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Background: Results of recent clinical trials have shown that in heart failure (HF) heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk. No information is available on whether the sympathetic nervous system is differently activated in HF patients displaying resting HR values above or below this cutoff. Methods: In 103 HF patients aged 62.7 ± 0.9 (mean ± SEM) years and in 62 heathy controls of similar age we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the subjects in different groups according to their resting clinic and 24-h HR values. Results: In HF progressively greater values of clinic or 24-h HR were associated with a progressive increase in both MSNA and NE. HR cutoff values adopted in large scale clinical trials for determining cardiovascular risk, i.e., 70 beats/minute, were associated with MSNA values significantly greater than the ones detected in patients with lower HR, this being the case also for NE. In HF both MSNA and NE were significantly related to clinic (r = 0.92, P < 0.0001 and r = 0.81, P < 0.0001, respectively) and 24-h (r = 0.91, P < 0.0001 and r = 0.79, P < 0.0001, respectively) HR. The behavior of sympathetic markers described in HF was specific for this clinical condition, being not observed in healthy controls. Conclusions: Both clinic and 24-h HR values greater than 70 beats/minute are associated with an increased sympathetic activation, which parallels for magnitude the HR elevations. These findings support the relevance of using in the therapeutic approach to HF drugs exerting sympathomoderating properties.

Objective: No trial-based evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection may be indirectly inferred, however, from the blood pressure (BP) effects of treatment, because in trials outcomes decrease is linearly related to BP reduction. We andomis the effect of antihypertensive treatment on office and out-of-office BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS). Design and method: Office and ambulatory BP were measured in 470 hypertensive patients andomisat to an ACE-inhibitor or a diuretic alone or combined with a statin before treatment and at yearly intervals during a 3-year follow-up. Patients were divided into two groups according to whether baseline data obtained before andomisation to treatment showed that 1) office and 24-hour mean BP were elevated (75.8% sustained hypertensive, SH) or 2) office BP was elevated but 24-hour BP values were normal (24.2% WCH). Results: Antihypertensive drug treatment was associated with an early marked reduction of BP, which persisted virtually unchanged throughout the treatment period and was only slightly and usually not significant different in SH and WCH (-18.9 ± 11.1/-12.7 ± 5.9 mmHg for SBP/DBP in SH and -18 ± 10.4/-12.3 ± 6.2 for SBP/DBP in WCH p = 0.43/p = 0.52). This was not the case, however, for 24-h BP which, fell consistently in SH while showing no change in WCH(-10.7 ± 10.8/1.0 ± 8.3 mmHg for SBP/DBP in SH and -7.4 ± 7.2/0.1 ± 4.8 for SBP/DBP in WCH p < 0.001/p < 0.001). In SH but not in WCH antihypertensive treatment consistently reduced either the higher daytime and the lower nighttime SBP and DBP values during the treatment. Conclusions: In WCH antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline.

Objective: According to some guidelines white-coat hypertension (WCH) carries little or no increase of cardiovascular (CV) risk in absence of organ damage (OD) but no data are available on this issue. Design and method: Using the population data from Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA), we evaluated CV and total mortality over a median follow-up of 29 years in WCH (elevated office and normal 24-hour or home blood pressure, BP) and normotensive controls (N, normal in- and out-of-office BP) with no echocardiographic left ventricular hypertrophy and no reduction of estimated glomerular filtration rate. Analysis was extended to sustained hypertension (SH, in- and out-of-office BP elevation) and to N, WCH and SH with cardiac and renal OD. Results: During the 29 years follow-up there were in the 1423 subjects nalysed 165 CV and 526 all cause deaths. OD was detected in 10.6%, 30.5% and 43.8% of N, WCH and SH, respectively. After adjustment for confounders no-ODWCH exhibited a risk of fatal CV events lower than that of no-ODSH but greater than that of no-ODN (HR 2.0, 95% CI: 1.1-3.6, P = 0.02), this being the case also for all cause mortality. Compared with no-ODN, no-ODWCH also exhibited a greater 10 year adjusted risk to develop new SH or OD. Similar findings were obtained in N, WCH and SH with OD. The present study provides the first evidence that WCH with no cardiac and renal OD is accompanied by an increased long-term risk of mortality, new hypertension and new OD, thereby not representing a clinically innocent condition. Conclusions: The present study provides the first evidence that WCH with no cardiac and renal OD is accompanied by an increased long-term risk of mortality, new hypertension and new OD, thereby not representing a clinically innocent condition.

Objective: Whether and to what extent the reported BP lowering effects of renal denervation (RD) are mediated by a sympathetic deactivation induced by the procedure is still largely undefined. We examined this issue by performing a meta-analysis of the microneurographic studies published so far based on the evaluation of the blood pressure (BP) and muscle sympathetic nerve traffic (MSNA) responses to RD. Design and method: The meta-analysis was based on 12 studies including a total of 394 patients with resistant hypertension underwent RD and followed up to 12 months. Evaluation was extended to the relationships of MSNA with heart rate (HR) and clinic or ambulatory blood pressure (BP) values (expressed such as mean and 95% confidence interval). Results: Baseline MSNA values amounted to 48.25 (43.86-52.64) bursts/minute, clinic HR to 66.35 (65.02-67.67) beats/minute and systo/diastolic clinic BP to 167.3 (157.6-177.01) and 90.54 (84.81-96.27) mmHg. RD caused a significant BP reduction at 3/6/12 months following the procedure amounting to 12.6 mmHg for systolic (range 20.9 to 4.39 mmhg, p = 0.003) and to 6.4 mmHg for diastolic BP (range -11.9 t0 0.9 mmHg, p = 0.02) respectively. No significant change in MSNA (-2.65, range -6.7 to 1.4 bursts/minute, P = NS) and HR (-0.58, range -3.98 to 2.81 b/min, P = NS) were concomitantly observed. No relationship was found between the number of renal ablations and the magnitude of the blood pressure or MSNA changes, this being the case also for HR. Conclusions: This meta-analysis, the first ever done on the MSNA responses to RD, shows that in a consistent number of patients underwent RD, the BP lowering effects of the procedure are not accompanied by any significant change in 2 adrenergic markers, i.e. MSNA and HR, and thus appear not to be mediated by any sympathetic deactivation.

Aims: We examined whether to what extent resting heart rate (HR) values are capable to reflect in the metabolic syndrome (MS) a different degree of sympathetic activation. We also thought to determine at which HR cutoff values the sympathetic nervous system becomes more activated in the MS. Methods: In 70 MS patients aged 55.5 ± 1.8 (mean ± SEM) years we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the study population in three different subgroups according to resting clinic and 24-h HR values (< 70, 70–79 and ≥ 80 beats/min). Results: MS patients with clinic HR values ≥ 80 beats/min displayed MSNA and NE values significantly increased when compared to those found in MS with HR between 70 and 79 beats/min or below 70 beats/min (MSNA: 55.2 ± 0.9 vs 44.6 ± 0.6 and 39.2 ± 0.6 bursts/min, P < 0.01, NE: 403.9 ± 6.9 vs 330.1 ± 4.3 and 258.3 ± 6.8 pg/ml, respectively, P < 0.01). A similar behavior was observed for 24-h HR. In the group as a whole both MSNA and plasma NE showed highly significant direct relationships with clinic HR, the correlation being similar for MSNA and NE (r = 0.89 and r = 0.91, P < 0.01 for both) Similar significant relationships were also found between 24-h HR values and MSNA or NE. Conclusions: In the MS HR values ≥ 80 beats/min are associated with an increased sympathetic activation, both when assessed by direct recording of MSNA and when evaluated as plasma NE. The sympathetic overdrive parallels for magnitude the HR elevations, this being the case for both clinic and 24-h HR.

BACKGROUND: According to some guidelines, white-coat hypertension (WCH) carries little or no increase of cardiovascular risk in the absence of organ damage (OD), but no data are available on this issue. METHODS: Using the population data from PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni), we evaluated cardiovascular and total mortality over a median follow-up of 29 years in WCH (elevated office and normal 24-hour or home blood pressure [BP]) and normotensive controls (normal in- and out-of-office blood pressure) with no echocardiographic left ventricular hypertrophy and no reduction of estimated glomerular filtration rate. Patients with sustained hypertension (SH, in- and out-of-office blood pressure elevation) and normotensive, WCH, and SH with cardiac and renal OD served as controls. RESULTS: In the 1423 subjects analyzed, there were 165 cardiovascular and 526 all-cause deaths. After adjustment for confounders, no-OD WCH exhibited a risk of fatal cardiovascular events lower than that of no-OD SH but greater than that of no-ODN (hazard ratio, 2.0 [95% CI, 1.1–3.6], P=0.02), this being the case also for all-cause mortality. Compared with no-OD normotensive, no-OD WCH also exhibited a greater 10-year adjusted risk to develop new SH or OD. Similar findings were obtained in normotensive, WCH, and SH with OD. CONCLUSIONS: The present study provides the first evidence that WCH with no OD is accompanied by a noticeable increase in long-term risk of mortality, new hypertension, and new OD, thereby differing from normotension.