Accepted Manuscript Is it Finally Time to Dispel the Concept of Metabolically Healthy Obesity? Rishi Puri, M.B.,B.S. PII:
S0735-1097(14)02052-X
DOI:
10.1016/j.jacc.2014.03.043
Reference:
JAC 20076
To appear in:
Journal of the American College of Cardiology
Received Date: 30 March 2014 Accepted Date: 31 March 2014
Please cite this article as: Puri R, Is it Finally Time to Dispel the Concept of Metabolically Healthy Obesity?, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.03.043. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Is It Finally Time To Dispel the Concept Of Metabolically Healthy Obesity? Rishi Puri, M.B.,B.S. Cleveland Clinic Coordinating Center for Clinical Research (C5R), and Department of
Metabolically healthy obesity
Contact details:
Dr. Rishi Puri,
SC
Running title:
RI PT
Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
Atherosclerosis Imaging Core Laboratory,
M AN U
C5Research, Cleveland Clinic
9500 Euclid Ave, Cleveland, Ohio, USA (Mail Code JJ65), 44195 E: [email protected]
TE D
P: +1-216-407-8217
No conflicts
EP
Key Words: coronary artery disease, coronary artery calcium score, metabolically healthy
AC C
obesity, obesity, cardiovascular disease
1
ACCEPTED MANUSCRIPT
We are in the midst of a well-publicized, worldwide obesity epidemic (1). Yet despite its known deleterious multi-organ effects at an individual level and the economic constraints of obesityrelated illnesses upon global health systems, there remains an ongoing debate regarding the
RI PT
impact of obesity on mortality rates. Fuelling this debate has been the recent publication of two large-scale, but somewhat conflicting meta-analyses. While one analysis concluded that nearly one-fifth of total mortality within the United States is attributable to obesity (2), by contrast, the
SC
other uncovered possible protective effects of being overweight, with greater survival observed amongst individuals with body-mass indices (BMI) between 25 to 30 kg/m2 compared with a
M AN U
normal weight cohort (BMI’s between 18.5 to 25 kg/m2) (3). Even more controversial has been the concept of ‘metabolically healthy obesity,’ defined by an obese (BMI >25 kg/m2) state without demonstrable obesity-related metabolic abnormalities such as dyslipidemia or impaired glucose tolerance. Consequently, some have postulated that ‘metabolically healthy’ obese
TE D
individuals need not receive preventative therapies, as they would seem unlikely to suffer longterm morbidity based upon their seemingly normal metabolic status (4). However the incidence of obesity-related metabolic abnormalities varies considerably amongst overweight and obese
EP
individuals. Prior analyses evaluating the prognosis of ‘metabolically healthy’ obese individuals have been flawed by their inability to quantify changes in metabolic parameters over time.
AC C
Additionally, the inclusion of patients with known cardiovascular risk factors in the ‘metabolically healthy’ obese group and overweight individuals in the normal comparator group, confounded some of these prior comparisons (5). Nevertheless, this has left many to ponder whether obesity per se or component metabolic abnormalities mediates cardiovascular risk. With this in mind, Chang and colleagues report in the current issue of the Journal a comparison of coronary artery calcium scores (CAC) between ‘metabolically healthy’ obese 2
ACCEPTED MANUSCRIPT
versus metabolically healthy normal weight Koreans (6). Their rationale was based on the notion that CAC scoring is a surrogate means of assessing sub-clinical coronary atherosclerosis, with known significant associations with incident major adverse cardiovascular events, and that this
RI PT
imaging method might illuminate the true relationship between obesity, metabolic health and subclinical atherosclerotic cardiovascular disease. The overall population sample consisted of 14,828 metabolically healthy individuals (mean age of 39 years, >74% male) who took part in a
SC
comprehensive regional health screening program. ‘Metabolic health’ was defined by the
absence of all of the following: fasting blood glucose ≥100 mg/dL (or use of glucose-lowering
M AN U
agents), blood pressure ≥130/85 mmHg (or use of blood pressure-lowering agents), triglycerides ≥150 mg/dL (or use of lipid-lowering therapies), high-density lipoprotein-cholesterol
S0735-1097(14)02052-X
DOI:
10.1016/j.jacc.2014.03.043
Reference:
JAC 20076
To appear in:
Journal of the American College of Cardiology
Received Date: 30 March 2014 Accepted Date: 31 March 2014
Please cite this article as: Puri R, Is it Finally Time to Dispel the Concept of Metabolically Healthy Obesity?, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.03.043. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Is It Finally Time To Dispel the Concept Of Metabolically Healthy Obesity? Rishi Puri, M.B.,B.S. Cleveland Clinic Coordinating Center for Clinical Research (C5R), and Department of
Metabolically healthy obesity
Contact details:
Dr. Rishi Puri,
SC
Running title:
RI PT
Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
Atherosclerosis Imaging Core Laboratory,
M AN U
C5Research, Cleveland Clinic
9500 Euclid Ave, Cleveland, Ohio, USA (Mail Code JJ65), 44195 E: [email protected]
TE D
P: +1-216-407-8217
No conflicts
EP
Key Words: coronary artery disease, coronary artery calcium score, metabolically healthy
AC C
obesity, obesity, cardiovascular disease
1
ACCEPTED MANUSCRIPT
We are in the midst of a well-publicized, worldwide obesity epidemic (1). Yet despite its known deleterious multi-organ effects at an individual level and the economic constraints of obesityrelated illnesses upon global health systems, there remains an ongoing debate regarding the
RI PT
impact of obesity on mortality rates. Fuelling this debate has been the recent publication of two large-scale, but somewhat conflicting meta-analyses. While one analysis concluded that nearly one-fifth of total mortality within the United States is attributable to obesity (2), by contrast, the
SC
other uncovered possible protective effects of being overweight, with greater survival observed amongst individuals with body-mass indices (BMI) between 25 to 30 kg/m2 compared with a
M AN U
normal weight cohort (BMI’s between 18.5 to 25 kg/m2) (3). Even more controversial has been the concept of ‘metabolically healthy obesity,’ defined by an obese (BMI >25 kg/m2) state without demonstrable obesity-related metabolic abnormalities such as dyslipidemia or impaired glucose tolerance. Consequently, some have postulated that ‘metabolically healthy’ obese
TE D
individuals need not receive preventative therapies, as they would seem unlikely to suffer longterm morbidity based upon their seemingly normal metabolic status (4). However the incidence of obesity-related metabolic abnormalities varies considerably amongst overweight and obese
EP
individuals. Prior analyses evaluating the prognosis of ‘metabolically healthy’ obese individuals have been flawed by their inability to quantify changes in metabolic parameters over time.
AC C
Additionally, the inclusion of patients with known cardiovascular risk factors in the ‘metabolically healthy’ obese group and overweight individuals in the normal comparator group, confounded some of these prior comparisons (5). Nevertheless, this has left many to ponder whether obesity per se or component metabolic abnormalities mediates cardiovascular risk. With this in mind, Chang and colleagues report in the current issue of the Journal a comparison of coronary artery calcium scores (CAC) between ‘metabolically healthy’ obese 2
ACCEPTED MANUSCRIPT
versus metabolically healthy normal weight Koreans (6). Their rationale was based on the notion that CAC scoring is a surrogate means of assessing sub-clinical coronary atherosclerosis, with known significant associations with incident major adverse cardiovascular events, and that this
RI PT
imaging method might illuminate the true relationship between obesity, metabolic health and subclinical atherosclerotic cardiovascular disease. The overall population sample consisted of 14,828 metabolically healthy individuals (mean age of 39 years, >74% male) who took part in a
SC
comprehensive regional health screening program. ‘Metabolic health’ was defined by the
absence of all of the following: fasting blood glucose ≥100 mg/dL (or use of glucose-lowering
M AN U
agents), blood pressure ≥130/85 mmHg (or use of blood pressure-lowering agents), triglycerides ≥150 mg/dL (or use of lipid-lowering therapies), high-density lipoprotein-cholesterol
