Managing Cardiometabolic Risk

1
Managing Cardiometabolic Risk

• Lifestyle modification and weight reduction
  strategies

2
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.
3
BMI classifications
NHLBI. www.nhlbi.nih.gov.
4
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

Iliac crest
NHLBI. www.nhlbi.nih.gov.
5
Diagnostic criteria for metabolic syndrome
Any 3 criteria
Dyslipidemia
Adiposity
HDL-C lt40 mg/dL (men) HDL-C lt50 mg/dL (women) TG
150 mg/dL
WC (men)35 (Asian)40 (other ethnicities) WC
(women)31 (Asian)35 (other ethnicities)
Dysglycemia
Hypertension
BP 130/85 mm Hg
FG 100 mg/dL
WC waist circumference (inches)
Grundy SM. J Am Coll Cardiol. 2006471093-100.
6
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 12 lb/week for 6 months
• Base subsequent strategies on the amount of
  weight lost (Evidence Category B)

NHLBI. www.nhlbi.nih.gov.
7
Guide to adiposity management
NHLBI. www.nhlbi.nih.gov.Lee M, Aronne LJ. Am J
Cardiol. 200799(suppl)68B-79B.
8
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.
9
Some moderate-intensity physical activities
Moderate activity ? 150 calories of energy per day
NHLBI. www.nhlbi.nih.gov.
10
3-Week diet exercise regimen yields favorable
metabolic changes
N 31 overweight/obese men weight ?8.4 lbs
µU/mL
Baseline
Follow-up
P lt 0.01 P lt 0.05
Roberts CK et al. J Appl Physiol.
20061001657-65.
11
Physical activity may reduce CV and all-cause
mortality
N 9791 moderate physical activity vs little or
no physical activity
Adjusted HR (95 CI)
Favorsexercise
Favorsno exercise
Normal BP
0.75 (0.531.05)
All-cause death
0.76 (0.391.49)
CV death
Prehypertension
0.79 (0.650.97)
All-cause death
CV death
0.79 (0.581.09)
Hypertension
All-cause death
0.88 (0.800.98)
CV death
0.84 (0.730.97)
1.5
1.0
0.5
0
2.0
Hazard ratio
NHANES 1 Epidemiological Follow-up Survey
(19711992)
Fang J et al. Am J Hypertens. 200518751-8.
12
Lifestyle modification associated with diabetes
prevention
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 Fixed
Combined Random
Combined Bayesian
0.1
0.5
1.0
5.0
10.0
Relative risk (95 CI)
Yamaoka K, Tango T. Diabetes Care. 2005282780-6.
13
DPP Benefit of diet exercise or metformin on
diabetes prevention in at-risk patients
N 3234 with IFG and IGT without diabetes
40
Placebo
P
30
Metformin
lt0.001
?31
Cumulative incidence of diabetes ()
20
Lifestyle
lt0.001
?58
10
0
0
1
2
3
4
Year
vs placebo (unadjusted) Achieve/maintain 7
reduction of initial body weight via diet
moderate-intensity physical activity 150
minutes/week

DPP Research Group. N Engl J Med.
2002346393-403.
14
Popular dietary programs Effective yet difficult
to maintain
N 160 overweight or obese with 1 CV risk factor
Dansinger ML et al. JAMA. 200529343-53.
15
Look AHEAD Study design
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 lifestyle intervention for
4 years, with maintenance counseling thereafter
Usual medical care diabetes support and
education for 4 years
Total follow-up 11.5 years
Primary endpoint CV death, nonfatal MI, nonfatal
stroke
7 mean weight loss with hypocaloric diet
pharmacologic therapy 175 min/week moderate
physical activity Diet 1200-1500 kcal/day
(lt250 lbs) or1500-1800 kcal/day (250 lbs)
Look AHEAD Research Group. Control Clin Trials.
200324610-28 Obesity. 200614737-52.
16
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.
17
Pharmacologic weight management options
Available Rx and OTC (1/2 dose) Placebo-correcte
d NE norepinephrine
Arterburn DE et al. Arch Intern Med.
2004164994-1003. Li Z et al. Ann Intern Med.
2005142532-46.
18
Efficacy of orlistat as adjunct to lifestyle
modification
N 3305, mean BMI 37 kg/m2
0
-3
-3.0 kg
P lt 0.001
? Body weight(kg)
-5.8 kg
-6
-9
-12
0
52
156
208
104
Weeks
Placebo lifestyle
Orlistat lifestyle
All subjects prescribed a reduced-calorie diet
(800 kcal/day deficit) and encouraged
to?physical activity
Torgerson JS et al. Diabetes Care. 200427155-61.
19
Efficacy of sibutramine as adjunct to lifestyle
modification
N 224 with obesity, mean BMI 38 kg/m2
All subjects prescribed balanced 1200-1500
kcal/day diet and encouraged to walk 30 min/day
Wadden TA et al. N Engl J Med. 20053532111-20.
20
Effects of sibutramine and lifestyle modification
on cardiometabolic risk factors
Change from baseline at 1 year
Wadden TA et al. N Engl J Med. 20053532111-20.
21
SCOUT Study design
Sibutramine Cardiovascular OUtcome Trial
N ? 9000 55 years with BMI 2745 kg/m2 (or 25
to lt27 kg/m2 waist 40" men, 35" women)
History of CV event (or T2DM 1 other CV risk
factor)
6-week single-blind lead-in Sibutramine 10 mg
lifestyle intervention
Sibutramine 1015 mg lifestyle intervention
Placebo lifestyle intervention
3-year randomized, double-blind phase
Primary endpoint MI, stroke, resuscitated
cardiac arrest, CV death
Hypocaloric diet (-600 kcal/day) 150
min/week moderate physical activity
James WPT. Eur Heart J Suppl. 20057(suppl
L)L44-8.
22
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.
23
SOS Bariatric surgery-associated improvements in
cardiometabolic risk
Swedish Obese Subjects (SOS) Study, N 4047,
mean BMI 41 kg/m2
At 2 years
Sjöström L et al. N Engl J Med. 20043512683-93.
24
Improved Framingham risk score following
bariatric surgery
N 109, mean BMI 49 kg/m2 (preoperative), 36
kg/m2 (13-month follow-up)
12
10
8
10-year CHD risk()
P 0.002
P lt 0.0001
6
4
2
Men
Women
Before surgery
After surgery
Vogel JA et al. Am J Cardiol. 200799222-6.