Secondary Prevention of Cardio-Vascular Disease

• NZ Guidelines Group

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• Overview

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• Treating to New Targets (TNT) trial
• Supports a lower LDL cholesterol target in stable coronary artery disease
• Comparison of the TNT trial with selected studies
• Apo B in TNT and IDEAL

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• PROVE IT
• Supports more intensive lipid lowering after acute coronary syndromes

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• Looking Beyond LDL
• Apolipoprotein-B and A1
  
  • Notes from ASEANZ 2009
  • Apo B in TNT and IDEAL
• HDL Cholesterol
• Non-HDL cholesterol Levels
• CRP in the PROVE IT trial

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• Diabetes
• New targets for management- notes from ASEANZ 2009
• Controversies- notes from ASEANZ 2009
• Macrovascular complications- more than just HbA1C- notes from ASEANZ 2009

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• Supplements
• Folic Acid

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• South Asians
  • Optimal Risk Factor Status for South Asians for Secondary Prevention
  • BMI measurement leads to underestimation of obesity

Apolipoprotein B/Apolipoprotein A1

Most of the Apo-B is found in LDL particles. Each LDL cholesterol particle has a single Apo-B molecule. Patients with the metabolic syndrome despite having average LDL cholesterol levels actually have greater numbers of LDL particles with greater proprotions of more atherogeneic dense LDL particles.

Other atherogenic particles that contain apo-B include VLDL and IDL. Usually there are fewer VLDL and IDL particles compared to the number of LDL particles. An idea of the total number of atherogenic particles can be obtained by measuring Apo-B levels. Apo-A1 is mostly found in HDL cholesterol particles.

Fasting lipid levels are normally done to enable calculation of LDL cholesterol levels. But if one simply wishes to measure Apo-B and Apo-A1 levels, then there is no requirement for the patient to be fasting. The Apo-B/Apo-A1 ratio was measured instead of total cholesterol/HDL cholesterol in the INTER-HEART study.

In the Quebec Cardiovascular Study measurement of Apo B levels were found to identify patients that were at even higher risk for primary events than assessed by measurement of the total cholesterol/HDL cholesterol ratio.

The Apo-B/Apo-A1 ratio is unlikely to replace risk stratification using fasting total cholesterol/HDL ratios. However, it may be a test that we should use to try to improve risk estimation in patients, particularly to help identify those at significant risk but who do not exceed the NZ Guidelines for pharmacologic therpy of risk factors. In the interests of reducing laboratory costs, I would recommend only selective measurements of these apolipoproteins- proponents of this test strongly beleive it is of value in guiding therapy.

The United States of America's ATP III guidelines recognised the role of atherogenic particles (other than LDL cholesterol) but decided against abandoning the use of total cholesterol, LDL cholesterol and HDL cholesterol in favour of the ratio of Apo-B/Apo-A1. Instead, these guidelines include a secondary goal for therapy termed "non-HDL cholesterol".

If one wishes to instead measure and lower apo-B levels then
• in the highest risk groups, a level less than 0.9/l is an alternative secondary target after attaining the LDL cholesterol target
• Apo B level less than 0.9 g/l would be the alternative target to LDL cholesterol less than 2.5 mmol/l
• Apo B levels of less than 0.8g/l would be an alternative target to LDL less than 2.0 mmol/l.

It is emphasized that instead of measuring apo-B levels, the USA guidelines recommend ensuring that after attaining the LDL target one pays attention to the non-HDL cholesterol levels.

Hitesh Patel, Cardiologist
July, 2009