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SECOND
EDITION
HYPERTENSION
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JAMES
SWAPNIL
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SECOND EDITION
HYPERTENSION
EDGAR V. LERMA, MD
Clinical Professor of Medicine
Section of Nephrology
University of Illinois at
Chicago College of Medicine
Associates in Nephrology, SC
Chicago, IL
JAMES M. LUTHER, MD
Associate Professor of Medicine
Clinical Pharmacology
Vanderbilt University Medical Center
Nashville, TN
SWAPNIL HIREMATH, MD
Associate Professor of Medicine
University of Ottawa;
Associate Scientist
Clinical Epidemiology
Ottawa Hospital Research Institute
Ottawa, ON
Canada
Elsevier
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
Hypertension Secrets, Second Edition ISBN: 978-0-323-75852-9
Copyright © 2023 by Elsevier, Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system,
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This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein)
Notices
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of
rapid advances in the medical sciences, in particular, independent verication of diagnoses and drug
dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier,
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Printed in the United states of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1
To all my mentors, colleagues, and friends, at the University of Santo Tomas
https://t.me/med1917
Faculty of Medicine and Surgery in Manila, Philippines, Mercy Hospital and
Medical Center and Northwestern University Feinberg School of Medicine in
Chicago, IL, who have in one way or another, influenced and guided me to
become the physician that I am.
To all the medical students, interns, and residents at Advocate Christ Medical
Center whom I have taught or learned from, especially those who eventually
decided to pursue nephrology as a career.
To my parents and my brothers, without whose unwavering love and support
through the good and bad times, I would not have persevered and reached my
goals in life.
Most especially, to my two lovely and precious daughters, Anastasia Zofia and
Isabella Ann, whose smiles and laughter constantly provide me unparalleled joy
and happiness, and my very loving and understanding wife Michelle, who has
always been supportive of my endeavors both personally and professionally,
and who sacrificed a lot of time and exhibited unwavering patience as I
devoted a significant amount of time and effort to this project. Truly, they
provide me with constant motivation and inspiration.
Edgar V. Lerma, MD
To my family, the primary source of joy in life. To my teachers, colleagues and
mentors who instilled the appreciation and love of hypertension physiology.
And especially to the late Dr. John Oates, who established an academic culture
of inquisitiveness in both the research and clinical settings and has trained
multiple generations of physicians.
James M. Luther, MD
To my mentors, colleagues, and teachers, in particular Marcel Ruzicka, Peter
To my long-suffering wife and children who have let me pursue the 5 to 9
Magner, George Fodor, and Alan Almeida.
passion of FOAMed.
Swapnil Hiremath, MD
CONTRIBUTORS
https://t.me/med1917
Blaise W. Abramovitz, DO
Division of Renal-Electrolyte, Department of Medicine,
University of Pittsburgh School of Medicine, Pittsburgh, PA
Rajiv Agarwal, MD, MS
Division of Nephrology, Department of Medicine,
Indiana University School of Medicine and Richard L.
Roudebush Veterans Administration Medical Center,
Indianapolis, IN
Sarah Ahmad, MD
Renal-Electrolyte and Hypertension Division,
Department of Medicine, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA
Matthew R. Alexander, MD, PhD
Department of Medicine, Division of Cardiovascular Medicine,
Vanderbilt University Medical Center, Nashville, TN
Ibrahim A. AlQassas, MD
Internal Medicne Specialist (Senior Registrar),
International Medical Center, Jeddah, Saudi Arabia
Juan P. Arroyo, MD PhD
Nephrology Fellow, Medicine, Vanderbilt University
Medical Center, Nashville, TN
Christopher Asuzu, MD
Division of Nephrology, Department of Medicine,
Duke University School of Medicine, Durham, NC
Ali Ayesh, MD
Nephrology
Wayne State University
Farmington, MI
George Bakris, MD, MA
Professor and Director, AHA Comprehensive Hypertension
Center, Medicine, The University of Chicago Medicine,
Chicago, IL
Atul Bali, MD, CHS, FASN, FNKF
Divisions of Nephrology, Department of Medicine,
University of Virginia Health System, Charlottesville, VA
Joshua A. Beckman, MD
Director, Section of Vascular Medicine,
Cardiovascular Division, Vanderbilt University Medical
Center, Nashville, TN
Fabian Bock, MD, PhD
Division of Nephrology and Hypertension,
Vanderbilt University Medical Center, Nashville, TN
Ann Bugeja, MD
University of Ottawa, Ottawa, Ontario, Canada;
The Ottawa Hospital, Ottawa, Ontario, Canada
Anna Burgner, MD, MEHP
Assistant Professor, Internal Medicine, Vanderbilt
University Medical Center, Nashville, TN;
Assistant Professor, Division of Nephrology and
Hypertension, Vanderbilt University Medical Center,
Nashville, TN
Robert M. Carey, MD, MACP
Divisions of Endocrinology and Metabolism,
Department of Medicine, University of Virginia Health System,
Charlottesville, VA
Jordana B. Cohen, MD, MSCE
Renal-Electrolyte and Hypertension Division, Department
of Medicine, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA;
Department of Biostatistics, Epidemiology and Informatics,
Perelman School of Medicine, University of Pennsylvania,
Philadelphia, PA
Beatrice P. Concepcion, MD
Division of Nephrology and Hypertension,
Vanderbilt University Medical Center, Nashville, TN
Christine Dillingham, MD
Eastern Nephrology Associates, North Myrtle Beach, SC
Luciano F. Drager, MD, PhD
Heart Institute (InCor), Hypertension Unit, University of
Sao Paulo Medical School, Brazil; Hypertension Unit,
Renal Division, University of Sao Paulo Medical School,
Brazil
George K. Dresser, MD, PhD, FRCPC, FACP
Associate Professor of Medicine, Schulich School of
Medicine and Dentistry, University of Western Ontario,
London, Ontario, Canada
Garabed Eknoyan, MD
Selzman Institute of Kidney Health, Section of Nephrology,
Department of Medicine, Baylor College of Medicine,
Houston, TX
David Ellison, MD
Professor, Internal Medicine, Oregon Health & Science
University, Portland, OR; Staff Physician,
VA Portland Health Care System, Portland, OR
Uta Erdbrugger, MD
Divisions of Nephrology, Department of Medicine,
University of Virginia Health System, Charlottesville, VA
Maureen C. Farrell, MS
Drexel University College of Medicine, Philadelphia, PA
Ryan P. Flood, DO
Division of Nephrology, Department of Medicine,
University of Colorado Anschutz Medical Campus,
Aurora, CO
vi
CONTRIBUTORS vii
https://t.me/med1917
Joseph T. Flynn, MD, MS
Professor of Pediatrics, University of Washington School
of Medicine; Division of Nephrology, Seattle Children’s
Hospital, Seattle, WA
Panagiotis I. Georgianos, MD, PhD
Section of Nephrology and Hypertension, 1st Department
of Medicine, AHEPA Hospital, Aristotle University of
Thessaloniki, Thessaloniki, Greece
Sarah Gilligan, MD MPH
Division of Nephrology and Hypertension,
University of Utah Health, Salt Lake City, UT
Christin Giordano McAuliffe, MD
Fellow, Medicine, Vanderbilt University Medical Center,
Nasvhille, TN
Swapnil Hiremath, MD
Associate Professor of Medicine
University of Ottawa;
Associate Scientist
Clinical Epidemiology
Ottawa Hospital Research Institute
Ottawa, ON
Canada
Tara A. Holder, MD
Cardiovascular Fellow, Cardiovascular Medicine,
Vanderbilt University Medical Center, Nashville, TN
Jiun-Ruey Hu, MD, MPH
Resident Physician, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN
Irma Husain, MD
Division of Nephrology, Department of Medicine,
Duke University School of Medicine, Durham, NC
Nashat Imran, MD, FASN, FACP
Associate Professor of Medicine, Division of Nephrology
and Hypertension, Wayne State University School of
Medicine, Detroit, MI
Eric Judd, MD, MS
Associate Professor of Medicine, University of Alabama at
Birmingham, Division of Nephrology, Birmingham, AL
Talar B. Kharadjian, MD
Fellow, Nephrology-Hypertension, University of California,
San Diego, San Diego, CA
Esther S. Kim, MD, MPH
Department of Medicine, Division of Cardiovascular Medicine,
Vanderbilt University Medical Center, Nashville, TN
Cassandra Kovach, MD
Nephrology and Hypertension, Cleveland Clinic,
Cleveland, OH
Arun Kumar, MD
Attending Physician, Nephrology, Emory North Decatur
Hospital, Decatur, GA
Edgar V. Lerma, MD
Clinical Professor of Medicine
Section of Nephrology
University of Illinois at Chicago College of
Medicine
Associates in Nephrology, SC
Chicago, IL
Julia B. Lewis, MD
Division of Nephrology and Hypertension,
Vanderbilt University Medical Center, Nashville, TN
Renata Libianto, MBBS, BMedSci, FRACP
Fellow, Endocrinology, Monash Health, Melbourne,
Australia
Matthew Lloyd, BSc, PhD
Department of Cardiac Sciences, Libin Cardiovascular
Institute of Alberta, University of Calgary, Calgary,
Alberta, Canada
James M. Luther, MD
Associate Professor of Medicine
Clinical Pharmacology
Vanderbilt University Medical Center
Nashville, TN
Rakesh Malhotra, MD, MPH
Division of Nephrology- Hypertension, University of California,
San Diego, San Diego, CA
Hina N. Mehta, MD
Division of Hospital Medicine, Department of Internal
Medicine, UT Southwestern Medical Center,
Dallas, TX
John R. Montford, MD
Division of Nephrology, Department of Medicine,
University of Colorado Anschutz Medical Campus,
Aurora, CO; Division of Nephrology, Eastern Colorado VA
Healthcare System, Rocky Mountain Regional VA Medical
Center, Aurora, CO
Jonathan D. Mosley, MD
Assistant Professor, Internal Medicine,
Vanderbilt University Medical Center, Nashville, TN;
Assistant Professor, Biomedical Informatics,
Vanderbilt University Medical Center, Nashville, TN
Bilal Munir, MD
Department of Internal Medicine, London Health Sciences
Centre, London, ON, Canada
Raj Padwal, MD, MSc
Department of Medicine, University of Alberta, Edmonton,
Alberta, Canada; Women and Children’s Health Research
Institute (WICHRI), Edmonton, Alberta, Canada
Trisha Patel, DO
Resident Physician, Department of Internal Medicine,
Advocate Christ Medical Center, Oak Lawn, IL
Aldo J. Peixoto, MD
Department of Internal Medicine and Section of
Nephrology, Yale School of Medicine. New Haven, CT;
Hypertension Program at the Yale New Haven Hospital
Heart and Vascular Center. New Haven, CT
Nishigandha Pradhan, MD
Division of Nephrology and Hypertension,
University Hospitals Cleveland Medical Center,
Case Western Reserve University, Cleveland, OH
J. Howard Pratt, MD
Division of Endocrinology, Department of Medicine,
Indiana University School of Medicine, Indianapolis, IN
viii CONTRIBUTORS
https://t.me/med1917
Akshan Puar, MD
Division of Endocrinology, Department of Medicine,
Indiana University School of Medicine, Indianapolis, IN
Simon W. Rabkin, MD, BSc(Med)
Division of Cardiology, Department of Medicine,
University of British Columbia, Vancouver, British Columbia,
Canada
Mahboob Rahman, MD
Division of Nephrology and Hypertension,
University Hospitals Cleveland Medical Center,
Case Western Reserve University, Cleveland OH;
Louis Stokes Cleveland VA Medical Center, Cleveland OH
Satish R. Raj, MD, MSCI, FHRS, FRCPC
Department of Cardiac Sciences, Libin Cardiovascular
Institute of Alberta, University of Calgary, Calgary,
Alberta, Canada; Autonomic Dysfunction Center, Division
of Clinical Pharmacology, Department of Medicine,
Vanderbilt University Medical Center, Nashville, TN
Nirupama Ramkumar, MD MPH
Division of Nephrology and Hypertension,
University of Utah Health, Salt Lake City, UT
Fitra Rianto, MD
Division of Nephrology, Department of Medicine,
Duke University School of Medicine, Durham, NC
Jennifer Ringrose, BSc, MSc, MD
Department of Medicine, University of Alberta, Edmonton,
Alberta, Canada; Women and Children’s Health Research
Institute (WICHRI), Edmonton, Alberta, Canada
Marcel Ruzicka, MD, PhD, FRCPC
Associate Professor, Division of Nephrology, University of
Ottawa, Ottawa, Ontario, Canada; Medical Director,
Renal Hypertension Program, TOH-Riverside Campus,
Ottawa, Ontario, Canada
Carlos A. Schiavon, MD
Bariatric Surgery Center - BP Hospital – Sao Paulo, Brazil;
Research Institute - Heart Hospital (HCor) - Sao Paulo,
Brazil
Michel Shamy, MD, MA, FRCPC
Department of Medicine, University of Ottawa and The
Ottawa Hospital & Research Institute
Saed Shawar, MD
Division of Nephrology and Hypertension,
Vanderbilt University Medical Center, Nashville, TN
Cyndya A. Shibao, MD, MSCI
Department of Medicine, Division of Clinical Pharmacology,
Vanderbilt Autonomic Dysfunction Center,
Vanderbilt University Medical Center, Nashville, TN
Matthew A. Sparks, MD
Division of Nephrology, Department of Medicine,
Duke University School of Medicine, Durham, NC;
Renal Section, Durham VA Medical Center, Durham, NC
Hillel Sternlicht, MD
Assistant Professor of Medicine
Internal Medicine, Division of Nephrology & Hypertension
Wayne State University School of Medicine
Detroit, MI
Craig Sussman, MD
Associate Professor of Clinical Medicine, Vanderbilt
University Medical Center, Nashville, TN
Andrew Terker, MD PhD
Fellow, Nephrology, Vanderbilt University Medical Center,
Nashville, TN
Yuta Tezuka, MD, PhD
Division of Metabolism, Endocrinology and Diabetes,
University of Michigan, Ann Arbor, MI
Karen C. Tran, MD, MHSc, FRCPC
Division of General Internal Medicine,
Department of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada
Adina F. Turcu, MD, MS
Division of Metabolism, Endocrinology and Diabetes,
University of Michigan, Ann Arbor, MI
Anand Vaidya, MD MMSc
Director, Center for Adrenal Disorders, Brigham and
Women’s Hospital, Boston, MA;
Associate Professor of Medicine, Harvard Medical School,
Boston, MA
Jun Yang, MBBS (Hon), PhD, FRACP
Endocrine Hypertension Service, Hudson Institute of
Medical Research, Clayton, Victoria, Australia
PREFACE
https://t.me/med1917
In medicine, the time-honored Socratic method has been the predominant influence in the teaching styles used by various institutions of higher learning, both locally and internationally. In keeping with this very effective teaching method,
the first edition of Anthony Zollo’s Medical Secrets was published in 1991. The subtitle was “Questions you will be
asked on rounds, in the clinic, and on oral exams.” The book was very successful, as it appealed not only to the learners but also to the teachers. Subsequently, various fields of medicine came out with their own editions, with particular
focus on individual specialties.
In 2020 we gathered a select group of highly motivated individuals who were well-renowned authoritative figures
in the field of hypertension and who had exemplary reputations with regard to the profession of teaching medicine. In
keeping with the design of the original Medical Secrets, we have included questions on everyday topics in addition to
some “zebras” with particular academic interest.
We hope that this book will be used not only by nephrologists and nephrology fellows, medical residents and
interns, and medical students, but also by primary care providers with particular interest in this very exciting field of
medicine.
From personal experience, we know that very few people read a textbook from cover to cover. For a variety of
reasons, the majority would read only one or a few chapters at any given time. Therefore, we tried to ensure that each
chapter would be complete in itself. As a consequence, there is unavoidable overlap among some of the information
provided in some chapters; we, however, feel that this was truly necessary, at least from an information-retrieving
standpoint, and in this way it will not be necessary for readers to read bits of information between one or more
chapters just to get complete information regarding a particular subject.
Certainly this book would not have been possible were it not for so many people. First, we would like to thank the
contributing authors, who have spent countless hours in producing high-quality, up-to-the-last-minute information that
we would characterize as “edutaining.” We spent a significant amount of time communicating via telephone and e-mail
as we reviewed the chapters and discussed recommendations, most of which were agreed upon, but, on occasion,
disputed. We express our sincere gratitude for their openness to this very collegial collaboration, which has been a truly
rewarding learning experience for us.
In particular, we appreciate the help and support of all the staff of Elsevier, most especially Sara Watkins and
Nicole Congleton, our Developmental Editors, and Marybeth Thiel, our Production Editor, all of whom have been very
patient with our procrastinations and stubbornness at times.
We thank our teachers and mentors, who devoted their own time to educate and train us to become who we
are. We thank all the medical students, residents, and fellows who in one way or another have given us inspiration
to persevere in the teaching profession. Mostly, we thank all of our patients, who have been truly instrumental in our
learning and devotion to medicine. On behalf of all the contributors to this book, we fervently hope that all our efforts
will contribute to relieving your suffering and perhaps lead to your recovery.
Edgar V. Lerma, MD
James M. Luther, MD
Swapnil Hiremath, MD
ix
B978-0-323-75852-9.00044-810.1016/B978-0-323-75852-9.00044-8978-0-323-75852-9Elsevier Inc.
https://t.me/med1917
TOP 100 SECRETS
1. Use of automated blood pressure (BP) measurement, particularly automated office BP (AOBP), minimizes
many common observer-related sources of error in office BP measurement.
2. Office BP measurement should be supplemented with out-of-office measurements to better inform diagnostic
and treatment decisions.
3. Out-of-office BP monitoring with ambulatory or home BP monitors (ABPM or HBPM) should be used for the
diagnosis and monitoring of hypertension due to the ability to identify abnormal BP patterns that cannot be
identified using clinic BP monitoring alone.
4. It is critical to use a validated device to perform home BP monitoring.
5. Pseudohypertension is thought to occur in elderly individuals who have stiff or rigid arteries; it should be
suspected in elderly patients who present with relatively elevated BP readings in the absence of target organ
damage.
6. A hypertensive urgency might not differ from asymptomatic hypertension and it is important to try to rule out
the ‘acute recognition’ of chronic hypertension.
7. Common etiologies of a hypertensive emergency include: acute aortic dissection, acute coronary syndrome,
acute kidney injury, acute left ventricular failure, catecholamine-associated hypertension, hemorrhagic stroke
or acute ischemic stroke, hypertensive encephalopathy, preeclampsia/eclampsia.
8. With each decade of life, hypertension (HTN) becomes more common. By 75 years of age, more than 70% of
Americans meet criteria for HTN based on the ACC/AHA definitions.
9. Fewer than 50% of people living with HTN are aware of their underlying condition and only 15% have
achieved optimal BP control.
10. Minorities including African Americans and Mexican Americans are at higher risk of developing HTN, uncontrolled BP, and its associated complications.
11. Short-term regulation of blood pressure is mediated by the central nervous system through the baroreceptor
reflex arc and chemoreceptors.
12. Long term blood pressure control is mediated by the kidney and hormonal systems.
13. Chronically and acutely elevated blood pressures can cause target organ damage to the heart, blood vessels,
brain, kidneys, and eyes.
14. Stringent and consistent blood pressure control is the most effective way to reduce the risk of developing
primary and secondary target organ damage.
15. Only a minority of patients with primary aldosteronism (30%) present with hypokalemia; routine screening
identifies even more patients with normokalemia.
16. Most patients with primary aldosteronism (PA) are indistinguishable from patients with other forms of hypertension.
17. The aldosterone-to-renin ratio (ARR) remains as the recommended screening test for primary aldosteronism on the basis that isolated measurements of either plasma aldosterone concentration (PAC), direct renin
concentration (DRC), or plasma renin activity (PRA) show overlap with unaffected patients.
18. Cortisol circulates in higher concentrations than aldosterone; whereas cortisol and aldosterone have similar
affinity for the mineralocorticoid receptors, the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2)
serves as a gatekeeper, by inactivating cortisol to cortisone.
19. Whereas exogenous or iatrogenic Cushing syndrome (CS) is relatively common, endogenous CS is a rare
disease, with an incidence of 1 to 2 per million per year. Endogenous CS is most commonly caused by an
ACTH-producing pituitary adenoma, and this form of CS is also known as Cushing disease.
20. Testing for CS should take into account the possibility of circadian rhythm disruptions (such as night-shifts or
recent travel across time zones).
21. Apparent mineralocorticoid excess (AME) shares several clinical and laboratory features with primary aldosteronism: hypertension, hypokalemia, metabolic alkalosis and low renin.
22. When pheochromocytoma or paraganglioma is suspected, measuring plasma metanephrines or 24-hour
urinary metanephrines are both appropriate and have similar diagnostic accuracy, with sensitivity ∼97% and
specificity ∼90%.
23. Surgery is the treatment of choice for symptomatic and functional pheochromocytomas and paragangliomas.
24. Use of anabolic androgen steroids (AAS) is associated with increased 24-hour ambulatory blood pressure,
prevalent hypertension, reduced ventricular function, vascular calcification, and aortic stiffness.
xiii
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