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New Canadian Guidelines

for the Diagnosis and
Management of Dyslipidemia
Contributors

David C.W. Lau,

MD, PhD, FRCPC
Professor of Medicine,
Biochemistry and Molecular Biology
Chair, Diabetes and Endocrine
Research Group
Julia McFarlane Diabetes Research Centre
University of Calgary
Calgary, Alta.

Many patients with high

cholesterol levels are
unaware that they are
at risk for heart disease.

Milan Gupta, MD, FRCPC

Associate Clinical Professor of Medicine
McMaster University, Hamilton, Ont.
Assistant Professor of Medicine
University of Toronto, Toronto, Ont.
Division of Cardiology,
Brampton Civic Hospital
Brampton, Ont.

Glen J. Pearson, BSc,

BScPhm, PharmD, FCSHP
Associate Professor of Medicine
Co-Director, Cardiac Transplant Clinic
Medical Co-Director/ Director of Research,
Cardiovascular Risk Reduction Clinic
Division of Cardiology
University of Alberta
Mazankowski Alberta Heart Institute
Edmonton, Alta.

Cardiovascular disease (CVD) continues to

claim more Canadian lives than any other cause, with
coronary artery disease (CAD) contributing the lions
share. Elevated cholesterol, low-density lipoprotein
cholesterol (LDL-C) in particular, is the most significant
risk factor for CAD, as noted by Dr. David Lau, professor
of medicine at the University of Calgary, and many
patients with high cholesterol levels are unaware that they
are at risk for heart disease,he added. In 2006, Canadian
specialists representing many different organizations
released guidelines on the diagnosis and management
of dyslipidemia to help practitioners identify and treat
patients at risk for primary and secondary CVD events.
Since then, a number of landmark studies have brought
new information to the table and this information, on
top of prior evidence, has now been analyzed in a highly
collaborative effort to translate what is best known into
new clinical practice guidelines. The new Canadian
Cardiovascular Society guidelines1 are the product of a
broad coalition of stakeholders, including, for the first
time, members from the Canadian Vascular Coalition and
the Canadian Institutes of Health Research but extending
to organizations as diverse as the Canadian Pharmacists
Association, the Canadian Council for Tobacco Control,
and Obesity Canada.
A lot of healthcare professionals are involved in the
direct management of patients at risk for CVD, said Glen

Pearson, associate professor of medicine, University of

Alberta, and medical co-director of the CV Risk Reduction Clinic in the Mazankowski Alberta Heart Institute,
Edmonton,so its important to ensure that the guidelines are as broadly applicable to other providers as they
are being disseminated on a national level. Beyond
the involvement of numerous new organizations in the
development of the 2009 guidelines, the updated recommendations better define strategies for secondary and
high-risk prevention of CVD. The definition of a high-risk
individual has also been expanded to include patients
with severe heart failure, those with renal insufficiency
and those on hemodialysis, as have recommendations
determining when to intervene in those with dyslipidemia, based on a lack of evidence that statins actually
alter CVD outcomes in these patient groups.
Certain new CVD risk evaluation tools have also been
introduced to prompt the initiation of strategies targeting
primary prevention, with recommended risk assessment
tools aimed at determining global CVD risk including
stroke and CAD. Family history has also been identified
as an important component of the risk stratification pro
cess while measurement of high-sensitivity C-reactive
protein (hs-CRP) is also recommended to help fine-tune
risk stratification in moderate (intermediate) risk individuals whose LDL-C levels would otherwise not indicate
they require treatment. Treatment targets have also been

Supported by an educational grant from AstraZeneca Canada Inc.

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New Canadian Guidelines for the Diagnosis and Management of Dyslipidemia

simplified and, for the first time, the guidelines have

singled out apolipoprotein B (apoB) as an alternative
target to LDL-C.
In contrast to the 2006 guidelines, secondary lipid
targets have taken a back-seat to LDL-C targets, a
reflection of the overwhelming evidence supporting
CVD risk reductions through the lowering of both
LDL-C and apoB.

Table 1
Assessing Patient Risk: Framingham Risk Assessment Score for 10-Year Risk
of Total CVD Risk in Men
Points

A baseline lipid profile should be obtained after a

10- to 12-hour fast, with patients preferably abstaining from alcohol for 24 to 48 hours prior to the screen.
The profile should include total cholesterol (TC),
high-density lipoprotein cholesterol (HDL-C) and
triglycerides. Labs will then calculate the LDL-C
value using the Friedewald formula. A fasting glucose
test should also be done at the same time to identify
patients with impaired fasting glucose or diabetes.
A lipid screen is indicated in all men 40 years of
age and older, and in all women 50 years of age or
older, or who are postmenopausal, regardless of age.
In addition, any patient, regardless of age, should
have their lipid profile done if they are diabetic,
hypertensive or obese. Similarly, patients who have
a first-degree relative under the age of 60 with premature CAD are candidates for early screening, as
are current smokers.
Patients with any type of autoimmune inflammatory disease, including rheumatoid arthritis, psoriasis
and systemic lupus erythematosis, are at elevated
risk for CVD and should be screened, as should any
renally impaired patient with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Because
erectile dysfunction can be a sign of underlying
atherosclerosis, men who present with erectile dysfunction are also candidates for lipid profiling.
Patients with clinical manifestations of genetic
lipid disorders, including xanthomas, xanthelasmas
and premature arcus cornealis, should be screened
since the presence of any of these signs may flag a
severe underlying lipid disorder. Patients with clinical manifestations of atherosclerosis also require
screening. Long-standing antiretroviral therapy
has greatly altered the prognosis of HIV-infected
patients but long-term, highly-active antiretroviral
therapy (HAART) can be associated with significant
lipid abnormalities and lipids should be screened in
all patients on HAART.
Lastly, the 2009 guidelines are targeted to adults
but if physicians have patients with a familial form
of hypercholesterolemia, their children should be
screened for lipid abnormalities.

How to Assess Level of CVD Risk

In the 2006 lipid guidelines,we used a Framingham Risk Score (FRS) that predicted hard coronary
events, noted Dr. Milan Gupta, cardiologist at the
Brampton Civic Hospital and associate clinical
professor of medicine at McMaster University in
Hamilton, Ontario. Now, however,weve moved to
a completely different risk algorithm the modified FRS for total CVD risk which predicts risk for
not only coronary events but also for total CV events
including stroke, which was missing in previous
guidelines, he added. Dr. Pearson also personally
feels that the new recommended risk assessment
approach represents the most important change
from the 2006 guidelines, because now practitioners are being asked to assess patients for their risk

HDL-C

-2

>1.6

-1

1.3-1.6

30-34

1
2

Who and When to Screen

Age

35-39

SBP not Rxed

SBP Rxed

Smoker

Diabetic

<120

No

No

<120

1.2-1.3

<4.1

120-129

0.9-1.2

4.1-5.2

130-139

<0.9

5.2-6.2

140-159

120-129

6.2-7.2

160+

130-139

>7.2

4
5

TC

140-159

40-44

Yes

160+

6
7

45-49

50-54

9
10

55-59

11

60-64

12
13

65-69

14

70-74

15

75+

Total Points

Points
allotted
CVD Risk for Men
Points

Risk %

Points

Risk %

Points

Risk %

Points

Risk %

Points

Risk %

-3 or less

<1

2.3

5.6

12

13.3

17

29.4

-2

1.1

2.8

6.7

13

15.6

18+

>30

-1

1.4

3.3

7.9

14

18.4

1.6

3.9

10

9.4

15

21.6

1.9

4.7

11

11.2

16

25.3

Table 2
Assessing Patient Risk: Framingham Risk Assessment Score for 10-Year Risk
of Total CVD Risk in Women
Points

Age

HDL-C

TC

SBP not Rxed

-2

>1.6

-1

1.3-1.6
30-34

1
2

Smoker

Diabetic

No

No

<120

-3

SBP Rxed

35-39

<120

1.2-1.3

<4.1

120-129

0.9-1.2

4.1-5.2

130-139

<0.9

140-159

120-129

5.2-6.2

130-139

40-44

6.2-7.2

150-159

45-49

>7.2

>160

Yes
Yes

140-149
150-159

6
7

50-54

55-59

60-64

10

65-69

11

70-74

12

75+

160+

Total Points

Points
allotted
CVD Risk for Women
Points

Risk %

Points

Risk %

Points

-2 or less

<1%

-1

1.0

1.2

1
2

Risk %

Points

Risk %

Points

2.0

2.4

4.5

13

10.0

18

21.5

5.3

14

11.7

19

24.8

2.8

10

6.3

15

13.7

20

27.5

1.5

3.3

11

7.3

16

15.9

21+

>30

1.7

3.9

12

8.6

17

18.51

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Yes

Risk %

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New Canadian Guidelines for the Diagnosis and Management of Dyslipidemia

of any vascular event, not just a heart attack. (See

Tables 1 and 2. Assessing Patient Risk: Framingham
Risk Assessment Score for Total CVD Risk in Men
and Women.)
As the 2009 guidelines indicate, the move towards
assessment of total CVD risk was done in order to
correct for underestimates of risk with the previous
FRS, especially in women, young patients and those
with the metabolic syndrome. As for the metabolic
syndrome, the 2009 guidelines indicate that practitioners should use the International Diabetes Federation (IDF) criteria to identify individuals with the
metabolic syndrome, as the IDF criteria are more
likely to identify the metabolic syndrome in patients
from certain ethnic backgrounds who would otherwise be missed by using NCEP-ATP-III criteria.
The new guidelines also support the use of the
Reynolds Risk Score (RRS) [www.reynoldsriskscore.
org] as an alternative risk assessment tool. Keep in
mind, however, that the Reynolds Risk Score has
not yet been validated in a Canadian population
and therefore may not predict 10-year CVD risk
as accurately as the FRS in Canadian patients.
The RRS is an option, confirmed Dr. Gupta,but
I think we would prefer that people use the FRS.
Looking at an individuals likelihood of having a
CV event over a 10 year-interval, Table 3 stratifies
patients by risk level.

Table 3
10-year risk of CV event
Risk level

Characteristics

High

FRS/RRS is 20% or greater

If they have CAD, PVD or atherosclerosis
Most patients with diabetes

Moderate

FRS is 10% to 19%

LCL-C > 3.5 mmol/L
TC/HDL-C > 5.0
hs-CRP > 2 mg/L in men > 50 years and in
women > 60 years

Low

FRS < 10%

Once a patients 10-year risk for having a CV

event has been determined, practitioners may need
to modify the risk category if key risk features are
present.
Ethnicity: The highest incidence of CAD occurs
among patients of South Asian ancestry and the
lowest among patients of Chinese ancestry. First
Nations patients are at markedly increased risk
for both CAD and diabetes. Practitioners should
focus on overweight and obese patients in these
groups in particular to ensure modifiable risks
are addressed.
Metabolic syndrome: Most patients who meet
IDF criteria for the metabolic syndrome are either
at intermediate or high risk for CVD. Use clinical
judgment to move a patient up on the FRS-determined risk category based on the patients load
of metabolic risk factors or the severity of the
metabolic syndrome present.
A family history: A history of CVD in a parent,
sibling or child < 60 years of age increases CVD
risk by 1.7-fold in women and 2.0-fold in men.
hs-CRP >2 mg/L: If men > 50 years or women
> 60 years are at intermediate risk by FRS and
their hs-CRP > 2 mg/L, they are at greater risk
for CVD events than those with an hs-CRP
< 2 mg/L, regardless of their LDL-C level.

Patients should be reassessed every three years

as the mix of risk factors change in individuals over
time and older patients are at increasing CVD risk
whether or not risk factors change.

When to Initiate Treatment

The new guidelines have been called LDL-C
centric by their authors because, by and large, they
advocate treatment with a statin first and foremost.
The need to initiate treatment is determined not
only by the patients FRS/RRS risk category, it is
also dictated by the presence of clinical signs of
CVD and co-morbidities.
Any patient who has evidence of atherosclerosis vascular bruits; ankle-brachial index <0.9;
documented CAD or carotid disease; previous myocardial infarction (MI); any prior revascularization
procedure or prior cerebrovascular (CVD) accident
(including a transient ischemic attack); or peripheral
vascular disease is high-risk. So, too, are most
men over the age of 45 and most women over the
age of 50 who have diabetes.
All high-risk patients require immediate statin
therapy in conjunction with lifestyle interventions.
Treatment in moderate (intermediate) risk patients
is more nuanced but should be initiated if any of the
following features are met, despite optimal efforts at
lifestyle intervention:
LCL-C > 3.5 mmol/L
apoB > 1.00 g/L
TC/HDL-C ratio > 5.0
hs-CRP is > 2 mg/L in men > 50 years and in
women > 60 years if LDL-C is < 3.5. Testing
is not, however, worthwhile in patients at low
risk because they would be unlikely candidates
for statin treatment anyway. It is generally
recommended that, should the initial hs-CRP
be > 2, the test be repeated two weeks later
and the lower value of the two tests be used
for risk assessment.
Treatment of low-risk patients is advised when:
LDL-C is 5.0 mmol/L or higher (usually indicative
of a genetically-based dyslipidemia).
Treatment of low-risk patients may be considered
when:
TC/HDL-C ratio > 6.0, especially if patients have
severely elevated triglycerides.
Weve tried to make it clearer that truly highrisk patients warrant therapy and truly low-risk
patients probably dont, but for those in the middle
of the spectrum of risk, weve put a lot of emphasis
on trying to determine which patients in this risk
category should be treated and how you can better
determine who these patients are, Dr. Gupta
confirmed.

How Low Should You Go?

Once physicians have committed a patient
to statin therapy, the benefit of treatment is
entirely contingent on the magnitude of LDL-C
reduction. Data from a meta-analysis of 14 statin
trials cited in the guidelines showed that for
every 1.0 mmol/L reduction in LDL-C, there is
a 20% to 25% reduction in CAD mortality and
non-fatal MI. Extrapolating from the available
data, a 2.0 mmol/L absolute reduction or a 50%
relative reduction in LDL-C provides optimal
benefit in terms of CVD reduction, guideline
authors state.

This, in a nutshell, is the pivotal treatment message in the new lipid guidelines. Yes, practitioners
still need to aim for an LDL-C level of < 2.0 mmol/L
for high-risk patients, as was recommended in the
past, since LDL-C < 2 mmol/L
confers optimal cardioprotective benefit.
However, practitioners can rest assured that
patients will still reap significant benefit from
treatment if their LDL-C is reduced by at least 50%
from baseline. As the guideline authors explain,
this either/or primary target was included in
recognition that an LDL-C < 2.0 mmol/L cannot
be achieved in every patient, especially in patients
with very high pre-treatment LDL-C levels.
Also a first, the new guidelines indicate that
physicians can target apoB instead of LDL-C,
aiming for an apoB value of <0.80 g/L. Many
of the major lipid-lowering trials have shown
similar risk reductions if you look at apoB
[when measured] instead of LDL-C targets,
Dr. Gupta explained. Moreover, epidemiologic
and observational data repeatedly indicate that
apoB may be a slightly better predictor of CVD
risk than LDL-C, he added.
Most importantly, two recent analyses of apoB
the JUPITER study2 and the INTERHEART study3
established apoB as being as reasonable a target as
LDL-C. But as Dr. Lau cautioned, the guidelines
are not asking every practitioner to monitor apoB
levels; in fact, most laboratories are not currently
measuring apoB fractions and these tests may not
be available to provide such values in all provinces.
Nor are the guidelines asking practitioners to target
both LDL-C and apoB.
On the other hand, measuring apoB levels
offers physicians who like to be more meticulous
in achieving lipid targets an opportunity to modify
apoB as well, Dr. Lau suggested. As he noted, apoB
is a more accurate measure of small, dense atherogenic particles that may be present. Many patients
with diabetes are prone to this particular type of
atherogenic profile and knowing apoB levels in this
patient group may be particularly helpful. Measuring
apoB can also be useful in patients with very high
triglyceride levels, in whom LDL-C cannot
be calculated.
For the first time as well, treatment goals of either
an LDL-C of < 2 mmol/L or at least a 50% reduction
in LDL-C from baseline, or the primary alternative target of an apoB <0.80 g/L are recommended
for both high- and moderate- (intermediate) risk
patients.
In low-risk patients, medical therapy can generally
be deferred unless there is categorical hypercholesterolemia (an LDL-C >5 mmol/L). If LDL-C levels
warrant intervention, then practitioners should
again aim to reduce LDL-C levels by at least 50%
from baseline.

Table 4
Risk level and targets
Risk level

Target LDL-C level

High- and
Moderaterisk

LDL-C< 2 mmol/L
OR
50% or greater reduction in LDL-C from
baseline
Primary alternative target: apoB < 0.80 g/L

Low-risk

50% or greater reduction in LDL-C from

baseline

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New Canadian Guidelines for the Diagnosis and Management of Dyslipidemia

What Else Should Patients Do to Lower

CVD Risk?
Health behaviours should be universally
recommended for the prevention of many chronic
diseases including CVD. Key recommendations
from the new guidelines include:
Smoking cessation (Use pharmacological therapy as
required)
A diet low in sodium and simple sugars, with substitutions of unsaturated fats for saturated and trans fats, as
well as increased consumption of fruits and vegetables
Caloric restriction to achieve and maintain ideal body
weight
Moderate to vigorous exercise for 30 to 60 minutes
most and preferably all days of the week
Psychological stress management
Alcohol consumption in moderation is not contraindicated provided there are no metabolic or clinical
restrictions against alcohol

What about Other Lipid Fractions?

In previous guidelines, a greater emphasis was
placed on the achievement of secondary lipid
targets, especially a TC/HDL-C ratio <4.0. The
problem with secondary lipid targets in general is
that there isnt the same gold standard level of
evidence as there is for LDL-C. There is, for example, no consistent evidence supporting achievement of a non-HDL-C level <3.5 mmol/L; an apoB/
apoA1 ratio <0.80; a triglyceride level <1.7 mmol/L
or an hs-CRP level <2.0 mg/L all are potential
targets for lipid-lowing therapy, but all of them are
inferred from clinical trials and epidemiological
data, and have not been tested as treatment endpoints in and of themselves.
Until such evidence is in and it is expected
from a number of on-going trials in the near future
practitioners may adjust therapy in high-risk
patients to optimize one or more of these secondary
targets but only after achieving recommended targets
for either LDL-C or apoB.
Secondary optional targets for high-risk patients
are:
TC/HDL-C < 4.0
Non-HDL-C <3.5 mmol/L
Triglycerides < 1.7 mmol/L
ApoB/ApoA1 ratio <0.80
Hs-CRP < 2 mg/L

How Do I Decide What Statin to Use?

The guidelines do not single out any statin as being
superior to any other. This was done for several reasons, the first being that patients can respond to a
certain dose of a given statin with either a minimal
reduction of LDL-C or a large reduction. Nevertheless,not all statins have the same efficacy in
lowering LDL-C, Dr. Lau observed,so with statin
therapy, we are essentially choosing the most potent
statins where starting doses are likely to reduce
LDL-C by at least 50%.
Guideline authors also suggest that if practitioners

want to achieve the same cardioprotective benefit

from statin therapy as was demonstrated in clinical trials, they must use the same statin at the same
dose as was used in the trial. This largely means
using simvastatin at a dose of 40 mg, atorvastatin
at a dose of 80 mg or rosuvastatin at a dose of
20 mg.If patients can achieve a 50% reduction
in LDL-C with doses other than these, thats just
fine, Dr. Gupta added.
If LDL-C cannot be reduced to the goal of
< 2 mmol/L or by at least 50% from baseline,then
combination therapy will have to be considered and
this may include the cholesterol absorption inhibitors, the fibrates, or niacin, Dr. Lau added. In fact,
evidence does suggest that a substantial care gap
exists between recommended LDL-C targets and
what is actually achieved in clinical practice.
At least part of the explanation behind this care
gap is the concern that patients will experience
adverse events if they are treated with maximal dose
statin therapy, especially muscle aches and pains,
and the rare but potentially life-threatening risk
of rhabdomyolysis. As the guideline authors note,
statin-related myalgias are characterized by dull
muscle aches and these aches can be made worse
by exercise.
Theres a lot of press around muscle issues with
the statins, Dr. Pearson acknowledged,but we
need to determine what is drug-related and what
is not before we discontinue treatment. Consider,
for example, patients who present for the first time
with an elevated LDL-C that requires treatment.
While they are receiving a prescription for statin
therapy, physicians are probably dispensing lifestyle
advice at the same time (see box What Else Should
Patients Do to Lower CVD Risk?) including the
need to exercise regularly.If patients arent used
to exercise, they may ache because they are doing
something they do not normally do, as Dr. Pearson
suggested,and we need to talk with patients to
determine if side effects are linked to the drug and
[if they are], to work on strategies that will allow
patients to continue on treatment and not miss the
opportunity for them to derive all the benefit there
is from statin therapy.
The guidelines also indicate that baseline
transaminases, creatinine and creatine kinase levels
are useful to measure because they will allow physicians to monitor patients for potential side-effects
once on therapy. Follow-up is still debated but
should probably be done semi-annually or when
any change in lipid-lowering therapy is required.
The guideline authors also recommend that primary care physicians refer patients to a specialized
lipid centre when confronted with issues of drug
intolerance, a complex diagnosis, seemingly unexplained atherosclerosis, extremes of lipid disorders
or lack of response to conventional therapies.

How to Evaluate the Guidelines

The guideline authors emphasize that the 2009
update on the diagnosis and treatment of dyslipidemia and the prevention of CVD is the product of
a truly collaborative approach where great efforts
were made to address all stakeholders concerns.
We also provided the strength behind any recommendations we were making as well as the level
of evidence behind it, Dr. Gupta observed. So, for
example, if a recommendation is graded as Class I,
evidence indicates that the procedure or treatment

is beneficial, useful and effective, and physicians

should take the recommendation to heart.
A recommendation graded as Class II is a sign
that the evidence behind it is conflicting or there
was a divergence of opinion about the usefulness or
efficacy of the treatment. Recommendations graded
as Class IIa suggest that the weight of evidence is in
favour of the recommendation, while recommendations rated as Class IIb indicate that the usefulness or efficacy of the recommendation is less well
established. Recommendations graded as Class III
indicate that treatment is not useful and in fact may
be harmful in some patients.
The level of evidence behind each recommendation was also provided, with Level A indicating
that data were derived from multiple randomized
clinical trials or meta-analyses and should be taken
seriously. Recommendations with Level B evidence
indicate that data were derived from a single randomized clinical trial or large nonrandomized studies,
while recommendations rated as Level C indicate
either that a consensus of opinion was reached by
experts or that data were derived from small studies,
retrospective studies or registries.
What we have done is empower physicians to
look at our recommendations and say, This is really
solid and Im going to follow this, or else they could
say, I dont think I am going to do this and that
would also be very reasonable, depending on the
level of evidence provided, said Dr. Gupta,and this
is another fundamental change from earlier guidelines which we think is relevant for practitioners.

References
1. Genest J. et al. 2009 Canadian Cardiovascular Society/Canadian
guidelines for the diagnosis and treatment of dyslipidemia and
prevention of cardiovascular disease in the adult2009 recommendation. Can J Cardiol. 2009;25 (10): 567-577.
2. Ridker PM et al. JUPITER study Group. Rosuvastatin to prevent
vascular events in men and women with elevated C-reactive protein.

N Engl J Med. 2008;359:2195-207.

3. Yusuf S. et al. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction
in 52 countries (the INTERHEART study): Case-control study.

Lancet. 2004;364:937-52.

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