Transcript Slide 1

Metabolic Syndrome and
Diabetes: Evaluating CVD
Risk and Strategies for CVD
Risk Reduction
Nathan D. Wong, PhD, FACC, FAHA
Professor and Director
Heart Disease Prevention Program
Division of Cardiology
University of California, Irvine
Immediate Past President, American Society
for Preventive Cardiology
Outline
• Review the role and limitations of global risk
assessment
• Review the evidence and recommendations for
biomarkers in CVD risk assessmennt
• Review the evidence and recommendations for
subclinical disease evaluation / imaging in CVD
risk assessment
• Discuss features that will be considered in the
new NHLBI risk assessment guidelines to be
released in 2013
Age-adjusted prevalence of obesity in adults 20–
74 years of age, by sex and survey year
(NHES: 1960–1962; NHANES: 1971–1975, 1976–
1980, 1988–1994, 1999-2002 and 2003-2006).
.
40
35
30
Percent of Population
34.0
33.1
35.2
28.1
26.0
25
20.6
20
15.7
15
10.7
12.2
16.8
17.1
12.8
10
5
0
Men
1960-62
Women
1971-75
1976-80
1988-94
1999-2002
2003-06
Obesity is defined as a BMI of ≥30.0. Source: Health, United States, 2009 (NCHS).
©2010 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2010
Diabetes: A Growing Challenge
Prevalence in the United States
7
20
Diagnosed Diabetes
16
Number (Millions)
5
% of Population
18
Percentage of Population
14
12
4
10
3
8
6
2
4
1
2
Centers for Disease Control and Prevention, Division of Diabetes Translation.
National Diabetes Surveillance System. Available at http://www.cdc.gov/diabetes/statistics.
2006
2003
2000
1997
1994
1991
1988
1985
1982
1979
1976
1973
1970
1967
1964
1961
0
1958
0
# of Patients in Millions
6
Age-Adjusted Prevalence of Type 2 DM: California Adults
Aged >18 Including Hispanic and Asian Subgroups 2009
N.D. Wong, California Health Interview Survey (unpublished)
Natural History of Type II Diabetes Mellitus
Years from
diagnosis
-10
-5
0
Onset
Diagnosis
5
10
Insulin resistance
Insulin secretion
Postprandial
glucose
Microvascular complications
Fasting glucose
Macrovascular complications
Pre-diabetes
Ramlo-Halsted BA et al. Prim Care. 1999;26:771-789
Nathan DM et al. NEJM 2002;347:1342-1349
Type II diabetes
15
Diagnostic Criteria for
Glycemic Abnormalities
FPG
Hemoglobin A1C
2-Hour PG on OGTT
Diabetes Mellitus
Diabetes Mellitus
Diabetes Mellitus
126 mg/dL
7.0 mmol/L
6.5%
Prediabetes
100 mg/dL
Prediabetes
5.6 mmol/L
Normal
200 mg/dL
6.0%
140 mg/dL
Impaired Glucose
Tolerance
Normal
11.1 mmol/L
7.8 mmol/L
Normal
To convert mg/dL to mmol/L multiply mg/dl by 0.055
FPG=Fasting plasma glucose, PG=Plasma glucose, OGTT=Oral glucose tolerance test
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2001;24:S5-S20
American Diabetes Association. Diabetes Care 2010;33:S11-61
Diabetes Mellitus:
Lifetime Risk
Narayan et al. JAMA 2003;290:1884-1890.
Diabetes and CVD
• Atherosclerotic complications responsible for
– 80% of mortality among patients with diabetes
– 75% of cases due to coronary artery disease
(CAD)
– Results in >75% of all hospitalizations for diabetic
complications
• 50% of patients with type 2 diabetes have
preexisting CAD. (This number may be less now
that more younger people are diagnosed with
diabetes.)
• 1/3 of patients presenting with myocardial
infarction have undiagnosed diabetes mellitus
Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28C
Norhammar A, et.al. Lancet 2002;359;2140-2144
Mechanisms by which Diabetes Mellitus
Leads to Coronary Heart Disease
Hyperglycemia
Insulin Resistance
Inflammation
Infection
 IL-6
 CRP
 SAA
 Defense
mechanisms
 Pathogen burden
HTN
Endothelial
dysfunction
 AGE
 Oxidative
stress
Dyslipidemia
 LDL
 TG
 HDL
Subclinical Atherosclerosis
Thrombosis
 PAI-1
 TF
 tPA
Disease Progression
Atherosclerotic Clinical Events
AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease HDL=Highdensity lipoprotein, HTN=Hypertension, IL-6=Interleukin-6, LDL=Low-density lipoprotein, PAI-1=Plasminogen
activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor, TG=Triglycerides, tPA=Tissue
plasminogen activator
Biondi-Zoccai GGL et al. JACC 2003;41:1071-1077.
Most Cardiovascular Patients Have
Abnormal Glucose Metabolism
GAMI
n = 164
31%
35%
34%
Normoglycemia
EHS
n = 1920
37%
18%
45%
Prediabetes
CHS
n = 2263
27%
37%
36%
Type 2 Diabetes
GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study;
EHS = Euro Heart Survey; CHS = China Heart Survey
Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38.
Risk of Cardiovascular Events in Patients
with Diabetes: Framingham Study
_________________________________________________________________
Cardiovascular Event
Age-adjusted
Biennial Rate
Per 1000
Men Women
Age-adjusted
Risk Ratio
Men Women
Coronary Disease
Stroke
Peripheral Artery Dis.
Cardiac Failure
All CVD Events
39
15
18
23
76
1.5**
2.9***
3.4***
4.4***
2.2***
21
6
18
21
65
2.2***
2.6***
6.4***
7.8***
3.7***
_________________________________________________________________
Subjects 35-64 36-year Follow-up
**P<.001,***P<.0001
Diagnostic Criteria for Metabolic Syndrome:
Modified NCEP ATP III
≥3 Components Required for Diagnosis
Components
Defining Level
Increased waist circumference
Men
Women
Elevated triglycerides
Reduced HDL-C
Men
Women
Elevated blood pressure
Elevated fasting glucose
AHA/NHLBI Scientific Statement; Circulation 2005; 112:e285-e290.
≥ 40 in
≥ 35 in
≥150 mg/dL
(or Medical Rx)
<40 mg/dL
<50 mg/dL
(or Medical Rx)
≥130 / ≥85 mm Hg
(or Medical Rx)
≥100 mg/dL
(or Medical Rx)
IDF Criteria: Abdominal Obesity and
Waist Circumference Thresholds
Men
Women
Europid
≥ 94 cm (37.0 in)
≥ 80 cm (31.5 in)
South Asian
≥ 90 cm (35.4 in)
≥ 80 cm (31.5 in)
Chinese
≥ 90 cm (35.4 in)
≥ 80 cm (31.5 in)
Japanese
≥ 85 cm (33.5 in)
≥ 90 cm (35.4 in)
• AHA/NHLBI criteria: ≥ 102 cm (40 in) in men, ≥ 88 cm (35 in) in women
• Some US adults of non-Asian origin with marginal increases should benefit
from lifestyle changes. Lower cutpoints (≥ 90 cm in men and ≥ 80 cm in
women) for Asian Americans
>90cm (male) and >80cm (female) recommended for persons of Central and
South American ancestry (including US Hispanics)
Alberti KGMM et al. Lancet 2005;366:1059-1062. | Grundy SM et al. Circulation 2005;112:2735-2752.
Intra-abdominal (Visceral) Fat
The dangerous inner fat!
Front
Visceral AT
Subcutaneous AT
Back
Abdominal Adiposity Is Associated
With Increased Risk of Diabetes
Relative Risk of Diabetes
25
P value for trend <0.001
20
15
10
5
0
<28 >28-29 30-31 32-33 34-35 36-37
Waist Circumference (in)
Carey VJ, et al. Am J Epidemiol. 1997;145:614-619
≥38
Pericardial Fat Predicts CVD Risk
MACE patient (CABG): 58-year-old woman with BMI 32.8 and CCS
= 0, PFV = 187 cm3 and TFV 315 cm3
After adjustment for Framingham risk score (FRS), CCS, and body mass
index, PFV and TFV were significantly associated with MACE (odds ratio
[OR]: 1.74, 95% confidence interval [CI]: 1.03 to 2.95 for each doubling of
PFV; OR: 1.78, 95% CI: 1.01 to 3.14 for TFV).
Cheng et al. JACC Img 2010;3:352-60
Metabolic Syndrome and Diabetes in Relation to CHD, CVD,
and Total Mortality: U.S. Men and Women Ages 30-74
(Risk-factor Adjusted Cox Regression) NHANES II Follow-up (n=6255)
7
***
6
Relative Risk
***
5
***
None
4
MetS
***
***
3
***
Diabetes
***
2
***
*
**
***
CVD
***
1
CVD+Diabetes
0
CHD Mortality
CVD Mortality
Malik and Wong, et al., Circulation 2004.
Total Mortality
* p<.05, ** p<.01, **** p<.0001 compared to none
Global Risk Assessment in DM:
10-year Total CVD Risk
(Wong ND et al., Diab Vas Dis Res 2012)
Annual CHD Event Rates (in %) by Calcium Score Events by CAC
Categories in Subjects with DM, MetS, or Neither Disease
(Malik and Wong et al., Diabetes Care 2011)
Coronary Heart Disease
4
Annual
CHD
Event
Rate
4
3.5
3
2.5
2
1.5
1
0.5
0
3.5
1.9
1.5
0.4
0.8
0.2
0.1
0
2.1
0.4
1-99
2.2
1.3
DM
MetS
Neither MetS/DM
100-399
400+
Coronary Artery Calcium Score
ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in
asymptomatic adults aged 40 and over with diabetes (Class IIa-B)
Mean Absolute Progression of CAC (Volume
Score) in Persons with and without MetS and
DM, CAC>0 at baseline, MESA Study
Wong ND et al., JACC Cadiovasc Imaging 2012
Progression of CAC and Incidence of CHD in Persons
with and without MetS and DM, MESA Study, by Tertile
of CAC Progression
Wong ND et al, JACC Cardiovasc Imaging 2012
Metabolic syndrome & Intimal Medial Thickness in
Caucasian (CS) and African American (AA) men and
women in ARIC Study
850
825
806
800
782
775
Carotid
IMT
750
(micromm)
725
748
734
720
705
700
685
675
652
650
625
600
CS Men
AA Men
MS(+ )
CS Women
AA Women
MS(-)
McNeill AM, et al. AJC 2004.
Prevalence of reduced Ankle Brachial Index according
to Increasing components of Metabolic Syndrome
30
25
P<0.001 for
trend
20
ABI<0.9 (%)
15
10
5
0
0 RF
1 RF
2 RF
3 RF
4 RF
5 RF
Olijhoek JK, et al. Eur Heart J 2004.
Metabolic Syndrome is an Inflammatory
Condition: Plasma hs-CRP Levels According to
Severity of the Metabolic Syndrome
C-reactive protein (mg/L)
8
6
4
2
0
0
1
2
3
4
5
Number of Components of the Metabolic Syndrome
Ridker et al, Circulation 2003;107:391-7
Summary of Care:
ABC's for Providers
A
B
C
D
E
F
A1c Target
Aspirin Daily
Blood Pressure Control
Cholesterol Management
Cigarette Smoking Cessation
Diabetes and Pre-Diabetes
Management
Exercise
Food Choices
A1c Target
Aspirin Therapy
• A1c Target: In persons with diabetes, glucose
lowering to achieve normal to near normal
plasma glucose, as defined by the HbA1c<7% also consider measurement of HbA1c for CVD
risk assessment in asymptomatic adults w/o DM
(ACCF/AHA 2010)
• Aspirin Daily: Patients with type 2 DM >40
years of age or with prevalent CVD, OR those
with metabolic syndrome without DM who are at
intermediate or higher risk (e.g., >=10% 10-year
risk of CHD)
Diabetes Mellitus:
Effect of Aspirin
25
p<0.002
p=NS
20
Endpoint (%)
No ASA
ASA
p < 0.001
p=.04
15
p<0.05
10
p=NS
5
p=NS
0
PHS
n=
Endpoint
# Events
ETDRS
APT
BIP
PPP
POPADAD
JPAD
533
3711
4502
2368
1031
1276
2539
5 yr MI
7 yr MI
1 yr MCE
5 yr CV Death 4 yr MCE 7yr MCE
4 yr MCE
26 vs 11 283 vs 241 502 vs 415 183 vs 133 20 vs 22
117 vs 116 86 vs 68
NS=Not Significant
1. Steering Committee of the Physicians' Health Study
Research Group. NEJM 1989;321:129-35
2. ETDRS Investigators. JAMA 1992;268:1292
3. Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81
4. Harpaz D et al. Am J Med 1998;105:494
3. Sacco M et al. Diabetes Care 2003;26:3264
4. Belch J et al. BMJ 2008; 337:a1840
5. Ogawa H et al. JAMA 2008; 300: 2134
Recommendations:
Antiplatelet Agents (1)
• Consider aspirin therapy (75–162 mg/day) (C)
– As a primary prevention strategy in those with type 1 or type 2
diabetes at increased cardiovascular risk (10-year risk >10%)
– Includes most men >50 years of age or women >60 years of age
who have at least one additional major risk factor
•
•
•
•
•
Family history of CVD
Hypertension
Smoking
Dyslipidemia
Albuminuria
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S32-S33.
Recommendations:
Antiplatelet Agents (2)
• Aspirin should not be recommended for CVD
prevention for adults with diabetes at low CVD
risk, since potential adverse effects from
bleeding likely offset potential benefits (C)
• 10-year CVD risk <5%: men <50 and women <60
years of age with no major additional CVD risk factors
• In patients in these age groups with multiple
other risk factors (10-year risk
5–10%), clinical judgment is required (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33.
Recommendations:
Antiplatelet Agents (3)
• Use aspirin therapy (75–162 mg/day)
– Secondary prevention strategy in those with diabetes with a
history of CVD (A)
• For patients with CVD and documented aspirin allergy
– Clopidogrel (75 mg/day) should be used (B)
• Combination therapy with aspirin (75–162 mg/day) and
clopidogrel (75 mg/day)
– Reasonable for up to a year after an acute coronary syndrome
(B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33-S34.
Summary of Intervention Studies
Risk Reduction with Individual Treatments
Persons with Diabetes Mellitus
Macrovascular
Event Reduction
Blood pressure treatment
30-50%
Lipid treatment
25-55%
Glucose treatment
per 1% HbA1c
10-20%
Poor Control of Multiple Cardiovascular Risk Factors
Among U.S. Adults with Type 2 Diabetes
– NHANES Survey 2003-2006, n=889 (14.3 million) or 6.6% of
adults aged >/=18 years had type 2 diabetes
– 58.2% at HbA1c goal <7%
– 44.2% at BP goal <130/80 mmHg
– 56.4% at recommended HDL-C >/=40 (M), >/=50 (F)
– 25.8% at recommended triglycerides <150 mg/dl
– 13.9% at BMI<25 kg/m2
– Overall, only 10.5% of men and 9.9% of women at
goal for HbA1c, BP, and LDL-C simultaneously;
only 0.3% at goal also including BMI.
Wong K, Wong ND et al . J Diab Complic 2012
Diabetes Mellitus:
Impact of Glycemic Control on CV Risk
United Kingdom Prospective Diabetes Study (UKPDS) 35
60
50
5.5%
6.5%
7.5%
8.5%
9.5%
10.5%
%
40
30
20
10
0
Myocardial Infarction
Microvascular Disease
CHD=Coronary heart disease, HbA1C=Glycated hemoglobin
Stratton IM et al. BMJ 2000;321:405-12
Diabetes Mellitus (Type II):
Effect of Intensive Glycemic Control
United Kingdom Prospective Diabetes Study (UKPDS)
3,867 patients with DM randomized to intensive therapy with a sulphonylurea
or insulin (mean HbA1C 7.0%) or conventional therapy (mean HbA1C 7.9%)
0
-10
-20
-30
-25
P<0.01
-21
P=0.02
-16
P=0.05
-12
P=0.03
-33
P<0.01
-40
-50
Microalbuminuria at 12 years
Retinopathy
Any DM endpoint
Microvascular complications
Myocardial infarction
Intensive glycemic control in DM reduces the risk of microvascular
complications
DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin
UKPDS Group. Lancet 1998;352:837-853
UKPDS Metformin Sub-Study:
CHD Events
Coronary Deaths
Myocardial Infarction
Incidence per 1000 patient years
20
10
p=0.01
p=0.02
NS
8
39%
Reduction
15
50%
Reduction
6
10
4
5
0
2
0
Conventional Insulin
SU’s
Diet
n=
#Events
411
73
UKPDS 34, Lancet 352: 854, 1998
951
139
Metformin
342
39
Conventional
Diet
Metformin
411
36
342
16
Glycemic Legacy?
N Engl J Med 2008;359:1577-89.
Recent Trials Show No Reduction in CV Events with
More Intensive Glycemic Control
25
20
Intensive therapy
Standard therapy
15
10
5
0
0
1
Number at Risk
Intensive 5128 4843
Standard 5123 4827
1ACCORD
ADVANCE: Primary Outcome
Cumulative incidence (%)
Patients with events (%)
ACCORD: Primary Outcome
2
3
Years
4390 2839
4262 2702
4
1337
1186
5
6
475
440
448
395
Study Group. N Engl J Med. 2008;358:2545-2559.
Collaborative Group. N Engl J Med. 2008;358:2560-2572.
2ADVANCE
25
20
Intensive therapy
Standard therapy
15
10
5
0
0
Number at Risk
Intensive 5570
Standard 5569
12
24
36
48
Months of follow-up
5369
5342
5100
5065
4867
4808
4599
4545
60
1883
1921
Was Intensive Glycemic Control Harmful?
A closer look at ACCORD AND ADVANCE
• ACCORD was discontinued early due to increased
total and CVD mortality in the intensive arm.
• VA Diabetes Trial showed severe hypoglycemia to
be a powerful predictor of CVD events.
• A recent analysis of ACCORD (Diabetes Care,
May 2010) showed deaths related to unsuccessful
intensive therapy where A1c remained high.
• But in both ACCORD AND ADVANCE, those
without macrovascular disease at baseline had an
actual benefit in the primary endpoint.
Metabolic Memory and Glycemic Legacy
UKPDS and VADT
Start of intensive therapy
in VADT
Start of intensive therapy
in UKPDS
9.5
Drives risk of Complications
A1C (%)
9.0
8.5
8.0
Bad Glycemic
Legacy
7.5
7.0
Ideal course =
early and sustained
glycemic control
Risk of complications continues
despite glycemic control
6.5
6.0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
Time Since Diagnosis (years)
Del Prato S. Diabetalogia. 2009;52:1219-1226.
American Diabetes Association
2012 Standards of Medical
Care: HbA1c Goals
• A reasonable A1C goal for many nonpregnant adults is
<7% due to efficacy in reducing microvascular complications.
• Consider more stringent A1C goals (such as <6.5%) for
selected patients, if this can be achieved without significant
hypoglycemia or other adverse effects of treatment.
• Less stringent A1C goals (such as <8%) may be
appropriate for patients with a history of severe hypoglycemia,
limited life expectancy, advanced microvascular or
macrovascular complications, and extensive comorbid
conditions and for those with longstanding diabetes in whom
the general goal is difficult to attain.
UKPDS: Effects of Tight vs. Less-Tight Blood
Pressure Control
UK Prospective Diabetes Study Group. BMJ. 1998; 317:703-713.
Diabetes Mellitus:
Effect of Blood Pressure Control
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood
Pressure Trial
4,733 diabetic patients randomized to intensive BP control (target SBP <120
mm Hg) or standard BP control (target SBP <140 mm Hg) for 4.7 years
HR=0.88
95% CI (0.73-1.06)
15
10
5
0
Patients with Events (%)
20
Total Stroke
Patients with Events (%)
Nonfatal MI, nonfatal
stroke, or CV death
20
HR=0.59
95% CI (0.39-0.89)
15
10
5
0
0
1
2
3
4
5
6
7
Years Post-Randomization
8
0
1
2
3
4
5
6
7
8
Years Post-Randomization
Intensive BP control in DM does not reduce a composite of adverse
CV events, but does reduce the rate of stroke
BP=Blood pressure, DM=Diabetes mellitus, HR=Hazard ratio, SBP=Systolic blood pressure
ACCORD study group. NEJM 2010
Recommendations: Hypertension/Blood
Pressure Control
Goals
• People with diabetes and hypertension should be treated to a
systolic blood pressure goal of <140 mmHg (B)
• Lower systolic targets, such as <130 mmHg, may be
appropriate for certain individuals, such as younger patients, if
it can be achieved without undue treatment burden (C)
• Patients with diabetes should be treated to a diastolic blood
pressure <80 mmHg (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (1)
• Patients with a blood pressure (BP) >120/80 mmHg
should be advised on lifestyle changes to reduce BP
(B)
• Patients with confirmed BP ≥140/80 mmHg should,
in addition to lifestyle therapy, have prompt initiation
and timely subsequent titration of pharmacological
therapy to achieve BP goals (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (2)
• Lifestyle therapy for elevated BP (B)
– Weight loss if overweight
– DASH-style dietary pattern including reducing sodium,
increasing potassium intake
– Moderation of alcohol intake
– Increased physical activity
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (3)
• Pharmacological therapy for patients with diabetes and
hypertension (C)
– A regimen that includes either an ACE inhibitor or angiotensin II
receptor blocker; if one class is not tolerated, substitute the other
• Multiple drug therapy (two or more agents at maximal doses)
generally required to achieve BP targets (B)
• Administer one or more antihypertensive medications at
bedtime (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (4)
• If ACE inhibitors, ARBs, or diuretics are used, kidney function,
serum potassium levels should be monitored (E)
• In pregnant patients with diabetes and chronic hypertension,
blood pressure target goals of 110–129/65–79 mmHg are
suggested in interest of long-term maternal health and
minimizing impaired fetal growth; ACE inhibitors, ARBs,
contraindicated during pregnancy (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S29.
Diabetes Mellitus:
Effect of an HMG-CoA Reductase Inhibitor
Meta-analysis of 18,686 patients with DM randomized to treatment
with a HMG-CoA Reductase Inhibitor
Statins reduce CV events 21% in diabetics (similar to non-diabetics)
Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet 2008;37:117-25
ACCORD Lipid Study Results
(NEJM 2010; 362: 1563-74)
• 5518 patients with type 2 DM treated with open
label simvastatin randomly assigned to
fenofibrate or placebo and followed for 4.7
years.
• Annual rate of primary outcome of nonfatal MI,
stroke or CVD death 2.2% in fenofibrate group
vs. 1.6% in placebo group (HR=0.91, p=0.33).
• Pre-specified subgroup analyses showed
possible benefit in men vs. women and those
with high triglycerides and low HDL-C.
• Results support statin therapy alone to reduce
CVD risk in high risk type 2 DM patients.
Recommendations:
Dyslipidemia/Lipid Management (1)
Screening
• In most adult patients, measure fasting lipid profile
at least annually (B)
• In adults with low-risk lipid values
(LDL cholesterol <100 mg/dL, HDL cholesterol >50
mg/dL, and triglycerides <150 mg/dL), lipid
assessments may be repeated every 2 years (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Recommendations:
Dyslipidemia/Lipid Management (2)
Treatment recommendations and goals (1)
• To improve lipid profile in patients with diabetes,
recommend lifestyle modification (A), focusing on
– Reduction of saturated fat, trans fat, cholesterol intake
– Increased n-3 fatty acids, viscous fiber,
plant stanols/sterols
– Weight loss (if indicated)
– Increased physical activity
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Recommendations:
Dyslipidemia/Lipid Management (3)
Treatment recommendations and goals (2)
• Statin therapy should be added to lifestyle therapy, regardless of baseline
lipid levels
– with overt CVD (A)
– without CVD >40 years of age who have one or more other CVD risk factors (A)
•
For patients at lower risk (e.g., without overt CVD, <40 years of age) (C)
– Consider statin therapy in addition to lifestyle therapy if LDL cholesterol remains >100
mg/dL
– In those with multiple CVD risk factors
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Recommendations:
Dyslipidemia/Lipid Management (4)
Treatment recommendations and goals (3)
• In individuals without overt CVD
– Primary goal is an LDL cholesterol
<100 mg/dL (2.6 mmol/L) (B)
• In individuals with overt CVD
– Lower LDL cholesterol goal of <70 mg/dL
(1.8 mmol/L), using a high dose of a statin,
is an option (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Recommendations:
Dyslipidemia/Lipid Management (5)
Treatment recommendations and goals (4)
• If targets not reached on maximal tolerated statin therapy
– Alternative therapeutic goal: reduce LDL cholesterol ~30–40% from baseline
(B)
• Triglyceride levels <150 mg/dL
(1.7 mmol/L), HDL cholesterol >40 mg/dL (1.0 mmol/L) in men and >50
mg/dL
(1.3 mmol/L) in women, are desirable (C)
– However, LDL cholesterol–targeted statin therapy remains the preferred
strategy (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Recommendations:
Dyslipidemia/Lipid Management (6)
Treatment recommendations and goals (5)
• Combination therapy has been shown not to provide
additional cardiovascular benefit above statin
therapy alone and is not generally recommended (A)
• Statin therapy is contraindicated in pregnancy (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S31.
Benefit of Comprehensive, Intensive
Management: STENO 2 Study
Primary End Point=CV events (%)
60
• Treatment Goals:
–
–
–
–
–
Intensive TLC
HgbA1c <6.5%
Cholesterol <175
Triglycerides <150
BP <130/80
Conventional Therapy
Intensive Therapy
50
40
30
20
n =80
10
0
0
12
24
36
48
60
Months of Follow Up
Gaede, P. et al, NEJM 2003;348:390-393
n =80
72
84
96
Nutrition, physical activity and NCD
prevention
• Up to 80% of heart disease,
stroke and type 2 diabetes and
over a third of the most common
cancers could be prevented by
eliminating obesity, unhealthy
diets and physical inactivity
• Call for commitments at the global
and national level to address these
risk factors including:
– Control food supply, food
information and marketing and
promotion of energy-dense,
nutrient-poor foods that are
high in saturated, trans-fat,
salt or refined sugars
The NCD Alliance: United by 4 risk factors
Modifiable causative risk factors
Non-communicable Diseases
Tobacco use
Unhealthy
diets
Physical
inactivity
Harmful use
of alcohol
Heart disease and
stroke




Diabetes




Cancer




Chronic lung
disease

The Global CVD Taskforce calls on the CVD
community to endorse and support the following top 4
targets to address NCDs and help ensure achievement of
the 2025 goal of reducing NCD mortality by 25%:
1) Physical inactivity: 10% relative reduction in prevalence
of insufficient physical activity
2) Raised blood pressure: 25% relative reduction in
prevalence of raised blood pressure
3) Salt/Sodium Intake: 30% relative reduction in mean
population intake of salt, with aim of achieving
recommended level of <5 g/d (2000 mg of sodium) (note
various organizations such as the AHA call for a limit of
1500 mg/day)
4) Tobacco: 30% relative reduction in prevalence of current
tobacco smoking
Smith SC et al., 2012
Weight Management Recommendations
Goals
Recommendations
Calculate BMI* and measure waist
circumference
BMI 18.5 to 24.9 kg/m2
Women: <35 inches
Men: <40 inches
Monitor response to treatment
I IIa IIb III
Start weight management and
physical activity as appropriate
10% weight reduction
within the 1st yr of Rx
*BMI is calculated as the weight in kilograms divided
by the body surface area in meters2
If BMI and/or waist circumference is
above goal, initiate caloric restriction
and increase caloric expenditure
BMI=Body mass index, Rx=Treatment
Source: Smith SC Jr. et al. JACC 2006;47:2130-9
Diabetes Prevention Program:
Reduction in Diabetes Incidence
Recommendations:
Medical Nutrition Therapy (MNT)
• Individuals who have prediabetes or diabetes
should receive individualized MNT as needed to
achieve treatment goals, preferably provided by
a registered dietitian familiar with the
components of diabetes MNT (A)
• Because MNT can result in cost-savings and
improved outcomes (B), MNT should be
adequately covered by insurance and other
payers (E)
ADA. V. Diabetes Care. Diabetes Care 2013;36(suppl 1):S22.
Look AHEAD (Action for Health in Diabetes):
Trial Halted Early
• Intensive lifestyle intervention resulted in1
– Average 8.6% weight loss
– Significant reduction of A1C
– Reduction in several CVD risk factors
• Benefits sustained at 4 years2
• However, trial halted after 11 years of follow-up
because there was no significant difference in
primary cardiovascular outcome between weight
loss, standard care group
1, 2. Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383 and Arch Intern Med.
2010;170:1566–1575; http://www.nih.gov/news/health/oct2012/niddk-19.htm.
American Heart Association (AHA) Nutrition Committee
Dietary Recommendations
Recommendations for Cardiovascular Disease Risk Reduction
• Balance calorie intake and physical activity to achieve or maintain a
healthy body weight
• Consume a diet rich in fruits and vegetables
• Consume whole-grain, high-fiber foods
• Consume fish, especially oily fish, at least twice a week
• Limit intake of saturated fat to <7%, trans fat to <1% of energy, and
cholesterol <300 mg/day by:
– Choosing lean mean and vegetable alternatives
– Choosing fat free (skim), 1% fat, and low-fat dairy products,
– Minimizing intake of partially hydrogenated fats
• Minimize intake of beverages and foods with added sugar
• Choose and prepare foods with little or no salt
(AHA 2011 rec. <1500mg/d)
• If alcohol is consumed, do so in moderation
Source: AHA Nutrition Committee. Circulation 2006;114:82-96
JNC VII Lifestyle Modifications for
BP Control
Modification
Recommendation
Approximate SBP
Reduction Range
Maintain normal body weight
(BMI=18.5-24.9)
5-20 mmHg/10 kg weight
lost
Diet rich in fruits, vegetables, low fat
dairy and reduced in fat
8-14 mmHg
Restrict sodium
intake
<2.4 grams of sodium per day
2-8 mmHg
Physical activity
Regular aerobic exercise for at least 30
minutes on most days of the week
4-9 mmHg
Moderate alcohol
consumption
<2 drinks/day for men and <1 drink/day
for women
2-4 mmHg
Weight reduction
Adopt DASH
eating plan
BMI=Body mass index, SBP=Systolic blood pressure
71
Chobanian AV et al. JAMA. 2003;289:2560-2572
Recommendations:
Smoking Cessation
• Advise all patients not to smoke or use tobacco
products (A)
• Include smoking cessation counseling and other
forms of treatment as a routine component of
diabetes care (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S34.
Recommendations: Physical Activity
• Advise people with diabetes to perform at least
150 min/week of moderate-intensity aerobic
physical activity (50–70% of maximum heart
rate), spread over at least 3 days per week with
no more than
2 consecutive days without exercise (A)
• In absence of contraindications, adults with type
2 diabetes should be encouraged to perform
resistance training at least twice per week (A)
ADA. V. Diabetes Care. Diabetes Care 2013;36(suppl 1):S24.
RCT Trial Assessment of Pedometer
Interventions
N=277; 8 Trials
Pedometer increased steps by 2500/day
Bravata, DM et al. JAMA 2007; 298:2296-2304
Recommendations:
Psychosocial Assessment and Care
• Ongoing part of medical management of diabetes
(E)
• Psychosocial screening/follow-up: attitudes about
diabetes, medical management/outcomes
expectations, affect/mood, quality of life, resources,
psychiatric history (E)
• When self-management is poor, screen for
psychosocial problems: depression, diabetes-related
anxiety, eating disorders, cognitive impairment (B)
ADA. V. Diabetes Care. Diabetes Care 2013;36(suppl 1):S25-S26.
SUMMARY
• MetS and DM confer increased risks for
CVD complications
• The wide spectrum in CVD risks, however,
warrants careful CVD risk assessment in
such individuals
• Lifestyle modification remains the
cornerstone of efforts to prevent and reduce
progression of MetS and DM globally
• Glycemic, blood pressure, lipid, and
antiplatelet therapy are key to reduce CVD
risks associated with MetS and DM
Thank You!
American Society for
Preventive Cardiology
www.aspconline.org
www.heart.uci.edu