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Regardless of cardiovascular disease history, N-terminal pro-brain natriuretic peptide (NT-proBNP) was a better predictor of cardiovascular events in older men than C-reactive protein (CRP), researchers said.

In prospective study of 3,649 British men 60 and older followed for nine years, adding NT-proBNP measurements to a standard model based on Framingham scores improved risk classifications significantly, whereas adding CRP did not, reported S. Goya Wannamethee, PhD, of University College London, and colleagues.

"These results may have clinical relevance, and other groups should now extend our observations in other prospective cohorts to establish whether NT-proBNP is indeed able to enhance risk prediction across a range of populations in a clinically meaningful, and cost-effective, manner," the researchers wrote in the June 28 issue of the Journal of the American College of Cardiology.

Brain (or B-type) natriuretic peptide (BNP) is enzymatically cleaved from a larger precursor protein, leaving the N-terminal end -- NT-proBNP -- as a waste product. In recent years, it has been found to be an accurate marker for heart failure.

Wannamethee and colleagues pointed out that it may also be a more general indicator of subclinical myocardial stress and therefore a potential marker of risk for serious events.

CRP has also been touted as a cardiovascular event marker because of its relationship to inflammation, though its value as a clinical risk factor remains controversial. Small elevations in CRP have been linked to increased event risk in some studies, though others have found that it adds little predictive value to standard risk factors such as smoking status, age, blood pressure, and lipid levels.

Wannamethee and colleagues reported findings from the British Regional Heart Study, which began in 1978 with an original enrollment of 7,735 men 40 to 59 years old.

From 1998 to 2000, participants still available for follow-up were asked to complete a detailed questionnaire and undergo physical exams and blood draws.

Information and blood samples adequate for CRP and NT-pro-BNP measurement were obtained from 3,649 who did not have heart failure at baseline. They were then followed for a mean of nine years.

After adjusting for all standard cardiovascular risk factors, the incidence of major events -- fatal and nonfatal MI, fatal and nonfatal strokes, and cardiovascular death -- was better predicted with NT-proBNP than with CRP.

Among men with no cardiovascular disease at 1998-2000 baseline, each standard deviation in the log of NT-proBNP increased the risk of all major events by 49% (hazard ratio 1.49, 95% CI 1.33 to 1.65) when added to the Framingham model.

Increases of 48% to 86% were also seen for event subgroups including cardiovascular mortality, major cardiac events, and fatal coronary heart disease, all significant with P<0.0001. In general, fatal events were the most strongly predicted by elevated NT-proBNP.

CRP also significantly predicted these events in men without baseline cardiovascular disease but less strongly: HR 1.22 for all major events for each standard deviation in log CRP (95% CI 1.1o to 1.34) and similar values for the event subgroups.

In men who did have evidence of cardiovascular disease at baseline, NT-proBNP remained a strong risk predictor (HR 1.52 for all major events for each standard deviation in log NT-proBNP, 95% CI 1.33 to 1.75), whereas CRP had no value (HR 1.00, 95% CI 0.86 to 1.38).

Adding NT-proBNP measurements to the Framingham model led to a net reclassification improvement of 8.8% in men without preexisting cardiovascular disease (P=0.0009) and 8.2% in those with preexisting disease (P=0.049), Wannamethee and colleagues reported.

CRP provided no significant added value to the Framingham model, they added.

"As a cardiovascular disease risk marker, NT-proBNP is pragmatically attractive for many of the same reasons as is CRP in that it can be routinely measured (currently to rule out heart failure diagnosis on admission) and there are robust and reproducible assays available commercially," the researchers wrote.

"Because the relative severity of underlying cardiovascular disease (including silent infarcts) in an apparently healthy patient may not always be obvious to an examining clinician, the information provided by NT-proBNP may also be useful in primary prevention risk prevention," they added.

But they noted that the biological linkages between NT-proBNP and underlying disease have not been conclusively identified. Other limitations to the study include its exclusion of women and the middle-aged, and its 99% Caucasian sample.

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