Lipid Disorders

The relationship between CAD and total cholesterol levels is continuous and curvilinear. LDL cholesterol (LDL-cholesterol) is a well-established risk for CAD¹.

Clinical Approach[1]

Please refer to the Cardiovascular Risk Assessment Protocol and 10 Year Cardiovascular Disease Risk Calculator where needed.
Screening for lipids should be performed as part of a global cardiovascular/cardiometabolic risk assessment. Clinicians should also consider screening for other risk factors such as blood pressure and blood glucose.
In the prevention of CAD, the intensity of risk reduction therapy should be adjusted to a persons risk of developing future coronary events. As such, the first step should be to assess the individuals risk status and assignment to one of four risk categories.

Risk Stratification and Treatment Goals (adapted from MOH CPG on Lipids Dec 2016) .

Cardiovascular Disease Risk Calculator
Estimation of 10-Year Coronary Artery Disease Risk for Men .
Estimation of 10-Year Coronary Artery Disease Risk for Women .
Secondary dyslipidaemia should be excluded in selected patients diagnosed with lipid disorders .

Hypertriglyceridaemia

Elevated blood TG levels are associated with CAD. However, this association is significantly attenuated after adjustment for other blood lipid levels.
Individuals with very high levels of fasting TG, i.e. >4.5mmol/L (400mg/dL) or especially >10mmol/L >900mg/dL), have an increased risk of acute pancreatitis. For such patients, the priority is to reduce the TG level to prevent acute pancreatitis through the initiation of fibrates.
For patients with very high or high CAD risk who have TG levels between 2.3mmol/L (200/dL) to 4.5mmol/L (400mg/dL), statins (with or without ezetimibe) should be used primarily to lower non-HDL C.

Special Considerations¹

Elderly

In the elderly (age >75 years), the decision to start treatment should consider the potential risk-reduction associated with treatment, risk of adverse effects, drug-drug interactions, and patient preferences.
In very high-risk elderly patients, more intensive therapy (achieving LDL-cholesterol in the range of 2.1mmol/L or 80mg/dL) has not shown additional benefit over less intensive therapy. Treatment for such patients should be individualised.
When used, lipid-lowering medications in the elderly should be started at the lowest dose and then titrated to achieve optimal LDL-cholesterol levels, in order to reduce possible statin-associated side effects. For patients on treatment with a statin and LDL-cholesterol <2.1mmol/L or 80mg/dL when they turn >75 years of age, there is no need to reduce therapy if the treatment is well-tolerated without any adverse effects.

Women

Statins are contraindicated in women who are pregnant, likely to be pregnant, or breastfeeding.

Renal Disease

The starting dose of statins in chronic kidney disease should be low (e.g. 10mg simvastatin or equivalent ). During therapy, serum creatine kinase (CK) and renal function should both be carefully monitored.
Fibrates can be used in patients with chronic kidney disease in stages 1 to 3, but the dosages should be reduced, with appropriate monitoring for side effects, especially myopathy.
When creatinine clearance is less than 30 ml/min (stage 4 or 5), fibrates are contraindicated.
In patients with end stage chronic kidney disease on dialysis, statins did not significantly improve cardiovascular outcomes.

Liver Disease

In patients with dyslipidemia and chronic liver disease, if the level of the two transaminases (ALT and/or AST) are elevated but < 3 times the upper limit of the normal range, statins can be given but the starting dose should be low. Careful monitoring of the serum transaminases and CK after commencement are recommended.
Fibrates can be given in patients whose transaminase levels are elevated < 3 times the upper limit of the normal range, but at a lower starting dosage. Careful monitoring of the serum transaminases and CK after commencement is recommended.

Familial Hypercholesterolaemia (FH)

Screening of all first degree relatives of diagnosed FH patients is recommended.
Clinical diagnosis may be made by the Simon Broome Trust diagnostic criteria .
Offer patients with possible or definite FH a referral to a specialist to make a recommendation on the need for therapy.
Coronary artery disease risk estimation tools should not be used because patients with FH are already at a high risk of premature coronary artery disease.
Early screening provides the opportunity to teach good eating habits from a young age, if a child is identified to have FH. Children who have a first degree relative diagnosed with FH can be screened within specialist centres starting from the age of 2 years.

Management[2]

Treatment Goals

Please refer to the Risk Stratification and Treatment Goals template under Clinical Approach (3) .
Recommended Care Components

Recommended Care Components	Minimum Frequency*	Remarks
Lipid Profile	Annually	All patients should be risk stratified (as recommended in the Lipids CPG) Targets of treatment should be personalised by levels of risk
Smoking Assessment	Annually for smokers; Once-off for non-smokers, unless there is a change in smoking habit	Assessment on smoking habits (estimated sticks/day; zero for non- or ex-smoker) and provide smoking cessation counselling For more details, please refer to the Smoking Cessation care protocol.
Serum transaminases (ALT/AST)	Before starting statins and as clinically indicated (e.g. symptoms suggestive of heptatotoxicity, increase in statin dose)	Especially when the statin dose is increased or when combination therapy is initiated Stop the statin / fibrate if patient is symptomatic or if transaminases exceed 3 times the upper limit of normal range.
Serum creatine kinase	Before starting statins and as indicated (e.g. muscle symptoms)	Look out for rapid increase in creatine kinase post-initiation or increase of statin or fibrate dose. Stop the medication if the CK is three times upper limit of normal (ULN)) or at about 800 IU/L (whichever is lower)

Lifestyle Changes¹

Smoking cessation and abstinence
Weight reduction
Exercise
Diet
Alcohol consumption reduction and abstinence
Plant sterols and stanols consumption

Pharmacological¹

Drug classes.
Initiating therapy.
Monitoring side effects of therapy.

Consideration for Specialist Referral²

Specialist Referral Recommended

Referral to Gastroenterologist

Pre-treatment sustained transaminases 3 times above normal range
Clinical presentation of acute hepatitis
If the ALT/AST is persistently elevated ≥ 3X Upper Limit Normal despite stopping statins.

Patients who are clinically unwell, jaundiced or who will benefit from urgent evaluation should be referred to the A&E.

Consider Specialist Input

Consider Referral to an Endocrinologist

Triglyceride level more than 4.5mmol/L (400mg/dL) despite dietary changes and maximum tolerated drug therapy
Target parameters not achieved despite maximal drug therapy
Definite or possible familial hypercholesterolemia on Simon Broome Trust diagnostic criteria (or other validated criteria)

GPs may use the CHAS Medical Referral Form to make subsidised SOC referrals. This can be found on Healthier SG compatible GP CMS and on the PCDS web-portal.

Data Submission

The following data fields should be documented in GPs' case notes as part of good clinical practice for all patients enrolled to their practice.

Submission of data fields marked with asterisks* is required for subsidy claims and Healthier SG payments.

Lipid Profile

LDL-cholesterol (mmol/L or mg/dL) *
HDL-cholesterol (mmol/L or mg/dL)
Triglycerides (mmol/L or mg/dL)
Total Cholesterol (mmol/L or mg/dL)
Date*

Blood Pressure

Systolic BP (mmHg)
Diastolic BP (mmHg)
Date

Blood Glucose

HbA1c (%) OR Fasting Plasma Glucose (FPG) (mmol/L or mg/ dL)
Date

Weight

BMI (kg/m²), calculated from height*, weight*
Waist Circumference (in cm; optional field to fill)
Date*

Smoking History

Smoking Status (Never smoker, Ex-smoker, Current Smoker) *
Year started smoking (if smoker)
No. of sticks smoked/day (if smoker) *
State of change: (i) Pre-contemplation, (ii) Contemplation, (iii) Preparation (iv) Action, OR (v) Maintenance.

Financing

CHAS/PG/MG cardholders who are Healthier SG enrolees would be eligible for the Healthier SG Chronic Tier, which provides percentage-based subsidies for a whitelist of drug products sold within the MOH price caps. When making claims, GPs will need to submit the quantities and selling prices for each whitelisted drug product prescribed.

Details on the GP annual service fee for enrolees with lipid disorders can be found in the Healthier SG Enrolment Programme Agreement.

References