Established Clinical Risk Factors Research Articles

Gender differences in contrast-enhanced magnetic resonance imaging after acute myocardial infarction

Besides different risk profiles for cardiovascular events in men and women, several studies reported gender differences in mortality after acute myocardial infarction (AMI). As infarct size has been shown to correlate with mortality, it is widely accepted as surrogate marker for clinical outcome. Currently, cardiovascular imaging studies covering the issue of gender differences are rare. As magnetic resonance scar characterization parameters are emerging as additional prognostic factors after acute myocardial infarction, we sought to evaluate gender differences in CMR infarct characteristics in patients after acute myocardial infarction. We prospectively analyzed patients (n = 448) with AMI and primary angioplasty, who underwent contrast enhanced cardiac magnetic resonance (CMR) imaging on a 1.5 T scanner in median 5 [Galatius-Jensen et al. in BMJ 313(7050):137–140, (1996), Burns et al. in J Am Coll Cardiol 39(1):30–36, (2002)] days after the acute event. CMR scar size was measured 15 min after gadolinium injection. In addition presence and extent of microvascular obstruction (MVO) was assessed. A matched pair analysis was performed in order to exclude confounding by gender related co-morbidities and gender differences in established clinical risk factors. Matching process according to clinical risk defined by GRACE score resulted in 93 mixed gender couples. Women were significantly older than men (64.4 ± 11.9 vs. 60.5 ± 12.3, p = 0.03) and presented with a significantly better ejection fraction before angioplasty (48.9 ± 8.4 vs. 46.2 ± 8.9, p = 0.04). Infarct size did not differ significantly between women and men (13.5 ± 10.7 vs. 15.1 ± 11.8, p = 0.32). Size of MVO was significantly smaller in women than in men (0.48 ± 1.3 vs. 1.2 ± 3.0, p = 0.03). Comparing scar characterization between women and men with similar risk profiles revealed no gender differences in scar size. Size of MVO, however, was significantly smaller in women and might reflect better cardioprotective mechanisms in women. Whether these changes have prognostic implications has to be tested on a larger patient population.

Abstract 9070: Secretoneurin is Produced in the Ischemic Border Zone of Animals with Myocardial Infarction and Heart Failure, Attenuates Ischemic Injury, and is Associated with the Progression of Heart Failure in Patients

Background: Secretoneurin (SN) is a peptide belonging to the granin protein family. As two other granin proteins, chromogranin A and B, are increased in cardiac tissue in heart failure (HF), we hypothesized that SN could play a role in cardiovascular pathophysiology. Methods: Production and functional aspects of SN were assessed in experimental models and circulating levels measured in two cohorts of HF patients. Results: Pro-SN mRNA levels were 11.5 fold increased in viable left ventricular (LV) tissue of mice subjected to coronary artery ligation and with echocardiographical confirmed HF. Protein levels were also increased in the LV of HF animals vs. sham-operated animals, including in the ischemic border zone where we observed increased processing from pro-SN to shorter SN fragments (>100% increase, p=0.001). Immunohistochemistry localized myocardial SN production to cardiomyocytes. We did not observe increased SN production in other organs than the LV. Perfusing isolated cardiomyocytes with SN rapidly induced Stat3 and Erk1/2 phosphorylation, protected from hydrogen peroxide-induced cardiomyocyte apoptosis in vitro , and reduced ischemia-reperfusion injury by 30% (p<0.05) in the isolated perfused rat heart. Circulating levels of SN were increased in patients with stable and acute HF compared to control subjects and increased in proportion to HF severity as evaluated by NYHA functional class (p=0.04 for trend). In 68 patients hospitalized for acute HF, admission SN levels provided excellent discrimination for all-cause mortality (n=17) during a median follow-up of 373 days: Hazard ratio [per 0.05 nmol/L increase of SN] 2.34 (95% CI 1.63-3.38), p<0.001. Adjustment for established clinical risk factors including comorbidities, renal function, and LV ejection fraction in multivariate analysis did not attenuate the association between SN levels and mortality: HR 2.43 (95% CI 1.63-3.61), p<0.001. Conclusion: SN production is increased in viable cardiomyocytes adjacent to the infarcted area in animals with myocardial infarction and HF, which could be beneficial as SN protects from myocardial ischemia. Based on our results, SN could represent a protective feedback response that is activated in proportion to the severity of HF.

C-Reactive Protein and the Risk of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention

Background: The relationship between preprocedural C-reactive protein (CRP) levels and the incidence of contrast-induced acute kidney injury (CI-AKI) is unknown. Methods: Documents of 7,310 consecutive patients undergoing percutaneous coronary intervention (PCI) were screened. Patients with acute myocardial infarction, cardiogenic shock, concomitant inflammatory conditions or undergoing CABG within 48 h were excluded due to potential confounding effects. Results: A total of 4,522 patients were valid for analysis. The median follow-up was 26 months (interquartile range 20–33 months). According to preprocedural CRP values, patients were divided into 3 groups: group 1: CRP <1.0 mg/l (n = 1,523); group 2: 1.0 mg/l ≤ CRP ≤ 3.0 mg/l (n = 1,626); group 3: CRP >3.0 mg/l (n = 1,373). Patients with higher preprocedural CRP levels were associated with a significantly increased rate of CI-AKI (10.6 vs. 14.9 vs. 23.5%, p < 0.0001). After adjustment for baseline covariates, CRP level was still an independent predictor for the incidence of CI-AKI, either as a continuous variable or a categorical variable. Patients with higher CRP values had a significantly higher rate of all-cause mortality and myocardial infarction during follow-up. Conclusion: Elevated preprocedural CRP is associated with an increased risk for CI-AKI in patients undergoing PCI. Preprocedural risk stratification with CRP as an adjunct to established clinical risk factors might be useful.

Prognostic value of PAX–FKHR fusion status in alveolar rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma study group (CWS)

Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis. Between 1986 and 2004, out of 446 patients with RMA treated in four consecutive CWS trials, tumor samples from 126 patients were available for RT-PCR analysis. Survival depending on fusion status in context with known clinical risk-factors was analyzed. Out of 126 samples, 121 had adequate quality for PAX-FKHR fusion status analysis. PAX-FKHR fusions were detected in 101 samples: 60% PAX3-FKHR and 24% PAX7-FKHR fusions, 17% were fusion-negative. There was no significant difference in survival between patients with PAX3-FKHR versus PAX7-FKHR positive tumors. The fusion transcript negative cohort showed a more favorable outcome than the fusion transcript positive cohort among patients with metastatic disease. From the established clinical risk-factors none was associated with a significantly higher risk of failure or death in a multivariate analysis. PAX-FKHR fusion type was not a significant predictor for survival in our analysis. More extensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact.

Baseline depression predicts malnutrition in head and neck cancer patients undergoing radiotherapy

Poor nutritional status is common and associated with mortality and morbidity in patients with head and neck cancer (HNC). While there are several established clinical risk factors for poor nutritional status during HNC radiotherapy, the complete aetiology is not known. The association of malnutrition with psychological factors has been recognised in other chronic illnesses but has not been studied in HNC patients who have higher levels of malnutrition and psychological disorder than many other patient populations. Patients with HNC were assessed at three time points: week 1 of radiotherapy treatment (T1, n = 72), end of radiotherapy treatment (T2, n = 64) and 4 weeks post-radiotherapy treatment (T3, n = 58). Nutritional outcome was measured using the Patient-Generated Subjective Global Assessment, and psychological factors measured were depression, anxiety and adjustment style. Linear mixed models indicated that a model containing the variables time, tumour site and baseline depression best explained malnutrition at T2 and T3 (-2 restricted log likelihood = 695.42). The clinical risk factors: cancer stage, number of radiotherapy fractionations, a PEG feeding tube, availability of a care giver and dietitian's informal clinical assessment did not predict later nutritional status. Depression is a modifiable risk factor for malnutrition among HNC patients undergoing radiation therapy, offering the potential to ameliorate malnutrition in this group. While the nature of any causal relationship between depression and malnutrition in HNC is yet to be understood, the utility of a short depression screen in predicting malnutrition has been demonstrated and could be adopted in clinical practice.

Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure

Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein-associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers. We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction <50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P<0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P<0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P<0.01) as well as B-type natriuretic peptide (r=-0.23, P<0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P<0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004). In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors.

Bilateral Renal Agenesis/Hypoplasia/Dysplasia (BRAHD): Postmortem Analysis of 45 Cases with Breakpoint Mapping of Two De Novo Translocations

BackgroundBilateral renal agenesis/hypoplasia/dysplasia (BRAHD) is a relatively common, lethal malformation in humans. Established clinical risk factors include maternal insulin dependent diabetes mellitus and male sex of the fetus. In the majority of cases, no specific etiology can be established, although teratogenic, syndromal and single gene causes can be assigned to some cases.Methodology/Principal Findings45 unrelated fetuses, stillbirths or infants with lethal BRAHD were ascertained through a single regional paediatric pathology service (male∶female 34∶11 or 3.1∶1). The previously reported phenotypic overlaps with VACTERL, caudal dysgenesis, hemifacial microsomia and Müllerian defects were confirmed. A new finding is that 16/45 (35.6%; m∶f 13∶3 or 4.3∶1) BRAHD cases had one or more extrarenal malformations indicative of a disoder of laterality determination including; incomplete lobulation of right lung (seven cases), malrotation of the gut (seven cases) and persistence of the left superior vena cava (five cases). One such case with multiple laterality defects and sirelomelia was found to have a de novo apparently balanced reciprocal translocation 46,XY,t(2;6)(p22.3;q12). Translocation breakpoint mapping was performed by interphase fluorescent in-situ hybridization (FISH) using nuclei extracted from archival tissue sections in both this case and an isolated bilateral renal agenesis case associated with a de novo 46,XY,t(1;2)(q41;p25.3). Both t(2;6) breakpoints mapped to gene-free regions with no strong evidence of cis-regulatory potential. Ten genes localized within 500 kb of the t(1;2) breakpoints. Wholemount in-situ expression analyses of the mouse orthologs of these genes in embryonic mouse kidneys showed strong expression of Esrrg, encoding a nuclear steroid hormone receptor. Immunohistochemical analysis showed that Esrrg was restricted to proximal ductal tissue within the embryonic kidney.Conclusions/SignificanceThe previously unreported association of BRAHD with laterality defects suggests that renal agenesis may share a common etiology with heterotaxy in some cases. Translocation breakpoint mapping identified ESRRG as a plausible candidate gene for BRAHD.

Bone densitometry and true BMD accuracy for predicting fractures: what are the alternatives?

Requirements for clinical densitometric evaluation of fracture risk of an individual patient are obvious: the method must be noninvasive and safe, it should provide adequate assessment of bone fragility, be sensitive and specific enough to detect small differences or changes in structural bone traits that are vital to bone strength, and appreciably add to the predictive ability of prior assessment of fracture risk based on established clinical risk factors of the given patient. At present, clinical evaluation of bone fragility largely rests on dual-energy x-ray absorptiometry (DXA) and the obtained areal bone mineral density (BMD) and the T- and Z-scores derived from it. Whereas BMD correlates strongly with bone strength and low BMD indicates increased relative risk of fragility fractures, the overall proportion of fractures attributable to osteoporosis, as diagnosed by low DXA-measured BMD, remains quite modest. This paradox apparently arises from the limited ability of areal BMD to elicit individual pat...

Plasma copeptin and the risk of diabetes mellitus.

Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.

Predictors of stroke in patients with severe systolic dysfunction in sinus rhythm: Role of echocardiography

Congestive heart failure in sinus rhythm ranks second after atrial fibrillation (AF) among cardiogenic risk-factors for stroke. Clinical and echocardiographic predictors of stroke in this high-risk population remain poorly defined. Retrospective screening of 1886 consecutive patients with severe systolic dysfunction (LVEF ≤35%) at a tertiary medical center echocardiography database (Nov 2005-Sep 2008) identified 83 patients in sinus rhythm with cardioembolic stroke. Patients with AF on follow-up, prosthetic valve, ventricular arrhythmia and lack of consensus between reviewing neurologists were excluded (n=10). Consecutive age and gender-matched controls in sinus rhythm formed GpII (n=73). The incidence of stroke was 3.9% (73/1886) over 35 months in this study. There were no significant differences in prevalence of established clinical risk-factors for stroke. There was a significantly higher prevalence of LV non-compaction (p=0.02), aneurysm (p<0.01), spontaneous echo-contrast (p<0.01) and pulmonary hypertension (p<0.001) in GpI. LV non-compaction, aneurysm, spontaneous echo-contrast and pulmonary hypertension are associated with an increased risk of stroke. While anticoagulation of these high-risk subgroups appears reasonable, further study in a prospective randomized clinical trial merits consideration.

Motor complications in patients form the German Competence Network on Parkinson's disease and the DRD3 Ser9Gly polymorphism

In addition to levodopa treatment and disease duration, genetic predisposition might contribute to the development of medication-related complications in Parkinson's disease (PD). As recent observations indicate the dopamine D(3) receptor (DRD3) to modulate both therapeutic action of levodopa and dyskinesia, we reappraised the impact of the DRD3 Ser9Gly polymorphism on development of motor complications in a large scale association study based on the gene bank of the German Competence Network on Parkinson's disease. Stepwise regression analysis revealed no effect of DRD3 Ser9Gly on chorea, dystonia, or motor fluctuations in PD, despite incorporating established clinical risk factors to avoid overlooking an effect of genotype. Duration of PD was confirmed as the most important clinical risk factor, followed by age of disease onset and female sex. Additional studies incorporating grading of motor complications, and combinations of risk genotypes, are warranted.

Primary Graft Dysfunction

Primary graft dysfunction (PGD) is a severe form of ischemia/reperfusion acute lung injury that is a major cause of early morbidity and mortality after lung transplantation. Survivors of PGD have worse long-term lung function and an increased chance of developing bronchiolitis obliterans syndrome (BOS), the manifestation of chronic rejection. This review examines the current state of PGD research in the context of a recent consensus statement by the International Society for Heart and Lung Transplantation (ISHLT) designed to standardize the definition of PGD in clinical research efforts. This article will review this definition and issues surrounding it, outcome studies examining the long-term effects of PGD, and the established clinical risk factors for PGD. Translational studies exploring the pathogenesis of PGD will be highlighted, and the current state of PGD prevention and management will also be described. Finally, we will summarize efforts at finding genetic and molecular markers for PGD and discuss future directions for PGD research.

Molecular staging of prostatic cancer with RT-PCR assay for prostate-specific antigen in peripheral blood and lymph nodes: 5 Year follow-up

Thirty percent of patients with localized prostate cancer undergoing radical prostatectomy experience biochemical recurrence with rising serum prostate-specific antigen (PSA). More than 50% of these develop distant metastases. Presence of PSA mRNA in pathologically normal pelvic lymph nodes from 154 patients undergoing radical prostatectomy was investigated with non-quantitative PSA reverse transcriptase polymerase chain reaction (RT-PCR). In 135 of these patients preoperative serum PSA RT-PCR was also assessed. RT-PCR positivity was correlated with biochemical recurrence and compared with other clinical risk factors. At a median follow-up of 58 months the biochemical failure-free survival of patients with positive versus negative lymph node RT-PCR was 68.4% and 76.7% respectively (p=0.2). Biochemical failure-free survival was not influenced by the serum PSA RT-PCR result either (72.3% versus 72.6%). Surgical margin status, preoperative serum PSA, pT category and Gleason score were independent prognostic risk factors for biochemical recurrence with a hazard ratio of 5.48, 2.56, 2.56 and 2.13 respectively. At 5 year follow-up after radical prostatectomy, both serum and lymph node RT-PCR are not correlated with biochemical failure-free survival. Established clinical risk factors have a much stronger impact on biochemical recurrence.

Clinical Predictors of Renal Allograft Histopathology: A Comparative Study of Single-Lesion Histology Versus a Composite, Quantitative Scoring System

Progressive injury that is refractory to conventional immunosuppression remains the major hurdle to indefinite survival of transplanted organs. Several clinical risk factors of chronic renal allograft rejection have been identified; although some (e.g., acute rejection) are direct manifestations of immunological injury, others (e.g., donor age) have been more difficult to conceptually link with graft dysfunction. We conducted formal multivariate statistical analyses to reveal associations between established clinical risk factors and allograft histopathology. In a multicenter protocol biopsy-controlled study, 17 clinical risk factors were studied in relation to either the composite Chronic Allograft Damage Index (CADI) score or, to each of eight individual histological indices, using multiple linear regression with forward selection. Nine clinical risk factors were not significantly associated with any histopathological index. Four (donor age, acute rejection, recipient age, and cold ischemia time) were associated both with the total CADI score and, to varying extents, with the individual histopathological indices. In our analysis, clinical risk factors accounted for, at best, only about 60% of the interindividual variation in histopathological score. Our study reveals a missing link between specific clinical risk factors and early histopathological findings that are known to presage accelerated failure of clinically healthy grafts. Given the complex relationship between clinical risk factors, early histopathological changes, and graft outcome, we conclude that composite, quantitative histological indices are best suited to for evaluation of the histological status of the transplant.

Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: The Strong Heart Study (SHS)

Echocardiographic left atrial (LA) volume has been documented to be an independent predictor of cardiovascular events. Less is known about the predictive ability of anteroposterior LA diameter, a simpler measure of LA size obtained routinely during echocardiographic evaluation. We investigated the prognostic value of LA diameter for incident cardiovascular events in 2804 American Indians free of clinical cardiovascular disease, valvular disease, and atrial fibrillation. Echocardiographic variables were obtained using standardized methods, and previously derived sex-specific partition values were used to define left ventricular (LV) hypertrophy indexed to height(2.7) (in meters) and LA enlargement (> 4.2 cm in men, > 3.8 cm in women). Cardiovascular events included nonfatal stroke, coronary heart disease, congestive heart failure, and fatal cardiovascular disease based on validated definitions. During a median follow-up of 7 years, 368 events occurred. LA diameter, both as a continuous and as a categorical variable, was significantly associated with incident cardiovascular events in unadjusted analyses. In multivariable analyses that adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol-high-density lipoprotein cholesterol, smoking, renal insufficiency, LV hypertrophy, abnormal LV systolic and diastolic function, mitral annular calcification, fibrinogen, and C-reactive protein, both LA diameter (risk ratio 1.04/mm, 95% CI 1.02-1.07, P < .002) and LA enlargement (risk ratio 1.57, 95% CI 1.17-2.10, P = .002) remained independent predictors of first cardiovascular events. In this population-based cohort, LA diameter independently predicted incident cardiovascular events after adjustment for established clinical, echocardiographic, and inflammatory risk factors. This simple measure of LA dilatation can identify individuals at heightened risk who may warrant more aggressive risk factor modification.

Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: A community-based cohort study

BackgroundLittle information is available from community-based long-term VTE cohort studies to compare the absolute thrombosis risk of established clinical and genetic risk factors.Materials and methodsThe occurrence of venous thromboembolism (VTE) was observed during a 10-year observation period in the BAvarian ThromboEmbolic Risk (BATER) study, a cohort study of 4337 women (age 18–55 years). We collected data on demographics, reproductive life, lifestyle, conditions/diseases, and particularly potential risk factors for VTE with a self-administered questionnaire. The objective was to present incidence rates of VTE and to show relative risk estimated associated with different clinical and genetic risk factors.Results34 new, by diagnostic means confirmed VTE events occurred during the observation time of 32,656 women-years (WY). The overall incidence of VTE was 10.4 per 104 WY. The incidence rates varied markedly among different risk cohorts. The highest incidence was observed in women with previous history of VTE, followed by family history of VTE. None of the measured "genetically-related risk markers" (antithrombin, protein C, FVL, prothrombin mutation, or MTHFR) showed a significant VTE risk.ConclusionMost of the discussed VTE risk factors showed no significant association with the occurrence of new VTEs due to smallness of numbers. Only first-degree family history of VTE and own history of a previous VTE event depicted a significant association with future VTE. Clinical information seems to be more important to determine future VTE risk than genetically related laboratory tests.

High D-dimer levels predict cardiovascular events in patients with chronic atrial fibrillation during oral anticoagulant therapy.

Atrial fibrillation (AF) is associated with hemostatic abnormalities and increased risk of thrombotic cardiovascular events even during oral anticoagulant therapy (OAT). The aim of our study was to evaluate the predictive value of hemostatic markers for the risk of major cardiovascular events during OAT. The study group comprised 113 patients with chronic AF (70.2 +/- 5.4 years old, 60% men), referred for OAT. Established clinical risk factors and levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen and activity, before and during OAT (after 3.9 +/- 0.7 months; INR 2.57 +/- 0.57) were determined. In all patients OAT significantly suppressed levels of F1+2 by 67%,TAT by 30% and D-dimer by 48% (all p <0.001). During an average follow-up of 44 months 22/111 (20%) patients suffered a combined cardiovascular event (stroke, myocardial infarction, peripheral vascular occlusion or vascular death). Patients with cardiovascular events were significantly older, had more frequent heart failure/systolic dysfunction and had significantly increased levels of D-dimer at entry (63 vs 39 ng/mL, p = 0.005) and during OAT (33 vs 18 ng/mL, p = 0.002), and of t-PA antigen at entry (14.3 vs 10.9 ng/mL, p = 0.02) and during OAT (15.0 vs 11.2 ng/mL, p = 0.05) (all values are medians). In multivariate Cox proportional hazard models, heart failure/systolic dysfunction (hazard ratio 2.91; 95% CI 1.17-7.26; p = 0.02), high levels of D-dimer on OAT (top vs. lower two quartiles) (hazard ratio 4.78, 95% CI 1.39-16.41; p = 0.01) and t-PA antigen levels (continuous variable) (hazard ratio 1.09; 95% CI 1.01-1.17; p = 0.02) were significantly associated with combined cardiovascular events. In conclusion, high levels of D-dimer and t-PA antigen during OAT are significant predictors of combined cardiovascular events in AF patients and, on this basis, could be useful additional markers of cardiovascular risk in such patients.

The value of patient-reported health status in predicting short-term outcomes after coronary artery bypass graft surgery.

Risk stratification for comparison of outcomes after coronary artery bypass grafting (CABG) typically includes only clinical measures of risk. Patient-reported health status may be an important independent predictor of short-term health outcomes. To determine whether patient-reported health status, as measured by the Physical and Mental Component Summary scores of the SF-36, predicts in-hospital mortality and prolonged length of stay after CABG, after controlling for other clinical predictors of those outcomes. Prospective cohort study conducted from September 1993 to November 1995. One thousand seven hundred seventy-eight adults who underwent isolated CABG for myocardial ischemia. In-hospital mortality and prolonged length of stay (> 14 days). There were 27 deaths and 223 patients with prolonged length of stay in the study sample. A 10-point decrease in the Physical Component Summary (PCS) score increased the odds of in-hospital mortality by 61% (OR, 1.61; 95% CI, 1.04-2.49), independent of established clinical risk factors. Similarly, a 10-point decrease in the PCS score increased the odds of prolonged length of stay by 33% (OR, 1.33; 95% CI, 1.13-1.57). A 10-point decrease in the Mental Component Summary score (MCS) decreased the odds of mortality by 36% (OR, 0.64; 95% CI, 0.43-0.95). The PCS score is independently and significantly associated with in-hospital mortality and prolonged length of stay, after controlling for clinical risk factors. The MCS score is independently and significantly associated only with mortality, though the direction of the effect is unexpected. The result likely reflects a property of the scoring of the MCS and not a finding of clinical substance. Although caution must be taken when interpreting the summary scores, the SF-36 yields information not otherwise captured by clinical data and may be useful in risk stratification for in-hospital mortality and prolonged length of stay after CABG.

Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease

Increased levels of hemostatic factors may play a role in the pathogenesis of myocardial infarction by triggering thrombin formation. We measured factor XII (FXII), factor XI (FXI), plasma prekallikrein (PK) and high-molecular-weight kininogen (HK) in 200 patients having survived myocardial infarction for at least 2 months, and in 100 healthy controls. We found significantly elevated levels of FXI clotting activity (FXI:C), HK:C and of the amidolytic activity of PK (PK:Am) among the patients as compared to the controls. Plasma levels of FXI:C, HK:C and PK:Am in the highest quartile were associated with an odds ratio of 1.9 (95% CI: 1.0–3.8), 2.0 (95% CI: 1.0–4.0) and 5.4 (95% CI: 2.6–11.2), respectively, compared to the respective plasma levels in the lowest quartile. After correction for established clinical and laboratory risk factors, the association between PK:Am plasma levels and myocardial infarction remained significant ( P=0.0007). Combination of high PK:Am plasma levels and smoking or arterial hypertension, respectively, resulted in a more than additive relative risk for myocardial infarction.

Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism.

Currently, the risk for postoperative acute pulmonary embolism (APE) is assessed clinically. We hypothesize that the expensive screening for the most common genetic thrombophilic clotting defect (factor V Leiden; R(506)Q) after exclusion of established clinical risk factors does not offer additional benefit to surgical patients. We reviewed protocols and histories from 8249 consecutive autopsies performed at the Mayo Clinic, Rochester, Minn. All patients who died of APE after routine surgery and who lacked any other clinical risk factors for APE were included and compared with matched controls. Genomic DNA was extracted from archival tissues and examined for R(506)Q by polymerase chain reaction amplification, restriction enzyme digestion, and direct sequencing. Acute pulmonary embolism was the immediate cause of death in 454 patients (5.5%). Of those, 32 (7.0%) had undergone routine surgery. These patients represent less than 0.07% of all case-adjusted surgical procedures in the same period. The rate of postoperative death from APE was higher after neurosurgical procedures (0.3%) than all other procedures (0.04%). Sixteen patients (50.0%) were morbidly obese. Only 1 patient was heterozygous and none were homozygous for R(506)Q. (1) Fatal APE is uncommon in surgical patients lacking clinically apparent risk factors for venous thromboembolism. (2) Neurosurgical patients are at increased risk for postoperative APE. (3) Morbid obesity is a major independent risk factor in cases of sudden death from APE postoperatively. (4) Routine preoperative screening for R(506)Q in the factor V gene does not appear to offer additional benefit in surgical patients without clinically recognizable thromboembolic risk factor(s).