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

Lipid Modifying Therapy for Secondary Prevention

Do Raised CRP Levels Warrant More Intensive LDL Cholesterol Lowering Therapy?

A further analysis of the PROVE IT trial suggests that CRP levels may have a role to play in adjusting the target LDL cholesterol level for secondary prevention.

• The lowest event rates were in the group that attained the dual goals of LDL cholesterol less than 1.8 mmol/l and CRP levels less than 2mg/l.
• The highest event rates were in the group that had LDL cholesterol levels over 1.8 mmol/l and CRP levels over 2mg/l.
• The other two groups had intermediate event rates.

The cut-off values for LDL cholesterol (1.8mmol/l) and CRP (2mg/l) were close to the median values. In other words, this analysis should not necessarily be regarded as providing the ideal cut-off values for these parameters.

An adjusted analysis of the impact of achieved LDL cholesterol levels found that the relative risk of a coronary event was 1.2 or lower for LDL choleterol levels below 2.4mmol/l. This analysis adjusted the relative risk for age, achieved CRP levels and for other risk factors. If this finding was confirmed in other studies the implication would be that LDL cholesterol levels under 2.4 mmol/l is acceptable if highly sensitive CRP levels are less than 2mg/l.

An adjusted analysis of the impact of achieved CRP levels found that the relative risk of a coronary event was 1.7 for CRP levels above 4.2mg/l. The relative risk for CRP levels of 0.9 to 4.1 mg/l was between 1.3 and 1.5. This analysis adjusted the relative risk for age, achieved LDL cholesterol levels and for other risk factors. If this finding was confirmed in other studies the implication would be that if the CRP levels can not be lowered, one need be less concerned about the increased risk associated with this provided LDL cholesterol levels are lowered intensively.

Thus, this analysis suggests that the lowest risk is attained by achieving dual goals of very low LDL cholesterol and CRP levels less than 2 mg/l. However, other data and, ideally, prospective data are required to determine the proper cut-off values of CRP if this parameter is to be used to guide therapy.

NOTE: the REVERSAL trial compared high dose atorvastatin vs standard dose pravastatin and assessed atheroma progression with intravascular ultrasound. The results of a further analysis of the outcome based on CRP levels also indicates a better outcome for those with lower CRP levels.

• PROVE IT-TIMI 22 Investigators. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med 2004;350:1495-504.
• PROVE IT-TIMI 22 Investigators. C-Reactive Protein Levels and Outcomes after Statin Therapy. N Engl J Med 2005;352:20-8.