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9, 2015





The CardioMetabolic Health Alliance

Working Toward a New Care Model for the Metabolic Syndrome

Laurence S. Sperling, MD,* Jeffrey I. Mechanick, MD,y Ian J. Neeland, MD,z Cynthia J. Herrick, MD,x
Jean-Pierre Desprs, PHD,k Chiadi E. Ndumele, MD, MHS,{ Krishnaswami Vijayaraghavan, MBBS, MD, MS,#
Yehuda Handelsman, MD,** Gary A. Puckrein, PHD,yy Maria Rosario G. Araneta, PHD,zz Quie K. Blum, PHD, NP,xx
Karen K. Collins, MS, RDN, CDN,kk Stephen Cook, MD, MPH,{{ Nikhil V. Dhurandhar, PHD,##
Dave L. Dixon, PHARMD,*** Brent M. Egan, MD,yyy Daphne P. Ferdinand, PHD, RN,zzz
Lawrence M. Herman, MPA, PA-C,xxx Scott E. Hessen, MD,kkk Terry A. Jacobson, MD,{{{ Russell R. Pate, PHD,###
Robert E. Ratner, MD,**** Eliot A. Brinton, MD,yyyy Alan D. Forker, MD,zzzz Laura L. Ritzenthaler, MBA, PA,xxxx
Scott M. Grundy, MD, PHDkkkk


The Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a call to action activity focused
on dening new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease.
Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank
consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of
clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and
extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately
identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct
prevention and therapies. This new MetS care model introduces both afrmed and emerging concepts that will require
consensus development, validation, and optimization in the future. (J Am Coll Cardiol 2015;66:105067) 2015 by the
American College of Cardiology Foundation.

EXECUTIVE SUMMARY community and supported in previous recommenda-

tions. Those afrmed concepts (ACs) presented here
AFFIRMED CONCEPTS. Think Tank (TT) partici- constitute a consensus, are consistent with the evi-
pants reviewed concepts accepted by the medical dence base established at the TT, and are deemed to

From the *Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia; yDivision of Endocrinology, Diabetes,
and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York; zDivision of Cardiology, University of Texas
Southwestern Medical Center, Dallas, Texas; xDivision of Endocrinology, Metabolism, and Lipid Research, Washington University
School of Medicine, St. Louis, Missouri; kQubec Heart and Lung Institute, Universit Laval, Qubec, Canada; {Division of Car-
diology, Johns Hopkins University School of Medicine, Baltimore, Maryland; #Scottsdale Cardiovascular Center, Scottsdale, Ari-
zona; **Metabolic Institute of America, Tarzana, California; yyNational Minority Quality Forum, Washington, DC; zzDepartment of
Family and Preventive Medicine, University of CaliforniaSan Diego, San Diego, California; xxInova Heart and Vascular Institute,
Fairfax, Virginia; kkPrivate Practice, Bemus Point, New York; {{Institute for Healthy Childhood Weight, American Academy of
Pediatrics, Chicago, Illinois, and Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York;
##Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas; ***Department of Pharmacotherapy and Outcomes
Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia; yyyDepartment of Medicine, University of
South Carolina School of Medicine, Greenville, South Carolina; zzzHealthy Heart Community Prevention Project, Inc., New
Orleans, Louisiana; xxxDepartment of Physician Assistant Studies, New York Institute of Technology, Old Westbury, New York;
kkkCardiology Consultants of Philadelphia and Department of Medicine, Perelman School of Medicine, University of Pennsyl-
vania, Philadelphia, Pennsylvania; {{{Ofce of Health Promotion and Disease Prevention, Emory University School of Medicine,
Atlanta, Georgia; ###Department of Exercise Science, University of South Carolina, Columbia, South Carolina; ****American
Diabetes Association, Alexandria, Virginia; yyyyUtah Foundation for Biomedical Research and Utah Lipid Center, Salt Lake City,
Utah; zzzzDepartment of Medicine, University of MissouriKansas City School of Medicine, Kansas City, Missouri; xxxxAmerican
JACC VOL. 66, NO. 9, 2015 Sperling et al. 1051
SEPTEMBER 1, 2015:105067 Proceedings of the CMHA Cardiometabolic Think Tank

have sufcient potential benet to warrant actionable AC.5. Treatment of MetS should prioritize ABBREVIATIONS

recommendations. therapeutic lifestyle changes, including AND ACRONYMS

a healthy diet and regular physical ac-

AC.1. Metabolic syndrome (MetS) is a progressive ACC = American College of
tivity, to address all risk factors. Treat- Cardiology
pathophysiological state associated with sub-
ment should also continue to be focused
stantially increased risk for development of type ACO = accountable care
on specic interventions for component organization
2 diabetes (T2D) and atherosclerotic cardiovas-
MetS risk factors. ASCVD = atherosclerotic
cular disease (ASCVD).
AC.6. The term Metabolic Syndrome will be cardiovascular disease
AC.2. MetS is clinically manifested by a cluster of risk
used to designate a portfolio of descriptors BMI = body mass index
factors that are causally inter-related (not
that have previously included the terms CMHA = CardioMetabolic
aggregating by chance alone).
cardiometabolic syndrome, insulin resis- Health Alliance
AC.3. Risk for adverse health outcomes increases sub-
tance syndrome, syndrome X, and others. MetS = metabolic syndrome
stantially with accumulation of component MetS
TT participants concluded that MetS was PCMH = patient-centered
risk factors, in addition to unmeasured (resid- medical home
the term most often used in the scientic
ual risk) factors. Timely recognition of MetS risk
published data and by health care pro- T2D = type 2 diabetes
factors helps to identify individuals at high risk
fessionals. Although arguments can be TT = think tank
for ASCVD and T2D and to initiate preventive
made for use of the other terms, the TT felt VAT = visceral adipose tissue
strategies before end-organ damage occurs.
that trying to replace MetS would distract
AC.4. Obesity is a MetS risk factor that is imperfectly
from its primary tasks.
gauged by body mass index and/or waist
circumference, and is modulated by adipocyte EMERGENT CONCEPTS. New concepts emerged dur-
distribution, size, and function, as well as race, ing the interdisciplinary discussions of the evidence
behavior, and lifestyle. Excess ectopic and/or base at the TT. These emergent concepts (ECs) require
visceral adiposity is fundamental to the path- validation, but may have sufcient potential to
ophysiology of MetS. generate actionable recommendations.

College of Cardiology, Washington, DC; and the kkkkDepartment of Clinical Nutrition, University of Texas Southwestern Medical
Center, Dallas, Texas. The Cardiometabolic Think Tank was sponsored through support from AstraZeneca, Boehringer Ingelheim
Pharmaceuticals, and Gilead Sciences. Dr. Sperling has served as a consultant to Esperion. Dr. Mechanick has received honoraria
for lectures and program development from Abbott Nutrition International. Dr. Desprs has served as a consultant to or on the
advisory board of Abbott Laboratories, Sano, and Torrent Pharmaceuticals Ltd.; has served as a consultant to Merck and Pzer
Canada; and has received speakers fees from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Merck, and Pzer Canada, Inc.
Dr. Vijayaraghavan has served on the speakers bureau for Aegerion, Amarin, Amgen, AstraZeneca, and Otsuka; has served as a
consultant to ZS Pharma; has received research support from CompanionDx, GlaxoSmithKline, and Johnson & Johnson; and has
served on the advisory board of Sano, Lilly, and ZS Pharma. Dr. Handelsman has received honoraria, research support, and/or
consultancy fees from Amarin, Amgen, AZ (Amylin), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Diadexus, DSI,
Eisai, Gilead, Grifolis, GlaxoSmithKline, Halozyme, Hanmi, Intarcia, Janssen, Lexicon, LipoScience, Merck, Novo Nordisk, Sano,
Santarus (Salix), Takeda, and Vivus; has served on the speakers bureau of Amarin, AstraZeneca (Amylin), Bristol-Myers Squibb,
Boehringer Ingelheim-Lilly, DSI, GlaxoSmithKline, Janssen, Novo Nordisk, Santarus (Salix), and Vivus; and is President of the
American College of Endocrinology, Past President of the American Association of Clinical Endocrinologists, and Associate Editor
of the Journal of Diabetes. Dr. Puckrein is founder and Chief Executive Ofcer of the National Minority Quality Forum. Ms. Collins
has served as a consultant to the American Institute for Cancer Research and the National Processed Raspberry Council. Dr. Cook
has served on the data monitoring committee of Novo Nordisk. Dr. Dhurandhar has received research funding from Vital Health
Interventions, the American Egg Board, and the Mathile Institute for the Advancement of Human Nutrition; has patents led that
relate to obesity of infectious origin and the use of adenoviral proteins to improve glycemic control or metabolic prole; and has
served as a consultant/speaker for Vivus and Novo Nordisk. Dr. Dixon has received honoraria from Sano; and has served on the
speakers bureau for Novartis. Dr. Egan has received consultancy fees and/or grant support from AstraZeneca, BlueCross Blue-
Shield South Carolina, Daiichi-Sankyo, Medtronic, and Novartis; and is an investigator for Medtronic. Mr. Herman has served as a
consultant to Boehringer Ingelheim, Merck, Novo Nordisk, and Sano; and has served on the speakers bureau for Merck and Novo
Nordisk. Dr. Pate has served as a consultant to Curves, Inc.; and has received research funding from The Duke Endowment and the
Coca-Cola Company. Dr. Brinton has received grant support from or honoraria as a speaker/consultant for Aegerion, Amarin,
Amgen, Arisaph, AstraZeneca, Atherotech, Essentialis, Genzyme, Health Diagnostic Laboratory, Janssen, Kowa, Lilly, Merck,
Novartis, PTS Diagnostics, Sano, Synageva, and Takeda. Dr. Forker has received research funding from Amylin, AstraZeneca,
Daiichi-Sankyo, GlaxoSmithKline, Intarcia, Janssen, Lilly, Johnson & Johnson, Merck, Novartis, Novo Nordisk, ZS Pharma, Sano,
Takeda, Pzer, and the National Institutes of Health. All other authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
Listen to this manuscripts audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

Manuscript received April 28, 2015; revised manuscript received June 23, 2015, accepted June 23, 2015.
1052 Sperling et al. JACC VOL. 66, NO. 9, 2015

Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

EC.1. MetS should be classied by subtype and INTRODUCTION

stage, which translate to specic evidence-
based management algorithms to improve clin- MetS recognizes a group of risk factors underlying
ical outcomes. cardiovascular and metabolic disease. The most
EC.2. Improved metrics to dene high-risk obesity accepted clinical denition, established by the
are needed and may be characterized by National Cholesterol Education Programs Adult
evidence-based assessments including, but not Treatment Panel III (NCEP-ATP III) in 2001, recognizes
limited to, waist circumference, body com- multiple components of the syndrome related to
position, and imaging-based assessments of atherosclerotic cardiovascular disease (ASCVD) risk:
ectopic fat and/or visceral adipose tissue. abdominal obesity, atherogenic dyslipidemia, ele-
EC.3. Structured lifestyle interventions for residual vated blood pressure, insulin resistance with or
risk reduction are required. Focused research without glucose intolerance, proinammatory state,
and improved education on lifestyle medicine and prothrombotic state. The criteria for clinical diag-
are also needed. nosis of MetS are 3 or more of the following: 1) waist
EC.4. Health care disparities need to be addressed circumference >102 cm (40 in) in men and 88 cm (35 in)
with respect to: 1) access to structured lifestyle in women; 2) triglycerides $150 mg/dl; 3) high-density
interventions; 2) integrated care delivery sys- lipoprotein cholesterol (HDL-C) <40 mg/dl in men
tems with enhanced provider awareness, and <50 mg/dl in women; 4) blood pressure $130/85
accountability, and communication, along with mm Hg; and 5) fasting glucose $100 mg/dl (1). In 2005,
tools to appropriately identify and treat those the NCEP-ATP III criteria were modied to suggest
at risk; and 3) community engagement. lower waist circumference cutpoints for Asian Ameri-
EC.5. New care models, such as the patient-centered cans ($90 cm [35 inches] in men and $80 cm [31 inches]
medical home (PCMH) and Accountable Care in women) (2). However, these criteria do not fully
Organizations (ACOs), are needed that incor- encompass the pathophysiological complexity of the
porate new technology, electronic health re- syndrome, recognize predisposition to different types
cords, and novel reimbursement paradigms. of end-organ damage, or account for health disparities
according to race, sex, or socioeconomic status, in
KEY FINDINGS. After reviewing the afrmed and
screening for or treating the syndrome.
emergent concepts, the writing committee formu-
MetS is typically under-recognized in the clinical
lated 5 key ndings (KFs).
setting, even just on the basis of the 5 standard
KF.1. MetS is a cluster of risk factors, both formally criteria. Additional elements of MetS include high
dened and less well recognized, that increase apolipoprotein B, small low-density lipoprotein (LDL)
the risk of certain diseases. particle size, endothelial dysfunction, insulin resis-
KF.2. The presence of ectopic fat and/or visceral tance, and prothrombotic and proinammatory
adipose tissue is critical to the pathogenesis of states. Not only are these less widely appreciated as
MetS and may explain some of the variability in components of MetS, but they are also not typically
phenotypic presentation across racial groups. measured in a clinical setting. MetS consists of ele-
KF.3. A new care model for patients with MetS is ments that do not aggregate by chance alone and are
essential and should include screening, risk causally inter-related, and each element contributes
stratication, and algorithmic management of independently to an increased risk for ASCVD (3).
patients according to the specic subtype and Factor analysis in epidemiological studies in different
stage. populations, including adolescents and ethnic
KF.4. Structured lifestyle interventions are required minorities, demonstrates clustering of risk in the do-
to adequately treat MetS and reduce residual mains of adiposity and/or dyslipidemia, hypergly-
ASCVD risk. cemia or insulin resistance, and hypertension that
KF.5. Implementation of a new patient care model explain 37% to 70% of variation and vary by sex and
should focus on integrated care delivery, race (47). For example, Malay women with MetS had
alternative reimbursement strategies (perhaps different factor patterns with greater importance of
utilizing the emerging constructs of the PCMH hypertension, insulin resistance, and triglycerides
and ACO), and education that uses structured when compared with other South Asian women (7).
lifestyle intervention; optimal use of pharma- These ndings highlight the racial phenotypic vari-
ceuticals, including combination therapies; and ability of MetS that is not well captured by standard
appropriate consideration of surgery. MetS paradigms.
JACC VOL. 66, NO. 9, 2015 Sperling et al. 1053
SEPTEMBER 1, 2015:105067 Proceedings of the CMHA Cardiometabolic Think Tank

Additionally, ASCVD risk rises exponentially as the adipocyte size and lack of hyperplasia is associated
number of MetS elements increases. In the Hoorn with adipose tissue dysfunction, inammatory
study in the Netherlands, the risk of cardiovascular markers, and insulin resistance (20,21). Given these
outcomes rose rapidly with an increasing number of ndings, using a combination of BMI and waist
MetS components, becoming statistically signicant circumference in MetS risk assessment may prove
at $3 factors for men and $2 factors for women (8). better than either measure alone (22). There may also
Other studies have demonstrated that MetS com- need to be thresholds for waist circumference and
pounds the risk for ASCVD when other known risk BMI that differ by race (23).
factors, such as T2D, are present. A meta-analysis, The challenge presented to the TT was 3-fold. First,
including 87 studies with 951,083 patients, demon- the current denition of MetS identies a population
strated that MetS was associated with a >2-fold at increased ASCVD risk, but does not accurately
increased risk for ASCVD and cardiovascular mor- assess that risk, nor does it account for susceptibility
tality (9). MetS is present in w50% of patients with for a given degree of adiposity, as noted earlier.
diagnosed vascular disease and may be even more Second, there is no targeted comprehensive care
prevalent among women with ASCVD (10,11). In the approach to address the needs of MetS patients.
Framingham Offspring Study, both MetS and T2D Third, assuming there was such an approach, there is
increased the risk of stroke by approximately 2-fold, no system to implement risk reduction and disease
and those patients with both had an even higher risk prevention. In the sections that follow, each of these
(12). ASCVD risk is higher with MetS in the absence issues is addressed, culminating in the formulation of
of T2D compared with T2D without MetS (13.9% vs. afrmed concepts, emergent concepts, and key nd-
7.5%, respectively) (13). ings relevant to MetS care.
The prevalence of MetS increases dramatically with
increasing obesity. In men in the NHANES (National
Health and Nutrition Examination Survey) from 2003
The Cardiometabolic TT was convened on June 20,
to 2006, MetS was present in 6.8% of normal weight,
2014, in Washington, DC, at the American College of
29.8 % of overweight, and 65% of obese individuals
Cardiology (ACC) Heart House as a call to action
(14). Similarly, among women, 9.3% of normal weight,
activity focused on dening new patient care models
33.1% of overweight, and 56.1% of obese individuals
and approaches to address contemporary issues of
had MetS (14). Susceptibility to MetS transcends
cardiometabolic risk and disease. The purpose of this
obesity, however, as there are obese individuals
event was for stakeholders to discuss how to best
without MetS and nonobese individuals with MetS.
coordinate care for patients with cardiometabolic risk
Several factors modulate the prevalence of MetS in the
factors and MetS. Findings from the PINNACLE reg-
presence of obesity, including lifestyle factors such as
istry (24) prompted ACC leadership to initiate the
poor nutritional quality and lack of physical activity.
TT concept and approach its partners in the Cardio-
Age, race, and sex also contribute to metabolic sus-
Metabolic Health Alliance (CMHA) to participate in
ceptibility, in part mediated by differences in adipose
the discussion. The CMHA includes 4 organizations:
tissue distribution and adipocyte size and function.
the ACC, the American Association of Clinical Endo-
For example, South Asians have higher body fat con-
crinologists (AACE), the Association of Black Cardi-
tent, waist to hip ratio, visceral fat to subcutaneous fat
ologists, and the National Minority Quality Forum,
ratio, and adipocyte area than Caucasians matched for
with a mission to improve cardiometabolic risk factor
age, sex, and body mass index (BMI) (15,16). Similarly,
control in diverse and high-risk populations and
Filipina women may have higher waist circumference
provide more effective coordinated care for patients
and truncal fat and 3- to 4-fold higher rates of type 2
with established cardiometabolic disease. CMHA
diabetes (T2D) and MetS compared with Caucasian
leadership identied and extended invitations to
women, controlling for other factors (17).
individual experts and representatives of other
In the Dallas Heart Study, total body fat correlated
organizations beyond the core CMHA members; all
with multiple metabolic risk factors, including insulin
participants are listed in Table 1.
resistance. Excess truncal fat further increased risk
The goal of the TT was to establish and organize
after adjusting for total body fat. Conversely, lower
an evidence base to address the following 3 key
body subcutaneous fat was protective, and waist
circumference appeared to be a better predictor of
total body fat than BMI (18). Visceral adipose tissue 1. What is MetS?
(VAT) appears to be associated with dyslipidemia and 2. What is the optimal care model for patients with
atherosclerosis, regardless of sex or race (19). Finally, MetS?
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Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

day-long session, the TT was directed to develop a

T A B L E 1 Cardiometabolic Think Tank Representatives and Participant Organizations
message patterned around afrmed concepts, emer-
Laurence S. Sperling, MD, Co-Chair American College of Cardiology
American Society for Preventive Cardiology
gent concepts, and key ndings to document the
Jeffrey I. Mechanick, MD, Co-Chair American Association of Clinical Endocrinologists current approach to cardiometabolic care (modeled
Maria Rosario G. Araneta, PhD National Minority Quality Forum after the 2013 AACE/ACE Consensus Conference on
Quie K. Blum, PhD, NP American Association of Nurse Practitioners Obesity) (25).
Eliot A. Brinton, MD American Heart Association
Karen K. Collins, MS, RDN, CDN Academy of Nutrition and Dietetics WHAT IS MetS AND WHY DOES IT MATTER?
Stephen Cook, MD, MPH American Academy of Pediatrics
Jean-Pierre Desprs, PhD International Chair on Cardiometabolic Risk DEFINITION: SYNDROME VERSUS DISEASE. A uni-
Nikhil V. Dhurandhar, PhD The Obesity Society fying denition is needed to facilitate communication
Dave L. Dixon, PharmD Virginia Commonwealth University School of Pharmacy
within the scientic community and between pro-
Brent M. Egan, MD Care Coordination Institute
viders and patients, and to underscore the impor-
Daphne P. Ferdinand, PhD, RN Association of Black Cardiologists
Patient/Community Advocate tance of incorporating MetS into a comprehensive
Alan D. Forker, MD* American College of Physicians preventive care assessment. There is signicant het-
Scott M. Grundy, MD, PhD Keynote Speaker erogeneity of expert opinion as to what constitutes
Yehuda Handelsman, MD American Association of Clinical Endocrinologists MetS, to what degree it represents a syndrome or a
Lawrence M. Herman, MPA, PA-C American Academy of Physician Assistants
disease, and whether it has any health-related effects
Cynthia J. Herrick, MD American Association of Clinical Endocrinologists
(Fellow Representative) beyond that of its component disorders (26,27). The
Scott E. Hessen, MD Health Information and Management Systems Society importance of MetS in cardiometabolic risk remains
Terry A. Jacobson, MD National Lipid Association widely under-recognized, as highlighted by the fact
Chiadi E. Ndumele, MD, MHS Association of Black Cardiologists that several of the most recent professional society
Ian J. Neeland, MD American College of Cardiology guidelines on heart disease and stroke prevention
(Fellow Representative)
give little or no attention to its role in disease pre-
Russell R. Pate, PhD National Physical Activity Plan Alliance
Gary A. Puckrein, PhD National Minority Quality Forum vention (2831). Furthermore, noncardiovascular
Robert E. Ratner, MD American Diabetes Association conditions promoted by MetS, such as endocrine,
Krishnaswami Vijayaraghavan American College of Cardiology respiratory, and renal disorders, remain under-
(Kris Vijay), MBBS, MD, MS
emphasized in clinical practice. Last, the current
*Dr. Forker was unable to attend the Think Tank, but contributed to this document.
approach to MetS diagnosis does not take into ac-
count that a greater number of MetS components
translate to a higher risk for adverse outcomes.
3. What is the optimal strategy to implement this
The past 2 decades have seen great debate over
what term most precisely articulates the adverse
To accomplish this, the TT was charged with cardiovascular and metabolic effects of MetS
formulating a paradigm to create and implement a (Table 2). In 1988, Reaven noted that hypertension,
new care model of patients with cardiometabolic risk insulin resistance, atherogenic dyslipidemia, and
factors and MetS. CMHA leadership organized the obesity tended to cluster to form a complex syn-
proceedings around 3 core topics: drome, syndrome X, dened by a unifying patho-
physiology leading to multiplicative risk for ASCVD
1. Deconstructing MetS into its components;
(32). A decade later, the World Health Organization
2. Constructing a new care model through an inter-
introduced the term metabolic syndrome, with a pri-
disciplinary approach; and
mary focus on insulin resistance and hyperglycemia,
3. Implementing a new care model in the real world.
creating controversy about whether the prime driver
The conference began with introductory remarks of MetS was insulin resistance or obesity (33). In 1999,
from the TT co-chairs (L.S.S. and J.I.M.) and a key- the European Group for the Study of Insulin Resis-
note address by Dr. Scott Grundy, followed by 3 tance (EGIR) modied the World Health Organization
discussion sessions organized around the core denition, replacing it with insulin resistance syn-
topics. Each topic session began with a brief pre- drome (34). Later, the NCEP-ATP III report codied
sentation by the topic co-chairs, followed by general the term metabolic syndrome, highlighting abdominal
discussion and debate moderated by the co-chairs. obesityspecically increased waist circumference
An effort was made to establish points of consensus and an inammatory/prothrombotic state as major
and identify alternative viewpoints and knowledge components of the syndrome (35). Terms for MetS
gaps requiring additional research. The proceedings have continued to evolve, each focused around
were recorded and transcribed. At the end of the varying aspects of its pathophysiology, and have
JACC VOL. 66, NO. 9, 2015 Sperling et al. 1055
SEPTEMBER 1, 2015:105067 Proceedings of the CMHA Cardiometabolic Think Tank

T A B L E 2 Previous Criteria Proposed for Clinical Diagnosis of Metabolic Syndrome

(Year) Insulin Resistance Elevated Blood
(Ref. #) MetS Denition or Hyperglycemia Body Weight Dyslipidemia Pressure Other

WHO (1998) (33) Insulin resistance Impaired glucose Men: waist to hip TG $150 mg/dl and/or $140/90 mm Hg Microalbuminuria
any other tolerance, impaired ratio >0.90 HDL-C <35 mg/dl
2 criteria fasting glucose, Women: waist to hip in men or <39 mg/dl
or lowered insulin ratio >0.85 and/or in women
sensitivity BMI >30 kg/m
EGIR (1999) (34) Insulin resistance Plasma insulin >75th WC $94 cm in men TG $150 mg/dl and/or $140/90 mm Hg or None
any other percentile, impaired or $80 cm HDL-C <39 mg/dl on hypertension
2 criteria glucose tolerance, in women in men or women therapy
or impaired fasting
glucose (but not
ATP III (2001) (35) Any 3 of 5 criteria >110 mg/dl (modied WC $102 cm in men TG $150 mg/dl, $130/85 mm Hg None
in 2004 to or $88 cm HDL-C <40 mg/dl
>100 mg/dl), diabetes in women in men or <50 mg/dl
in women
AACE (2003) (36) Insulin resistance Impaired glucose BMI $25 kg/m2 TG $150 mg/dl and $130/85 mm Hg Other features
any of the tolerance or HDL-C <40 mg/dl of insulin
other criteria impaired fasting in men or <50 mg/dl resistance including
glucose (but not in women family history
diabetes) of diabetes,
polycystic ovary
syndrome, sedentary
lifestyle, and so on
IDF (2005) (49) Body weight >100 mg/dl, diabetes Increased WC TG $150 mg/dl or $130 mm Hg systolic None
any other (population on therapy, HDL-C or $85 mm Hg
2 criteria specic) <40 mg/dl in men diastolic or on
or <50 mg/dl therapy
in women or
on therapy
AHA/NHLBI Any 3 of 5 criteria >100 mg/dl or on therapy WC $102 cm in men TG $150 mg/dl or $130 mm Hg systolic None
(2005) (2) or $88 cm on therapy, or $85 mm Hg
in women HDL-C <40 mg/dl diastolic or on
in men or <50 mg/dl therapy
in women or on therapy

Adapted from Grundy et al. (2).

AACE American Association of Clinical Endocrinologists; AHA American Heart Association; ATP III National Cholesterol Education Programs Adult Treatment Panel III; BMI body mass index; EGIR
European Group for the Study of Insulin Resistance; HDL-C high-density lipoprotein cholesterol; IDF International Diabetes Federation; MetS metabolic syndrome; NHLBI National Heart, Lung, and
Blood Institute; TG triglycerides; WC waist circumference; WHO World Health Organization.

included the dysmetabolic syndrome (36), insulin by a unifying pathophysiology; and 3) is associated
resistance syndrome (36), and cardiometabolic syn- with increased risk for ASCVD, T2D, and other
drome, originally introduced by the pharmaceutical related disorders. It is imperative to recognize that
industry. The position of others, such as the Inter- MetS is not just a repackaging of its individual
national Chair on Cardiometabolic Risk, has been to risk components, but, as demonstrated in at least
identify excess visceral/ectopic fat as the most pre- 1 analysis, is a clinical entity associated with an
valent form of MetS (37). In 2009, several major increased risk of ASCVD or death, even after con-
organizations released a statement harmonizing the trolling for its component risk factors (risk ratio:
criteria for MetS, which is in use today (38). Until 1.54; 95% condence interval: 1.32 to 1.79) (39).
recently, medical billing codes experienced a lack of Furthermore, MetS incorporates so-called residual
uniform terminology as well, with the descriptor risk markers that associate with cardiovascular and
dysmetabolic syndrome X (277.7) chosen to represent a metabolic disease risk, but are not universally agreed
diagnosis of MetS. The more recent International upon as criteria for MetS diagnosis. These include
Classication of Diseases-10 coding terminology, elevated levels of apolipoprotein B and small, dense
however, has shifted to the more accepted term, LDL particles; a prothrombotic and proinammatory
metabolic syndrome (E88.81). state signied by high levels of circulating inam-
These denitions are organized around the con- matory markers, such as C-reactive protein and
cepts that MetS: 1) is a chronic and progressive brinogen; and microalbuminuria (2). It is important
pathophysiological state; 2) represents a clustering to recognize this construct because it provides
of risk factors that form a complex syndrome dened an opportunity to identify and treat residual risk
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Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

markers beyond the standard management of estab- morbidity and mortality (40), with MetS as 1 such
lished risk factors. important consequence. MetS is strongly linked to the
Another concept essential to the MetS denition obesity epidemic in the United States (41). The latest
is that people with MetS have or are at risk for prevalence estimates of MetS in men and women are
multiend-organ damage. This includes, but is not 35% and 33%, respectively (42). Because forecasts
limited to, cardiovascular (atherosclerosis and non- suggest that over one-half of the U.S. population will
atherosclerosis types), metabolic (e.g., T2D and be obese by the year 2030, rates of MetS will almost
dyslipidemia), hormonal (e.g., polycystic ovarian certainly increase over the next decade. However,
syndrome), sleep-disordered breathing, certain ma- there is a growing appreciation that obesity per se, as
lignancies, psychological distress (e.g., depression), dened by simple anthropometric measures, such as
chronic kidney disease, orthopedic/joint diseases, BMI or waist circumference, is neither a necessary nor
and nonalcoholic fatty liver disease (NAFLD). Sub- a sufcient descriptor of MetS and its consequences.
stantial variability in end-organ consequences Rather, it appears that risk for MetS varies substan-
emphasizes a need to identify subtypes of MetS on tially by distribution of both adipocyte and non-
the basis of their underlying pathophysiology and adipocyte (ectopic) fat, as well as by adipocyte size
predisposition to adverse consequences, which can and function. Excess intra-abdominal (i.e., visceral)
then be targeted for specic preventive and thera- adipose tissue may be a primary driver of the car-
peutic management strategies (Figure 1). diometabolic complications of obesity (43), and
FOCUS ON PATHOPHYSIOLOGY. O b e s i t y . Recently, ectopic fat may be linked to VAT and may itself play
the AACE and the American College of Endocrinology a key contributory role. An increase in VAT is thought
developed an advanced framework for dening to reect the relative inability of the subcutaneous
obesity as a chronic disease characterized by patho- adipose tissue depot to sufciently expand its clear-
physiological processes that result in increased ance and storage capacity in response to caloric
adipose tissue mass and can result in increased excess (44). Defects in adipocyte maturation and

F I G U R E 1 Paradigm for Subtyping MetS

- Sleep Disordered
- Fatty Liver Disease



-ASCVD Metabolic -Type 2 diabetes

-Prothrombotic and Syndrome -Gestational diabetes
Proinflammatory states -Polycystic Ovary
-Hypertension Syndrome

Lipid Other Risk

Dominant Factors

-Atherogenic dyslipidemia -Hormonal dysfunction

-Chronic kidney disease

Substantial variability in end-organ consequences related to MetS underscores a need to identify subtypes of MetS on the basis of
pathophysiology that can be targeted for specic evidence-based management strategies. ASCVD atherosclerotic cardiovascular disease;
MetS metabolic syndrome.
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differentiation (21) cause adipocyte dysfunction, I n s u l i n r e s i s t a n c e . Insulin resistance tracks very

resulting in spillover of excess triglycerides and pro- closely with MetS, playing a key role in MetS patho-
motion of ectopic fat deposition in the viscera, liver, genesis and relation to ASCVD risk (55). Although in-
heart, and skeletal muscle. The ensuing milieu of sulin resistance may be associated with impairment
overactive lipolysis, altered glucose homeostasis, of fasting glucose, insulin resistance itself seems to
proinammatory adipocytokine release, and endo- worsen in severity across added components of
thelial dysfunction appears to be a primary cause of the syndrome, suggesting an independent associa-
the pathophysiological alterations observed in MetS. tion with MetS beyond glycemic effects (56) and
The several ectopic fat depots associated with strengthening the evidence for a pathogenic role of
increased cardiometabolic risk include excess liver, insulin resistance. Moreover, insulin resistance has
pericardial and epicardial, retroperitoneal, and in- been associated with atherogenic dyslipidemia,
tramuscular fat (45). Further evidence for the role of including elevated levels of triglycerides and low
adipocyte dysfunction in adverse metabolic changes concentrations of HDL-C (2); prothrombotic and
comes from the lipodystrophies, a group of rare proinammatory markers, such as plasminogen acti-
genetic disorders that result in severe, generalized vator inhibitor-1, brinogen (57), and C-reactive pro-
loss of adipose tissue. Although obesity and lipodys- tein (58); increased sympathetic nerve activity and
trophy represent 2 extremes of the physiological sodium retention predisposing to hypertension (59);
spectrum, the underlying mechanisms causing insu- androgen excess and polycystic ovarian syndrome
lin resistance and MetS in both sets of patients may (60); sleep-disordered breathing (60); chronic kidney
be similar; specically, limited storage capacity in disease (61); and some cancers (62,63). It remains
adipose tissue results in diversion of excess tri- unclear whether the insulin resistance seen in MetS is
glycerides to ectopic sites, with adverse metabolic a purely independent etiological factor, or mostly a
sequelae (46,47). Notably, ectopic fat-associated car- downstream consequence of ectopic/dysfunctional
diometabolic risk in MetS may be further modulated adiposity, or a combination of both.
by race (e.g., South Asians are predisposed), nutri-
RESIDUAL RISK. TT participants afrmed the con-
tional factors, and lifestyle behaviors.
cept of residual MetS risk indicators. This concept
Although an increased waist circumference is
recognizes that there are additional markers/factors
central to the current clinical diagnosis of MetS and
not incorporated within the traditional diagnostic
identies individuals at increased risk for athero-
framework of MetS that nonetheless relate to MetS
sclerosis (48) and mortality across different levels of
and are associated with adverse health outcomes.
BMI (22), it is an imprecise surrogate for the VAT
These may vary by individual or group, may be
phenotype. First, the correlation among BMI, waist
modiable or nonmodiable, and may have genetic or
circumference, and VAT is highly variable among
environmental determinants. This is critical because
different racial groups, prompting the American
differences in risk factor burden early in life translate
Diabetes Association and the International Diabetes
into marked differences in the risk of adverse health
Federation to dene different cutoffs for abnormal
outcomes later in life (64). One element of this has
BMI and waist circumference, respectively, in Asian
been highlighted in the ticking-clock hypothesis,
populations (49,50). Second, waist circumference
which recognizes the detrimental effects of long-term
measurement includes both VAT and abdominal
exposure to MetS on future development of end-
subcutaneous adipose tissue compartments. These
organ damage. For example, multiple factors that
2 depots are anatomically and physiologically
begin before birth and continue through delivery,
distinct, especially within the obese population, and
such as low birth weight, small head circumference,
are differentially associated with markers of car-
gestational diabetes, and lack of breastfeeding, place
diometabolic risk (19). VAT, but not abdominal sub-
children at risk for MetS in adolescence and adulthood
cutaneous fat, has been shown to associate with
(65). It is important for practitioners to recognize
incident T2D and pre-T2D (51), incident hypertension
these and other social determinants of MetS suscep-
(52), and alterations in left ventricular structure and
tibility, such as low socioeconomic status and parental
function (53), and has also been linked to increased
history of MetS; to consider providing primordial
risk of developing CVD and cancer (54). Therefore,
prevention (66) when possible; and to move toward
the TT recognized the central role of ectopic fat
identication and treatment of vulnerable families
and/or visceral adipose tissue in the pathophysiology
and communities to improve public health.
of MetS and endorsed evidence-based strategies
to identify and treat these dangerous fat depots in LIFESTYLE. The TT recognized lifestyle, referring to
individuals with or at risk for MetS. physical activity and nutrition, as being a modiable
1058 Sperling et al. JACC VOL. 66, NO. 9, 2015

Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

factor crucial to prevent and treat MetS and its con- was an emergent need for a new care model for
sequences. Many observational studies show an patients with or at risk for MetS. Participants identi-
association between higher levels of physical activity ed several essential considerations in response to
and lower rates of chronic diseases and increased the dynamic health care environment of the 21st
longevity (67). Even in the presence of MetS, century. These included: focusing on comprehensive
increased physical activity is associated with a sub- screening/case-nding strategies; considering vary-
stantially lower risk of ASCVD (68). The proposed ing MetS phenotypes; formulating a staging system
mechanisms include benecial effects on blood to facilitate communication between patients and
pressure and lipids, key components of MetS (28). providers; and building a paradigm of care involving
Appropriate nutritional choices can also modify the individual, community, and public/global health that
risk of cardiometabolic disease. The Strong Heart emphasizes lifestyle choices.
Study identied specic dietary patterns associated STAGING SYSTEM FOR THE METABOLIC SYNDROMEA
with improved health outcomes (69). Several dietary FRAMEWORK. The TT recognized that providers need
patterns, such as the DASH (Dietary Approaches a more comprehensive, but simply communicated,
to Stop Hypertension) and Mediterranean diets, framework through which they can identify and
may reduce blood pressure, improve lipids, reduce risk-stratify patients with or at risk for MetS. Such a
inammation, and reduce risk for ASCVD (28,70). framework can be used to apply evidence-based,
Emphasis should be placed on dietary patterns, rather targeted therapeutic interventions. By highlighting
than specic macronutrients, given inconclusive the progressive nature of MetS in stages, participants
evidence to date for an independent effect of macro- proceeded to devise a theoretical system with sug-
nutrient composition on outcomes (71). Emerging gested criteria and recommended therapy for each
from these recent data is the belief that focused stage (Figure 2). The system starts by recognizing
research and improved education on lifestyle inter- persons who are at risk for MetS, but without any of
ventions should be prioritized. the 5 criteria required to meet a MetS diagnosis.
DISPARITIES. The TT identied disparity in care of Factors to consider at this stage include overweight
patients with MetS to be a critical area for improve- (incorporating the recent AACE framework [40]),
ment. Disparity can manifest as decreased accessi- evidence for ectopic fat deposition by imaging, racial,
bility to health care and failure to recognize or or parental susceptibility to MetS, and adverse life-
appropriately treat at-risk populations. For example, style choices. Therapeutic interventions would be
current guidelines do not recognize racial-specic implemented to address specic health behaviors
differences in lipid levels between Caucasian and or markers of susceptibility to prevent progression
African-American populations (30). On average, (primary prevention). The model then moves toward
African-Americans have higher HDL-C and lower tri- increasingly severe stages of MetS on the basis of
glyceride levels (72). This paradox may translate to established risk factors/diagnostic criteria and resid-
underdiagnosis of MetS in African-Americans using ual risk markers. Each stage, considered secondary
current diagnostic criteria, which would likely result prevention, proposes more intensive therapeutic
in lack of treatment of MetS in this population. strategies to treat MetS and its risk factors. It should
In addition to this and other race-specic issues, be noted that although risk for adverse outcomes
however, TT participants recognized that well- generally increases with each subsequent stage, the
intentioned alteration of existing diagnostic criteria absolute risk for developing MetS consequences
around racial differences could stigmatize minority varies substantially within populations. Thus, it is
populations and lead to undesirable consequences. imperative that treatment decisions be incorporated
Other nonracial, high-risk, under-represented pop- within the context of absolute risk.
ulations likely requiring more intensive consideration In summary, this model categorizes patients rst
include patients with human immunodeciency on the basis of the stage of their disease progression
virus/acquired immunodeciency syndrome, cancer and second by underlying MetS pathophysiology. The
survivors, individuals with severe mental illness, and strengths of this model are that it: 1) recognizes the
children with developmental disabilities. heterogeneity of MetS and the need for individual-
ized care strategies; 2) highlights the importance of
WHAT IS THE OPTIMAL INTERDISCIPLINARY disease-specic pathophysiology in the evolution of
CARE MODEL FOR PATIENTS WITH MetS? MetS; 3) acknowledges that many patients with MetS
have overlapping subtypes requiring a multidisci-
Dening and deconstructing MetS laid the ground- plinary approach to their care; and 4) maps MetS
work for the TT to begin discussing what they agreed stages with specic management strategies. The TT
JACC VOL. 66, NO. 9, 2015 Sperling et al. 1059
SEPTEMBER 1, 2015:105067 Proceedings of the CMHA Cardiometabolic Think Tank

F I G U R E 2 Stages in the Evolution of MetS and Recommended Therapy by Stage

Absolute Risk for End-Organ Damage

Stage A Stage B Stage C Stage D

At risk for At risk for MetS without MetS with
MetS, no MetS, 1 end-organ end-organ
criteria met criterion damage damage

Patients with: Patients with: Patients with: Patients with:

-Overweight 1 or 2 criteria 3/5 criteria CVD
-Ectopic fat -WC -WC Diabetes
-Racial -BP -BP CKD
susceptibility -Glucose -Glucose OSA
-Poor physical -TGs -TGs NAFLD
activity -HDL-C -HDL-C Other
-Parental MetS -Alt risk factors -Alt risk factors

Therapy Therapy Therapy Therapy

-Physical activity -All measures under -All measures under -All measures under
-Nutrition Stage A Stage B Stage C
-Obesity prevention -Medical therapy & -Adiposity reduction -Disease-specific
Risk Factor Modification surgery therapies

This staging system highlights the progressive nature of MetS, with suggested criteria and recommended therapy for each stage. All thera-
peutic decisions should be made within the context of absolute risk for end-organ damage. Alt alternative; BP blood pressure; CKD
chronic kidney disease; CVD cardiovascular disease; HDL-C high-density lipoprotein cholesterol; MetS metabolic syndrome; NAFLD
nonalcoholic fatty liver disease; OSA obstructive sleep apnea; TG triglycerides; WC waist circumference.

acknowledges that the concepts of staging and sub- augment screening by increasing awareness of MetS
typing are works in progress and require further and promoting healthy behaviors. These include
modication, testing, and validation before they can making healthy eating and regular physical activity
be used routinely in clinical care. accessible, affordable, and acceptable. One successful
BUILDING A NEW CARE PARADIGM: THE INTEGRATED example of this approach is the community-based
CARE MODEL. The TT agreed that care for patients with practice network, where community leaders partner
MetS should focus on disease prevention and man- with health care practices to create public health
agement within a continuum of individual, commu- awareness, with real-time feedback and data analysis
nity, and public/global health (Central Illustration). for quality improvement (73). This approach can be
Focusing on prevention requires more comprehensive improved by increasing patient access to ancillary
screening for MetS in the community. Some examples services using ZIP code analysis to focus resources on
include opportunities to screen families at well-child high-risk areas (74) and using public health and com-
pediatric or pharmacy visits; using electronic medical munity initiatives. By engaging the community more
records to improve screening/case nding; and broadly, the focus can begin to shift from the indivi-
expanding screening efforts to schools, worksites, dual to larger units (families, communities, neighbor-
places of worship, and community businesses. hoods, and populations), which will increase the
Screening should use measurable biomarkers (e.g., effectiveness of screening and start to change the
blood pressure, lipids, BMI, and waist circumference), culture of care.
as well as better assess and target behaviors, such as Second, participants felt that better metrics are
physical inactivity and nutritional quality. Taking needed to dene abdominal obesity, as current deni-
advantage of emerging technologies (e.g., wearable tions are imprecise and not well suited for many pop-
devices) should be further explored to enhance ulations. As technology develops and the critical role
screening. Community engagement strategies can of ectopic fat and/or visceral adipose tissue continues
1060 Sperling et al. JACC VOL. 66, NO. 9, 2015

Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

CENTR AL I LLU ST RAT ION Integrated Care Model for Patients With MetS: Proceedings of the CardioMetabolic Health
Alliance Think Tank


Lipid Dominant Vascular Dominant Adiposity Dominant Insulin Resistance Other Risk Factors

Atherogenic Prothrombotic and Sleep disordered Hormonal dysfunction

dyslipidemia proinflammatory states breathing Type 2 diabetes Chronic kidney disease
Hypertension Fatty liver disease Gestational diabetes Hyperuricemia
Polycystic ovary


(Absolute risk for end-organ damage)


At risk for MetS, At risk for MetS, MetS without MetS with
no criteria met 1 criterion end-organ damage end-organ damage
Overweight 1 or 2 criteria 3/5 criteria Cardiovascular disease
Ectopic fat High waist circumference High waist circumference Diabetes
Patient profile

Racial susceptibility High blood pressure High blood pressure Chronic kidney disease
Poor physical activity High glucose levels High glucose levels Obstructive sleep apnea
Parental MetS High triglycerides High triglycerides Nonalcoholic
High-density lipoprotein High-density lipoprotein fatty liver disease
cholesterol cholesterol Other risk factors
Other risk factors Other risk factors

Physical activity All Stage A measures, plus: All Stage B measures, plus: All Stage C measures, plus:
Nutrition Medical therapy Adiposity reduction surgery Disease-specific therapies
Obesity prevention Risk factor modification


Community health Healthcare system Industry


Peer leaders Physician Drug companies

Community health Physician assistants Device companies
department workers Nurse practitioners
Community organizations Ancillary health professionals

Create opportunities to screen families Form an integrated network of care Focus on ectopic fat
Increase awareness through (general practitioners and specialists) Provide evidence-based therapy
community engagement strategies Gather more data/evidence for MetS Provide alternative methods

Promote healthy behaviors care; Share with real-time data of measuring obesity
Provide robust and focused health
promotion training to clinicians
Insurers to cover those at-risk

Sperling, L.S. et al. J Am Coll Cardiol. 2015; 66(9):105067.

Care for patients with MetS should be focused on prevention and disease management within a continuum of individual, community, and public/global
health. MetS metabolic syndrome.

to emerge, metrics should evolve to consider alterna- modifying factors should be taken into account,
tive methods of measuring obesity. Simpler and less including race susceptibility, lifestyle, and evidence
expensive methods than computed tomography and for metabolic dysfunction beyond the specic MetS
cardiac magnetic resonance imaging to measure fat criteria, such as NAFLD or sleep-disordered breathing.
distribution are needed to better characterize car- Finally, with the advent of the PCMH and ACOs,
diometabolic risk. In the interim, other potentially care of patients with or at risk for MetS will likely
JACC VOL. 66, NO. 9, 2015 Sperling et al. 1061
SEPTEMBER 1, 2015:105067 Proceedings of the CMHA Cardiometabolic Think Tank

change dramatically, with an increasing emphasis on as ancillary health professionals such as dietitians,
interdisciplinary care and greater involvement of exercise physiologists, psychologists, behavioral
family and community resources. The vision of the TT specialists, and certied diabetes educators. Disci-
was to integrate care across general practitioners and plines to be involved include family practice, pedi-
specialists, in addition to ancillary resources, with a atrics, internal medicine, obstetrics and gynecology,
patient-centered and culturally sensitive approach. geriatrics, and specialists in cardiology (hypertension
This will create a virtually integrated network of care and lipid) and endocrinology (diabetes and obesity).
providers sharing information with real-time data Other medical specialties that may also be involved
gathering and quality improvement to help patients with this population presenting with a particular
reach their goals. For example, the ACO Shared Savings phenotype include gastroenterology (NAFLD), sleep
Program has reported substantial improvements in medicine (obstructive sleep apnea), nephrology (car-
blood pressure screening (76%), achieving glycosy- diorenal syndrome), surgery (bariatric, vascular, and
lated hemoglobin (HbA1c) <8% (69%), LDL cholesterol cardiothoracic), psychiatry (depression, other behav-
<100 mg/dl (55%), and aspirin use (75%) in participants ioral), and oncology (obesity-associated malig-
with T2D compared with current NHANES reports for nancies). Finally, industry is another key stakeholder,
the general population with T2D (75). as pharmaceuticals and surgical interventions com-
Integrated health networks allow patients to prise important treatment options for patients with
monitor their own progress, which improves self- MetS. It is important to note that many of the pro-
motivation and patient engagement in self-care. The visions of the Affordable Care Act (ACA) would sup-
TT recognized several key issues required to achieve port this implementation.
this goal. First, time constraints placed on clinicians Dissemination of the Diabetes Prevention Program
necessitate more robust and focused training to (DPP) in community settings can serve as a model
address health promotion during brief patient- for the MetS population. The DEPLOY (Diabetes Ed-
provider encounters. Second, funding should extend ucation & Prevention with a Lifestyle Intervention
beyond covering end-organ consequences to include Offered at the YMCA) study was a pilot cluster-
covering those at risk for MetS. Payers and employer- randomized trial comparing group-based DPP life-
based insurers must see MetS as a priority. Increased style intervention through a Young Mens Christian
emphasis on MetS staging paradigms should help Association (16 group sessions with goals of 5% to
demonstrate that early intervention prevents more 7% reduction in baseline body weight and 150 min/
costly end-organ consequences. Finally, there is a week of moderate exercise) with brief counseling.
need for more data/evidence for MetS care within Among 92 randomized participants, at both 4 to 6
diverse populations. One example is the new Diabetes and 12 to 14 months, the percent change in weight
Collaborative Registry (76), housed in the ACC and and BMI, as well as the change in total cholesterol,
linked to the PINNACLE registry, which will facilitate was signicantly greater in the intervention group
crosstalk between registries and improve research. As (78). An extension study in which both the control
health care evolves to become more prevention- and intervention arms were offered an 8-month
focused, a new care model for patients with MetS lifestyle maintenance program found that both
should continue to encourage high-intensity lifestyle groups maintained weight changes compared with
interventions to reduce morbidity and mortality from baseline, and those in the initial intervention group
MetS and its consequences (31,77). lost a further 1.5% of body weight, with signicant
decreases in total cholesterol and systolic blood
WHAT IS THE OPTIMAL STRATEGY pressure (79). A larger implementation of the DPP
FOR IMPLEMENTING A NEW CARE MODEL intervention across 14 Young Mens Christian Asso-
FOR MetS? ciations in New York demonstrated that among 254
participants, 40.2% and 60.8% achieved a weight
The nal challenge for TT participants was imple- loss $5% at 16 weeks and 10 months, respectively
mentation of a new care model for MetS. Clear (80). Lessons could be drawn from these in-
consensus was that stakeholders from the community terventions to benet other communities, such as
and public health arena, the health care system, and the workplace, where many large employers already
industry must be involved and that patient advo- offer wellness programs. A systematic review of
cates, community health workers, and peer leaders randomized controlled trials on worksite wellness
are essential to bridging the community and the programs demonstrated a statistically signicant 3-lb
health care system. Stakeholders include physicians, weight reduction and 0.5 kg/m 2 BMI reduction over
nurse practitioners, and physician assistants, as well 6 to 12 months (81).
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The TT also recognized the National Physical multivariable models, those receiving a follow-up call
Activity Plan as an overarching framework for had greater improvement in Framingham Risk Score
implementation. The plan has 5 primary strategies than those who did not (85). A randomized controlled
and proposes evidence-based interventions within 8 trial in 2 community health centers enrolled 525 pa-
economic sectors. Strategies include launching tients with uncontrolled ASCVD, T2D, hypertension,
advocacy efforts to increase public support, mounting or hyperlipidemia; results showed that pairing nurse
a national physical activity education program, practitioners and community health workers dem-
disseminating best practice models, creating a na- onstrated signicant reductions in blood pressure,
tional resource center, and establishing a center for cholesterol, and HbA1c over 1 year of follow-up
physical activity policy development and research. compared with usual care (86). Finally, peer leaders
Involved sectors include: business and industry; can effectively provide education and support for
education; health care; mass media; parks, recrea- lifestyle. This was demonstrated in a study where 116
tion, tness, and sports; public health; transpor- Latino adults with T2D were randomized to receive
tation; land use; community design; volunteer; and diabetes self-management education and either
nonprot. Specic strategies within these sectors 12 months of weekly group sessions with peer leaders
include providing incentives to increase active or 12 months of telephone outreach with health
transportation (walking, biking) through community workers (87). Both groups achieved signicant HbA1c,
design, making physical activity a vital sign in the blood pressure, and waist circumference reductions
health care setting, and ensuring access to high- and improved diabetes support with less distress.
quality physical activity programs in early childhood However, only the peer leader group sustained HbA1c
education and grade school (82). and blood pressure reductions over 18 months (87).
The TT proposed that community health workers To further highlight lifestyle change, the TT pro-
and peer leaders play an integral role in implement- posed campaigns such as the Exercise is Medicine
ing the new care model and discussed several exam- initiative (88), which assesses patient readiness for
ples. The Healthy Living Partnerships to Prevent exercise and provides handouts to help patients start
Diabetes Study implemented a DPP-like lifestyle a program. It also provides materials to help tness
weight-loss program over 2 years by using a local professionals communicate with health care per-
diabetes education program with community health sonnel. To emphasize the importance of addressing
workers, involving weekly visits over the rst disparities, the TT discussed key studies such as the
6 months and twice monthly visits over the next Lawrence Latino Diabetes Prevention project (89),
18 months (83). Among 301 randomized patients, the which recruited 312 participants at high risk for T2D
intervention group achieved signicant reductions in for a lifestyle intervention involving 3 individual and
weight, BMI, waist circumference, glucose, insulin, 13 group sessions over 12 months versus usual care.
and homeostatic model assessment of insulin resis- The curriculum was adapted to address knowledge
tance measures compared with control subjects, with gaps and language barriers, customize dietary advice
46.5% of the intervention group achieving $5% to Latino cuisine, and use the popular novella media
weight loss and 21.3% achieving $10 % weight loss format to deliver messages. At 1 year, there was a
(83). The Look AHEAD (Action for Health in Diabetes) signicant reduction in weight, BMI, and HbA1c in the
trial provides the longest-term evidence of the effect intervention group as compared with usual care (89).
of an intensive lifestyle intervention in overweight Another cultural adaptation of the DPP in African-
and obese adults with T2D. The curriculum was American churches involved 37 participants and
modied from the DPP and included structured meal compared an abbreviated 6-week program to a longer
plans and moderate exercise up to 200 min/week. At 16-week program; it found that fasting glucose and
8 years, 50.3% in the intervention group versus 35.7% BMI decreased signicantly in both groups at
in the usual care group lost $5% of body weight, and 12 months (90). A program targeting a predominantly
26.9% versus 17.2% lost $10% of body weight (84). low-income non-Caucasian urban population deliv-
In Colorado Heart Healthy Solutions, community ered a lifestyle intervention in 12 weeks using group
health workers conducted screenings, assessed read- sessions and found signicant reductions in the pro-
iness for change, and provided education and medical portion of subjects meeting the MetS waist circum-
referrals to patients with an uncontrolled risk factor ference (90% to 68%; p 0.009) and hypertension
for coronary heart disease or a Framingham Risk (68% to 48%; p 0.04) criteria over 6 months. At 3
Score $10%. They provided further phone follow-up, months, 46.4% lost $5% of body weight and 26%
and found signicant reductions in Framingham Risk lost $7% of body weight, with 87.5% and 66.7% sus-
score, blood pressure, and cholesterol at retesting. In taining these losses at 6 months, respectively (91).
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Araneta et al. (92) piloted a 12-week Zumba tness month follow-up (97). The PCMH model affects MetS
program in sedentary obese women with $2 MetS sequelae and outcomes. For example, the Geisinger
criteria (77% ethnic minorities), demonstrating sig- ProvenHealth Navigator demonstrated a reduction in
nicant blood pressure and fasting triglyceride re- the incidence of end-stage renal disease and amputa-
ductions among the participants. The investigators tion among patients with T2D over 4 years, although
also conducted a 48-week randomized controlled trial without a change in myocardial infarction or stroke
comparing restorative yoga to active stretching (98). Evaluation of another such model in West Vir-
among adults with MetS, nding signicantly lower ginia found that an EHR-based screening tool identi-
fasting glucose in the yoga group at 12 months (93). ed 11% of over 94,000 patients as being at risk for T2D
Principles for implementing a new care model (99), enabling the facility to better screen and connect
within the health care system should include: care patients to local lifestyle intervention programs.
coordination and team-based care; education in MetS There is less published data available to assess
recognition and treatment; technology to facilitate PCMH reimbursement strategies to facilitate coordi-
communication among providers and patients; dis- nated care or on how this model addresses health care
ease registries for population management; social disparities. Although different nancial models have
media for distributing health messages; reimburse- been proposed and are incorporated in some PCMH
ment alignment to facilitate coordinated care; and models, evaluations do not specically address the
further development of strategies to address health effectiveness of these strategies, nor have most
care disparities and barriers to care. The TT recog- studies demonstrated overall short-term cost savings
nized that the ACA supports 2 emerging models that (100). A recent review of 27 PCMH studies found that
seek to address these issues and improve integrated only 11 provided any detail on their nancial models
care for complex patients. (101). There is also a limited evidence base for
PATIENT-CENTERED MEDICAL HOME. To varying addressing disparities. In fact, in a retrospective
degrees, the PCMH addresses each of the aforemen- cohort study of 1,457 diabetic patients receiving care
tioned principles of care model implementation. The in a PCMH academic practice, African-American pa-
PCMH is organized around several core principles: tients were less likely to receive HbA 1c testing or
1) comprehensive team-based care; 2) patient- inuenza vaccination or to meet LDL or blood pres-
centered care; 3) care coordination; 4) accessible ser- sure targets than non-Hispanic Caucasians, after
vices; and 5) quality improvement and safety (94). A adjusting for multiple demographic factors and com-
systematic review of 31 studies found a positive effect orbidities (102). Similar to the cultural adaptations of
of components of the PCMH model on patient and the community-level interventions discussed earlier,
staff experiences, as well as positive effects on pre- new PCMH models must be modied to specically
ventive services, with reduction in emergency address the needs of particular populations.
department visits in older adults, but no effect on ACCOUNTABLE CARE ORGANIZATIONS. The ACO is
hospital admissions or total costs (95). However, another mechanism relevant to implementing a new
comparisons across studies on the PCMH are often MetS care model. Although the PCMH focuses on
difcult because of differences in denition and focus. coordination at the level of primary care, the ACO is a
In another study of 36 family practices implementing larger organization that includes hospitals and spe-
PCMH components over 26 months, improvement cialty care. Compared with many PCMH models, the
was seen in prevention and chronic care quality ACOs reimbursement changes and cost-saving goals
metrics, but not in patient-assessed outcomes (96). are more explicit and are better aligned to facilitate
Long-term data is also limited, as most of these coordinated care. Most ACO models are very new,
models were implemented over the last 5 to 10 years. but available evaluations indicate that health care
The Group Health Cooperative reduced physician spending has declined. Medicare beneciaries in the
panel sizes, increased ancillary staff, lengthened same market as a commercial ACO realized decreases
visit times, and provided time for team care planning, in total health care spending over 2 years, primarily due
in addition to expanding technology to better engage to reduced outpatient ofce visits, minor procedures,
patients. Comparison with control clinics in the imaging, and laboratories. There were some improve-
area demonstrated better patient satisfaction scores, ments in LDL testing for patients with T2D and ASCVD
reduced provider burnout, improved performance but not on other quality metrics (103). An evaluation of
on quality of care metrics, and reduced emergency Medicare enrollees in the Medicare Physician Group
department visits and inpatient admissions for Practice Demonstration compared with control sub-
ambulatory sensitive conditions over a 12- to 24- jects found that the savings were highest for acute
1064 Sperling et al. JACC VOL. 66, NO. 9, 2015

Proceedings of the CMHA Cardiometabolic Think Tank SEPTEMBER 1, 2015:105067

care and dually-eligible beneciaries, with an overall diagnostic subtyping and staging to improve risk
reduction in 30-day medical readmissions (104). Ac- stratication and personalized medical care. Future
cording to a Centers for Medicare & Medicaid Services TT initiatives will provide objective data on the
release of 1-year data, ACOs have also slowed cost combined use of pharmaceuticals, structured life-
growth (0.3% vs. 0.8% in 2012), reduced readmission style, behavioral interventions, and surgical/non-
rates, improved blood pressure control, and better surgical bariatric procedures to improve morbidity
assessed LDL in patients with T2D (105). and mortality among patients with or at risk for
In addition to cost savings, ACOs have successfully MetS. A greater emphasis on assessing nutritional
implemented quality improvement initiatives, as quality and levels of physical activity, with a focus
demonstrated by 1 evaluation in 11 primary care on lling the gap between public health approaches
clinics that employed care coordination, a care gap and implementation in clinical practice, will be
summary tool, staff education, and workow redesign needed. Care models will continue to incorporate
(106). Although integration of care into larger orga- ACOs, but uncertainty exists as to how the ACA will
nizations may address health care disparities, this has affect MetS care in the future. It is foreseen that
not been specically addressed in ACO design. An health care will transition to a greater degree from
evaluation examining differences in care provided to the clinic to the community, improving access to
Caucasian and African-American Medicare bene- care, and that there will be a broadening of stake-
ciaries according to size of provider group found that holders to include public health, community, and
beneciaries assigned to larger groups were more industry sectors. Screening and performance metrics
likely to be Caucasian with lower poverty rates and will enhance implementation of new care models in
higher educational attainment compared with those the future. Finally, the TT afrmed a call to action to
in small or medium groups. African-American bene- encourage ongoing partnerships, funding, and ini-
ciaries with T2D were less likely to receive LDL tiatives to improve the lives of people with or at risk
testing and retinal examinations and were more likely for MetS.
to be hospitalized than Caucasian beneciaries.
ACKNOWLEDGMENTS The authors thank Dr. William
Although larger provider groups attenuated racial
Oetgen, Ms. Nicole Wilson, and the staff at the
disparities in some areas, they did not change dis-
American College of Cardiology who were instru-
parities on other metrics, such as hospitalization rates
mental in planning and coordinating the Car-
(107). ACOs will need to specically address health
diometabolic Think Tank.
care disparities among patients with MetS.


Laurence S. Sperling, Emory University School of
Several important challenges remain in the care of Medicine, 1365 Clifton Road Northeast, Building A,
patients with MetS. These include collecting more Suite 2200, Atlanta, Georgia 30322. E-mail: lsperli@
data and developing expert consensus on MetS


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