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Primary Prevention of Cardio-Vascular Disease

NZ Guidelines on Assessment and Management of Cardiovascular Risk

Threshold for Pharmacological Intervention

The New Zealand Guidelines Group published its guidelines in December, 2003 . It is a comprehensive document dealing with both primary and secondary prevention, and undoubtedly will be an excellent resource for all of us. Patients' five year risk of cardiovascular events is assessed by reference to tables based on the data from the Framingham Heart Study.

Treatment targets for those with "[cardiovascular] risk clinically determined [to be] more than 20 percent"

It is recommended that LDL-cholesterol levels are reduced below 2.5 mmol/l. It is recommended that those that have had coronary bypass surgery should have LDL-cholesterol reduced below 2.0mmol/l. Other risk factors should be modified to attain optimal levels.

This group includes:

  • those who have already had a cardiovascular event
  • those who have genetic lipid disorders
  • diabetics with overt nephropathy, including with significant microalbuminuria
There will be other patients that have a calculated 5 year risk of over twenty percent and the recommendation is for drug treatment of all modifiable risk factors, until recalculated five year risk is reduced below fifteen percent. This is in contrast to the patient group listed above where it is recommended that risk factors be modified to optimal levels.

No specific targets for risk factors for other groups, but recommends lowering five-year risk below 15 percent

These guidelines do not recommend a specific LDL-cholesterol target for these patients but recommend modification of risk factors to reduce estimated risk below 15 percent.

Implicitly, this recommendation asserts that lowering LDL cholesterol or blood pressure (for example) reduces the risk by the same amount as increased blood pressure raises risk. I suspect this is an assumption that has been accepted to make the guidelines easier to use rather than based on convincing supportive evidence. In particular, it is recognised that treatment of hypertension does not reduce the risk of ischaemic heart disease as much as it increases risk.

Although it is established that hypertension is a risk factor for ischaemic cardiac events, hypertension trials have struggled to show reduction in these events with treatment of hypertension. This is in contrast to trials using lipid modifying therapy. In other words, treatment of hypertension does not lower risk of ischaemic cardiac events as much as hypertension increases risk.

The guidelines do recommend treatment for specific risk factors regardless of overall risk if blood pressure is greater than 170/100 mmHg, or if total cholesterol levels are over 8mmol/l, or if the total cholesterol/HDL ratio is greater than 8. No specific target is provided for individual risk factors apart from urging a re-calculation of estimated risk after treatment to ensure the estimated risk is less than 15% over 5 years.

A forty year old non-smoking non-diabetic male with a blood pressure of 165/95 and a total/HDL cholesterol ratio of 6.0 would not get pharmacological treatment for hypertension or dyslipidaemia until he reaches the age of 60 years.

Once this male reaches the age of sixty years, assuming that his blood pressure and lipid profile is the same, and he is still not a diabetic and remains a non-smoker (!); to reduce the patient's 5-year estimated risk below 15 percent one could:

  • treat hypertension so that blood pressure is reduced to 140/85, or
  • treat mild dyslipidaemia so that total cholesterol/HDL ratio is reduced to 5.0, or
  • treat hypertension and dyslipidaemia but not necessarily reduce blood pressure to 140/85 or total cholesterol/HDL ratio below 5.0.

The NZ guidelines recommend treating risk factors to reduce five year risk below fifteen percent. In another part of the document, the guidelines also recommend low dose aspirin and drug treatment of all modifiable risk factors if the calculated risk before treatment is above fifteen percent.

In the short time frame of many clinical trials that have enrolled "middle-aged males", reduction of stroke is more easily shown by treating hypertension, and reduction of ischaemic cardiac events by treatment of dyslipidaemia. In other words, I think both dyslipidaemia and hypertension should be treated and we should not focus on just one of these factors to reduce the estimated risk below 15%.

These guidelines clearly have set the pharmacological treatment threshold at 15% estimated risk over 5 years of a cardiovascular event. That is not to state that patients with a lower risk can not get benefit from treatment, but presumably this threshold has been set based on some assessment of "cost-effectiveness".

As illustrated in the example above, it should be noted that a patient's risk estimate will increase as they get older even if there is no change to the level of various risk factors, mandating more intervention to try to maintain the estimated risk below 15% over five years.

It seems reasonable to assume that patients who are close to the threshold for pharmacological treatment should be given the benefit of the doubt and offered drug therapy if lifestyle changes are ineffective.

The North American guidelines set specific targets for lipids and blood pressure once the threshold for treatment has been exceeded, rather than assume a re-calculation of risk is an appropriate long-term treatment strategy for a patient. In the absence of NZ specific guidelines until December, 2003, many had embraced the "treat to target" approach of the North American guidelines.

Hitesh Patel, Cardiologist
11th July, 2004

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