial α-diversity (r=-0.244, P=0.046). MBPS was also negatively associated with plasma levels of microbial metabolites called short-chain fatty acids (r=-0.305, P=0.020), particularly acetate (r=-0.311, P=0.017). CONCLUSIONS: Gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability and Clostridium and Prevotella with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.

Vasoplegia Following Orthotopic Heart Transplantation: Prevalence, Predictors and Clinical Outcomes.

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease.

[Figure: see text].

The Gut Microbiota and Their Metabolites in Human Arterial Stiffness.

AIM: Gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) have vasodilator properties in animal and human ex vivo arteries. However, the role of the gut microbiota and SCFAs in arterial stiffness in humans is still unclear. Here we aimed to determine associations between the gut microbiome, SCFA and their G-protein coupled sensing receptors (GPCRs) in relation to human arterial stiffness. METHODS: Ambulatory arterial stiffness index (AASI) was determined from ambulatory blood pressure (BP) monitoring in 69 participants from regional and metropolitan regions in Australia (55.1% women; mean, 59.8± SD, 7.26 years of age). The gut microbiome was determined by 16S rRNA sequencing, SCFA levels by gas chromatography, and GPCR expression in circulating immune cells by real-time PCR. RESULTS: There was no association between metrics of bacterial α and ß diversity and AASI or AASI quartiles in men and women. We identified two main bacteria taxa that were associated with AASI quartiles: Lactobacillus spp. was only present in the lowest quartile, while Clostridium spp. was present in all quartiles but the lowest. AASI was positively associated with higher levels of plasma, but not faecal, butyrate. Finally, we identified that the expression of GPR43 (FFAR2) and GPR41 (FFAR3) in circulating immune cells were negatively associated with AASI. CONCLUSIONS: Our results suggest that arterial stiffness is associated with lower levels of the metabolite-sensing receptors GPR41/GPR43 in humans, blunting its response to BP-lowering metabolites such as butyrate. The role of Lactobacillus spp. and Clostridium spp., as well as butyrate-sensing receptors GPR41/GPR43, in human arterial stiffness needs to be determined.

Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation.

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (-8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.

Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease.

Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline (P<0.001), and compared with sham control rabbits, renal sympathetic nerve activity was 1.2±0.5 normalized units greater (P=0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both P<0.05). RDN CKD rabbits only increased blood pressure by 8.0±1.5 mm Hg. Renal sympathetic activity, the response to ganglion blockade and diuresis were similar to sham denervated rabbits (non-CKD). CKD rabbits had intact renal sympathetic baroreflex gain and range, as well as normal sympathetic responses to airjet stress. However, hypoxia-induced sympathoexcitation was reduced by -9±0.4 normalized units. RDN did not alter the sympathetic response to hypoxia or airjet stress. CKD increased oxidative stress markers Nox5 and MCP-1 (monocyte chemoattractant protein-1) in the kidney, but RDN had no effect on these measures. Thus, RDN is an effective treatment for hypertension in this model of CKD without further impairing renal function or altering the normal sympathetic reflex responses to various environmental stimuli.

Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6th of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-ß, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.

The Emerging Role of Gut Dysbiosis in Cardio-metabolic Risk Factors for Heart Failure.

PURPOSE OF REVIEW: To summarize the recent evidence that supports a role for the gut microbiota, microbiota-derived metabolites, and dysbiosis on cardiovascular risk factors, and to discuss the neuro-cardio-metabolic mechanisms that link gut microbiota and heart failure. RECENT FINDINGS: There is growing evidence that the gut microbiota communicates with and impacts the cardiovascular system, contributing to the development of heart failure once it becomes out of balance (i.e. gut dysbiosis). The exact mechanisms of how the gut microbiota influences cardiovascular outcomes are not fully understood, but immune dysregulation and disturbance of neuro-enteroendocrine hormones seem to be involved. The disturbances in the gut microbiota influence the progression of several risk factors for heart failure, including atherosclerosis, obesity, diabetes, kidney disease and hypertension. In turn, these conditions also act to regulate the gut microbiota through the deterioration of the integrity of the intestinal barrier and the release of neurotransmitters and gastrointestinal hormones. In normal and healthy physiological conditions, these interactions are homeostatic and tightly controlled. However, a combination of environmental exposures (e.g. antibiotics use and Western diet) and the host's intrinsic conditions (e.g. genetics and fluid status) can result in the breakdown of intestinal homeostasis and further progression of cardiovascular risk factors, which lead to the development of heart failure. Manipulation of the gut microbiota may have the potential to improve cardiovascular outcomes by ameliorating immune system dysregulation, enteroendocrine disruptions, and neurohormonal activation in patients with cardiovascular risk factors for heart failure.

Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes.

AIMS/HYPOTHESIS: We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. METHODS: Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits. RESULTS: Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05). CONCLUSIONS/INTERPRETATION: As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.

Threshold and saturation pressures of baroreflex-mediated myocardial interstitial acetylcholine release in rats.

Cardiac microdialysis allows the assessment of cardiac efferent vagal nerve activity from myocardial interstitial acetylcholine (ACh) levels with minimal influence on the neural control of the heart; however, a total picture of the baroreflex-mediated myocardial interstitial ACh release including the threshold and saturation pressures has yet to be quantified. In eight anesthetized Wistar-Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release simultaneously with efferent sympathetic nerve activity (SNA) during a carotid sinus baroreceptor pressure input between 60 and 180 mm Hg. The baroreflex-mediated ACh release approximated a positive sigmoid curve, and its threshold and saturation pressures were not significantly different from those of an inverse sigmoid curve associated with the baroreflex-mediated SNA response (threshold: 94.3 ± 8.6 vs. 99.3 ± 6.0 mm Hg; saturation: 150.0 ± 10.3 vs. 158.8 ± 5.8 mm Hg). The sympathetic and vagal systems have certain levels of activities across most of the normal pressure range.

Successful renal denervation decreases the platelet activation status in hypertensive patients.

AIMS: To determine whether renal denervation (RDN) in hypertensive patients affects the platelet activation status. METHODS AND RESULTS: We investigated the effect of RDN on the platelet activation status in 41 hypertensive patients undergoing RDN. Ambulatory blood pressure (BP), plasma sympathetic neurotransmitter Neuropeptide Y, and platelet activation markers were measured at baseline, at 3 months, and 6 months after RDN. RDN significantly decreased BP at 3 months (150.6 ± 11.3/80.9 ± 11.4 mmHg to 144.7 ± 12.0/77.1 ± 11.1 mmHg; P < 0.01) and at 6 months (144.3 ± 13.8/78.3 ± 11.1 mmHg; P < 0.01). Plasma levels of the sympathetic neurotransmitter Neuropeptide Y, an indicator of sympathetic nerve activity, were significantly decreased at 3 months (0.29 ± 0.11 ng/mL to 0.23 ± 0.11 ng/mL; P < 0.0001) and at 6 months (0.22 ± 0.12 ng/mL; P < 0.001) after RDN. This was associated with a reduction in platelet membrane P-selectin expression (3 months, P < 0.05; 6 months, P < 0.05), soluble P-selectin (6 months, P < 0.05), circulating numbers of platelet-derived extracellular vesicles (EVs) (3 months, P < 0.001; 6 months, P < 0.01), and phosphatidylserine expressing EVs (3 months, P < 0.001; 6 months, P < 0.0001), indicative of a reduction in platelet activation status and procoagulant activity. Only patients who responded to RDN with a BP reduction showed inhibition of P-selectin expression at 3 months (P < 0.05) and 6 months (P < 0.05) as well as reduction of glycoprotein IIb/IIIa activation at 3 months (P < 0.05). Notably, 13 patients who took aspirin did not show significant reduction in platelet P-selectin expression following RDN. CONCLUSION: Our results imply a connection between the sympathetic nervous system and the platelet activation status and provide a potential mechanistic explanation by which RDN can have favourable effects towards reducing cardiovascular complications.

Moderate morning rise in blood pressure has lowest risk of stroke but only in women.

BACKGROUND: The morning period which is recognized as the highest risk for cardiovascular events is associated with a surge in blood pressure (BP). However, it is unclear what aspect of this rise is important. AIM: To determine whether the rate of rise (RoR), the magnitude (day night difference) or the product [BP power (BPPower)] is associated with increased cardiovascular risk. METHODS: We developed a logistic equation method to fit individual 24-h patterns of BP to determine RoR, amplitude and BPPower using the ambulatory recordings from the Ohasama study including 564 men and 971 women (16.6 years follow-up). RESULTS: Men had a higher risk of cardiovascular events than women (24, 16%, P < 0.001). Age and night BP were strong linear risk predictors. In men sorting risk by quintiles of BPPower (adjusted for age, night BP, smoking status) revealed no clear linear or nonlinear pattern. However, in women BPPower had a U-shaped relationship with the lowest risk being the 2-3rd quintile for all cardiovascular events (Pquadratic = 0.01) including cardiovascular death (Pquadratic = 0.03) and nonfatal stroke (Pquadratic = 0.02). A similar but less clear trend was observed with the RoR but only stroke (infarct) reached significance (Pquadratic = 0.03) while sorting by range showed a U shaped pattern for combined cardiovascular events (Pquadratic = 0.04). CONCLUSION: These findings suggest that the morning BPPower is an important independent risk factor for predicting cardiovascular events and stroke but only in women with median levels having the lowest risk.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Ambulatory arterial stiffness index as a predictor of blood pressure response to renal denervation.

BACKGROUND: Renal denervation (RDN) can reduce blood pressure (BP) in patients with resistant hypertension, but less so in patients with isolated systolic hypertension. A possible explanation is that patients with stiffer arteries may have lesser neural contribution to their hypertension. METHOD: We hypothesized that arterial stiffness predicts the response to RDN. From ambulatory BP monitoring (ABPM), ambulatory arterial stiffness index (AASI) was calculated as 1 - the regression slope of DBP versus SBP. RESULTS: In 111 patients with resistant hypertension, RDN reduced office and 24-h SBP after 3, 6, and 12 months (by -11 ±â€Š22, -11 ±â€Š25, -14 ±â€Š21 mmHg for office, and -4 ±â€Š11, -5 ±â€Š12, -5 ±â€Š15 mmHg for 24-h SBP, respectively, P < 0.01). Patients with baseline AASI above the median (>0.51) showed no change in 24-h SBP at 6 months after RDN (-0.4 ±â€Š12.3 mmHg, P > 0.05), whereas an AASI below 0.51was associated with a marked reduction (-9.3 ±â€Š11.0 mmHg, P < 0.01). Across AASI quartiles, patients in the highest quartile (AASI ≥ 0.60) had lower muscle sympathetic nerve activity than the other three quartiles (39 ±â€Š13 versus 49 ±â€Š13 bursts/min, P = 0.035). The responder rate, defined as a 24-h SBP reduction of at least 5% was 58% in the lowest AASI quartile (<0.45) and 16% in the highest quartile (≥0.60). After adjustment for age, sex, BMI, office and 24-h SBP, an AASI less than 0.51predicted those who respond to RDN (odds ratio 3.46, P = 0.04). CONCLUSION: We conclude that in patients with resistant hypertension, a lower AASI is an independent predictor of the BP response to RDN, possibly explained by a more pronounced neurogenic rather than biomechanical contribution to their BP elevation.

Factors Responsible for Obesity-Related Hypertension.

PURPOSE OF REVIEW: The major health issue of being overweight or obese relates to the development of hypertension, insulin resistance and diabetic complications. One of the major underlying factors influencing the elevated blood pressure in obesity is increased activity of the sympathetic nerves to particular organs such as the kidney. RECENT FINDINGS: There is now convincing evidence from animal studies that major signals such as leptin and insulin have a sympathoexcitatory action in the hypothalamus to cause hypertension. Recent studies suggest that this may involve 'neural plasticity' within hypothalamic signalling driven by central actions of leptin mediated via activation of melanocortin receptor signalling and activation of brain neurotrophic factors. This review describes the evidence to support the contribution of the SNS to obesity related hypertension and the major metabolic and adipokine signals.