New markers for CVD risk
Get a grip on complicated cases
by Gregory P. Curnew, MD
Vol.16, No.06, June 2008

Mr. Low is a 45-year-old accountant with normal blood pressure. He doesn’t smoke, his fasting blood sugar is at 5.5 mmol/L, and his cholesterol indicates that he’s at low risk for cardiovascular disease (CVD). We’re both concerned, though, because of his peculiar family history: his brother, uncle and father all died of heart disease before the age of 50. Having a first-degree relative with premature atherosclerosis — i.e. before age 55 for men and 65 for women — can double your Framingham score. So in Mr. Low’s case, the score goes up by a factor of 2, at least. But what exactly is his risk for CVD?

While traditional cardiac risk factors such as hypertension, diabetes, family history, smoking and hyperlipidemia explain ≥ 50% of vascular disease on the population level, these predictors may be less reliable for individuals. Obviously, you don’t need additional indicators to determine that a 55-year-old person with hyperlipidemia, who’s also diabetic, overweight and a smoker, is at very high risk for future CVD. But for patients such as Mr. Low, novel markers for cardiac risk can come in handy.

Which tests to order

Start with apolipoprotein B (Apo B), which is somewhat better than LDL-cholesterol at predicting risk because it helps identify the proportion of small, dense LDL particles — the crucial players in atherosclerosis. Ideally, Apo B should be below 1.2 g/L in low-risk patients, according to the Canadian Cardiovascular Society position statement from 2006. For those at moderate risk, aim for values < 1.05 g/L, and in high-risk patients, < 0.85 g/L would be optimal. A high Apo B to LDL-C ratio implies increased risk; it means that more small dense particles are present.

High sensitivity C-reactive protein, an indicator for central adiposity and inflammation, is another useful marker. Make sure to get at least 2 values before you declare someone high risk, however, because this number tends to fluctuate in some patients.

Also consider homocysteine levels to assess atherosclerosis risk. When a patient’s value rises from 10 to 15 µmol/L, vascular risk doubles, and from 15 to 20, it doubles again. Levels < 10 µmol/L are considered safe. Vitamins B6, B12 and folic acid lower this amino acid, but they don’t change the risk. I therefore use high homocysteine values as an indicator for increased risk, but I don’t dismiss patients based on low readings.

Other options are ferritin (possible marker for oxidative stress), lipoprotein(a) and fibrinogen, and also don’t forget to test exercise capacity. An increase in activity that translates into 1 metabolic equivalent unit (MET), as measured by a stress test, lowers CV mortality by at least 10%.

Non-conventional markers such as Apo B can help redefine risk in difficult cases, but you need to decide on an individual basis whether these tests are necessary. I also use them to help explain to patients why they may be at higher CVD risk than others. This allows me to treat traditional risk factors more aggressively, and it may also strengthen my argument when recommending lifestyle changes. Maybe one of these days, people will listen.

Gregory P. Curnew, MD, FRCPC is Associate Professor at McMaster University in Hamilton, ON, and Director of the Coronary Care Unit at Hamilton General Hospital.

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