Dyslipidemia

Introduction

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

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.

Dyslipidemia to CVD



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?



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.
Dyslipidemia Targets

LDL-C is the primary target of therapy.

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.

ESC Lipid Targets 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.

AHA Lipid Targets 2019

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

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

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



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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