Breitling, Lutz P. and Koenig, Wolfgang and Fischer, Marcus and Mallat, Ziad and Hengstenberg, Christian and Rothenbacher, Dietrich and Brenner, Hermann (2011) Type II Secretory Phospholipase A(2) and Prognosis in Patients with Stable Coronary Heart Disease: Mendelian Randomization Study. PLOS ONE, 6 (7): e22318. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background: Serum type II secretory phospholipase A(2) (sPLA(2)-IIa) has been found to be predictive of adverse outcomes in patients with stable coronary heart disease. Compounds targeting sPLA(2)-IIa are already under development. This study investigated if an association of sPLA(2)-IIa with secondary cardiovascular disease (CVD) events may be of causal nature or mainly a matter of confounding by correlated cardiovascular risk markers. Methodology/Principal Findings: Eight-year follow-up data of a prospective cohort study (KAROLA) of patients who underwent in-patient rehabilitation after an acute cardiovascular event were analysed. Associations of polymorphisms (SNP) in the sPLA(2)-IIa-coding gene PLA2G2A with serum sPLA(2)-IIa and secondary fatal or non-fatal CVD events were examined by multiple regression. Hazard ratios (HR) were compared with those expected if the association between sPLA(2)-IIa and CVD were causal. The strongest determinants of sPLA(2)-IIa (rs4744 and rs10732279) were associated with an increase of serum concentrations by 81% and 73% per variant allele. HRs (95% confidence intervals) estimating the associations of the SNPs with secondary CVD events were increased, but not statistically significant (1.16 [0.89-1.51] and 1.18 [0.91-1.52] per variant allele, respectively). However, these estimates were very similar to those expected when assuming causality (1.18 and 1.17), based on an association of natural log-transformed sPLA(2)-IIa concentration with secondary events with HR = 1.33 per unit. Conclusion: The present findings regarding genetic polymorphisms, determination of serum sPLA(2)-IIa, and prognosis in CVD patients are consistent with a genuine causal relationship and thus might point to a valid drug target for prevention of secondary CVD events.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; EPIC-NORFOLK; SERUM-LEVELS; HEALTHY-MEN; EVENTS; ASSOCIATION; RISK; ATHEROGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jun 2020 07:17 |
| Last Modified: | 05 Jun 2020 07:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20532 |
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