Dyslipidemia

Introduction

Cardiovascular disease (CVD) has been the leading cause of death in Malaysia for over a decade.

CVD includes coronary heart disease (CHD), cerebrovascular disease (strokes) and peripheral arterial disease (PAD).
The common cardiovascular risk factors include dyslipidemia, hypertension, diabetes mellitus, smoking and overweight/obesity

Commonly used cut off values for dyslipidemia are

Total cholesterol (TC) > 5.2 mmol/L
High density lipoprotein cholesterol (HDL-C) <1.0 mmol/L (males) or <1.2 mmol/L (females)
Triglycerides (TG) >1.7 mmol/L
Low density lipoprotein cholesterol (LDL-C) levels - will depend on the patient's CV risk

Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD).

Higher lifelong exposure to LDL-C lead to acute coronary syndromes earlier in life.

Measurement of Lipids

A standard lipid profile includes measurement of plasma or serum TC, LDL-C, HDL-C and TG.

LDL-C is usually calculated by the Freidewald equation which is not valid in the presence of elevated TG (TG >4.5 mmol/L).

Fredeiwald equation: LDL-C (mmol/L) = TC - HDL-C - TG/2.2

Do we need to fast before lipid measurement?

Non-fasting lipid testing is acceptable. The difference in the values between a fasting and non-fasting sample is small and has been shown to have no impact on CV risk estimation even in diabetics.

Management

All individual should be risk stratified.

Patients with established CVD, CKD and diabetes fall into the very high and high risk categories.
All other individuals should be risk stratified at the outset using the Framingham General CVD risk score to determine if they are at High, Intermediate (Moderate) or Low Risk.
The intensity of risk factor reduction and target lipid levels will depend on their CV risk.

LDL-C is the primary target of therapy.

Numerous randomized clinical trials have consistently shown that reducing TC and LDL-C reduces vascular risk and prevents CVD.
Every 1 mmol/L LDL-C reduction is associated with ~20% reduction of CV events.

Non-HDL Cholesterol may be considered as a secondary target when treating individuals with

Combined hyperlipidemias
Diabetes
Metabolic syndrome
Chronic kidney disease

In patients with high triglyceride >4.5 mmol/L, when the LDL-C cannot be calculated, non-HDL-C level becomes the primary target of therapy and can be calculated from a non-fasting serum.

NOTE: The targets for non-HDL-C are 0.8 mmol/L higher than the corresponding LDL-C goal.

The lipid targets are similar to ESC/EAS Guidelines for the Management of Dyslipidemias 2019.

Based on ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, 2019, maximally tolerated statin therapy is recommended as primary prevention in patients 20 to 75 years of age with an LDL-C level of 190 mg/dL (4.9 mmol/L) or higher.

Dyslipidemia in specific conditions

For patients with hypertension, initiate statins for primary prevention if LDL-C >3.4 mmol/L. Assess CV risk using the FRS-General CVD risk score in all other patients.
All persons with diabetes above the age of 40 should be treated with a statin regardless of baseline LDL-C level.

Therapeutic lifestyle changes (TLC)

Therapeutic lifestyle changes (TLC) are a critical component of health promotion and CV risk reduction efforts both prior to and after commencement of lipid-lowering therapies in all individuals.

Healthy diet

Primarily fruits and vegetables
Minimally processed foods.
Low added sugar and salt in beverages and foods
Limit trans unsaturated fatty acid intake to <1% of total energy intake.

Regular exercise

≥150 minutes a week of moderate aerobic or 75 minutes a week of vigorous aerobic exercise

Avoidance of tobacco smoking (including passive smoking)

Alcohol restriction

Maintenance of an ideal weight of BMI 20-23.5 kg/m² and waist circumference <90 cm (men), <90 cm (women).

Pharmacological Treatment

LDL-C reduction with statin treatment remains the cornerstone of lipid lowering therapy to reduce CVD risk.

The amount of CV risk reduction seen will depend on the absolute risk of the individual and the degree of LDL-lowering that is achieved.
An achieved on-treatment LDL-C level of <1.6 mmol/L appears to significantly slow down progression of atherosclerosis.
Statins also have moderate effect in lowering TC and in elevating HDL-C.

If the LDL-target level is not achieved with the maximum tolerated dose of a statin, consider

Ezetimibe and/or
PCSK 9 inhibitors, e.g. alirocumab and evolocumab subcutaneous injection or
Inclisran

If the triglyceride target is not achieved with the maximum tolerated dose of a statin, consider

Adding fenofibrate

NOTE: Gemfibrozil should not be used in combination with statins due to the myopathy risk.

Complementary Supplements

Beta-Glucan

Meta-analysis of randomised controlled trials found ≥3 g/day of oat beta-glucan may decrease LDL by 0.25 mmol/L and total cholesterol by 0.30 mmol/L without changing HDL cholesterol or triglycerides.
Also, clinical trials find oats decrease blood pressure and may be beneficial in glucose control.
On the other hand, yeast-derived beta-glucan, with a different types of linkages between the glucose molecules, better known for its ability to enhance the immune function.

Fish Oil

The American Heart Association (AHA) recommends a minimum of 2 fatty fish servings per week. Clinical trials suggest fish oil supplementation of omega-3 fatty acids 1 g/day in coronary heart disease, and when triglycerides are elevated, a minimum of omega-3 fatty acids 2 g/day, up to a maximum of 4 g/day. Fish oil supplements contain varying ratios of EPA and DHA.
Fish oil supplements have been reported to cause inconsistent but significant increases in LDL-C.
High doses of fish oil (>3 g/day omega-3 fatty acids) may increase the risk of bleeding with anticoagulant and antiplatelet agents.

Garlic

Garlic preparations may reduce total serum cholesterol and LDL in individuals with hyperlipidaemia when used for longer than 2 months. No improvement in HDL or triglycerides levels.
A 2020 meta-analysis of 12 trials and 553 hypertensive participants showed that garlic supplements lower systolic blood pressure by an average of 8.3±1.9 mm Hg and diastolic blood pressure by 5.5±1.9 mm Hg.

Plant Sterols

The Australian Heart Foundation concludes a daily intake of plant sterols around 2 g/day may reduce LDL by approximately 10%, but has little effect on HDL or triglycerides.

Coenzyme Q10

Several reviews have found CoQ10 supplementation may help replenish plasma/serum CoQ10 levels reduced by statin therapies with a daily dose of ≥100 mg/day.
NICE guidance on cardiovascular disease: risk assessment and reduction, including lipid modification, does not support the use of coenzyme Q10 supplements as a strategy to improve adherence to statin therapy due to insufficient evidence.

Summary

Despite dyslipidemia being a major risk factor for CVD, there is some unmet needs in dyslipidemia management.

Lack of awareness of updated LDL-C target.
Inability to reach treatment goals.
Treatment adherence, including patient reluctance to high-intensity lipid-lowering therapies and concern about statin-related adverse effects.

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