Metabolic Syndrome in Women

1
Metabolic Syndrome in Women

• Lori Mosca MD MPH PhD
• Director, Preventive Cardiology
• NewYork-Presbyterian Hospital
• Associate Professor of Medicine
• Columbia University
• New York, New York

2
CVD is the leading cause of mortality in every
region of the world except sub-Saharan Africa2

• In Europe CVD causes 4 million deaths each year4

• In the US in 2002, CVD caused 1.4 million
  deaths(38 of all deaths)3

• Almost 6 million people died due to CVD just in
  China and India in 20025

2. Bonow RO et al. Circulation 20021061602-1605
3. AHA Heart disease and stroke statistics-2005
update 4. Rayner M and Petersen S in European
cardiovascular disease statistics-2000 edition 5.
WHO Global Infobase Online available at
http//www.who.int/chp/countries/en/
3
As the Population Ages, the Risk Increases6
6. US Bureau of the Census, Adapted from Himes
CL. Elderly Americans, Population Bulletin, 2002
56 44
4
Overall Cardiovascular Risk May Be Reduced
Modifying Risk Factors May Have a Significant
Effect on Overall CV Risk13
Comparison of 10-year Risk for Age and
Gender-matched Pair
Female smoker with high blood pressure (systolic
blood pressure 180 mm Hg) and high cholesterol
(total cholesterol 271 mg/dL or 7 mmol/L)
20
18
16
14
12
10-year risk of fatal CVD () based on SCORE
Female non-smoker with controlled blood pressure
(systolic BP 140 mm Hg) and controlled
cholesterol (Total cholesterol 194 mg/dL or 5
mmol/L)
10
8
6
4
The SCORE data (a risk calculator for European
populations) gives some indications of the effect
of changes from one risk category to another,
such as when a person stops smoking or reduces
other risk factors.
2
0
40
50
55
60
65
Age (years)
The calculation shows a persons risk for the
next 10 years at each time period to illustrate
how age affects the future risk for a CV
event. 13. Adapted by Erhardt L from the Score
data, De Backer G et al. Eur Heart J.
2003241601-1610.
5
(No Transcript)
6
NHANES III Age-Adjusted Prevalence of 3 Risk
Factors for the Metabolic Syndrome
Criteria based on ATP III diabetics were
included in diagnosis overall unadjusted
prevalence 21.8. Ford ES et al. JAMA.
2002287356-359.
7
CVD Events in Patients With Diabetes Framingham
Heart Study 30-Year Follow-Up
.001ltPlt.01 Plt.05 For diabetic patient
relative to nondiabetic patient aged 3564
years. Wilson et al. In Ruderman et al, eds.
Hyperglycemia, Diabetes, and Vascular Disease.
199221-29.
8
Elevated Triglycerides Increase CHD Risk
Framingham Heart Study
Relative Risk for CHD
Women
Men
Sf 20-400 (TGs in VLDL and IDL)
For every increase in serum TG level of 89 mg/dL,
risk of CHD increases 30 in men and 69 in
women13.14
Meta-Analysis of 17 Prospective Studies
9
Coronary Heart Disease in Relation to HDL-C and
Triglyceride Levels in Women
Framingham Heart Study National Heart, Lung,
and Blood Institute
Women
200
150
CHD/1000/10 yr
100
gt119
50
80-119
Triglycerides (mg/dL)
lt80
0
lt50
50-59
gt59
HDL Cholesterol (mg/dL)
Castelli WP. Can J Cardiol. 198845A-10A.
10
Evidence-Based Guidelines for CVD Prevention in
Women
Mosca L et al. Circulation. 2004109672-693.
11
High CVD Risk in Women Clinical Examples

• Established CHD
• Cerebrovascular disease
• Peripheral arterial disease
• Abdominal aortic aneurysm
• Diabetes mellitus
• Chronic kidney disease

Cerebrovascular disease may not confer high risk
for CHD if the affected vasculature is above the
carotids. Carotid artery disease (symptomatic or
asymptomatic with gt50 stenosis) confers high
risk. As chronic kidney disease deteriorates and
progresses to end-stage kidney disease, the risk
of CVD increases substantially. Mosca L et al.
Circulation. 2004109672-693.
12
Intermediate CVD Risk in Women Clinical Examples

• Subclinical CVD
• Metabolic syndrome
• Multiple risk factors
• Markedly elevated levels of a single risk factor
• 1st degree relative(s) with onset of
  atherosclerotic CVD at 55 years in men and65
  years in women

Patients with subclinical CVD and gt20 10-year
CHD should be elevated to the high-risk
category. Patients with multiple risk factors
can fall into any of the 3 categories by
Framingham scoring. Most women with a single,
severe risk factor will have a 10-year risk
gt10. Mosca L et al. Circulation.
2004109672-693.
13
Lower/Optimal CVD Risk in Women Clinical
Examples

• Lower
• May include women with multiple risk factors,
  metabolic syndrome, or 1 risk factors
• Optimal
• Optimal levels of risk factors and heart-healthy
  lifestyle

Mosca L et al. Circulation. 2004 109672-693.
14
Lipids and Lipoproteins Pharmacotherapy

• High-Risk Women (10-year absolute CHD risk gt20)
• Initiate LDL-Clowering (preferably statin)
  therapy with lifestyle therapy when LDL-C is
  gt100 mg/dL (Class I, Level A)GI1, and initiate
  statin therapy when LDL-C is lt100 mg/dL, unless
  contraindicated (Class 1, Level B)GI1
• Initiate niacin or fibrate therapy when HDL-C is
  low or nonHDL-C (Class I, Level B)GI1 is
  elevated

Class I. Intervention is useful and
effective.Level A. Sufficient evidence from
multiple randomized trials.Level B. Limited
evidence from single randomized trial or other
nonrandomized studies. Mosca L et al.
Circulation. 2004109672-693.
15
Achievement of Optimal Lipid Levels in High-Risk
Women Results
57
60 TG lt150 mg/dL
56 HDL gt50 mg/dL
57
Patients Achieving Optimal Value ()
x
32 Non-HDL lt130 mg/dL
LDL lt100 mg/dL
29
x
x
19
x
17

Combined (LDL, HDL, TG)
12



7
Baseline
6 Months
12 Months
36 Months
Mosca L et al. Circulation. 2005111488-493.
16
Attainment of Class I Pharmacotherapy
Recommendations in High-Risk Women in a Managed
Care Setting
Optimal
100
90
80
70
60
50
Observed
32
40
30
20
11
10
10
0
LDL-C gt100 Statin
LDL-C lt100 Statin
HDL-C lt50 and/or non-HDL-C gt130Niacin or
Fibrate
Baseline Lipids (mg/dL) Therapy
Therapy initiated 8 9 months following index
lipid panel
Mosca L et al. Circulation. 2005111488-493.
17
Physician Awareness and Implementation of
Guidelines
Plt.001 PCP vs OB ATP, JNC 7 Plt.001 Card vs OB
ATP, JNC 7 Plt.01 PCP vs OB, AHA Womens Plt.01
Card vs OB, AHA Womens
NCEP ATPIII National Cholesterol Education
Program Adult Treatment Panel III JNC 7
Seventh report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure. AHA Womens American
Heart Association Evidence-Based Guidelines for
Women. Mosca L et al. Circulation.
2005111499-510.
18
FIELD Study Gender Differences in CVD Events
Adapted from FIELD Study Investigators. Lancet.
20053661849-1861.
19
National Study of Waist Size and Cardiovascular
Risk in Women

• n6938 female participants ages 18-93 who
  attended free public screenings during National
  Womens Heart Day 2006 n 12 major US cities.
• Completion of standardized questionnaire
  including demographic data, medical history,
  medication use, and personal and family history
  of CVD.
• Screenings included blood pressure, BMI, waist
  circumference, total cholesterol, HDL
  cholesterol, and glucose.

Mosca L et al. Journal of Womens Health.
20061524.
20
Modifiable risk factors in women without CVD or
diabetes
n5651 note that 676 observations are missing
from analysis due to lack of information on at
least one risk factor. Risk factors are blood
pressure 140/90 mm Hg, smoking, HDL cholesterol
lt50 mg/dL, total cholesterol 200 mg/dL, and BMI
25 kg/m2 or waist circumference 35 in.
Mosca L et al. Journal of Womens Health.
20061524.
21
Percent of women without CVD or diabetes at goal
risk factor level by race/ethnicity
p value across the four groups adjusted for age,
education, family history of CVD, personal
history of hypertension, and screening city.
Mosca L et al. Journal of Womens Health.
20061524.
22
Percent of newly identified risk factors in women
with no previously documented history of risk
factor
50
40
30
20
10
0
Risk factors for each condition are hypertension,
blood pressure 140/90 mm Hg high cholesterol,
total cholesterol 200 mg/dL dyslipidemia, HDL
cholesterol lt50 mg/dL diabetes mellitus, fasting
blood glucose 126 mg/dL and impaired glucose
tolerance, fasting blood glucose 100-lt126 mg/dL.
Mosca L et al. Journal of Womens Health.
20061524.
23
Association between cardiovascular risk factors
and Framingham risk and waist size in women
Odds ratio and p value adjusted for age,
race/ethnicity, education, family history of CVD,
personal history of hypertension, and screening
city.
Mosca L et al. Journal of Womens Health.
20061524.
24
Waist Circumference an Independent Predictor of
Cardiometabolic Risk?

• Intra- and inter-rater reliability of waist
  circumference measurements was evaluated
• Two simple anthropometric indices (BMI and WC)
  were tested for predictive value
• Sample a diverse group of women (n846 mean age
  53.2 15.1 years, 53 minority) who attended a
  free, standardized CVD risk factor public health
  screening event in New York City in February 2006

Christian AH et al. Draft Copy. 2006.
25
Association between cardiometabolic risk factors
and increased waist size and/or BMI univariate
model
Christian AH et al. Draft Copy. 2006.
26
Association between cardiometabolic risk factors
and increased waist size and/or BMI
multivariable model
27
Waist Circumference Measurement Reliability
Sub-study (n104)
Christian AH et al. Draft Copy. 2006.
28
Conclusions

• A simple, inexpensive anthropometric index
  waist circumference may be useful to health
  care providers in the clinical office setting as
  well as to patients in the home setting both
  because of its high predictive power to identify
  individuals with cardiometabolic risk factors
  that may have heightened risk for CVD and the
  exceptional simplicity of its determination.
• Future research/programs should standardize WC
  measurement technique, recommend the combined
  measurement of WC and BMI in clinical practice,
  provide patients with instructions to self-assess
  WC, and test interventions to minimize
  cardiometabolic risk and improve the quality of
  preventive care among those at increased risk due
  to overweight/obesity.

Christian AH et al. Draft Copy. 2006.
29
Cardiovascular Health From Awareness to Action
PROMOTERS
INHIBITORS
Awareness ofCVD Risk
Personalizationof Risk
Action to Lower Personal Risk
BARRIERS
MOTIVATORS
CardiovascularHealth
30
The Perils of Prevention Guidelines
I have some bad news. While your cholesterol
level has remained the same, the research
findings have changed.