Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome Nathan D. Wong, PhD,...

Cardiovascular Disease and the

Patient with Diabetes and Metabolic Syndrome

Nathan D. Wong, PhD, FACC, FAHAProfessor and Director

Heart Disease Prevention ProgramDivision of Cardiology

University of California, IrvinePresident, American Society for

Preventive Cardiology

Presenter Disclosure

• Dr. Wong has received research support through Bristol-Myers Squibb, Novartis, and Forest Laboratories through the University of California, Irvine

Presentation Objectives

• Review the epidemiology implicating metabolic syndrome and diabetes in cardiovascular risk

• Discuss the clinical trial evidence for the role of lifestyle management, glycemic, lipid, and blood pressure control.

• Address the ABCs of lifestyle and clinical management of metabolic syndrome and diabetes aimed to reduce cardiovascular disease risk.

Diagnosed Diabetes in the US: 2008

http://apps.nccd.cdc.gov/brfss/list.asp?cat=DB&yr=2008&qkey=1363&state=All

4 – 6% 6 – 8% 8 – 10% 10 – 12%

CDC BRFSS: Self-Reported Diabetes: 8.2% Nationwide

Prevalence of physician-diagnosed diabetes in Adults age 20 Prevalence of physician-diagnosed diabetes in Adults age 20 and older by race/ethnicity and sex (NHANES: 2005-2006). and older by race/ethnicity and sex (NHANES: 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.Source: NCHS and NHLBI. NH – non-Hispanic.

5.8 6.1

14.9

13.1

11.3

14.2

0

2

4

6

8

10

12

14

16

Men Women

Pe

rce

nt

of

Po

pu

lati

on

NH Whites NH Blacks Mexican Americans

The Continuum of CV Risk in Type 2 The Continuum of CV Risk in Type 2 DiabetesDiabetes

Adapted from American Diabetes Association. Diabetes Care. 2003;26:3160-3167.Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953.Hsueh WA, et al. Am J Med. 1998;105(1A):4S-14S.American Diabetes Association. Diabetes Care. 1998;21:310-314.

Diagnostic Criteria for Metabolic Diagnostic Criteria for Metabolic Syndrome: Modified NCEP ATP IIISyndrome: Modified NCEP ATP III

AHA/NHLBI Scientific Statement; Circulation 2005; 112:e285-e290.

≥3 Components Required for Diagnosis

Components Defining Level

Increased waist circumferenceMenWomen

≥ 40 in≥ 35 in

Elevated triglycerides≥150 mg/dL

(or Medical Rx)

Reduced HDL-CMenWomen

<40 mg/dL<50 mg/dL

(or Medical Rx)

Elevated blood pressure≥130 / ≥85 mm Hg

(or Medical Rx)

Elevated fasting glucose≥100 mg/dL

(or Medical Rx)

IDF Criteria: Abdominal Obesity and IDF Criteria: Abdominal Obesity and Waist Circumference ThresholdsWaist Circumference Thresholds

Men WomenEuropid ≥ 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

Alberti KGMM et al. Lancet 2005;366:1059-1062. | Grundy SM et al. Circulation 2005;112:2735-2752.

Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994

Pre

vale

nc

e (

%)

P

reva

len

ce

(%

)

05

10

15

2025

3035

40

45

20-29 30-39 40-49 50-59 60-69 > 70

MenMenWomenWomen

Age (years)Age (years)Ford E et al. JAMA. 2002(287):356.Ford E et al. JAMA. 2002(287):356.

1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+)NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women

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-28CNorhammar A, et.al. Lancet 2002;359;2140-2144

Risk of Cardiovascular Events in Patients Risk of Cardiovascular Events in Patients withwith Diabetes: Diabetes: Framingham StudyFramingham Study

Age-adjusted

Biennial Rate Age-adjusted

Per 1000 Risk RatioCardiovascular Event Men Women Men Women

Coronary Disease 39 21 1.5** 2.2***Stroke 15 6 2.9*** 2.6***Peripheral Artery Dis. 18 18 3.4*** 6.4***Cardiac Failure 23 21 4.4*** 7.8***All CVD Events 76 65 2.2*** 3.7***

Subjects 35-64 36-year Follow-up **P<.001,***P<.0001

_________________________________________________________________

_________________________________________________________________

Diabetes as a CHD Risk Equivalent: Diabetes as a CHD Risk Equivalent: Type 2 DM and CHD Type 2 DM and CHD

7-Year Incidence of Fatal/Nonfatal MI 7-Year Incidence of Fatal/Nonfatal MI (East West Study)(East West Study)

No Diabetes Diabetes

3.5%

18.8%20.2%

45.0%P<0.001 P<0.001

7-ye

ar i

nci

den

ce r

ate

of

MI

CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus

Haffner SM et al. N Engl J Med. 1998;339:229-234.

Cardiovascular Disease (CVD) and Total Cardiovascular Disease (CVD) and Total Mortality: U.S. Men and Women Ages 30-74Mortality: U.S. Men and Women Ages 30-74

* p<.05, ** p<.01, **** p<.0001 compared to none

*

***

***

***

**

***

***

***

***

***

***

Malik and Wong, et al., Circulation 2004; 110: 1245-1250.

(Risk-factor adjusted Cox regression) NHANES II Follow-Up (n=6255)

***

Odds of CVD Stratified by CRP Levels in U.S. Persons (Malik and Wong et al., Diabetes Care 2005; 28: 690-3)

–*p<.05, **p<.01, **** p<.0001 compared to no disease, low CRP

–CRP categories: >3 mg/l (High) and <3 mg/L (Low)

–age, gender, and risk-factor adjusted logistic regression (n=6497)age, gender, and risk-factor adjusted logistic regression (n=6497)

Nodisease Metabolic

Syndrome Diabetes

Low CRP

High CRP0

1

2

3

4

5

6

**

***

**

***Odds

Rat io

Example of Significant Coronary Calcification from Multidetector CT (Siemens Sensation 64) scanner

10-Year CHD Event Rates (per 1000 person years) by Calcium Score by CAC Categories in

Subjects with Neither MetS nor DM, MetS only, or DMCoronary Heart Disease

Coronary Artery Calcium Score

0 1-99 100-399 400+0 1-99 100-399 400+

CH

D even

ts per 1000

CH

D even

ts per 1000

perso

n years

perso

n years DiabetesDiabetes

MetSMetSNeither MetS/DMNeither MetS/DM

Malik and Wong et al. (AHA 2009)Malik and Wong et al. (AHA 2009)

Under-Treatment of Cardiovascular Risk Under-Treatment of Cardiovascular Risk Factors Among U.S. Adults with DiabetesFactors Among U.S. Adults with Diabetes

– NHANES Survey 2001-2002, 532 (projected to 15.2 million) or 7.3% of adults aged >/=18 years had diabetes

– 50.2% not at HbA1c goal <7%– 64.6% not at LDL-C goal <100 mg/dl– 52.3% not at recommended HDL-C >/=40 (M), >/=50 (F)– 48.6% not at recommended triglycerides <150 mg/dl– 53% not at BP goal of <130/80 mg/dl

– Overall, only 5% of men and 12% of women at goal for HbA1c, BP, and LDL-C simultaneously

Malik S, Wong ND et al. Diab Res Clin Pract 2007;77:126-33.

Summary of Care: ABC's for ProvidersA A1c Target

Aspirin Daily

B Blood Pressure Control

C Cholesterol ManagementCigarette Smoking Cessation

D Diabetes and Pre-Diabetes Management

E Exercise

F Food Choices

Summary of Care: ABC's for Providers

A A1c Target Aspirin Daily




E Exercise

F Food Choices

A1c TargetA1c TargetAspirin TherapyAspirin Therapy

• A1c Target: In persons with diabetes, glucose lowering to achieve normal to near normal plasma glucose, as defined by the HbA1c<7%

• 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)

Type 2 Diabetes: Type 2 Diabetes: A1C Predicts CHDA1C Predicts CHD

CHD Mortality Incidence (%) in 3.5 Years

All CHD Events Incidence (%) in 3.5 Years

A1C=hemoglobin A1C*P<0.01 vs lowest tertile**P<0.05 vs lowest tertile

0

2

4

6

8

10

12

Low<6%

High>7.9%

**

Middle6-7.9%

0

5

10

15

20

25

Middle6-7.9%

High>7.9%

**

Low<6%

Adapted with permission from Kuusisto J et al. Diabetes. 1994;43:960-967.

% r

ela

tive r

isk r

ed

ucti

on

P=0.03

P<0.01

P<0.01

P=0.05

P=0.02

UKPDS Group. Lancet. 1998;352:837-853.

UKPDS Relative Risk Reduction UKPDS Relative Risk Reduction for Intensive vs. Less Intensive Glucose Controlfor Intensive vs. Less Intensive Glucose Control

Over 10 years, HbA1c was 7.0% (6.2-8.2) in the intensive group (n=2,729) compared with 7.9% (6.9-8.8) in the conventional group (n=1,138).

UKPDS 34, Lancet 352: 854, 1998

UKPDS Metformin Sub-Study: UKPDS Metformin Sub-Study: CHD EventsCHD Events

Myocardial InfarctionMyocardial Infarction

0

5

10

15

20

Inci

den

ce

per

100

0 p

atie

nt

yea

rs

ConventionalDiet

InsulinSU’s

Metformin

p=0.01

NS

39%Reduction

Coronary DeathsCoronary Deaths

0

2

4

6

8

10 p=0.02

50%Reduction

Metformin

Inci

den

ce

per

100

0 p

atie

nt

yea

r s

ConventionalDiet

n= 411 951 342 411 342#Events 73 139 39 36 16

Recent Trials Show No Reduction in CV Events with Recent Trials Show No Reduction in CV Events with More Intensive Glycemic ControlMore Intensive Glycemic Control

1ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.2ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572.

Number at RiskIntensive 5570 5369 5100 4867 4599 1883Standard 5569 5342 5065 4808 4545 1921

25

20

15

10

5

00 12 24 36 48 60

Cu

mu

lati

ve i

nci

de

nce

(%

)

Months of follow-up

Standard therapyIntensive therapy

ADVANCE: Primary Outcome

Number at RiskIntensive 5128 4843 4390 2839 1337 475 448Standard 5123 4827 4262 2702 1186 440 395

Pat

ien

ts w

ith

ev

ents

(%

)

0 1 2 3 4 5 6

25

20

15

10

5

0

Years

Standard therapyIntensive therapy

ACCORD: Primary Outcome

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. Major hypoglycemia 3-fold higher too.

• And the VA Diabetes Trial did show severe hypoglycemia to be a powerful predictor of CVD events.

• But a more recent analysis of ACCORD just published (Diabetes Care, May 2010) showed deaths to be associated with unsuccessful intensive therapy where A1c remained high.

• However, in both ACCORD AND ADVANCE, the subgroups without macrovascular disease at baseline had an actual benefit in the primary endpoint.

2009 ADA/AHA/ACC Statement 2009 ADA/AHA/ACC Statement RecommendationsRecommendations

• Goal of A1c<7% remains reasonable – for uncomplicated patients

• ACC/AHA Class I (A)

– and for those with macrovascular disease • ADA Level B; ACC/AHA Class IIb (A)

• Incremental microvascular benefit may be obtained from even lower goals

• ADA Level B; ACC/AHA Class IIa (C)

• Less stringent goals may be appropriate for those with labile glucose control or with advanced micro- or macrovascular disease

• ADA Level C; ACC/AHA Class IIa (C)

Circulation 2009; 119: 351-357



B Blood Pressure ControlC Cholesterol Management

Cigarette Smoking Cessation


E Exercise

F Food Choices

Prevalence of Hypertension* in Adults Prevalence of Hypertension* in Adults with Diabetes: NHANES III 1988-1994with Diabetes: NHANES III 1988-1994

% w

ith

Hy

per

ten

sio

n

Geiss LS, et al. Am J Prev Med. 2002;22:42-48.

*BP ≥130/85 or therapy for hypertension

HTN Control Rate Remains Poor in US Adults with MetS and DM from NHANES

2003-2004(Wong ND et al., Arch Intern Med 2007)

• Only 35% of those with DM on treatment for HTN are controlled to a goal of <130/80 mmHg

• Only 47% of those with MetS on treatment for HTN have a blood pressure of <130/85 mmHg

• Thus, JNC-7 recommendations to begin with combination therapy to improve goal attainment should be adhered to, esp. if SBP/DBP exceeds 20/10 mmHg from goal.

UKPDS: Effects of Tight vs. Less-Tight UKPDS: Effects of Tight vs. Less-Tight Blood Pressure ControlBlood Pressure Control

UK Prospective Diabetes Study Group. BMJ. 1998; 317:703-713.

HOT Trial: HOT Trial: Effect of BP Control on CV Event RateEffect of BP Control on CV Event Rate

Hansson L et al. Lancet. 1998;351:1755-1762.

Diastolic Blood Pressure goal

Patients without Diabetes Patients with Diabetes

Major CV events per1000 patient-years

ACCORD: Effects of Intensive BP Control (NEJM 2010: 362: 1575-85)

• 4733 participants with type 2 DM randomly assigned to intensive therapy targeting a SBP <120 mmHg vs. standard therapy targeting a SBP<140 mmHg.

• Mean follow-up 4.7 years.• SBP after 1 year was 119 vs. 133 mmHg.• No difference in the primary endpoint of nonfatal MI,

stroke, or CVD death (annual rate): 1.9% vs. 2.1% (HR=0.88), p=0.20.

• Stroke annual rates significantly lower 0.32% vs. 0.53%, HR=0.59, p=0.01. Thus, overall benefit may be greater in populations with higher stroke risk.

Scientific Statements: Scientific Statements: Diabetes, CV Disease and HypertensionDiabetes, CV Disease and Hypertension

• JNC VII Report on Diabetic Hypertension– BP goal (<130/80 mm Hg)

• Commonly requiring combinations of ≥2 drugs

– ACEIs, CCBs, Thiazide-diuretics, -blockers, and ARBs shown to reduce CVD/CVA risk

– ACEIs/ARBs reduce progression of diabetic nephropathy and reduce albuminuria

– ARBS reduce progression of macroalbuminuria

Grundy SM, et al. Circulation. 1999;100:1134-1146. Chobanian AV, et al. JAMA. 2003;289:2560-2572.






E Exercise

F Food Choices

LDL-C as a Predictor of CAD LDL-C as a Predictor of CAD in Patients with Diabetesin Patients with Diabetes

0

1

2

70 mg/dl 98 mg/dl 118 mg/dl 151 mg/dl

Haz

ard

rat

io

LDL-C quartile mean

Adapted with permission from Howard BV et al. Arterioscler Thromb Vasc Biol. 2000;20:830-835.

LDL=low-density lipoprotein cholesterol; CAD=coronary artery disease.

Relative Risk Reduction 37% (95% CI: 17-52)

Years

328305

694651

10741022

13611306

13921351

AtorvaPlacebo

14281410

Placebo127 events

Atorvastatin83 events

Cu

mu

lati

ve H

aza

rd (

%)

0

5

10

15

0 1 2 3 4 4.75

P = 0.001

CARDS: Primary EndpointCARDS: Primary Endpoint

Colhoun HM et al. Lancet 2004;364:685-96.

HPS Substudy: HPS Substudy: First Major Vascular Event by LDL-C and First Major Vascular Event by LDL-C and

Prior Diabetes StatusPrior Diabetes Status

Simvastatin(10,269)

Placebo(10,267)

Rate ratio (95% CI)

Statin better Placebo better

LDL-C anddiabetes status

<116 mg/dL

With diabetes 191 (15.7%) 252 (20.9%)

No diabetes 407 (18.8%) 504 (22.9%)

116 mg/dL

With diabetes 410 (23.3%) 496 (27.9%)

No diabetes 1,025 (20.0%) 1,333 (26.2%)

All patients 2,033 (19.8%) 2,585 (25.2%)24% reduction

(P<0.0001)

0.4 0.6 0.8 1.0 1.2 1.4

HPS Collaborative Group. Lancet. 2003;361:2005-2016.

Reducing CVD Risk with Statin Therapy Reducing CVD Risk with Statin Therapy in Patients with Diabetesin Patients with Diabetes

• Number needed to treat to prevent 1 major CVD event

– From HPS and 4S• Without coronary disease 14• With coronary disease 4

– From meta-analysis• Without vascular disease 39

• With vascular disease 19

HPS Collaborative Group. Lancet. 2003;361:2005-2016.Pyorala K, et al. Diabetes Care. 1997;20:614-620Kearney PM Lancet;2008:371:227-239

Lipid Goals for Persons with Metabolic Syndrome and DM (Grundy et al., 2005)

LDL-C targets, ATP III guidelines

–High Risk: CHD, CHD risk equivalents (incl. DM or >20% 10-year risk): <100 mg/dL (option <70 mg/dl if CVD present)

– Moderately High Risk (10-20%) 2 RF: <130 mg/dL, option <100 mg/dL

– Moderate Risk (2+ RF, <10%) <130 mg/dL

-- Low Risk: 0-1 RF: <160 mg/dL

HDL-C: >40 mg/dL (men)

>50 mg/dL (women)

TG: <150 mg/dL

Non-HDL: Secondary Target

• Non-HDL = TC – HDL

• Non-HDL: secondary target of therapy when serum triglycerides are 200 mg/dL (esp. 200-499 mg/dl)

• Non-HDL goal: LDL goal + 30 mg/dL

Specific Dyslipidemias: Specific Dyslipidemias: Elevated Triglycerides Elevated Triglycerides

Management of Low HDL

• LDL is primary target of therapy

• Weight reduction and increased physical activity (if the metabolic syndrome is present)

• Non-HDL is secondary target of therapy (if triglycerides 200 mg/dL)

• Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents)

Specific Dyslipidemias: Specific Dyslipidemias: Low HDL CholesterolLow HDL Cholesterol

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.




C Cholesterol Management

Cigarette Smoking Cessation


E Exercise

F Food Choices

Smoking CessationSmoking Cessation

• What you do does matter. Physicians who intervene influence cigarette smoking behavior.

• How do you get your patients to quit smoking?– Identify i.e.: in vitals signs

– Interventions as brief as 3 minutes can significantly increase quit rates

– Dose dependent changes in behavior

– 5-10% may quit within 1 year with MD advice alone

• Smoking cessation aids

EFFICACY OF SMOKING CESSATION EFFICACY OF SMOKING CESSATION INTERVENTIONS (1 YEAR QUIT RATES)INTERVENTIONS (1 YEAR QUIT RATES)

EFFICACY OF SMOKING CESSATION EFFICACY OF SMOKING CESSATION INTERVENTIONS (1 YEAR QUIT RATES)INTERVENTIONS (1 YEAR QUIT RATES)

ACUPUNCTUREACUPUNCTURE ---- ----

HYPNOSISHYPNOSIS ---- ----

PHYSICIAN ADVICEPHYSICIAN ADVICE 6% 6%

SELF-HELP METHODSSELF-HELP METHODS 14%14%

NICOTINE PATCHNICOTINE PATCH 11-15% 11-15%

PHYSICIAN ADVICE/SELF-HELP PAMPHLETSPHYSICIAN ADVICE/SELF-HELP PAMPHLETS 22%22%

AVERSIVE SMOKING (RAPID PUFFING)AVERSIVE SMOKING (RAPID PUFFING) 25%25%

PHARMACOTHERAPY/BEHAVIORAL THERAPYPHARMACOTHERAPY/BEHAVIORAL THERAPY 25% 25%

BEHAVIORAL STRATEGIES (GROUP PROG.)BEHAVIORAL STRATEGIES (GROUP PROG.) 40%40%

ACUPUNCTUREACUPUNCTURE ---- ----

HYPNOSISHYPNOSIS ---- ----

PHYSICIAN ADVICEPHYSICIAN ADVICE 6% 6%

SELF-HELP METHODSSELF-HELP METHODS 14%14%

NICOTINE PATCHNICOTINE PATCH 11-15% 11-15%

PHYSICIAN ADVICE/SELF-HELP PAMPHLETSPHYSICIAN ADVICE/SELF-HELP PAMPHLETS 22%22%

AVERSIVE SMOKING (RAPID PUFFING)AVERSIVE SMOKING (RAPID PUFFING) 25%25%

PHARMACOTHERAPY/BEHAVIORAL THERAPYPHARMACOTHERAPY/BEHAVIORAL THERAPY 25% 25%

BEHAVIORAL STRATEGIES (GROUP PROG.)BEHAVIORAL STRATEGIES (GROUP PROG.) 40%40%

The 5 “A’s” for Effective The 5 “A’s” for Effective Smoking InterventionSmoking Intervention

1. ASK about smoking

2. ADVISE to quit

3. ASSESS willingness to make a quit attempt

4. ASSIST if ready - offer therapy and consultation for quit plan and if not, then offer help when ready

5. ARRANGE follow up visits






E Exercise

F Food Choices

CHD Mortality RatesCHD Mortality Rates(by Degree of Glucose Tolerance)(by Degree of Glucose Tolerance)

0

1

2

3

4

5

NGT IGT Diabetes*

Inci

den

ce

rat

e/1

00

0

*Indicates patients known to have diabetes prior to the study.CHD=coronary heart disease; NGT=normal glucose tolerance; IGT=impaired glucose tolerance

Adapted with permission from Eschwege E et al. Horm Metab Res Suppl. 1985;15:41-46.

Most Cardiovascular Patients Have Most Cardiovascular Patients Have Abnormal Glucose MetabolismAbnormal Glucose Metabolism

35% 31%

34%

37%18%

45%

37% 27%

36%

GAMIn = 164

EHSn = 1920

CHSn = 2263

GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey

PrediabetesNormoglycemia Type 2 Diabetes

Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38.

Diabetes Prevention Program: Protocol Design

Diabetes Prevention Program: Reduction in Diabetes Incidence

Benefit of Comprehensive, Intensive Benefit of Comprehensive, Intensive Management: STENO 2 StudyManagement: STENO 2 Study

• Treatment Goals:– Intensive TLC– HgbA1c <6.5%– Cholesterol <175– Triglycerides <150– BP <130/80 00

00

1010

2020

4040

5050

6060

Conventional TherapyConventional Therapy

Intensive TherapyIntensive Therapy

3030

Months of Follow UpMonths of Follow Up

Primary End Point=CV events (%)

1212 2424 3636 4848 6060 7272 8484 9696

n =80n =80

n =80n =80

Gaede, P. et al, NEJM 2003;348:390-393






E ExerciseF Food Choices

Metabolic Syndrome: Lifestyle Management: Obesity / Physical Activity

• Obesity / weight management: low fat – high fiber diet resulting in 500-1000 calorie reduction per day to provide a 7-10% reduction on body weight over 6-12 mos, ideal goal BMI <25

• Physical activity: at least 30, pref. 60 min moderate intensity on most or all days of the week as appropriate to individual

Grundy SM, Hansen B, Smith SC, et al. Clinical management of metabolic syndrome. Report of the American Heart Association / National Heart, Lung, and Blood Institute / American Diabetes Association Conference on Scientific Issues Related to Management. Circulation 2004; 109: 551-556

Physical Inactivity: A Call to ArmsPhysical Inactivity: A Call to Arms

10,000 Steps Daily

30 minutes most days

Physical Activity Physical Activity RecommendationsRecommendations

• Aerobic exercise a minimum of 30 minutes, 5 times weekly

• Optimal physical activity is at least 30 minutes daily

• Resistance exercise training using free weights or machines 2 days a week in the absence of contraindications

Summary of Care: ABC's for ProvidersA A1c Target

Aspirin Daily




E Exercise

F Food Choices

ADA Nutritional GuidelinesADA Nutritional Guidelines

• Patients with pre-diabetes should receive individualized Medical Nutrition Therapy (MNT)

• Weight loss recommended for all overweight or obese individuals who have or are at risk for diabetes

• Physical activity and behavior modification effective for weight loss and maintenance

• Fiber 14 g/1000 kcal intake

• Saturated fat 7% with minimal trans fat

Therapeutic Lifestyle ChangesTherapeutic Lifestyle ChangesNutrient Composition of TLC DietNutrient Composition of TLC Diet

Nutrient Recommended Intake• Saturated fat Less than 7% of total calories• Polyunsaturated fat Up to 10% of total calories• Monounsaturated fat Up to 20% of total calories• Total fat 25–35% of total calories• Carbohydrate 50–60% of total calories• Fiber 20–30 grams per day• Protein Approximately 15% of total

calories• Cholesterol Less than 200 mg/day• Total calories (energy) Balance energy intake and

expenditure to maintain desirable body weight/prevent weight gain

Effect of Mediterranean-Style Diet Effect of Mediterranean-Style Diet in the Metabolic Syndromein the Metabolic Syndrome

• 180 pts with metabolic syndrome randomized to Mediterranean-style vs. prudent diet for 2 years

• Those in intervention group lost more weight (-4kg) than those in the control group (+0.6kg) (p<0.01), and significant reductions in CRP and Il-6

Esposito K et al. JAMA 2004; 292(12): 1440-6.

Conclusions

• Metabolic syndrome and diabetes are associated with increased levels of atherosclerosis and cardiovascular disease event risk

• Lifestyle measures focusing on weight reduction, dietary, and physical activity guidance are crucial in initial management.

Conclusions (cont.)

• Clinical management emphasizes achievement of BP and lipid goals, glycemic control, and antiplatelet therapy.

• Multidisciplinary programs including primary care physicians, specialists (endocrinologists and cardiologists), dietitians, and exercise specialists are key for the successful management of these conditions.

Thank you for your attention!

Now Published from Informa Healthcare …

For more information For more information visit our website at visit our website at www.heart.uci.eduwww.heart.uci.edu

Question #1Question #1

Which of the following statements is true?

a) Diabetes prevalence is higher in African Americans and Hispanics compared to Caucasians

b) The prevalence of diabetes is approaching the prevalence of obesity

c) The impact of diabetes on CVD is similar in men and women

d) All of the above


What are the recommended target levels for LDL-C and BP for most uncomplicated

patients with DM?a) LDL-C <100 mg/dl and 120/80 mmHg

b) LDL-C <100 mg/dl and 130/80 mmHg

c) LDL-C <70 mg/dl and 140/90 mmHg

d) None of the above


Diabetes has been considered a CHD risk equivalent because:

a) Nearly all persons with CHD also have diabetes

b) Persons with diabetes have a similar risk of developing CHD than those who already have CHD (e.g., myocardial infarction)

c) Both a and b


Recent large clinical trials such as ACCORD and ADVANCE suggest:

a) Aggressive glycemic control significantly reduces the risk of future CVD events in high risk persons with diabetes

b) The HbA1c target should be set closer to 6% than the conventional target of <7%

c) A less stringent goal than <7% for HbA1c might be considered in more complicated patients with diabetes (e.g., those difficult to control, with known macrovascular disease, or with long-standing diabetes)

Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome Nathan D. Wong, PhD,...

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Transcript of Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome Nathan D. Wong, PhD,...