Estimated number and percentage of US adults with atherosclerotic cardiovascular disease recommended add-on lipid-lowering therapy by the 2018 AHA/ACC multi-society cholesterol guideline

Study objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline recommends a maximally-tolerated statin with add-on lipid-lowering therapy, ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) for adults with very-high atherosclerotic cardiovascular disease (ASCVD) risk to achieve a low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. We estimated the percentage of US adults with ASCVD recommended, by the 2018 AHA/ACC cholesterol guideline, and receiving add-on lipid-lowering therapy. Design, setting, and participants: Cross-sectional study including 805 participants from the US National Health and Nutrition Examination Survey (NHANES) 2013–2020 data. NHANES sampling weights were used to obtain estimates for the US adult population. Main measures: Very-high ASCVD risk was defined as either: ≥2 ASCVD events, or one ASCVD event with ≥2 high-risk conditions. Being recommended add-on lipid-lowering therapy was defined as having very-high ASCVD risk and LDL-C ≥ 70 mg/dL, or LDL-C < 70 mg/dL while taking ezetimibe or a PCSK9 inhibitor. Results: An estimated 18.7 (95%CI, 16.0–21.4) million US adults had ASCVD, of whom 81.6 % (95%CI, 76.7 %–86.4 %) had very-high ASCVD risk, and 60.1 % (95%CI, 54.5 %–65.7 %) had very-high ASCVD risk and LDL-C ≥ 70 mg/dL. Overall, 61.4 % (95%CI, 55.8 %–66.9 %) were recommended add-on lipid-lowering therapy and 3.2 % (95 % CI, 1.2 %–5.3 %) were taking it. Smokers, adults with diabetes, hypertension and chronic kidney disease were more likely, while those taking atorvastatin or rosuvastatin were less likely, to be recommended add-on lipid-lowering therapy. Conclusion: The majority of US adults with ASCVD are recommended add-on lipid-lowering therapy by the 2018 AHA/ACC cholesterol guideline but few are receiving it

The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients

BACKGROUND: Among older cancer patients, there is uncertainty about the degree to which venous thromboembolism (VTE) and its treatment increase the risk of death or major hemorrhage. OBJECTIVE: To determine the prevalence of VTE in a cohort of older cancer patients, as well as the degree to which VTE increased the risk of death or major hemorrhage. METHODS: We conducted a retrospective cohort study of linked Surveillance, Epidemiology, and End Results cancer registry and Medicare administrative claims data. Patients with any of ten invasive cancers diagnosed during 1995 through 1999 were included; the independent variable was VTE diagnosed concomitantly with cancer diagnosis. Outcomes included major hemorrhage during the first year after cancer diagnosis and all-cause mortality; RESULTS: Overall, about 1% of patients who were diagnosed with cancer also had a VTE diagnosed concomitantly. After adjusting for sociodemographic factors and cancer stage and grade, concomitant VTE was associated with a relative increase in the risk of death for 8 of the 10 cancer types; the increase in risk tended to range 20–40% across most cancer types. Approximately 16.8% (95% confidence interval [CI] 14.9–18.8%) of patients with a concomitant VTE and 7.9% (95% CI 7.7–8.0%) of patients without a VTE experienced a major hemorrhage during the year after cancer diagnosis (P value <.001). The excess risk of hemorrhage associated with VTE varied substantially across cancer types, ranging from no significant excess (kidney and uterine cancer) to 11.5% (lymphoma). CONCLUSION: Concomitant VTE is not only a marker and potential mediator of increased risk of death among older cancer patients, but patients with a VTE have a marked increased risk of major hemorrhage

Markers of Dysglycaemia and Risk of Coronary Heart Disease in People without Diabetes: Reykjavik Prospective Study and Systematic Review

BACKGROUND: Associations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations. METHODS AND FINDINGS: Fasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants). CONCLUSIONS: In the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk

Neonatal Brain Injury and Neuroanatomy of Memory Processing following Very Preterm Birth in Adulthood: An fMRI Study

Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT) compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI) study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ) at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and right medial frontal gyrus decreased with increasing severity of neonatal brain injury. However, the significant between-group functional neuroanatomical differences were not directly attributable to the detected structural regional differences

Molecular Etiology of Atherogenesis – In Vitro Induction of Lipidosis in Macrophages with a New LDL Model

BACKGROUND: Atherosclerosis starts by lipid accumulation in the arterial intima and progresses into a chronic vascular inflammatory disease. A major atherogenic process is the formation of lipid-loaded macrophages in which a breakdown of the endolysomal pathway results in irreversible accumulation of cargo in the late endocytic compartments with a phenotype similar to several forms of lipidosis. Macrophages exposed to oxidized LDL exihibit this phenomenon in vitro and manifest an impaired degradation of internalized lipids and enhanced inflammatory stimulation. Identification of the specific chemical component(s) causing this phenotype has been elusive because of the chemical complexity of oxidized LDL. METHODOLOGY/PRINCIPAL FINDINGS: Lipid "core aldehydes" are formed in oxidized LDL and exist in atherosclerotic plaques. These aldehydes are slowly oxidized in situ and (much faster) by intracellular aldehyde oxidizing systems to cholesteryl hemiesters. We show that a single cholesteryl hemiester incorporated into native, non-oxidized LDL induces a lipidosis phenotype with subsequent cell death in macrophages. Internalization of the cholesteryl hemiester via the native LDL vehicle induced lipid accumulation in a time- and concentration-dependent manner in "frozen" endolysosomes. Quantitative shotgun lipidomics analysis showed that internalized lipid in cholesteryl hemiester-intoxicated cells remained largely unprocessed in those lipid-rich organelles. CONCLUSIONS/SIGNIFICANCE: The principle elucidated with the present cholesteryl hemiester-containing native-LDL model, extended to other molecular components of oxidized LDL, will help in defining the molecular etiology and etiological hierarchy of atherogenic agents