Showing papers by "Giuseppe Mancia published in 2017"

Clinical and prognostic significance of a reverse dipping pattern on ambulatory monitoring: An updated review.

Abstract: Reverse or inverted dipping (ie, the phenomenon characterized by higher nighttime compared with daytime blood pressure values) is an alteration of circadian blood pressure rhythm frequently documented in hypertension, type 2 diabetes mellitus, chronic kidney disease, and sleep apnea syndrome, and generally regarded as a harmful condition. Available literature on the clinical and prognostic implications of reverse dipping is scanty. The present article will review a number of relevant issues concerning reverse dipping, in particular: (1) its possible mechanisms; (2) prevalence and clinical correlates, (3) concomitant cardiac and extracardiac subclinical organ damage; (4) association with acute and chronic cardiovascular diseases; (5) prognostic value in predicting cardiovascular events and mortality; and (6) therapeutic interventions aimed at reverting this abnormal circadian blood pressure rhythm.

The technical report on sodium intake and cardiovascular disease in low- and middle income countries by the joint working group of the World Heart Federation, the European Society of Hypertension and the European Public Health Association

Abstract: Ingestion of sodium is essential to health, but excess sodium intake is a risk factor for hypertension and cardiovascular disease. Defining an optimal range of sodium intake in populations has been challenging and controversial. Clinical trials evaluating the effect of sodium reduction on blood pressure have shown blood pressure lowering effects down to sodium intake of less than 1.5 g/day. Findings from these blood pressure trials form the basis for current guideline recommendations to reduce sodium intake to less than 2.3 g/day. However, these clinical trials employed interventions that are not feasible for population-wide implementation (i.e. feeding studies or intensive behavioural interventions), particularly in low and middle-income countries. Prospective cohort studies have identified the optimal range of sodium intake to reside in the moderate range (3-5 g/day), where the risk of cardiovascular disease and death is lowest. Therefore, there is consistent evidence from clinical trials and observational studies to support reducing sodium intake to less than 5 g/day in populations, but inconsistent evidence for further reductions below a moderate intake range (3-5 g/day). Unfortunately, there are no large randomized controlled trials comparing low sodium intake ( 5 g/day), which should be embedded within an overall healthy dietary pattern.

Developing and validating a novel multisource comorbidity score from administrative data: a large population-based cohort study from Italy.

Abstract: Objective To develop and validate a novel comorbidity score (multisource comorbidity score (MCS)) predictive of mortality, hospital admissions and healthcare costs using multiple source information from the administrative Italian National Health System (NHS) databases. Methods An index of 34 variables (measured from inpatient diagnoses and outpatient drug prescriptions within 2 years before baseline) independently predicting 1-year mortality in a sample of 500 000 individuals aged 50 years or older randomly selected from the NHS beneficiaries of the Italian region of Lombardy (training set) was developed. The corresponding weights were assigned from the regression coefficients of a Weibull survival model. MCS performance was evaluated by using an internal (ie, another sample of 500 000 NHS beneficiaries from Lombardy) and three external (each consisting of 500 000 NHS beneficiaries from Emilia-Romagna, Lazio and Sicily) validation sets. Discriminant power and net reclassification improvement were used to compare MCS performance with that of other comorbidity scores. MCS ability to predict secondary health outcomes (ie, hospital admissions and costs) was also investigated. Results Primary and secondary outcomes progressively increased with increasing MCS value. MCS improved the net 1-year mortality reclassification from 27% (with respect to the Chronic Disease Score) to 69% (with respect to the Elixhauser Index). MCS discrimination performance was similar in the four regions of Italy we tested, the area under the receiver operating characteristic curves (95% CI) being 0.78 (0.77 to 0.79) in Lombardy, 0.78 (0.77 to 0.79) in Emilia-Romagna, 0.77 (0.76 to 0.78) in Lazio and 0.78 (0.77 to 0.79) in Sicily. Conclusion MCS seems better than conventional scores for predicting health outcomes, at least in the general population from Italy. This may offer an improved tool for risk adjustment, policy planning and identifying patients in need of a focused treatment approach in the everyday medical practice.

Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes

Abstract: Microvascular disease is associated with a high risk of macrovascular events in patients with type 2 diabetes, but the impact of macrovascular disease on the risk of microvascular events remains unknown. We sought to evaluate the respective effects of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients. Participants in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394). Outcomes were all-cause mortality, major macrovascular events (MACE), and major clinical microvascular events. All-cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow-up of 9.9 (inter-quartile interval 5.6–10.9) years. The adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20–1.71], 1.64 [1.37–1.97], and 4.74 [3.86–5.82], respectively), macrovascular disease (1.43 [1.30–1.57], 2.04 [1.86–2.25], and 1.26 [1.06–1.51]) or both (2.01 [1.65–2.45], 2.92 [2.40–3.55], and 6.30 [4.93–8.06]) compared with those without these conditions. No interaction was observed between baseline microvascular and macrovascular disease for these events. The addition of microvascular disease (change in c-statistic [95% CI] 0.005 [0.002–0.008], p = 0.02) or macrovascular disease (0.005 [0.002–0.007], p < 0.0001) considered separately or together (0.011 [0.007–0.014], p < 0.0001) improved the discrimination and the classification (integrated discrimination improvement (IDI): 0.013 [0.010–0.016], p < 0.001; net reclassification improvement (NRI): 0.021 [0.011–0.032], p < 0.001) of the risk of all-cause mortality. Microvascular disease improved discrimination (0.009 [0.003–0.014]) and classification (IDI: 0.008 [0.006–0.010]; NRI: 0.011 [0.001–0.020]) of MACE. Baseline macrovascular disease modestly enhanced IDI (0.002 [0.001–0.002]) and NRI (0.041 [0.002–0.087]), but not discrimination, of major clinical microvascular events. Microvascular and macrovascular disease are independently associated with the 10-year risk of death, MACE, and major clinical microvascular events in patients with type 2 diabetes. The coexistence of these conditions was associated with the highest risks.

Non-invasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: A consensus paper from the European Association of Cardiovascular Imaging (EACVI), the European Society of Cardiology Council on Hypertension, and the European Society of Hypertension (ESH).

Abstract: Arterial hypertension (HTN) accounts for the largest amount of attributable cardiovascular (CV) mortality worldwide, and risk stratification in hypertensive patients is of crucial importance to manage treatment and prevent adverse events. Asymptomatic involvement of different organs in patients affected by HTN represents an independent determinant of CV risk and the identification of target organ damage (TOD) is recommended to further reclassify patients' risk. Non-invasive CV imaging is progressively being used and continues to provide new technological opportunities to TOD evaluation at early stage. The aim of this article is to provide the community of cardiology with an update on appropriate and justified use of non-invasive imaging tests in the growing population of hypertensive patients.

Prognostic Value of Variability in Systolic Blood Pressure Related to Vascular Events and Premature Death in Type 2 Diabetes Mellitus: The ADVANCE-ON Study.

Abstract: Visit-to-visit variability in systolic blood pressure (SBP) is a risk factor for cardiovascular events. However, whether it provides additional predictive information beyond traditional risk factors, including mean SBP, in the long term is unclear. The ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) was a randomized controlled trial in patients with type 2 diabetes mellitus; ADVANCE-ON (ADVANCE-Observational) followed-up patients subsequently. In these analyses, 9114 patients without major macrovascular or renal events or death during the first 24 months were included. Data on SBP from 6 visits during the first 24 months after randomization were used to estimate visit-to-visit variability in several ways: the primary measure was the standard deviation. Events accrued during the following 7.6 years. The primary outcome was a composite of major macrovascular and renal events and all-cause mortality. Standard deviation of SBP was log-linearly associated with an increased risk of the primary outcome ( P P

The polypill in cardiovascular prevention: evidence, limitations and perspective - position paper of the European Society of Hypertension.

Abstract: Antihypertensive, lipid lowering, antidiabetic and antiplatelet treatments all substantially reduce the risk of cardiovascular morbid and fatal events. In real life, however, effective implementation of these treatments is rare, and thus their contribution to cardiovascular prevention is much less than it could be, based on research data. This article reviews the pros and cons of cardiovascular prevention by the polypill approach. It is argued that the high prevalence of individuals with a multifactorial risk profile provides a strong rationale for a therapeutic strategy based on the combination in a single tablet of drugs against different risk factors. It is further argued that other important favourable arguments exist. First, in real-life adherence to all above treatments is very low, leading to a major increase in the incidence and risk of cardiovascular outcomes. Second, although a large number of factors are involved, adherence is adversely affected by the complexity of the prescribed treatment regimen and can be considerably improved by treatment simplification. Third, recent studies in patients with a history of manifest cardiovascular disease have documented that different cardiovascular drugs can be combined in a single tablet with no loss of their individual efficacy or unexpected inconveniences and this does favour adherence to treatment and multiple risk factor control, supporting use of the polypill in secondary cardiovascular prevention. It is finally also mentioned, however, that the polypill may have some drawbacks and that at present no evidence is available that this approach reduces cardiovascular outcome to a greater degree than standard treatment strategies. Trials are under way to provide an answer to this question and thus allow the therapeutic value of this approach to be known.

Blood pressure control in hypertension. Pros and cons of available treatment strategies.

Abstract: The low rate of blood pressure (BP) control that characterizes the hypertensive population in real life is traditionally associated to factors such as low adherence of patients to the prescribed treatment regimen, physicians' therapeutic inertia, and deficiencies of the healthcare systems. This study will focus on a fourth factor that may also be importantly involved, i.e. reluctance to adopt drug treatment strategies that more effectively reduce an elevated BP. The point will be made that, vis-a-vis strategies based on patients' persistence in monotherapy, drug combinations are accompanied by a much more frequent BP control. In particular, it will be argued that compared with the administration of additional drugs after initial monotherapy, use of combination treatment from the beginning may carry important advantages, such as a faster BP control, and thus an earlier protection in patients at a high cardiovascular risk and a better adherence to the prescribed drugs and thus a more frequent long-term achievement of target BP values, possibly also with a more effective cardiovascular protection. This may justify a more clear support of this treatment strategy by future guidelines, in the attempt to lessen the contribution of hypertension to cardiovascular disease and death.

Blood pressure monitoring: theory and practice. European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability Teaching Course Proceedings.

Abstract: The European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring and Cardiovascular Variability organized a Teaching Course on 'Blood Pressure Monitoring: Theory and Practice' during the 2017 ESH Meeting in Milan, Italy. This course performed by 11 international BP monitoring experts covered key topics of BP monitoring, including office BP measurement, ambulatory BP monitoring, home BP monitoring, ambulatory versus home BP, white-coat and masked hypertension, cuff use, and BP variability. This article presents a summary of the proceedings of the ESH BP Monitoring Teaching Course, including essential information, practical issues, and recommendations on the clinical application of BP monitoring methods, aiming to the optimal management of patients with suspected or diagnosed hypertension.

Noninvasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: a consensus article from the European Association of Cardiovascular Imaging, the European Society of Cardiology Council on Hypertension and the European Society of Hypertension.

Abstract: Arterial hypertension accounts for the largest amount of attributable cardiovascular mortality worldwide, and risk stratification in hypertensive patients is of crucial importance to manage treatment and prevent adverse events. Asymptomatic involvement of different organs in patients affected by hypertension represents an independent determinant of cardiovascular risk, and the identification of target organ damage is recommended to further reclassify patients' risk. Noninvasive cardiovascular imaging is progressively being used and continues to provide new technological opportunities to target organ damage evaluation at early stage. The aim of this article is to provide the community of cardiology with an update on appropriate and justified use of noninvasive imaging tests in the growing population of hypertensive patients.

Cardiovascular Risk Associated With White Coat Hypertension: Pro Side of the Argument

Abstract: This article will support the view that white-coat hypertension (WCH), that is, the association of an elevated office with a normal ambulatory or home blood pressure (BP),1 is not an innocent condition but a condition associated with an increased cardiovascular risk. This will be based on the evidence that compared with normotensive controls, subjects with WCH (1) have an increased prevalence of metabolic risk factors and asymptomatic organ damage; (2) more frequently progress to high cardiovascular risk states such as sustained hypertension, diabetes mellitus, and left ventricular hypertrophy; and (3) exhibit, over the mid and long term, a greater risk of cardiovascular morbid and fatal events. It will also be mentioned, however, that important clinical and mechanistic aspects of WCH remain incompletely clarified: the contribution of office versus out-of-office BP to the increased risk; the biomarkers that may allow to distinguish, within the WCH population, subjects at greater versus those at normal risk; and the effect of antihypertensive drug administration on patients’ prognosis. Clarification of these aspects represents a priority for medical research because WCH is common in all hypertension grades, its prevalence accounting for more than one third of the hypertensive population when the office BP elevation is mild.2 ### Metabolic Risk Factors Evidence is available that subjects with WCH have an unfavorable metabolic profile. This was already observed many years ago3 and has since been confirmed by virtually all studies that have addressed this matter. A pertinent example is the PAMELA study (Pressioni Arteriose Monitorizzate e Loro Associazioni) on a population living in the north-east outskirt of Milan, in which measurements included a large number of metabolic variables. As shown in Figure 1, compared with normotensive controls, individuals with WCH (identified by an office BP ≥140/90 mm Hg and a 24-hour or home BP, respectively, <125/80 and 135/85 mm Hg) …

Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial.

Abstract: OBJECTIVE: This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS: A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [ 10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS: Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.

Protective effects of antihypertensive treatment in patients aged 85 years or older.

Abstract: Objective To assess whether in individuals aged 85 years or older, adherence to antihypertensive drugs is accompanied by a reduced risk of cardiovascular events. Methods A nested case-control study was carried out on a cohort of patients aged 85 years or older, who were newly treated with antihypertensive drugs between 2007 and 2009, using the database available for all citizens (about 10 million) of Lombardy (Italy). Cases were the cohort members who experienced death or hospital discharge for stroke, myocardial infarction (MI) or heart failure from the initial prescription until 2012. Up to five controls were randomly selected for each case. Logistic regression was used to model the outcome risk associated with the adherence with antihypertensive drug therapy. A patient cohort aged 70-84 years was taken for comparison. Results Compared with patients with very low adherence, those aged 85 years or older (average 88 years) with high adherence showed a risk reduction for death (47%; 95% confidence interval, 5-57%) and all the outcomes combined (34%; 95% confidence interval, 21-45%). The risk of heart failure and stroke was also reduced, whereas the risk of MI was not affected by adherence with antihypertensive drugs. Similar findings were obtained in the cohort of patients aged 70-84 years. Conclusion Adherence with antihypertensive drug therapy reduced the risk of cardiovascular morbidity in patients aged 85 years or more, the benefit including heart failure and stroke, although not MI, and extending to all-cause death.

Relative and Combined Prognostic Importance of On-Treatment Mean and Visit-to-Visit Blood Pressure Variability in ONTARGET and TRANSCEND Patients.

Abstract: In 28 790 patients recruited for the ONTARGET (Ongoing Treatment Alone and in Combination With Ramipril Global End Point Trials) and TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease) trials, we investigated the prognostic value for cardiovascular events (primary outcome) of (1)on-treatment visit-to-visit systolic blood pressure (SBP) variability versus mean SBP and (2) the 2 measures together. SBP variability was measured by the coefficient of variation (CV) of mean SBP to which it was unrelated. Confounders such as variable time and number of visits from which to calculate SBP-CV were avoided by using the same number of visits at identical times in all patients. The covariate-adjusted risk of the primary outcome (Cox models) increased as SBP-CV or mean on-treatment quintile SBP increased, but only for mean on-treatment SBP, the relationship achieved statistical significance: global test for trend, P =0.12 versus P P Clinical Trial Registration— URL: http//www.clinicaltrial.gov. Unique identifier: NCT153.101.

Restoration of normal sympathetic neural function in heart failure following baroreflex activation therapy: final 43-month study report.

Abstract: BACKGROUND Baroreflex activation therapy (BAT) exerts in severe heart failure sympathoinhibitory effects, improving clinical variables and reducing hospitalization rate. The current follow-up study was aimed at determining the long-term effects of BAT, assessing whether BAT in heart failure allows to restore physiological levels of sympathetic function. METHODS Seven patients out of the 11 heart failure patients aged 66.5 ± 3 years (mean ± SEM) in New York Heart Association Class III with left ventricular ejection fraction 40% or less and impaired functional capacity recruited in the study survived at the final follow-up (43.5 ± 2.1 months). Measurements included muscle sympathetic nerve activity (MSNA, microneurography) and spontaneous baroreflex-MSNA sensitivity together with hospitalization rate, echocardiography, Minnesota score, New York Heart Association class and standard clinical data. Measurements were collected before and at 6, 21 and 43 months following BAT. Data were compared with those collected in 17 age-matched healthy controls. All assessments were made with the heart failure patient on optimal active therapy. RESULTS In the seven patients, BAT maintained its beneficial effects over 43.5 ± 2.1 months of follow-up. MSNA values underwent a progressive significant reduction from baseline to 21 and 43 months follow-up following BAT (from 46.2 ± 2.4 to 31.3 ± 3.0 e 26.6 ± 2.0 bursts/min, P < 0.05 at least), becoming almost superimposable to the ones seen in healthy controls (25.5 ± 0.8 bursts/min). Baroreflex-MSNA sensitivity improved, without achieving, however, a full normalization. Blood pressure and heart rate did not change. Left ventricular ejection fraction improved significantly from 32.3 ± 2 to 36.7 ± 3% (P < 0.05). Hospitalization rate decreased substantially when measured as days/year/patients it decreased from 10.3 ± 2.5 preimplant to 1.01 ± 1.4 at the 43.5th month follow-up (P < 0.02). No side effects were reported in the long-term period. CONCLUSION The current study provides evidence that BAT in heart failure with reduced ejection fraction allows not only to improve hemodynamic and clinical profile but also to exert profound sympathoinhibitory effects, allowing an almost complete restoration of physiological levels of the sympathetic neural function.

Renal artery denervation for treatment of patients with self-reported obstructive sleep apnea and resistant hypertension: Results from the Global SYMPLICITY Registry

Abstract: Background:Sleep-disordered breathing, predominantly obstructive sleep apnea (OSA), is highly prevalent in patients with hypertension OSA may underlie the progression to resistant hypertension, partly due to increased activation of the sympathetic nervous system This analysis of patients with and

The Un-Observed Automated Office Blood Pressure Measurement Technique Used in the SPRINT Study Points to a Standard Target Office Systolic Blood Pressure <140 mmHg.

Abstract: The SPRINT study investigators used the un-observed automated office blood pressure measurement technique. When their achieved systolic blood pressure is corrected, target systolic blood pressure for most people remains unchanged: <140mmHg for prevention of cardiovascular diseases and death.

Sympathetic nerve traffic and blood pressure changes after bilateral renal denervation in resistant hypertension: a time-integrated analysis

Abstract: Background Renal denervation reduces blood pressure (BP) and sympathetic drive in experimental animal models, but the effect of this intervention on sympathetic activity in patients with treatment-resistant hypertension is still unclear. Methods In an incident series of 29 patients with treatment-resistant hypertension, we performed serial measurements (n = 123) of muscle sympathetic nerve activity (MSNA, microneurography) and standardized BP measurements. Data were analysed by mixed linear modelling (MLM) and by regression analysis of time-integrated changes of both MSNA and synchronous, standardized (in-lab) BP measurements. Results Bilateral renal denervation was accompanied by a marked reduction in MSNA (P = 0.01 by MLM), which was parallelled by a reduction in systolic (from 175 ± 14 to 156 ± 16 mmHg) and, to a lesser extent, in diastolic (from 96 ± 12 to 87 ± 6 mmHg) BP over time. Neither systolic nor diastolic BP associated to a significant extent with corrected MSNA (MSNAC) in the MLM analysis (systolic BP versus MSNAC: β = -0.08, P = 0.08; diastolic BP versus MSNAC: β = -0.007, P = 0.75). However, the study of time-integrated changes in MSNA and BP showed a robust association between proportional changes in MSNA over time and simultaneous changes in systolic and diastolic BP (β = 0.61, P < 0.001 and β = 0.37 P < 0.05). Conclusions Time-integrated changes in MSNAC and BP after bilateral renal denervation document a close link between the sympathetic activity and BP responses to this procedure. These findings further strengthen the relevance of the sympathetic nervous system both in the pathophysiology of resistant hypertension and in the BP-lowering effect of the procedure.

Is night-time hypertension worse than daytime hypertension? A study on cardiac damage in a general population: the PAMELA study.

Abstract: Aim Scanty information is available about the association of isolated daytime hypertension (IDH) and isolated night-time hypertension (INH) with subclinical cardiac damage in the general population. We examined this issue in patients enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study. Methods The analysis included 2021 participants with valid ambulatory blood pressure (BP) monitoring at baseline evaluation. IDH and INH were defined according to current guidelines. Subclinical organ damage was assessed by validated electrocardiographic and echocardiographic criteria. Results A total of 1258 patients (62.3%) had daytime/night-time normotension, 376 (18.6%) daytime/night-time hypertension, 231 (11.4%) INH and 156 (7.7%) IDH, respectively. Participants with hypertension, compared with their normotensive counterparts were older, included a higher fraction of men, had higher BMI, LDL cholesterol, triglyceride and glucose levels and exhibited a greater subclinical cardiac involvement. Furthermore, INH and IDH patients showed a similar degree of cardiac damage (i.e. left ventricular mass index: 89 ± 18 vs 90 ± 20 g/m), intermediate between normotensive (82 ± 19 g/m) and day-night hypertensive patients (99 ± 24 g/m). Conclusion The present study shows that IDH and INH exert similar detrimental effects on cardiac structure. In a practical perspective, appropriate antihypertensive chrono-therapeutic approaches in these opposite ambulatory hypertensive subtypes may have important implications in cardiovascular prevention.

Reliability of heart rate as neuroadrenergic marker in the metabolic syndrome.

Abstract: Metabolic syndrome is characterized by a pronounced sympathetic overactivity as documented by the marked increase in muscle sympathetic nerve traffic (MSNA) as well as in plasma norepinephrine values reported in this condition. Whether and to what extent heart rate (HR) reflects the abovementioned adrenergic alterations in metabolic syndrome remains largely undefined. It is also undefined the validity of the abovementioned adrenergic markers in reflecting the main features of the metabolic syndrome. In 65 metabolic syndrome patients, aged 56.5 ± 1.3 years (mean ± SEM), we measured over a 30-min resting period blood pressure, HR (ECG), venous plasma norepinephrine (HPLC) and MSNA (microneurography). We also evaluated anthropometric and metabolic variables including HOMA index, correlating them with the adrenergic markers. The same measurements were also made in 48 age-matched healthy controls. HR was significantly greater in the metabolic syndrome patients than in controls (74.6 ± 1.5 versus 67.5 ± 1.5 bpm, P < 0.001) and significantly and directly correlated with the elevated norepinephrine and MSNA values (r = 0.25 and 0.33, P < 0.05 and 0.01, respectively). MSNA was significantly and directly related to blood pressure (r = 0.27 and 0.31 SBP and DBP, respectively, P < 0.05 for both), BMI (r = 0.36, P < 0.01), waist circumference (r = 0.34, P < 0.01), waist-to-hip ratio (r = 0.49, P < 0.01) and plasma insulin (r = 0.57, P < 0.01). In contrast, no significant correlation was detectable between HR or norepinephrine and the abovementioned anthropometric and metabolic variables. Our data show that in the metabolic syndrome not only peripheral but also cardiac sympathetic drive is markedly potentiated and HR can be regarded as a marker of adrenergic overdrive characterizing this clinical condition. The reliability of HR (and of plasma norepinephrine) as sympathetic marker appears to be limited, however, this variable being unable to reflect, at variance from MSNA, the main metabolic and anthropometric abnormalities characterizing the metabolic syndrome.

Clinical and prognostic value of hypertensive cardiac damage in the PAMELA Study.

Abstract: Because subclinical alterations in cardiovascular structure reflect cumulative damage induced by risk factors and represent an intermediate stage between risk factor exposure and cardiovascular events, this damage is regarded as a marker of increased cardiovascular risk in different clinical settings, including the general population. The Pressioni Monitorate e Loro Associazioni (PAMELA) is an originally designed research study aimed at assessing the normal values and prognostic significance of ambulatory and home blood pressure in a representative sample of the Northern Italian general population. Because the study protocol included the collection of electrocardiographic (ECG) and echocardiographic (ECHO) data, the prevalence and clinical correlates, as well as the prognostic value of subclinical cardiac alterations, have been extensively investigated. This article is a review of the findings of the PAMELA study regarding the clinical aspects and prognostic significance of cardiac abnormal phenotypes such as left ventricular hypertrophy, left atrial dilatation and aortic root dilation.

Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.

Abstract: Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls. The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P < 0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3 ± 8 to 157.1 ± 9 mg/dl, P < 0.05, from 7.9 ± 0.1 to 6.9 ± 0.2%, P < 0.001 and from 3.6 ± 0.3 to 7.4 ± 0.8%, respectively P < 0.05). No significant difference was detected in the other parameters, including blood pressure. Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.

Expertise: no longer a sine qua non for guideline authors?

Abstract: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.

Renal artery stenosis and left ventricular hypertrophy: An updated review and meta-analysis of echocardiographic studies

Abstract: Aim:Data on left ventricular hypertrophy (LVH) in patients with renal artery stenosis (RAS) and its regression following renal revascularization are scanty. We performed a meta-analysis to provide comprehensive information on this clinically relevant issue.Methods:Full articles providing data on: LV

Renin-Angiotensin-Aldosterone System Is Not Involved in the Arterial Stiffening Induced by Acute and Prolonged Exposure to High Altitude.

Abstract: This randomized, double-blind, placebo-controlled study was designed to explore the effects of exposure to very high altitude hypoxia on vascular wall properties and to clarify the role of renin–angiotensin–aldosterone system inhibition on these vascular changes. Forty-seven healthy subjects were included in this study: 22 randomized to telmisartan (age, 40.3±10.8 years; 7 women) and 25 to placebo (age, 39.3±9.8 years; 7 women). Tests were performed at sea level, pre- and post-treatment, during acute exposure to 3400 and 5400-m altitude (Mt. Everest Base Camp), and after 2 weeks, at 5400 m. The effects of hypobaric hypoxia on mechanical properties of large arteries were assessed by applanation tonometry, measuring carotid–femoral pulse wave velocity, analyzing arterial pulse waveforms, and evaluating subendocardial oxygen supply/demand index. No differences in hemodynamic changes during acute and prolonged exposure to 5400-m altitude were found between telmisartan and placebo groups. Aortic pulse wave velocity significantly increased with altitude ( P P P P P Clinical Trial Registration— URL: https://www.clinicaltrialsregister.eu/. Unique identifier: 2008-000540-14.