Abstract Background An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether ...sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). Methods In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. Results BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mm Hg, P < 0. 01 ). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0. 01 ). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r2partial = 0.04405 and r2partial = 0.00878, P < 0. 05 for both). Conclusions These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon.
Obesity is associated with a higher risk of developing diabetes mellitus (DM), hypertension (HT), and left ventricular hypertrophy (LVH). The present study assessed in the general population the ...impact of body weight and visceral obesity on the development of alterations in glucose metabolism and cardiac structure, as well as of elevation in blood pressure. In 1412 subjects randomly selected and representative of the general population of Monza, we assessed twice (in 1990/1991 and 2000/2001) body mass index (BMI); waist circumference; office, home, and 24-hour ambulatory (24-hour) blood pressure, fasting glycemia, and left ventricular mass (echocardiography). New-onset high-risk conditions were DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH. The incidence of new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased progressively from the quintile with the lowest to the quintile with the highest BMI values. Adjusting for confounders, the risk of developing new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased significantly for an increase of 1 kg/m(2) of BMI and 1 cm of waist circumference (respectively, 8.4% P<0.01, 9.5% P<0.0001, 4.2% P<0.0001, 3.9% P<0.001, 2.5% P<0.05, and 5.1% P<0.001 for BMI and 3.2% P<0.001, 3.5% P<0.0001, 1.8% P<0.0001, 1.5% P<0.0001, 1.4% P<0.001, and 2.6% P<0.0001). These data provide evidence that an increase in BMI and waist circumference is associated with a linearly increased adjusted risk of developing conditions with high cardiovascular risk, such as DM, impaired fasting glucose, in- and out-of-office HT, and LVH.
In hypertensive patients the risk of developing cardiovascular events and complications depends not only on the magnitude of the blood pressure elevation, but also, and to a consistent extent, on the ...presence of associated cardiovascular risk factors, concomitant disease and target organ damage. Recent findings suggest that also sympathetic overdrive and alterations in blood pressure variability (which are detected in hypertension) may participate at the increased cardiovascular risk of the patients with high blood pressure. This review will discuss the evidence collected over the past few years on the relationships between sympathetic activation and blood pressure variability and their impact on cardiovascular risk profile.
Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern ...European countries.
In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients' age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure.
These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.
Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large- and medium-size arteries. We hypothesized that normotensive ...subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m2, mean ± s.e.m.) and 17 age-matched severely obese (BMI: 41.1 ± 2.3 kg/m2) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross-sectional area (CSA), and media-to-lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm2, and media-to-lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine-induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (−40.4 ± 1.3%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.
Several studies have investigated the behavior of sympathetic cardiovascular drive in essential hypertension, providing conclusive evidence of the adrenergic activation characterizing this condition. ...These studies have also shown the importance of neuroadrenergic overdrive in the development and progression of the hypertensive state as well as in the pathogenesis of hypertension-related end-organ damage. The information available on the sympathetic nervous system's behavior in 'pseudo-resistant' and 'true resistant' hypertension is much more scarce. This paper will review the available knowledge on this issue by examining the data collected via indirect and direct approaches to investigate adrenergic function in resistant hypertension as well as the effects of pharmacological and non-pharmacological interventions.
Abstract The sympathetic nervous system is activated in a variety of cardiovascular and metabolic diseases. This is particularly the case for essential hypertension, in which various indices of ...adrenergic activity, such as plasma norepinephrine, norepinephrine spillover, and sympathetic nerve firing rate, are all well above the reference range of values, thereby documenting sympathetic overdrive. Evidence is available that sympathetic neural factors participate in disease progression, as well as in the development of cardiac and renal organ damage. These findings represent the rationale for therapeutic interventions that counteract the adrenergic overdrive in the hypertensive state. This paper, after reviewing the key findings of the neuroadrenergic abnormalities occurring in hypertension, examines the rationale and the technical details, as well as the results achieved so far, with the use of a new technique that allows the elimination of afferent and efferent innervation of the kidney in resistant hypertension, ie, the ablation of renal nerves. Strengths and potential limitations of the renal denervation approach are briefly addressed.
PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) is an epidemiological study, originally designed to determine the normality of home and ambulatory blood pressure values. The study was ...performed on 3,200 subjects, aged 25 to 74 years, randomly selected from the general population of Monza (Milan, Italy). In the study context we performed clinical, home and ambulatory blood pressure measurements, echocardiographic assessment of cardiac structure and function as well as laboratory examinations (glucose and lipids). Personal and family histories were collected. The same procedures were repeated 10 years later. During a 12-year follow-up, the incident cardiovascular events were validated. Cardiovascular and all-cause fatal events were collected for a 16-year follow-up. This article will review the main results of the PAMELA study, with particular emphasis on (1) the prognostic value of the different blood pressure measurements, (2) the relationships between metabolic variables and blood pressure and (3) the clinical relevance and prognostic importance of left ventricular mass values and alterations.
Objective:
To assess the reproducibility of the two markers of adrenergic drive, venous plasma norepinephrine (NE) and efferent postganglionic muscle sympathetic nerve activity (MSNA), in reflecting ...the sympathetic activation characterizing congestive heart failure (CHF).
Methods and measurements:
In 19 CHF male normotensive patients (mean age: 53.0±2.1 years, NYHA classes II and III, left ventricular ejection fraction 35.9±2.9%), blood pressure (BP, Finapres), heart rate (EKG), plasma NE (HPLC assay) and MSNA (microneurography, peroneal nerve) were measured in two experimental sessions separated by a week interval. At each session, three NE samples were obtained and NE reproducibility between sessions was assessed by considering single NE samples or averaging 2-3 samples.
Results:
While MSNA values showed a highly significant correlation between sessions (r = 0.85, P<0.001), NE values based on a single blood sample evaluation did not correlate with each other (r = 0.41, P = NS). NE correlation coefficients improved and achieved statistical significance when average data from 2 and 3 blood samples were examined (r = 0.54 and r = 0.57, P<0.02 for both).
Conclusions:
In CHF, MSNA displays a better reproducibility pattern than plasma NE. The reproducibility of the NE approach, however, can be improved by performing the assay on multiple blood samples.
The two novel approaches recently introduced for the treatment of resistant hypertension, i.e. carotid baroreceptor stimulation and renal denervation, share a number of similarities but are also ...characterized by important differences. The similarities include the evidence that both interventions have as common pathophysiological background the state of sympathetic overdrive characterizing essential hypertension. In addition both procedures 1) are invasive, 2) exert in the short-term period clearcut blood pressure lowering effects and 3) still face a number of open questions, particularly related to the long-term blood pressure lowering effects, impact on end-organ damage and on cardiovascular events. The differences include the fact that two procedures act on distinct targets that trigger sympathetic activation and consequently blood pressure increase. In addition, only in the case of carotid baroreceptor stimulation the blood pressure effects can be easily assessed immediately following the implantation. Finally, the economic costs, metabolic effects and impact on vagal modulation of heart rate are different between the two interventions. This paper will provide a comparison of the background, effects and outcome of renal denervation and carotid baroreceptor stimulation, stressing whenever possible the clinical implications of the main features of the two interventions.
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