Chicago, IL - A new report using data from the Northern Manhattan Stroke Study (NOMASS) suggests that inflammatory markers provide complementary information about prognosis and recurrence after a first ischemic stroke [1].

The researchers report that C-reactive protein (CRP) is correlated with stroke severity and with mortality, whereas lipoprotein-associated phospholipase A₂ (Lp-PLA₂) appears to be a stronger predictor of recurrent stroke risk.

However, lead author Dr Mitchell VS Elkind (Columbia University, New York, NY), said, "Certainly, larger studies are needed before this can be incorporated into routine stroke evaluation." His group's study was published in the October 23, 2006 issue of the Archives of Internal Medicine.

Both CRP and Lp-PLA₂ have been investigated in the setting of first MI and first stroke and have been shown to predict risk independently for recurrent MI and stroke, "so they seem to have some additive value, one beyond the other," Elkind said.

Although both are markers of inflammation, CRP and Lp-PLA₂ act through different mechanisms, he noted: CRP is an acute-phase reactant, a nonspecific marker of inflammation produced by the liver that is elevated in many acute illnesses and chronic inflammatory diseases. Lp-PLA₂ is an enzyme produced by white blood cells that appears to play a role in the atherosclerotic vessel wall.

In the current study, the researchers used data from NOMASS, an ongoing population-based study looking at predictors of stroke recurrence and prognosis in a multiethnic population in the Washington Heights area of Manhattan, to look at the relationship between these markers, measured about three days after a first ischemic stroke, and outcomes, including stroke recurrence, other vascular events, and death.

In 467 patients with a first ischemic stroke, there were 80 recurrent strokes (15 of which were fatal), 18 MIs, 53 vascular deaths, and 159 deaths over four years of follow-up.

They found that levels of Lp-PLA₂ and high-sensitivity CRP (hs-CRP) were weakly correlated with each other, with an r value of 0.09 (p=0.045).

Hs-CRP, but not Lp-PLA₂, was closely associated with stroke severity and, perhaps not surprisingly given the known association between stroke severity and long-term mortality, with the risk of death.

There was no relationship found between hs-CRP and stroke recurrence. However, compared with those with the lowest levels of Lp-PLA₂, those in the highest quartile for this marker had an increased risk for recurrent stroke and for the combined outcome of recurrent stroke, MI, and vascular death, after adjustment for a variety of factors, including hs-CRP.

Their findings fall in line with previous data about these markers, Elkind noted: hs-CRP as an acute-phase reactant was associated with severity of illness and death but not recurrent stroke. Lp-PLA₂ was not clearly associated with stroke severity but was related to stroke recurrence, suggesting it is more closely linked to vascular disease pathology.

"What we've concluded from this is that we get complementary information from the CRP and Lp-PLA₂ measurements," he said.

Investigation of the clinical utility of these markers will continue in a study nested within an ongoing clinical trial in patients with lacunar strokes, called the Secondary Prevention of Small Subcortical Strokes (SPS3). The trial is testing, in a factorial design, the benefits of combined aspirin plus clopidogrel vs aspirin alone as well as aggressive vs less aggressive blood-pressure control in patients with small vessel strokes, Elkind said.

Their nested study is collecting blood from these patients and looking at the relationship between hs-CRP and Lp-PLA₂ and stroke recurrence and outcome.

If there is further confirmation of these relationships, it is possible that these markers might be used not only for risk stratification of stroke patients but also as targets for treatment, much in the way that cholesterol levels are used now, he noted. Statins, for example, affect both CRP and Lp-PLA₂ levels. Lp-PLA₂ is an enzyme, and other agents that block its activity might also reduce its proinflammatory effects.

"Those studies are going on primarily in heart disease at this time, but it will be interesting to see what happens in the future," Elkind said.