Prevalence and Predictors of Out-of-Target LDL Cholesterol 1 to 3 Years After Myocardial Infarction. A Subanalysis From the EYESHOT Post-MI Registry

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI). Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI. Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C >= 70 mg/dL. Results: The study population included 903 patients (mean age 65.5 +/- 11.5 years). Among them, LDL-C was >= 70 mg/dL in 474 (52.5%). Male sex (p = 0.031), hypertension (p = 0.024), prior percutaneous coronary intervention (p = 0.016) and high education level (p = 0.008) were higher in the LDL-C < 70 group. At multivariable analysis, low education level was an independent predictor of LDL-C >= 70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; p = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; p = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%). Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting

Brain tumours in the time of COVID-19: An online survey on patients’ disease experience in one Italian region

BackgroundSince the outbreak, in 2019, of COVID-19, the world has experienced marked changes in daily habits, partly reflecting the exceptional social restrictions and health measures adopted to contain the disease. All these measures significantly affected not only peoples’s daily lives and psychological well-being but also the possibility for the healthcare system to function properly. In this setting, brain tumour patients were at risk due to their higher physical and mental fragility and their need for regular care. The aim of the present study was to assess, using a self-reported online questionnaire, the patients’s perceptions regarding their disease experience.Materials and methodsWe developed an online anonymous self-report survey to assess patients’s disease experience during the pandemic. We investigated the impact of the COVID-19 pandemic on patients’s cancer care schedules, their psychological distress and emotions felt during the pandemic, their levels of worry about COVID-19, and their oncological conditions.Results107 patients answered our survey, most of them suffering from a glioma. Less than one-third of the sample had their appointments cancelled, delayed or converted into online visits due to the pandemic. Of the patients who answered the survey, 95% declared they were satisfied with their Institute’s oncological management. The feelings reported most often were peacefulness or anxiety/worry; the majority of the sample reported high levels of loneliness, which tended to increase with age, whilst the psychological distress was correlated with age and with having a recurrence of the disease. Half of the sample declared severe worry about their oncological condition, in particular subjects with a recurrence or who were receiving adjuvant therapies. Patients with recurrence tended to worry more about the possibility of contracting COVID-19, and its effects.ConclusionOur findings illustrate how fragile and in need of care patients with a brain tumour may be, especially those with more severe clinical conditions. These data may help boost healthcare professionals’s knowledge about brain tumour patients’s needs and fears, so as to be able to offer them a better hospital experience and improve their clinical management, while possibly also reducing the psychological burden on patients and their families

Revisiting the obesity paradox in heart failure:Per cent body fat as predictor of biomarkers and outcome

Aims - Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). Methods - In an individual patient dataset, BMI was calculated as weight (kg)/height (m)2, and PBF through the Jackson–Pollock and Gallagher equations. Results - Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5–2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4–33.0%) with the Jackson–Pollock equation, and 28.0% (23.8–33.5%) with the Gallagher equation, with an extremely strong correlation (r = 0.996, p 2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion - In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients

Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial

BackgroundThe Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported.MethodsParticipants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State–Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models.ResultsIn total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS.ConclusionDepression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014)

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). CONCLUSIONS: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk

Osteopontin as Candidate Biomarker of Coronary Disease despite Low Cardiovascular Risk: Insights from CAPIRE Study

Stratification according high cardiovascular (CV) risk categories, still represents a clinical challenge. In this analysis of the CAPIRE study (NCT02157662), we investigate whether inflammation could fit between CV risk factors (RFs) and the presence of coronary artery disease (CAD). In total, 544 patients were included and categorized according with the presence of CAD and CV risk factor burden (low/multiple). The primary endpoint was to verify any independent association of neutrophil-related biomarkers with CAD across CV risk categories. The highest values of osteopontin (OPN) were detected in the low RF group and associated with CAD (23.2 vs. 19.4 ng/mL; p = 0.001), although no correlation with plaque extent and/or composition were observed. Conversely, myeloperoxidase (MPO) and resistin did not differ by CAD presence. Again, OPN was identified as independent variable associated with CAD but only in the low RF group (adjOR 8.42 [95% CI 8.42–46.83]; p-value = 0.015). As an ancillary finding, a correlation linked OPN with the neutrophil degranulation biomarker MPO (r = 0.085; p = 0.048) and resistin (r = 0.177; p = 3.4 × 10−5). In the present study, OPN further strengthens its role as biomarker of CAD, potentially bridging subclinical CV risk with development of atherosclerosis

Assessment of mortality risk in elderly patients after proximal femoral fracture

Mortality after hip fracture is a major problem in the Western world, but its mechanisms remain uncertain. This study assessed the 2-year mortality rate after hip fracture in elderly patients by including hospital factors (eg, intervention type, surgical delay), underlying health conditions, and, for a subset, lifestyle factors (eg, body mass index, smoking, alcohol). A total of 828 patients (183 men) 70 to 99 years old experiencing a hip fracture in 2009 in the province of Varese were included in the study. The risk factors for death were assessed through Kaplan-Meier analysis and Cox proportional hazards analysis. Hip fracture incidence per 1000 persons was higher in women (8.4 vs 3.7 in men) and in elderly patients (12.4 for 85-99 years vs 4.4 for 70-84 years). The mortality rate after 1, 6, 12, and 24 months was 4.7%, 16%, 20.7%, and 30.4%, respectively. For the province of Varese, sex (hazard ratio, 0.39 for women), age group (hazard ratio, 2.2 for 85-99 years), and Charlson Comorbidity Index score (hazard ratio, 2.06 for score greater than 1) were found to be statistically significant. The 2-year mortality rate in hip fractures is associated with sex, age, and comorbidities. Male sex, age older than 85 years, and Charlson Comorbidity Index score greater than 1 are associated with a higher risk. Surgical delay was significant in the Kaplan-Meier survival time analysis but not in the Cox hazard analysis, suggesting that early surgery reduces risk in patients with numerous comorbidities

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI-HF trial

Aims Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.Methods and results In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure (GISSI-HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow-up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high-risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer (d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin-3 levels, and, especially, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P-threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).Conclusions Higher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT-proBNP concentrations