Transcript Mixed Dyslipidemia - National Lipid Association

Comprehensive
Cardiometabolic
Risk-Reduction
Program
Phase 2
2009
Sponsored by National Lipid Association
Case Study
Mixed Dyslipidemia in the Patient
With Cardiometabolic Risk
Case Study
Overview
• 57-year-old white female presents for new
patient examination
– History of hypertension and borderline high cholesterol
– Family history of heart disease (mother, age 57-years) and
diabetes
– Does not smoke and is not on hormone-replacement
therapy
• Current medications: none
• On examination
– Blood pressure: 139/84 mm Hg, BMI: 29.6, height: 65
inches, weight: 178 lbs, waist: 37 inches
– No peripheral bruits, normal heart exam, and normal
peripheral pulses
BMI=body mass index
Case Study
Laboratory Results
• TC: 219 mg/dL
• TG: 330 mg/dL
• HDL-C: 44 mg/dL
•
•
•
•
LDL-C: 109 mg/dL
Non–HDL-C: 175 mg/dL
FPG: 108 mg/dL
TSH: within normal limits
• ALT: 68 U/L
• AST: 46 U/L
TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol,
LDL-C=low-density lipoprotein cholesterol, FPG=fasting plasma glucose,
TSH=thryoid-stimulating hormone, ALT=alanine aminotranferase, AST=aspartate aminotransferase
ARS Question
What is her Framingham risk for future
coronary heart disease events in the
next 10 years?
A. Low
B. Intermediate
C. High
Case Study
Framingham Risk Score
Age: 57-years
TC
Nonsmoker
HDL-C
SBP
Total points
Points
8
4
0
1
2
15
10-year risk=3%
TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, SBP=systolic blood pressure
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA. 2001;285:2486-2497.
Case Study
Patient Characteristics
Meeting Metabolic Syndrome Criteria
• Waist: 37 inches
• TG: 330 mg/dL
• HDL-C: 44 mg/dL
• Blood pressure: 139/84 mm Hg
• Glucose: 108 mg/dL
TG=triglycerides, HDL-C=high-density lipoprotein cholesterol
ARS Question
What is her risk for developing diabetes
in the next 10 years?
A. ≤5%
B. 10%
C. 20%
D. 30%
E. ≥50%
Prediction of Diabetes in ARIC:
9-Year Follow-Up
Percent of Total Incident Cases
of Diabetes Per Decile
60
50
40
30
20
10
0
1 2 3 4 5 6 7 8 9 10
Percent of People in Each Decile
Who Developed Diabetes
60
50
40
30
20
10
0
1 2 3 4 5 6 7 8 9 10
Decile of Estimated Risk
Clinical information (waist, height, hypertension, blood pressure, family history, ethnicity, age)
Fasting glucose
Clinical information plus fasting glucose
Clinical information, fasting glucose, high-density lipoprotein cholesterol, triglycerides
Schmidt MI, et al. Diabetes Care. 2005;28:2013-2018.
ARS Question
In your opinion, which of the following is
the most useful motivator to get this patient
to embark on a weight-reduction program?
A. Reduce blood pressure
B. Improve lipids
C. Prevent diabetes
D. Prevent heart attack
Diabetes Prevention Program: Modest Weight-Loss
Reduces the Incidence of New-Onset Diabetes in an
At-Risk Population
Cumulative Incidence
of Diabetes (%)
40
Weight Decrease
loss
in risk*
Placebo
0.1 kg
30
Metformin
20
Lifestyle
10
0
0
1
2
3
4
Years
P<0.001 for each comparison
*Decrease in risk of developing diabetes compared to placebo group
Knowler WC, et al. N Engl J Med. 2002;346:393-403.
2.1 kg
31%
5.6 kg
58%
Diabetes Prevention Program: Greater WeightLoss Further Reduces the Incidence of NewOnset Diabetes
Incidence Rate per
100 Person-Years
20
15
=Overall risk at the
mean weight-loss*
10
5
0
-15
-10
5
0
Change in Weight from Baseline (kg)
*In the lifestyle intervention group over an average 3.2 years of follow-up
Hamman RF, et al. Diabetes Care. 2006;29:2102-2107.
5
Clinical Pearl
Weight loss of 9–18 lbs (5–10%) would
markedly reduce the risk of diabetes in
a patient with these characteristics
Case Study
• What is her lipid phenotype?
• What would be the impact of losing
15 lbs with lifestyle modification?
Change from Baseline (%)
Look AHEAD (Action for Health in
Diabetes): Lipid Results
10
LDL-C
TG
HDL-C
Weight Loss
*
*
*
5
0
-5
-10
-15
-20
*P<0.001
Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383.
Lifestyle
Control
ARS Question
Which additional laboratory test would be
helpful for cardiovascular risk assessment?
A. hs-CRP
B. Lp(a)
C. Lp-PLA2
D. apo B
E. Lipoprotein particle size/number
hs-CRP=high-sensitivity C-reactive protein, Lp(a)=lipoprotein a,
Lp-PLA2=lipoprotein-associated phospholipase A2, apo B=apolipoprotein B
Treatment of “Metabolic Syndrome” or
“Cardiometabolic Risk”
• According to guidelines from
– Adult Treatment Panel III (ATP III)*
– The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC VII)†
– American Diabetes Association (ADA)‡
First-line therapy=weight reduction
with lifestyle modification
*Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
†Chobanian AV, et al. JAMA. 2003;289:2560-2572.
‡American Diabetes Association. Diabetes Care. 2004;27:S36-S46.
Dietary Approaches to Cardiometabolic
Health
Metabolic
Target
Diets or Dietary Components
Regardless of what
LDL-C
Diet portfolio: fats, fiber, stanols
dietary approach is
High TG, low taken, all patients
Weight loss, low glycemic index (GI)
HDL
will benefit
Blood pressurecardiometabolically
Weight loss, DASH diet
by Weight
increasing
Diabetes,
loss, ↓ their
refined carbohydrates,
prediabetes
↑ fiber activity
physical
level
Weight
loss, Mediterranean, DASH diet,
Metabolic
syndrome
low GI, therapeutic lifestyle change
(TLC)
Comparison of Popular Diets
Attrition and Mean Changes in Weight and LDL-C at 12 Months
Attrition (%)
Atkins®
Zone Diet®
Weight
Watchers®
Ornish Program
48
35
35
Intent-to-Treat Population
Weight,
kg
LDL-Cholesterol, mg/dL
0
50
Mean Change
-2
-4
-3.2 -3.0 -3.3
-6
-8
-7.1
-10
-12
-14
Dansinger, et al. JAMA. 2005;293:43-53.
-2.1
-9.3
-11.8
-12.6
Comparison of Popular Diets
Adherence and Weight Loss Are Paramount
“Short-term metabolic studies support
that metabolic risk factors are affected
by carbohydrate restriction, but longerterm effectiveness trials suggest the
degree of dietary adherence and
associated weight losses, rather than
diet type, are the key predictors of
metabolic cardiac risk factor reduction.”
Dansinger ML. Curr Diabetes Reports. 2006;6(1):55-63.
Clinical Pearl
The most effective diet
is the one that the patient has the
best chance of following
Case Study
Additional Laboratory Tests
• hs-CRP: 6.5 mg/L (high risk: >3 mg/L)
• Lp-PLA2: 180 ng/mL (high risk: >200 ng/mL)
• Lp(a): 130 nmol/L (ULN: 75 mmol/L)
• apo B: 122 mg/dL
hs-CRP=high-sensitivity C-reactive protein, Lp-PLA2=lipoprotein-associated
phospholipase A2, Lp(a)=lipoprotein a, apo B=apolipoprotein B
Case Study
Reynolds Risk Score*
• 10-year risk of having a heart attack,
stroke, or other heart disease event
6%
*Includes high-sensitivity C-reactive protein and family history
ARS Question
What are her ADA/ACC lipid goals?
A.
B.
C.
D.
E.
F.
LDL-C <100 mg/dL
Non–HDL-C <130 mg/dL
TG <150 mg/dL
HDL-C >50 mg/dL
All of the above
A and C
LDL-C=low-density lipoprotein cholesterol, HDL-C=high-density lipoprotein cholesterol,
TG=triglycerides
ADA/ACC Consensus Conference Report:
Suggested Treatment Goals in Patients With
Cardiometabolic Risk and Lipoprotein Abnormalities
Goals, mg/dL
Risk Category
LDL-C
Non–HDL-C
apo B
Highest-risk patients, including those with
• Known CVD or
• Diabetes + 1 other major CVD risk-factor*
<70
<100
<80
High-risk patients, including those with
• No diabetes or known clinical CVD, but 2
other major CVD risk factors or
• Diabetes, but no other major CVD riskfactors*
<100
<130
<90
*Other major risk factors (beyond dyslipoproteinemia) include smoking,
hypertension, and family history of premature CAD
ADA=American Diabetes Association, ACC=American College of Cardiology,
CVD=cardiovascular disease, CAD=coronary artery disease
Brunzell JD, et al. J Am Coll Cardiol. 2008;51:1512-1524.
Case Study
Intervention
• The doctor explains that she has
metabolic syndrome and high levels of
–
–
–
–
Non–HDL-C
apo B
hs-CRP
Lp(a)
• She was told
– She has high-risk for diabetes and intermediaterisk for heart disease
– With improvements in lifestyle and weight loss
she could probably avoid both
HDL-C=high-density lipoprotein cholesterol, apo B=apolipoprotein B,
hs-CRP=high-sensitivity C-reactive protein, Lp(a)=lipoprotein a
Clinical Pearl
“Retirement Plan” for Your Health
A small investment in lifestyle
on a daily basis will result in a large
return in health dividends
Questions to Ask Before Prescribing Diet and
Lifestyle Modification
• Are they ready/able to change their lifestyle?
– If no, do not prescribe; focus on increasing awareness of their risk
 This patient: “tried to lose weight in the past but nothing worked.”
Closer questioning reveals patient used magazine or fad diets
• Is cost an issue?
– Low cost options include Weight Watchers and the
Cardiometabolic Support Network
 This patient: Yes
• Do they eat for emotional reasons?
– If yes, Overeaters Anonymous® or working with therapist or registered
dietitian will be more effective
 This patient: Often, especially in the last year
• Do they prefer working in groups or individually?
– Group: Weight Watchers. Individually: registered dietitian
 This patient: Not sure
Questions to Ask Before Prescribing Diet and
Lifestyle Modification (cont.)
• Do they have access to a track or a gym?
– Need for a safe, accessible, and affordable place to be active
 This patient: There’s a mall where she can walk
• Do they have Internet capability and do they feel
comfortable on the Internet?
– Internet weight-loss support programs like LivestrongTM.com,
chat rooms, Weight Watchers® online, CMSNonline, eDiets®
 This patient: Limited – not comfortable on the Internet
• Do they have time to plan and prepare food?
– If yes, any option is viable. If no, meal replacements, Jenny Craig®,
use of lean frozen entrees
 This patient: Yes, she is organized and likes to cook for her family
Clinical Pearl
Patients may lack confidence if they’ve
been unsuccessful at weight loss in the past,
even if they’ve only followed fad diets
that had little chance of working
Reassure them that the prescribed changes
will be a medically sound, comprehensive
approach to managing their health
Case Study
Intervention
• Goals were set for weight loss of 10 lbs
(6%* body weight) with a program of diet
and exercise
– She was referred to a commercial weight-loss
program
– Advised to walk 30-minutes daily
– Prescribed a statin
*Per Diabetes Prevention Program
ARS Question
What are the benefits of starting statin therapy
in a person of her age, with metabolic
syndrome, elevated hs-CRP, and LDL-c less
than 130 mg/dL?
A. Decreases the rate of myocardial infarction
B. Decreases the rate of stroke
C. Decreases the rate of hospitalization for
unstable angina
D. All of the above
hs-CRP=high-sensitivity C-reactive protein, LDL-C=low-density lipoprotein cholesterol
JUPITER: Primary Endpoint (MI, Stroke,
UA/Revascularization, CV Death)
Cumulative Incidence
0.08
Placebo
251/8901
Hazard Ratio (HR) 0.56,
95% Confidence Interval
(CI) 0.46-0.69
P<0.00001
0.06
-44%
0.04
Rosuvastatin
142/8901
0.02
0.00
0
1
2
3
4
Follow-Up (years)
Although a little younger than the JUPITER population,
this patient would most likely see similar benefits
Ridker PM ,et al. N Engl J Med. 2008;359:2195-2207.
MI=myocardial infarction, UA=unstable angina,
CV=cardiovascular
Case Study
Intervention Follow-Up
• Patient calls the office
– After 3 weeks, the patient leaves a commercial
weight-program
• She felt uncomfortable working in a group setting
– She called her insurance company, they will
cover 4 visits with a registered dietitian
Update on Reimbursement for Medical Nutrition
Therapy (MNT) With Registered Dietitian
• Most insurances cover MNT for diabetes and renal
disease
• Medicare bill HR-6331 expands use of MNT by a
registered dietitian to Medicare beneficiaries with risk
factors for developing diabetes
– January 1, 2009: bill being reviewed by CMS
• Medicare can cover preventive services that are
USPSTF grade-A or grade-B recommendations
• American Dietetic Association is preparing an evidencebased report of the effectiveness/cost-effectiveness of
MNT for dyslipidemia and hypertension with hopes of
future coverage
USPSTF=United States Preventive Service Task Force, CMS=Centers for Medicare & Medicaid Services
Case Study
Initial Meeting With Dietitian
• Diet
– Eats 3 meals, 2 snacks/day (~2100 calories/day)
– Snacks on salty, crunchy foods (pretzels, crackers, chips) “during
periods of stress”
– ~30% of calories come from snacks and calorie-containing
beverages
– Wants to change diet, but not sure she has the “willpower”
• Activity
– Began walking after MD told her to walk 30 minutes, 5 days/week
– Currently walking 20 minutes, 3 days/week
• Psychosocially
– Experiences stress often
– Has supportive husband
Case Study
Lifestyle Plan of Action
•
•
To build patient’s self-efficacy,* dietitian will focus on
small, consistent changes
Goals should be set by both dietitian and patient
1. Diet
•
•
500/day caloric reduction from usual intake
Focus on reducing snack foods; replace with crunchy,
lower-calorie snacks and water
2. Emotional eating
•
Over next 2-weeks, complete food-records with hunger
scales to increase awareness of hunger, satiety, and
reasons for eating
3. Physical activity
•
Gradually increase walking to 30 minutes, 6 days/week
*Self-efficacy is the belief that one can make and sustain lifestyle changes
Case Study
6–Week Interim Laboratory Data
• TC: 133 mg/dL
• TG: 185 mg/dL
• HDL-C: 41 mg/dL
• LDL-C: 55 mg/dL
• Non–HDL-C: 92 mg/dL
• ALT: 46 U/L
• AST: 37 U/L
• Glucose: 104 mg/dL
TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol,
LDL-C=low-density lipoprotein cholesterol, ALT=alanine aminotranferase, AST=aspartate aminotransferase
Case Study
3 Months: MD Follow-Up Visit
• The patient continues statin therapy
– Lost 9 pounds and feels much better
– Has decreased her snack-food intake, which has
decreased her fat intake; now consumes more
fruits/vegetables and water
• Feels more confident about maintaining these changes
– Has realized and addressed some negative eating
patterns
– Walks 30 minutes, 5 days/week and usually 1x/weekend
• Physical examination
– Blood pressure: 128/82 mm Hg, pulse: 72 bpm
– Height: 65 inches, weight: 169 lbs
– Waist: 34 inches, body mass index: 28.1
Case Study
3 Months: MD Follow-Up Visit (cont.)
• Action plan
– Encourage patient to continue statin and
advise her that  HDL-C is related to
caloric restriction/weight loss
– Instruct her to increase her exercise
• Aim for 30-minutes/day on weekdays, more
on weekends; goal of ≥180 minutes/week
– Encourage her to continue dietitian visits
HDL-C=high-density lipoprotein cholesterol
Case Study
6 Months: MD Follow-Up Visit
• The patient is continuing her statin therapy
• She seems a little embarrassed that she lost
only 3 lbs in the last 3 months, but overall she
feels well
– She has lost 3 inches from her waist
– She is consistently eating a lower-fat diet with greater
intake of fiber, fruits, and vegetables
– She walks 30 minutes, 5 days/week and for 1 hour, 1
day/weekend
• Physical examination
– Blood pressure: 128/82 mm Hg, pulse: 72 bpm
– Height: 65 inches, weight: 166 lbs
– Waist: 34 inches, body mass index: 27.6
Case Study
6-Month Laboratory Data
• TC: 135 mg/dL
• TG: 170 mg/dL
• HDL-C: 46 mg/dL
• LDL-C: 55 mg/dL
• Non–HDL-C: 89 mg/dL
• ALT: 43 mg/dL
• AST: 36 mg/dL
• Glucose: 101 mg/dL
TC=total cholesterol, TG=triglycerides, HDL-C=high-density lipoprotein cholesterol,
LDL-C=low-density lipoprotein cholesterol, ALT=alanine aminotranferase, AST=aspartate aminotransferase
Case Study
6 Months: MD Follow-Up Visit
• The patient is praised for her sustained weight
loss and the improvements in lipids, glucose,
and weight, as well as for her exercise and diet
• Action plan
– Continue statin
– Maintain or increase exercise
• Key to maintaining weight loss and metabolic benefits
– Discuss use of meal replacements for weight
maintenance, self monitoring
– Encourage her to follow-up with dietitian as needed
– Schedule follow-up appointment in 3 months
Case Study
• Redefine success
– Patient’s image of success may be unrealistic and wanting
to please MD
– Weight loss and stabilization (12 lbs, 3 inches off waist),
improved diet quality, and increased physical activity are
successes that need reinforcement
• Tools to use if patients believe they are slipping
–
–
–
–
Monitor weight regularly
Complete diet records
Use meal replacements for 1 meal/day
Get support (friends, family, commercial or medical
programs)
Key Learnings: Medical
• The Framingham score may underestimate risk in
women, especially those with the metabolic syndrome
• The risk levels for CHD and diabetes may be very
different in a patient with the metabolic syndrome
– Avoidance of diabetes is a strong motivator for patients to lose
weight
• Patients without diabetes or CVD, but with ≥2 major CV
risk-factors need to be treated to goal
– LDL-C: <100 mg/dL, non–HDL-C: <130 mg/dL, apo B: <90
mg/dL
• 5%–10% weight-loss can greatly improve a patient’s lipid
profile and markedly reduce the risk of diabetes in a
patient with IFG
CHD=coronary heart disease, CVD=cardiovascular disease, LDL-C=low-density lipoprotein cholesterol,
HDL-C=high-density lipoprotein cholesterol, apo B=apolipoprotein B, IFG=impaired fasting glucose
Key Learnings: Behavioral
• Before prescribing general lifestyle advice, ask the
patient questions to help you tailor the initial approach
• The most successful diet is the one to which the patient
can adhere
• Lifestyle self-efficacy—the belief that one can make and
sustain lifestyle changes—is often undermined by
repeated failures in “dieting,” even though some of those
attempts were not reliable approaches to weight loss
• Small, simple, consistent changes over time make the
biggest difference