Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database.

Am J Blood Res 2023;13(6):207-212 www.AJBlood.us /ISSN:2160-1992/AJBR0151469 Original Article Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database Luis Zuniga1, Mitchell Davis2, Mohammad Reza Movahed3,5, Mehrtash Hashemzadeh3, Mehrnoosh Hashemzadeh3,4 University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Dermatology, University of California, San Francisco, CA, USA; 3College of Medicine, University of Arizona, Phoenix, AZ, USA; 4Pima Community College, Tucson, AZ, USA; 5College of Medicine, University of Arizona, Tucson, AZ, USA 1 Received May 27, 2023; Accepted December 22, 2023; Epub December 25, 2023; Published December 30, 2023 Abstract: Factor V Leiden is an inheritable pro-thrombotic genetic condition caused by a point mutation at the 506th codon, resulting in activated protein C resistance. APC resistance has been shown to contribute to the development of venous thrombosis. However, the role of FVL in AMI has yet to be well defined in the current literature. To assess whether a mutation carrier is more apt to develop an AMI, we conducted a retrospective observational analysis of two populations aged 18-40 and 18 through end of life. We used ICD-10 codes to search the NIS, an electronic nationwide patient database, to establish our populations and obtain our data. The ICD-10 codes were specific for activated protein C resistance and acute myocardial infarction. Preliminary data indicated that FVL was related to AMI; however, this finding became insignificant in both populations when stratified for age. We concluded there was no association between Factor V Leiden and acute myocardial infarction across both examined populations. Future investigations into this field of research are warranted as there remains a need for more consensus among the scientific community. Background: Medical literature regarding the correlation between Factor V Leiden (FVL) and acute myocardial infarctions (AMI) is controversial. We aim to investigate the association between FVL and AMI. Materials and Methods: Using the Nationwide Inpatient Sample database, we evaluated any association between Factor V Leiden and acute myocardial infarction in 2016 using ICD-10 codes. Results: Univariate analysis (18-40) showed an increase of AMI in patients with FVL 0.6% vs. 0.4%. However, after adjustment for age and comorbid conditions in multivariate analysis, FVL was not significantly associated with acute myocardial infarction (OR 1.44 (95% CI 0.913-2.273, p-value 0.117)). Univariate analysis (all patients over 18 years old) found that 2.9% of patients with FVL experienced AMI vs. 4.4% without the mutation. Multivariate analysis of the entire population ultimately showed no correlation between FVL and AMI. Conclusion: In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population. Keywords: Factor V Leiden, FVL, myocardial infarction, MI, primary hypercoagulable state, deep venous thrombosis, activated protein C resistance Introduction Factor V, an essential procoagulant protein produced by the liver, plays a significant role in blood coagulation and hemostasis [1-3]. The typical sequence of thrombosis and hemostasis includes the sequential activation and deactivation of a series of clotting factors following an injury to tissue or the vasculature [4]. These injury pathways culminate with activated Factor V promoting thrombin and clot formation. Once the appropriate degree of clot formation has developed, activated protein C (APC) will inhibit Factor V, thus returning the body to normal homeostasis. Factor V Leiden, present in 3-8% of European Caucasians, is the most common genetic etiology of inherited hypercoagulability affecting this clotting cascade. A myocardial infarction, by contrast, “usually develops as a result of thrombosis originating from a ruptured atherosclerotic plaque in one of the coronary arteries” [11]. FVL is caused by a gain-of-function point mutation exchanging guanine for adenine at the 506th codon, causing the amino acid arginine to be replaced by glutamine [1, 5, 6]. This mutation results in activated Factor V resistant to https://doi.org/10.62347/XQBZ7374 Factor V Leiden and acute myocardial infarction cleavage by activated protein C, thus encouraging a hypercoagulable state [1-4]. Inheritance of this hypercoagulable state is a known risk factor for developing venous thrombus and thromboemboli [2, 5-10]. The inheritance pattern of the mutation also determines the degree of risk, with heterozygosity accounting for 3-8 times increased risk of venous blood clots, and homozygous inheritance demonstrates up to an 80 times increased risk profile [1]. There is a well-established and clinically significant link between FVL and venous thromboemboli in the medical literature. Interestingly, there is significantly less information examining the association between FVL and acute myocardial infarction (AMI) [10, 12-14]. a collection of hospital inpatient databases from the Healthcare Cost and Utilization Project (HCUP). The NIS was designed for trending national healthcare utilization, quality of healthcare, and patient outcomes. Part of its’ design is to maintain a database of patient demographics and their reasons for hospitalization via ICD-10 billing codes. By searching for specific ICD-10 codes, we extracted patient demographics relevant to our study from each associated billing code. We then built our statistical model and drew comparative data from this pool. The NIS database is available at www. hcup-us.ahrq.gov. Methods We utilized the NIS database to collect the data for our analysis. First, we determined the total population of individuals aged 18-40 who were seen at NIS-affiliated hospitals in 2016. We then narrowed the parameters of our search using the International Classification of Diseases, tenth revision, and Modification (ICD-10CM) codes D68.51 (activated protein C resistance) and I21, I22, I23, and I24 (acute myocardial infarctions) to determine the number of individuals in this population group who carried the diagnosis of activated protein C resistance or acute myocardial infarction. This population was subjected to a univariate analysis to determine the prevalence of AMI in the FVL and the non-FVL populations. A multivariate analysis of individuals positive for FVL was then conducted with and without age adjustment. A second series of searches utilizing the same parameters and ICD-10 codes was performed without the 40-year age restriction. This newly expanded population was subjected to the same univariate and multivariate analysis as the 18-40 age group. The multivariate analysis of both demographics included accounting for diabetes, hypertension, hyperlipidemia, race, and gender. Inclusion into our study was purposefully broad to avoid a selection bias. Still, it was limited to individuals admitted to NIS (...truncated)