Abstract
AimsPreventing sudden cardiac death (SCD) due to acute myocardial infarction (MI) in previously healthy patients is challenging. Proteomic analysis may lead to an understanding of biological mechanisms and provide predictive biomarkers. MethodsIn this prospective, nested case-control study from northern Sweden, 87 candidate cardiovascular protein biomarkers were studied in 244 individuals who later died within 24 h from an incident MI and 244 referents without MI and individually matched for age, sex and date of health examination and alive at the date of event in the index person. Association analysis was conducted using conditional logistic regression. Bonferroni correction was applied to avoid false positive findings. ResultsTen proteins were associated with future SCD due to acute MI in the non-adjusted analysis. The strongest association were found for growth differentiation factor 15 (GDF-15) with an odds ratio (OR) of 1.79 (95% confidence interval [CI] 1.41, 2.25) per standard deviation increase in protein, and urokinase-type plasminogen activator receptor with an OR of 1.66 (95% CI 1.34, 2.06). In models adjusted for lipid levels, body mass index, education, smoking, hypertension and C-reactive protein, only association with GDF-15 remained (OR 1.47 (95% 1.11, 1.95)). ConclusionElevated levels of GDF-15 are associated with increased risk of SCD within 24 h of incident MI. Further research may enable the use of GDF-15 together with other clinical and biological markers to guide primary preventive interventions for individuals at high risk for SCD.
Highlights
Cardiovascular disease (CVD) accounts for one-third of all deaths globally and is the single leading cause of premature mortality.[1,2] About 50% of all heart-related deaths is caused by sudden cardiac death (SCD) triggered by coronary heart disease events.[3]
We previously reported that type 2 diabetes mellitus as well as a high body mass index (BMI) predict an eightfold risk for SCD due to acute myocardial infarction (MI).[6]
The strongest associations were found for growth differentiation factor 15 (GDF-15), with an odds ratio (OR) per standard deviation (SD) increase in protein of 1.79 and urokinase plasminogen activator surface receptor (U-PAR) 1.66
Summary
Cardiovascular disease (CVD) accounts for one-third of all deaths globally and is the single leading cause of premature mortality.[1,2] About 50% of all heart-related deaths is caused by sudden cardiac death (SCD) triggered by coronary heart disease events.[3] In northern Sweden the yearly incidence of SCD in individuals aged 35À64 without previous CVD is 12 per 100,000 for women and 65 for men,[4] and the incidence rate increases rapidly with higher age.[5] Prevention is challenging as SCD might be the first clinical manifestation of CVD and because the underlying etiology is not fully understood. “Among individuals without known heart disease many suffers from a concealed ischemic heart disease. When this is not the case genetic and other still unknown causes predispose individuals to SCD.”. When this is not the case genetic and other still unknown causes predispose individuals to SCD.” Risk factor profiling is proposed to be a feasible strategy to identify individuals with increased risk for SCD
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