vitamin-k-semiquinone-radical and Myocardial-Ischemia

In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT).. A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method.. Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]).. In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome; Vitamin K

Clinical trials have assessed the effect of direct oral antagonists (DOACs) in patients with atrial fibrillation (AF) after percutaneous coronary interventions (PCI). Studies were designed to test the effect on bleeding incidence, but concerns related to safety on ischemic events remain.. We performed a meta-analysis with currently available studies involving DOACs versus Vitamin-K antagonist (VKA) in patients with AF after PCI. The primary endpoint was the incidence of cardiac ischemic events, including myocardial infarction and stent thrombosis. Secondary endpoints were the incidence of stroke, all-cause mortality, and major bleeding.. Eleven thousand twenty-three patients were included in the analysis: 5510 receiving DOACs and 5513 VKA. A total of 190 cases of myocardial infarction were registered in patients treated with DOACs and 177 in patients on VKA, and no statistical difference was noted [relative risk (RR): 1.07 95% confidence interval (CI) 0.88-1.31]. The incidence of stent thrombosis was very low with no differences between both treatment strategies (RR: 1.14 95% CI 0.76-1.71). The incidence of cardiac ischemic events was the same in patients receiving DOACs or VKA (HR 1.09 95% CI 0.91-1.30). No differences were observed in the incidence of stroke (RR: 0.86 95% CI 0.61-1.23) or mortality (RR: 1.09, 95% CI 0.90-1.31). Treatment with DOACs was associated with 34% reduction in major bleeding (RR: 0.66, 95% CI 0.54-0.81).. Treatment with DOACs in patients with AF after a PCI do not increase the risk of cardiac ischemic events, stroke, or death and reduce the incidence of major bleeding by 34% as compared with VKA.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Thrombosis; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Risk Assessment; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome; Vitamin K

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes.. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding).. The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Rivaroxaban; Thiophenes; Ticlopidine; Treatment Outcome; Vitamin K

Cancer may complicate the clinical course of nonvalvular atrial fibrillation (AF) but its association with cardiovascular events (CVEs) remains unclear. We performed a prospective cohort study including 2092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/nonfatal myocardial infarction and ischemic stroke/transient ischemic attack and cardiovascular death. Secondary endpoints were major adverse cardiac events (MACEs) and thromboembolism (TE). Mean age was 73.7 ± 9.1 years and 42.1% were women; 367 (17.5%) patients had cancer: 21% gastrointestinal (GI), 10% respiratory, 28% genitourinary and 41% had other localization. Cancer patients were older but with similar comorbidities than those without. During a mean of 35.9 months, 203 CVEs occurred (incidence rate [IR] = 3.24 per 100 patient-years): 133 MACEs (IR = 2.12 per 100 patient-years) and 70 TE (IR = 1.12 per 100 patient-years). Multivariable Cox proportional hazards regression analysis showed an association between GI cancer and MACE occurrence (hazard ratio [HR] = 3.22, 95% confidence interval [CI] = 1.59-6.52, P = .001) and between respiratory cancer and TE (HR = 3.37, 95% CI = 1.30-8.75, P = .013). These associations were confirmed at competing risk analysis. In conclusion, AF patients with cancer have specific vascular outcomes according to cancer site, as indicated by the higher risk of MACE and TE in patients with gastrointestinal and respiratory cancer, respectively.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Comorbidity; Cross-Sectional Studies; Female; Humans; Male; Myocardial Ischemia; Neoplasms; Proportional Hazards Models; Prospective Studies; Thromboembolism; Vitamin K

Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet).. This was a prospective single-center study including 912 AF patients treated with vitamin K antagonists (3716 patient-years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med-diet (n=704), and urinary excretion of 11-dehydro-thromboxane B. In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med-diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bacteria; Biomarkers; Cerebrovascular Disorders; Diet, Mediterranean; Female; Gastrointestinal Microbiome; Humans; Intestines; Kaplan-Meier Estimate; Lipopolysaccharides; Male; Myocardial Ischemia; Patient Compliance; Platelet Activation; Prospective Studies; Protective Factors; Risk Factors; Rome; Time Factors; Treatment Outcome; Vitamin K

Direct oral anticoagulants (DOACs) have been promoted in patients with nonvalvular atrial fibrillation (nv-AF) as a more convenient alternative to vitamin K antagonists. We estimated 1-year dabigatran and rivaroxaban adherence rates in nv-AF patients and assessed associations between baseline patient characteristics and nonadherence.. This cohort study included OAC-naive nv-AF patients with no contraindications to OAC, who initiated dabigatran and rivaroxaban, using nationwide data from French national health care databases. One-year adherence was defined by the proportion of days covered of 80% or more over a fixed 1-year period after treatment initiation. Associations between nonadherence and baseline patient characteristics were assessed using multivariate logistic regression models.. The population was composed of 11 141 dabigatran (women: 48%; mean age: 74 ± 10.7 y; ≥80 y: 34.9%) and 11 126 rivaroxaban (46.5%; 74 ± 10.9 y; 34.8%) new users. One-year adherence was 53.3% in dabigatran-treated and 59.9% in rivaroxaban-treated patients, consistent with numerous subgroup analyses. A switch to vitamin K antagonist was observed in 14.5% of dabigatran and 11.7% of rivaroxaban patients; 10.2% and 5.9% of patients switched to another DOAC, respectively; and 4.3% of patients died in the 2 cohorts. In patients who did not die or switch during the follow-up, 1-year adherence was 69.6% in dabigatran-treated and 72.3% in rivaroxaban-treated patients. Having concomitant ischemic heart diseases was associated with an increased risk of nonadherence in the 2 cohorts.. In this real-life study, 1-year adherence to DOAC is poor in nv-AF new users. Despite the introduction of DOAC, adherence to OACs may remain a significant challenge in AF patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Comorbidity; Dabigatran; Databases, Factual; Female; France; Health Care Surveys; Humans; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Rivaroxaban; Stroke; Vitamin K

Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.. VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake.. In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Prothrombin; Risk Assessment; Risk Factors; Stroke; Time Factors; United States; Vitamin K; Vitamin K Deficiency

Essentials Vitamin K plays a role in coagulation, and deficiency may promote coronary artery calcification. The role of vitamin K1 in heart disease was assessed using Mendelian randomization in Caucasians. Genetically higher vitamin K1 was associated with a higher risk of ischemic heart disease. Further research elucidating the role of vitamin K1 in ischemic heart disease could be useful.. Background Vitamin K1 is a nutrient in green leafy vegetables; deficiency may promote coronary artery calcification. Warfarin, an anticoagulant used in secondary prevention of thrombotic events, is a vitamin K antagonist. Thrombotic and coronary events may share risk factors. Objectives To clarify the role of vitamin K1 in ischemic heart disease, the risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically determined vitamin K1 levels. Given vitamin K1 is fat soluble, associations with lipids were similarly assessed to assess pleotropic effects via lipids. Methods Separate sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used to obtain an unconfounded estimate of the association of vitamin K1 (based on rs2108622 [CYP4F2], rs4645543 [KCNK9] and rs2192574 [CTNNA2] from a genome-wide association study) with CAD/MI using CARDIoGRAMplusC4D (cases = 64 374; controls = 130 681) and with lipids using Global Lipids Genetics Consortium Results (n = 196 475). Results Vitamin K1 single nucleotide polymorphisms were positively associated with CAD/MI (odds ratio [OR], 1.17 per unit [nmol L(-1) ] of natural log-transformed genetically predicted vitamin K1 ; 95% confidence interval [CI], 1.08-1.26), but not with inverse normal transformed low-density lipoprotein cholesterol (-0.0003; 95% CI, -0.03 to 0.03), high-density lipoprotein cholesterol (0.02; 95% CI, -0.01 to 0.05) or triglycerides (-0.01; 95% CI, -0.04 to 0.02). Considering only rs2108622, which is functionally relevant to vitamin K1 , the association for CAD/MI was stronger (OR, 1.21; 95% CI, 1.08-1.36). Conclusions Vitamin K may cause CAD/MI; whether vitamin K or other determinants of coagulation could be relevant to primary prevention might be worth considering.

Topics: Calcinosis; Case-Control Studies; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Diet; Female; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Male; Mendelian Randomization Analysis; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Polymorphism, Single Nucleotide; Risk Factors; Triglycerides; Vitamin K; Warfarin; White People

Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease.. We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK).. During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥ 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32-2.72) and 1.88 (95% CI, 1.22-2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18-2.61) and 1.79 (95% CI, 1.12-2.57).. In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.

Topics: Aged; Biomarkers; Calcium-Binding Proteins; Cardiovascular Diseases; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Humans; Kaplan-Meier Estimate; Male; Matrix Gla Protein; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Treatment Outcome; Vascular Diseases; Vitamin K

This study sought to evaluate whether prasugrel may serve as an alternative to clopidogrel in patients with triple therapy.. Approximately 10% of patients who receive dual antiplatelet therapy after percutaneous coronary intervention have an indication for oral anticoagulation and are thus treated with triple therapy. The standard adenosine diphosphate receptor blocker in this setting is clopidogrel. Data regarding prasugrel as part of triple therapy are not available.. We analyzed a consecutive series of 377 patients who underwent drug-eluting stent implantation and had an indication for oral anticoagulation between February 2009 and December 2011 and were treated with a 6-month regimen of aspirin and oral anticoagulation with either prasugrel or clopidogrel. The primary endpoint was a composite of Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding at 6 months. The secondary endpoint was a composite of death, myocardial infarction, ischemic stroke, or definite stent thrombosis.. Twenty-one patients (5.6%) received prasugrel instead of clopidogrel. These patients had a higher-risk profile at baseline, and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel compared with the clopidogrel group (6 [28.6%) vs. 24 [6.7%]; unadjusted hazard ratio (HR): 4.6, 95% confidence interval [CI]: 1.9 to 11.4], p < 0.001; adjusted HR: 3.2, 95% CI: 1.1 to 9.1], p = 0.03). There was no significant difference regarding the combined ischemic secondary endpoint (2 [9.5%] vs. 25 [7.0%]; unadjusted HR: 1.4, 95% CI: 0.3 to 6.1], p = 0.61).. These findings suggest that substitution of prasugrel for clopidogrel in patients needing triple therapy increases the risk of bleeding. However, specific randomized trials are needed to define the role of newer adenosine diphosphate receptor antagonists in this setting.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Selection; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Vitamin K

Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with increasing age and the most important complication of the disease is thromboembolic events that may be prevented by antivitamin K. They are the most efficient therapeutic class for the prevention of these events but they are associated with an increased haemorrhagic risk leading to a reduced prescription in general practice. Optimisation of the management should be based on an individual evaluation of the thromboembolic and haemorrhagic risks, taking into account age, the presence of an associated heart disease, hypertension, diabetes, history of cerebrovascular event, history of previous haemorrhagic event and the ability to achieve a stable target INR. The challenge in ventricular arrhythmias lies in identifying a high risk of sudden death, mainly related to ventricular fibrillation. In patients with structural heart disease, left ventricular dysfunction is the strongest predictor of sudden death. Non invasive markers such as non sustained ventricular tachycardia, late ventricular potentials, decreased heart rate variability and baroreflex sensitivity, and repolarization altemans are further elements to assess risk. However, most of these markers have a poor positive predictive value and a low specificity. In patients with normal hearts, genetic predisposition may in the future identify high risk patients. The electrophysiologic study with programmed ventricular stimulation remains a costly and invasive method and only has a strong positive predictive value in ischemic cardiomyopathy. More precise algorithms for risk stratification are thus needed that may help the strategy of therapy with prophylactic implantable cardioverter defibrillator in the future.

Topics: 4-Hydroxycoumarins; Age Factors; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Baroreflex; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Diabetes Complications; Electrocardiography; Heart Diseases; Heart Rate; Hemorrhage; Humans; Hypertension; Indenes; International Normalized Ratio; Myocardial Ischemia; Risk Assessment; Risk Factors; Stroke; Tachycardia, Ventricular; Thromboembolism; Ventricular Dysfunction, Left; Ventricular Fibrillation; Vitamin K

Topics: Anticoagulants; Antifibrinolytic Agents; Contraindications; Humans; Myocardial Ischemia; Thrombolytic Therapy; Vitamin K

An increase in factor VII was found to be a risk factor for ischemic heart disease. The present study was designed to test the hypothesis that this increase in factor VII is part of a general increase in vitamin K-dependent clotting factors. Initially, a prospective analysis of factor VII antigen and prothrombin activity was performed in two groups of young subjects without symptoms who differed in their risk of ischemic heart disease based on a history (or lack thereof) of premature heart disease in a first-degree relative. A statistically significant increase in prothrombin activity and factor VII antigen was found in the high-risk group of subjects when compared with the low-risk group. In a second series of subjects, factor IX and X activity assays were also performed, and all four of the vitamin K-dependent clotting factors were found to be significantly higher in high-risk subjects when compared with low-risk subjects. A second goal of the study was to explore whether correlations between factor VII and cholesterol and triglycerides might be due to binding of factor VII with apolipoprotein B. Although a significant correlation of factor VII antigen with apolipoprotein B (rho = 0.523, p < 0.025) was found in our high-risk group of subjects, the correlation between factor VII and triglycerides (rho = 0.641, p < 0.005) was even stronger statistically, suggesting a probable interaction of factor VII with very-low-density lipoproteins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Apolipoproteins B; Blood Coagulation Factors; Cholesterol; Factor IX; Factor VII; Factor X; Female; Humans; Male; Myocardial Ischemia; Prospective Studies; Prothrombin; Regression Analysis; Risk Factors; Triglycerides; Vitamin K