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The blood protein surfactant protein-D (SP-D) has been found to be a good predictor of cardiovascular disease (CVD) in a large study published recently in the European Heart Journal.1

Investigators led by Dr Don Sin, University of British Columbia, Canada, found that circulating SP-D levels were strongly associated with CVD and total mortality in patients with angiographically diagnosed coronary artery disease.  The association was found to be independent of other established risk factors.

Researchers measured plasma SP-D levels in 806 patients referred for coronary angiography between 1992 and 1995, derived from the Vancouver Coronary Angiography Cohort. Coronary artery disease (CAD) was defined as any lesion causing at least 20% stenosis (and severe CAD at least 50%). Follow-up continued until 2007, with primary outcome defined as CVD mortality.

The angiography patients who died during follow-up  had significantly higher plasma SP-D levels than those who survived (p <0.0001). Those in the highest quintile of SP-D had a 4.4-fold higher risk of CVD mortality than those in the lowest quintile, independent of age, sex, and plasma lipid levels.  8% of the patients in this group had CAD (verified by angiography), 71% had severe CAD, and 29% had angiographic evidence of triple vessel disease. CVD accounted for 45% of the total deaths in this group.  In the group of current and ex-smokers serum SP-D levels were higher in those who died or were hospitalised for CVD than in those who did not (p = 0.0001).

“We’ve known for a long time that chronic lung inflammation is associated with an increased risk of cardiovascular and total mortality,” said Dr Sin. “However, apart from lung function tests, there are no universally accepted biomarkers that could clearly predict these events. Recent studies have identified SP-D as a promising biomarker of lung inflammation and injury – for example, circulating SP-D levels are nearly 40% higher in active smokers than in lifetime non-smokers, and rise further in subjects with impaired lung function. It was our hypothesis that in the systemic circulation SP-D may promote atherosclerosis.”

Dr Sin described the association between circulating SP-D levels and CVD as “strong” but emphasised that the study was designed to determine causality. “Based on our data,” he said, “we cannot determine whether SP-D was intrinsically involved in the pathogenesis of cardiovascular events or an epiphenomenon of lung inflammation”.

However, he said that circulating SP-D levels were a strong predictor of future CVD mortality, independent of other risk factors. “Our data certainly implicate lung inflammation in the pathogenesis of heart and blood vessel disease and raise the possibility of using this protein as a biomarker for risk stratification in CVD patients above and beyond the traditional biomarkers of serum cholesterol and C-reactive protein. SP-D may provide a simple blood test to determine who has lung disease and is also at high risk of heart and blood vessel disease. Such patients could be targeted for interventions such as smoking cessation and drug therapy to lower their heart disease risk”.


1 Hill J, Heslop C, Man SFP, et al.  Circulating surfactant protein-D and the risk of cardiovascular morbidity and mortality.  Eur Heart J 2011;doi: 10.1093/eurheartj/ehr124.

Published on: July 6, 2011

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