Body-Weight Fluctuations and Outcomes in Coronary Disease.

BackgroundBody-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease.MethodsWe determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke.ResultsAmong 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models.ConclusionsAmong participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .)

Visit-to-visit variability of lipid measurements as predictors of cardiovascular events.

BACKGROUND:Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events. OBJECTIVE:The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease. METHODS:We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9 years. RESULTS:In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11-1.21, P < .0001), for triglycerides (HR 1.09, 95% CI 1.04-1.15, P = .0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09-1.19, P < .0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak. CONCLUSION:Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined

Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial

CARDS was partially funded by Diabetes UK and the National Health Service Research and Development Forum (England)

Relation of Improvement in Estimated Glomerular Filtration Rate With Atorvastatin to Reductions in Hospitalizations for Heart Failure (from the Treating to New Targets [TNT] Study)

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF (−0.09 ± 7.89 vs 0.81 ± 6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5-ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to 0.94, p = 0.002). This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization. This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization

Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

BACKGROUND: A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. CASE PRESENTATION: A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The echocardiographic examination revealed pericardial effusion and an inhomogeneous mobile mass located in the pericardial sac around the left ventricle. Cardiac magnetic resonance (MRI) examination showed an intrapericardial, semilunar-shaped mass attached to the pulmonary trunk with an intermediate signal intensity on proton density-weighted images and high signal intensity on T2-weighted spectral fat saturation inversion recovery images. First-pass perfusion and early and late gadolinium-enhanced images showed a vascularized mass with septated, patchy, inhomogeneous late enhancement. Coronary computed tomography angiography revealed no invasion of the coronaries. Based on the retrospectively analysed screening chest X-rays, the mass had started to form at least 7 years earlier. Complete resection of the tumour with partial resection of the pulmonary trunk was performed. Histological evaluation of the septated, cystic mass revealed tumour cells forming an irregular patternless pattern; immunohistochemically, the cells tested positive for vimentin, CD34, CD99 and STAT6 but negative for keratin (AE1-AE3), CD31 and S100. Thus, the diagnosis of an intrapericardial solitary fibrous tumour was established. There has been no recurrence for 3 years based on the regular MRI follow-up. CONCLUSION: Intrapericardial SFTs, showing slow growth dynamics, can present with massive extent even in completely asymptomatic patients. MRI is exceedingly useful for characterizing intrapericardial masses, allowing precise surgical planning, and is reliable for long-term follow up

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Body Weight Variability and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus.

BACKGROUND:Some studies have shown that body weight variability is a risk factor for cardiovascular events, but this has not been studied in subjects with diabetes mellitus. METHODS AND RESULTS:We measured intraindividual variations in body weight from baseline and follow-up visits in 6408 subjects with type 2 diabetes mellitus from 3 clinical trials. The primary end point, any coronary event, was a composite of coronary heart disease death, myocardial infarction, resuscitated cardiac arrest, coronary revascularization, and unstable or new-onset angina. After adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body weight variability, measured as average successive variability and used as a time-dependent covariate, was associated with an increase in the risk of any coronary event (hazard ratio, 1.08; 95% CI, 1.01-1.14; P=0.017), major coronary event (hazard ratio, 1.12; 95% CI, 1.04-1.20; P=0.002), any cardiovascular event (hazard ratio, 1.08; 95% CI, 1.03-1.14; P=0.0015), and death (hazard ratio, 1.16; 95% CI, 1.10-1.22; P&lt;0.0001). Among patients in the quintile with the highest variation in body weight compared with the lowest, the risk of any coronary event was 59% higher; the risk of a major coronary event, 82% higher; any cardiovascular event, 75% higher; death, 82% higher; myocardial infarction, 99% higher; and stroke, 92% higher in adjusted models. The results were consistent in a number of sensitivity analyses. CONCLUSIONS:Among subjects with type 2 diabetes mellitus, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events, independent of traditional cardiovascular risk factors. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov . Unique identifier: NCT00327691 and NCT00327418