Key points are not available for this paper at this time.
Dr Thomas George Pickering, physician, clinical scientist, professor and mentor, editor, husband, father, and grandfather, died on May 14, 2009, at the age of 69 from complications of brain cancer, an illness that he had fought with dignity and courage for more than a year1 (Figure 1). Thomas George Pickering (1940–2009). Tom was educated at Bryanston School in Blandford, England, where he won state and entrance scholarships. He went on to study medicine at Trinity College, Cambridge, and the Middlesex Hospital Medical School, London, where he graduated in 1966, being awarded the first Broderip Scholarship.2 His early postgraduate years were spent at Middlesex Hospital and the Radcliffe Infirmary. He sat for the membership of the Royal College of Physicians of London in 1968 (becoming a fellow in 1980) and went on to earn a PhD degree at Oxford University in 1970. In 1972, he went to New York to take up appointments as Associate Physician at the Rockefeller University Hospital and Assistant Professor at Cornell University, and he spent 2 years as Assistant Professor at the Rockefeller University working with Neal Miller on biofeedback mechanisms. He was appointed Assistant Physician to the New York Hospital in 1974. He later returned to the Radcliffe Infirmary to work with Peter Sleight on research into baroreceptor function, the autonomic nervous system, and the emerging class of cardiovascular medications, known as the adrenoreceptor blockers. He was attracted back to New York City by the possibility of being able to work as both a practicing physician and a clinical investigator and he spent more than 20 years in a productive career in behavioral cardiovascular medicine, clinical hypertension, and blood pressure (BP) measurement research at Cornell University Medical College. In 2000, he became Director of Behavioural Cardiovascular Health and the Hypertension Program at the Cardiovascular Institute of Mount Sinai Medical Center and in 2003 he moved to Columbia University Medical College as Professor of Medicine and Director of the Behavioural Cardiovascular Health and Hypertension Program.3 So much for Dr Pickering, the scientist, what about Tom the man we came to love and admire? Tom was the quintessential Englishman, mannerly, gentle, and gentlemanly (the two must not be confused) whose enquiring mind was tinged with that spirit of philosophy whereby he knew nothing was new under the sun, but that what was fundamental to science was the expression of fact and the style of that expression. He was aware that each small brick added to the edifice of knowledge would enhance our understanding of hypertension and ultimately benefit those we graduated to serve as doctors—our patients. My first contact with the Pickering family was with Tom’s father, Sir George Pickering, when we were seated together on a bus taking us from the airport to a hotel in Valetta in 1975. I recall a man of small stature in an incredibly grubby raincoat who talked animatedly to me about the new drugs for the treatment of hypertension. However, my abiding memory is of his kindness to me the following morning when I was the first speaker in a session chaired by him in what was probably my first address to an international audience (Figure 2). As I prepared to begin my presentation there was the unmistakable sound of slides cascading from a carousel to the floor, whereupon Sir George looking encouragingly at me said “And now we will see how the young doctor from Dublin can convince us without slides!” Fortunately, during my sleepless night of rehearsing my lecture I had written prompt cards for each slide a precaution acknowledged by Sir George as “being a lesson to us all not to rely on slides.” Tom’s mother, Lady Carola, was a regular attendee at the British Hypertension Memorial Lectures named after her late husband. The most memorable of these was the ninth Sir George Pickering Lecture delivered in Dublin by Tom in September 1991 on “Ambulatory Monitoring and the Definition of Hypertension.” At dinner at the Royal College of Surgeons she remarked to me: “Eoin, I am so pleased; I never thought Tom had it in him.” How little mothers know their sons and how much more science Tom had in him! Sir George Pickering (1904–1980). Ambulatory BP measurement (ABPM), which has been available in one form or another for some 40 years, was developed initially to determine the efficacy of BP-lowering drugs.4, 5 Although assessing the BP-lowering efficacy of antihypertensive drugs over the 24-hour period is a logical scientific premise, the ability to do so has been dependent on technological developments. The first advance was the introduction of a direct intra-arterial technique for the measurement of BP continuously over the 24-hour period.5 More than 30 years ago, a series of studies using direct intra-arterial ABPM to provide continuous 24-hour BP was conducted by Jim Raftery and his group at Northwick Park Hospital in London and by John Floras and Peter Sleight at the John Radcliffe Hospital in Oxford in which the value of ABPM in assessing the efficacy of BP-lowering drugs was dramatically demonstrated.6-9 In the earliest of these studies, atenolol taken once daily in the morning was shown to lower BP during the day but to have little effect on either nighttime BP or the morning rise in BP (Figure 3). The prescient conclusions of this study merit quoting in full because they are as relevant today as when they were written in 1979: Plot of the effect of atenolol on 24-hour ambulatory blood pressure monitoring.7 The circadian rhythm of BP raises many questions about the timing of antihypertensive drug dosage and the effects of traditional regimens. Single measurements in outpatient clinics are unlikely to yield useful information on the effects of drugs on this basic cycle. If treatment aims at lowering BP to a ‘normal’ level (140/90 mm Hg) clearly it is desirable to lower it to that level throughout the 24-hour cycle. 7 The Oxford Group used intra-arterial ABPM to demonstrate the difference in efficacy and 24-hour duration of action between four β-blocking drugs—atenolol, metoprolol, pindolol, and slow-release propranolol—in a double-blind randomized study (Figure 4). Whereas all 4 β-blockers achieved a significant reduction in mean arterial BP 28 hours after the last single daily dose was taken, the extent to which each drug lowered BP differed during 24 hours and had clinic BP only been measured no difference between these 4 drugs would have emerged.8 However, direct intra-arterial ABPM was not without risk and the technique posed ethical issues that precluded its use except in a few specialized centers.9 Plot of the effect of four beta-blockers on 24-hours ambulatory blood pressure monitoring.8 Efforts were focused, therefore, on developing a device that would record ambulant BP noninvasively and, in the 1960s, the Remler device, which was capable of measuring BP intermittently during the daytime period, provided clinicians with a new technique for evaluating antihypertensive drugs.10, 11 This device yielded interesting information on drug efficacy but was limited by having to be operated by the patient, which made the recording of nocturnal BP impractical. The early studies on drug efficacy using ABPM yielded interesting information on the discrepancy between clinic BP and ABPM.9 First, ABPM could be in agreement with clinic BP measurements. In such studies, where a clinic fall in BP was confirmed by ABPM, the latter also demonstrated what conventional BP measurement can never show, namely, the duration of antihypertensive effect over the dosing interval. Second, clinic BP measurement could fail to detect the BP-lowering effect demonstrated by ABPM. The studies showing this phenomenon used smaller numbers, and for this reason their power to detect differences between treatments with clinic BP measurement was low. However, the greater number of observations available with ABPM, by reducing within-subject variability, compensated to some extent for this deficiency. Finally, reductions in clinic BP could be significant, but ABPM might be either nonconfirmatory or show that the clinic BP reduction coincided only with a brief period of BP reduction on ABPM. Of considerable practical importance was the fact that many drugs would have been declared as effective BP-lowering agents by conventional BP measurement, whereas ABPM showed a pattern of activity that was far less impressive.9 That drugs continue to be assessed for efficacy with conventional clinic BP is an even greater indictment of clinical science today than when the following statement was made in 1989: “The time has surely come where studies of antihypertensive drug efficacy which do not assess BP over 24 hours should no longer be acceptable.12” Although ABPM was confined initially to clinical trials, the advent of automated devices capable of measuring BP at predetermined intervals over the 24-hour period in the 1980s allowed ABPM to be hailed as “an idea whose time has come.13” The broader use of ABPM in clinical practice was given major expression with the publication of a seminal paper by Dorothee Perloff and Maurice Sokolov in The Journal of the American Medical Association (JAMA) in 1983 when they showed for the first time that ABPM was superior to conventional BP in predicting cardiovascular outcome.14 These pioneering contributions provided Thomas Pickering with the solid foundations on which to build a lasting edifice to ABPM. Whereas Tom would be the first to acknowledge that his contributions were dependent on the supportive research from his many international collaborators and friends, the constraints of time and space do not make it possible for me to indicate these here. Pickering was an advocate of out-of-office BP measurement and his publications, particularly in the technique of ABPM, were influential in changing our approach to the diagnosis and management of hypertension. When he wrote, “The addition of ABPM to conventional clinic measurements for defining BP status in clinical practice has added a new complexity to the process, because the separation of normotension and hypertension can be assessed independently by each of the two methods,”15 he research and practice on two of who are of such importance that the practice of medicine has had to to their with and hypertension. with these continue to and but their on clinical practice is a to in to He also made a significant to the BP during the nocturnal period of ABPM. His to of hypertension most the of and the of BP by is the my In his seminal paper in in Pickering the hypertension to whose BP is in the but not during daytime the of the of the ambulatory BP in mm Hg) as a he showed that of with hypertension and of with hypertension had hypertension. He that by conventional BP measurement with ABPM, it would possible to at in the of treatment might be and in a longer period of might be as Pickering on their the of this study do not or when in the of they the possibility of being able to a group in the to treatment is in for hypertension or effect up over to the that the importance of the in clinical practice However, the practical is by a study showing that of hypertension with ABPM would in antihypertensive drug treatment being in and drug treatment being in of At an the benefit of hypertension using ABPM has been clearly demonstrated in the which showed that BP was assessed by ABPM so that the effect was of were as with only when BP was assessed by conventional These from clinical and practice should with who should that could be made by ABPM for the diagnosis and of with hypertension (Figure hypertension. In another paper in Pickering the to what had hypertension and This who to be in a but who have an ABPM. of the of ABPM over BP measurement in predicting such can be as In with this Pickering showed that with hypertension have more than He that the of hypertension in to be at with a to with is a thought that even hypertension is only in of the this into in the The clinical importance of the is that BP is assessed with BP measurement in a with a of cardiovascular a or the doctor will and a but the the most treatment to a cardiovascular BP-lowering in the that the is The has been to in the is as Pickering has to up to the of hypertension in and it is not practical to ABPM in all with normotension in the or clinic to those with ambulatory hypertension. the of not hypertension for patients. The of hypertension in at of and and the of the phenomenon of hypertension in some of that conventional measurement has the for more than of who to to have BP the many of ABPM, this which is must surely make the for ABPM being an for the diagnosis and management of hypertension in and (Figure Pickering the nocturnal period of the 24-hour as being of importance both as a of BP and also as a for we first the to who had a fall in nocturnal BP as from those who had of nocturnal BP and a cardiovascular studies have this In Pickering 24-hour BP in with hypertension, and with In this study he the of his some 20 years he not state showing that had their BP during work or at the clinic and the during studies have clearly demonstrated that ABPM should be during the day so as to detect the of BP in the day time and nighttime each of which hypertension. ambulatory blood pressure daytime hypertension mm daytime hypertension mm and and blood ambulatory blood pressure 24-hour and hypertension mm daytime and mm and by of was the and he to This was particularly in the research he with his the of the morning of BP in the of cardiovascular study on the of the morning in form the value of the morning in BP in morning the of the was an risk for and cardiovascular and in whereas a or morning in BP mm was probably not with an risk of or cardiovascular The of the morning with the being in the as to how the phenomenon is In Pickering the international for ABPM and that there was international agreement in of the use of ABPM in clinical In a later in in the New Journal of he the of the Institute for in the when he ABPM for all of having ABPM is used only in the of with hypertension, but its use is The are to and Ambulatory can be as the for the of risk to studies have shown that it clinical than conventional blood pressure measurements. a can be made for using this technique in all in hypertension has been by of clinic blood pressure measurements. is therefore, to the international from to the time to see the for the use of ABPM in clinical practice have Pickering made his prescient not only the clinical practice of medicine, but they also serve as a of Of the all were in agreement that ABPM is for the or of hypertension. but one were in agreement that ABPM is for the of a diagnosis of and to with ABPM to assess drug efficacy over the 24-hour period and for the of the nocturnal status and more than the ABPM to hypertension 1). The Institute for Health and in has a considerable of for its for when the ABPM are it will be that they are at with international in that not advocate the use of ABPM to with hypertension, to drug efficacy over the 24-hour period, to assess nocturnal or to hypertension on the that as not the technique in these the form international is that for the first time it is that ABPM should be to of having hypertension by of having had an conventional BP the clinic BP is mm or ABPM to the diagnosis of In the has for what international have been as This is not only a on but by has to the that hypertension can be when in fact there are no clinical or that of the on the I it is now on all who with hypertension to be able to ABPM to of having hypertension, which whose BP has been to be and that the technique should be an of with this and in with what I know would have been I will now address what I are for science and how a technique be it is not made and it will not its When I became in hypertension in the I was by Sir George from direct 24-hour BP using direct intra-arterial BP measurement, but I that the technique would not be to clinical the Remler as an the considerable of ABPM became with a with hypertension, the doctor should be to hypertension some has been made to the of BP over ambulatory BP measurement is the to do When Pickering was his for the in we how ABPM might be made more to with hypertension and he the for the from a 24-hour ambulatory recording in this paper and later me to continue with my to ABPM and make it more this I had developed with my the that was capable of the following with presentation and of with for clinical use with of more for for so as to the for a physician to with benefit (Figure of showing the efficacy or of treatment during the day time and nighttime of to the of BP of to and to to ABPM by patients. of ambulatory blood pressure ABPM and by In years, have been as having an in and particularly in BP ABPM has been to in using the of and The is with and is being by the If the ABPM in a is the is to the to at their but the ABPM is as is given to make an as as The of an ABPM in are greater of ABPM to the in a and than having to a or the of an and to the who is as to the or in BP between the and the and of in a to provide information in a on BP is that an ABPM provided by less than when it is by The of in the management of hypertension has been one of the most of the ABPM in In Pickering for the first time that the of from and would provide a of assessing the of of the ABPM and on cardiovascular and he that having from a number of would for the of differences in the expression of cardiovascular from the international showed that hypertension might not be a for in the and that a or pattern at cardiovascular risk at level of 24-hour mean Pickering was to the in his scientific to the value of the value of which have been The of a is to a that study to so as to be able to the and to study to that scientific research and and of are many from a practicing a might provide that can be used to assess the degree to which clinicians are a in with on of a that might be or provide for clinicians to with their a can provide information from of on how or are used and on their in This information also be useful for a drug or device a study might demonstrate the of a in the a or or that will be useful for clinical and ultimately benefit by having their the of and should a new treatment can in has been shown that in clinical than the research in with hypertension, in a clinical to which by to BP should the of and cardiovascular of from and can provide a of clinical and and and an in the use of such can and for and, most can take one in which the for and is to its for from to by about and in during to If the could its of to by it would of a of number of have to for ABPM but it is to that some of these are in that they do not the full for the of a an being the Dublin which has from more than over a as the for a The scientific to of ABPM is now with of being in and the be a of ABPM must use a that is capable of and of for and scientific The of ABPM are that are able to rely on for the management of hypertension and to the degree of BP The most of a ABPM has been the ABPM which has the of BP in that and the international approach to the diagnosis and treatment of The by Pickering to international ABPM by has been with the of two major international The on Ambulatory Monitoring in to Cardiovascular has on ABPM from in many and has a number of on the value of The is an international ABPM of from hypertension clinics in that aims to assess the of of measurement in cardiovascular is the of in the and of which the in the Medical has from of the in to in This in has been by an in that the in is a but there are clearly in which both could be made and could be in in the and less than have it is now that and are at and are of in the If all were to the in clinical might be each The with hypertension are of and of In an to these and the of Health and has the which aims to and in the 5 This is but it will not be achieved BP measurement to be measured with conventional in the I have and demonstrated that ABPM is not only for clinical but that it is also to make it available on a in the is that the that two of its will be to on the use of information to management of risk and and to make use of that will such as in and risk to be as a from a small that has had with but made by the of the that Tom Pickering I would the that are on the of the on and of to what has been so in the in to I would that should be in one than or international in not only ABPM as an technique in clinical but that in the from ABPM should be so as to provide a BP with the of such a and the of ABPM in and as in and in the of the can be achieved and even us not in our for than we should the for to our The of the the in the for that not only will be but the of clinical science be the studies to are that in some could take more than a This is not to that the for should be but that it should not by the of is an that I have not but one which I the to acknowledge the of to do so on it with the of international in hypertension having the in many that ABPM should be to from hypertension, surely the to provide such a for who the cardiovascular complications of hypertension must be a for in the us as and to acknowledge the of and no longer to the to make ABPM available not only for the diagnosis but also for the management of with hypertension. I that Tom would the I have in the first lecture to his to the science and practice of hypertension (Figure I know that he would be in agreement with the made in years to make ABPM more to and that he would be that international is at last his that the technique should be to clinical is a to be able to acknowledge the of and in this In the American of Hypertension for me with this I would to that the might to now a Thomas Pickering to young in hypertension Dr Pickering in a with the and a at the Ambulatory Monitoring Group in the Royal College of Surgeons of of is Medical and of
Eoin OʼBrien (Mon,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: