Factor V Leiden Does Not Modify the Phenotype of Acute Coronary Syndrome or the Extent of Myocardial Necrosis

Abstract

Background The prothrombotic defect factor V Leiden (FVL) may confer higher risk of ST-segment-elevation myocardial infarction (STEMI), compared with non-ST-segment-elevation acute coronary syndrome, and may be associated with more myocardial necrosis caused by higher thrombotic burden. Methods and Results Patients without history of cardiovascular disease were selected from 2 clinical trials conducted in patients with acute coronary syndrome. FVL was defined as G-to-A substitution at nucleotide 1691 in the factor V (factor V R506Q) gene. Odds ratios were calculated for the association of FVL with STEMI adjusted for age and sex in the overall population and in the subgroups including sex, age (≥70 versus <70 years), and traditional cardiovascular risk factors. The peak biomarker levels (ie, creatine kinase-myocardial band and high-sensitivity troponin I or T) after STEMI were contrasted between FVL carriers and noncarriers. Because of differences in troponin assays, peak high-sensitivity troponin levels were converted to a ratio scale. The prevalence of FVL mutation was comparable in patients with STEMI (6.0%) and non-ST-segment-elevation acute coronary syndrome (5.8%). The corresponding sex- and age-adjusted odds ratio was 1.06 (95% CI, 0.86-1.30; P=0.59) for the association of FVL with STEMI. Subgroup analysis did not show any differences. In patients with STEMI, neither the median peak creatine kinase-myocardial band nor the peak high-sensitivity troponin ratio showed any differences between wild-type and FVL carriers (P for difference: creatine kinase-myocardial band=0.33; high sensitivity troponin ratio=0.54). Conclusions In a general population with acute coronary syndrome, FVL did not discriminate between a STEMI or non-ST-segment-elevation acute coronary syndrome presentation and was unrelated to peak cardiac necrosis markers in patients with STEMI. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00391872 and NCT01761786.

Keywords: cardiovascular disease; cardiovascular disease risk factors; coagulation/thrombosis; factor V Leiden; genetic polymorphism.

Conflict of interest statement

Dr Mahmoodi received a VENI grant from the Dutch Research Council for investigating the role of factor V Leiden in the pathogenesis of myocardial infarction. Dr Meijer reports receiving research grants from Pfizer, Bayer, and Sanquin; lecturing fees from Bayer, Sanquin, Boehringer Ingelheim, BMS, and Aspen; and consulting fees from Uniqure. All fees were paid to the institute. Dr James has received grants from AstraZeneca, The Medicines Company, Swedish Heart and Lung Foundation, Swedish Research Council, and Janssen; and personal fees from Bayer. Dr Wallentin reports institutional research grants, consultancy fees, lecture fees, and travel support from Bristol‐Myers Squibb/Pfizer, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim; institutional research grants from Merck and Co. and Roche Diagnostics; consultancy fees from Abbott; and holds patents (EP2047275B1, US8951742B2) licensed to Roche Diagnostics. Dr ten Berg reports receiving fees for board membership from AstraZeneca; consulting fees from AstraZeneca, Eli Lilly, and Merck; and lecture fees from Daiichi Sankyo, Eli Lilly, AstraZeneca, Sanofi, and Accumetric.

Figures

Figure 1. Association of factor V Leiden mutation with ST‐segment–elevation myocardial infarction (STEMI) compared with non–ST‐segment–elevation acute coronary syndrome (NSTE‐ACS) in the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial.

P‐int denotes P value for interaction, that is, the difference between the strata. Estimates are adjusted for sex and age, when appropriate. OR indicates odds ratio.

Figure 2. Median and interquartile range (IQR) of the peak creatine kinase‐myocardial band (CK‐MB) and high‐sensitivity (hs)‐troponin ratio in the POPular Genetics trial.

CK‐MB values are measured in units per liter, and the hs‐troponin values are ratio of the peak hs‐troponin divided by the upper limit of the normal range of the same hs‐troponin assay. Whiskers represent IQR. N indicates the number of patients contributing data in each group.