Managing Cardiometabolic Risk

Lifestyle modification and weight reduction strategies

NHLBI guidelines: Adiposity assessment

• Use BMI to assess body fat– Body weight alone can be used to track weight loss, and to

determine efficacy of therapy(Evidence Category C)

• Use BMI to classify overweight/obesity– Estimate relative risk of disease compared to normal weight

(Evidence Category C)

• Use waist circumference to assess abdominal fat content (Evidence Category C)

NHLBI. www.nhlbi.nih.gov.

BMI classifications

BMI (kg/m2)

Underweight <18.5

Normal weight 18.5-24.9

Overweight 25-29.9

Class 1 obesity 30-34.9

Class 2 obesity 35-39.9

Class 3 (extreme) obesity ≥40

NHLBI. www.nhlbi.nih.gov.

Measuring waist circumference

• Locate upper hip bone and top of right iliac crest

• Place measuring tape horizontally around abdomen at level of iliac crest

• Tape should be snug without causing compression

NHLBI. www.nhlbi.nih.gov.

Iliac crest

Hypertension

Dyslipidemia

BP ≥130/85 mm Hg

HDL-C <40 mg/dL (men)

HDL-C <50 mg/dL (women)

TG ≥150 mg/dL

Diagnostic criteria for metabolic syndrome

Grundy SM. J Am Coll Cardiol. 2006;47:1093-100.

Adiposity

Dysglycemia

WC (men)≥35 (Asian)≥40 (other ethnicities)

WC (women)≥31 (Asian)≥35 (other ethnicities)

FG ≥100 mg/dL

WC = waist circumference (inches)

Any 3 criteria

NHLBI guidelines: Weight loss goals

• Goal is ~10% reduction from baseline weight (Evidence Category A)

• If successful, assess continued weight loss (Evidence Category A)

• Aim for weight loss ~1–2 lb/week for 6 months– Base subsequent strategies on the amount of weight lost

(Evidence Category B)

NHLBI. www.nhlbi.nih.gov.

Guide to adiposity management

BMI category (kg/m2)

Strategy 25.0-26.9 27.0-29.9 30.0-34.9 35.0-39.9 ≥40

DietPhysical activityBehavior therapy

With

comorbidities

With

comorbidities

Pharmacotherapy

With comorbidities

Surgery

With comorbidities

NHLBI. www.nhlbi.nih.gov.Lee M, Aronne LJ. Am J Cardiol. 2007;99(suppl):68B-79B.

NHLBI guidelines: Lifestyle modification

• Combined intervention of a calorie-deficit diet, physical activity, and behavioral treatment is most successful for weight loss and maintenance (Evidence Category A)– 500-1000 kcal/day deficit– Moderate physical activity 30-45 min, 3-5 days/week, with

eventual goal of ≥30 min on most (and preferably all) days of the week

• Maintain for ≥6 months before considering pharmacotherapy

NHLBI. www.nhlbi.nih.gov.

Some moderate-intensity physical activities

Daily life Sports

Washing car, 45–60 min Walking 3 mph, 35 min Less vigorous

Washing windows or floors, 45–60 min

Bicycling 10 mph, 30 min

Gardening, 30–45 min Dancing, 30 min

Raking leaves, 30 min Water aerobics, 30 min

Swimming, 20 min

Jogging 1 mile, 15 min

More vigorous

Moderate activity 150 calories of energy per day

NHLBI. www.nhlbi.nih.gov.

3-Week diet + exercise regimen yields favorable metabolic changes

*

*

†

*

*

0

50

100

150

200

250

Total-C LDL-C HDL-C TG Fastingglucose

mg/dL

*P < 0.01†P < 0.05 Roberts CK et al. J Appl Physiol. 2006;100:1657-65.

*

0

5

10

15

20

25

30

35

Insulin

μU/mL

N = 31 overweight/obese men; weight 8.4 lbs

Baseline Follow-up

Physical activity may reduce CV and all-cause mortality

Fang J et al. Am J Hypertens. 2005;18:751-8.

N = 9791; moderate physical activity vs little or no physical activity

0.75 (0.53–1.05)

0.76 (0.39–1.49)

0.79 (0.65–0.97)

All-cause death

CV death

All-cause death

Prehypertension

CV death

Hypertension

Hazard ratio

1.51.00.5

Normal BP

0 2.0

All-cause death

CV death

0.79 (0.58–1.09)

0.88 (0.80–0.98)

0.84 (0.73–0.97)

Adjusted HR (95% CI)Favorsexercise

Favorsno exercise

NHANES 1 Epidemiological Follow-up Survey (1971–1992)

Lifestyle modification associated with diabetes prevention

Yamaoka K, Tango T. Diabetes Care. 2005;28:2780-6.

Meta-analysis of 5 randomized, controlled trials

Pan et al, 1997

Wein et al, 1999

Tuomilehto et al, 2001

DPPRG, 2002

Watanabe et al, 2003

Combined: FixedCombined: RandomCombined: Bayesian

Relative risk (95% CI)0.1 0.5 1.0 5.0 10.0

*vs placebo (unadjusted)†Achieve/maintain ≥7% reduction of initial body weight via diet + moderate-intensity physical activity ≥150 minutes/week

DPP: Benefit of diet + exercise or metformin on diabetes prevention in at-risk patients

DPP Research Group. N Engl J Med. 2002;346:393-403.

Year

N = 3234 with IFG and IGT without diabetes

0

0

10

20

30

40

1 2 3 4

Placebo

Metformin

Lifestyle†

Cumulativeincidence

of diabetes(%)

31%

58%

P*

<0.001

<0.001

Popular dietary programs: Effective yet difficult to maintain

-4.7

-7.3-6.7 -7.1-8

-4

0

Atkins OrnishWeight

Watchers The Zone

Weight loss after 1 year

(lbs)

50

3535

48

01020304050

Drop out rateat 1 year

(%)

N = 160 overweight or obese with ≥1 CV risk factor

Dansinger ML et al. JAMA. 2005;293:43-53.

Look AHEAD: Study design

Usual medical care+ lifestyle intervention* for 4 years, with maintenance

counseling thereafter

*≥7% mean weight loss with hypocaloric diet ± pharmacologic therapy + ≥175 min/week moderate physical activity Diet = 1200-1500 kcal/day (<250 lbs) or1500-1800 kcal/day (≥250 lbs)

Primary endpoint: CV death, nonfatal MI, nonfatal stroke

Look AHEAD Research Group. Control Clin Trials. 2003;24:610-28; Obesity. 2006;14:737-52.

Look Action for Health in Diabetes

N = 5145 45-74 years with T2DM, BMI ≥25 kg/m2 (≥27 kg/m2 if taking insulin)

Usual medical care + diabetes support and education for 4 years

Total follow-up 11.5 years

NHLBI guidelines: Pharmacologic therapy

• FDA-approved drugs may be used as part of a comprehensive weight-loss program, including dietary therapy and physical activity (Evidence Category B) in these individuals:– BMI ≥30 kg/m2 with no concomitant risk factors or diseases– BMI ≥27 kg/m2 with concomitant risk factors or diseases

(hypertension, dyslipidemia, CHD, T2DM, sleep apnea)

• Herbal preparations are not recommended. These preparations have unpredictable amounts of active ingredients and unpredictable, and potentially harmful, effects.

NHLBI. www.nhlbi.nih.gov.

Pharmacologic weight management options

Orlistat* Sibutramine

Mechanism of action Inhibits fat absorption

Inhibits NE and serotonin reuptake

Mean weight loss 1 yr† 6.4 lbs 9.9 lbs

Pooled data 22 trials 5 trials

Adverse events GI discomfort BPHeart rate

*Available Rx and OTC (1/2 dose)†Placebo-correctedNE = norepinephrine

Arterburn DE et al. Arch Intern Med. 2004;164:994-1003. Li Z et al. Ann Intern Med. 2005;142:532-46.

Efficacy of orlistat as adjunct to lifestyle modificationN = 3305, mean BMI 37 kg/m2

All subjects prescribed a reduced-calorie diet (~800 kcal/day deficit) and encouraged tophysical activity Torgerson JS et al. Diabetes Care. 2004;27:155-61.

P < 0.001Δ Body weight

(kg)

Weeks0 52 156 208

-12

-9

-6

-3

0

Placebo + lifestyle Orlistat + lifestyle

104

-3.0 kg

-5.8 kg

Efficacy of sibutramine as adjunct to lifestyle modification

Wadden TA et al. N Engl J Med. 2005;353:2111-20.

All subjects prescribed balanced 1200-1500 kcal/day diet and encouraged to walk 30 min/day

N = 224 with obesity, mean BMI 38 kg/m2

Weight loss (kg)

Sibutramine alone

Lifestyle modification aloneSibutramine + brief therapy

Combined therapy

Weeks

0 3 6 10 18 40 52

16

14

12

10

8

6

4

2

0

Effects of sibutramine and lifestyle modification on cardiometabolic risk factors

Sibutramine alone

Lifestylemodification alone Combined

Total-C (mg/dL) 3.4 2.7 7.9

LDL-C (mg/dL) 2.2 1.0 4.6

HDL-C (mg/dL) 0.9 0.8 2.7

TG (mg/dL) 12.0 31.6 33.9

Glucose (mg/dL) 0.6 4.2 3.0

Insulin (U/mL) 0.5 4.3 6.2

HOMA-IR 0.3 1.1 1.5

Wadden TA et al. N Engl J Med. 2005;353:2111-20.

Change from baseline at 1 year

SCOUT: Study design

6-week single-blind lead-inSibutramine 10 mg + lifestyle intervention*

Sibutramine 10–15 mg + lifestyle intervention*

*Hypocaloric diet (-600 kcal/day) + ≥150 min/week moderate physical activity

Primary endpoint: MI, stroke, resuscitated cardiac arrest, CV death

James WPT. Eur Heart J Suppl. 2005;7(suppl L):L44-8.

Sibutramine Cardiovascular OUtcome Trial

N 9000 ≥55 years with BMI 27–45 kg/m2 (or 25 to <27 kg/m2 + waist ≥40" men, ≥35" women)

+ History of CV event (or T2DM + 1 other CV risk factor)

Placebo + lifestyle intervention*

3-year randomized, double-blind phase

NHLBI guidelines: Weight loss surgery

• An option for carefully selected patients when less-invasive methods have failed and the patient is at high risk for obesity-associated morbidity or mortality (Evidence Category B)– BMI ≥40 kg/m2 – BMI ≥35 kg/m2 with comorbid conditions

NHLBI. www.nhlbi.nih.gov.

SOS: Bariatric surgery-associated improvements in cardiometabolic risk

-25

-20

-15

-10

-5

0

5

10

15

20

25

Weight SBP DBP HDL-C FPG

Change from

baseline* (%)

Sjöström L et al. N Engl J Med. 2004;351:2683-93.

Conventional treatment (n = 1660)

Gastric surgery (n = 1845)

*At 2 years

Swedish Obese Subjects (SOS) Study, N = 4047, mean BMI 41 kg/m2

Improved Framingham risk score following bariatric surgery

Vogel JA et al. Am J Cardiol. 2007;99:222-6.

N = 109, mean BMI 49 kg/m2 (preoperative), 36 kg/m2 (13-month follow-up)

10-year CHD risk

(%)

2

4

6

8

10

12

Men Women

P < 0.0001

P = 0.002

Before surgery After surgery