Risk Factors For Clinical Events Research Articles

Clinical event rate in patients with and without left main disease undergoing isolated coronary artery bypass grafting: results from the European DuraGraft Registry.

Left main coronary artery disease (LMCAD) is considered an independent risk factor for clinical events after coronary artery bypass grafting (CABG). We have conducted a subgroup analysis of the multicentre European DuraGraft Registry to investigate clinical event rates at 1 year in patients with and without LMCAD undergoing isolated CABG in contemporary practice. Patients undergoing isolated CABG were selected. The primary end point was the incidence of a major adverse cardiac event (MACE) defined as the composite of death, myocardial infarction (MI) or repeat revascularization (RR) at 1 year. The secondary end point was major adverse cardiac and cerebrovascular events (MACCE) defined as MACE plus stroke. Propensity score matching was performed to balance for differences in baseline characteristics. LMCAD was present in 1033 (41.2%) and absent in 1477 (58.8%) patients. At 1 year, the MACE rate was higher for LMCAD patients (8.2% vs 5.1%, P = 0.002) driven by higher rates of death (5.4% vs 3.4%, P = 0.016), MI (3.0% vs 1.3%, P = 0.002) and numerically higher rates of RR (2.8% vs 1.8%, P = 0.13). The incidence of MACCE was 8.8% vs 6.6%, P = 0.043, with a stroke rate of 1.0% and 2.4%, P = 0.011, for the LMCAD and non-LMCAD groups, respectively. After propensity score matching, the MACE rate was 8.0% vs 5.2%, P = 0.015. The incidence of death was 5.1% vs 3.7%, P = 0.10, MI 3.0% vs 1.4%, P = 0.020, and RR was 2.7% vs 1.6%, P = 0.090, for the LMCAD and non-LMCAD groups, respectively. Less strokes occurred in LMCAD patients (1.0% vs 2.4%, P = 0.017). The MACCE rate was not different, 8.5% vs 6.7%, P = 0.12. In this large registry, LMCAD was demonstrated to be an independent risk factor for MACE after isolated CABG. Conversely, the risk of stroke was lower in LMCAD patients. ClinicalTrials.gov NCT02922088.

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial

Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite usage of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group. Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association class [NYHA] II-IV) and ejection fraction <45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical endpoints, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, non-linearities, and interactions with treatment. Optimism-corrected c-indices were calculated using 200 bootstrap samples. During a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 (38.5%) patients. Independent predictors of increased risk for the primary endpoint included HF characteristics (longer HF duration and worse NYHA class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death. Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk HF patients who were receiving excellent guideline-based clinical care. Clinicaltrials.gov identifier, NCT02861534. Patients with heart failure may benefit from tools that help clinicians better understand patient's risk for future events like hospitalization. Relatively few risk models have been created after worsening of heart failure in a contemporary cohort. We provide insights on risk factors for clinical events from a recent large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.

Risk factors for systemic and venous thromboembolism, mortality and bleeding risks in 1125 patients with COVID-19: relationship with anticoagulation status.

Aim: Coronavirus disease 2019 (COVID-19) has been associated with increased mortality and morbidity from thromboembolism, especially venous thromboembolism. There are more limited data for systemic thromboembolism. The present study aimed to investigate the prevalence of systemic and venous thromboembolism as well as major bleeding and mortality in relation to underlying risk factors and the impact of anticoagulation use in hospitalized patients with COVID-19.Methods and results: Patients with COVID-19 admitted to Union Hospital, Wuhan, Hubei, China between January 08, 2020 and April 7, 2020 were enrolled in this retrospective study. Cox proportional hazard models were utilized to determine associated risk factors for clinical events, adjusting for the severity of COVID-19 infection, drug therapies, comorbidities, surgery, and use of antithrombotic drugs.There were 1125 patients (49.9% male; mean age 58 years (standard deviation, SD, 15 years)) with a mean follow-up of 21 (SD 13) days. Approximately 25 (30%) patients with thromboembolism also suffered bleeding events.Age was an independent risk factor for thromboembolism, bleeding events, and death (all p<0.05). After adjusting for the severity of COVID-19 infection, comorbidities, surgery, antiviral drugs, immunomodulators, Chinese herbs, and antithrombotic drugs, low lymphocyte counts (hazard ratio, HR, 95% confidence interval (CI), 1.03, 1.01-1.05, p=0.01) and surgery (HR 2.80, 1.08-7.29, p=0.03) independently predicted the risk for major bleeding, whereas liver dysfunction (HR 4.13, 1.30-13.1, p=0.02) was an independent risk factor for patients with both thromboembolism and bleeding events.Conclusions: Patients with COVID-19 were at high risk for thromboembolic and bleeding events as well as mortality. The use of anticoagulants, especially parenteral anticoagulants, significantly reduced the risk for composite outcomes of thromboembolism, bleeding events, and death. The presence of AF was a contributor to systemic thromboembolism in COVID-19 patients.

Severity of Intrarenal Arterial Lesions Can Predict the Clinical Prognosis of Hepatitis B Virus-Associated Glomerulonephritis: A Retrospective Study

Background: Intrarenal arterial lesions (IALs) have been studied in immunoglobulin A nephropathy and lupus nephritis, but this has not been reported in hepatitis B virus-associated glomerulonephritis (HBV-GN). This study aims to investigate the prevalence and the role of IALs in HBV-GN. Methods: IALs were examined in kidney biopsy specimens from 205 patients with HBV-GN retrospectively. The severity of IALs and tubular interstitial lesions was scored semi-quantitatively. The severity of IALs was divided into 4 groups on the basis of ILA score, which were no IALs (Score 0), mild IALs (Score 1–2), moderate IALs (Score 3–4), and severe IALs (Score 5–10) groups. Survival analysis was performed using the Kaplan-Meier method between the severity of IALs and clinical events (doubling of serum creatinine [SCr], ESRD, and death due to the kidney disease). Results: Among 205 patients with HBV-GN, 143 (69.8%) had IALs in their kidney biopsy specimens. IALs were mild in 28 (19.6%) patients, moderate in 101 (70.6%) patients, and severe in 14 (9.8%) patients. The severity of IALs was associated with high blood pressure (BP), high SCr, and severe tubulointerstitial injuries. The average follow-up time of these 205 HBV-GN patients was 94.2 ± 47.1 months, in which 46 cases had clinical event. The proportions of clinical events in no IAL, mild IAL, moderate IAL, and severe IAL groups were 9.7, 14.3, 25.7, and 71.4%, respectively. Event-free survival of patient in IAL group was significantly lower than that in the no IAL group (p = 0.000). Multivariate cox regression analysis indicated SCr (1.011, 1.007–1.016), hypertension (1.767, 1.004–3.108), and IAL (2.194, 1.062–4.530) were independent risk factors for clinical events after adjustment for age and gender. Event-free clinical survival in moderate and severe IAL groups was significantly lower than that in the no IAL group (p = 0.0111 and p = 0.0001, respectively). Besides, event-free renal survival in severe IAL group was significantly lower than that in moderate IAL group (p = 0.009). Multivariate cox regression analysis showed that the more severe the IALs, the higher the risk of the clinical event, with a hazard ratio of 2.284 for moderate IALs (1.085–4.907) and 3.315 for severe IALs (1.296–8.482). Conclusions: Severity of IALs is associated with high BP, reduced renal function, and poor clinical prognosis in HBV-GN patients.

Risk factors of clinical dysimmune manifestations in a cohort of 86 children with 22q11.2 deletion syndrome: A retrospective study in France.

In this study, we describe the biological immune profiles and clinical dysimmune manifestations (infections, autoimmune diseases, and allergies) of patients with 22q11.2 deletion syndrome with the aim of determining risk factors for clinical events. This retrospective study concerned all the patients with 22q11 deletion syndrome attending the Montpellier University Hospital from January 1, 1992, to December 31, 2014 who had at least one immune investigation before the age of 18. We analyzed the clinical features, biological tests and the course of infections, autoimmunity, and allergy of 86 children. Among these 86 children, 48 (59%) had a low T lymphocyte level. Twenty-nine patients (34%) had a severe infection. The only risk factor for severe infection was the low level of CD4+ T-cells (OR: 3.3; 95% confidence interval (CI) [1.020-11.108]). Eleven patients (13%) developed an autoimmune disease; the only risk factor was an antecedent of severe infection (OR: 4.1; 95% CI [1.099-15.573]). Twenty-three patients (27%) had allergic episodes. A low level of CD8+ T-cells (OR: 3.2; 95% CI [1.07-9.409]) was significantly associated with allergy manifestations. Patients with 22q11 deletion syndrome have a high rate of dysimmune manifestations. We found statistic correlations among CD4+ T-cell count, infectious manifestations, and autoimmunity.

Editor's Choice – Metformin Prescription is Associated with a Reduction in the Combined Incidence of Surgical Repair and Rupture Related Mortality in Patients with Abdominal Aortic Aneurysm

Currently there is no drug therapy for abdominal aortic aneurysm (AAA) and most previous investigations have focused on imaging rather than clinical outcomes. The aim of this study was to assess whether AAA related clinical events were lower in patients prescribed metformin. This was a prospective cohort observational study performed in three cities in Australia, which was designed to study risk factors for clinical events not simply to focus on metformin. Patients with an asymptomatic unrepaired AAA of any diameter ≥30mm were recruited from hospital outpatient clinics and surveillance programs run at four centres. The main outcome was the requirement for AAA repair or AAA related mortality (AAA events). The association between metformin prescription and AAA events was assessed using Kaplan-Meier analysis and Cox proportional hazard analysis. Patients (1,080) with a mean (SD) initial AAA diameter of 46.1 (11.3) mm were followed for a mean (SD) of 2.5 (3.1) years until an AAA event (n=454), death (n=176), loss to follow up (n=128), or completion of current follow up (n=322). Patients with diabetes who were prescribed metformin (adjusted HR 0.63, 95% CI 0.44-0.93), but not patients with diabetes who were not prescribed metformin (adjusted HR 1.15, 95% CI 0.83-1.59), had a lower incidence of AAA events compared with those without diabetes. Findings were similar in sensitivity analyses restricted to patients with an initial AAA diameter ≤50mm and patients with a minimum follow up of six months before an AAA event. These findings suggest that clinically important AAA events may be reduced in patients with diabetes who are prescribed metformin, but not those with diabetes receiving other treatments. A randomised controlled trial is needed to definitively test whether metformin reduces AAA related clinical events in patients with small AAAs who do not have diabetes.

Clinical utility of the global anti-phospholipid syndrome score for risk stratification: a pooled analysis.

Recently, our group conceived a risk score for clinical manifestations of APS (the global APS score, or GAPSS) that takes into account the combination of independent cardiovascular risk factors and the aPL positivity profile. These include hyperlipidaemia, arterial hypertension, aCL, anti-β2 glycoprotein-I, aPS-PT and the LA. A complementary version, the adjusted GAPSS (aGAPSS), which excludes aPS-PT, was also designed. The aim of our study was to systematically review the literature to assess the clinical utility of the GAPSS and aGAPSS for risk stratification of any APS clinical manifestation. We pooled data from available cohort studies, including a total of 10 studies, comprising 2273 patients, in which the GAPSS has been applied. A search strategy was developed a priori to identify an available cohort that reported findings which investigated the clinical utility of GAPSS or aGAPSS. Seven studies used the GAPSS in their cohort, whereas three studies used the aGAPSS. In brief, we found a statistically significant difference in the cumulative GAPSS and aGAPSS between patients that experienced an arterial and/or venous thrombotic event [cumulative mean GAPSS (s.d.) 10.6 (4.74) and aGAPSS 7.6 (3.95)], patients without any thrombotic manifestation [cumulative GAPSS 7.01 (5.46) and aGAPSS 4.9 (4.33)] and patients with pregnancy morbidity [cumulative GAPSS 8.79 (2.59) and aGAPSS 6.7 (2.8)]. The highest levels of GAPSS were found in patients that experienced arterial thrombosis [mean GAPSS 12.2 (5.2)] and patients that experienced any recurrences of clinical manifestations of APS [mean GAPSS 13.7 (3.1)]. GAPSS may represent a useful tool to assess the thrombosis or pregnancy loss risk in aPL-positive patients, switching from the concept of aPL as a sole diagnostic antibody to aPL as risk factors for clinical events.

Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in heart failure patients with reduced ejection fraction: Comparison with soluble AXL and BNP

BackgroundPrognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP. MethodsHF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation. ResultsHs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events. ConclusionsIn this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.

Retrospective evaluation of all recorded horse race starts in Switzerland during a four year period focusing on discipline‐specific risk factors for clinical events

Racetrack injuries are of welfare concern and the prevention of injuries is an important goal in many racing jurisdictions. Over the years this has led to more detailed recording of clinical events on racecourses. However, risk factor analyses of clinical events at race meetings have not been previously reported for Switzerland. To identify discipline-specific factors that influence the occurrence of clinical events during race meetings with the ultimate aim of improving the monitoring and safety of racetracks in Switzerland and optimising racehorse welfare. Retrospective study of horse race data collected by the Swiss horse racing association. All race starts (n = 17,670, including 6198 flat, 1257 obstacle and 10,215 trot race starts) recorded over a period of 4 years (2009-2012) were analysed in multivariable mixed effect logistic regression models including horse and racecourse related data. The models were designed to identify discipline-specific factors influencing the occurrence of clinical events on racecourses in Switzerland. Factors influencing the risk of clinical events during races were different for each discipline. The risk of a clinical event in trot racing was lower for racing on a Porphyre sand track than on grass tracks. Horses whose driver was also their trainer had an approximately 2-fold higher risk for clinical events. In obstacle races, longer distances (2401-3300 m and 3301-5400 m, respectively) had a protective effect compared with racing over shorter distances. In flat racing, 5 racecourses reported significantly fewer clinical events. In all 3 disciplines, finishing 8th place or later was associated with clinical events. Changes in management that aim to improve the safety and welfare of racehorses, such as racetrack adaptations, need to be individualised for each discipline.

Impact of fractional phosphate excretion on the relation of FGF23 with outcome in CKD patients.

BackgroundCardiovascular risk is increased in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) has emerged as an important, independent predictor of outcome in CKD patients. High FGF23 may, however, be a reflection of renal tissue resistance to its actions, reflected by low fractional excretion of phosphate (FePi). We evaluated the modifying effect of FePi on the association between FGF23 and outcome in patients with CKD stage 3–4.MethodsAn analysis was performed in a subset of 166 adult patients of two participating centers of the MASTERPLAN trial of whom urine samples at baseline were available to calculate FePi. Outcome was defined as a composite of death, renal failure (defined as need for renal replacement therapy or doubling of serum creatinine) and cardiovascular events (myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty or coronary artery bypass graft. Patients were categorized by FGF23 and FePi. A product term was added to Cox regression and RERIs were calculated.ResultsPatients had a median estimated glomerular filtration rate (eGFR) of 36 ml/min/1.73 m2 [interquartile range (IQR) 27–44], serum phosphate 1.04 mmol/l (IQR 0.92–1.20), FGF23 140 RU/ml (IQR 81–236) and FePi 0.32 (IQR 0.25–0.44). A total of 96 events occurred during 5 years of follow up. LnFGF23 was a significant, independent predictor for the composite outcome [hazard ratio (HR) 2.13, 95 % confidence interval (CI) 1.53–2.95]. FePi did not modify the relation between FGF23 and outcome in these patients with CKD.ConclusionsOur study shows that FGF23 itself, but not its renal tissue resistance as reflected by FePi, is an important risk factor for clinical events in subjects with CKD stage 3–4.

Abstract P318: Risk factors for 10-year coronary artery calcium progression in the Multi-Ethnic Study of Atherosclerosis

Coronary artery calcium (CAC) progression has previously been observed to predict coronary events above and beyond its association with baseline CAC. Prior studies show associations between CAC progression and risk factors, but were limited by short follow-up or restriction to individuals with advanced disease. We examined the relationship between risk factors for clinical events and the progression of CAC in MESA, a prospective cohort study. Participants were 6810 adults without CVD at recruitment in 2000-2002. Agatston scores for extent of calcification were assessed 1-4 times (mean 2.5) over a 10-year period with interim exams spaced at approximately 2-4 years. Mean follow-up time for those with at least 2 scans was 5.0 years. An innovative approach to mixed effects models jointly modeled the associations between risk factors and CAC both at baseline and with CAC progression rate. This method is less biased than controlling for baseline CAC, since the same risk factors are associated with both baseline and progression. Hence, time-varying factors can adjust progression rate, and data from participants with varying follow-up time and number of measurements_even those measured only at baseline_are incorporated. Mean CAC progression rate was 25 CAC units/year. All models were adjusted for age, sex, site, and race/ethnicity. Strong effects were observed for age, male sex, hypertension, and diabetes. Effects for statins likely reflect poor health status, rather than a causal effect of medication. Simultaneous adjustment for all risk factors produced similar results except the effect of statin use was not observed. See table for estimates and confidence intervals. In conclusion, CAC progression is associated with risk factors for clinical coronary events, confirming that processes involved in CAC progression mirror development of clinical atherosclerosis. The methods applied for the analysis of repeated continuous noninvasive measures of atherosclerosis extent can also be applied to evaluating novel risk factors.

Risk factors for clinical events at 1-year follow-up after drug-eluting stent implantation: results from the prospective multicenter German DES.DE registry

Drug-eluting stents (DES) have substantially reduced target vessel revascularization (TVR) after percutaneous coronary interventions. Risk factors for clinical events need to be redefined with this treatment option. In the prospective DES.DE registry, baseline clinical and angiographic characteristics as well as in-hospital and follow-up events were recorded for all enrolled patients. Between October 2005 and May 2009, 21,774 patients receiving DES were enrolled at 98 DES.DE sites. The composite of death, myocardial infarction (MI) and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and TVR were predefined as primary endpoints. At 1-year follow-up rates for overall death, MI, stroke, MACCE, TVR and definite stent thrombosis were 2.7, 3.1, 1.4, 7.1, 11.5 and 0.6 %, respectively. Aside from well-known risk factors like age, diabetes mellitus and triple-vessel disease, stratification in patients with or without MACCE revealed atrial fibrillation, non-ST-segment elevation myocardial infarction, renal failure, impaired ejection fraction and peripheral vascular disease as strong predictors of MACCE at 1 year. Data collected in the DES.DE registry, reflecting the clinical practice in Germany, revealed favorable clinical outcomes after DES implantation in a real world setting but also identifying several high-risk populations.

Time-averaged level of fibroblast growth factor-23 and clinical events in chronic kidney disease

A single time-point fibroblast growth factor-23 (FGF23) level is a strong, well-established risk factor for clinical events in chronic kidney disease (CKD). This study investigated whether repeated measurements of FGF23 after 2 years, allowing the calculation of time-averaged FGF23 and the rate of change in FGF23, provided a better prediction of clinical events in CKD than a single time-point value. A post-hoc analysis was performed in a subset of 439 adult patients with a median estimated glomerular filtration rate of 36 (interquartile range 28-48) mL/min per 1.73 m(2) of the prospective multicentre MASTERPLAN study, in which paired samples to measure FGF23 were available. The primary outcome was defined as a composite of myocardial infarction, stroke and cardiovascular mortality and secondary end points, which were overall mortality, congestive heart failure (CHF) and start of renal replacement therapy. Only events occurring after Month 24 were included in the analysis. Analysis of different FGF23 measures showed that a single time-point value and time-averaged FGF23 were positively associated with the primary end point, and also with overall mortality, start of renal replacement therapy and CHF. The adjusted hazard ratios of a single value of FGF23 and of time-averaged FGF23 for the composite end points were 1.71 (CI 1.20-2.43) and 1.91 (CI 1.29-2.82), respectively. Change in FGF23 was not associated with any outcome except for the initiation of renal replacement therapy. Our study confirms that FGF23 is an important cardiovascular risk factor. Two measurements of FGF23 have no added value over a single value to predict the cardiovascular outcome. This study demonstrates that, under routine clinical practice, the variability of FGF23 in 2 years' time is small. Concomitantly, this study showed no benefit of consecutive FGF23 testing for estimating the risk of a clinical event in an individual patient.

Abstract 132: Simulated Intraplaque Hemorrhage Stimulates Plaque Progression in an Animal Model

Intraplaque hemorrhage (IPH) is a feature of advanced plaques and a risk factor for clinical events. Several studies have demonstrated a link between carotid IPH and subsequent cerebrovascular events. Deposited RBCs contribute ingredients likely to promote plaque instability. In this study, a catheter-based approach was used for intramural injection of RBCs into atherosclerotic plaques. We explored the hypothesis that an animal model of atherosclerosis demonstrates increased macrophage infiltration and neovascularization in plaques injected with RBCs. Rabbits (n=4) were administered high cholesterol diet starting 2 weeks prior to endothelial denudation. Five weeks after denudation, a microinfusion catheter with a balloon-actuated microneedle delivered 70-100 μl of RBC and iodinated contrast mixture at multiple sites along the aorta. X-ray fluoroscopy and CT identified plaque injection sites and aortas were harvested for histopathology 5 weeks later. Only sections from plaque injection sites (n=14) were positive for Perl’s iron stain. In the 3 aortas analyzed with immunohistochemistry (1 excluded due to plaque variability), plaque macrophage area proportion was significantly higher in plaque injection sites vs. non-injected vessel sections. Increase in plaque neovessel density was not significant. In conclusion, intraplaque deposition of RBCs in the atherosclerotic rabbit aorta increases measures of plaque instability. Micrographs show Perl’s iron (a), macrophage (b), and neovessel (c) staining in an RBC-injected plaque. Scale bars represent 250 μm. Mean macrophage proportion and microvessel density and associated SEM are shown in bar graphs.

Frequencies of -308G/A (TNFA) and -509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil

Sickle cell anemia is an affection that causes chronic inflammation, with consequences for vaso-occlusion, oxidative stress and cytokine production. Genetic polymorphisms in markers involved in this process can modulate the inflammatory response, including polymorphisms -308G/A of TNFA (tumor necrosis factor alpha) and -509C/T of TGFB1 (transforming growth factor beta 1), reported to increase TNF-α and TGF-β1 production, respectively. Changes in the cytokine balance are important risk factors for clinical events; consequently, we examined the frequencies of these polymorphisms in 240 Brazilian sickle cell anemia patients from southeast Brazil. PCR-RFLP was used to detect these polymorphisms. The -509C/T (TGFB1) polymorphism was more frequent than -308G/A (TNFA), with allelic frequency of 0.3 for the mutant allele T (TGFB) agaist 0.1 for the mutant allele A (TNFA). These allelic frequencies are similar to those known from populations with ethnicity similar to the Brazilian population. Inheritance of these polymorphisms does not seem to be associated with that of the Hb S mutation; however, this information could be useful in analyses of specific clinical characteristics of sickle cell anemia.

Abstract 9592: Left Ventricular Hypertrophy Reduction and Clinical Events. A Meta-regression Analysis of 14 Studies in 12,809 Hypertensive Patients

Objective: Left ventricular hypertrophy (LVH) is an independent risk factor for clinical events (CE), and disappearance of LVH is associated with reduction of cardiovascular risk. However, whether a continuous relationship between reduction of LVH and risk of CE exists has not been investigated. Methods: Randomized clinical trials evaluating LVH at baseline and reporting quantitative LVH changes and CE (all-cause death, myocardial infarction (MI), stroke or new onset heart failure) were included. Meta-regression analysis was performed to test the relationship between changes in LVH and incidence of the composite outcome (all-cause death, MI, stroke or new onset heart failure) and between changes of LVH and occurrence of each component of the composite outcome. Analysis of potential confounder variables was also performed. Results: Fourteen trials including 12,809 participants and reporting 2,259 events were included. Follow-up ranged from 0.50 to 5 years, with mean 1.97±1.50 years. Mean age was 62±5 years and 52% of patients were women. The composite outcome was significantly reduced by active treatments (odds ratio [OR]: 0.851, 95% confidence intervals [CI]: 0.780 to 0.929, p&lt;0.001), as well stroke (OR: 0.756, CI:0.638 to 0.895, p&lt;0.001) whereas MI (OR:1.031, CI:0.846 to 1.255, p=0.763) and new onset heart failure (OR:0.994, CI:0.798 to 1.238, p=0.955) were not significantly reduced by treatments. LVH changes did not predict the reduction of the risk of the composite outcome (t=0.69, p=0.50)(Figure) or all-cause death (t=-1.27, p=0.26), stroke (t=0.15, p=0.89), MI (t=1.20, p=0.28) and new onset heart failure (t=0.69, p=0.50). No significant influence on the association of baseline patients and studies characteristics was found. Conclusions: A significant continuous relationship between LVH changes and CE could not be demonstrated in hypertensive patients, independently on the technique or drug used. patients.

Left ventricular hypertrophy reduction and clinical events. A meta-regression analysis of 14 studies in 12,809 hypertensive patients

BackgroundLeft ventricular hypertrophy (LVH) is an independent risk factor for clinical events (CE), and regression of LVH is associated with reduction of cardiovascular risk. However, whether a continuous relationship between reduction of LVH and risk of CE exists has not been investigated. MethodsRandomized clinical trials evaluating LVH at baseline and reporting quantitative LVH changes and CE, stroke or new onset heart failure) were included. Meta-regression analysis was performed to test the relationship between changes in LVH and incidence of the composite outcome (all-cause death, MI, stroke or new onset heart failure) and between changes of LVH and occurrence of each component of the composite outcome. Analysis of potential confounder variables was also performed. ResultsFourteen trials including 12,809 participants and reporting 2259 events were included. Follow-up ranged from 0.50 to 5years, with mean 1.97±1.50years. Mean age was 62±5years and 52% of patients were women. The composite outcome was significantly reduced by active treatments (OR: 0.851, IC: 0.780 to 0.929, p<0.001), as well stroke (OR: 0.756, IC: 0.638 to 0.895, p<0.001) whereas MI and new onset heart failure were not significantly reduced by treatments. LVH changes did not predict the reduction of CE. No significant influence on the association of baseline patients and studies characteristics was found. ConclusionsA significant continuous relationship between LVH changes and CE could not be demonstrated in hypertensive patients, independently on the technique or drug used. Ad hoc designed studies should further explore the relationship between LVH modification and outcomes in hypertensive patients.

Standardization of lupus anticoagulant. The Lupus Anticoagulant Sensitivity Index (LASI)

Results for lupus anticoagulant (LA) are expressed as ratio of patient-to-normal clotting times (LA-ratio) according to the equation LA-ratio = (Patient(Clotting time)/Normal(Clotting time)). However, numerical results vary according to the method used for testing, thus making difficult the between-method and between-laboratory comparison of results. The hypothesis that the standardization model currently employed for the international normalized ratio for patients on warfarin is valid also for LA standardization has been taken into consideration. The model calls for the determination of a LA-sensitivity index (LASI) for each commercial method for LA detection against a common standard method. The LASI is then used to convert the LA-ratio into a scale called standardized LA-ratio (SLA-ratio) according to the equation SLA-ratio = (LA-ratio)(LASI). The model proved effective in minimizing the between-method variability of results for LA detection. If implemented it could be a valuable tool to improve the comparability of results obtained in different laboratories, to quantify the LA potency and thus pave the way to the organization of collaborative clinical trials aimed at assessing whether the potency of LA is a risk factor for clinical events.

Albuminuria in Hematopoietic Cell Transplantation Patients: Prevalence, Clinical Associations, and Impact on Survival

Chronic kidney disease (CKD) is common after hematopoietic cell transplantation (HCT). We prospectively measured the urinary albumin:creatinine ratio (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after HCT. Albuminuria was defined as ACR (mg/g creatinine) > 30; proteinuria, as ACR >300. Cox and logistic regression analyses evaluated ACR as a risk factor for clinical events. The prevalence of albuminuria was 37% at baseline, 64% at day 100, and 50% at 1 year. Proteinuria occurred in 4% of patients at baseline, in 15% at day 100, and in 4% at 1 year. Characteristics associated with albuminuria include age, sex, donor type, hypertension, and sinusoidal obstruction syndrome (SOS). Albuminuria was associated with an increased risk of acute graft-versus-host disease (aGVHD) and bacteremia, but not acute kidney injury (AKI). Albuminuria at day 100 was associated with CKD at 1 year (odds ratio = 4.0; 95% confidence interval [CI] = 1.1 to 14.6). Nonrelapse mortality (NRM) risk was elevated (hazard ratio = 6.8; 95% CI = 1.1 to 41.5) in patients with overt proteinuria at day 100. Albuminuria occurs frequently after HCT and is correlated with aGVHD, bacteremia, hypertension, and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of NRM by 1 year after HCT.

Androgens Promote Calcification of Advanced Atherosclerotic Lesions

Background: Coronary calcification is an independent risk factor for clinical events. Men have more coronary calcification than women, however, it remains unclear whether this discrepancy reflects estrogen protection in women or androgen-aggravation in men.