Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Integration of a polygenic score into guideline-recommended prediction of cardiovascular disease.

BACKGROUND AND AIMS: It is not clear how a polygenic risk score (PRS) can be best combined with guideline-recommended tools for cardiovascular disease (CVD) risk prediction, e.g. SCORE2. METHODS: A PRS for coronary artery disease (CAD) was calculated in participants of UK Biobank (n = 432 981). Within each tenth of the PRS distribution, the odds ratios (ORs)-referred to as PRS-factor-for CVD (i.e. CAD or stroke) were compared between the entire population and subgroups representing the spectrum of clinical risk. Replication was performed in the combined Framingham/Atherosclerosis Risk in Communities (ARIC) populations (n = 10 757). The clinical suitability of a multiplicative model 'SCORE2 × PRS-factor' was tested by risk reclassification. RESULTS: In subgroups with highly different clinical risks, CVD ORs were stable within each PRS tenth. SCORE2 and PRS showed no significant interactive effects on CVD risk, which qualified them as multiplicative factors: SCORE2 × PRS-factor = total risk. In UK Biobank, the multiplicative model moved 9.55% of the intermediate (n = 145 337) to high-risk group increasing the individuals in this category by 56.6%. Incident CVD occurred in 8.08% of individuals reclassified by the PRS-factor from intermediate to high risk, which was about two-fold of those remained at intermediate risk (4.08%). Likewise, the PRS-factor shifted 8.29% of individuals from moderate to high risk in Framingham/ARIC. CONCLUSIONS: This study demonstrates that absolute CVD risk, determined by a clinical risk score, and relative genetic risk, determined by a PRS, provide independent information. The two components may form a simple multiplicative model improving precision of guideline-recommended tools in predicting incident CVD.

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm.

BACKGROUND: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population. METHODS: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed. RESULTS: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity. CONCLUSIONS: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib.

Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high-very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1-4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection.

Cardiovascular risk and the COVID-19 pandemic: a population-based and case‒control studies.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is associated with increases in morbidity and mortality worldwide. The mechanisms of how SARS-CoV-2 may cause cardiovascular (CV) complications are under investigation. The aim of the study was to assess the impact of the COVID-19 pandemic on CV risk. METHODS: These are single-centre Bialystok PLUS (Poland) population-based and case‒control studies. The survey was conducted between 2018 and 2022 on a sample of residents (n = 1507) of a large city in central Europe and patients 6-9 months post-COVID-19 infection (n = 126). The Systematic Coronary Risk Estimation 2 (SCORE2), the Systematic Coronary Risk Estimation 2-Older Persons (SCORE2-OP), the Cardiovascular Disease Framingham Heart Study and the LIFEtime-perspective model for individualizing CardioVascular Disease prevention strategies in apparently healthy people (LIFE-CVD) were used. Subsequently, the study populations were divided into CV risk classes according to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. RESULTS: The study population consisted of 4 groups: a general population examined before (I, n = 691) and during the COVID-19 pandemic (II, n = 816); a group of 126 patients post-COVID-19 infection (III); and a control group matched subjects chosen from the pre-COVID-19 pandemic (IV). Group II was characterized by lower blood pressure, low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) values than group I. Group III differed from the control group in terms of lower LDL-c level. There was no effect on CV risk in the general population, but in the population post-COVID-19 infection, CV risk was lower using FS-lipids, FS-BMI and LIFE-CVD 10-year risk scores compared to the prepandemic population. In all subgroups analysed, no statistically significant difference was found in the frequency of CV risk classes. CONCLUSIONS: The COVID-19 pandemic did not increase the CV risk calculated for primary prevention. Instead, it prompted people to pay attention to their health status, as evidenced by better control of some CV risk factors. As the COVID-19 pandemic has drawn people's attention to health, it is worth exploiting this opportunity to improve public health knowledge through the design of wide-ranging information campaigns.

The prehospital NEW score to assess septic shock in-hospital, 30-day and 90-day mortality.

BACKGROUND: The early identification of sepsis presenting a high risk of deterioration is a daily challenge to optimise patient pathway. This is all the most crucial in the prehospital setting to optimize triage and admission into the appropriate unit: emergency department (ED) or intensive care unit (ICU). We report the association between the prehospital National Early Warning Score 2 (NEWS-2) and in-hospital, 30 and 90-day mortality of SS patients cared for in the pre-hospital setting by a mobile ICU (MICU). METHODS: Septic shock (SS) patients cared for by a MICU between 2016, April 6th and 2021 December 31st were included in this retrospective cohort study. The NEWS-2 is based on 6 physiological variables (blood pressure, heart rate, respiratory rate, temperature, oxygen saturation prior oxygen supplementation, and level of consciousness) and ranges from 0 to 20. The Inverse Probability Treatment Weighting (IPTW) propensity method was applied to assess the association with in-hospital, 30 and 90-day mortality. A NEWS-2 ≥ 7 threshold was chosen for increased clinical deterioration risk definition and usefulness in clinical practice based on previous reports. RESULTS: Data from 530 SS patients requiring MICU intervention in the pre-hospital setting were analysed. The mean age was 69 ± 15 years and presumed origin of sepsis was pulmonary (43%), digestive (25%) or urinary (17%) infection. In-hospital mortality rate was 33%, 30 and 90-day mortality were respectively 31% and 35%. A prehospital NEWS-2 ≥ 7 is associated with an increase in-hospital, 30 and 90-day mortality with respective RRa = 2.34 [1.39-3.95], 2.08 [1.33-3.25] and 2.22 [1.38-3.59]. Calibration statistic values for in-hospital mortality, 30-day and 90-day mortality were 0.54; 0.55 and 0.53 respectively. CONCLUSION: A prehospital NEWS-2 ≥ 7 is associated with an increase in in-hospital, 30 and 90-day mortality of septic shock patients cared for by a MICU in the prehospital setting. Prospective studies are needed to confirm the usefulness of NEWS-2 to improve the prehospital triage and orientation to the adequate facility of sepsis.

The combined use of the Charlson Comorbidity Index and National Early Warning Score 2 helps predict the prognosis of candidemia.

BACKGROUND: The National Early Warning Score 2 (NEWS2) standardizes assessment and response to acute illnesses using vital signs. Whether NEWS2 is useful in predicting the prognosis of candidemia remains to be determined. METHODS: Our study, conducted as a rigorous and retrospective analysis, examined patients with candidemia who were hospitalized between January 2014 and December 2023. We assessed candidemia severity using the Pitt Bacteremia Score (PBS) and NEWS2, while the Charlson Comorbidity Index (CCI) was used to assess underlying medical conditions. The endpoint was all-cause mortality within 30 days of candidemia onset, ensuring comprehensive evaluation of the patient's prognosis. RESULTS: Overall, 93 patients with candidemia were included. The 30-day all-cause mortality rate was 29.0 %. The area under the receiver operating characteristic curve (AUC) for CCI, PBS, and NEWS2 were 0.87 (95 % confidence interval [CI]: 0.80-0.95), 0.75 (95 % CI: 0.66-0.85), and 0.92 (95 % CI: 0.87-0.97), respectively, for predicting the 30-day mortality in patients with candidemia. The AUC values for CCI combined with PBS and NEWS2 were 0.89 (95 % CI: 0.83-0.96) and 0.96 (95 % CI: 0.93-1.00) for predicting the 30-day mortality in candidemia. Among the items that were significant in the univariate analysis, multivariate analysis showed that the combination of NEWS2 ≥ 10 and CCI ≥4 was the helpful prognostic factor for 30-day mortality. CONCLUSIONS: The combination of NEWS2 ≥ 10 and CCI ≥4 scores may be useful in predicting the risk of 30-day mortality in patients with candidemia.

Association between healthy lifestyle on life course and multimorbidity in adults: results from two national prospective cohort studies.

OBJECTIVES: To examine the correlation between healthy lifestyle patterns, their change trajectories, and the risk of multimorbidity in adults. METHODS: Based on two representative national cohorts, the English Longitudinal Study of Aging (ELSA) and the Health and Retirement Study (HRS) including adults aged 50 years and over. We employed Cox regression, lifestyle change trajectories, and restricted mean survival times to explore the relationship between lifestyle (assessed by SCORE2, LE'8, and HLS scores) and multimorbidity. We also conducted mediation analysis to investigate the underlying mechanisms. RESULTS: A healthy lifestyle (higher LE'8, higher HLS, or lower SCORE2) can reduce the risk of multimorbidity. 2-10% lower multimorbidity risk per one-point increase in LE'8 and HLS. The hazard ratio of multimorbidity for improvements in unhealthy lifestyles or deterioration in healthy lifestyles compared to always healthy lifestyles ranged from 1.598 to 5.602. Besides, for LE'8 and HLS, participants with higher scores had a slower decrease in survival probability in ELSA. Triglyceride, C-reaction protein, fibrinogen, and cystatin C partly mediate the association between lifestyle and multimorbidity. CONCLUSIONS: Keeping a healthy lifestyle over time can help reduce the risk of multimorbidity.

Epidemiology and Severity of Medical Events for Mountain Bikers and Hikers Transported by Ambulance in Western Australia, 2015 to 2020.

INTRODUCTION: Outdoor activities offer physical and mental health benefits. However, incidents can occur requiring ambulance transport to hospital. This study aimed to describe the epidemiology and severity of traumatic and medical incidents for mountain bikers and hikers transported by ambulance within Western Australia. METHODS: This was a retrospective cohort study of ambulance-transported mountain bikers and hikers within Western Australia from 2015 to 2020. Data were extracted from ambulance electronic patient care records. Multivariable analyses were undertaken to identify variables associated with higher patient severity based on the National Early Warning Score 2 (NEWS2). RESULTS: A total of 610 patients required ambulance transport to hospital while mountain biking (n=329; 54%) or hiking (n = 281; 46%). Median age of mountain bikers and hikers was 38 (24-48) y and 49 (32-63) y, respectively. Paramedics reported a fracture in 92 (28%) mountain bikers and 78 (28%) hikers. The predominant injury locations for mountain bikers were upper limbs and for hikers, lower limbs. Cases were trauma related in 92% of mountain bikers and 55% of hikers. A significant association (P<0.001) between the etiology of the ambulance callout and patient severity was found. In trauma etiology cases, the frequency of medium-risk+ NEWS2 severity was 21.4%. In medical cases, the frequency of medium-risk+ severity was 40.8%. CONCLUSION: Both mountain bikers and hikers experienced incidents requiring ambulance transport to hospital. Incidents of a medical etiology had a higher clinical risk, as determined by the NEWS2 scores, regardless of activity being undertaken.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

To What Extent Does Cardiovascular Risk Classification of Patients with Type 2 Diabetes Differ between European Guidelines from 2023, 2021, and 2019? A Cross-Sectional Study.

Background and Objectives: Type 2 Diabetes (T2DM) is intricately associated with an increased cardiovascular (CV) risk, highlighting the imperative for tailored intervention in the prevention and management of CV diseases. To assess the CV risk and subsequent interventions in patients with diabetes, the European Society of Cardiology (ESC) has been consistently developing and updating specific guidelines for risk assessment and patient management since 2019. The 2023 risk classification method has significantly changed, introducing a novel probability-based assessment through the implementation of SCORE2-Diabetes instrument. This marks a shift from the risk factor-based classification employed in the 2019 and 2021 methods, representing an innovative approach in risk assessment for individuals with T2DM. This study aims to evaluate the differences in the CV risk classification among hospitalized patients with T2DM using the three proposed methods within the Romanian population, a European population considered to be at very high cardiovascular risk. Materials and Methods: in a consecutive-case, population-based study design, 70 patients hospitalized with T2DM from a European population characterized by very high CV risk were assessed for CV risk using the three proposed methods. The differences between these classifications were subsequently analyzed. Results: In the study group, according to 2023 classification, one patient (1.4%) was classified with moderate CV risk, eight (11.4%) with high cardiovascular risk, and sixty-one (87.2%) with very high cardiovascular risk. A total of 36 patients (51.4%) were classified differently compared to 2021 criteria, the differences being statistically significant (p = 0.047), while 13 (18.6%) were different compared to 2019 criteria, the differences being statistically non-significant (p = 0.731). By comparing the 2021 to the 2019 ESC Guidelines recommendations, 40 patients had a one-step decrease in cardiovascular risk category, from very high to high risk. Conclusions: Most patients included in the analysis were classified as very high CV risk (87.2%). Within a European population characterized by very high CV risk, the SCORE2-Diabetes instrument proves to be a valuable tool, contributing to most step-ups in CV risk classes within the 2023 classification. In a very-high-risk demographic, the 2023 algorithm resulted in different classifications in contrast to the 2021 method but similar classifications observed with the 2019 method.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 European Society of Cardiology Congress.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 European Society of Cardiology (ESC) congress. RECENT FINDINGS: The NATURE-PARADOX was a naturally randomized trial that used genetic data from the UK Biobank registry to create "cumulative exposure to low-density lipoprotein-cholesterol (LDL-C)" biomarker and evaluate its association with major CV events regardless of plasma LDL-C levels or age. Safety and efficacy data of inclisiran, a PCSK9-interfering mRNA (PCSK9i) administered subcutaneously twice annually, were presented. Data on two new PCSK9is were presented, recaticimab, an oral drug, and lerodalcibep, a subcutaneous drug with a slightly different architecture than currently available PSCK9is. A phase 1 trial on muvalaplin, an oral lipoprotein (a) inhibitor, was presented. An atherosclerotic CV disease (ASCVD) risk prediction algorithm for the Asian population using SCORE2 data was presented. Long-term follow-up of patients enrolled in the CLEAR outcomes trial showed sustained and more significant ASCVD risk reduction with bempedoic acid in high-risk patients. The late-breaking clinical science at the 2023 congress of the ESC extends the known safety and efficacy data of a PCSK9i with the introduction of new drugs in this class. Using cumulative exposure to LDL-C rather than a single value will help clinicians tailor the LDL-C reduction strategy to individual risk and is an important step towards personalized medicine.

Cardiovascular risk and the COVID-19 pandemic: A retrospective observational study in a population of healthcare professionals.

BACKGROUND AND AIM: To contain the spread of COVID-19, many countries imposed several restrictive measures, leading to radical changes in daily life behaviors. Healthcare workers experienced additional stress due to the increased risk of contagion, possibly causing an increase in unhealthy habits. We investigated changes in cardiovascular (CV) risk assessed by the SCORE-2 in a healthy population of healthcare workers during the COVID-19 pandemic; an analysis by subgroups was also conducted (sportspeople vs sedentary subjects). METHODS AND RESULTS: We compared medical examination and blood tests in a population of 264 workers aged over 40, performed yearly before (T0) and during the pandemic (T1, T2). We found a significant increase in the average CV risk, according to SCORE-2, during the follow-up in our healthy population, with a shift from a mean low-moderate risk profile at T0 (2.35%) to a mean high-risk profile at T2 (2.80%). Furthermore, in sedentary subjects was observed a greater and early increase in SCORE-2 compared to sportspeople. CONCLUSIONS: Since 2019, we observed an increase in CV risk profile in a healthy population of healthcare workers, particularly in sedentary subjects, highlighting the need to reassess SCORE-2 every year to promptly treat high-risk subjects, according to the latest Guidelines.

The pattern of epistaxis recurrence in patients taking prophylactic acetylsalicylic acid (ASA) from a 10 year cohort.

OBJECTIVES: Epistaxis is the most common otolaryngological emergency and one-third of epistaxis patients regularly take low-dose acetylsalicylic acid (ASA) for the prevention of cardiovascular disease (CVD). The shift in contemporary guidelines identifies little benefit of ASA intake in patients who have not previously had an infarction. Existing evidence confirms ASA intake as a factor for severe epistaxis, while the evidence concerning its impact on recurrence is ambiguous. There are no available studies which justify the administration of these drugs nor are there any studies correlating the effects of these drugs to the SCORE2 CVD risk stratifying scale. STUDY DESIGN: A retrospective analysis of all admitted epistaxis patients in a tertiary academic hospital for the 10 year period 2011 to 2021. METHODS: Patient data were analysed using the hospital information software. A recurrence was defined as an epistaxis episode requiring hospital readmittance for at least one night. Patients taking anticoagulants were excluded (N = 421). RESULTS: 444 patients were included: 246 were taking ASA and 198 were not (NoASA). ASA patients had more frequent recurrence in general (p = 0.03), more recurrences per patient (p = 0.002), and more changes in bleeding localisation (p = 0.04). Recurrence in the ASA group was associated with lower haemoglobin values (HR 0.62, p < 0.0001), while surgery (HR 6.83, p < 0.0001) was associated with recurrence in the NoASA group. ASA patients had a statistically significant (r 0.33, p = 0.032) correlation between the total number of epistaxis recurrences and SCORE2. The indication for drug intake was highly questionable in as much as 40% of ASA patients. Follow-up time was 5.27 years. CONCLUSIONS: Epistaxis patients taking prophylactic ASA are significantly more burdened by recurrence, because they have more frequent recurrences, a greater number of recurrences per patient, and more changes in bleeding localisations when compared to control patients. The drug indication is questionable in up to 40% of ASA patients, exposing them unnecessarily to recurrence.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

[The new ESC guidelines 2021 on prevention of cardiovascular diseases : Appeal for prevention]. / Neue ESC-Leitlinien 2021 zur Prävention von kardiovaskulären Erkrankungen : Aufruf zur Prävention.

This article summarizes the innovations and most important points of the recently published and updated ESC guidelines 2021 on the prevention of cardiovascular diseases. Developments in risk stratification and further developments with respect to targets and options for the treatment of risk factors necessitated an update of the guidelines from 2016. The innovations incorporate a staged and individualized approach to the prevention targets, an implementation of the systematic coronary risk evaluation 2 (SCORE 2 update) and the SCORE 2­older persons (OP) systems on risk stratification, including age-dependent estimations for young (<50 years old) and older people (≥70 years old) as well as for patients with diabetes mellitus and atherosclerotic cardiovascular diseases. Furthermore, specific recommendations are given for coronary heart disease, heart failure and chronic kidney insufficiency. In addition to recommendations on individualized treatment, the relevance of cardiovascular prevention at the population level, including environmental protection is underlined.

Lactate improves the predictive ability of the National Early Warning Score 2 in the emergency department.

AIMS: The aim of this study was to compare the ability to predict 2-, 7-, 14-, and 30-day in-hospital mortality of lactate vs the National Early Warning Score 2 (NEWS2) vs the arithmetic sum of the NEWS2 plus the numerical value of lactate (NEWS2-L). METHODS: This was a prospective, multicentric, emergency department delivery, pragmatic cohort study. To determine the predictive capacity of lactate, we calculated the NEWS2 and NEWS2-L in adult patients (aged >18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon (Spain) between November 1, 2019, and September 30, 2020. The area under the receiver operating characteristic curve of each of the scales was calculated in terms of mortality for every time frame (2, 7, 14, and 30 days). We determined the cut-off point of each scale that offered highest sensitivity and specificity using the Youden index. RESULTS: A total of 1716 participants were included, and the in-hospital mortality rates at 2, 7, 14, and 30 days were of 7.8% (134 cases), 11.6% (200 cases), 14.2% (243 cases), and 17.2% (295 cases), respectively. The best cut-off point determined in the NEWS2 was 6.5 points (sensitivity of 97% and specificity of 59%), and for lactate, the cut-off point was 3.3 mmol/L (sensitivity of 79% and specificity of 72%). Finally, the combined NEWS2-L showed a cut-off point of 11.7 (sensitivity of 86% and a specificity of 85%). The area under the receiver operating characteristic curve of the NEWS2, lactate, and NEWS2-L in the validation cohort for 2-day mortality was 0.889, 0.856, and 0.923, respectively (p<0.001 in all cases). CONCLUSIONS: The new score generated, NEWS2-L, obtained better statistical results than its components (NEWS2 and lactate) separately.

Whats new in 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice?

2021 ESC Guidelines on cardiovascular disease prevention in clinical practice provides a comprehensive view on preventive cardiology. It presents strategies to reduce the burden of atherosclerotic cardiovascular disease (CVD), both at the individual level and at the population level. Healthy lifestyle and aggressive control of cardiovascular risk factors remain the cornerstone of prevention. Classification of individuals into risk groups based on their clinical characteristics followed by a stepwise treatment-intensification is a novel recommended approach. Updated risk charts - SCORE2 and SCORE2-OP - are intended for estimation of 10-year fatal and non-fatal CVD risk in apparently healthy individuals. Targets and goals for LDL cholesterol, blood pressure, and glycaemic control remain as recommended in recent ESC Guidelines.

National Early Warning Score 2 (NEWS2) better predicts critical Coronavirus Disease 2019 (COVID-19) illness than COVID-GRAM, a multi-centre study.

PURPOSE: Clinical scores to rapidly assess the severity illness of Coronavirus Disease 2019 (COVID-19) could be considered of help for clinicians. Recently, a specific score (named COVID-GRAM) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, based on a nationwide Chinese cohort, has been proposed. We routinely applied the National Early Warning Score 2 (NEWS2) to predict critical COVID-19. Aim of this study is to compare NEWS2 and COVID-GRAM score. METHODS: We retrospectively analysed data of 121 COVID-19 patients admitted in two Clinics of Infectious Diseases in the Umbria region, Italy. The primary outcome was critical COVID-19 illness defined as admission to the intensive care unit, invasive ventilation, or death. Accuracy of the scores was evaluated with the area under the receiver-operating characteristic curve (AUROC). Differences between scores were confirmed used Hanley-McNeil test. RESULTS: The NEWS2 AUROC curve measured 0.87 (standard error, SE 0.03; 95% CI 0.80-0.93; p < 0.0001). The COVID-GRAM score AUROC curve measured 0.77 (SE 0.04; 95% CI 0.68-0.85; p < 0.0001). Hanley-McNeil test showed that NEWS2 better predicted severe COVID-19 (Z = 2.03). CONCLUSIONS: The NEWS2 showed superior accuracy to COVID-GRAM score for prediction of critical COVID-19 illness.

Identification of early and extra-early maturing tropical maize inbred lines resistant to Exserohilum turcicum in sub-Saharan Africa.

Northern corn leaf blight (NCLB) incited by the fungus Exserohilum turcicum is a foliar disease that significantly limits maize production and productivity in West and Central Africa (WCA), particularly in the mid-altitudes but during the last decade it has become a menace in lowland agro-ecologies. The most economical and environmentally friendly disease management strategy is the cultivation of maize varieties resistant or tolerant to NCLB. However, no early maturing (EM) and extra-early maturing (EEM) NCLB resistant varieties are commercially available in WCA. One hundred inbred lines each of EM and EEM derived from tropical maize germplasm were inoculated with a virulent isolate of E. turcicum at five locations in Nigeria during the 2017 and 2018 growing seasons. The objective of the study was to identify promising NCLB resistant lines and to investigate inter-relationships among the traits. Analysis of variance revealed highly significant genotype and genotype by environment (G × E) interactions for disease severity, grain yield (GYLD), and other agronomic traits. The average disease severity (TURC) values ranged from 1.9 to 5.8 and 2.9 to 5.7 for the EM and EEM inbred lines, respectively. The levels of reaction of the inbred lines to NCLB ranged from highly resistant to highly susceptible. Stepwise regression analysis showed that ears per plant, ear and plant aspects were significantly influenced by the disease scores. Ears per plant, ear and plant aspects, TURC and GYLD traits were employed to develop a base index (BI) for selecting NCLB resistant inbred lines for hybrid development. TZEI 135 and TZEEI 1 were outstanding in GYLD and also had the highest positive BI values in the EM and EEM inbred lines, respectively. The identification of NCLB resistant lines in this study has set the premise for development of NCLB resistant hybrids for WCA as well as the improvement of tropical maize breeding populations for NCLB resistance.