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HISTORICAL PERSPECTIVE The man who coined the term “blood pressure” almost 300 years ago was an En­ glish scientist, the Reverend Stephen Hales (1, 2). Hales first mea­ sured blood pressure (BP) in a series of famous experiments during the first quarter of the eigh­ teenth ­ century. He assessed arterial BP directly and invasively, first in dogs in 1708 and ­ later in­ horses in 1714, by vertically inserting a long glass tube directly into an incision made in the carotid artery and recording the height of blood in the tube (3). In 1628, the En­ glish physician William Harvey introduced the theory of blood circulation, in which the arterial pulse was first understood to be a pressure wave originating from the heart’s contractions (4). By the eigh­ teenth ­ century, pulsus magnus durus et tardus—­ a hardness of the pulse—­ was well associated with increased arterial pressure (5). The sphygmometer, or sphygmograph, was introduced in 1834 by the French physician Jules Hérisson to display and rec­ ord the arterial pulse wave (6), and his countryman, physiologist Etienne-­ Jules Marey, performed the first proper analy­ sis of the pulse wave in ­ humans (7). In 1896 and 1897, an Italian doctor, Scipione Riva-­ Rocci, described a ­ simple mercury sphygmomanometer that was the forerunner of the modern device (8,9). In 1905, Nicolai Korotkoff, a Rus­ sian physician, described the auscultatory sounds that ­ today bear his name and provide the basis for modern noninvasive BP mea­ sure­ ment (10,11,12). Misunderstanding of the Use of Blood Pressure in Diagnosing Hypertension Soon ­ after the sphygmomanometer was introduced into medical practice, observations based on case studies documented the association of high levels of arterial pressure with renal, vascular, and cardiac diseases (13,14). Recommended upper limits of normal BP ­ were based on arbitrary values, depending on the opinions of individual medical prac­ ti­ tion­ ers (15,16). Yet, in the opinion of some eminent prac­ ti­ tion­ ers, high BP was considered beneficial (17). In an address given in 1912 before the Glasgow Southern Medical Society, Sir William Osler made the following statement about high BP CHAPTER 9 Iatrogenicity of Blood Pressure Mea­ sure­ ment in the Diagnosis of Hypertension Thomas D. Giles, Gary E. Sander, and Camilo Fernandez Role of Drugs in Producing Hypertension / 89 respond with the value of the BP recordings that he obtained in his office. He then arranged for the recording of BP outside of the office and reported the discordance (22). This has since been termed “white-­ coat effect” (23). Unfortunately, no conclusive agreement exists on ­ whether WCH individuals have shown more pronounced subclinical organ damage and a less favorable cardiovascular prognosis than their true normotensive counter­ parts (24,25,26). Cross-­ sectional studies aimed at investigating organ damage (as assessed by markers with proven prognostic value such as left ventricular hypertrophy, carotid intima-­ media thickness [IMT], and microalbuminuria ) in patients with WCH compared with normotensive and sustained hypertensives have yielded equivocal findings (25,27,30). Moreover , in some studies the risk of cardiovascular events in the WCH group has been shown to be similar to that in the masked hypertension group (28,29,30). ROLE OF DRUGS IN PRODUCING HYPERTENSION Drugs, as well as herbal preparations and industrial chemicals, may elevate BP or impair responses to antihypertensive medi­ cations; thus, elevated blood pressure in individuals exposed to such molecules may artificially suggest chronic cardiovascular disease (31,32,33). This “hypertension ” is iatrogenic and can be cured simply by removing the offending substance (31). It is imperative to consider the role of such substances in the evaluation of BP, particularly hypertension of recent-­ onset and resistant hypertension, as has been emphasized in the Seventh Report of the Joint National Committee on Prevention, Detection , Evaluation, and Treatment of High Blood Pressure (JNC 7) (34).The so-­ called iceberg effect refers to a very common situation in which a drug may significantly increase BP, but the resultant BP still remains within the normal range according to JNC 7 (34) or JNC 8 (35) criteria. Clinical trial data and adverse drug reporting most often describe only new hypertension (equal to or greater than 140/90 mmHg), rather than significant increases within the normal range (e.g., 20/10 mmHg). ­ These small but significant increases within the normal range elevate associated with atherosclerosis: “In this group of cases it is well to recognize that the extra pressure is a necessity—as purely a mechanical affair as in any ­ great irrigation system...


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