Good outcomes of liver transplantation for hepatitis C at a low volume centre

Background and aims. Concerns exist about outcomes of liver transplantation (LT) from low volume centres, especially for hepatitis C (HCV) patients. The aim of the study was to assess patient outcomes as well as their predictors post LT for HCV in a small volume Australian unit (< 25 LTs/year), comparing these with the average outcomes obtained from national and international transplant registries. Patients transplanted for HCV at the South Australian Liver Transplant Unit between 1992 and 2012 were studied. Outcomes assessed were patient and graft survival at 1,3, and 5 years. Factors independently associated with the outcomes were assessed using Cox regression model.Results. 1, 3, and 5-year patient survival for HCV patients was 95.2, 82.9, and 78.2%, graft survival were 93.7, 80.1, and 75.5% respectively. The total follow-up time observed was 299.9 years amongst 61 patients in which there were 16 deaths. The expected number of deaths was 40.4 and the standardized mortality ratio 0.40 (95% CI = 0.24, 0.65). These results compared favourably to those obtained from the SRTR registry. Variables independently associated with lower patient survival: donor age (HR = 1.06, 95% CI 1.02 - 1.11; P = 0.003), and post LT cytomegalovirus (CMV) disease requiring treatment (HR = 4.03, 95% CI 1.48 - 10.92;P = 0.06).Conclusion. In conclusion, high rates of patient and graft survival for HCV liver transplantation can be obtained in a small volume unit. Young donor age and lack of CMV disease post-transplant were associated with better outcomes. Institutional factors may be influential determinants of outcomes.     

The stress echo prognostic gender gap.

AIMS: To investigate whether myocardial ischaemia elicitable during pharmacological stress echocardiography portends different prognosis in men and women.METHODS AND RESULTS: The study group was made by 1733 patients (941 men, 792 women) who underwent dipyridamole (n=1008) or dobutamine (n=725) stress echo for evaluation of known or suspected coronary artery disease. An ischaemic response was found in 460 patients (308 men, 152 women). Considering the whole ischaemic population, women were older (P<0.0001) and more likely to have hypertension (P=0.02) and hypercholesterolaemia (P=0.04) than men. No difference in age and risk factors was evidenced between the two sexes in the subset of 203 patients with ischaemia and suspected coronary artery disease. During follow-up (25 +/- 24 months for the ischaemic and 37 +/- 25 months for the non-ischaemic sample), there were 113 cardiac events (45 deaths and 68 infarctions) and 232 revascularizations. Revascularization rate in ischaemic population was similar in both sexes (P=0.36). Multivariate predictors of cardiac events in the whole ischaemic group were resting WMSI (HR=2.7, 95% CI 1.3--3.3;P=0.0050), female gender (HR=2.2, 95% CI 1.2--3.7;P=0.0062), age > or = l65 years (HR=1.9, 95% CI=1.0--3.6;P=0.0427), and Delta WMSI (HR=2.1, 95% CI=1.0--3.7;P=0.0447). Female gender (HR=2.7, 95% CI 1.1--6.3;P=0.0233) was the only independent prognostic predictor in patients with ischaemia and suspected coronary artery disease. Five-year infarction-free survival was 82% in men and 71% in women in the whole ischaemic population (P=0.0041) as well as in the ischaemic group with suspected coronary artery disease (CAD) (P=0.0175). In the non-ischaemic sample resting WMSI (HR=4.8), history of myocardial infarction (HR=2.5), and hypercholesterolaemia (HR=1.8) were independent predictors of outcome at multivariate analysis, whilst the gender had no prognostic importance.Conclusions: Our results show that female gender is an independent predictor of cardiac events in patients with myocardial ischaemia induced by pharmacological stress echocardiography.     

Increased hepatocellular carcinoma recurrence in women compared to men with high alpha fetoprotein at liver transplant

Introduction. Men have higher risk for hepatocellular carcinoma (HCC) than women. Pre liver transplant (LT) alpha fetoprotein (AFP) levels strongly predict post LT HCC recurrence. Though women with HCC have higher AFP, the contribution of AFP level by gender to post LT HCC recurrence is unknown.Material and methods. In this UNOS-based, retrospective cohort study we investigate sex differences in HCC recurrence among LT recipients with MELD exception between 2006-2010. Covariates include race, disease etiology, co-morbidities, AFP at listing and LT, tumor burden, loco-regional therapy, and donor risk index. HCC recurrence was assessed by competing risks regression.Results. Of the eligible cohort (n = 5,002) included 3,872 men and 1,130 women. HCC recurred in 258 men (7%) and 66 women (6%). Median listing AFP was higher in women than men (14 vs. 11 ng/dL, p < 0.001). While no sex difference in overall HCC recurrence was detected (HR 0.9, 95% CI 0.7-1.2, p = 0.38), there was a strong interaction between gender and AFP on recurrence risk (p = 0.02). HCC recurrence was nearly three times higher in women (HR 4.2, 95% CI 2.2-8.2, p < 0.001) than men (HR 1.5, 95% CI 1.1-2.1, p = 0.02) with AFP at LT between 101-500 ng/dL.Conclusion. This study reveals novel sex differences in post LT HCC recurrence, which was nearly three times higher in women than men with high AFP at LT. Pre-LT AFP levels appear to carry a different prognosis in women than men, and a subset of female LT recipients may benefit from more intensive HCC surveillance after LT.     

Effect of female gender on the outcome of coronary artery bypass surgery for left main coronary artery disease.

OBJECTIVE: Early mortality after coronary artery bypass grafting is generally higher in women than in men. This study analyzes the effect of female gender on early mortality of coronary artery bypass grafting particularly for left main coronary artery disease. METHODS: Study population consisted of 144 consecutive patients (33 women, 111 men) undergoing coronary artery bypass grafting for left main coronary artery disease. Mean follow-up was 25.1 +/- 14.0 months. Data were collected retrospectively and presented as mean +/- standard deviation. Survival analysis was done using Kaplan-Meier actuarial curve method with the log rank univariate test, followed by Cox's proportional rate multivariate model. RESULTS: Overall mortality was 7% in the patient population. Cox regression analysis revealed that the independent predictors of increased total mortality were female gender (HR 8.34, 95% CI 1.79 - 38.76, p=0.007), advanced age (HR 1.12, 95% CI 1.02-1.23, p=0.014), degree of left main coronary artery stenosis (HR 1.068, 95%CI 1.005-1.135, p=0.03), and left ventricular ejection fraction (HR 0.93, 95% CI 0.87-0.99, p=0.03). Female gender was found to be the only independent predictor of increased early mortality (HR 13.18, 95%CI 1.444-120.343, p=0.02). After discharge from the hospital, female gender was no more a predictor of increased mortality. CONCLUSION: According to these data, we may assume that female gender is related with increased mortality in coronary artery surgery for left main disease in the pre-discharge period however after discharge from hospital, long-term benefit of female survivors of coronary artery bypass grafting operated on for left main coronary artery disease might be as good as in men.     

Association of endothelial shear stress with plaque thickness in a real three-dimensional left main coronary artery bifurcation model

Women with advanced heart failure have better prognosis than men (men versus women HR 2.5, 95% CI 1.1-5.5, p=0.03). Although interaction ischemic heart disease-gender was not significant, HR was 1.6 (95% CI 0.5-5.6, p=0.43) for patients with coronary artery disease and 3.4 (95% CI 1.1-10.5, p=0.03) for patients without.     

Spontaneous bacterial peritonitis prevalence in pretransplant patients and its effect on survival and graft loss post-transplant

AIM To investigate the incidence of spontaneous bacterial peritonitis(SBP) in pre-transplant patients and its effect on post transplant mortality and graft failure. METHODS We conducted a retrospective cohort study of patient records from the organ procurement and transplant network data set. Patients were identified by the presence of SBP pre-transplant. Univariate post-transplant survival models were constructed using the Kaplan-Meier technique and multivariate models were constructed using the Cox proportional hazards model. Variables that affected post-transplant graft survival were identified in the SBP population. RESULTS Forty-seven thousand eight hundred and eighty patient records were included in the analysis for both groups, and 1966(4.11%) patients were identified in the data set as having pre-transplant SBP. Patients that had pre-transplant SBP had higher rates of graft loss from recurrent hepatitis C virus(HCV)(3.6% vs 2.0%, P 0.0001), infections leading to graft loss(1.9% vs 1.3%, P = 0.02), primary non-function(4.3% vs 3.0%, P 0.0001) and chronic rejection(1.1% vs 0.7%, P = 0.04). Kaplan-Meier survival analysis showed a statistically significant difference in all-cause survival in patients with a history of SBP vs those without(P 0.0001). Pretransplant history of SBP was independently predictiveof mortality due to recurrent HCV(HR = 1.11, 95%CI: 1.02-1.21, P 0.017) after liver transplantation.CONCLUSION HCV patients prior to the advent of directing acting anti-viral agents had a higher incidence of pre-transplant SBP than other patients on the liver transplant wait list. SBP history pre-transplant resulted in a higher rate of graft loss due to recurrent HCV infection and chronic rejection.     

The impact of gender and income on survival and retention in a South African antiretroviral therapy programme

Objectives Despite the rapid expansion of antiretroviral therapy (ART) services in Africa, there are few data on whether outcomes differ for women and men and what factors may drive such variation. We investigated the association of gender and income with survival and retention in a South African ART programme. Methods A total of 2196 treatment‐naïve adults were followed for 1 year on ART. Proportional hazards regression was used to explore associations between baseline characteristics and survival and loss‐to‐follow‐up (LTFU). Results Patients were predominantly female (67%). Men presented at an older age and with more advanced HIV disease, and during early ART the crude death rate was higher among men than women (22.8 vs 12.5/100 person‐years; P = 0.002). However in multivariate analysis, gender was not significantly associated with survival after adjusting for baseline clinical and immunovirological status (HR = 1.46, 95% CI = 0.96–2.22; P = 0.076). In late ART (4–12 months), there was no gender difference in mortality rates (3.5 vs 3.8/100 person‐years; P = 0.817). In multivariate analysis, survival was strongly associated with age (HR = 1.05, 95% CI = 1.02–1.09; P < 0.001), CD4 count >150 vs <50 cells/μl (HR = 0.35, 95% CI = 0.14–0.87; P = 0.023) and any monthly income vs none (HR = 0.47, 95% CI = 0.25–0.88; P = 0.018). Having some monthly income was protective against LTFU at 1 year on ART (adjusted HR = 0.56, 95% CI = 0.39–0.82; P = 0.002). Conclusion Men’s high early mortality on ART appears due largely to their presentation with more advanced HIV disease. Efforts are needed to enrol men into care earlier in HIV disease and to reduce socio‐economic inequalities in ART programme outcomes.     

A prospective study of HIV disease progression in female and male drug users

OBJECTIVE: To compare HIV disease progression and mortality in a cohort of female and male drug users. DESIGN: A prospective cohort study of 222 HIV-seropositive women and 302 HIV-seropositive men who attended a hospital-affiliated methadone maintenance program with on-site primary care. METHODS: Regression slopes of CD4+ cell decline were compared using the two sample t-test, and the distribution of AIDS-defining illnesses evaluated by Mantel-Haenszel chi2 test. Time to AIDS-defining clinical conditions and death were compared using the Kaplan-Meier log-rank test. Multivariate estimates of progression to clinical AIDS or death, for all participants, stratified by sex, were derived from Cox proportional hazards models. RESULTS: Ninety-five persons (43 women and 52 men) developed AIDS-defining conditions. Analyses of the rates of CD4+ cell decline, the distribution of first AIDS-defining illnesses, and the time to clinical AIDS did not differ by sex. In the multivariate model, sex was not associated with an AIDS outcome, whereas crack-cocaine use [hazards ratio (HR), 1.815; 95% confidence interval (CI), 1.151-2.863], CD4+ cell count (100 x 10(6)/l; HR, 0.589; 95% CI, 0.511-0.679), and two or more HIV-related symptoms (HR, 1.702; 95% CI, 1.125-2.576) were associated. Mortality rates (8.71 per 100 person-years in women and 9.85 per 100 person-years in men) were similar, using univariate or multivariate methods. CONCLUSIONS: There was little difference in clinical outcomes or mortality between HIV-seropositive female and male drug users with access to primary care. However, crack-cocaine use was independently associated with progression to clinical AIDS.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

High HIV, hepatitis C and sexual risks among drug-using men who have sex with men in northern Thailand

BACKGROUND: Men who have sex with men (MSM) and who use drugs have shown high HIV risks in Europe, and the Americas. We investigated MSM-drug user demographics, HIV sexual and drug use risks and behaviors in Chiang Mai, northern Thailand to identify prevention targets. METHODS: A total of 2005 males aged 13 years and older were enrolled during inpatient drug treatment from 1999-2000 and assessed for HIV, hepatitis C virus (HCV), syphilis, and for demographics and risks by questionnaire. Data were analyzed using chi and multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 2005 males in treatment, 1752 (87.4%) had ever had sex, and 66 of 1752 (3.8%) reported ever having sex with another man; mostly Katoey (transgendered male) partners. MSM had higher HIV rates (OR, 2.32; 95% CI, 1.36-3.96) and were younger (P = 0.002); more likely to be Thai (P < 0.0001); better educated (P < 0.0001); had more lifetime sex partners (P < 0.0001), more female partners (P = 0.002), more female paid partners (P < 0.0001), and been paid for sex (P < 0.0001). MSM were more likely to have ever injected (P < 0.0001), sold drugs, been in prison, injected in prison, used heroin, and to have HCV (OR, 2.59; 95% CI, 1.55-4.34). CONCLUSIONS: Northern Thai MSM-drug users are at high HIV and HCV risk. In addition to sex risks with men, they have more sex with women and sex workers than other men, which fits Thai MSM patterns but not Western ones. Prevention must take into account their high rates of substance use and multiple partner types.     

Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis

Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. CONCLUSION: LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score.     

ST-elevation myocardial infarction in a real world population - An observational retrospective study with a sex perspective

BackgroundMortality after myocardial infarction is higher in women than in men. Data on the association between sex and mortality are conflicting and inconclusive. We evaluated whether there is a sex difference in survival and if sex is associated with the outcome in patients with ST-elevation myocardial infarction (STEMI).MethodsWe analyzed 3671 STEMI patients. Long-term and 30-day mortality in men and women were compared.ResultsUnadjusted mortality at day 30 was higher in women [221 (8.7%) men died compared to 147 (13.1%) women; p < 0.0001]. After multivariate adjustments, this became insignificant (OR 1.65; 95% CI; 0.81 to 1.40). The long-term, unadjusted mortality was also higher in women [674 (26.3%) men died compared to 382 (34%) women; p < 0.0001]. After multivariable adjustments, female sex (adjusted HR 0.81; 95% CI 0.71 to 0.93; p = 0.002), bleeding (adjusted HR 1.79; 95% CI 1.52 to 2.10; p < 0.0001), renal dysfunction adjusted HR (1.60; 95% CI 1.40 to 1.84; p < 0.0001), hyperlipidemia (adjusted HR 1.61; 95% CI 1.40 to 1.85; p < 0.0001), arterial hypertension (adjusted HR 1.17; 95% CI 1.03 to 1.33; p = 0.015), diabetes (adjusted HR 1.55; 95% CI 1.35 to 1.78; p < 0.0001), age (adjusted HR 1.05; 95% CI 1.04 to 1.06; p < 0.0001), anemia on admission (adjusted HR 1.38; 95% CI 1.23 to 1.58; p < 0.0001), and heart failure (adjusted HR 2.40; 95% CI 2.09 to 2.75; p < 0.0001) predicted long-term mortality.ConclusionFemale sex was associated with a lower risk of dying in the long term. However, risk factors, age, and comorbidities associated with female patients affected the worse outcome.     

Sex Differences in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant.In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.     

Effects of losartan in women with hypertension and left ventricular hypertrophy: results from the Losartan Intervention for Endpoint Reduction in Hypertension Study

Hypertension is a risk factor for cardiovascular disease and outcomes in women. These posthoc analyses from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study evaluated losartan- versus atenolol-based therapy on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and other end points in 4963 women. Fewer events occurred in women versus men. Women in the losartan group had significant reductions in the primary end point (215 [18.2 per 1000 patient-years] versus 261 [22.5 per 1000 patient-years]; hazard ratio [HR]: 0.82 [95% CI: 0.68 to 0.98]; P=0.031), stroke (109 versus 154; HR: 0.71 [95% CI: 0.55 to 0.90]; P=0.005), total mortality (HR: 0.77 [95% CI: 0.63 to 0.95]; P=0.014), and new-onset diabetes (HR: 0.75 [95% CI: 0.59 to 0.94]; P=0.015) versus the atenolol group, with no between-treatment difference for myocardial infarction (HR: 1.02 [95% CI: 0.74 to 1.39]; P=0.925), cardiovascular mortality (HR: 0.86 [95% CI: 0.64 to 1.14]; P=0.282), or hospitalization for heart failure (HR: 0.94 [95% CI: 0.68 to 1.28]; P=0.677). More women in the losartan group required hospitalization for angina (HR: 1.70 [95% CI: 1.16 to 2.51]; P=0.007). Risk reductions for the primary composite end point, stroke, total mortality, and new-onset diabetes were significantly greater with losartan- versus atenolol-based treatment in women with hypertension and left ventricular hypertrophy in the LIFE study. The risk reductions for losartan, along with the tests for the interaction of treatment and gender, indicated that the treatment effect was consistent in men and women for all of the end points tested, with the exception of hospitalization for angina.     

Stem cell transplantation for chronic myeloid leukemia in children

Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome-positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P =.05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P =.001; LFS HR, 1.8; 95% CI, 1.2-2.6; P =.003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P =.006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P =.003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.     

Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry

As arterial and venous thrombosis share common risk factors, a link between arterial and venous thrombosis has been suggested recently. Therefore, we aimed to investigate the impact of established cardiovascular risk factors on the risk of recurrent venous thromboembolism (VTE). With a cross-sectional study design, we analyzed the data of 1006 patients (582 F, 424 M) consecutively treated in our outpatient department for VTE (i.e. lower extremity deep vein thrombosis and/or pulmonary embolism) and registered in the MAISTHRO (MAin-ISar-THROmbosis) database. Of the total cohort, 324 (32.2%) patients suffered a recurrent VTE. Compared with the patients with a single thromboembolic event, patients with recurrent VTE were more frequently male (39.4 vs. 27.0%, P < 0.001). In univariate analysis, the relative risk of recurrent VTE was 1.9 [95% confidence interval (CI) 1.53-2.39] for male sex and 1.6 (1.25-1.95) for age over 50 years (PAOD). After adjustments for age, sex, thrombophilia and other common VTE risk factors, male sex [hazard ratio (HR) = 1.7 (1.38-21.9)] and arterial hypertension [HR = 1.4 (1.05-1.78)] were independent risk factors of recurrent VTE. The higher risk in men than in women persisted even after the exclusion of women with transient hormonal risk factors [HR = 1.57 (1.19-2.07)]. In contrast, no association between the presence of diabetes, obesity, hypercholesterolemia or smoking and the risk of VTE recurrence was observed. Male sex and arterial hypertension are independently associated with an increased risk of recurrent VTE after termination of anticoagulant therapy for the first VTE event.     

Fasting insulin is a stronger cardiovascular risk factor in women than in men

Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than in men. It is not known whether there is also a sex difference in the association between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively recorded after the baseline survey. Cox-regression models were used to investigate the association of fasting insulin with subsequent development of MACE. Fasting insulin was 54 [38-77]pmol/l in women (age 48+/-12yrs) and 57 [40-88] pmol/l in men (age 49+/-13yrs). During follow-up for 7.5 [6.9-7.8]yrs, 98 cardiovascular events were recorded in 3626 women and 242 events in 3290 men. There was a significant (P<0.001) interaction between sex and fasting insulin for MACE, with the strongest association in women. In women, there was a logarithmic association for insulin with MACE, independent of age, alcohol consumption, and smoking (HR=1.50 [95% CI 1.17-1.91] per doubling of insulin, P=0.001). In men, for a similar multivariate model, there was a logarithmic association (HR=1.13 [95% CI [0.97-1.32] per doubling of insulin, P=0.1). Further adjustment for components of the insulin resistance syndrome weakened the association more in men than in women. With HOMA instead of insulin, results were essentially similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin resistance in non-diabetic subjects is associated with an increased risk for cardiovascular disease, which is more pronounced in women than in men.     

Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy

Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation. We evaluated the effectiveness, tolerability, and outcome of a low accelerating dose regimen (LADR) of antiviral therapy in the treatment of patients with advanced HCV. One hundred twenty-four patients (male/female ratio 81:43; age range 37-71 years; 70% genotype 1) were treated with LADR. Sixty-three percent had clinical complications of cirrhosis (ascites, spontaneous bacterial peritonitis, varices, variceal hemorrhage, encephalopathy). The mean Child-Turcotte-Pugh (CTP) score was 7.4 +/- 2.3, and the mean MELD score was 11.0 +/- 3.7. Fifty-six patients were CTP class A, 45 were class B, and 23 were class C. Forty-six percent were HCV RNA-negative at end of treatment, and 24% were HCV RNA-negative at last follow-up. Sustained virological response (SVR) was 13% in patients infected with genotype 1 HCV and 50% in patients infected with non-1 genotypes (P < .0001). Non-1 genotype, CTP class A (genotype 1 only), and ability to tolerate full dose and duration of treatment (P < .0001) were predictors of SVR. Twelve of 15 patients who were HCV RNA-negative before transplantation remained HCV RNA-negative 6 months or more after transplantation. In conclusion, in a sizeable proportion of patients with advanced HCV, LADR may render blood free of HCV RNA, stabilize clinical course, and prevent posttransplantation recurrence.     

Sex and racial/ethnic disparities in outcomes after acute myocardial infarction: a cohort study among members of a large integrated health care delivery system in northern California

BACKGROUND: Previous studies have documented sex and racial/ethnic disparities in outcomes after acute myocardial infarction (AMI), but the explanation of these disparities remains limited. In a setting that controls for access to medical care, we evaluated whether sex and racial/ethnic disparities in prognosis after AMI persist after consideration of socioeconomic background, personal medical history, and medical management. METHODS: We conducted a prospective cohort study of the members (20,263 men and 10,061 women) of an integrated health care delivery system in northern California who had experienced an AMI between January 1, 1995, and December 31, 2002, and were followed up for a median of 3.5 years (maximum, 8 years). Main outcome measures included AMI recurrence and all-cause mortality. RESULTS: In age-adjusted analyses relative to white men, black men (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.26-1.65), black women (HR, 1.47; 95% CI, 1.26-1.72), and Asian women (HR, 1.37; 95% CI, 1.13-1.65) were at increased risk of AMI recurrence. However, multivariate adjustment for sociodemographic background, comorbidities, medication use, angiography, and revascularization procedures effectively removed the excess risk of AMI recurrence in these 3 groups. Similarly, the increased age-adjusted risk of all-cause mortality seen in black men (HR, 1.55; 95% CI, 1.37-1.75) and black women (HR, 1.45; 95% CI, 1.27-1.66) was greatly attenuated in black men and reversed in black women after full multivariate adjustment. CONCLUSION: In a population with equal access to medical care, comprehensive consideration of social, personal, and medical factors could explain sex and racial/ethnic disparities in prognosis after AMI.