Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

ObjectivesWe sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.BackgroundEpidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.MethodsA systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.ResultsA total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).ConclusionsThere is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking

Alcohol's Collateral Damage: Childhood Exposure to Problem Drinkers and Subsequent Adult Mortality Risk

The importance of childhood circumstances, broadly defined, for shaping adult health and longevity is well-established. But the significance of one of the most prevalent childhood adversities—exposure to problem drinkers—has been understudied from a sociological perspective and remains poorly understood. We address this gap by drawing on cumulative inequality theory, using data from the 1988–2011 National Health Interview Survey-Linked Mortality Files, and estimating Cox proportional hazards models to examine the relationship between exposure to problem drinkers in childhood and adult mortality risk. Childhood exposure to problem drinkers is common (nearly 1 in 5 individuals were exposed) and elevates adult overall and cause-specific mortality risk. Compared to individuals who had not lived with a problem drinker during childhood, those who had done so suffered 17 percent higher risk of death (p<.001) over the follow-up period, net of age, sex, and race/ethnicity. We find compelling evidence that the duration, source, and intensity of exposure to problem drinkers in childhood contributes to inequality in adult mortality risk. Favorable socioeconomic status in adulthood does not ameliorate the consequences of childhood exposure to problem drinkers. The primary intervening mechanisms are risky behaviors, including adult drinking and smoking. The findings—which reveal that the influence of problem drinking is far-reaching and long-term—should inform policies to improve childhood circumstances, reduce detrimental effects of problem drinking, and increase life expectancy

Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights From Large Randomized Statin Trials

ObjectivesWe sought to assess the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering and rates of elevated liver enzymes, rhabdomyolysis, and cancer.BackgroundAlthough it is often assumed that statin-associated adverse events are proportional to LDL-C reduction, that assumption has not been validated.MethodsAdverse events reported in large prospective randomized statin trials were evaluated. The relationship between LDL-C reduction and rates of elevated liver enzymes, rhabdomyolysis, and cancer per 100,000 person-years was assessed using weighted univariate regression.ResultsIn 23 statin treatment arms with 309,506 person-years of follow-up, there was no significant relationship between percent LDL-C lowering and rates of elevated liver enzymes (R2<0.001, p = 0.91) or rhabdomyolysis (R2= 0.05, p = 0.16). Similar results were obtained when absolute LDL-C reduction or achieved LDL-C levels were considered. In contrast, for any 10% LDL-C reduction, rates of elevated liver enzymes increased significantly with higher statin doses. Additional analyses demonstrated a significant inverse association between cancer incidence and achieved LDL-C levels (R2= 0.43, p = 0.009), whereas no such association was demonstrated with percent LDL-C reduction (R2= 0.09, p = 0.92) or absolute LDL-C reduction (R2= 0.05, p = 0.23).ConclusionsRisk of statin-associated elevated liver enzymes or rhabdomyolysis is not related to the magnitude of LDL-C lowering. However, the risk of cancer is significantly associated with lower achieved LDL-C levels. These findings suggest that drug- and dose-specific effects are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer

Liver and brain abscess caused by Aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Introduction Aggregatibacter paraphrophilus (former name Haemophilus paraphrophilus) is a normal commensal of the oral flora. It is a rare cause of hepatobiliary or intracerebral abscesses. Case presentation We report a case of a 53-year-old Caucasian man with a liver abscess and subsequent brain abscesses caused by Aggregatibacter paraphrophilus. The probable source of the infection was the oral flora of our patient following ingestion of a dental filling. The presence of a large patent foramen ovale was a predisposing factor for multifocal abscesses. Conclusion In this case report, we describe an unusual case of a patient with both liver and brain abscesses caused by an oral commensal Aggregatibacter paraphrophilus that can occasionally show significant pathogenic potential.Published versio

CRT-100.04 Delaying Reperfusion Plus LV Unloading Reduces Infarct Size: A Per-Protocol-Analysis of the STEMI_DTU Pilot Study

Background: Myocardial infarct size (IS) and microvascular obstruction (MVO) are well-established prognostic markers in STEMI. The STEMI-DTU pilot trial was the first exploratory study to identify that LV unloading and delayed reperfusion was feasible. We now report new findings in patients from per-protocol cohort on the basis of magnitude of sum of precordial ST-segment elevation. Method: In a multicenter, prospective, randomized safety and feasibility trial, 50 patients with anterior STEMI to LV unloading using Impella CP were assigned into two different arms including immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). Cardiac magnetic resonance (CMR) imaging assessed infarct size normalized to the area at risk (IS/AAR) 3-5 days after PCI. Patients without CMR at 3-5 days, without PCI of a culprit LAD lesion and without STEMI were not per-protocol and thus excluded from this analysis. Results: 32 patients meeting all inclusion and exclusion criteria (U-IR,n=15; U-DR,n=17) were included in our analysis. Despite longer symptom-to-balloon times in the U-DR arm, IS/AAR was significantly lower with 30 minutes of delay to reperfusion in the presence of active LV unloading (47±16% vs 60±15%, p=0.02) and remained lower irrespective of the magnitude of precordial ΣSTE (Figure 1). MVO was not significantly different between groups (1.5±2.8% vs 3.5±4.8%,p=0.15), but significantly lower in the U-DR arm among patients with precordial ΣSTE≥8mm (1.5±2.5% vs 5.6±5.3%, p=0.04). Conclusion: This analysis supports the paradigm-changing concept that when treated per protocol, 30 minutes of delay to reperfusion with active LV unloading may reduce infarct size irrespective of precordial STE magnitude. Ongoing STEMI-DTU Pivotal trial will provide us further information on these findings

Augmentation Index Derived from Peripheral Arterial Tonometry Correlates with Cardiovascular Risk Factors

Background. Augmentation index (AIx) is traditionally obtained from pressure waveforms via arterial applanation tonometry. We sought to evaluate the association between AIx obtained from peripheral arterial tonometry (PAT) with cardiovascular risk factors (CRF) and coronary artery disease (CAD). Methods. 186 patients were enrolled in the study. The presence or absence of CRFs and CAD was assessed in each subject. AIx was calculated by an automated algorithm averaging pulse wave amplitude data obtained via PAT. Central blood pressures were assessed in a subset of patients undergoing clinically indicated cardiac catheterization. Results. An association was observed between AIx and age, heart rate, systolic blood pressure, mean arterial pressure, pulse pressure, body weight and body mass index. AIx was significantly lower in patients with <3 CRFs compared to those with >5 CRFs ( P = .02). CAD+ patients had significantly higher AIx compared to CAD− patients ( P = .008). Area under the ROC curve was 0.604 (P < .01). In patients undergoing cardiac catheterization, after adjusting for age, height and heart rate, AIx was a significant predictor of aortic systolic and pulse pressures (P < .05) Conclusion. AIx derived from PAT correlates with cardiac risk factors and CAD. It may be a useful measure of assessing overall risk for coronary artery disease

Smooth muscle cell specific deletion of the PKGIα target RGS2 induces vascular dysfunction and hypertension

International audiencen.

Brief Intervention for Truant Youth Sexual Risk Behavior and Alcohol Use: A Parallel Process Growth Model Analysis

Truant youths frequently experience family problems, emotional/psychological issues, substance misuse, and delinquency. They are likely engaging in alcohol use and sexual risk behavior at a higher rate than the general youth population. Early intervention services would benefit them, their families, and society. We present interim findings from an ongoing, National Institute on Drug Abuse-funded, experimental, brief intervention (BI) study involving truant youths and their parent/guardians. Baseline, 3-, 6-, and 12-month follow-up data were analyzed to determine whether alcohol use and sexual risk behaviors were longitudinally related, to examine the effects of the BI on alcohol use and sexual risk behaviors, to identify subgroups of youths involved in alcohol use and sexual risk behaviors, and to assess the impact of the BI on these subgroups. Results indicated alcohol use and sexual risk were longitudinally related. Limited treatment effects were observed for alcohol use. Implications for future research and service delivery are considered. © 2014 Copyright Taylor & Francis Group, LLC