Dyslipidemia and Cardiovascular Risk: Lipid Ratios as Risk Factors for Cardiovascular Disease
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2009 Guidelines for the Diagnosis and Treatment of Dyslipidemia and
Prevention of Cardiovascular Disease
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INTRODUCTION AND RATIONALE2009 Dyslipidemia Guidelines
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*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).
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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
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22%
78%
Nurses (n=123)
No Yes
6%
94%
Physicians (n=344)
No Yes
5%
95%
Nurse Practioners (n=125)
No Yes
23%
77%
Pharmacists (n=545)
No Yes
2011 Survey of Canadian Health Care Professionals asked if they were aware of the 2009 CCS Dyslipidemia Guidelines
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2011 Survey of Canadian Health Care Professionals asked if they usethe 2009 CCS Dyslipdemia Guidelines in their practice
216 (63%)
95 (28%)
13 (4%) 10 (3%) 9 (3%) 2 (1%)0
50
100
150
200
250
Yes I use these recommendations in
my practice
I have adopted some but not all of the
guideline recommendations
No, I do not use these guidelines
I am bound to adhere to current
institutional guidelines for lipid-
lowering medications
I use other Canadian or international lipid
guidelines
These guidelines are not relevant to my
practice
Physicians (n=345) 89 (71%)
27 (22%)
4 (3%) 4 (3%) 2 (2%)
0
10
20
30
40
50
60
70
80
90
100
Yes I use these recommendations in
my practice
I have adopted some but not all of the
guideline recommendations
I use other Canadian or international lipid
guidelines
These guidelines are not relevant to my
practice
I am bound to adhere to current
institutional guidelines for lipid-
lowering medications
No, I do not use these guidelines
226 (49%)
125 (27%)
49 (11%)
30 (7%)17 (4%)
10 (2%)
0
50
100
150
200
250
Yes I use these recommendations in
my practice
I have adopted some but not all of the
guideline recommendations
No, I do not use these guidelines
These guidelines are not relevant to my
practice
I am bound to adhere to current
institutional guidelines for lipid-
lowering medications
I use other Canadian or international lipid
guidelines
Pharmacists (n=457)
0
10
20
30
40
50
60
70
Yes I use these recommendations in
my practice
I have adopted some but not all of the
guideline recommendations
I am bound to adhere to current
institutional guidelines for lipid-
lowering medications
These guidelines are not relevant to my
practice
I use other Canadian or international lipid
guidelines
No, I do not use these guidelines
Nurses (n=100)
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THE SCREENING PROCESS2009 Dyslipidemia Guidelines
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No.Name
20600
William D.
Dyslipidemia ScreeningDyslipidemia 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 ½ pack of cigarettes per day
• Father suffered fatal MI at age 59
• Mother has type 2 diabetes
Would you screen William’s plasma lipid profile?Would you screen William’s plasma lipid profile?
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• Men ≥40 years
• Women ≥50 years or postmenopausal
• Children with family history of hypercholesterolemia or chylomicronemia
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• 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
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• 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
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Central Obesity (waist circumference criteria)*:
• Europids • South Asians• Chinese • Japanese
Men ≥94 cm; women ≥80 cm Men ≥90 cm; women ≥80 cmMen ≥90 cm; women ≥80 cmMen ≥90 cm; women ≥80 cm
PLUS 2 of the following factors:
•Plasma triglycerides•Blood pressure
•HDL-C
•Fasting plasma glucose
>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
HDL-C=high-density lipoprotein cholesterol
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CARDIOVASCULAR RISK ASSESSMENT 2009 Dyslipidemia Guidelines
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No.Name
20600
William D.
CV Risk AssessmentCV Risk Assessment
• William’s 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%
How would you categorize William’s CV Risk?How would you categorize William’s CV Risk?
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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
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CVD=Cardiovascular disease; hs-CRP=High-sensitivity C-reactive protein; LDL-C=Low density lipoprotein cholesterol
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• 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
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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
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• 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
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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
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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
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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
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RECOMMENDED APPROACH TO TREATMENT
2009 Dyslipidemia Guidelines
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No.Name
20600
William D.
Approach to TreatmentApproach to Treatment
• According to the guidelines William's CV risk is moderate
Would you treat William for dyslipidemia?Would you treat William for dyslipidemia?
If yes, how?If yes, how?
Health behaviour/lifestyle?Health behaviour/lifestyle?
Pharmacotherapy?Pharmacotherapy?
What are your treatment targets for William?What are your treatment targets for William?
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* 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
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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
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• 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
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BMI=Body mass index
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Smoking Cessation• Address the issue clearly• Provide counseling, repetition• Offer medical options• Review aids and programs• Be supportive and non-
judgmental (respect patient’s choice)
• Consider what motivates patient (family, reasons, concerns)
Smoking Cessation• Address the issue clearly• Provide counseling, repetition• Offer medical options• Review aids and programs• Be supportive and non-
judgmental (respect patient’s 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!
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 Lifestyle intervention is cornerstone therapy
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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
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
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
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
Lifestyle intervention is cornerstone therapy Lifestyle intervention is cornerstone therapy
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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
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• 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
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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
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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
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Statins Niacin Fibrates
• Well-tolerated• Most common side-
effects:- Myopathy- GI distress• Semi-annual liver enzyme
monitoring recommended
• May elevate ALT and/or blood glucose levels
• Extended-release niacin is better tolerated
• ASA 325 mg 30-60 min before niacin attenuates flushing
• Small risk of hepatotoxicity
• Monitor uric acid levels• Semi-annual follow-up
recommended
• May cause reversible increases in plasma creatinine
• Monitor renal function and lipid parameters → avoid in renal insufficiency or dose adjust
ALT=alanine aminotransferase; ASA=acetylsalicylic acid (aspirin)
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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
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No.Name
20600
• Patient has moderate 10-year risk for CVD
• Patient was started on a statin therapy, and provided with lifestyle recommendationsincluding smoking cessation
• After one month of treatment, his lipids were within target and he had stopped smoking
Treatment OutcomesTreatment Outcomes
William D.
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Risk Factor Risk Points Points
Men Women
Age
30-34 0 0
35-39 2 2
40-44 5 4
45-49 7 5
50-54 8 7
55-59 10 8
60-64 11 9
65-69 13 10
70-74 14 11
75+ 15 12
HDL-C (mmol/L)
>1.6 -2 -2
1.3-1.6 -1 -1
1.2-1.3 0 0
0.9-1.2 1 1
<0.9 2 2
Total Cholesterol
<4.1 0 0
4.1-5.2 1 1
5.2-6.2 2 3
6.2-7.2 3 4
>7.2 4 5
Systolic BloodPressure (mmHg)
NotTreated
TreatedNot
TreatedTreated
<120 -2 0 -3 -1
120-129 0 2 0 2
130-139 1 3 1 3
140-149 2 4 2 5
150-159 2 4 4 6
160+ 3 5 5 7
Diabetes
Yes 3 4
No 0 0
Smoker
Yes 4 3
No 0 0
Total Points
Total Points 10-Year CVD Risk (%)
Men Women
-3 or less <1 <1
-2 1.1 <1
-1 1.4 1.0
0 1.6 1.2
1 1.9 1.5
2 2.3 1.7
3 2.8 2.0
4 3.3 2.4
5 3.9 2.8
6 4.7 3.3
7 5.6 3.9
8 6.7 4.5
9 7.9 5.3
10 9.4 6.3
11 11.2 7.3
12 13.3 8.6
13 15.6 10.0
14 18.4 11.7
15 21.6 13.7
16 25.3 15.9
17 29.4 18.51
18 >30 21.5
19 >30 24.8
20 >30 27.5
21+ >30 >30
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
Relativerisk
Low
Moderate
Very High