A randomized crossover trial of regional anticoagulation modalities for intermittent hemodialysis.

INTRODUCTION: The optimal regional anticoagulation (RA) of dialysis filters in patients at risk of bleeding remains elusive. Inducing hypocalcemia within the filter by using a calcium-free dialysate has emerged as an easy-to-use heparin-free RA, including in critically ill patients, but comparative studies are lacking. METHODS: We conducted a multicentre, randomized, crossover trial to compare the efficacy and tolerance of two RAs (heparin-coated membrane (HCM) or calcium free dialysate with calcium reinjection according to ionic dialysance (CFD)) in patients requiring hemodialysis and at risk of bleeding. During the study period, each patient received two dialysis sessions (one with each RA in a randomly assigned order). The primary endpoint was the proportion of dialysis sessions completed (≥ 240 min). RESULTS: 94 patients were included in the intention-to-treat analysis, including 16 critically ill patients (17.0%). Coagulation and inflammation parameters, as well as hemodynamic status at baseline, were balanced between groups. Premature coagulation of the filter occurred in 19 HCM (20.9%) compared to 3 (3.2%) CFD sessions. In half of the sessions with premature termination, coagulation occurred before 180 minutes. The proportion of patients who completed the CFD session while failing to complete the HCM session (n = 17) was significantly higher than the proportion of patients who completed the HCM session while failing to complete the CFD session (n = 1; p < 0.001). Hemodynamic and metabolic tolerance were not different between groups. CONCLUSIONS: In individuals at risk of bleeding, RA with calcium-free dialysate significantly reduces the incidence of premature dialysis termination compared to heparin-coated membrane without safety concerns. Trial registration and statistical analysis plan: ClinicalTrials.gov identifier: NCT03842657.

New Strategy for Breast Cancer Related Lymphedema Treatment by Endermology: ELOCS Phase II Randomized Controlled Trial.

BACKGROUND: This phase II trial sought to be the first of its kind to estimate the success rate of endermology in reducing breast cancer-related lymphedema. PATIENTS AND METHODS: ELOCS is a French, monocentric, randomized, open-label phase II trial. Patients were randomized to receive the following over a 5-day treatment period: standard intensive decongestant treatment (IDT) (bandages and manual lymphatic drainage MLD) (group 1); IDT including bandages, MLD, and Cellu M6 (group 2); and IDT including bandages and Cellu M6 (Group 3). The main endpoint was the success rate in each group, (reduction of at least 30% in the excess volume). We estimated that endermology treatment (groups 2 and 3) would be of interest successes occurred in at least 21 out of 31 patients. RESULTS: A total of 93 patients were included (31 patients in each of the 3 groups). The median age was 64.5 years (IQR: [56.4-71.3]). Patients were treated with mastectomy (n = 35), axillary lymphadenectomy (n = 80), radiotherapy (n = 91), and chemotherapy (n = 68). The mean relative reduction in excess volume was 38% in group 1, 33% in group 2, and 34% in group 3. Success rate was 58.1% in group 1 (18/31, P = ,0237), 51.6% (16/31, P = ,5) in group 2, and 64.5% (20/31, P = ,075) in group 3. In the LPG groups (2 and 3), 10/62 (16%) patients found LPG painful and 9/62 (15%) patients considered it to be unpleasant. CONCLUSION: Even though the critical threshold of 21 successes was not met, this study was the first to validate a standardized and reproducible endermology protocol.

The real incidence of sudden death: Fair estimations or futile speculations?

BACKGROUND: The true incidence of sudden death remains undetermined, with controversial results from various publications over time and countries. AIM: To investigate if different estimations would reach the values usually reported for France. METHODS: Three different kinds of estimations were used. First, the number of resuscitated sudden deaths and necropsies for sudden death in the Haute-Garonne French administrative department (i.e. county) over the last 10years was expanded to the national level. Second, sudden death coding of death certificates was collected at the national level. Third, the total number of out-of-hospital cardiac arrests leading to any emergency call (with/without intervention) in Haute-Garonne over the last 10years was expanded to the national level. RESULTS: There was a mean of 26 resuscitated sudden deaths and 145 necropsies for sudden death each year in Haute-Garonne, i.e. 12 to 14 sudden deaths for 100,000 inhabitants, and 7700 to 9400 sudden deaths yearly when related to the whole French population, according to the year of inclusion. Based on death certificates, a mean of 6584 sudden deaths was registered each year in France. Finally, there were about 600 yearly calls/interventions for out-of-hospital cardiac arrests in Haute-Garonne, i.e. 40 to 50 sudden deaths for 100,000 inhabitants, and 16,000 to 27,000 sudden deaths yearly for the whole French territory, according to the year of inclusion. CONCLUSIONS: The incidence of sudden death ranges from 6500 to 27,000 in France according to the calculation methods. This huge difference raises the question of the true current incidence of sudden death, which may have been overestimated previously or may be underestimated in France. More straight prospective surveys are needed to solve this question, because of relevant implications for priorities that should be given to sudden death.

Lack of temporal correlations between COVID pandemic waves and the occurrence of malignant ventricular arrhythmias.

AIMS: Correlations between malignant ventricular arrhythmias and the COVID waves have never been investigated. METHODS AND RESULTS: Prevalence of malignant ventricular arrhythmias/sudden cardiac death has been correlated to the four COVID waves between the onset of pandemic and end 2021. No significant correlation was present in the temporal evolution of both COVID patients/positive tests and incidence of malignant ventricular arrhythmias, which tended to decrease after vaccination onset. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

Cardiogenic shock in adults with congenital heart disease: Insights from the FRENSHOCK registry.

BACKGROUND: Data on cardiogenic shock in adults with congenital heart disease (ACHD) are scarce. AIM: We sought to describe cardiogenic shock in ACHD patients in a nationwide cardiogenic shock registry. METHODS: From the multicentric FRENSHOCK registry (772 patients with cardiogenic shock from 49 French centres between April and October 2016), ACHD patients were compared with adults without congenital heart disease (non-ACHD). The primary outcome was defined by all-cause mortality, chronic ventricular assist device or heart transplantation at 1year. RESULTS: Out of the 772 patients, seven (0.9%) were ACHD, who were younger (median age: 56 vs. 67years), had fewer cardiovascular risk factors, such as hypertension (14.3% vs. 47.5%) and diabetes (14.3% vs. 28.3%), and no previous ischaemic cardiopathy (0 vs. 61.5%). Right heart catheterization (57.1% vs. 15.4%), pacemakers (28.6% vs. 4.6%) and implantable cardioverter-defibrillators (28.6% vs. 4.8%) were indicated more frequently in the management of ACHD patients compared with non-ACHD patients, whereas temporary mechanical circulatory support (0 vs. 18.7%) and invasive mechanical ventilation (14.3% vs. 38.1%) were less likely to be used in ACHD patients. At 1year, the primary outcome occurred in 85.7% (95% confidence interval: 42.1-99.6) ACHD patients and 52.3% (95% confidence interval: 48.7-55.9) non-ACHD patients. Although 1-year mortality was not significantly different between ACHD patients (42.9%) and non-ACHD patients (45.4%), ventricular assist devices and heart transplantation tended to be more frequent in the ACHD group. CONCLUSIONS: Cardiogenic shock in ACHD patients is rare, accounting for only 0.9% of an unselected cardiogenic shock population. Despite being younger and having fewer co-morbidities, the prognosis of ACHD patients with cardiogenic shock remains severe, and is similar to that of other patients.

Hemodynamical consequences and tolerance of sustained ventricular tachycardia.

AIMS: Factors underlying clinical tolerance and hemodynamic consequences of monomorphic sustained ventricular tachycardia (VT) need to be clarified. METHODS: Intra-arterial pressures (IAP) during VT were collected in patients admitted for VT ablation and correlated to clinical, ECG and baseline echocardiographical parameters. RESULTS: 114 VTs from 58 patients were included (median 67 years old, 81% ischemic heart disease, median left ventricular ejection fraction 30%). 61 VTs were untolerated needing immediate termination (54%). VT tolerance was tightly linked to the evolution of IAPs. Faster VT rates (p<0.0001), presence of resynchronization therapy (p = 0.008), previous anterior myocardial infarction (p = 0.009) and more marginally larger baseline QRS duration (p = 0.1) were independently associated with VT tolerance. Only an inferior myocardial infarction was more often present in patients with only tolerated VTs vs patients with only untolerated VTs in multivariate analysis (OR 3.7, 95% CI 1.4-1000, p = 0.03). In patients with both well-tolerated and untolerated VTs, a higher VT rate was the only variable independently associated with untolerated VT (p = 0.02). Two different patterns of hemodynamic profiles during VT could be observed: a regular 1:1 relationship between electrical (QRS) and mechanical (IAP) events or some dissociation between both. VT with the second pattern were more often untolerated compared to the first pattern (78% vs 29%, p<0.0001). CONCLUSION: This study helps to explain the large variability in clinical tolerance during VT, which is clearly related to IAP. VT tolerance may be linked to resynchronization therapy, VT rate, baseline QRS duration and location of myocardial infarction.

Predictors of recurrence of cancer-associated venous thromboembolism after discontinuation of anticoagulant therapy: a multicenter cohort study.

BACKGROUND: Data on recurrence after the end of anticoagulation for a first event of cancer-associated venous thromboembolism (VTE) are scarce. OBJECTIVES: Our aim was to assess predictors of VTE recurrence during a 1-year follow-up period. METHODS: This study is an analysis of RIETE, an international, multicenter, prospective cohort study of patients diagnosed with VTE. Patients had to have active cancer at the time of VTE and to have withdrawn from anticoagulation after 3 months of full treatment. Analyses were performed using Fine and Gray models, with death as a competing risk, and multiple imputation of missing data was performed by chained equations. RESULTS: Among 14 318 patients with cancer-associated VTE, 3414 had undergone time-limited anticoagulation for at least 3 months. The cumulative incidence function for recurrent VTE was 10.2% (95% CI, 9.1-11.5) at 1 year. Chronic kidney disease (a subhazard ratio [sHR] of 1.08 for 10-mL/min decrease in glomerular filtration rate; 95% CI, 1.02-1.14); cancer of the lung, brain, stomach, esophagus, liver, or ovary (sHR, 3.56; 95% CI, 1.07-11.80; compared with cancer of the oropharynx, larynx, or melanoma); cancer of the pancreas, the biliary tract, or of unknown origin (sHR, 6.86; 95% CI, 1.89-24.85); inferior vena cava filter (sHR, 3.16; 95% CI, 1.75-5.71); postthrombotic syndrome (sHR, 2.09; 95% CI, 1.06-4.15); and residual pulmonary thrombotic obstruction (sHR, 2.58; 95% CI, 1.38-4.82) were predictive of recurrence. Surgery during the 2 months before VTE was predictive of absence of recurrence (sHR, 0.60; 95% CI, 0.40-0.92). CONCLUSION: One year after anticoagulant cessation for cancer-associated VTE, approximately 10% of patients experienced recurrence. Discontinuing anticoagulant therapy seems safe, mainly in surgery-associated VTE.

TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement: The TIRATROP Study, A Randomized Controlled Trial.

BACKGROUND: Because rotational atherectomy (RA) is associated with arterial trauma and platelet activation, patients treated with RA may benefit from more potent antiplatelet drugs. The aim of this trial was to assess the superiority of ticagrelor over clopidogrel in reducing post procedure troponin release. METHODS: TIRATROP (TIcagrelor in Rotational Atherectomy to reduce TROPonin enhancement) is a multicenter double-blind randomized controlled trial that included 180 patients with severe calcified lesions requiring RA who received either clopidogrel (300 mg loading dose, then 75 mg/d) or ticagrelor (loading dose 180 mg then 90 mg twice daily). Blood samples were collected at the beginning (T0), and 6, 12, 18, 24 and 36 h after the procedure. Primary end point was troponin release within the first 24 h using area under the curve analysis (troponin level as a function of time). RESULTS: The mean age of patients was 76 ± 10 years, 35% had diabetes. RA was used to treat 1, 2 or 3 calcified lesions in 72%, 23% and 5% of patients, respectively. Troponin release within the first 24 h was similar in both the ticagrelor (adjusted mean ±SD of ln AUC 8.85 ± 0.33) and the clopidogrel (8.77 ± 0.34, p = 0.60) arms. Independent predictors for troponin enhancement were acute coronary syndrome presentation, renal failure, elevated C-Reactive protein and multiple lesions treated with RA. CONCLUSION: Troponin release did not differ among treatment arms. Our results suggest that greater platelet inhibition does not affect periprocedural myocardial necrosis in the setting of RA.

Exposure to environmental occupational constraints and all-cause mortality: Results for men and women from a 20-year follow-up prospective cohort, the VISAT study. Be aware of shift-night workers!

Objective: To determine the predictive value of the large panel of occupational constraints (OC) on all-cause mortality with a 20-year follow-up, in general population of workers. Methods: In VISAT prospective cohort study, 3,138 workers (1,605 men; 1,533 women) were recruited during the periodic work health visits conducted by occupational physicians. OC (physical, organizational, psychological and employment categories) were collected through self-questionnaires. Exposure durations of each OC were divided by tertile distribution. Cox-regression models were performed to analyze the associations between all-cause mortality and each OC first separately and simultaneously in a single model. Results: The mortality rates were higher among exposed participants to most of OC compared to those unexposed. Being exposed and longer exposure increased the risks of all-cause mortality for exposures to carrying heavy loads, loud noise, working more than 48 h/week, starting its first job before 18 years old although these risks became non-significant after adjustments for cardiovascular risk factors. Shift work and night work confirmed a high risk of mortality whatever the adjustments and notably when the other occupational exposures were taking into account, with, respectively: HR: 1.38 (1.01-1.91) and 1.44 (1.06-1.95). After adjustments being exposed more than 13 years to a work requiring getting-up before 5:00 a.m. and more than 16 years in rotating shift work significantly increased the risk of mortality by one and a half. Conclusion: The links between each OC and all-cause mortality and the role of individual factors were stressed. For night-shift workers, it is urgent to implement preventive strategies at the workplace.

Telephone and Smartphone-Based Interventions for Cognitive and Cardio-Metabolic Health in Middle-Aged and Older Adults: A Systematic Review.

Purpose: Dementia and cardio-metabolic diseases share many risk factors. Management of these risk factors could contribute to successful aging, including the prevention of cardio-metabolic disease and dementia. The increasing use of smartphones offers an opportunity for remote preventive interventions. We provided a systematic review of telephone and smartphone-based interventions targeting the prevention of cognitive decline, dementia cardio-metabolic diseases or their risk factors among adults aged over 50 years. Patients and Methods: We searched Pubmed and the International Clinical Trials Registry Platform for experimental studies. We used the Cochrane risk-of-bias tool (Version 2) for randomized trials or TREND (Transparent Reporting of Evaluations with Nonrandomized Designs) checklists to assess study quality for completed studies. Results: We analyzed 21 completed (3 for cognition, 18 for cardio-metabolic outcomes) and 50 ongoing studies (23 for cognition, 27 for cardio-metabolic outcomes). Smartphone interventions were used in 26 studies (3 completed, 23 ongoing). Other interventions involved telephone vocal support and text messaging. Few studies were at low risk of bias. There were heterogeneous cognitive and cardio-metabolic outcomes. The highest quality studies found no significant effects on cognition, and inconsistent results for HbA1c, blood pressure or physical activity. The lower quality-studies found effects on global cognition, working memory, memory and language and inconsistent results for clinical, biological or behavioral cardio-metabolic outcomes. Conclusion and Implications: Despite the large number of commercially available mobile health applications, the magnitude of the scientific evidence base remains very limited. Based on published studies, the added value of telephone and smartphone tools for the prevention of cardio-metabolic diseases, cognitive decline or dementia is currently uncertain, but, there are several ongoing studies expected to be completed in the coming years.

One-Year Impact of COVID-19 Lockdown-Related Factors on Cardiovascular Risk and Mental Health: A Population-Based Cohort Study.

Lockdown measures have obvious psychological impacts, which could, in turn, increase cardiovascular risk. We assessed the association between lockdown-related factors and the worsening of cardiovascular risk, incident anxiety and depression during 12 months' follow-up. During lockdown (April-May 2020), 534 subjects, aged 50-89 years, were included in the PSYCOV-CV study (NCT04397835) and followed for up to 12 months post-lockdown. We found that participants with symptoms of depression during lockdown were more likely to report increased cardiovascular drug treatment (Odds-Ratio (OR) = 5.08 (1.78-14.5), p = 0.002), decreased physical activity (OR = 1.76 (1.10-2.82), p = 0.019) and weight gain (OR = 1.85 (1.08-3.17), p = 0.024) after lockdown. Moreover, changes in sleep patterns (OR = 2.35 (1.13-4.88), p = 0.022) or living in a rural area during lockdown (OR = 1.70 (0.96-3.03, p = 0.069) were associated with higher incident depression, whereas a better relationship with one's partner during lockdown was associated with less incident depression (OR = 0.56 (0.29-1.08), p = 0.084). Finally, we found that continuing to work during lockdown in a role requiring in-person contact with the public (such as cashiers, nurses or physicians) was associated with more incident anxiety after lockdown (OR = 3.38 (1.12-10.2), p = 0.031). Interestingly, decreased consumption of alcohol during lockdown was associated with less incident anxiety (OR = 0.30 (0.10-0.90), p = 0.032). Our study, conducted in a representative sample of an age group at increased risk of both cardiovascular disease and severe COVID-19, increases the understanding of modifiable factors associated with the health impacts of lockdown measures.

Relationships between left ventricular mass and QRS duration in diverse types of left ventricular hypertrophy.

AIMS: Hypertrophic cardiomyopathy (HCM) may be associated with very narrow QRS, while left ventricular hypertrophy (LVH) may increase QRS duration. We investigated the relationships between QRS duration and LV mass (LVM) in subtypes of abnormal LV wall thickness. METHODS AND RESULTS: Automated measurement of LVM on MRI was correlated to automated measurement of QRS duration on ECG in HCM, left ventricular non compaction (LVNC), left ventricular hypertrophy (LVH), and controls with healthy hearts. Uni and multivariate analyses were performed between groups including explanatory variables expected to influence LVM and QRS duration. The relationships between QRS duration and LVM were further studied within each group. Two hundred and twenty-one HCM, 28 LVNC, 16 LVH, and 40 controls were retrospectively included. Mean QRS duration was 92 ms for HCM, 104 for LVNC, 110 for LVH, and 92 for controls (P < 0.01). Mean LVM was 100, 90, 108, and 68 g/m2 (P < 0.01). QRS duration, LVM, hypertension, maximal wall thickness, and late gadolinium enhancement were significantly linked to HCM in multivariate analysis (w/wo bundle branch block). An independent negative correlation was found between LVM and QRS duration in the HCM group, while the relationship was reverse in LVNC, LVH, and controls. CONCLUSION: QRS duration increases with LVM in LVNC, LVH, or in healthy hearts, while reverse relationship is present in HCM. These relationships were independent from other parameters. These results warrant additional investigations for refining diagnosis criteria for HCM in the future.

Mortality, Cardiovascular and Limb Events in Patients With Symptomatic Lower Extremity Artery Disease and Diabetes.

The aim of this study was to compare the prognosis of patients according to diabetes status, during a 1-year follow-up after hospital admission for lower extremity artery disease, in the prospective COPART (COhorte de Patients ARTériopathes) registry. Inclusion criteria were intermittent claudication, ischemic rest pain, tissue loss, or acute limb ischemia, with radiological and hemodynamic confirmation. Among 2494 patients, 1235 (49.5%) had diabetes. Incidence rates for major adverse cardiovascular events (MACE) were 18.0/100 person-years (95% confidence interval [CI], 15.4-21.0) for the diabetes group and 11.1/100 person-years (95% CI, 9.2-13.4) for the non-diabetes group. Incidence rates of all-cause mortality were 29.8/100 person-years (95% CI, 26.5-33.4) for the diabetes group and 19.7/100 person-years (95% CI, 17.2-22.7) for the non-diabetes group. Incidence rates of major limb amputation were 24.2/100 person-years (95% CI, 21.1-27.8) for the diabetes group and 11.6/100 person-years (95% CI, 9.6-14.0) for the non-diabetes group. Diabetes was associated with MACE, adjusted hazard ratio 1.60 (95% CI, 1.16-2.22), and all-cause mortality, unadjusted HR 1.49 (95% CI, 1.24-1.78). In the multivariate analysis, diabetes was no longer associated with major amputation, adjusted HR 1.15 (95% CI, .87-1.51). Patients hospitalized for LEAD with diabetes had a higher risk of MACE than those without diabetes.

Editor's Choice - External Applicability of the COMPASS and VOYAGER-PAD Trials on Patients with Symptomatic Lower Extremity Artery Disease in France: The COPART Registry.

OBJECTIVE: The aim of this study was to examine the external applicability of the COMPASS and the VOYAGER-PAD trials in patients with lower extremity artery disease (LEAD) in the real world. METHODS: This was a multicentre retrospective analysis of prospectively collected COPART data, a French multicentre registry of patients hospitalised for symptomatic LEAD. The proportion of patients eligible for the combination of rivaroxaban 2.5 mg twice daily plus aspirin based on either COMPASS or VOYAGER-PAD criteria is reported. The one year cumulative incidence of outcomes between eligible and non-eligible patients, as well as eligible patients vs. control arms of the COMPASS (LEAD patient subgroup) and the VOYAGER-PAD trials were compared. Analyses were performed using Cox models. RESULTS: Of 2 259 evaluable patients, only 679 (30.1%) were eligible for a low dose rivaroxaban plus aspirin regimen. Others were not eligible because of the need for anticoagulant (48.5% and 38.9% of patients meeting COMPASS and VOYAGER-PAD exclusion criteria, respectively) or dual antiplatelet therapy use (15.7% and 16.5%, respectively), high bleeding risk (14.4% and 11.6%, respectively), malignancy (26.1% and 21.0%, respectively), history of ischaemic/haemorrhagic stroke (21.1% and 19.8%, respectively), and severe renal failure (13.2% and 10.5%, respectively). COMPASS and VOYAGER-PAD eligible and ineligible patients were at higher risk of ischaemic events than participants in these trials. The one year cumulative incidences were 6.0% (95% CI 4.3 - 8.1) in the COMPASS eligible subset vs. 3.5% (95% CI 2.9 - 4.3) in the COMPASS control arm for major adverse cardiovascular events, and 27.9% (95% CI 19.9 - 38.3) in the VOYAGER-PAD eligible subset vs. 6.0% (95% CI 5.3 - 6.9) in the VOYAGER-PAD control arm for major adverse limb events. CONCLUSION: Many patients hospitalised for symptomatic LEAD in France are not eligible for the low dose rivaroxaban plus aspirin combination. In turn, those eligible may potentially have greater absolute benefit because of higher risk than those enrolled in the trials.

Real-World Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Heterozygous Familial Hypercholesterolemia Patients Referred for Lipoprotein Apheresis.

BACKGROUND A small proportion of familial hypercholesterolemia (FH) patients can adequately control this condition, although achieving the recommended targets for low-density lipoprotein cholesterol (LDL-c) levels remains a challenge. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are new and potent lipid-lowering drugs. However, there is scarce literature on real-world data about their use in patients with FH. MATERIAL AND METHODS We examined the reduction in LDL-c levels from the baseline, after PCSK9i initiation in heterozygous familial hypercholesterolemia patients referred for lipoprotein apheresis in our regional lipid clinic. The study was conducted from March 2018 to September 2019, the period immediately after PCSK9i reimbursement was available in France. PCSK9i was added on top of the patients' maximal tolerated lipid-lowering regimens. RESULTS The study had 123 patients with heterozygous FH. The mean age of the patients was 59±11 years. The mean baseline LDL-c for all the participants was 277±78 mg/dl. It was 283±81 mg/dl in the PCSK9i monotherapy group (n=83), 247±68 mg/dl in the PCSK9i plus ezetimibe group (n=12), and 264±78 mg/dl in the PCSK9i plus statin and ezetimibe group (n=28). The mean decrease observed in the LDL-c level from baseline was 136±70 mg/dl (n=123), 125±60 mg/dl (n=83), 103±77 mg/dl (n=12), and 175±70 mg/dl (n=28), respectively. CONCLUSIONS An overall reduction of 49.1% from the baseline LDL-c was observed in the heterozygous FH population after PCSK9i initiation in a real-world experience. The group treated with PCSK9i ezetimibe plus statin showed further reduction of their LDL-c levels with a better responder rate, achieving the target 50% reduction in LDL-c from the baseline.

Prediction of coronary heart disease incidence in a general male population by circulating non-coding small RNA sRNY1-5p in a nested case-control study.

During the development of atherosclerotic lesion, s-RNYs (small RNAs of about 24/34 nucleotides) are derived by the processing of long Ro-associated non-coding RNAs (RNYs) in macrophages. The levels of serum s-RNYs have been found significantly upregulated in patients with coronary heart disease (CHD) compared to age-matched CHD-free individuals. The present study aimed to examine the predictive value of serum s-RNYs for CHD events in the general male population. Within the frame of nested-case-control study, the GENES study, we measured the absolute expression of a RNY-derived small RNA, the s-RNY1-5p, in the serum of individuals (without CHD at baseline) who encountered a CHD event within 12 years of follow-up (n = 30) (Cases) and compared them to individuals who remained event-free (Controls) (n = 30). The expression of s-RNY1-5p in serum was significantly upregulated in Cases compared to Controls (p = 0.027). The proportion of CHD event-free was significantly higher among individuals with serum s-RNY1-5p below the median value (631 molecules/mL). In a multivariable model adjusted for age, smoking, hypertension, diabetes and dyslipidemia, the risk of CHD events increased more than fourfold in individuals with serum s-RNY1-5p above the median value (HR, 4.36; 95% CI 1.22-15.60). A positive association with CHD events was also observed when considering s-RNY1-5p as a continuous variable (p = 0.022). Based on our results, we conclude that serum s-RNY1-5p is an independent predictor of CHD events in a general male population and might be a relevant biomarker for early detection of cardiovascular diseases.