RESUMEN
BACKGROUND: Long-term control of cardiovascular risk factors after acute coronary syndrome (ACS) is the cornerstone for preventing recurrence. We investigated the extent of cardiovascular risk factor management in males and females with and without familial hypercholesterolemia (FH) 5 years after ACS. METHODS: We studied patients hospitalized for ACS between 2009 and 2017 in a Swiss multicenter prospective cohort study. FH was defined based on clinical criteria from the Dutch Lipid Clinic Network and Simon Broome definitions. Five years post-ACS, we assessed low-density lipoprotein-cholesterol (LDL-c) levels, lipid-lowering therapy (LLT), and other cardiovascular risk factors, comparing males to females with and without FH using generalized estimating equations. RESULTS: A total of 3139 patients were included; mean age was 61.4 years (SD, 12.1), 620 (19.8%) were female, and 747 (23.5%) had possible FH. Compared with males at 5-years post-ACS, females were more likely to not use statins (odds ratio, 1.61 [95% CI, 1.28-2.03]) and less likely to have combination LLT (odds ratio, 0.72 [95% CI, 0.55-0.93]), without difference between patients with FH and without FH. Females in both FH and non-FH groups less frequently reached LDL-c values ≤1.8 mmol/L (odds ratio, 0.78 [95% CI, 0.78-0.93]). Overall, patients with FH were more frequently on high-dose statins compared with patients without FH (51.0% versus 42.9%; P=0.001) and presented more frequently with a combination of 2 or more LLT compared with patients without FH (33.8% versus 17.7%; P<0.001), but less frequently reached LDL-c targets of ≤1.8 mmol/L (33.5% versus 44.3%; P<0.001) or ≤2.6 mmol/L (70.2% versus 78.1%; P=0.001). CONCLUSIONS: Five years after ACS, females had less intensive LLT and were less likely to reach target LDL-c levels than males, regardless of FH status. Males and females with FH had less optimal control of LDL-c despite more frequently taking high-dose statins or combination LLT compared with patients without FH. Long-term management of patients with ACS and FH, especially females, warrants optimization.
Asunto(s)
Síndrome Coronario Agudo , Biomarcadores , LDL-Colesterol , Factores de Riesgo de Enfermedad Cardiaca , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Femenino , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/sangre , Persona de Mediana Edad , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/complicaciones , Factores Sexuales , Anciano , Factores de Tiempo , Estudios Prospectivos , Resultado del Tratamiento , LDL-Colesterol/sangre , Suiza/epidemiología , Medición de Riesgo , Biomarcadores/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Recurrencia , Disparidades en Atención de Salud , Prevención Secundaria , Disparidades en el Estado de SaludAsunto(s)
Proteínas Adaptadoras Transductoras de Señales , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Marcadores Genéticos , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/patología , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologíaRESUMEN
AIMS: This study aimed to evaluate the stepwise approach for cardiovascular (CV) risk factor treatment as outlined by the European Society for Cardiology 2021 guidelines on CV disease (CVD) prevention in patients with established atherosclerotic CVD (ASCVD). METHODS AND RESULTS: In patients with ASCVD, included in UCC-SMART (n = 8730) and European parts of the REACH registry (n = 18 364), the 10-year CV risk was estimated using SMART2. Treatment effects were derived from meta-analyses and trials. Step 1 recommendations were LDL cholesterol (LDLc) < 1.8â mmol/L, systolic blood pressure (SBP) < 140â mmHg, using any antithrombotic medication, sodium-glucose co-transporter 2 (SGLT2) inhibition, and smoking cessation. Step 2 recommendations were LDLc < 1.4â mmol/L, SBP < 130â mmHg, dual-pathway inhibition (DPI, aspirin plus low-dose rivaroxaban), colchicine, glucagon-like peptide (GLP)-1 receptor agonists, and eicosapentaenoic acid. Step 2 was modelled accounting for Step 1 non-attainment. With current treatment, residual CV risk was 22%, 32%, and 60% in the low, moderate, and pooled (very) high European risk regions, respectively. Step 2 could prevent up to 198, 223 and 245 events per 1000 patients treated, respectively. Intensified LDLc reduction, colchicine, and DPI could be applied to most patients, preventing up to 57, 74, and 59 events per 1000 patients treated, respectively. Following Step 2, the number of patients with a CV risk of <10% could increase from 20%, 6.4%, and 0.5%, following Step 1, to 63%, 48%, and 12%, in the respective risk regions. CONCLUSION: With current treatment, residual CV risk in patients with ASCVD remains high across all European risk regions. The intensified Step 2 treatment options result in marked further reduction of residual CV risk in patients with established ASCVD. KEY FINDINGS: Guideline-recommended intensive treatment of patients with cardiovascular disease could prevent additional 198-245 new cardiovascular events for every 1000 patients treated.
Patients with established cardiovascular disease are at high risk for new cardiovascular events. The European Society of Cardiology guideline for the prevention of cardiovascular disease introduced a stepwise treatment approach. Step 1 in this approach are treatments that apply to all patients, and Step 2 are intensive treatments that can be prescribed to patients who are still at high risk of new events even with Step 1 treatments. The current study investigates the effect of Steps 1 and 2 on the risk of cardiovascular disease in 27 094 patients all across Europe. With the conventional treatments of Step 1 the risk of cardiovascular disease remains high, with a 10-year risk of new events higher than 10% in 8099% of patients. The intensive treatment options from Step 2 could prevent additional 198245 new cardiovascular events for every 1000 patients that are treated. With intensive treatment, up to 63% of patients could achieve a 10-year risk of new cardiovascular disease below 10%.
Asunto(s)
Aterosclerosis , Cardiología , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Aterosclerosis/prevención & control , LDL-Colesterol , Factores de Riesgo de Enfermedad Cardiaca , Colchicina , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
AIMS: The HEYMANS study observed patients receiving evolocumab as part of routine clinical hyperlipidemia management. It was designed to capture data on clinical parameters relevant to health authorities and physicians. METHODS: This was a European multi-country observational cohort serial chart review study; data on the Swiss cohort are reported here. Patients were prescribed evolocumab as per the Swiss reimbursement criteria in force at the time and were invited chronologically. The study consisted of a 6-month period prior to initiation of evolocumab, a 12-month core observation period (entered by 75 patients, completed by 74 patients), and an 18-month extended observation period (entered by 40 patients, completed by 34 patients). The primary objective was to describe the clinical characteristics of patients receiving evolocumab. Secondary objectives included to describe lipid levels, evolocumab use, and patterns of use of other lipid-lowering therapies (LLT, that is, statins and/or ezetimibe) over time. The study was conducted in the Swiss cohort between May 2017 and June 2021. RESULTS: Patients who received evolocumab in Swiss routine practice mostly were in secondary prevention (93%) and had a history of statin intolerance (85%) with 53% receiving no background LLT. One-third had familial hypercholesterolemia. Patients initiated evolocumab at a median low-density lipoprotein cholesterol (LDL-C) of 3.6 mmol/L, which decreased by 54% within 3 months to 1.6 mmol/L and was stable thereafter. Overall, 61% achieved the LDL-C goal of <1.4 mmol/L with more patients attaining this goal when they received evolocumab with a statin and/or ezetimibe (84%) compared to 41% when receiving evolocumab alone. An LDL-C reduction of ⩾50% was achieved by 85% of patients. Persistence with evolocumab at 12 months was 85%. CONCLUSION: In Swiss clinical practice, evolocumab was mainly prescribed to patients with very high cardiovascular risk, who had very high LDL-C levels. Most patients continued to use evolocumab throughout the study period. In these patients, LDL-C was reduced by >50% within 3 months and LDL-C reductions were maintained over time. Guideline-recommended LDL-C goals for this very high-risk cohort were more frequently attained in patients receiving a combination of statin and/or ezetimibe and evolocumab. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02770131.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , LDL-Colesterol , Estudios de Cohortes , Ezetimiba/uso terapéutico , SuizaRESUMEN
AIMS: PCSK9 inhibition intensively lowers low density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH. METHODS AND RESULTS: HAUSER-OLE was an 80-week open-label extension of HAUSER-RCT, a randomized, double-blind, 24-week trial evaluating the efficacy and safety of evolocumab in paediatric patients (ages 10-17 years) with FH. During the OLE, all patients received monthly 420â mg subcutaneous evolocumab injections. Tests of psychomotor function, attention, visual learning, and executive function were administered at baseline and Weeks 24 and 80 of the OLE. Changes over time were analysed descriptively and using analysis of covariance. Cohen's d statistic was used to evaluate the magnitude of treatment effects. Analysis of covariance results indicated no decrease in performance across visits during 80 weeks of evolocumab treatment for Groton Maze Learning, One Card Learning accuracy, Identification speed, or Detection speed (all P > 0.05). Performance on all tasks was similar for those who received placebo or evolocumab in the RCT (all P > 0.05). For all tests, the least square mean differences between patients who received placebo vs. evolocumab in the parent study were trivial (all Cohen's d magnitude < 0.2). CONCLUSION: In paediatric patients with FH, 80 weeks of open-label evolocumab treatment had no negative impact on cognitive function. REGISTRATION: ClinicalTrials.gov identifier: NCT02624869.
Some children are born with a genetic disorder that causes high cholesterol, which leads to heart disease. Children with high cholesterol can be treated with evolocumab, a medication that lowers blood cholesterol. Because cholesterol is important for development and adequate function of the brain, there is a concern that lowering cholesterol in children may affect mental ability. In this study, we tested whether treating children with evolocumab for 80 weeks affected mental ability in performing several tasks. A battery of tests that measure executive function (Groton Maze Learning Test), visual learning (One Card Learning Test), visual attention (Identification Test), and psychomotor function (Detection Test) showed no decrease in performance across visits during 80 weeks of evolocumab treatment. Performance on all tasks was similar for the children who received placebo for the first 24 weeks then received evolocumab for an additional 80 weeks (placebo/evolocumab) and those who received evolocumab for 24 weeks then received evolocumab for an additional 80 weeks (evolocumab/evolocumab).
Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticolesterolemiantes , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Niño , Proproteína Convertasa 9 , Anticolesterolemiantes/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Cognición , Resultado del Tratamiento , Método Doble CiegoRESUMEN
BACKGROUND: Acute coronary syndromes (ACS) occurring on rest days have been associated with higher mortality, but the current literature remains inconsistent in this regard. This study included ACS patients presenting with acute decompensated heart failure (ADHF) investigating the relationship between time of coronary catheterization and outcomes. METHODS: Analyses were performed from the prospective, multicentric Special Program University Medicine Acute Coronary Syndromes and Inflammation (SPUM-ACS) Cohort. Patients were divided into two groups according to time of coronary catheterization on either workdays (Monday, 00:00 to Friday, 23:59) or rest days (Saturday, 00:00 to Sunday, 23:59 and public holidays). ADHF was defined by Killip Class III or IV upon presentation. Patients were followed over 1 year. RESULTS: Out of 4787 ACS patients enrolled in the SPUM-ACS Cohort, 207 (4.3%) presented with ADHF. 52 (25.1%) and 155 (74.9%) patients underwent coronary angiography on rest days or workdays, respectively. Baseline characteristics were similar among these groups. ACS patients with ADHF showed increased 1-year mortality on rest days (34.6% vs. 17.4%, p-value = 0.009). After correction for baseline characteristics, including the GRACE 2.0 Score, rest day presentation remained a significant predictor for 1-year mortality (adjusted hazard ratio = 2.42 [95% confidence interval: 1.14-5.17], p-value = 0.022). CONCLUSIONS: One-year all-cause mortality was high in ACS patients with ADHF and doubled for patients admitted on rest days. The present data support the association of a rest day effect and long-term patient survival and indicate a need for further investigations.
Asunto(s)
Síndrome Coronario Agudo , Insuficiencia Cardíaca , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Estudios Prospectivos , Resultado del Tratamiento , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Modelos de Riesgos ProporcionalesRESUMEN
AIM: To evaluate the risk of alcohol consumption after acute coronary syndromes (ACS). METHODS: A total of 6557 patients hospitalized for ACS at 4 Swiss centres were followed over 12 months. Weekly alcohol consumption was collected at baseline and 12 months. Binge drinking was defined as consumption of ≥6 units of alcohol on one occasion. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, stroke or clinically indicated target vessel coronary revascularization. Cox regression analysis was performed to assess the risk of MACE in patients with heavy (>14 standard units/week), moderate (7-14 standard units per week), light consumption (<1 standard unit/week) or abstinence, and with binge drinking episodes, adjusted for baseline differences. RESULTS: At baseline, 817 (13.4%) patients reported heavy weekly alcohol consumption. At one-year follow-up, 695/1667 (41.6%) patients reported having at least one or more episodes of binge drinking per month. The risk for MACE was not significantly higher in those with heavy weekly consumption compared to abstinence (8.6% vs. 10.2%, HR 0.97, 95%CI 0.69-1.36) or light consumption (8.6% vs. 8.5 %, HR 1.41, 95%CI 0.97-2.06). Compared to patients with no-binge drinking, the risk of MACE was dose-dependently higher in those with binge drinking with less than one episode per month (9.2% vs 7.8%, HR 1.61, 95%CI 1.23-2.11), or one or more episodes per month (13.6% vs 7.8%, HR 2.17, 95%CI 1.66-2.83). CONCLUSION: Binge drinking during the year following an ACS, even less than once per month, is associated with worse clinical outcomes.
The cardiovascular risk of alcohol consumption and of binge drinking episodes after acute coronary syndrome (ACS) has not been established. Our data suggested the following: After ACS, regular weekly alcohol consumption is not associated with the risk of major adverse cardiovascular events (MACE), except for patients reporting binge drinking who have a two-fold increased risk of MACE within one year of the index event.After ACS, episodes of binge drinking, even less than once per month, are associated with worse clinical outcomes. It is not the frequency, but rather the quantity of alcohol intake in a binge drinking episode, that is associated with worse prognosis in patients after an ACS.
RESUMEN
Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, the disease entity has been associated with cardiovascular complications. This study sought to assess the effect of concomitant SARS-COV-2 infection on clinical outcomes of patients hospitalized primarily for acute cardiac conditions on cardiology wards in Switzerland. Methods: In this prospective, observational study conducted in 5 Swiss cardiology centers during the COVID-19 pandemic, patients hospitalized due to acute cardiac conditions underwent a reverse-transcriptase polymerase chain reaction test at the time of admission and were categorized as SARS-COV-2 positive (cases) or negative (controls). Patients hospitalized on cardiology wards underwent treatment for the principal acute cardiac condition according to local practice. Clinical outcomes were recorded in-hospital, at 30 days, and after 1 year and compared between cases and controls. To adjust for imbalanced baseline characteristics, a subgroup of patients derived by propensity matching was analyzed. Results: Between March 2020 and February 2022, 538 patients were enrolled including 122 cases and 416 controls. Mean age was 68.0 ± 14.7 years, and 75% were men. Compared with controls, SARS-COV-2-positive patients more commonly presented with acute heart failure (35% vs. 17%) or major arrhythmia (31% vs. 9%), but less commonly with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases vs. controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%: p < 0.001 for all); this was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, and was accompanied by a greater incidence of worsening renal function in cases vs. controls. These findings were maintained in a propensity-matched subgroup of 186 patients (93 cases and 93 controls) with balanced clinical presentation and baseline characteristics. Conclusions: In this observational study of patients hospitalized for acute cardiac conditions, SARS-COV-2 infection at index hospitalization was associated with markedly higher all-cause and non-cardiovascular mortality throughout one-year follow-up. These findings highlight the need for effective, multifaceted management of both cardiac and non-cardiac morbidities and prolonged surveillance in patients with acute cardiac conditions complicated by SARS-COV-2 infection.
RESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease increasing cardiovascular disease (CVD) morbidity and mortality. Autoantibodies against apolipoprotein A-1 (AAA-1) are a possible novel CVD risk factor promoting inflammation and disrupting cellular lipid homeostasis, two prominent pathogenic features of NAFLD. We explored the role of AAA-1 in NAFLD and their association with CVD risk. METHODS: HepaRG cells and liver sections from ApoE-/- mice exposed to AAA-1 were used for lipid quantification and conditional protein expression. Randomly selected sera from 312 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND) general population cohort were used to measure AAA-1. A Fatty Liver Index (FLI) ≥ 60 and a 10-year Framingham Risk Score (FRS) ≥ 20% were used as proxy of NAFLD and high CVD risk, respectively. RESULTS: In-vitro and mouse models showed that AAA-1 increased triglyceride synthesis leading to steatosis, and promoted inflammation and hepatocyte injury. In the 112 PREVEND participants with FLI ≥ 60, AAA-1 were associated with higher FRS, alkaline phosphatase levels, lower HDL cholesterol and tended to display higher FLI values. Univariate linear and logistic regression analyses (LRA) confirmed significant associations between AAA-1, FLI and FRS ≥ 20%, while in adjusted LRA, FLI was the sole independent predictor of FRS ≥ 20% (OR: 1.05, 95%CI 1.01-1.09, P = 0.003). AAA-1 was not an independent FLI predictor. CONCLUSIONS: AAA-1 induce a NAFLD-compatible phenotype in vitro and in mice. Intricate associations exist between AAA-1, CVD risk and FLI in the general population. Further work is required to refine the role of AAA-1 in NAFLD and to determine if the AAA-1 association with CVD is affected by hepatic steatosis.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Factores de Riesgo , Enfermedades Cardiovasculares/complicaciones , Apolipoproteína A-I , Ratones Noqueados para ApoE , Inflamación/complicaciones , Factores de Riesgo de Enfermedad CardiacaRESUMEN
AIMS: The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-ß superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing. METHODS AND RESULTS: In contrast to endogenous Mstn, myocardial Gdf11 declined during the course of ageing and was particularly reduced following ischaemia/reperfusion (I/R) injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by recombinant GDF11 delivery (0.1â mg/kg body weight over 30 days) prior to myocardial I/R augmented myocardial infarct size in C57BL/6 mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. While intrinsic cardioprotective signalling pathways remained unaffected by high circulating GDF11, targeted transcriptomics and immunomapping studies focusing on GDF11-associated downstream targets revealed attenuated Nkx2-5 expression confined to CD105-expressing cells, with pro-apoptotic activity, as assessed by caspase-3 levels, being particularly pronounced in adjacent cells, suggesting an indirect effect. By harnessing a highly specific and validated liquid chromatography-tandem mass spectrometry-based assay, we show that in prospectively recruited patients with MI circulating GDF11 but not MSTN levels incline with age. Moreover, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event, with circulating GDF11 emerging as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels. CONCLUSION: Our data challenge the initially reported heart rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice and humans alike. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of cardioprotective mechanisms and thus poor outcomes of elderly patients following acute MI.
Asunto(s)
Factores de Diferenciación de Crecimiento , Lesiones Cardíacas , Infarto del Miocardio , Anciano , Animales , Humanos , Ratones , Envejecimiento/metabolismo , Proteínas Morfogenéticas Óseas , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/metabolismo , Corazón , Lesiones Cardíacas/complicaciones , Lesiones Cardíacas/metabolismo , Ratones Endogámicos C57BL , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismoRESUMEN
BACKGROUND: Carnitine metabolism produces numerous molecular species of short-, medium-, and long-chain acylcarnitines, which play important roles in energy homeostasis and fatty acid transport in the myocardium. Given that disturbances in the carnitine metabolism are linked to cardiometabolic disease, we studied the relationship of circulating acylcarnitines with outcomes in patients with acute coronary syndromes (ACS) and evaluated differences in circulating levels of these metabolites between diabetic and non-diabetic patients. METHODS: Harnessing a prospective multicentre cohort study (SPUM-ACS; NCT01000701), we measured plasma levels of acylcarnitines, carnitine, and carnitine metabolites to assess their relationship with adjudicated major adverse cardiac events (MACE), defined as composite of myocardial infarction, stroke, clinically indicated revascularization, or death of any cause. The SPUM-ACS study enrolled patients presenting with ACS to Swiss University Hospitals between 2009 and 2012. Acetylcarnitine, octanoylcarnitine, proprionylcarnitine, butyrylcarnitine, pentanoylcarnitine, hexanoylcarnitine, carnitine, γ-butyrobetaine, and trimethylamine N-oxide were measured in plasma using stable isotope dilution high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. RESULTS: A total of 1683 patients with ACS were included in the study. All measured metabolites except γ-butyrobetaine and carnitine were higher in diabetic subject (n = 294) than in non-diabetic subjects (n = 1389). On univariate analysis, all metabolites, apart from octenoylcarnitine, were significantly associated with MACE at 1 year. After multivariable adjustment for established risk factors, acetylcarnitine remained an independent predictor of MACE at 1-year (quartile 4 vs. quartile 1, adjusted hazard ratio 2.06; 95% confidence interval 1.12-3.80, P = 0.020). CONCLUSION: Circulating levels of acetylcarnitine independently predict residual cardiovascular risk in patients with ACS.
Asunto(s)
Síndrome Coronario Agudo , Diabetes Mellitus , Humanos , Acetilcarnitina , Síndrome Coronario Agudo/diagnóstico , Carnitina , Estudios de Cohortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Estudios Clínicos como AsuntoRESUMEN
Importance: The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury. Objective: To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury. Design, Setting, and Participants: This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023. Exposures: In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE). Main Outcomes and Measures: The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event. Results: Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-year mortality: AUC, 0.785 vs 0.778; NRI, 0.078) in the derivation cohort. These findings were confirmed in the validation cohort. In the pooled population of 9450 patients, modified GRACE risk score showed superior performance compared with the original GRACE risk score in terms of reclassification and discrimination for in-hospital mortality end point (AUC, 0.878 vs 0.780; NRI, 0.097), 30-day mortality end point (AUC, 0.858 vs 0.771; NRI, 0.08), and 1-year mortality end point (AUC, 0.813 vs 0.797; NRI, 0.056). Conclusions and Relevance: In this study, using continuous rather than binary hs-cTn T at presentation, a proxy of the extent of myocardial injury, in the GRACE risk score improved the mortality risk prediction in patients with ACS.
Asunto(s)
Síndrome Coronario Agudo , Medición de Riesgo , Infarto del Miocardio con Elevación del ST , Troponina T , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/terapia , Estudios Longitudinales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico , Troponina T/sangre , AncianoRESUMEN
BACKGROUND AND AIMS: Low-density lipoprotein (LDL)-cholesterol (LDL-C) promotes atherosclerotic cardiovascular disease (ASCVD), with changes in LDL electronegativity modulating its pro-atherogenic/pro-thrombotic effects. Whether such alterations associate with adverse outcomes in patients with acute coronary syndromes (ACS), a patient population at particularly high cardiovascular risk, remains unknown. METHODS: This is a case-cohort study using data from a subset of 2619 ACS patients prospectively recruited at four university hospitals in Switzerland. Isolated LDL was chromatographically separated into LDL particles with increasing electronegativity (L1-L5), with the L1-L5 ratio serving as a proxy of overall LDL electronegativity. Untargeted lipidomics revealed lipid species enriched in L1 (least) vs. L5 (most electronegative subfraction). Patients were followed at 30 days and 1 year. The mortality endpoint was reviewed by an independent clinical endpoint adjudication committee. Multivariable-adjusted hazard ratios (aHR) were calculated using weighted Cox regression models. RESULTS: Changes in LDL electronegativity were associated with all-cause mortality at 30 days (aHR, 2.13, 95% CI, 1.07-4.23 per 1 SD increment in L1/L5; p=.03) and 1 year (1.84, 1.03-3.29; p=.04), with a notable association with cardiovascular mortality (2.29; 1.21-4.35; p=.01; and 1.88; 1.08-3.28; p=.03). LDL electronegativity superseded several risk factors for the prediction of 1-year death, including LDL-C, and conferred improved discrimination when added to the updated GRACE score (area under the receiver operating characteristic curve 0.74 vs. 0.79, p=.03). Top 10 lipid species enriched in L1 vs. L5 were: cholesterol ester (CE) (18:2), CE (20:4), free fatty acid (FA) (20:4), phosphatidyl-choline (PC) (36:3), PC (34:2), PC (38:5), PC (36:4), PC (34:1), triacylglycerol (TG) (54:3), and PC (38:6) (all p < .001), with CE (18:2), CE (20:4), PC (36:3), PC (34:2), PC (38:5), PC (36:4), TG (54:3), and PC (38:6) independently associating with fatal events during 1-year of follow-up (all p < .05). CONCLUSIONS: Reductions in LDL electronegativity are linked to alterations of the LDL lipidome, associate with all-cause and cardiovascular mortality beyond established risk factors, and represent a novel risk factor for adverse outcomes in patients with ACS. These associations warrant further validation in independent cohorts.
Asunto(s)
Síndrome Coronario Agudo , Aterosclerosis , Humanos , LDL-Colesterol , Estudios de Cohortes , Triglicéridos , Colesterol , Aterosclerosis/epidemiología , Factores de RiesgoRESUMEN
In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical development. This advice counters the attitude: "Why should I measure Lp(a) if I can't lower it?". Subsequent to publication, questions have arisen relating to how the recommendations of this statement impact everyday clinical practice and ASCVD management. This review addresses 30 of the most frequently asked questions about Lp(a) epidemiology, its contribution to cardiovascular risk, Lp(a) measurement, risk factor management and existing therapeutic options.
Asunto(s)
Estenosis de la Válvula Aórtica , Aterosclerosis , Enfermedades Cardiovasculares , Humanos , Lipoproteína(a) , Factores de Riesgo , Medición de Riesgo , Estenosis de la Válvula Aórtica/complicaciones , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & controlRESUMEN
BACKGROUND: Patients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. METHODS: Among ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. RESULTS: Out of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14-2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71-1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. CONCLUSIONS: In this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention.