2009 Guidelines for the Diagnosis and Treatment of Dyslipidemia and Prevention of Cardiovascular Disease

2009 Dyslipidemia Guidelines

INTRODUCTION AND RATIONALE

Burden of Disease: Cardiovascular Disease in Canada

*Causes of death are coded to the 10th revision of the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10).

A Look at Canada
In the last decade 40% in mortality from CVD Improvements in control of CVD risk factors and medical management of patients with CVD New clinical data available may enhance prevention and management of CVD Despite these improvements, CVD remains a major societal burden

Need for harmonization of CVD prevention practices across Canada

CVD=Cardiovascular disease

Use of the 2009 CCS Dyslipidemia Guidelines

2011 Survey of Canadian Health Care Professionals asked if they were aware of the 2009 CCS Dyslipidemia Guidelines
Physicians (n=344)
6%

Nurse Practioners (n=125)

5%

94%

95%

No

Yes

No

Yes

Pharmacists (n=545)
23%

Nurses (n=123)
22%

77%

78%

No

Yes

No

Yes

Use of the 2009 CCS Dyslipidemia Guidelines

2011 Survey of Canadian Health Care Professionals asked if they use the 2009 CCS Dyslipdemia Guidelines in their practice
250
216 (63%)

100

Physicians (n=345)

90 80 70

89 (71%)

200

150
95 (28%)

60
50

100

40 30
27 (22%)

50
13 (4%) 10 (3%)
9 (3%) 2 (1%)

20 10 0
4 (3%) 4 (3%) 2 (2%)

0 Yes I use these I have adopted some No, I do not use these I am bound to adhere I use other Canadian These guidelines are recommendations in but not all of the guidelines to current or international lipid not relevant to my my practice guideline institutional guidelines practice recommendations guidelines for lipidlowering medications

Yes I use these I have adopted some I use other Canadian These guidelines are I am bound to adhere recommendations in but not all of the or international lipid not relevant to my to current my practice guideline guidelines practice institutional recommendations guidelines for lipidlowering medications

No, I do not use these guidelines

Pharmacists (n=457)
250
226 (49%)

Nurses (n=100)
70 60

200

50
150
125 (27%)

40 30
49 (11%) 30 (7%) 17 (4%) 10 (2%)

100

20 10 0 Yes I use these I have adopted some I am bound to adhere These guidelines are I use other Canadian recommendations in but not all of the to current not relevant to my or international lipid my practice guideline institutional practice guidelines recommendations guidelines for lipidlowering medications No, I do not use these guidelines

50

0 Yes I use these I have adopted some recommendations in but not all of the my practice guideline recommendations No, I do not use these guidelines These guidelines are I am bound to adhere I use other Canadian not relevant to my to current or international lipid practice institutional guidelines guidelines for lipidlowering medications

2009 Dyslipidemia Guidelines

THE SCREENING PROCESS

Name

William D.

No.

Dyslipidemia Screening
Male; bank manager; 38 years of age

Height: 180 cm (5 11)

Weight: 98.5 kg (217 lbs) BMI: 30.3 kg/m2 Waist circumference: 97cm Fasting glucose: 5.8 mmol/L Blood pressure: 132/95 mmHg (not on any medication) Smokes pack of cigarettes per day Father suffered fatal MI at age 59 Mother has type 2 diabetes

2 0
6 0 0

Would you screen Williams plasma lipid profile?

Target Patients
Men 40 years Women 50 years or postmenopausal Children with family history of hypercholesterolemia or chylomicronemia

Target Patients Contd

Adults of any age with:
Hypertension Diabetes Current cigarette smoking Overweight (BMI 27-30kg/m2) or obesity (BMI >30kg/m2) Family history of premature CAD (<60 years in first-degree relatives) Inflammatory diseases* (systemic lupus erythematosis, rheumatoid arthritis, psoriasis)

Evidence of atherosclerosis Chronic renal disease (eGFR <60 mL/min/1.73m2) HIV infection treated with highly active antiretroviral therapy Clinical manifestations of hyperlipidemia (xanthomas, xanthelasmas, premature arcus cornealis) Erectile dysfunction Smoking

* Data on inflammatory bowel diseases are lacking. BMI=body mass index; CAD=coronary artery disease; eGFR=estimated glomerular filtration rate

The Metabolic Syndrome (MetS)

The MetS is an association of several metabolic abnormalities including:

Visceral adipose tissue mass (i.e. toxic waist) Dyslipidemia (elevated triglycerides and low HDL-C) Elevated blood pressure Elevated serum glucose

Individuals with the metabolic syndrome are more likely to be at higher long-term cardiovascular risk than estimated by the Framingham Risk Score (FRS) alone.
HDL-C=high-density lipoprotein cholesterol

International Diabetes Federation Classification of the Metabolic Syndrome

Central Obesity (waist circumference criteria)*:

Europids South Asians Chinese Japanese

Men 94 cm; women 80 cm Men 90 cm; women 80 cm Men 90 cm; women 80 cm Men 90 cm; women 80 cm PLUS 2 of the following factors:

Plasma triglycerides Blood pressure HDL-C

Fasting plasma glucose

HDL-C=high-density lipoprotein cholesterol

>1.7 mmol/L >130/85 mmHg or treatment for hypertension - Men <1.03 mmol/L - Women <1.3 mmol/L >5.6 mmol/L

2009 Dyslipidemia Guidelines

CARDIOVASCULAR RISK ASSESSMENT

Name

William D.

No.

CV Risk Assessment
Williams lipid profile:
HDL-C: 1.0 mmol/L LDL-C: 3.8 mmol/L Total cholesterol: 5.3 mmol/L

Triglycerides: 2.2 mmol/L

TC/HDL-C: 5.3

FRS: 18.8%

2 0
6 0 0

How would you categorize Williams CV Risk?

Risk Assessment
Risk assessment options Framingham Risk Score [FRS] - Commonly preferred measures CVD (validated in Canada*) - May underestimate risk in some patients Reynolds Risk Score [RRS] - Measures CVD optional risk engine (includes family history and hsCRP)

Cardiovascular (CV) risk assessment remains imperfect

Total Cardiovascular Disease (CVD) Risk assessment recommended

hsCRP=high-sensitivity C-reactive protein; CVD=cardiovascular disease *Validated with Cardiovascular Life Expectancy Model

Special Considerations

If CVD present in 1st degree relative before 60 years

CVD Risk (by FRS) x 2

If male 50 or female 60 years, intermediate risk, LDL-C does not suggest treatment

hs-CRP can be used for risk stratification

CVD=Cardiovascular disease; hs-CRP=High-sensitivity C-reactive protein; LDL-C=Low density lipoprotein cholesterol

Screening for High-Sensitivity C-reactive Protein (hsCRP)

Baseline criteria Men 50 years and women 60 years Moderate risk for CVD (by FRS) LDL-C is <3.5mmol/L Free of acute illness Baseline value Lower of two hs-CRP values, taken at two weeks apart

Not required for all patients

FRS=Framingham risk score; LDL-C=low density lipoprotein cholesterol; hsCRP=high-sensitivity C-reactive protein; CVD=cardiovascular disease

Testing for Atherosclerosis

Noninvasive assessment of atherosclerosis Ankle-brachial index Exercise stress test Carotid B mode ultrasonography Coronary calcium score Cardiac computed tomography (Electron beam computed tomography [EBCT]); Multi-detector computed tomography coronary angiography (MDCT-CA)

Atherosclerosis places the patient at HIGH RISK

Short-term versus Long-term Risk

FRS estimates 10-year risk Family history increases risk: 1.7-fold in women 2-fold in men Elevated hs-CRP may also modulate risk Risk levels change over time

Reassess CVD risk every 3 years

FRS=Framingham risk score, hsCRP=high-sensitivity C-reactive protein; CVD=Cardiovascular disease

High Risk Level

Target Demographic Diabetic adults >45 (men), >50 (women) Documented evidence of atherosclerosis Risk Score FRS or RRS 20% Overview of Treatment Recommendations Provide intensive lifestyle modification advice Pharmacological lowering of LDL-C

FRS= Framingham risk score; RRS=Reynolds Risk Score; LDL-C=low-density lipoprotein cholesterol

Moderate Risk Level

Target Demographic Middle-aged Canadians Risk Score FRS 10-19% Family history and high hsCRP modulate risk RRS may be useful Overview of Treatment Recommendations Provide lifestyle modification advice May require pharmacological lowering of LDL-C
FRS= Framingham risk score; RRS=Reynolds Risk Score; hsCRP= high-sensitivity C-reactive protein; LDL-C=low-density lipoprotein cholesterol

Low Risk Level

Risk Score FRS <10% Careful family history may add risk factors RRS may re-classify low-risk patients

Overview of Treatment Recommendations Use clinical judgment and proper timing for initiation of pharmacological lipid-lowering therapy

FRS=Framinham risk score; RRS= Reynolds risk score

2009 Dyslipidemia Guidelines

RECOMMENDED APPROACH TO TREATMENT

Name

William D.

No.

Approach to Treatment
According to the guidelines William's CV risk is moderate

Would you treat William for dyslipidemia?

If yes, how? Health behaviour/lifestyle?

Pharmacotherapy?
What are your treatment targets for William?

2 0
6 0 0

Targets of Therapy
Risk Level High FRS, RRS 20% Most patients with diabetes CAD, PVD, atherosclerosis* Initiate Treatment if: Consider treatment in all patients Primary Target (LDL-C) 2 mmo/L or 50% LDL-C Alternate apoB <0.80 g/L LDL-C >3.5mmol/L TC/HDL-C >5.0 hs-CRP >2mg/L in men >50 years, women >60 years Family history and hs-CRP modulates risk (RRS) LDL-C 5 mmol/L 2 mmo/L or 50% LDL-C Alternate apoB <0.80 g/L

Moderate FRS 10-19%

Low FRS <10%

50% LDL-C

* Atherosclerosis in any vascular bed, including carotid arteries. apoB=apolipoprotein B level; CAD=coronary artery disease; FRS=Framingham risk score; HDL-C=high-density lipoprotein cholesterol; hs-CRP=high-sensitivity C-reactive protein; PVD=peripheral vascular disease; RRS=Reynolds Risk Score; TC=total cholesterol

Secondary Targets of Therapy (once LDL-C is at goal)

TC to HDL-C ratio <4.0

Non-HDL C*

<3.5 mmol/L

Triglycerides

<1.7 mmol/L

apoB to apoAI ratio

<0.80

hs-CRP

2 mg/L

TC=Total cholesterol; HDL-C=High-density lipoprotein cholesterol ; LDL-C=low-density lipoprotein cholesterol ; apoAI/B=apolipoprotein AI/B;evel; hsCRP= high-sensitivity C-reactive protein

Residual Risk
Clinical data suggests patients achieving secondary targets have better outcomes Therapeutic options may include: - Fibrates lower triglycerides, - Niacin increase HDL-C, - Increase statins and/or, - Add cholesterol absorption inhibitors (i.e. ezetimibe*) to further lower LDL-C, apo B and hsCRP Must be clinically tested with CV outcome data

HDL-C=High-density lipoprotein cholesterol ; LDL-C=low-density lipoprotein cholesterol ; apoB=apolipoprotein B; hsCRP= high-sensitivity C-reactive protein; CV=Cardiovascular *No outcome data available

Health Behaviour and Lifestyle Changes

Smoking Cessation
Referral to smoking cessation program Behavioural counseling Nicotine replacement therapy

Diet
Low sodium and simple sugars Substitute unsaturated fats for saturated trans fats Increase intake of fruits, vegetables and fiber Moderate alcohol intake 1 drink/day for women, 2 drinks/day for men

Exercise and Weight Management

Caloric restriction Daily exercise BMI <25 kg/m2 (<23 kg/m2 for Asian, Chinese, and Japanese)

Psychological Factors
Stress management

BMI=Body mass index

What Works
Smoking Cessation
Address the issue clearly Provide counseling, repetition Offer medical options Review aids and programs Be supportive and nonjudgmental (respect patients choice) Consider what motivates patient (family, reasons, concerns)

Alcohol Intake
Men: 2 drinks per day, not more than 14/week Women : 1 drink a day, not more than 9 drinks/week Should not be saved up to be had all at once!

Lifestyle intervention is cornerstone therapy

What Works
Weight Management
Provide realistic dietary options Encourage physical activity Establish multi-disciplinary team Consider behavior modification (i.e. motivational enhancement) Assess readiness and barriers to change

Physical Activity
Recommend 30-60 min of moderate activity every day of the week slow start, gradual increase in frequency, duration, consistency Consider exercise prescriptions

Lifestyle intervention is cornerstone therapy

Lipid-Lowering Pharmacotherapy
Rationale Meta-analysis of statin trials show: 1.0 mmol/L decrease in LDL-C 20% to 25% RR reduction

Intensive LDL-C lowering therapy is associated with decreased CV risk

Clinicians must exercise expert judgment and caution when implementing lipid-lowering therapy

CV=cardiovascular; LDL-C=low-density lipoprotein cholesterol

Overview of Lipid-Lowering Medications

Statins: Lower LDL-C Bile Acid and/or Cholesterol absorption inhibitors: May lower LDL-C Fibrates: May lower triglycerides, prevent pancreatitis in patients with extreme hypertriglyceridemia (>10 mmol/L) Niacin: May raise HDL-C, lower LDL-C

LDL-C=low-density lipoprotein cholesterol, HDL-C=High-density lipoprotein cholesterol

Recommendations for Treatment

LDL-C
Most patients will achieve target LDL-C levels on statin monotherapy Ezetimibe, cholestyramine or colestipol, niacin may be required in a minority of cases In high-risk individuals, treatment should be started immediately

HDL-C
Low HDL-C may pose no risk, depending on genetic type Medications may not increase HDL-C to a clinically significant extent Health behaviour interventions increase HDL-C

LDL-C=low-density lipoprotein cholesterol ; HDL-C=high-density lipoprotein cholesterol

Recommendations for Treatment

Triglycerides
No specific target level for high-risk Lower triglyceride levels are associated with decreased CVD risk Health behaviour interventions are first-line Fibrates may prevent pancreatitis in patients with extreme hypertriglyceridemia (>10 mmol/L)

Combination Therapy
Statin with niacin - For combined dyslipidemia and low HDL-C Statin with a fibrate - Close patient follow-up required Statin with omega-3 fatty acids - May lower triglycerides and help achieve TC/HDL-C ratio target in patients with moderate hypertriglyceridemia

CVD=cardiocascular disease; HDL-C=high-density lipoprotein cholesterol; TC=total cholesterol

Safety and Monitoring

Statins Niacin Fibrates
May cause reversible increases in plasma creatinine Monitor renal function and lipid parameters avoid in renal insufficiency or dose adjust

Well-tolerated May elevate ALT and/or Most common sideblood glucose levels effects: Extended-release niacin is - Myopathy better tolerated - GI distress ASA 325 mg 30-60 min Semi-annual liver enzyme before niacin attenuates monitoring recommended flushing Small risk of hepatotoxicity Monitor uric acid levels Semi-annual follow-up recommended

ALT=alanine aminotransferase; ASA=acetylsalicylic acid (aspirin)

Referral and Advanced Testing

Referral may be warranted in the following cases: Drug intolerance or lack of response to therapy Complex diagnostic cases Lack of laboratory resources Unexplained atherosclerosis Extremes of lipoprotein disorders Genetic testing required

Name

William D.

No.

Treatment Outcomes
Patient has moderate 10-year risk for CVD Patient was started on a statin therapy, and provided with lifestyle recommendations including smoking cessation After one month of treatment, his lipids were within target and he had stopped smoking

2 0
6 0 0

Framingham Risk Score

Risk Factor Risk Points Points Total Points 10-Year CVD Risk (%)

Men
Age
30-34

Women
-3 or less

Men
<1 1.1

Women
<1 <1

-2

35-39 40-44
45-49 50-54

2 5
7 8

2 4
5 7

-1 0
1 2

1.4 1.6
1.9 2.3

1.0 1.2
1.5 1.7

55-59
60-64 65-69 70-74

10
11 13 14

8
9 10 11

3
4 5 6

2.8
3.3 3.9 4.7

2.0
2.4 2.8 3.3

75+

15

12

7
8

5.6
6.7 7.9 9.4

3.9
4.5 5.3 6.3

HDL-C (mmol/L)
>1.6

-2

-2

9 10

1.3-1.6
1.2-1.3 0.9-1.2 <0.9

-1
0 1 2

-1
0 1 2

11
12 13 14

11.2
13.3 15.6 18.4

7.3
8.6 10.0 11.7

Total Cholesterol
<4.1 4.1-5.2 5.2-6.2

0 1

0 1

15
16 17

21.6
25.3 29.4

13.7
15.9 18.51

2 3
4 Not Treated -2 0 Treated 0 2 Not Treated -3 0

3 4
5 Treated -1 2

6.2-7.2
>7.2 Systolic Blood Pressure (mmHg) <120 120-129

18
19 20 21+

>30
>30 >30 >30

21.5
24.8 27.5 >30

130-139
140-149 150-159 160+

1
2 2 3

3
4 4 5

1
2 4 5

3
5 6 7

Double cardiovascular disease risk percentage if any cardiovascular disease is present in a first-degree relative before 60 years of age.
In men older than 50 years and women older than 60 years of age, of intermediate risk whose LDL-C is <3.5mmol/L, hs-CRP can be used for risk stratification the lower of 2 values taken 2 weeks apart, when free of acute illness, is the baseline value.

Legend Relative risk

Low Moderate Very High

Diabetes
Yes No

3 0

4 0

Smoker
Yes
No

4
0

3
0

Total Points