Profile of cardiovascular risk factors and mortality in patients with symptomatic peripheral arterial disease

Introduction: The present study examines cardiovascular risk factor profiles and 24-month mortality in patients with symptomatic peripheral arterial disease. Design Study: Prospective observational study including 75 consecutive patients with PAD (67 ± 9.7 years of age; 52 men and 23 women) hospitalized for planned peripheral vascular reconstruction. Doppler echocardiograms were performed before surgery in 54 cases. Univariate analyses were performed using Student's t-test or Fisher's exact test. Survival analysis at 24-month follow-up was performed using the Cox regression model and Kaplan-Meier method including age and chronic use of aspirin as covariates. Survival curves were compared using the log-rank test. Results: Hypertension and smoking were the most frequent risk factors (52 cases and 51 cases, respectively), followed by diabetes (32 cases). Undertreated dyslipidemia was found in 26 cases. Fasting glycine levels (131 ± 69.1 mg/dl) were elevated in 29 cases. Myocardial hypertrophy was found in 18 out of 54 patients. Thirty-four patients had been treated with aspirin. Overall mortality over 24 months was 24% and was associated with age (HR: 0.064; CI95: 0.014-0.115; p=0.013) and lack of use of aspirin, as no deaths occurred among those using this drug (p<0.001). No association was found between cardiovascular death (11 cases) and the other risk factors. Conclusion: There is a high prevalence of uncontrolled (treated or untreated) cardiovascular risk factors in patients undergoing planned peripheral vascular reconstruction, and chronic use of aspirin is associated with reduced all-cause mortality in these patients.

Low serum potassium levels increase the infectious-caused mortality in peritoneal dialysis patients: a propensity-matched score study

Background and ObjectivesHypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.Design, Setting, Participants and MeasurementsThis is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.ResultsThere was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K < 3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).ConclusionsHypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up

Purpose To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors. Methods Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ2 tests, and regression analyses. Results In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased. Conclusion This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.

Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings

Objectives: We assessed mortality associated with immunologic and virologic patterns of response at 6 months of highly active antiretroviral therapy (HAART) in HIV-infected individuals from resource-limited countries in Africa and South America. Methods: Patients who initiated HAART between 1996 and 2007, aged 16 years or older, and had at least 1 measurement (HIV-1 RNA plasma viral load or CD4 cell count) at 6 months of therapy (3-9 month window) were included. Therapy response was categorized as complete, discordant (virologic only or immunologic only), and absent. Associations between 6-month response to therapy and all-cause mortality were assessed by Cox proportional hazards regression. Robust standard errors were calculated to account for intrasite correlation. Results: A total of 7160 patients, corresponding to 15,107 person-years, were analyzed. In multivariable analysis adjusted for age at HAART initiation, baseline clinical stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS-defining condition within the first 6 months of treatment, and discordant and absent responses were associated with increased risk of death. Conclusions: Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries. Our results support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings.

Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality

Context: IGF-I plays a central role in metabolism and growth regulation. High IGF-I levels are associated with increased cancer risk and low IGF-I levels with increased risk for cardiovascular disease. Objective: Our objective was to determine the relationship between circulating IGF-I levels and mortality in the general population using random-effects meta-analysis and dose-response metaregression. Data Sources: We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies. Study Selection: Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility. Data Extraction: Data extraction was performed by two investigators independently, using a standardized data extraction sheet. Data Synthesis: Twelve studies, with 14,906 participants, were included. Overall, risk of bias was limited. Mortality in subjects with low or high IGF-I levels was compared with mid-centile reference categories. All-cause mortality was increased in subjects with low as well as high IGF-I, with a hazard ratio (HR) of 1.27 (95% CI = 1.08–1.49) and HR of 1.18 (95% CI = 1.04–1.34), respectively. Dose-response metaregression showed a U-shaped relation of IGF-I and all-cause mortality (P = 0.003). The predicted HR for the increase in mortality comparing the 10th IGF-I with the 50th percentile was 1.56 (95% CI = 1.31–1.86); the predicted HR comparing the 90th with the 50th percentile was 1.29 (95% CI = 1.06–1.58). A U-shaped relationship was present for both cancer mortality and cardiovascular mortality. Conclusions: Both low and high IGF-I concentrations are associated with increased mortality in the general population.

Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism

Although the Pulmonary Embolism Severity Index (PESI) accurately identifies 35% of patients with acute pulmonary embolism (PE) as being low risk, some patients deemed high risk by the PESI on admission might be treated safely in the outpatient environment. This retrospective cohort study included a total of 304 consecutive patients with acute PE, classified at the time of hospital admission into PESI class III. The PESI was recalculated 48 h after admission (PESI(48)) and each patient reclassified into the corresponding risk category. The primary outcome of the study was all-cause mortality between day 2 and day 30 after PE diagnosis. 26 (8.5%) patients (95% CI 5.4-11.7%) died between day 2 and day 30 after PE diagnosis. Investigators reclassified 83 (27.3%) patients (95% CI 22.3-32.3%) as low risk (classes I and II) at 48 h. 30-day mortality in these patients was 1.2% (95% CI 0-3.5%) as opposed to 11.3% (95% CI 7.1-15.5%) in those who remained high risk. The net improvement in reclassification was estimated at 54% (p<0.001). In a cohort of intermediate-risk patients with acute PE, calculation of the PESI(48) allows identification of those patients at very low risk of dying during the first month of follow-up.

A 3-center comparison of 1-year mortality outcomes between transcatheter aortic valve implantation and surgical aortic valve replacement on the basis of propensity score matching among intermediate-risk surgical patients

This study sought to compare all-cause mortality in patients at intermediate surgical risk undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).

Culture, risk factors and mortality: can Switzerland add missing pieces to the European puzzle?

BACKGROUND: The aim was to compare cause-specific mortality, self-rated health (SRH) and risk factors in the French and German part of Switzerland and to discuss to what extent variations between these regions reflect differences between France and Germany. METHODS: Data were used from the general population of German and French Switzerland with 2.8 million individuals aged 45-74 years, contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were calculated from the Swiss National Cohort, a longitudinal census-based record linkage study. Results were contrasted with cross-sectional analyses of SRH and risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar all-cause mortality, there were substantial differences in cause-specific mortality between Swiss regions. Deaths from circulatory disease were more common in German Switzerland, while causes related to alcohol consumption were more prevalent in French Switzerland. Many but not all of the mortality differences between the two regions could be explained by variations in risk factors. Similar patterns were found between Germany and France. CONCLUSION: Characteristic mortality and behavioural differentials between the German- and the French-speaking parts of Switzerland could also be found between Germany and France. However, some of the international variations in mortality were not in line with the Swiss regional comparison nor with differences in risk factors. These could relate to peculiarities in assignment of cause of death. With its cultural diversity, Switzerland offers the opportunity to examine cultural determinants of mortality without bias due to different statistical systems or national health policies.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (mortality. We found little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort

BACKGROUND Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC). METHODS The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991-2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death. RESULTS SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4%-17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75-84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between -1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12%-28%) and prostate (16% less, 95% confidence interval: 7%-23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy. CONCLUSIONS Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.

Alcohol-selling outlets and mortality in Switzerland--the Swiss National Cohort

AIM To examine the association of alcohol-related mortality and other causes of death with neighbourhood density of alcohol-selling outlets for on-site consumption. DESIGN, SETTING AND PARTICIPANTS Longitudinal study of the adult Swiss population (n = 4 376 873) based on census records linked to mortality data from 2001 to 2008. MEASUREMENTS Sex-specific hazard ratios (HR) for death and 95% confidence intervals (95%CI) were calculated using Cox models adjusting for age, educational level, occupational attainment, marital status and other potential confounders. The density of alcohol-selling outlets within 1000 m of the residence was calculated using geocodes of outlets and residences. FINDINGS Compared with >17 outlets within 1000 m the HR for alcohol-related mortality in men was 0.95 (95%CI: 0.89-1.02) for 8-17 outlets, 0.84 (95%CI: 0.77-0.90) for 3-7 outlets, 0.76 (95%CI: 0.68-0.83) for 1-2 outlets and 0.60 (95%CI: 0.51-0.72) for 0 outlets. The gradient in women was somewhat steeper, with a HR comparing 0 with >17 outlets of 0.39 (95%CI: 0.26-0.60). Mortality from mental and behavioural causes and lung cancer were also associated with density of alcohol-selling outlets: HRs comparing 0 outlets with >17 outlets were 0.64 (95%CI: 0.52-0.79) and 0.79 (95%CI: 0.72-0.88), respectively, in men and 0.46 (95%CI: 0.27-0.78) and 0.63 (95%CI: 0.52-0.77), respectively, in women. There were weak associations in the same direction with all-cause mortality in men but not in women. CONCLUSIONS In Switzerland, alcohol-related mortality is associated with the density of outlets around the place of residence. Community-level interventions to reduce alcohol outlet density may usefully complement existing interventions.

Influence of Geographical Origin and Ethnicity on Mortality in Patients on Antiretroviral Therapy in Canada, Europe, and the United States

Our objective was to assess differences in all-cause mortality, as well as AIDS and non-AIDS death rates, among patients started on antiretroviral therapy (ART) according to their geographical origin and ethnicity/race in Europe, Canada, and the United States. METHODS: This was a collaboration of 19 cohort studies of human immunodeficiency virus-positive subjects who have initiated ART (ART Cohort Collaboration) between 1998 and 2009. Adjusted mortality hazard ratios (AHRs) were estimated using Cox regression. A competing risk framework was used to estimate adjusted subdistribution hazard ratios for AIDS and non-AIDS mortality. RESULTS: Of 46 648 European patients, 16.3% were from sub-Saharan Africa (SSA), 5.1% Caribbean and Latin America, 1.6% North Africa and Middle East, and 1.7% Asia/West; of 1371 patients from Canada, 14.9% were First Nations and 22.4% migrants, and of 7742 patients from North America, 55.5% were African American and 6.6% Hispanic. Migrants from SSA (AHR, 0.79; 95% confidence interval [CI], .68-.92) and Asia/West (AHR, 0.62; 95% CI, .41-.92) had lower mortality than Europeans; these differences appeared mainly attributable to lower non-AIDS mortality. Compared with white Canadians, mortality in Canadian First Nations people (AHR, 1.48; 95% CI, .96-2.29) was higher, both for AIDS and non-AIDS mortality rates. Among US patients, when compared with whites, African Americans had higher AIDS and non-AIDS mortality, and hazard ratios for all-cause mortality increased with time on ART. CONCLUSIONS: The lower mortality observed in migrants suggests "healthy migrant" effects, whereas the higher mortality in First Nations people and African Americans in North America suggests social inequality gaps. KEYWORDS: HIV infection, antiretroviral therapy, ethnic minorities, migrants Comment in Addressing disparities in HIV mortality: antiretroviral therapy is necessary but not sufficient. [Clin Infect Dis. 2013]

Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).

AIMS The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known. METHODS AND RESULTS We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ε22 or ε23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43-0.71; ε24 or ε34 or ε44: OR 1.10, 95% CI 0.89-1.37 compared with ε33] and moderately with cardiovascular mortality [ε22 or ε23: hazard ratio (HR) 0.71, 95% CI 0.51-0.99; ε33: HR 0.92, 95% CI 0.75-1.14 compared with ε24 or ε34 or ε44]. HRs for total mortality were 1.39 (95% CI 0.39-0.1.67), 2.29 (95% CI 1.85-2.83), 2.07 (95% CI 1.64-2.62), and 2.95 (95% CI 2.10-4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ε4 allele, respectively, compared with never-smokers. Carrying ε4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04-2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ε4 was seen regarding non-cardiovascular mortality. Smokers with ε4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2. CONCLUSION In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ε4 allele in current smokers increases cardiovascular and all-cause mortality.

Cystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

AIMS Cystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with mortality. The present analysis prospectively evaluated the associations of cystatin C with all-cause and cardiovascular (CV) mortality in a well-characterized cohort of persons undergoing angiography, but without overt renal insufficiency. METHODS Cystatin C was available in 2998 persons (mean age: 62.7 ± 10.5 years; 30.3% women). Of those 2346 suffered from coronary artery disease (CAD) and 652 (controls) did not. Creatinine (mean ± SD: 83.1 ± 47.8 vs. 74.1 ± 24.7 μmol/L, p = 0.036) but not Cystatin C (mean ± SD: 1.02 ± 0.44 vs. 0.92 ± 0.26 mg/L, p = 0.065) was significantly higher in patients with CAD. After a median follow-up of 9.9 years, in total 898 (30%) deaths occurred, 554 (18.5%) due to CV disease and 326 (10.9%) due to non-CV causes. Multivariable-adjusted Cox analysis (adjusting for eGFR and established cardiovascular risk factors, lipid lowering therapy, angiographic coronary artery disease, and C-reactive protein) revealed that patients in the highest cystatin C quartile were at an increased risk for all-cause (hazard ratio (HR) 1.93, 95% CI 1.50-2.48) and CV mortality (HR 2.05 95% CI 1.48-2.84) compared to those in the lowest quartile. The addition of cystatin C to a model consisting of established cardiovascular risk factors increased the area under the receiver-operating characteristic curve for CV and all-cause mortality, but the difference was statistically not significant. However, reclassification analysis revealed significant improvement by addition of cystatin C for CV and all-cause mortality (p < 0.001), respectively. CONCLUSION The concentration of cystatin C is strongly associated with long-term all-cause and cardiovascular mortality in patients referred to coronary angiography, irrespective of creatinine-based renal function.

The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis-related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis-related event or death) in one patient was determined with the adjusted (event-free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2-11.1) years. Fifty-nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5-year survival and event-free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all-cause mortality (HR 0.15, 95% CI 0.05-0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07-0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937-1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54-101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38-71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271-407), 18 (95% CI 16-24) and 13 (95% CI 11-17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.