Showing papers by "Giuseppe Mancia published in 2015"

Serum uric acid and the risk of cardiovascular and renal disease.

Abstract: Substantial evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, chronic kidney disease (CKD) and cardiovascular diseases. This highlights the need for greater attention to serum uric acid levels when profiling patients, and suggests that the threshold above which uricemia is considered abnormal is 6 mg/dl, in light of the available evidence. Another important question is whether lowering serum uric acid can improve cardiovascular and renal outcomes, and what therapeutic mechanism of action could provide more clinical benefits to patients; the available literature shows a trend toward improvement associated with administration of urate-lowering drugs, in particular for the xanthine oxidase inhibitors. The demonstrated efficacy of urate-lowering therapy on outcomes other than gout flares leads to the consideration that treatment may be beneficial even in the absence of overt gout when hyperuricemia accompanies other clinical conditions, such as urate deposition, advanced CKD or cardiovascular risk factors.

First Report of the Global SYMPLICITY Registry on the Effect of Renal Artery Denervation in Patients With Uncontrolled Hypertension

Abstract: This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were −11.6±25.3 and −6.6±18.0 mm Hg for all patients ( P P 70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01534299

Clinical Value of Ambulatory Blood Pressure: Evidence and Limits

Abstract: This article reviews the clinical value of ambulatory blood pressure (BP) vis-a-vis the traditional BP measurements taken in the physician's office or in the hospital. Mention is initially made that longitudinal studies conducted in the general population or in hypertensive cohorts have shown that ambulatory BP provides a more accurate prediction of outcome than office BP. Namely, that (1) the risk of cardiovascular events increases in a less steep fashion with office than with 24-hour mean BP, (2) the 24-hour BP-dependent prediction is maintained after adjustment for office BP values, and (3) among individuals with normal office BP, those with increased ambulatory BP (masked hypertension) have an increased prevalence of organ damage, a more frequent unfavorable metabolic profile and a higher risk of new onset sustained hypertension, diabetes mellitus, and cardiovascular events than those with normal ambulatory BP. It is further mentioned, however, that more recently similar observations have been made for individuals with high office but normal ambulatory BP (white coat hypertension) suggesting a complementary role of out-of-office and office BP values in the determination of patients' prognosis. The evidence in favor of an independent prognostic value also of some within 24-hour BP phenomena (night BP reduction or absolute values, short-term BP variations, and morning BP surge) is then critically appraised for its elements of strength and weakness. Finally, whether the clinical advantages of ambulatory BP make this approach necessary for all patients with hypertension is discussed. The conclusion is that this is at present still premature because crucial evidence pro or against routine use of this approach in untreated and treated hypertensives is not yet available. It will be crucial for future studies to determine whether, compared with a treatment guided by office BP, a treatment tailored on ambulatory BP allows to improve prevention or regression of organ damage as well as protection from major cardiovascular complications to a degree that justifies the complexity and cost of the procedure.

Sympathetic activation in cardiovascular disease: Evidence, Clinical Impact and Therapeutic Implications

Abstract: Background The sympathetic nervous exerts a key role in cardiovascular homeostasis control by regulating cardiac output, systemic vascular resistance, heart rate and blood pressure. Materials and methods Data collected during the past 30 years have unequivocally shown that in a considerable number of cardiovascular as well as noncardiovascular disease there is a marked activation of the sympathetic nervous system which exerts in the long-term period unfavourable haemodynamic, metabolic, cardiovascular and renal effects. Results This paper will review the current knowledge on the alterations in sympathetic function described in cardiovascular disease, with particular focus on hypertension, heart failure and myocardial infarction. Conclusions The consequences of the phoenomenon will be discussed together with its therapeutic implications. This will be done by examining the impact of nonpharmacological as well as pharmacological interventions on sympathetic cardiovascular drive. The effects of new invasive approaches, such as carotid baroreceptor stimulation as well as renal nerves ablation, will be also briefly discussed.

Reducing Cardiovascular Mortality Through Prevention and Management of Raised Blood Pressure A World Heart Federation Roadmap

Abstract: Dr. Prabhakaran receives grants for a training program of primary care physicians from multiple pharmaceutical sources (MSD and Abbott) to train primary care physicians in evidence-based manageReducing Cardiovascular Mortality Through Prevention and Management of Raised Blood Pressure A World Heart Federation Roadmap Alma J. Adler*, Dorairaj Prabhakarany, Pascal Bovetz, Dhruv S. Kazix, Giuseppe Manciak, Vash Mungal-Singh{, Neil Poulter Geneva, Switzerland; London, United Kingdom; New Delhi, India; Lausanne, Switzerland; San Francisco, CA, USA; Milan, Italy; and Cape Town, South Africa

Systolic Blood Pressure Variation and Mean Heart Rate Is Associated With Cognitive Dysfunction in Patients With High Cardiovascular Risk

Abstract: — Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coefficient of variation [standard deviation/mean×100%], CV), mean HR, and visit to visit HR variation (HR-CV) in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Cognitive function was assessed with mini mental state examination. Cognitive dysfunction (fall in mini mental state examination ≤24 points), important cognitive decline (drop of ≥5 points), and cognitive deterioration (drop of >1 point per year or decline to 24 points) were assessed. SBP and HR were measured over 10.7±2.2 (mean±SD) visits. Mean SBP, mean HR, and SBP-CV were associated with cognitive decline, dysfunction, and deterioration (all P P =0.0030) and mean HR ( P =0.0008) remained predictors for cognitive dysfunction (odds ratios [95% confidence intervals], 1.32 [1.10–1.58] for 5th versus 1st quintile of SBP-CV and 1.40 [1.18–1.66] for 5th versus 1st quintile of mean HR). Similar effects were observed for cognitive decline and deterioration. SBP-CV and mean HR showed additive effects. In conclusion, SBP-CV and mean HR are independent predictors of cognitive decline and cognitive dysfunction in patients at high CV risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00153101.

Ethnic Differences in the Degree of Morning Blood Pressure Surge and in Its Determinants Between Japanese and European Hypertensive Subjects Data From the ARTEMIS Study

Abstract: Morning blood pressure (BP) surge has been reported to be a prognostic factor for cardiovascular events. Its determinants are still poorly defined, however. In particular, it is not clear whether ethnic differences play a role in determining morning surge (MS) size. Aim of our study was to explore whether differences exist in the size of MS between Japanese and Western European hypertensive patients. We included 2887 untreated hypertensive patients (age 62.3±8.8 years) from a European ambulatory BP monitoring database and 811 hypertensive patients from a Japanese database (Jichi Medical School Ambulatory Blood Pressure Monitoring WAVE1, age 72.3±9.8 years) following the same inclusion criteria. Their 24-hour ambulatory BP monitoring recordings were analyzed focusing on MS. Sleep-trough MS was defined as the difference between mean systolic BP during the 2 hours after awakening and mean systolic BP during the 1-hour night period that included the lowest sleep BP level. The sleep-trough MS was higher in Japanese than in European hypertensive patients after adjusting for age and 24-hour mean BP levels (40.1 [95% confidence interval 39.0-41.2] versus 23.0 [22.4-23.5] mm Hg; P<0.001). This difference remained significant after accounting for differences in night-time BP dipping. Age was independently associated with MS in the Japanese database, but not in the European subjects. Our results for the first time show the occurrence of substantial ethnic differences in the degree of MS. These findings may help in understanding the role of ethnic factors in cardiovascular risk assessment and in identifying possible ethnicity-related differences in the most effective measures to be implemented for prevention of BP-related cardiovascular events.

New developments in the pathogenesis of obesity-induced hypertension.

Abstract: Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.

White-coat hypertension, as defined by ambulatory blood pressure monitoring, and subclinical cardiac organ damage: a meta-analysis.

Abstract: Aim:The clinical and prognostic relevance of white-coat hypertension (WCH) has not been fully elucidated; in particular, the association of this blood pressure phenotype with suclinical organ damage remains unclear. We performed a systematic meta-analysis in order to provide a comprehensive informat

Antihypertensive Medications, Loop Diuretics, and Risk of Hip Fracture in the Elderly: A Population-Based Cohort Study of 81,617 Italian Patients Newly Treated Between 2005 and 2009

Abstract: Our objective was to assess the relationship between antihypertensive drugs, loop diuretics, and the risk of hospitalization for hip fracture (HF). We conducted a population-based study in a cohort of 81,617 patients from Lombardy (Italy) aged 70–90 years who were newly treated with antihypertensive agents or loop diuretics between 2005 and 2009. Cases were the 2153 patients who experienced the outcome (hospitalization for HF before 31 December 2012). For each case, up to three controls were randomly selected from the cohort to be matched for sex, age at cohort entry, and date of initial prescription. The case–control and case-crossover designs and the logistic regression for matched sets were used to measure the strength of the association between current use of an antihypertensive drug (within 30 days before the HF hospitalization) and the risk of outcome. Case–control and case-crossover odds ratios (ORs) for current use of loop diuretics were 1.67 (95 % confidence interval [CI] 1.28–2.18) and 1.49 (95 % CI 1.05–2.10), respectively. Among patients aged 81–90 years, case–control and case-crossover ORs were 1.52 (95 % CI 1.04–2.21) and 1.82 (95 % CI 1.10–3.00) for current use of loop diuretics and 1.86 (95 % CI 1.03–3.35) and 1.88 (95 % CI 1.01–3.48) for α-blockers. No other agent was associated with the outcome. Evidence that loop diuretics and α-blockers are associated with a higher risk of HF was consistent in the two observational approaches. Clinicians should carefully consider the risk of falls in their selection of drugs for hypertension and in the clinical use of loop diuretics.

Adherence With Antihypertensive Drug Therapy and the Risk of Heart Failure in Clinical Practice

Abstract: Randomized clinical trials have shown that antihypertensive treatment reduces the risk of heart failure (HF). Limited evidence exists, however, on whether and to what extent this benefit is translated into real-life practice. A nested case-control study was carried out by including the cohort of 76 017 patients from Lombardy (Italy), aged 40 to 80 years, who were newly treated with antihypertensive drugs during 2005. Cases were the 622 patients who experienced hospitalization for HF from initial prescription until 2012. Up to 5 controls were randomly selected for each case. Logistic regression was used to model the HF risk associated with adherence to antihypertensive drugs, which was measured by the proportion of days covered by treatment (PDC). Data were adjusted for several covariates. Sensitivity analyses were performed to account for possible sources of systematic uncertainty. Compared with patients with very low adherence (PDC, ≤25%), low, intermediate, and high adherences were associated with progressively lower risk of HF, reduction in the high-adherence group (>75%) being 34% (95% confidence interval, 17%-48%). Similar effects were observed in younger (40-70 years) and older (71-80 years) patients and between patients treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. There was no evidence that adherence with calcium-channel blockers reduced the HF risk. Antihypertensive treatment lowers the HF risk in real-life practice, but adherence to treatment is necessary for a substantial benefit to take place. This is the case with a variety of antihypertensive drugs.

Generating Evidence From Computerized Healthcare Utilization Databases

Abstract: Randomized clinical trials (RCTs) are regarded as the highest level of therapeutic evidence because they are based on random allocation of participants to ≥2 treatment groups, which provides patients with superimposable initial demographic and clinical characteristics and allows the results to reflect the effect of the treatment strategies under study safely. Also, new treatments are compared with placebo or current interventions, which offers information on their absolute or added value. Finally, end points of documented clinical relevance are selected, the results having an immediate bearing for patients’ health. However, RCTs also have limitations that can make their results of uncertain and limited application to daily life medicine.1–4 For example, in RCTs, treatments are delivered according to preselected plans that make management more rigid than the one adopted in real-life. Two, treatments are delivered in a highly controlled environment by operators with specific competence, which results into a much lower chance of mistreatment or errors. Three, for several reasons (cost, progressive patients’ dropout, changes of patient residence, job instability of investigators, etc), RCTs can have a few year duration only, extrapolation been required to apply their results to daily life patients with a much longer life expectancy. Four, to make data scientifically interpretable, in RCTs, vulnerable patients are usually avoided and patients are recruited based on restricted eligibility criteria, which do not reflect the demographic and clinical heterogeneity of the individuals to whom the trial results are eventually applied. Finally, in RCTs, high motivation and close follow-up make patients well compliant to treatment, at variance from clinical practice in which a low and variable treatment adherence is common, with unmeasured but probably substantial modifications of the original trial results.5–12 Recognition of the above limitations has favored the design and conduction of trials, which could may …

Blood Pressure Responses to Renal Denervation Precede and Are Independent of the Sympathetic and Baroreflex Effects

Abstract: It is still largely unknown whether the neuroadrenergic responses to renal denervation (RD) are involved in its blood pressure (BP)-lowering effects and represent predictors of the BP responses to RD. In 15 treated true resistant hypertensives, we measured before and 15 days, 1, 3, and 6 months after RD clinic, ambulatory and beat-to-beat BP. Measurements included muscle sympathetic nerve traffic (MSNA), spontaneous baroreflex-MSNA sensitivity, and various humoral and metabolic variables. Twelve treated hypertensives served as controls. BP, which was unaffected 15 days after RD, showed a significant decrease during the remaining follow-up period. MSNA and baroreflex did not change at 15-day and 1-month follow-up and showed, respectively, a decrease and a specular increase at 3 and 6 months after RD. No relationship, however, was detected between baseline MSNA and baroreflex, MSNA changes and BP changes. At the 6-month follow-up, the MSNA reduction was similar for magnitude in patients displaying a BP reduction greater or lower the median value. Similarly, the BP reduction detected 6 months after RD was similar in patients displaying a MSNA reduction greater or lower median value. No significant BP and MSNA changes were detected in the control group. Thus, the BP reduction associated with RD seems to precede the MSNA changes and not to display a temporal, qualitative, and quantitative relationship with the MSNA and baroreflex effects. Given the small sample size of the present study further investigations are warranted to confirm the present findings.

Systolic and Diastolic Blood Pressure Changes in Relation With Myocardial Infarction and Stroke in Patients With Coronary Artery Disease

Abstract: — Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by –34/–21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associated with an increased risk of stroke, whereas the risk of MI increased with systolic BP and not with diastolic BP. In conclusion, in patients with coronary artery disease and initially free from congestive heart failure, a BP reduction from baseline over the examined BP range had little effect on the risk of MI and predicted a lower risk of stroke. An increase in systolic BP from baseline increased the risk of stroke and MI. The relationships of BP with risk were much steeper for stroke than for MI. A treatment-induced BP reduction over the explored range seems to be safe in patients with coronary artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

Sympathetic nerve traffic and baroreflex function in optimal, normal, and high-normal blood pressure states.

Abstract: Objective: Adrenergic activation and baroreflex dysfunction are common in established essential hypertension, elderly hypertension, masked and white-coat hypertension, resistant hypertension, and obesity-related hypertension. Whether this autonomic behavior is peculiar to established hypertension or is also detectable in the earlier clinical phases of the disease, that is, the high-normal blood pressure (BP) state, is still largely undefined, however. Methods: In 24 individuals with optimal BP (age: 37.1 ± 2.1 years, mean ± SEM) and in 27 with normal BP and 38 with high-normal BP, age matched with optimal BP, we measured clinic, 24-h and beat-to-beat BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) at rest and during baroreceptor stimulation and deactivation. Measurements also included anthropometric as well as echocardiographic and homeostasis model assessment (HOMA) index. Results: For similar anthropometric values, clinic, 24-h ambulatory, and beat-to-beat BPs were significantly greater in normal BP than in optimal BP. This was the case when the high-normal BP group was compared to the normal and optimal BP groups. MSNA (but not HR) was also significantly greater in high-normal BP than in normal BP and optimal BP (51.3 ± 2.0 vs. 40.3 ± 2.3 and 41.1 ± 2.6 bursts per 100 heartbeats, respectively, P < 0.01). The sympathetic activation seen in high-normal BP was coupled with an impairment of baroreflex HR control (but not MSNA) and with a significant increase in HOMA Index, which showed a significant direct relationship with MSNA. Conclusion: Thus, independently of which BP the diagnosis is based, high-normal BP is a condition characterized by a sympathetic activation. This neurogenic alteration, which is likely to be triggered by metabolic rather than reflex alterations, might be involved, together with other factors, in the progression of the condition to established hypertension.

Ambulatory Blood Pressure in Untreated and Treated Hypertensive Patients at High Altitude The High Altitude Cardiovascular Research–Andes Study

Abstract: Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this conditi...

Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy.

Abstract: BACKGROUND Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH). METHODS In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24 months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events). RESULTS In multiple regression models adjusted for mean BP6-24 months and treatment allocation, neither high BP6-24 months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24 months SD and range (both β = 0.04, P < 0.01). Independently of mean BP6-24 months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24 months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P = 0.004), SBP6-24 months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6-24 months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P = 0.001), SBP6-24 months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P = 0.05), but MI was not. CONCLUSION In LIFE patients, higher in-treatment BP6-24 months variability was independently of mean BP6-24 months associated with later CEP and stroke, but not with MI or TOD after 24 months.

Adverse Prognostic Value of Persistent Office Blood Pressure Elevation in White Coat Hypertension

Abstract: Stratification of cardiovascular risk is of fundamental importance in white coat hypertension (WCH) to identify individuals in need of closer follow-up and perhaps antihypertensive drug treatment. In subjects representative of the general population of Monza (Italy), the risk of cardiovascular and all-cause mortality was assessed >16 years in stable and unstable WCH individuals, that is, those in whom ambulatory blood pressure (BP) normality was associated with a persistent or nonpersistent office BP elevation at 2 consecutive visits, respectively. Data were compared with those from an entirely normotensive group, that is, ambulatory and persistent office BP normality. Compared with the normotensive group, the risk of cardiovascular and all-cause death was not significantly different in unstable WCH, whereas in stable WCH the risk was increased also when data were adjusted for baseline confounders, including ambulatory BP (hazard ratio, 16; P=0.001 for cardiovascular death and 1.92; P=0.02 for all-cause death). At a multivariable analysis, office BP was among the factors independently predicting death, and results were superimposable with use of Monza population-derived and guidelines-derived cutoff values for ambulatory BP normality (125/79 and 130/80 mm Hg, respectively). Thus, only when office BP is persistently elevated does WCH reflect the existence of an abnormal long-term mortality risk. This means that in WCH office BP is prognostically relevant and that repeated collection of its values is clinically important to better define patient risk.

Long-term chronic baroreflex activation: Persistent efficacy in patients with heart failure and reduced ejection fraction

Abstract: Aims: Baroreflex activation therapy (BAT) has recently been shown to reduce muscle sympathetic nerve activity and hospitalization rate while improving clinical variables through 6 months of therapy in patients with heart failure and reduced ejection fraction (HFrEF). The objective of the present study is to extend the information on this patient cohort over a long-term follow-up. Methods and results: Eleven patients were enrolled in the study and presented with optimized, stable medical therapy, New York Heart Association Class III HFrEF with left ventricular ejection fraction 40% or less, impaired functional capacity and no active cardiac resynchronization therapy. For the present report, muscle sympathetic nerve activity, baroreflex sensitivity data and hospitalization rate together with standard clinical data were collected at 12 and 21.5 � 4.2 months following BAT activation. Two patients died during long-term follow-up. The remaining nine patients maintained the improvements observed at 6 months, including reduced sympathetic activity and rates of hospitalization. Conclusion: BAT provides long-term chronic reductions in sympathetic activity and utilization of hospital resources in patients with HFrEF. General clinical presentation, quality of life and functional capacity are likewise improved and maintained. The temporal association of BAT with sympathetic drive diminution and improvement in objective clinical measures suggests a cause-and-effect relationship that will be verified in future randomized controlled trials of outcome.

Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000-2005 and 2005-2011 hypertension surveys.

Abstract: This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000–2005 and 2005–2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m−2, BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.

Risk of mortality in relation to an updated classification of left ventricular geometric abnormalities in a general population : the PAMELA study

Abstract: AIM We estimated the risk of cardiovascular and all-cause mortality associated with left ventricular geometric patterns, as defined by a new classification system proposed by the Dallas Heart Study, in 1716 representatives of the general population of Monza enrolled in the Pressioni Monitorate e Loro Associazioni (PAMELA) study. METHODS Cut-points for abnormal left ventricular geometric patterns were derived from reference values of the healthy fraction of the PAMELA population by combining left ventricular mass (LVM) index, left ventricular diameter and relative wall thickness. Death certificates were collected over an average 211 months follow-up period. RESULTS During follow-up, 89 fatal cardiovascular events and 264 all-cause deaths were recorded. Concentric remodelling was the most common left ventricular geometric abnormality (9.4%) followed by eccentric nondilated left ventricular hypertrophy (LVH) (6.3%), concentric LVH (4.6%) and eccentric dilated LVH (3.5%). Compared with normal left ventricular geometry, concentric LVH [hazard ratio 2.20, 95% confidence interval (95% CI) 1.44-3.37, P < 0.0003], eccentric dilated LVH (hazard ratio 1.90, 95% CI 1.17-3.08, P = 0.009) and eccentric nondilated LVH (hazard ratio 1.57, 95% CI 1.07-2.31, P = 0.02) predicted the risk of cardiovascular mortality, after adjustment for baseline covariates, including ambulatory blood pressure. Similar findings were observed for all-cause mortality. Only concentric LVH maintained a significant prognostic value for both outcomes after adjustment for baseline differences in LVM index. CONCLUSION The new classification system of left ventricular geometric patterns may improve mortality risk stratification in a general population. The risk is markedly dependent on LVM values; only concentric LVH provides a prognostic information beyond that conveyed by cardiac mass.

Untreated masked hypertension and carotid atherosclerosis: a meta-analysis

Abstract: Aim. Masked hypertension (MH) is recognized as a clinical entity with an unfavorable cardiovascular prognosis; a limited number of reports, however, investigated the impact of this condition on subclinical vascular damage. We performed a meta-analysis aimed at evaluating the association of MH with subclinical carotid atherosclerosis in initially untreated subjects. Design. Studies were identified by the following search terms: “masked hypertension”, “isolated clinic normotension”, “white coat normotension”, “carotid artery”, “carotid atherosclerosis”, “carotid intima-media thickness”, “carotid damage” and “carotid thickening”. Full articles published in English language reporting data from studies performed in untreated adult individuals were considered. Results. Overall, 2752 untreated subjects (1039 normotensive, 497 MH and 766 hypertensive individuals) of both genders were included in five studies (sample size range 18–222 for MH participants). Common carotid intima-media thickness (IMT) showed...

Diagnostic and therapeutic problems of isolated systolic hypertension

Abstract: Prevalence of isolated systolic hypertension increases with age, due to progressive elevation of SBP, and is a major risk factor for cardiovascular morbidity and mortality. Extensive research has shown that lowering SBP improves cardiovascular outcomes in patients with isolated systolic hypertension, yet SBP control rates remain largely inadequate regardless of antihypertensive treatment. Arterial stiffness is a major determinant of elevated SBP resulting from structural changes in the vascular system, mediated by neurohormonal alterations that occur with vascular ageing. Clinical data have demonstrated an independent association between arterial stiffness and cardiovascular outcomes. Therefore, arterial stiffness has the potential to be an important therapeutic target in the management of isolated systolic hypertension. Current antihypertensive treatments have limited effects on arterial stiffness, so the development of new treatments addressing neurohormonal alterations central to vascular ageing is important. Such therapies may represent effective strategies in the future management of SBP.

Statins use and the risk of all and subtype hematological malignancies: a meta‐analysis of observational studies

Abstract: In order to quantify the association between use of statins and the risk of all hematological malignancies and of subtypes, we performed a meta-analysis of observational studies. We achieved a MEDLINE/EMBASE comprehensive search for studies published up to August 2014 investigating the association between use of statins and the risk of hematological malignancies, including Hodgkin- and non-Hodgkin lymphoma, leukemia, and myeloma. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR) based on adjusted study-specific results. Between-study heterogeneity was assessed using the Q and I2 statistics and the sources of heterogeneity were investigated using Deeks' test. Moreover, an influence analysis was performed. Finally, publication bias was evaluated using funnel plot and Egger's regression asymmetry test. Fourteen studies (10 case–control and four cohort studies) contributed to the analysis. Statin use, compared to nonuse of statins, was negatively associated with all hematological malignancies taken together (summary RR 0.86; 95% CI: 0.77–0.96), with leukemia (0.83; 0.74–0.92), and non-Hodgkin lymphoma (0.81; 0.68 to 0.96), but it was not related to the risk of myeloma (0.89; 0.53–1.51). Long-term users of statins showed a statistically significant reduction in the risk of all hematological malignancies taken together (0.78; 0.71–0.87). Statistically significant between-studies heterogeneity was observed for all outcome except for leukemia. Heterogeneity was caused by differences confounding-adjustment level of the included studies only for Myeloma. No significant evidence of publication bias was found.

Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study.

Abstract: INTRODUCTION AND OBJECTIVE Blood pressure variability (BPV) within 24 h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit. METHODS BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients' history, physical and laboratory examinations. RESULTS The 6425 hypertensive patients had an age of 59.2 ± 11 years (mean ± SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1 ± 6.2 mmHg and 3.5 ± 4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5 ± 11 vs. Q4: 60.3 ± 11 years, P < 0.001), serum total cholesterol (Q1: 213.0 ± 46 vs. Q4: 216.4 ± 51 mg/dl, P < 0.05), blood glucose (Q1: 106.2 ± 35 vs. Q4: 109.8 ± 39 mg/dl, P < 0.005), previous cardiovascular events (Q1: 57.4 vs. Q4: 63.9%, P < 0.001), and resistant hypertension (Q1: 26.3 vs. Q4: 34.1%, P < 0.001). They also showed higher office (Q1: 143.2 ± 18 vs. Q4: 154.3 ± 19 mmHg, P < 0.001) and 24-h ambulatory SBP values (Q1: 134.8 ± 17 vs. Q4: 141.2 ± 18 mmHg, P < 0.001). Similar results were obtained when BPV was expressed as SD. CONCLUSION Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance.

Prognostic value of left ventricular mass normalized to different body size indexes: findings from the PAMELA population.

Abstract: Aim:We estimated the risk of cardiovascular and all-cause mortality associated with left ventricular hypertrophy (LVH) as assessed by left ventricular mass (LVM), normalized by various indexation methods in 1716 representatives of the general population of Monza, enrolled in the Pressioni Arteriose

Blood pressure variability after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Abstract: Background:Renal denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. Increased 24-h BP variability is associated with adverse cardiovascular outcomes and related to sympathetic activation.Methods and results:This multicenter study investiga

Introduction to a Compendium on Hypertension

Abstract: Hypertension is by far the most common disease that affects human beings, its high prevalence involving both sexes and extending to either industrialized and developing countries.1 Compared with normotensives, individuals with a high blood pressure stand a much greater chance of having during their life a stroke, coronary heart disease, heart or renal failure, and peripheral artery disease,2 with a substantially higher risk also of developing atrial fibrillation,3 deterioration of cognitive function, and dementia.4 The high prevalence and the multifold important contribution of hypertension to cardiovascular and renal risk account for its position as the top contributor to the burden of disease worldwide.5 Despite extensive research the cause or causes of hypertension in a given patient remain in most instances as unclear today as they were decades ago. Yet, the data that have been obtained by basic and clinical studies have provided considerable knowledge of the factors that may be potentially involved as well as of the molecular, humoral, neural, and structural mechanisms through which a blood pressure increase may occur. The aim of this compendium, the first devoted to hypertension by Circulation Research , is to offer clinicians and investigators a critical review of this knowledge, covering a large spectrum of data, that is, from genetic and molecular to integrated pathophysiology, epidemiology, diagnosis, and treatment. Rahimi et al6 open the series with a survey of the epidemiology of hypertension. Evidence of the progressive increase in the risk of cardiovascular or renal diseases with the increasing blood pressure values is reviewed together with issues of great current interest …