In memoriam: Alberto Zanchetti

Professor Alberto Zanchetti passed away on March 24 at the age of 91 years after a brief period of severe illness. Alberto was active as long as he could touch the keyboard of his computer, as reflected in the brilliantly crafted editorial that he wrote for the May (2018) issue of the Journal of Hypertension. In this editorial [1] he gently commented on every article almost as if he had reviewed and edited all of them himself, though we all know that a hierarchy of hypertension experts had been involved in the process.

Alberto joined the research group of Cesare Bartorelli at the University of Milan in the 1950s and explored the neural basis of blood pressure control. This was a time when the only available treatment for severe hypertension was total abdominal sympathectomy, a radical surgical procedure associated with multiple complications and a high failure rate. Alberto and his associates took on the challenge of finding effective medical treatments for these critically ill patients and demonstrated that ganglion blockers like hexamethonium and mecamylamine effectively lowered their blood pressure and improved their survival [2]. This was the start of one of the greatest success stories of modern medicine, the development of pharmacotherapy for hypertension. Alberto went on to work with nearly all of the scores of antihypertensive drugs to come in the course of a lengthy and highly productive research career.

Much of Alberto’s fundamental research effort was focused on baroreceptor control of blood pressure and on the interactions between neural and renal mechanisms in blood pressure control and in the regulation of renin release [3]. Alberto and coworkers carried out pioneering neck chamber studies, first in normal people at rest and later under conditions of exercise and aging, in order to understand the role of the carotid baroreceptor in blood pressure control, including blood pressure variability [4]. Alberto’s early work on ambulatory blood pressure measurement, the white coat effect, assessment of target organ damage and ways to prevent hypertension and its cardiovascular disease complications set the stage for modern approaches to the diagnosis and treatment of human hypertension that are still under development today.

In order to disseminate the findings of his distinguished group and learn from the experiences of colleagues from other European countries and, eventually, throughout the world, Alberto was instrumental in starting the European Society of Hypertension (ESH). He organized the biennial ESH meetings on the old university campus in Milan, with the plenary sessions in Aula Magna and with the prestigious poster sessions held in the old courtyard of the university. These were times when 80% of submitted abstracts were rejected, every single acceptance was competitive, and no-show was unthinkable.

Alberto has also played a major role in translating basic and clinical research findings into guidelines for antihypertensive treatment. Alberto took on the onerous task of chairing the writing committee of the first full ESH guidelines [5]. These guidelines were enormously successful, and the paper was the most quoted paper in the medical literature in 2003 and 2004. There were many reasons for the wide acceptance of the guidelines, including the principle that most of the benefit of antihypertensive treatment was due to blood pressure lowering per se, reflected in the famous hexagon for drug treatment (one important drug class in each corner), the assessment of total cardiovascular risk, which included all important cardiovascular risk factors in addition to blood pressure, consideration of subclinical target organ damage and measurement of out-of-office blood pressure.

Alberto has edited the Journal of Hypertension since 1995 and has maintained a high impact factor for the journal with great enthusiasm and an extraordinary level of personal engagement with the journal’s day to day activities. A large part of the Journal of Hypertension’s appeal to clinicians has been based on Alberto’s ability to capture European guidelines for the management of arterial hypertension [5], as well as meta-analyses of the key elements [6] of hypertension treatment for publication in its pages.

Alberto was also a major world leader in the design, conduct and interpretation of important randomized controlled clinical trials of antihypertensive treatment. He was Principal Investigator or member of the Steering Committee of HOT, SCOPE, EWPHE, SystEur, ELSA, PHYLLIS, CONVINCE, FEVER and VALUE. In this capacity, he used his prestige to effectively champion the use of outcome data from clinical trials to shape clinical practice. One example of this is his use of the neutral findings of the VALUE trial, the only large outcome trial ever done to compare head-to-head calcium channel blockade with angiotensin II receptor blockade treatment of hypertension [7], to establish the principle that blood pressure lowering per se, rather than choice of a specific antihypertensive drug class, should drive therapeutic decision making in hypertension management. He also argued for earlier and better control of high blood pressure as the most effective method for preventing heart disease, stroke and kidney failure. His influence in the clinical trial world reached as far as China, where he organized the Felodipine Event Reduction (FEVER) Study, and later the ongoing SHOT randomized trial [8], thus introducing evidence based medicine to clinical practice in that huge country.

Alberto was born in Parma, Italy in 1926, and he married Carla, who helped him in daily research activities but who sadly passed away many years ago. He is survived by two sons Mario and Giorgio, daughter Silvia and seven grandchildren Oscar, Anna, Cristina, Alberto, Luisa, Giovanni and Giacomo.

Most of all, Alberto was a great teacher and mentor who inspired large numbers of trainees to go on to distinguished careers in hypertension research and clinical practice. For his contributions, he has received numerous prestigious awards and honors including the International Achievement Award (1977) of the American Heart Association, the Franz Volhard Lecture Award (1986) of the International Society of Hypertension, the Henri Denolin Lecture Award (1991) of the European Society of Cardiology and Riva-Rocci Award (1997) of the Italian Society of Hypertension.

The European Society of Hypertension instituted the Zanchetti Award, an award given for excellence in lifetime research, in his name.

He will be greatly missed.

Acknowledgments

The authors are thankful to Clara Sincich of University of Milan Bicocca for valuable help.

Disclosure statement

S.E.K., K.N., M.B. and S.O. are editors of Blood Pressure and report no relevant conflicts of interest to disclose related to this editorial.