Journal of Clinical Lipidology (2014) 8, 644–645
Obituary
Tribute to Dr Peter O. Kwiterovich, Jr, MD
The worlds of preventive cardiology, lipidology, and cardiovascular medicine lost one of its pioneers with the passing of Dr Peter O. Kwiterovich, Jr He succumbed after a long battle with metastatic prostate cancer at the age of 74. Peter was an internationally known expert on atherosclerotic vascular disease. He was the founder and director of the Johns Hopkins University Lipid Clinic. Dr George Dover, pediatrician-in-chief at Hopkins, said it best when he stated that Peter’s work transformed our understanding of fat metabolism and lipid malfunction and the role they play in fueling premature heart disease. His investigative and clinical work spanned nearly 50 years and defined what normal cholesterol values were for children. He also helped demonstrate the safety of statin therapy in adolescents with familial hypercholesterolemia. His research helped to delay or avert premature disability and death for many thousands of young adults. The University Lipid Clinic’s work was an early catalyst that shaped our approach to screening and cardiovascular disease prevention. It also filled important gaps in our understanding of the evolution of atherosclerotic vascular disease across the life spectrum. The way that he set up his University Lipid Clinic with a strong focus on lifestyle changes for the entire family was how we modeled the
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Peter greatly enjoyed teaching 2 generations of students, house staff, and postdoctoral fellows as well as his patients and their families. He loved science and he became a full professor at Johns Hopkins at a young age. As the son of a physician, he was exposed to science as a child. He was raised in Danville, Pennsylvania, and graduated from the College of Holy Cross in Worcester, Massachusetts. His interest in genetics was nurtured at both Dartmouth Medical School and at the Johns Hopkins School of Medicine under the tutelage of late Dr Victor A. McKusick, also known as the father of modern human genetics. He did his internship in pediatrics at Harvard’s Children’s Hospital and then worked for 3 years in the molecular disease branch of the National Heart, Lung, and Blood Institute. It was at the National Institutes of Health (NIH) that he developed a passion for understanding and treating inherited disorders of cholesterol metabolism. At NIH, he trained under Drs. Donald Fredricskon and Robert Levy, pioneers in lipid and lipoprotein metabolism and metabolic basis of inherited diseases. He subsequently completed his pediatrics residency at Hopkins in 1972. Upon joining the Hopkins faculty that year, he received research funding from the NIH that allowed him to establish the Johns Hopkins University Lipid Clinic, which he directed until this past spring. His group often saw more than 2000 pediatric and adult patients each, year and he was able to collect and compare biochemical and genetic data across multiple generations in families afflicted with premature vascular disease. In 1973, he was the first author of an article in the Lancet entitled ‘‘Neonatal diagnosis of familial type-II hyperlipoproteinemia’’; his co-authors were the legendary Robert Levy and Donald Fredrickson. The following year, Peter was again lead author with Drs. Levy and Frederickson on a classic article in the Journal of Clinical Investigation entitled ‘‘Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical presentation in childhood.’’ During the 1980s, Peter and his colleague Dr Allan Sniderman discovered that apolipoprotein B (apoB) was often a better predictor of atherosclerotic cardiovascular
1933-2874/$ - see front matter Ó 2014 National Lipid Association. All rights reserved. http://dx.doi.org/10.1016/j.jacl.2014.09.003
Blumenthal and Jones
Tribute to Dr Peter O. Kwiterovich
disease (ASCVD) risk than traditional lipid measurements. They were among the first to note that the LDL-C may appear to be normal or average, but the apoB measurement was often high in the presence of an elevated triglyceride level or a low HDL-C level. Peter was an outstanding lecturer, teacher, and writer who would emphasize that atherosclerotic lesions begin in childhood and are directly related to traditional CVD risk factors. He emphasized that environmental factors (such as diet, overweight status, and exercise habits) as well as inherited dyslipidemias would influence the progression of such lesions. He emphasized a comprehensive integrated evaluation of all predisposing factors in the family members of those with premature vascular disease. He was a strong advocate for weight control, better exercise habits, and a diet that was low in saturated and trans fats as well as cholesterol, but one that was supplemented with water-soluble fibers. His research showed the safety and efficacy of resin and statin treatment in young adults with familial hypercholesterolemia and familial combined hyperlipidemia. He participated in several impactful studies that found that more than half of the children of individuals with premature ASCVD had prominent dyslipidemias. Elevated levels of apoB in the presence of normal LDL-C (HyperapoB) were common in the young offspring of adults with premature ASCVD. Subsequently, the Bogalusa research group found that the levels of apoB and apo A-I and the ratio of apoB to apo A-I were stronger predictors of premature coronary artery disease in their parents than were levels of either LDL-C or high-density lipoprotein cholesterol (HDL-C). For more than 20 years, he directed a lipid disorders training center–a continuing medical education program that involved a basic course and an advanced update course. Through these educational programs, he taught a generation of physicians and trainees that inherited lipoprotein disorders that often present in youth at high risk for future CVD include familial hypercholesterolemia (FH), caused by a defect in the LDL receptor, and familial combined hyperlipidemia and its metabolic cousin hyperapoB. The latter two are prototypes for the overproduction of very LDL in the liver. He often reminded us that increased synthesis and secretion of very LDL are usually driven by an increased flux of free fatty acids from the adipose tissue to the liver, which is a metabolic abnormality often accompanied by insulin resistance, elevated triglycerides, low HDL-C, and increased numbers of small, dense LDL particles. That was precisely why he preached that lifestyle changes were the cornerstone of prevention for the entire family. In 1997, he was the lead author of the Dietary Intervention Study in Children. Symptomatic atherosclerosis early in life is often recognized in patients with xanthomatosis and sitosterolemia. Dr Kwiterovich conducted metabolic studies to show
645 that increased absorption of dietary sitosterol and decreased removal may well contribute to sitosterolemia with xanthomatosis. Further, he identified 7 different mutations in genes encoding members of the adenosine triphosphate-binding cassette (ABC) transporter family. Specifically, these were 6 mutations of ABCG8 and 1 mutation in ABCG5 in patients with sitosterolemia. Thus, although the normal ABCG5 and ABCG8 facilitate the biliary excretion of cholesterol and limited intestinal absorption of dietary cholesterol, the mutated forms predispose patients to absorb and store large amounts of sterols and to atherosclerosis. Pete had a great sense of humor, and we will always remember his classic laugh. He was a consummate mentor who taught thinking outside the box and provided an experimental approach that was both meticulous in its design and well thought-out. During his weekly laboratory meetings, Pete would listen intently to ideas that came up and always seemed provide insightful and meaningful responses. What was most impressive was his easygoing demeanor, generosity with his time, and humility. Rather than focusing on his own numerous accomplishments, he was always looking into what the future might bring and how he could facilitate the efforts and ultimate successes of his colleagues. As a testament to his reputation, Dr Mike Miller recalled the opportunity to present a case with Nobel Laureate Dr Joe Goldstein at Victor McKusick’s Annual Medical Genetics Course in Bar Harbor, Maine (1994): ‘‘The case involved a teen age girl with FH, whom Joe and I examined. Before presenting our recommendations to this prominent and well-celebrated group, Joe turned to me and asked: What would Pete do?’’
When one thinks of the student–teacher relationship, one often recalls Homer’s epic, The Odyssey, and the relationship between Odysseus’s son Telemachus and his teacher, Mentor. Pete inspired 2 generations of physicians, other health care professionals, patients, and their families to live longer and healthier lives. Much of the progress in preventive cardiology has come from the mentorship of giants such as Dr Kwiterovich, to whom so many of us will be eternally grateful. We are honored to have the opportunity to build upon Pete’s pioneering work as the University Lipid Clinic will live on as part of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Roger S. Blumenthal, MD Steven R. Jones, MD The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease Johns Hopkins Hospital Baltimore, MD
Obituary
Tribute to Dr Peter O. Kwiterovich, Jr, MD
The worlds of preventive cardiology, lipidology, and cardiovascular medicine lost one of its pioneers with the passing of Dr Peter O. Kwiterovich, Jr He succumbed after a long battle with metastatic prostate cancer at the age of 74. Peter was an internationally known expert on atherosclerotic vascular disease. He was the founder and director of the Johns Hopkins University Lipid Clinic. Dr George Dover, pediatrician-in-chief at Hopkins, said it best when he stated that Peter’s work transformed our understanding of fat metabolism and lipid malfunction and the role they play in fueling premature heart disease. His investigative and clinical work spanned nearly 50 years and defined what normal cholesterol values were for children. He also helped demonstrate the safety of statin therapy in adolescents with familial hypercholesterolemia. His research helped to delay or avert premature disability and death for many thousands of young adults. The University Lipid Clinic’s work was an early catalyst that shaped our approach to screening and cardiovascular disease prevention. It also filled important gaps in our understanding of the evolution of atherosclerotic vascular disease across the life spectrum. The way that he set up his University Lipid Clinic with a strong focus on lifestyle changes for the entire family was how we modeled the
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Peter greatly enjoyed teaching 2 generations of students, house staff, and postdoctoral fellows as well as his patients and their families. He loved science and he became a full professor at Johns Hopkins at a young age. As the son of a physician, he was exposed to science as a child. He was raised in Danville, Pennsylvania, and graduated from the College of Holy Cross in Worcester, Massachusetts. His interest in genetics was nurtured at both Dartmouth Medical School and at the Johns Hopkins School of Medicine under the tutelage of late Dr Victor A. McKusick, also known as the father of modern human genetics. He did his internship in pediatrics at Harvard’s Children’s Hospital and then worked for 3 years in the molecular disease branch of the National Heart, Lung, and Blood Institute. It was at the National Institutes of Health (NIH) that he developed a passion for understanding and treating inherited disorders of cholesterol metabolism. At NIH, he trained under Drs. Donald Fredricskon and Robert Levy, pioneers in lipid and lipoprotein metabolism and metabolic basis of inherited diseases. He subsequently completed his pediatrics residency at Hopkins in 1972. Upon joining the Hopkins faculty that year, he received research funding from the NIH that allowed him to establish the Johns Hopkins University Lipid Clinic, which he directed until this past spring. His group often saw more than 2000 pediatric and adult patients each, year and he was able to collect and compare biochemical and genetic data across multiple generations in families afflicted with premature vascular disease. In 1973, he was the first author of an article in the Lancet entitled ‘‘Neonatal diagnosis of familial type-II hyperlipoproteinemia’’; his co-authors were the legendary Robert Levy and Donald Fredrickson. The following year, Peter was again lead author with Drs. Levy and Frederickson on a classic article in the Journal of Clinical Investigation entitled ‘‘Familial hypercholesterolemia (one form of familial type II hyperlipoproteinemia). A study of its biochemical, genetic and clinical presentation in childhood.’’ During the 1980s, Peter and his colleague Dr Allan Sniderman discovered that apolipoprotein B (apoB) was often a better predictor of atherosclerotic cardiovascular
1933-2874/$ - see front matter Ó 2014 National Lipid Association. All rights reserved. http://dx.doi.org/10.1016/j.jacl.2014.09.003
Blumenthal and Jones
Tribute to Dr Peter O. Kwiterovich
disease (ASCVD) risk than traditional lipid measurements. They were among the first to note that the LDL-C may appear to be normal or average, but the apoB measurement was often high in the presence of an elevated triglyceride level or a low HDL-C level. Peter was an outstanding lecturer, teacher, and writer who would emphasize that atherosclerotic lesions begin in childhood and are directly related to traditional CVD risk factors. He emphasized that environmental factors (such as diet, overweight status, and exercise habits) as well as inherited dyslipidemias would influence the progression of such lesions. He emphasized a comprehensive integrated evaluation of all predisposing factors in the family members of those with premature vascular disease. He was a strong advocate for weight control, better exercise habits, and a diet that was low in saturated and trans fats as well as cholesterol, but one that was supplemented with water-soluble fibers. His research showed the safety and efficacy of resin and statin treatment in young adults with familial hypercholesterolemia and familial combined hyperlipidemia. He participated in several impactful studies that found that more than half of the children of individuals with premature ASCVD had prominent dyslipidemias. Elevated levels of apoB in the presence of normal LDL-C (HyperapoB) were common in the young offspring of adults with premature ASCVD. Subsequently, the Bogalusa research group found that the levels of apoB and apo A-I and the ratio of apoB to apo A-I were stronger predictors of premature coronary artery disease in their parents than were levels of either LDL-C or high-density lipoprotein cholesterol (HDL-C). For more than 20 years, he directed a lipid disorders training center–a continuing medical education program that involved a basic course and an advanced update course. Through these educational programs, he taught a generation of physicians and trainees that inherited lipoprotein disorders that often present in youth at high risk for future CVD include familial hypercholesterolemia (FH), caused by a defect in the LDL receptor, and familial combined hyperlipidemia and its metabolic cousin hyperapoB. The latter two are prototypes for the overproduction of very LDL in the liver. He often reminded us that increased synthesis and secretion of very LDL are usually driven by an increased flux of free fatty acids from the adipose tissue to the liver, which is a metabolic abnormality often accompanied by insulin resistance, elevated triglycerides, low HDL-C, and increased numbers of small, dense LDL particles. That was precisely why he preached that lifestyle changes were the cornerstone of prevention for the entire family. In 1997, he was the lead author of the Dietary Intervention Study in Children. Symptomatic atherosclerosis early in life is often recognized in patients with xanthomatosis and sitosterolemia. Dr Kwiterovich conducted metabolic studies to show
645 that increased absorption of dietary sitosterol and decreased removal may well contribute to sitosterolemia with xanthomatosis. Further, he identified 7 different mutations in genes encoding members of the adenosine triphosphate-binding cassette (ABC) transporter family. Specifically, these were 6 mutations of ABCG8 and 1 mutation in ABCG5 in patients with sitosterolemia. Thus, although the normal ABCG5 and ABCG8 facilitate the biliary excretion of cholesterol and limited intestinal absorption of dietary cholesterol, the mutated forms predispose patients to absorb and store large amounts of sterols and to atherosclerosis. Pete had a great sense of humor, and we will always remember his classic laugh. He was a consummate mentor who taught thinking outside the box and provided an experimental approach that was both meticulous in its design and well thought-out. During his weekly laboratory meetings, Pete would listen intently to ideas that came up and always seemed provide insightful and meaningful responses. What was most impressive was his easygoing demeanor, generosity with his time, and humility. Rather than focusing on his own numerous accomplishments, he was always looking into what the future might bring and how he could facilitate the efforts and ultimate successes of his colleagues. As a testament to his reputation, Dr Mike Miller recalled the opportunity to present a case with Nobel Laureate Dr Joe Goldstein at Victor McKusick’s Annual Medical Genetics Course in Bar Harbor, Maine (1994): ‘‘The case involved a teen age girl with FH, whom Joe and I examined. Before presenting our recommendations to this prominent and well-celebrated group, Joe turned to me and asked: What would Pete do?’’
When one thinks of the student–teacher relationship, one often recalls Homer’s epic, The Odyssey, and the relationship between Odysseus’s son Telemachus and his teacher, Mentor. Pete inspired 2 generations of physicians, other health care professionals, patients, and their families to live longer and healthier lives. Much of the progress in preventive cardiology has come from the mentorship of giants such as Dr Kwiterovich, to whom so many of us will be eternally grateful. We are honored to have the opportunity to build upon Pete’s pioneering work as the University Lipid Clinic will live on as part of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Roger S. Blumenthal, MD Steven R. Jones, MD The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease Johns Hopkins Hospital Baltimore, MD
