Giuseppe Mancia

Bio: Giuseppe Mancia is an academic researcher from University of Milano-Bicocca. The author has contributed to research in topics: Blood pressure & Ambulatory blood pressure. The author has an hindex of 145, co-authored 1369 publications receiving 139692 citations. Previous affiliations of Giuseppe Mancia include University of Milan & Instituto Politécnico Nacional.

A smooth blood pressure control is obtained over 24 h by Delapril in mild to moderate essential hypertensives

Abstract: Objective: To assess the homogeneity of the antihypertensive effect of delapril over 24 h. Design and methods: After 2 weeks of placebo 50 mild to moderate essential hypertensives (age 54 - 5 years) were subjected to 8 weeks of treatment with delapril 30 mg once daily. At the end of each period, blood pressure (BP) was assessed by conventional sphygmomanometry (clinic or CBP) and ambulatory (A) BP monitoring. Twenty-four-hour means, trough-to-peak ratio (T/P) and smoothness index (SI, the ratio between the average of the 24-h BP changes after T and its standard deviation) were calculated for systolic (S) and diastolic (D) BP. Results: CBP and ABP were significantly reduced by treatment. Pulse pressure (PP, the SBP-DBP difference) was also significantly ( p < 0.01) reduced by delapril (5.7 - 6.2 and 3.3 - 3.8 mmHg, CPP and APP). The median T/P was higher (0.51 and 0.62, SBP and DBP) in the 43 responders at trough than in the whole group (0.44 and 0.51). The SI was similarly high in the whole group...

Reflex control of renin release in essential hypertension.

Abstract: 1. The reflex control of renin release was studied in subjects with essential hypertension by comparing the effects of a variable-pressure neck chamber and head-up tilting. 2. Increase in carotid sinus transmural pressure (obtained by reducing tissue pressure outside the carotid sinus by 34 ± 3 mmHg) decreased mean arterial pressure by 16 ± 2 mmHg, but did not reduce significantly the renal venous—arterial difference in plasma renin activity. Likewise decrease in carotid sinus transmural pressure (obtained by increasing tissue pressure outside the carotid sinus by 39 ± 2 mmHg) increased mean arterial pressure by 14 ± 3 mmHg, but caused only a very slight increase in the renal venous—arterial difference in plasma renin activity. 3. Passive tilting reduced mean arterial pressure by 9 ± 1 mmHg. In this circumstance the renal venous—arterial difference in plasma renin activity increased significantly and markedly. 4. It is concluded that in essential hypertension the carotid sinus baroreceptors, though active in blood pressure control, do not exert a major influence on renin release. In these patients reflex increase of renin during tilting is apparently mediated through other receptors than those in the carotid sinuses.

COVID-19, hypertension, and RAAS blockers: the BRACE-CORONA trial

Abstract: At the beginning of the COVID-19 pandemic, the hypertension world was shaken by the evidence that, as shown in 2003 for the severe acute respiratory syndrome (SARS)-corona virus, the SARS coronavirus-2 (SARS-CoV-2) virus entered the cell via an enzyme, the angiotensinconverting enzyme 2 (ACE2), which is part of the renin–angiotensin–aldosterone system (RAAS) and thus, albeit somewhat collaterally, of the mechanisms through which ACE-inhibitors, angiotensin receptor blockers and, to a lesser extent, mineralocorticoid receptor antagonists exert their therapeutic lifesaving influence in hypertension, heart failure, chronic kidney disease, and the post-myocardial infarction state. Evidence that these drugs might up-regulate ACE2 in several organs, including the lungs and the heart, favoured the hypothesis, widely reported by the press, that the susceptibility to the infection, as well as its severity, might increase by their chronic use, and that thus their discontinuation might represent an appropriate defense measure against the expanding rate of the disease and its lethality. Large observational studies performed in the subsequent months have made the hypothesis of an adverse effect of pretreatment with RAAS blockers on the risk and severity of the COVID-19 infection unlikely, offering support to the recommendations of Scientific Societies and Health-Care Organizations to continue assumption of these drugs and thus avoid the well-known increase of cardiovascular risk that follows their discontinuation. The same studies showed that pretreatment with RAAS blockers did not reduce the risk and severity of the COVID19 infection, offering no support also to the counter-hypothesis, i.e. that, because ACE2 metabolizes angiotensin II from a powerful vasoconstrictor to a vasodilator or inactive substance, RAAS blocker pretreatment might protect against the SARS-CoV-2 virus. In more recent months, attention has shifted from the effects of RAAS-blocker-based pretreatment to those that may be associated with their administration during the infection, due to reports that the virusrelated death was less common in patients in whom this treatment was continued, even when compared with use of other antihypertensive agents. The reports were generated by uncontrolled studies, which limited their scientific strength and made their conclusion largely hypothetical. This is now no more the case, however, because the hypothesis has been tested by a trial (BRACE-CORONA) which has examined the outcome of hospitalized COVID-19 positive patients randomized to temporary suspension or continuation of ACE inhibitors or angiotensin receptor blocker treatment. The trial involved 34 Brazilian medical sites which recruited 659 hypertensive patients defined as having a COVID-19 infection of moderate severity and elected to take, as the primary endpoint, the number of days they were alive and out-of-hospital over a 30-day period. The design was open label and the endpoint estimate was blind. As shown in the presentation of the trial at the recent virtual meeting of the European Society of Cardiology, the number of alive and out-of-hospital patients was similar between the two groups, the mean risk ratio being 0.95 (95% confidence interval 0.90–1.01, P = 0.09) with a between-group not significant difference of just 1.1 days. The same was true for the number of patients who died (9 in either group) which exhibited a risk ratio of 0.97 and a 95% confidence interval of 0.38–2.52 (P = 0.95). This justified the conclusion that the results offered no evidence that during a COVID-19 infection ACE inhibitors and angiotensin receptor blockers affect the disease outcome, in line with the previous evidence that this is the case for pretreatment with these drugs as well. Do the results of the BRACE-CORONA trial provide a final negative answer to the hypothesis of a relationship between RAAS blockers and the SARS-CoV-2 virus? Although the BRACE-CORONA trial was correctly designed and well conducted, the trial has limitations that make confirmatory studies desirable. First, although further data may be made available in the published paper, the presentation did not include ontreatment variables, leaving without answer the possibility for the between-group outcome similarity to be driven by BP or other differences that moved to the null some direct effect of RAAS blockers on the disease severity. Second, rather than assessing the disease severity by death or need of intensive care, the trial made use of an unusual primary endpoint, i.e. patients alive and out-of-hospital, which might have been influenced by differences in dismissal criteria from hospital between medical sites. Third, although the included patients had a high prevalence of factors that are known to increase COVID-19 severity (hypertension: 100%, diabetes: >30%, obesity: >55%), mortality was so low as to prevent any meaningful analysis of an endpoint such as death as well as to use death to reliably back the primary endpoint results. Finally, the study was not planned to separately analyse the effect of ACE inhibitors and angiotensin receptor blockers, despite previous reports that during the COVID-19 infection their effect may differ Because the number of patients under ACE inhibitors was much greater than that of patients under angiotensin receptor blockers, it seems unlikely that this question will be convincingly addressed by subgroup analysis.

Effect of detraining on the cardiopulmonary reflex in professional runners and hammer throwers

Abstract: In professional athletes with marked cardiac hypertrophy, reflex influences originating from cardiopulmonary receptors are impaired. To determine whether the reflex is restored after termination of physical training and regression of cardiac hypertrophy 8 former athletes (age 31 +/- 6 years, mean +/- SD) who stopped agonistic activity for 5 +/- 1 years were compared with 15 sedentary subjects (27 +/- 7 years) and 19 active professional athletes (22 +/- 7 years). Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter (echocardiography) through leg raising and nonhypotensive lower body negative pressure, respectively. Left ventricular mass index (echocardiography) was markedly and significantly (p less than 0.01) greater in athletes (135 +/- 6 g/m2) than in former athletes (105 +/- 4 g/m2) whose value was similar to that of sedentary subjects (98 +/- 4 g/m2). The reduction in forearm vascular resistance and plasma norepinephrine induced by increasing left ventricular end-diastolic diameter was 24 and 23% less in athletes than in former athletes whose responses were similar to those of sedentary subjects. This was the case also for the responses induced by reducing left ventricular end-diastolic diameter. In contrast, the hemodynamic responses to cold pressor test were similar in the 3 groups. It is concluded that the impairment of the cardiopulmonary reflex observed in athletes is largely reversible when physical training is terminated. This may be due to regression of left ventricular hypertrophy.

Clinical benefits of a consistent reduction in blood pressure.

Abstract: This paper briefly reviews the epidemiological evidence that hypertension is a major cardiovascular risk factor. It also summarizes the data from controlled intervention trials that show antihypertensive treatment to be accompanied by a reduction in cardiovascular morbidity and mortality. The inability of antihypertensive treatment to offer full protection to the hypertensive individual is then discussed, together with the therapeutic strategies to increase the benefits, particularly with respect to limiting end-organ damage and reduction of cardiovascular events. In this context, emphasis is given to the potential additional benefit conferred by control of 24-h blood pressure and to the compliance advantage of using drugs with a long duration of action. The longevity of the blood pressure lowering effect can compensate for delayed or missed drug consumption, a frequent phenomenon in the chronically treated hypertensive patient.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …