Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon ...represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age60.7±1.8 years, mean±SEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate40.7 mL/min per 1.73 m, MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0±2.1 versus 45.7±2.0 bursts per 100 heartbeats; P<0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first41.0±2.7; second51.9±1.7; third59.8±3.0; fourth61.9±3.3 bursts per 100 heartbeats), the statistical significance (P<0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (r=−0.59; P<0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression.
Nerve traffic recordings (muscle sympathetic nerve traffic MSNA) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of ...comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio (r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure (r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides (r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive.
In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on ...visit-to-visit 24-h BPV.
In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared.
Twenty-four-hour SBP-CV was about 20% less than office SBP-CV ( P < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values.
Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability.
Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic ...activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly (P<0.02 at least) greater in HT+ than in patients with hypertension without iron overload and normotensive subjects both when expressed as bursts incidence over time (41.8±1.4 versus 31.5±1.4 and 23.6±0.9 bursts/min) and as bursts corrected for heart rate (55.3±1.8 versus 42.3±1.2 and 31.7±1.2 bursts/100 heartbeats). In HT+, low-frequency systolic blood pressure variability was significantly reduced. In HT+, but not in the other 2 groups, muscle sympathetic nerve traffic was significantly related to serum ferritin (r=0.51, P<0.03), transferrin saturation (r=0.47, P<0.03), and hepatic iron load (r=0.76, P<0.0001, magnetic resonance imaging), as well as to homeostatic model assessment index values (r=0.46, P<0.05). These data provide the first evidence that in HT+ elevated serum ferritin is associated with a hyperadrenergic state of greater magnitude than the one seen in patients with hypertension without iron overload. They also show that the potentiation of the sympathetic activation detected in HT+ is related to elevated serum ferritin and to the associated metabolic alterations, possibly participating in the increased cardiovascular risk characterizing iron overload.
We assessed the value of 3 electrocardiographic (EKG) voltage criteria in detecting variations of left ventricular mass (LVM) over time, taking echocardiographic (ECHO) LVM as reference, in the ...Pressioni Arteriose Monitorate E Loro Associazioni study. In 927 subjects (age 47 ± 13 years on entry, 49.9% men) an ECHO evaluation of LVM and EKG suitable for measurement of EKG‐LVH criteria (Sokolow‐Lyon voltage, Cornell voltage and R‐wave voltage in aVL) were available at baseline and at a 2nd evaluation performed 10 years later. Δ (delta) LVM, Δ LVMI, and Δ EKG parameters values were calculated from 2nd evaluation to baseline. The sensitivity of the EKG criteria in the diagnosis of LVH, poor at baseline, becomes even worse after 10 years, reaching very low values. Only the sensitivity of R‐wave amplitude exhibited slight increase over time but with unsatisfactory absolute values. Despite the prevalence of ECHO‐LVH at the 2nd evaluation was threefold increased compared to baseline (29.3% and 33.7% for LVM indexed to BSA and height2.7, respectively), the prevalence of EKG‐LVH was unchanged when evaluated by Sokolow‐Lyon criteria, significantly reduced when assessed by Cornell voltage index, while significantly increased using R‐wave voltage in aVL criteria. Despite an ECHO‐LVM increase over the time, mean EKG changes were of opposite sign, except for R‐wave amplitude in aVL. Our study highlights the discrepancy between ECHO and EKG in monitoring LVM changes over the time, especially for Sokolow‐Lyon and Cornell voltage. Thus, EKG is an unsuitable method for the longitudinal evaluation of LVM variations.
We evaluated the relationships between Berlin questionnaire (BQ) scores, hypertension and other metabolic variables in 598 subjects (age: 65.8 ± 10 years, mean ± SD) enrolled in the PAMELA (Pressioni ...Arteriose Monitorate E Loro Associazioni) study representative of the general population, treated or untreated with antihypertensive drugs. Two hundred and eleven subjects (35%) had a positive BQ with two or more positive categories of the inquiry. Compared to those without sleep disorders these subjects showed a greater male prevalence (55.9%), worse serum cholesterol, triglycerides and glucose profile, greater body mass index (BMI) (28.9 ± 4.9 vs. 24.9 ± 3.4 kg/m2), higher office (and to a lesser extent 24‐h) BP and HR values, higher serum creatinine values and greater rate of echocardiographic left ventricular (LV) hypertrophy (25% vs. 13%). These differences were not detected when the data analysis was restricted to treated hypertensive patients. Thus, BQ scores allow to identify among subjects belonging to a general population those with elevated BP, organ damage and altered metabolic. When antihypertensive drug treatment is present, however, the approach fails to detect differences between groups with low or high BQ index.
OBJECTIVESPrevious studies have shown that left ventricular hypertrophy (LVH) represents a cardiovascular risk factor independently of clinic blood pressure (BP). The present study was aimed at ...determining the impact of LVH on the incidence of cardiovascular morbid and fatal events taking into account not only classical risk factors but also home and ambulatory BP values, which have been shown to have an important independent prognostic impact.
METHODSIn 1716 patients belonging to the ‘Pressioni Arteriose Monitorate E Loro Associazioni’ population of Monza, we quantified left ventricular mass index and identified LVH by standard cutoff values. We also measured clinic, home and 24-h ambulatory BPs together with serum glucose and lipids.
RESULTSDuring a follow-up of 148 months, the rate of fatal and nonfatal (hospitalizations) cardiovascular events as well as of all-cause death was markedly greater (four-fold to five-fold) in patients as compared with those without LVH. In LVH individuals, the increased risk remained significant even when data were adjusted for a large number of other confounding factors including home BP, 24-h mean BP and ambulatory BP. Results were similar when left ventricular mass was indexed by height and body surface area. A 10% increase in left ventricular mass index was associated with a significant increase in cardiovascular risk or all-cause deaths. In multivariate analysis, left ventricular mass index was always an independent predictor of cardiovascular events and death for any cause.
CONCLUSIONOur data provide evidence that LVH is an important risk factor even when the contribution of different BPs to risk is fully taken into account.
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.
The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence ...demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.
Scarce and non-homogeneous data are available on the prognostic value of clinic heart rate (HR) in coronavirus disease 2019 (COVID-19).
The present study evaluated in 389 patients hospitalized for ...COVID-19 the in-hospital prognostic value of resting HR, assessed over different time periods, i.e., at hospital admission, during initial 3 days and 7 days of hospitalization.
Results show that assessment of this hemodynamic variable during hospitalization provides information on the clinical outcome of the patients, greater HR values being associated with a worse inhospital prognosis. The prognostic value of elevated HR during COVID-19: 1) was independent on other confounders such as age, gender, comorbidities and fever, 2) appeared to be strengthened by repeated measurements of HR during the initial 3/7 days of hospitalization, and 3) was detectable in patients in which the therapeutic intervention did not include drugs, such as beta-blockers, calcium antagonists, digoxin, ivabradine and antiarrhythmic compounds known to interfere with HR.
Heart rate may represent an important marker of a patient's outcome in COVID-19.
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