Associations of Dietary Intake with Cardiovascular Risk in Long-Term "Plant-Based Eaters": A Secondary Analysis of a Cross-Sectional Study.

A plant-based diet rich in whole foods and fiber is beneficial for cardiovascular (CV) health. This impact is often linked to specific food groups and their preparation methods, reflecting the overall dietary pattern. However, research on the long-term effects of a carefully designed plant-based diet on adults transitioning from a typical Western lifestyle is limited. Notably, studies on people managing CV risk factors effectively are scarce. As part of a cross-sectional study, we examined 151 individuals committed to a long-term, well-designed plant-based diet and active lifestyle. We investigated how specific food groups and macronutrient intake are related to various CV health markers. In this secondary analysis, our comprehensive approach encompassed several methods: 3-day weighted dietary records, fasting blood lipid and blood pressure measurements, body composition assessments, and evaluations of lifestyle status. We adjusted our analysis for multiple variables, such as age, sex, current body mass index, smoking status, physical activity, and time (years) following the plant-based diet. Our findings revealed several associations between macronutrient intake (per 50 g) and CV risk markers, although these associations were generally weak. Individuals who consumed more whole grains and fruits had lower levels of total, low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) cholesterol. We also found associations between the intake of legumes and nuts/seeds and reduced HDL-C levels. These findings suggested that these food groups might influence the lipid profile, contributing to CV health in a plant-based diet. A greater intake of spices/herbs was associated with lower uric acid levels, while diets rich in plant-based fast food and pasta (made from white flour) were associated with higher uric acid levels. A greater intake of various macronutrients, such as fiber, carbohydrates (from whole-food sources), proteins, and different types of fats (saturated fatty acids [SFAs], monounsaturated fatty acids [MUFAs], and polyunsaturated fatty acids [PUFAs]), was associated with lower levels of total cholesterol, LDL-C (only for carbohydrates), and HDL-C. We found a unique negative correlation between PUFA intake and LDL-C, suggesting that PUFAs might significantly affect LDL-C levels. In contrast, increased fiber, protein and SFA consumption were associated with increased uric acid levels. These findings support the impact of dietary patterns on CV risk factors, highlighting that even small amounts of unhealthy food groups can significantly influence specific CV risk markers, regardless of the overall diet.

Lipid Disorders Management Strategies (2024) in Prediabetic and Diabetic Patients.

Dyslipidaemia is a modifiable risk factor commonly associated with diabetes mellitus and prediabetes, with a major impact on the early development of atherosclerotic cardiovascular disease. Various studies have tried to identify the key treatment targets, their optimal values according to patients' CV risk, and the most efficient yet safe therapeutic agents which, alongside lifestyle changes, would improve lipid levels and reduce cardiovascular mortality and morbidity. Currently, there are multiple pharmacologic options that can be used in the management of dyslipidaemia, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, n-3 polyunsaturated fatty acids or fibrates, to name only a few, while many other are under development. In the current setting of a continuously increasing population of patients with metabolic disorders, this review aims to summarise current knowledge regarding lipid disorders and the recommendations of recent guidelines in treating dyslipidaemia in patients with diabetes mellitus or prediabetes.

Prognostic impact of optimal lifestyle advice and medical therapy in patients with peripheral arterial disease.

Background: Secondary prevention remains under-implemented in patients with peripheral arterial disease (PAD). In the present study, we sought to assess the extent, the predictors and the prognostic impact of optimal lifestyle advice (OLA) and optimal medical therapy (OMT) given at discharge to patients with PAD undergoing invasive peripheral procedures. Patients and methods: We included consecutive patients with PAD undergoing invasive peripheral procedures, between 2012 and 2013. Data were obtained from a mandatory fill-in clinical pathway. The primary outcome was all-cause mortality, verified using the National Mortality Registry. Results: A total of 2014 participants were included (mean age 70±11 years, 38.1% women). OLA was given to 279 (14%), OMT to 1186 (59%) participants. Male gender and absence of chronic limb-threatening ischaemia were significant predictors of OLA and OMT. During the median follow-up of 729 days (interquartile range 645) 392 (19.5%) participants died giving an overall mortality rate of 97/1000 patient years. On multivariate analysis both OLA and OMT emerged as independent predictors of survival (HR for all-cause mortality: 0.59; 95% CI: 0.42-0.82, p 0.005 and HR: 0.41; 95% CI: 0.22-0.76, p 0.002). Conclusions: OLA and OMT are associated with better long-term prognosis in patients with PAD, however they are still under-implemented, suggesting a considerable potential for improvement, especially in women.

Vegan Diets for Children: A Narrative Review of Position Papers Published by Relevant Associations.

The scientific discourse on vegan diets for children and adolescents primarily involves referencing position statement papers from different scientific and professional organizations, including paediatric associations. Over the past two decades, specialized associations have issued official statements and published position papers about adopting well-designed vegan diets during crucial life stages, including pregnancy and lactation, infancy, and childhood. A subset of these associations firmly supports the notion that a well-designed vegan diet can indeed be healthy and support normal growth and development during particularly delicate life stages, emphasizing careful planning, vitamin B12 supplementation, and regular supervised medical and dietetics oversight. In contrast, specific paediatric associations caution against vegan diets for children and adolescents, citing potential harm and the lack of adequate substantiation. These criticisms in position papers frequently point to lower-quality studies and/or outdated studies. Additionally, concerns extend to comparing vegan and omnivorous diets, considering public health issues such as obesity and early stages of cardiovascular disease as well as the risk of prediabetes and type 2 diabetes. Notably, some scepticism stems from studies where children's adherence to a well-designed vegan diet is incomplete. Scientific rigor suggests performing a comparable assessment of omnivorous and vegan diets. This narrative review highlights the need for a comprehensive, up-to-date literature review to inform balanced perspectives on vegan diets for children and adolescents. Researchers and decision-makers should aim to actively improve the design and consistent implementation of both diet types.

The Activities of the Slovenian Strategic Council for Nutrition 2023/24 to Improve the Health of the Slovenian Population and the Sustainability of Food: A Narrative Review.

The health status of individuals in Slovenia across age groups is a matter of concern, as current unsustainable lifestyle choices are already leading to various chronic noncommunicable diseases (NCDs). Outdated national dietary guidelines, their inconsistent implementation, and a lack of structural changes represent obstacles to promoting healthy and sustainable nutrition. Limited access to and rising prices of healthy, sustainable foods, in addition to the high availability of low-priced, highly processed foods, increase the risk of NCDs. The lack of systematic health monitoring and early disease detection poses a challenge. Global and local environmental issues, resistance, and/or the inability to adopt healthier diets hinder individuals from changing their nutritional behaviours. In this narrative review, we provide an overview of the current situation in Slovenia as well as planned activities initiated by the Slovenian government and the Prime Minister's Strategic Council for Nutrition, aiming to make progress in supporting healthy and sustainable nutrition, limiting food waste, and increasing the availability of healthier foods for all. Improving the sustainability of the Slovenian food system can contribute to several Sustainable Development Goals (SDGs), ensuring Slovenia's commitment to internationally agreed-upon targets. This could lead Slovenia to take a role as a pilot country in testing and implementing the necessary systemic changes, which could be further applied in other countries.

Effects of statins on the incidence and outcomes of acute kidney injury in critically ill patients: a systematic review and meta-analysis.

Introduction: In critically ill patients, acute kidney injury (AKI) is a common complication with very high mortality rates. Several studies indicated that statin therapy, primarily due to its so-called pleiotropic effects, may beneficially affect the course of the disease, otherwise leading to significant clinical complications. However, both the original research as well as available meta-analyses on these associations report equivocal results. This leaves open a question whether pre- and perioperative statins might prevent AKI and improve overall prognosis in patients undergoing surgery. Material and methods: Following a systematic search of the literature, we performed a meta-analysis of selected clinical studies investigating the impact of statin treatment on the development and the clinical outcomes of AKI among subjects undergoing surgeries. The pooled odds ratios (OR) with 95% confidence intervals (CI) for the development of AKI and AKI-associated mortality, as well as the pooled mean differences (MD) and 95% CI for mean intensive care unit (ICU) stay and overall hospital length of stay were calculated for statin users compared to non-users. Results: Our results showed a highly significant association between statin use and the decrease in mortality of patients with AKI (OR = 0.73, 95% CI: 0.69-0.77; p<0.001). The development of AKI (OR = 0.92, 95% CI: 0.63-1.33; p = 0.659) as well as the ICU stay (MD = -0.02, 95% CI: -0.06 - 0.02; p = 0.321) were not significantly affected, while the overall hospital length of stay (MD = -0.49, 95% CI: -0.91 -0.07; p = 0.020) was reduced. Subgroup analysis showed that both pre- and postoperative statin use were not associated with the risk of AKI. Conclusions: Our analysis showed a significant association between statin therapy and overall mortality of critically ill surgical patients diagnosed with AKI, while at the same time the use of statins did not affect the length of their stay in ICU.

Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP).

Cardiovascular disease (CVD) is a chronic non-communicable disease (NCD) and the predominant cause of morbidity and mortality worldwide. Substantial reductions in the CVD prevalence have been achieved in recent years by the attenuation of risk factors (particularly hypertension and dyslipidaemias) in primary and secondary prevention. Despite the remarkable success of lipid lowering treatments, and of statins in particular, in reducing the risk of CVD, there is still an unmet clinical need for the attainment of guideline lipid-targets in even 2/3 of patients. Bempedoic acid, the first in-class inhibitor of ATP-citrate lyase presents a new approach to lipid-lowering therapy. By reducing the endogenous production of cholesterol, upstream of the rate-limiting enzyme HMG-CoA-reductase, i.e., the target of statins, bempedoic acid reduces circulating plasma concentrations of low-density lipoprotein cholesterol (LDL-C), and major adverse CVD events (MACE). Bempedoic acid has the potential to contribute to the reduction of CVD risk not only as monotherapy, but even further as part of a lipid-lowering combination therapy with ezetimibe, reducing LDL-C cholesterol up to 40%. This position paper of the International Lipid Expert Panel (ILEP) summarises the recent evidence around the efficacy and safety of bempedoic acid and presents practical recommendations for its use, which complement the 'lower-is-better-for-longer' approach to lipid management, which is applied across international guidelines for the management of CVD risk. Practical evidence-based guidance is provided relating to the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia, and statin intolerance. Although there are still no sufficient data avilable for the role of bempedoic acid in the primary prevention of CVD, its favourable effects on plasma glucose and inflammatory markers makes this drug a rational choice in the patient-centred care of specific groups of primary prevention.

Transiently achieved very low LDL-cholesterol levels by statin and alirocumab after acute coronary syndrome are associated with cardiovascular risk reduction: the ODYSSEY OUTCOMES trial.

AIMS: Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus PCSK9 inhibitor. METHODS AND RESULTS: In 18,924 patients post-acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score-matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median 8.3 months from randomization, after a median 6.0 months with LDL-C < 0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C versus 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). CONCLUSIONS: A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01663402.

Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022).

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group.

Similar clinical outcomes with transcatheter aortic valve implantation and surgical aortic valve replacement in octogenarians with aortic stenosis.

Background: Transcatheter aortic valve implantation (TAVI) is the preferred treatment option for severe aortic stenosis in the elderly and in patients with comorbidities. We sought to compare outcomes after TAVI and surgical aortic valve replacement (SAVR) in octogenarians. Methods: In this retrospective cohort study conducted at our tertiary center, clinical data were gathered before and after TAVI and SAVR procedures performed from January 2013 to May 2019; follow-up completed in March 2021. The primary outcome was 1-year mortality. Patients were stratified according to Society of Thoracic Surgeons (STS) score and procedure type. Propensity score-based matching was also performed. Results: Of 542 patients who matched the inclusion criteria, 273 underwent TAVI and 269 SAVR. TAVI patients were older (85.8 ± 3.0 vs. 82.2 ± 2.2 years; P < 0.001) and had a higher mean STS score (5.0 ± 4.0 vs. 2.8 ± 1.3; P < 0.001) and EuroSCORE II (5.3 ± 4.1 vs. 2.8 ± 6.0; P < 0.001). Rates of postoperative permanent pacemaker insertion (15.0% vs. 9.3%; P = 0.040) and paravalvular leak (9.9% vs. 0.8%; P < 0.001) were higher and acute kidney injury lower (8.8% vs. 32.7%; P < 0.001) after TAVI, with no difference between treatment groups for major bleeding (11.0% vs. 6.7%; P = 0.130) or 30-day mortality (5.5% vs. 3.7%; P = 0.315). A statistically significant difference was found between TAVI and SAVR in low- and intermediate-risk groups when it came to occurrence of paravalvular leak, acute kidney injury, and new onset AF (all P < 0.001). Conclusion: This analysis of an octogenarian "real-life" population undergoing TAVI or SAVR (with a biological valve) showed similar outcomes regarding clinical endpoints in low- and medium-risk (STS score) groups.

Effects of Cardiac Rehabilitation and Diet Counselling on Adherence to the Mediterranean Lifestyle in Patients after Myocardial Infarction.

Adherence to the Mediterranean lifestyle­as captured by the Medlife Index Questionnaire (i.e., encompassing a Mediterranean diet as well as other aspects of healthy living, such as food preparation, physical activity, and socializing)­has been associated with reduced cardiovascular events in healthy individuals. In the present study, we sought to determine the adherence to, and the effect of comprehensive cardiac rehabilitation on, Mediterranean lifestyle adherence in patients after myocardial infarction. We included 121 patients (mean age, 55 years; women, 37%) undergoing comprehensive cardiac rehabilitation­i.e., exercise training 3 times per week for 12 weeks plus dedicated workshops promoting the Mediterranean lifestyle. Before and after cardiac rehabilitation, patients completed the Medlife Index Questionnaire. High baseline adherence was associated with favourable glucose (5.39 vs. 6.1 mmol/L; p < 0.001), triglycerides (1.1 vs. 1.5 mmol/L; p = 0.002), and HDL cholesterol levels (1.32 vs. 1.12 mmol/L; p = 0.032). More importantly, the Medlife Score significantly improved following comprehensive cardiac rehabilitation in patients with low baseline adherence (from 13.8 to 16.7 points; p < 0.001), but not in patients with high baseline adherence (from 19.4 to 18.8 points; p = 0.205). Our findings suggested that Mediterranean lifestyle promotion during cardiac rehabilitation improved adherence to the Mediterranean lifestyle, especially in low-adherence patients.

Association between the rs2279238 of the Liver X receptor alpha gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort.

BACKGROUND: Liver X receptor alpha (LXRA) plays important role in cholesterol and lipid homeostasis and lipid metabolism; moreover, it has been investigated as a candidate gene in a number of conditions, including onset and progression of atherosclerosis. We hypothesized that the LXRA gene rs2279238 polymorphism may be associated with the onset and progression of carotid atherosclerosis in the Slovenian cohort. METHODS: 783 unrelated Slovenian patients were included in this cross-sectional case-control study: 308 patients in the group of cases with severe internal carotid artery (ICA) stenosis (>75 %) and 475 patients with hemodynamically insignificant ICA stenosis (<50 %) in the control group. Medical records were used to acquire patient laboratory and clinical data. The TaqMan SNP Genotyping assay was used to genotype the rs2279238 polymorphism. RESULTS: Between the case and control groups, we identified a statistically significant variation in genotype distribution (p = 0.04), but not in allele frequency (p = 0.13) of the LXRA gene polymorphism rs2279238. The results, also show that there is a statistically significant association (p = 0.04) between the two genetic models (codominant and recessive) of the LXRA gene rs2279238 polymorphism and carotid atherosclerosis. CONCLUSION: In the Slovenian cohort, we found a significant association between the TT genotype of rs2279238 and advanced carotid artery disease, suggesting that this polymorphism might be a genetic risk factor for ICA atherosclerosis.

Translating results from the cardiovascular outcomes trials with glucagon-like peptide-1 receptor agonists into clinical practice: Recommendations from a Eastern and Southern Europe diabetes expert group.

Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice.

Preclinical atherosclerosis and cardiovascular events: Do we have a consensus about the role of preclinical atherosclerosis in the prediction of cardiovascular events?

Atherosclerosis has a long preclinical phase, and the risk of cardiovascular (CV) events may be high in asymptomatic subjects. Conventional risk factors provide information for the statistical probability of developing CV events, but they lack precision in asymptomatic subjects. This review aims to summarize the role of some widely publicized indicators of early atherosclerosis in predicting CV events. The earliest measurable indicator of the atherosclerotic process is endothelial dysfunction, measured by flow-mediated dilation (FMD) of the brachial artery. However, reduced FMD is a stronger predictor of future CV events in patients with existing CV disease than in apparently healthy persons. Alternatively, measurement of carotid artery intima-media thickness does not improve the predictive value of risk factor scores, while detection of asymptomatic atherosclerotic plaques in carotid or common femoral arteries by ultrasound indicates high CV risk. Coronary calcium is a robust and validated help in the estimation of vascular changes and risk, which may improve risk stratification beyond traditional risk factors with relatively low radiation exposure. Arterial stiffness of the aorta, measured as the carotid-femoral pulse wave velocity is an independent marker of CV risk at the population level, but it is not recommended as a routine procedure because of measurement difficulties. Low ankle-brachial index (ABI) indicates flow-limiting atherosclerosis in the lower limbs and indicates high CV risk, while normal ABI does not rule out advanced asymptomatic atherosclerosis. Novel circulating biomarkers are associated with the atherosclerotic process. However, because of limited specificity, their ability to improve risk classification at present remains low.

Potential for optimizing management of obesity in the secondary prevention of coronary heart disease.

AIMS: Prevention guidelines have identified the management of obese patients as an important priority to reduce the burden of incident and recurrent cardiovascular disease. Still, studies have demonstrated that over 80% of patients with coronary heart disease (CHD) fail to achieve their weight target. Here, we describe advice received and actions reported by overweight CHD patients since being discharged from hospital and how weight changes relate to their risk profile. METHODS AND RESULTS: Based on data from 10 507 CHD patients participating in the EUROASPIRE IV and V studies, we analysed weight changes from hospital admission to the time of a study visit ≥6 and <24 months later. At hospitalization, 34.9% were obese and another 46.0% were overweight. Obesity was more frequent in women and associated with more comorbidities. By the time of the study visit, 19.5% of obese patients had lost ≥5% of weight. However, in 16.4% weight had increased ≥5%. Weight gain in those overweight was associated with physical inactivity, non-adherence to dietary recommendations, smoking cessation, raised blood pressure, dyslipidaemia, dysglycaemia, and lower levels of quality of life. Less than half of obese patients was considering weight loss in the coming month. CONCLUSIONS: The management of obesity remains a challenge in the secondary prevention of CHD despite a beneficial effect of weight loss on risk factor prevalences and quality of life. Cardiac rehabilitation programmes should include weight loss interventions as a specific component and the incremental value of telehealth intervention as well as recently described pharmacological interventions need full consideration.

Exercise capacity improvement after cardiac rehabilitation following myocardial infarction and its association with long-term cardiovascular events.

AIMS: Cardiovascular rehabilitation (CR) improves aerobic capacity and quality of life in patients after myocardial infarction (MI). The aim was to examine the associations between exercise capacity improvement and different clinically relevant cardiovascular events. METHODS AND RESULTS: This was a registry-based study of post-MI patients, referred to CR. All patients were submitted to exercise testing before and after CR (36 sessions, 2-3 times/week, and combined exercise). Patients were divided into two groups, based on the difference in exercise capacity before and after the CR programme with the cut-off of two metabolic equivalents (METs) improvement. We assessed the correlation between the extent of exercise capacity improvement and the following cardiovascular events: major adverse cardiac events (MACE), cardiovascular-related hospitalizations, and unplanned coronary angiography. A total of 499 patients were included (mean age 56 ± 10 years, 20% women). Both groups significantly improved in terms of exercise capacity, natriuretic peptide levels, resting heart rate, and resting diastolic pressure; however, lipid status significantly improved only in patients with ≥2 METs difference in exercise capacity. A total of 13.4% patients suffered MACE (median follow-up 858 days); 21.8% were hospitalized for cardiovascular reasons (median follow-up 791 days); and 19.8% had at least one unplanned coronary angiography (median follow-up 791 days). Exercise capacity improvement of ≥2 METs was associated with lower rates of MACE, cardiovascular hospitalizations, and unplanned coronary angiography in all examined univariate and multivariate models. CONCLUSION: This study has shown that exercise improvement of ≥2 METs is associated with a significant decrease in MACE, cardiac hospitalizations, and unplanned coronary angiography.

Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model.

AIMS: Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years. METHODS AND RESULTS: Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD. CONCLUSION: In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.

CRISPR Gene Editing in Lipid Disorders and Atherosclerosis: Mechanisms and Opportunities.

Elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C) have been conclusively demonstrated in epidemiological and intervention studies to be causally associated with the development of atherosclerotic cardiovascular disease. Enormous advances in LDL-C reduction have been achieved through the use of statins, and in recent years, through drugs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of the hepatic LDL-receptor. Existing approaches to PCSK9 targeting have used monoclonal antibodies or RNA interference. Although these approaches do not require daily dosing, as statins do, repeated subcutaneous injections are nevertheless necessary to maintain effectiveness over time. Recent experimental studies suggest that clustered regularly interspaced short palindromic repeats (CRISPR) gene-editing targeted at PCSK9 may represent a promising tool to achieve the elusive goal of a 'fire and forget' lifelong approach to LDL-C reduction. This paper will provide an overview of CRISPR technology, with a particular focus on recent studies with relevance to its potential use in atherosclerotic cardiovascular disease.

Correction: Complete Revascularization and Survival in STEMI.

[This corrects the article DOI: 10.5334/gh.1040.].

Complete Revascularization and Survival in STEMI.

Background: Complete revascularization (CR) of ST-elevation myocardial infarction patients with multivessel coronary artery disease (MVD) has proven better regarding combined endpoints than incomplete revascularization (IR) in recent randomized control trials with no impact on survival. Objective: To retrospectively evaluate the impact of complete CR during the index hospitalization on survival in STEMI patients with MVD. Methods and results: We included all patients with MVD who underwent successful primary percutaneous coronary intervention for STEMI during their index hospitalization at the University Medical Centre Ljubljana, Slovenia (from 1 January 2009 to 3 April 2011). Coronary angiograms were reviewed for non-culprit coronary arteries (>2 mm in diameter and ≥50% stenosis) treated with percutaneous coronary intervention. Rates of all-cause and cardiovascular death were compared between 235 patients who underwent CR (N = 70) or IR (N = 165). After a median follow-up of 7.0 years (interquartile range 6.0-8.2) the CR group had lower rates of all-cause death (15.7% vs 35.8%, log-rank p = 0.003) and cardiovascular death (12.9% vs 23.6%, log-rank p = 0.046). Multivariable analysis with adjustment for confounders showed no benefit of CR for all-cause death (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.31-1.18, p = 0.139) or cardiovascular death (HR 0.80, 95% CI 0.37-1.72, p = 0.560). Age, elevated serum creatinine at inclusion, diabetes and cardiogenic shock at presentation were predictors of death. Conclusions: Patients with STEMI and MVD who underwent CR showed lower all-cause and cardiovascular death during follow-up than those who underwent IR. However, after adjustment for confounders, the real determinates of survival were independent of the revascularization method.