Publications by authors named "Fabio Angeli"

221 Publications

The pivotal link between ACE2 deficiency and SARS-CoV-2 infection.

Eur J Intern Med 2020 06 20;76:14-20. Epub 2020 Apr 20.

Dipartimento di Medicina e Chirurgia, Università degli Studi dell'Insubria, Varese; Dipartimento di Medicina e Riabilitazione Cardio-Respiratoria, Istituti Clinici Scientici Maugeri, IRCCS Tradate (VA).

Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the 'adverse' ACE→Angiotensin II→AT1 receptor axis and the 'protective' ACE2→Angiotensin→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin. In this setting, recombinant ACE2, angiotensin and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.ejim.2020.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167588PMC
June 2020

Alcohol intake and atrial fibrillation: A new topic in gender medicine.

Eur J Intern Med 2020 06 20;76:23-25. Epub 2020 Apr 20.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Piazzale Giorgio Menghini, 1, 06129, Perugia - Italy.

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http://dx.doi.org/10.1016/j.ejim.2020.04.034DOI Listing
June 2020

[ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus].

G Ital Cardiol (Rome) 2020 May;21(5):321-327

Dipartimento di Medicina e Chirurgia, Università degli Studi dell'Insubria, Varese; Dipartimento di Medicina e Riabilitazione Cardio-Respiratoria, Istituti Clinici Scientifici Maugeri, IRCCS, Tradate (VA).

Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1714/3343.33127DOI Listing
May 2020

Optimal Use of the Non-Inferiority Trial Design.

Pharmaceut Med 2020 06;34(3):159-165

Department of Medicine, University of Perugia, 06156, Perugia, Italy.

Superiority trials are conducted to test the hypothesis that a treatment or strategy A is superior to (i.e., better than) treatment strategy B in reducing the impact of disease. However, A may be considerably safer, more convenient, or cheaper than B. These features may make A more attractive than B even if the burden of disease is reduced comparably by the two treatments, or even a bit worse by A over B. In this context, non-inferiority trials have become increasingly popular to test the hypothesis that a new treatment is not 'unacceptably worse' than an active comparator by more than a predefined non-inferiority margin. Non-inferiority trials have unique design features and methodology and require a different analysis than traditional superiority trials. The main aim of this overview is to analyze the role of non-inferiority trials in the development of new treatments, involving some scientific, statistical, and practical considerations. We elucidate some aspects of non-inferiority trials that contribute to the validity of the results. The unique design features and methodology of non-inferiority trials are summarized and key findings to consider when evaluating a non-inferiority trial are illustrated.
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http://dx.doi.org/10.1007/s40290-020-00334-zDOI Listing
June 2020

Device-Pocket Hematoma After Cardiac Implantable Electronic Devices.

Circ Arrhythm Electrophysiol 2020 04 20;13(4):e008372. Epub 2020 Mar 20.

Struttura Complessa di Cardiologia, Hospital 'Santa Maria della Misericordia', Piazzale Giorgio Menghini (F.N., P.V., G.Z., L.S., R.A., M.R.R., S.P., S.N., C.C.).

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http://dx.doi.org/10.1161/CIRCEP.120.008372DOI Listing
April 2020

Blood pressure variability and risk of stroke in chronic kidney disease.

J Hypertens 2020 04;38(4):599-602

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1097/HJH.0000000000002339DOI Listing
April 2020

Use of Antibiotics and Mortality in Women: Does Duration of Exposure Matter?

Circ Res 2020 01 30;126(3):374-376. Epub 2020 Jan 30.

Department of Medicine, University of Perugia, Italy (G.R.).

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http://dx.doi.org/10.1161/CIRCRESAHA.119.316406DOI Listing
January 2020

Echocardiography in Low-Risk Hypertensive Patients.

J Am Heart Assoc 2019 12 16;8(24):e013497. Epub 2019 Dec 16.

Department of Medicine University of Perugia Italy.

Background It is debated whether echocardiography should be part of the diagnostic workup in all hypertensive patients. We identified some factors potentially associated with left ventricular hypertrophy (LVH) at echocardiography in untreated hypertensive patients. Methods and Results We studied 2150 patients without LVH at ECG. All patients underwent standard 12-lead ECG and echocardiography. Mean age was 48.7 years, and mean office blood pressure was 154/97 mm Hg. Prevalence of echocardiographic LVH (LV mass >47.0 g/m in women and >50.0 g/m in men) was 37.1%. We developed a nomogram based on 7 items (age, smoking, body mass index, office systolic and diastolic blood pressure, Cornell voltage, and chronic kidney disease) on the basis of a multivariable logistic regression analysis. We internally validated the model by bootstrap recalibration and obtained a calibration curve to assess agreement in the validation data set. Probability of LVH at echocardiography ranged from <10% (score, ≤100 points) to >90% (score, ≥180 points). Proportion of patients with LVH progressively increased with the total score (χ=444.8; <0.001). Prevalence of LVH was <2% and 90% at the lower 5th and upper 95th percentile of its distribution, respectively. Conclusions We developed and validated a novel score to assess the probability of LVH at echocardiography in hypertensive patients without LVH at ECG. The score may guide the appropriateness of echocardiographic study in low-risk hypertensive patients. Echocardiography appears most appropriate for score values >136 in men and >124 in women.
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http://dx.doi.org/10.1161/JAHA.119.013497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951057PMC
December 2019

Hypertensive urgencies and emergencies: Misconceptions and pitfalls.

Eur J Intern Med 2020 01 6;71:15-17. Epub 2019 Nov 6.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia Italy.

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http://dx.doi.org/10.1016/j.ejim.2019.10.031DOI Listing
January 2020

Non-inferiority Trial Design in Drug Development: A Primer for Cardiovascular Healthcare Professionals.

Am J Cardiovasc Drugs 2020 Jun;20(3):229-238

Department of Medicine, University of Perugia, Perugia, Italy.

Noninferiority trials, in which a new treatment is compared with a standard active treatment, are becoming increasingly popular in cardiovascular medicine. A noninferiority trial seeks to test whether the effect of a new drug is not unacceptably worse than that of an active comparator by more than a predefined noninferiority margin. Noninferiority trials are typically used when a new drug is anticipated to have an efficacy profile similar to its comparator and offers advantages over the existing drug (better toxicity profile, less expensive, less invasive, simpler regimen, shorter treatment duration, different resistance profile). Given the high number of noninferiority trials, it is vital that clinicians fully understand the clinical impacts of the results. Nonetheless, assessing noninferiority in a trial is complex, in both the design and the analysis phases. The crucial issue in the design of a noninferiority trial is the definition of the noninferiority margin, accounting for both statistical (summarizing the historical evidence of the active comparator from randomized controlled trials) and clinical (choosing the fraction of the effect of the old drug that should be "preserved" by the new drug) considerations. We review the role of noninferiority trials in the development of new cardiovascular treatments and discuss a variety of key issues involved in the design and conduction of noninferiority trials, using some examples from real clinical trials in cardiovascular medicine.
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http://dx.doi.org/10.1007/s40256-019-00378-wDOI Listing
June 2020

Systolic and Diastolic Blood Pressure and Cardiovascular Outcomes.

N Engl J Med 2019 10;381(17):1691-1692

University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1056/NEJMc1911059DOI Listing
October 2019

Detrimental Impact of Chronic Obstructive Pulmonary Disease in Atrial Fibrillation: New Insights from Umbria Atrial Fibrillation Registry.

Medicina (Kaunas) 2019 Jul 9;55(7). Epub 2019 Jul 9.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria Della Misericordia, 06156 Perugia, Italy.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Among extra-pulmonary manifestations of COPD, atrial fibrillation (AF) is commonly observed in clinical practice. The coexistence of COPD and AF significantly affects the risk of cardiovascular morbidity and mortality. Nonetheless, the mechanisms explaining the increased risk of vascular events and death associated to the presence of COPD in AF are complex and not completely understood. We analyzed data from an Italian network database to identify markers and mediators of increased vascular risk among subjects with AF and COPD. Cross-sectional analysis of the Umbria Atrial Fibrillation (Umbria-FA) Registry, a multicenter, observational, prospective on-going registry of patients with non-valvular AF. Of the 2205 patients actually recruited, 2159 had complete clinical data and were included in the analysis. the proportion of patients with COPD was 15.6%. COPD patients had a larger proportion of permanent AF when compared to the control group (49.1% vs. 34.6%, < 0.0001) and were more likely to be obese and current smokers. Other cardiovascular risk factors including chronic kidney disease (CKD), peripheral artery disease and subclinical atherosclerosis were more prevalent in COPD patients (all < 0.0001). COPD was also significantly associated with higher prevalence of previous vascular events and a history of anemia (all < 0.0001). The thromboembolic and bleeding risk, as reflected by the CHADSVASc and HAS-BLED scores, were higher in patients with COPD. Patients with COPD were also more likely to have left ventricular (LV) hypertrophy at standard ECG than individuals forming the cohort without COPD ( = 0.018). AF patients with COPD have a higher risk of vascular complications than AF patients without this lung disease. Our analysis identified markers and mediators of increased risk that can be easily measured in clinical practice, including LV hypertrophy, CKD, anemia, and atherosclerosis of large arteries.
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http://dx.doi.org/10.3390/medicina55070358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681215PMC
July 2019

Response by Verdecchia et al to Letter Regarding Article "Sudden Cardiac Death in Hypertensive Patients".

Hypertension 2019 Jul 1:HYPERTENSIONAHA11913441. Epub 2019 Jul 1.

Department of Medicine, University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13441DOI Listing
July 2019

Tight Blood Pressure Control Saves Lives in Hypertensive Patients With Chronic Kidney Disease.

Hypertension 2019 06;73(6):1172-1173

Department of Medicine, University of Perugia, Italy (G.R.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12855DOI Listing
June 2019

Managing hypertension in 2018: which guideline to follow?

Heart Asia 2019 22;11(1):e011127. Epub 2019 Feb 22.

Fondazione Umbra Cuore e Ipertensione-ONLUS, Perugia, Italy.

Hypertension is a global public health issue and a major cause of morbidity and mortality. Its prevalence is increasing in many Asian countries, with a number of countries with blood pressure above the global average. Although the average systolic blood pressure is decreasing worldwide since the 1980s at the rate of about 1 mm Hg systolic blood pressure per decade, it is increasing in low-income and middle-income countries, especially in the East and South Asian population. Of note, the much larger base Asian population results in a considerably larger absolute number of individuals affected. When compared with Western countries, hypertension among Asian populations has unique features in terms of its onset, clustering of associated cardiovascular risk factors, complications and outcomes. Moreover, only a minority of hypertensive individuals are receiving treatment and achieving control. Projected number of deaths related to hypertension dramatically increased in the last 25 years in some Asian regions with a disproportionately high mortality and morbidity from stroke compared with Western countries. The relation between blood pressure and the risk of stroke is stronger in Asia than in Western regions. Although new Guidelines for hypertension diagnosis and management have been recently released from Europe and North America, the unique features of Asian hypertensive patients raise concerns on the clinical applicability of Western Guidelines to Asian populations. To this purpose, we critically reviewed key elements from the most updated Guidelines. We also discussed their core concepts to verify the impact on hypertension prevention and management in Asian countries.
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http://dx.doi.org/10.1136/heartasia-2018-011127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454321PMC
February 2019

Electrocardiography for diagnosis of left ventricular hypertrophy in hypertensive patients with atrial fibrillation.

Int J Cardiol Hypertens 2019 May 10;1:100004. Epub 2019 Apr 10.

Department of Medicine, University of Perugia, Perugia, Italy.

Left ventricular (LV) hypertrophy at electrocardiography (ECG) predicts incident atrial fibrillation (AF). However, the diagnostic performance of ECG for diagnosis of LV hypertrophy in patients with AF is still not well characterized. We analyzed 563 hypertensive patients enrolled in the Umbria-Atrial Fibrillation (Umbria-FA) registry, an ongoing prospective observational registry in patients with AF. All patients underwent ECG and standard echocardiography at their entry in the Register. Mean age was 74 years and 43% of patients were women. Prevalence of ECG-LV hypertrophy, defined by Perugia criterion corrected for body mass index, was 23%. Echocardiographic LV mass was the reference standard. Sensitivity, specificity and diagnostic accuracy of ECG-LV hypertrophy were 37.4% (95% confidence interval [CI]: 31.6-43.4), 90.0% (95% CI: 86.0-93.2) and 64.5% (95% CI: 60.4-68.3), respectively. Performance was comparable in patients with AF or sinus rhythm at ECG recording. The area under the receiver-operating characteristic (ROC) curve was 0.622 (95% CI: 0.580-0.664) in the group with AF and 0.662 (95% CI: 0.605-0.720) in that with sinus rhythm (p ​= ​0.266 for comparison). These data suggest that standard ECG is reliable for diagnosis of LV hypertrophy in patients with a history of AF, regardless of the presence of AF or sinus rhythm at the time of ECG recording.
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http://dx.doi.org/10.1016/j.ijchy.2019.100004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803070PMC
May 2019

Sudden Cardiac Death in Hypertensive Patients.

Hypertension 2019 05;73(5):1071-1078

Department of Medicine, University of Perugia, Italy (M.D.F., G.R.).

In patients with hypertension, but without established cardiovascular disease, predictive factors for sudden cardiac death (SCD) remain undefined. We followed for an average of 10.3 years a cohort of 3242 initially untreated hypertensive patients without evidence of coronary or cerebrovascular heart disease at entry. All patients underwent a complete clinical examination which included ECG and 24-hour ambulatory blood pressure monitoring. At entry, the mean age of patients was 50.0 years, 45% were women, and 6.1% had type 2 diabetes mellitus. Average office blood pressure was 154/96 mm Hg, and average 24-hour ambulatory blood pressure was 136/86 mm Hg. Prevalence of left ventricular hypertrophy at ECG was 13.9%. During follow-up, SCD occurred in 33 patients at a rate of 0.10 per 100 patient-years (95% CI, 0.07-0.14). The rate of SCD was 0.07 and 0.30 per 100 patient-years, respectively, in the cohort of patients without and with ECG left ventricular hypertrophy ( P<0.01). In a multivariable Cox model with Firth penalized maximum bias reduction method for rare outcome events, left ventricular hypertrophy almost tripled the risk of SCD (adjusted hazard ratio, 2.99; 95% CI, 1.47-6.09; P=0.002) after adjustment for age ( P<0.0001), sex ( P=0.019), diabetes mellitus ( P<0.0001), and 24-hour ambulatory pulse pressure ( P=0.036). For each 10 mm Hg increase in 24-hour ambulatory pulse pressure, the risk of SCD increased by 35%. The time-dependent area under the receiver operating characteristic curve was 0.85 (95% CI, 0.74-0.96). We conclude that in patients with hypertension without established cardiovascular disease, age, diabetes mellitus, ECG left ventricular hypertrophy, and 24-hour ambulatory pulse pressure are independent prognostic markers for SCD in the long-term.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12684DOI Listing
May 2019

European and US guidelines for arterial hypertension: similarities and differences.

Eur J Intern Med 2019 05 4;63:3-8. Epub 2019 Feb 4.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

Hypertension is one of the most common chronic diseases in adults and a leading cause of disability and mortality worldwide. Recently, new Guidelines for the diagnosis and management of hypertension have been released in Europe and in the United States, with changes regarding how to diagnose and treat the condition, and the extent to which intensive blood pressure control should be pursued. Important differences between the Guidelines exist in the classification of blood pressure levels and definition of treatment goals. Diagnosis of hypertension starts at 140/90 mmHg for the European Guidelines, and 130/80 mmHg for the US Guidelines. Besides, the European guidelines introduced the concept of "safety boundaries", consisting of BP thresholds not to be exceeded towards lower levels (120 mmHg for age < 65 years, 130 mmHg for older people) because of the fear of important adverse events associated with overtreatment. Such discrepancies can indeed have an impact on treatment attitudes and outcome incidence. Hence, we appraised facts in favor and against each of these controversial issues. In conclusion we believe that, instead of fixing rigid BP targets and boundaries, modern hypertension management should be aimed to achieve in each patient an optimal balance between intensive BP reduction and treatment safety.
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http://dx.doi.org/10.1016/j.ejim.2019.01.016DOI Listing
May 2019

Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the  RE - LY Trial.

J Am Heart Assoc 2019 01;8(2):e010107

1 Department of Medical Sciences Cardiology Uppsala University Uppsala Sweden.

Background Cardiac biomarkers and left ventricular hypertrophy ( LVH ) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes. Methods and Results Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE - LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. NT -proBNP (N-terminal pro-B-type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor-15 were determined using high-sensitivity (hs) assays. LVH was defined by ECG . Cox models were adjusted for baseline characteristics, LVH , and biomarkers. LVH was present in 1257 patients. During a median follow-up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly ( P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT -pro BNP , 1.32 (1.25-1.38); hs cardiac troponin I, 1.67 (1.57-1.78); hs troponin T, 1.38 (1.32-1.44); and growth differentiation factor-15, 1.09 (1.05-1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT -pro BNP, 1.09 (1.00-1.19); hs cardiac troponin I, 1.09 (1.03-1.15); hs troponin T, 1.14 (1.06-1.24); and growth differentiation factor-15, 1.22 (1.08-1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT -pro BNP , 1.24 (1.17-1.31); hs cardiac troponin I, 1.13 (1.10-1.17); hs troponin T, 1.28 (1.23-1.34); and growth differentiation factor-15, 1.31 (1.22-1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers. Conclusions Cardiac biomarkers are significantly associated with LVH . The prognostic value of biomarkers for stroke and death is not affected by LVH . The prognostic information of LVH is attenuated in the presence of cardiac biomarkers. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00262600.
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http://dx.doi.org/10.1161/JAHA.118.010107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497355PMC
January 2019

Keep Blood Pressure Low, but Not Too Much….

Circ Res 2018 11;123(11):1205-1207

Dipartimento di Medicina, Università di Perugia, Italy (G.R.).

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http://dx.doi.org/10.1161/CIRCRESAHA.118.314017DOI Listing
November 2018

Amlodipine and celecoxib for treatment of hypertension and osteoarthritis pain.

Expert Rev Clin Pharmacol 2018 Nov 3;11(11):1073-1084. Epub 2018 Nov 3.

b Department of Medicine , University of Perugia , Perugia , Italy.

Introduction: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.
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http://dx.doi.org/10.1080/17512433.2018.1540299DOI Listing
November 2018

Long-term outcome in patients with non-valvular atrial fibrillation on dabigatran: a prospective cohort study.

Expert Opin Drug Saf 2018 Nov 8;17(11):1063-1069. Epub 2018 Oct 8.

b Internal, Vascular and Emergency Medicine - Stroke Unit , University of Perugia , Perugia , Italy.

Introduction: Most studies on thromboembolic and bleeding risk in patients with non-valvular atrial fibrillation (NVAF) exposed to non-vitamin K oral anticoagulants stem from interrogation of insurance databases. Areas covered: We studied 742 consecutive patients with NVAF who started treatment with dabigatran in three hospitals in Italy. Average follow-up was 1.80 years. Mean age was 76.2 years. CHADSVASc score was 0-1 in 37 (5%), 2 in 97 (13%) and ≥ 3 in 604 (82%) patients. NVAF was permanent in 349 (48%). Overall, 76% of patients remained on treatment over the entire follow-up period. Among 180 patients who discontinued permanently, the most frequent reasons were dyspepsia (33.9%), bleeding (17.8%), and renal worsening (12.1%). About 48% and 74% of permanent discontinuations occurred during the first 6 and 12 months of treatment, respectively. Rates of major events (per 100 patient-years) were 0.75 for stroke, 0.31 for myocardial infarction, 1.50 for all-cause death, and 1.80 for major bleedings. The rate of intracranial bleedings was 0.45 and that of major gastrointestinal bleedings was 0.75. Expert opinion: This prospective cohort study confirms the low incidence of stroke, major bleeding and intracranial bleeding, and a 76% persistence with treatment, in patients with NVAF treated with dabigatran over about 2 years.
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http://dx.doi.org/10.1080/14740338.2018.1529166DOI Listing
November 2018

Gathering evidence on the prognostic role of central blood pressure in hypertension.

Hypertens Res 2018 11 26;41(11):865-868. Epub 2018 Sep 26.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital Santa Maria della Misericordia, Perugia, Italy.

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http://dx.doi.org/10.1038/s41440-018-0108-3DOI Listing
November 2018

What to Do When Blood Pressure Is Between 130/80 and 139/89 mm Hg?

J Am Coll Cardiol 2018 09;72(11):1198-1200

Department of Medicine, University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.1016/j.jacc.2018.07.010DOI Listing
September 2018

The 2018 ESC/ESH hypertension guidelines: Should nephrologists always stop at the lower boundary?

J Nephrol 2018 Oct 30;31(5):621-626. Epub 2018 Aug 30.

Fondazione Umbra Cuore e Ipertensione-ONLUS e Struttura Complessa di Cardiologia, Ospedale S. Maria della Misericordia, Perugia, Italy.

In patients with chronic kidney disease (CKD), hypertension is a major challenge because of its high prevalence, the consequent increase in cardiovascular morbidity and mortality, and the risk it confers specifically to the progression of kidney disease. Hence, establishing evidence-based blood pressure targets and treatment strategies is a clinical priority of paramount importance. Over the last few years, different guidelines have advocated different blood pressure treatment thresholds and goals in CKD patients, including a target < 140/90 mmHg and a more intensive target-lower than 130/80 mmHg-in the presence of albuminuria ≥ 300 mg/daily. Aim of this article is to critically appraise the evidence base of the freshly released 2018 ESC/ESH European Guidelines, which recommend to lower systolic BP to a range 130 to < 140 mmHg in patients with diabetic or non-diabetic CKD, also in view of the 2017 US guidelines, which favor a more intensive strategy with a BP target lower than 130/80 mmHg.
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http://dx.doi.org/10.1007/s40620-018-0526-yDOI Listing
October 2018

[Evaluation of cardiovascular risk and perioperative management of patients undergoing noncardiac surgery. Results of an ANMCO web survey].

G Ital Cardiol (Rome) 2018 Sep;19(9):504-509

U.O. Cardiologia, A.O. San Giovanni Addolorata, Roma.

Background: Cardiovascular risk stratification and perioperative management of subjects undergoing non-cardiac surgery have recently been updated in the 2014 European Society of Cardiology guidelines. Nevertheless, and notwithstanding the epidemiological relevance of this condition, an underevaluation of the importance of perioperative risk stratification is a common feeling.

Methods: The ANMCO Cardiovascular Prevention Area organized, last year, a web-based survey with 15 questions to investigate perioperative management and care pathways in non-cardiac surgery and to evaluate guideline adherence of Italian cardiologists. Participation in the survey was anonymous.

Results: Respondents had a homogeneous geographical, as well as working (coronary care unit, post-intensive care unit, ambulatory service) distribution. Among respondents, 38% evaluated more than 20 patients each month, and 25% more than 20 patients aged >75 years. Local diagnostic guidelines were available according to 60% of respondents. Despite guideline recommendations, cardiological evaluation preceded the anesthesiologic one according to 36% of respondents, and 42% reported that it was performed independent of baseline risk. In addition, perioperative use of risk scores was low (1%), and functional capacity was reported from only 56% of respondents. Half of them used bridge therapy with heparin after stopping direct oral anticoagulants.

Conclusions: The results of the ANMCO web-based survey confirm the need to promote educational programs on risk stratification and to raise awareness of Italian cardiologists on this matter in order to improve guideline adherence.
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http://dx.doi.org/10.1714/2951.29669DOI Listing
September 2018

Heart failure, pulse pressure and heart rate: Refining risk stratification.

Int J Cardiol 2018 11 17;271:206-208. Epub 2018 Jul 17.

Fondazione Umbra Cuore e Ipertensione-ONLUS, Hospital S. Maria della Misericordia, Perugia, Italy; Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2018.07.072DOI Listing
November 2018

Role and prognostic value of individual ambulatory blood pressure components in chronic kidney disease.

J Hum Hypertens 2018 09 13;32(8-9):625-632. Epub 2018 Jun 13.

Department of Medicine, University of Perugia, Perugia, Italy.

Hypertension is a key risk factor for chronic kidney disease (CKD), but can also be a detrimental consequence of established CKD. Unsurprisingly, the majority of subjects with abnormal creatinine in the general population are also hypertensive, with a huge toll on national health care systems worldwide due to a staggering increase in the risk of cardiovascular complications and end-stage renal disease requiring renal replacement therapy. In this setting, a comprehensive and careful assessment of the whole 24-h blood pressure (BP) profile could be of paramount importance in ensuring a timely diagnosis of hypertension and an optimal therapeutic control. Hence, ambulatory BP monitoring (ABPM) has the potential to become the preferred method for optimal clinical management of CKD patients. ABPM might better define the relationship between BP, target organ damage (TOD), and clinical outcomes. Current evidence suggests that specific day-night BP components, along with average BP values, may have clinical relevance in such patients, despite the suboptimal statistical power of available studies and inconsistencies on the prognostic value of individual BP components. The main aim of our review is to scrutinize the evidence for the usage of ABPM in CKD patients, including the relationship between ambulatory BP recordings and cardiovascular events, and the distinctive features of ABPM in these subjects.
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http://dx.doi.org/10.1038/s41371-018-0081-yDOI Listing
September 2018
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