IT'S quite commonplace these days to hear about apparently 'healthy' people - with normal blood pressure, low LDL or 'bad cholesterol' levels - who get a heart attack. So maybe standard tests to assess cardiovascular risk in the population aren't sufficient and should be re-examined?
One recent study does suggest so, showing that an additional bio-marker should be the high sensitivity C-reactive Protein (hsCRP) test.
'The crucial issue is that the standard tests to identify those at risk of a cardiovascular event isn't sufficient. We need to consider other bio-markers, such as CRP,' says Robert Rosenson, professor of medicine at the University of Michigan School of Medicine, Ann Arbor, Michigan.
The additional test will identify individuals not captured in standard tests which look at age, family history, hypertension, high blood pressure and whether a person is a smoker.
Prof Rosenson was one of the key investigators of the AstraZeneca-sponsored Crestor Jupiter (Justification for the use of statins in primary prevention: an intervention trial evaluating rosuvastatin) trial which involved 18,000 patients from 26 countries.
CRP is an inflammatory marker, which has been shown to identify people for first stroke or heart attack. 'Individuals who have high CRP despite low cholesterol, when identified, can have their lives prolonged for two years,' he points out.
So what's this CRP test? It's been available for many years, says Prof Rosenson, but is usually used to test inflammation in people with bacterial infections in the lungs or in the blood, for example.
Of late however, more sensitive CRP tests have been developed, which can detect low-grade infection in the walls of the arteries. 'Recent developments now allow for more accurate and more sensitive measures of CRP that were previously undetectable,' he says.
Previously, the test could only capture measurements of CRP above five mg per litre. Now the hsCRP test measures 0.1 mg per litre which is 50 times lower than the older test.
The sensitive test was applied to multiple population studies and what it showed was that an individual with elevated levels of CRP was at risk of a first heart attack or stroke. 'As CRP concentration increased, there was progressive increase in risk,' he notes.
CRP is a general inflammatory marker, which goes up with viral or bacterial infection, tissue injury or surgery, but now, it's also shown to be present in high levels in people with atherosclerosis (a build up of plaque in the arteries, caused by LDL-C, or 'bad' cholesterol).
Because CRP is a non-specific inflammatory marker, patients being measured shouldn't have a recent infection, trauma or have undergone a surgical procedure recently. Even chronic conditions like lupus or rheumatoid will show elevated levels of CRP.
'For the purposes of detecting inflammation in the blood vessels and therefore cardiovascular risk, the person must be healthy and not be suffering from any other condition,' he highlights.
Prof Rosenson says that during the trial, the hsCRP test was repeated within two weeks to make sure that patients were accurately categorised into the right risk category - low, immediate or high.
What studies showed is that even low levels of CRP, previously considered normal by less sensitive laboratory methods, may be important for cardiovascular risk analysis.
'One interesting aspect of CRP was the prediction of stroke. It was shown in a pooled analysis of 252,000 patients that LDL cholesterol doesn't predict risk of stroke. In contrast, elevated CRP does,' says Prof Rosenson.
That result was encountered in the Jupiter trial which showed that detection of high levels of CRP could lead to a 48 per cent risk reduction of stroke.
Would an hsCRP test result in 'over-diagnosis' though? Prof Rosenson says that the Jupiter showed that even though the LDL-C levels in men over 50 years and women over 60 years were low, you'd only have to treat 25 people with high CRP for five years to avoid a single event. 'That's equivalent to picking out those with high LDL-C levels.'
'If you have LDL-C that's considered optimal, your risk may not be optimal when CRP levels are elevated,' he says.
The average age of those who are eligible for hsCRP tests is 66 years, he clarifies.
What this means is that those who don't qualify for treatment under the current lipid-lowering guidelines because their LDL-C is low can get treatment if their CRP is high. 'There is a case for preventive therapy for those who may show 'normal' LDL-C results based on their hsCRP reading,' says Prof Rosenson.
Current American Heart Association and American Centre for Disease Control and Prevention guidelines now identify hsCRP as an independent marker of cardiovascular risk, and the test can be suggested at the discretion of a physician.
Peter Yan, specialist in cardiology at Gleneagles Medical Centre and Mount Elizabeth Medical Centre, says that the hsCRP test is available widely in Singapore and costs approximately $30.
'The cost of hsCRP is similar to that of a standard cholesterol evaluation and certainly it is far less than other most sophisticated alternative screening approaches including coronary CT angiography,' he points out. Because hsCRP is not affected by food intake and exhibit almost no diurnal variation (ie day and night surges) clinical testing for hsCRP can be accomplished without regard for fasting status or time of the day.
The test is based on a blood sample, and if the reading is higher than two mg/dl, it could indicate a risk of inflammation of the arteries especially the arteries that supply the heart and may lead to progression of atherosclerosis.
Doctors might recommend the test, he says, if a patient is found on the risk assessment to be in the intermediate risk group. 'And if the patient's hsCRP is high, it may now be useful to use a statin to reduce not only the bad cholesterol (LDL-cholesterol) but also to reduce the hsCRP to below two mg/dl and preferably below one mg/dl,' says Dr Yan.
'The biggest message of this Jupiter trial is that we can now identify men above 60 years and women above 50 years who were 'healthy' by standard tests, but actually had cardiovascular risk. LDL-C tests only ferreted out half of the people at risk,' concludes Prof Rosenson.
