High CV Risk Research Articles

Efficacy and safety of inclisiran in real-world clinical practice. Results from the CHOLINET Registry

Abstract Background/Introduction Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real-world settings are limited. Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry including 36 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran treatment, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH). Methods From November 2022 through February 2024, the Cholinet registry enrolled patients receiving inclisiran according to standard clinical practice. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at subsequent follow-up. Results We enrolled 668 patients in treatment with inclisiran (15.1% with FH, 30.7% female, mean age 63 years), Data on follow-up at 3 months (booster time) were available for 495 of them. At the time of inclisiran first prescription median LDL-C was 102 mg/dl and reached 51 mg/dl at the time of 3 months observation (50% mean reduction, 51 mg/dl absolute median reduction). None of the 495 patients reaching 3 months follow up missed the reinjection dose administration. Of 668 patients enrolled, 553 patients (82.7%) were on LLT, of them 107 (19.3%) were on ezetimibe alone, 67 (12.1%) on statin alone and 379 (68.5%) on a statin and ezetimibe combination. Of the enrolled patients, 45 (6.7%) were previously treated with evolocumab and 34 (5%) with alirocumab. Among the patients evaluated at the 3-month follow-up, 307 patients (62%) achieved the LDL cholesterol target; of them, 450 (91%) were treated with inclisiran and statin±ezetimibe. Evaluating the distribution of the percentage reduction in LDL cholesterol values, a heterogeneity emerged that was partly explainable by the concomitant lipid-lowering therapy and partly by the previous exposure to PCSK9 inhibitors. Conclusions These preliminary data from the Cholinet Italian registry show that inclisiran effectively reduces (50%) LDL-C in real-world settings. The LDL-C target was achieved in 62% of patients; of them 91% were on lipid-lowering therapy, showing that combination therapy is necessary in most of these patients.

In adults with hypertension and high CV risk, intensive vs. standard BP-lowering therapy reduced major vascular events.

Liu J, Li Y, Ge J, et al; ESPRIT Collaborative Group. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial. Lancet. 2024;404:245-255. 38945140.

Assessing Cardiovascular Target Attainment in Type 2 Diabetes Mellitus Patients in Tertiary Diabetes Center in Romania.

Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) share a bidirectional link, and the innovative antidiabetic molecules GLP-1 Ras and SGLT-2is have proven cardiac and renal benefits, respectively. This study aimed to evaluate CV risk categories, along with lipid-lowering and antidiabetic treatments, in patients with T2DM from a real-life setting in Romania. A cross-sectional evaluation was conducted on 405 consecutively admitted patients with T2DM in an ambulatory setting, assessing them according to the 2019 ESC/EAS guidelines for moderate, high, and very high CV risk categories. The average age of the group was 58 ± 9.96 years, with 38.5% being female. The mean HbA1C level was 7.2 ± 1.7%. Comorbidities included HBP in 88.1% of patients, with a mean SBP and DBP of 133.2 ± 13.7 mm Hg and 79.9 ± 9 mm Hg, respectively, and obesity in 66.41%, with a mean BMI of 33 ± 6.33 kg/m2. The mean LDL-C levels varied by CV risk category: 90.1 ± 34.22 mg/dL in very high risk, 98.63 ± 33.26 mg/dL in high risk, and 105 ± 37.1 mg/dL in moderate risk. Prescribed treatments included metformin (100%), statins (77.5%), GLP-1 Ras (29.4%), and SGLT-2is (29.4%). In Romania, patients with T2DM often achieve glycemic control targets but fail to meet composite targets that include glycemic, BP, and lipid control. Additionally, few patients benefit from innovative glucose-lowering therapies with proven cardio-renal benefits or from statins.

Mediterranean Diet Modulation of Neuroinflammation-Related Genes in Elderly Adults at High Cardiovascular Risk.

Individuals with dementia and neurodegenerative diseases (NDDs) often suffer from cardiovascular diseases (CVDs). Neuroinflammation driven by conditions involved in CVDs is linked to disruptions in the central nervous system triggering immune reactions, perpetuating an "inflammatory-like" environment. The Mediterranean diet (MedDiet), known for its anti-inflammatory and antioxidant properties, has been proposed as a key factor to attenuate these risks. Blood nuclear cell samples were collected from 134 participants of the PREDIMED trial, which randomized participants to three diets: one supplemented with extra-virgin olive oil (MedDiet-EVOO), another with nuts (MedDiet-Nuts), and a low-fat control diet. These samples were analyzed at baseline and 12-month follow-up to assess the impact of these dietary interventions on gene expression markers. We first selected target genes by analyzing intersections between NDD and CVD associations. Significant gene expression changes from baseline to 12 months were observed in the participants allocated to the MedDiet-EVOO, particularly in CDKN2A, IFNG, NLRP3, PIK3CB, and TGFB2. Additionally, TGFB2 expression changed over time in the MedDiet-Nuts group. Comparative analyses showed significant differences in TGFB2 between MedDiet-EVOO and control, and in NAMPT between MedDiet-Nuts and control. Longitudinal models adjusted for different covariates also revealed significant effects for TGFB2 and NAMPT. In conclusion, our results suggest that one year of traditional MedDiet, especially MedDiet-EVOO, modulates gene expression associated with CVD risk and NDDs in older adults at high CV risk.

Monoclonal Anti-PCSK9 Antibodies: Real-World Data.

Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines' recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines' recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines' recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients.

Do genetically determined very high and very low LDL levels contribute to Lp(a) plasma concentration?

Background and aimsLipoprotein(a) [Lp(a)] is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Few data are available on the distribution of Lp(a) levels among subjects at different cardiovascular risk and in subjects with monogenic and polygenic dyslipidemias (familial hypercholesterolemia, FH and familial hypobetalipoproteinemia type 1, FHBL1).The aim of this study was to investigate the distribution of Lp(a) plasma levels in subjects with high and low LDL-C levels (FH and FHBL1) and in the general population. Methods and resultsThe study cohorts included 356 hypercholesterolemic patients, 212 carrying a FH causative mutation, 144 with clinical FH (mutation negative - FHneg), 52 FHBL1 and 797 free-living subjects. Lp(a) levels were significantly higher in FH subjects (both FH and FHneg) (median 12.46 mg/dl and 14.0 mg/dl, respectively) compared with FHBL1 and free-living subjects (7.68 mg/dl and 7.18 mg/dl, respectively). More, Lp(a) levels were similar in FH subjects carrying LDLR defective and null mutations and FHneg. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels (median 10.68 mg/dl and 9.20 mg/dl, respectively) compared with low and moderate CV risk (median 5.72 mg/dl and 7.80 mg/dl, respectively) (p < 0.0008). ConclusionsFH subjects exhibit higher Lp(a) levels than FHBL1 and general population. Lp(a) slightly contribute to hypercholesterolemia in FH patients. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels compared with low and moderate CV risk. Combined evaluation of Lp(a) levels in FH subjects with other traditional risk factors could identify very high-risk individuals who may benefit from early aggressive treatments to avoid premature CV events.

An overview of the CANVAS Program and CREDENCE trial: The primary outcomes and key clinical implications for those managing patients with type 2 diabetes.

To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

Vaccinations, cardiovascular drugs, hospitalization, and mortality in COVID-19 and Long COVID

ObjectiveTo identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD). MethodsUsing national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions. ResultsHospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively. InterpretationPrior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions. FundingNIHR. HDR UK.

Healthcare Resource Utilization, Costs, Clinical Events, and Treatment Patterns in Extreme High-Risk Patients for Cardiovascular Events Undergoing Lipoprotein Apheresis: A German Claims Data Analysis

Abstract Aim Insights into treatment patterns, clinical and economic burden of patients undergoing Lipoprotein apheresis (LA). 3 cohorts were characterized: newly treated [Cohort A], experienced [B], matched cohort [C, high CV risk without LA]. Method Clinical burden was assessed by cardiovascular-related hospitalizations and procedures. Economic and clinical outcomes were described over a 12-month baseline period up to 3 years after LA initiation. Results Absolute LA cases decreased from 1.7 to 1.1 per 100,000 patients. In Cohort A, rate of major cardiovascular hospitalizations decreased, while annual healthcare expenditure increased. Cohort B had significantly higher costs than C. Conclusion LA may be associated with a reduced frequency of myocardial infarction-related hospitalizations. However, it is expensive. Alternatives are needed to reduce its high economic burden.

Cardiovascular Risk Profile in Master Paralympic Athletes, a High-Risk Undertreated Population: A Cross-Sectional Longitudinal Study.

Recently, European Society of Cardiology (ESC)validated aprediction model to estimate 10-year fatal and non-fatal cardiovascular disease risk (CVDR) in individuals (aged 40-60 years) without previous cardiovascular disease or diabetes(ESC-SCORE2)and to provide indications for treatment. At present, data describing the CVDR in Paralympic athletes (PAs) are scarce and inconsistent. Therefore,we sought to assess the prevalence of risk factors in PAs to estimate their CVDR through SCORE2. Weenrolled 99 PAs aged ≥40 y.o., who participated at 2012-2022 Paralympic Games, competing in 22 different sport disciplines classified according to sport type (power, skills, endurance and mixed) and disabilities: spinal cord injuries (SCI) and non-SCI. CVDR factors,anthropometric measurements and blood samples were collected. Among the 99 PAs (78% males, mean age 45.7±4.7 y.o.), 52.5% had SCI; 54% were dyslipidemic and 23% were smokers. According to ESC-SCORE2, 29% had high and 1% very-high CVDR. Women (compared to men) and endurance (compared to other sport) exhibited better CV profile. SCI showed no differences when compared with non-SCI for CVDR, excepted for a lower HDL and lower exercise performance.None of the dyslipidemic athlete was on pharmacologically treatment, despitethe altered lipid profile had already been detected at younger age. PAs are a selected population, presenting a high CV risk profile, with 30% showing either high or very-high CVDR according to ESC-SCORE2. Dyslipidemiawas the most common risk factor, underestimated and undertreated, emphasizing the need for specific preventive strategies in this special setting of athletes.

WHITE-COAT EFFECT AND MASKED HYPERTENSION IN HIGH-NORMAL OFFICE BLOOD PRESSURE: RESULTS OF THE HUNGARIAN ABPM REGISTRY

Objective: White-coat hypertension refers to the untreated condition in which BP is elevated in the office but is normal when measured by ambulatory blood pressure monitoring (ABPM), home blood pressure monitoring (HBPM) or both. However, white-coat effect can be present in high-normal blood pressure (BP) category as well. The aims of this study were to evaluate the presence of white-coat effect and masked hypertension in high-normal office BP (OBP) and also to explore the prevalence of untreated very high CV risk (CVD) patients with high-normal OBP. Design and method: Data of the Hungarian ABPM Registry were used in our analysis. Results: From 14 817 uploaded ABPM curves with clinical data 1 255 subjects were categorized as having high-normal OBP. 999 (79.6%) were on antihypertensive treatment. Based on the ABPM recordings apparent high-normal BP was found in 35.9% (n=450), white-coat effect was present in 28.5% (n=358) and masked hypertension was diagnosed in 35.6% (n=447). Similar results were found in treated and untreated subjects as well. Independent predictors of white-coat effect were age (OR: 1.014 (95%CI:1.006-1.023), p=0.001), male sex (OR: 0.565 (0.432-0.739), p&lt;0.001), and obesity (OR: 1.994 (1.480-2.687), p&lt;0.001). Independent predictors of masked hypertension were age (OR: 1.014 (95%CI:1.005-1.023), p=0.003), heart rate (OR: 1.028 (1.011-1.044), p=0.01) and obesity (OR:1.679 (1.262-2.234), p&lt;0.001). 142 subjects had very high CV risk with high-normal OBP and only 7 of them were untreated. With ABPM only one of them had apparent high-normal BP. Conclusions: In high-normal OBP ABPM is a useful tool to diagnose white-coat effect and masked hypertension. Untreated high-normal OBP with very high CV risk is a very rare condition in the general practitioner practice when ABPM is also recommended to evaluate the true blood pressure phenotype before therapeutic decisions.

THE INVESTIGATION OF TRANSFERABILITY OF DEFINITIONS OF CARDIOMETABOLIC AND VASCULAR AGING PHENOTYPES ACROSS MULTIPLE COHORTS

Objective: According to the European guidelines for the prevention of cardiovascular diseases (CVD) (2021), Russia was identified as a country with a very high CV risk. We aimed to investigate the applicability of the standardized definitions of vascular aging phenotypes (VP) in Russian population and align them with the existing reference datasets. Design and method: In 2012-2013 1,600 residents of St. Petersburg (age 21-67) were randomly examined as a part of the multicenter epidemiological study. Anthropometry, blood pressure measurement, blood biochemistry analysis were taken. Subjects completed questionnaires describing their lifestyle, current health condition and medication usage. 618 patients (42% men) from initial cohort with a mean age of 48 [37;55] years were randomly subsampled for carotid-femoral pulse wave velocity assessment (Sphygmocor). The VP were defined using the ‘Reference Values for Arterial Stiffness’ Collaboration database which included 16,867 measurements from eight European countries populations15 to 97 years. According to the criteria, patients with overt CVD, diabetes mellitus and the use of antihypertensive, lipid-lowering therapy were excluded from the analysis of VP. Results: The Russian cohort had significantly higher prevalence of CVD (11,4% compared to 6,9% in the Nreference population, p=5.65x10-5), intake of antihypertensives (28,1% compared to 14,3% in the reference, p&lt;1x10-16) and lipid-lowering therapy (6,1% compared to 4,1%, p=0.025, Figure 1A). Additionally, our cohort had significantly higher prevalence of optimal BP (40,2% vs 28%, p=4.6x10-7) and lower prevalence of first-degree (p=0.048) and second degree (p=0.00084) hypertension (Figure 1B). Comparison of the prevalence of VP between the European and Russian cohorts showed a significant decrease of the early vascular aging (EVA) phenotype with age in the Russian population (p=0.011). The prevalence of the supernormal vascular aging phenotype (SUPERNOVA) in the group of 60-69 years old was higher in the Russian population (p=0.0035) Conclusions: A higher prevalence of CVD was demonstrated in the study cohort despite lower hypertension burden and higher CV drugs intake compared to the European cohort. Multidirectional trajectories of EVA and SUPERNOVA VP with age were detected in Russian population, potentially indicating the presence of the clearing selection pressure at the older age (Agreement No 075-15-2022-301).

Risk Factors and Modifiers for Cardiovascular Disease Assessment of Patients with Heterozygous Familial Hypercholesterolaemia.

Background: The assessment of the risk of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HeFH) is determined by conventional risk factors. However, factors modifying CVD, or risk modifiers, beyond conventional risk factors may inform their CVD risk assessment and the subsequent use of new therapies. This work identifies and characterises patients within a lipid clinic cohort with regards to conventional CVD risk factors and risk modifiers with a focus on those with HeFH. Methods: A study of consecutive adult patients attending our specialist lipid clinic was performed over a six-month period. The patient data recorded included demographics, clinical characteristics, risk factors and risk modifiers, biochemical profiles and genetic testing results. Risk modifiers were identified based on ESC/EAS guidance, and those with HeFH were compared to those without. Results: A total of 370 patients were included. Of these, 98 HeFH patients were identified (26%). Then, 52% of HeFH patients were stratified into the very-high risk category due to the presence of CVD risk factors. Risk modifiers were present in 73%. These included a family history of premature CVD (56%), obesity (28%), a sedentary lifestyle (13%) and a major psychiatric disorder (12%). Compared to the rest of the cohort, those with HeFH were less likely to have hypertension and more likely to have a family history of premature CVD. Conclusions: Half of patients with HeFH are categorised as having very high CV risk. Consideration of risk modifiers, particularly a family history of premature CV disease, increases this very-high-risk category further. This may have implications for the clinical application and access to novel treatments.

Prevalence, impact and management of hypertension-mediated organ damage in type 2 diabetes patients

ObjectiveTo determine the prevalence, impact and management of hypertension-mediated organ damage (HMOD) according to the presence of type 2 diabetes (T2DM). MethodsIBERICAN is an ongoing multicenter, observational and prospective study, including outpatients aged 18–85 years who attended the Primary Care setting in Spain. In this study, the prevalence, impact and management of HMOD according to the presence of T2DM at baseline were analyzed. ResultsAt baseline, 8066 patients (20.2% T2DM, 28.6% HMOD) were analyzed. Among patients with T2DM, 31.7% had hypertension, 29.8% dyslipidemia and 29.4% obesity and 49.3% had ≥1 HMOD, mainly high pulse pressure (29.6%), albuminuria (16.2%) and moderate renal impairment (13.6%). The presence of T2DM significantly increased the risk of having CV risk factors and HMOD. Among T2DM population, patients with HMOD had more dyslipidemia (78.2% vs 70.5%; P=0.001), hypertension (75.4% vs 66.4%; P=0.001), any CV disease (39.6% vs 16.1%; P=0.001) and received more drugs. Despite the majority of types of glucose-lowering agents were more frequently taken by those patients with HMOD, compared to the total T2DM population, the use of SGLT2 inhibitors and GLP-1 receptor agonists was marginal. ConclusionsIn patients daily attended in primary care setting in Spain, one in five patients had T2DM and nearly half of these patients had HMOD. In patients with T2DM, the presence of HMOD was associated with a higher risk of CV risk factors and CV disease. Despite the very high CV risk, the use of glucose-lowering agents with proven CV benefit was markedly low.

Real-world data on treatment patterns in at least high cardiovascular risk patients on dual and triple lipid lowering therapy in a Hellenic nationwide e-prescription database

BackgroundDespite recent guidelines appropriate lipid-lowering treatment (LLT) remains suboptimal in everyday clinical practice. AimsWe aimed to describe clinical practice of use of LLT for at least high CV risk populations in a Hellenic real-world setting and assess how this relates to the European Society of Cardiology treatment guidelines. MethodsWe analyzed data from a retrospective cohort study of the National Registry of patients with dyslipidemia between 1/7/2017 and 30/6/2019 who were at least of high CV risk and filled a dual or triple lipid-lowering treatment (dLLT, tLLT) prescription. The primary outcomes of interest of this analysis were to report on the patterns of LLT use in at least high CV risk patients. ResultsA total of 994,255 (45.4% of Greeks on LLT) were of at least high CV risk and 120,490 (5.5%) were on dLLT or tLLT. The percentage of patients with reported statin intolerance ranged from 2 to 10%. While persistence was reported to be satisfactory (>85% for both dLLT or tLLT), adherence was low (ranging between 14 and 34% for dLLT). In 6-month intervals, the percentage of patients achieving a low-density lipoprotein cholesterol (LDL-C) target below 100 md/dL ranged from 20% to 23% for dLLT and 34%–37% for tLLT. ConclusionsThe prevalence of at least high CV risk patients among patients receiving LLT in Greece is substantial. Despite the high persistence and probably due to the low adherence to treatment, LDL-C remains above targets in more than two thirds of patients.

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

A decrease in cardiovascular event risk with a decrease in total and LDL – cholesterol level is termed as “cholesterol paradox” or “risk factor reversal”. Cardiovascular risk does not have a linear relationship between LDL – cholesterol levels, and other substantial risk factors of cardiovascular events are being disregarded.The aim of this study is, to identify modifiable risk factors of cardiovascular events other than those well proved to cause dyslipidemia. A cross-sectional study was conducted with 652 participants in a tertiary care hospital. Patients were grouped into two, based on the history of cardiovascular events. Demographics and patient responses captured using pre-validated questionnaires were analyzed. 5mL blood samples were collected by venipuncture and lipid profile was estimated. Association between cardiovascular events and explanatory variables. was determined using Chi square test and Odds ratio at 95% confidence intervals. Higher risk of CV events was found among smokers 0.232 [0.144 – 0.373]. Consumption of white sugar, refined oil, processed cold beverages and fast food products increased CV risk respectively. Moreover, total cholesterol, LDL-C and triglycerides were found to decrease after one year of counselling the patients. The classical hypothesis of dyslipidemia induced atherosclerosis may not be the predominant cause of CV events. Herein, we report no association between high fat diet and CV risk while we observed higher risk in consumers of refined and ultra processed food products. However, significant control of cholesterol was observed in patients who shifted to Unrefined food products.

Is there still a place for fenofibrate-statin combination therapy?

Although low-density lipoprotein cholesterol (LDL-C) is the main target for the prevention of atherosclerotic cardiovascular disease (ASCVD), hypertriglyceridaemia (HTG), a common condition characterised by elevated blood triglyceride (TG) levels, contributes to residual cardiovascular risk independently of LDL-C levels. Elevated TG levels are a feature of atherogenic dyslipidaemia, which also includes low HDL-C levels and high levels of atherogenic small, dense LDL, together with accumulation of atherogenic remnant particles. Treatment of HTG includes lifestyle interventions, but these are not always sufficient to significantly reduce TG levels in people at high cardiovascular risk. Current guidelines for the treatment of dyslipidaemias recommend the use of statins as the first choice in people with HTG (TG &gt;200 mg/dL) and high CV risk, and consideration of the use of specific TG-lowering drugs, such as fenofibrate, bezafibrate or icosapent ethyl if HTG persists. Fenofibrate acts by activating the peroxisome proliferator receptor alpha (PPARα), a nuclear receptor that plays an important role in lipid and lipoprotein metabolism, glucose homeostasis and inflammation. Several clinical trials have shown that fibrates may reduce the incidence of major cardiovascular events only in patients with high TG levels and low HDL-C levels, a finding that was also observed with fenofibrate in combination with a statin compared to statin therapy alone. The recent failure of the PROMINENT trial with pemafibrate in combination with a statin highlighted the notion that treatment with fibrates provides a clinical benefit only if they lower apoB levels.

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies

ObjectivesArterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. MethodsObservational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. ResultsAfter nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. ConclusionsMore than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE.

Real-Life Data of Bosutinib Treatment for Chronic Myeloid Leukemia: The Multi-Center Experience of the Gruppo Di Miglioramento Sicilia-Calabria

Background and rationale: Bosutinib is a second generation tyrosine kinase inhibitor (TKI), which has been indicated in Italy in the second line of CML treatment, since 2014. Thanks to its safety profile, bosutinib is frequently chosen as an advanced line of treatment in fragile patients. We collected retrospective data from patients treated with bosutinib in any line of TKI therapy, in order to study the role that this drug has in real-life, compared to clinical trials in terms of treatment line, dosage, toxicity and efficacy. Patients and methods: We collected data from65 chronic phase CML patients treated with bosutinib between 2015-08-18 and 2023-04-27, followed at 12 Haematology centers in Sicily and Calabria. Of these patients, 42 (64.6%) were male, and had a median follow-up of 29 months (range 1-96). Mean age at diagnosis was 62, and mean age at bosutinib start was 67. Median therapies prior bosutinib treatment was 2. Fourtyfour patients (67.7%) had cardiovascular comorbidities (CV) at diagnosis: 37 patients (55%) had at least one cardiovascular risk factor: in particular, arterial hypertension in 31 patients (70.4%), dyslipidaemia in 10 patients (22.7%), diabetes mellitus in 14 patients (31.8%), obesity (grade 3) in 2 patients (4.5%); 7 patients (10.7%) had already experienced an acute cardiovascular or cerebrovascular event. Finally, only 12 patients (18.4%) had no comorbidity at diagnosis. Mean age at the start of bosutinib for CV-risk patients was 70 years. Among 44 patients with CV risk before starting bosutinib, 38 patients were still alive (86.4%) at last follow-up. Fifteen patients with CV risk discontinued bosutinib (34%), while none presented new CV events during treatment. In terms of efficacy, however, in patients with CV risk, the median molecular response, at the last follow-up, is MR2. Results: Thirty-eight patients (58.5%) discontinued bosutinib, while 27 (41.5%) were still on treatment at the time of the last follow-up. Of the 38 patients who discontinued bosutinib, 5 discontinued due to resistance (13.8%) and 19 due to intolerance (50%). Of these 19 intolerant patients, only 1 patient discontinued bosutinib due to CV event (heart failure) and only 1 patient discontinued due to gastrointestinal toxicity (grade 3 diarrhea). Most reported toxicities were as follows: Skin Toxicity 3 pt 5%Perpheral edema 2 pt 3%Hepatototoxicity 2 pt 3% In the efficacy evaluation, early-suspenders (bosutinib treatment duration &amp;lt; 6 months) were, therefore, cut out, 55 patients (84.6%) were evaluated in this sub-analysis, 34 (61.8%) male and 21 (38.2%) female. Median age in this subanalysis is 67 years. Bosutinib was second-line treatment in 35 cases (63.6%), third-line therapy in 15 cases (27.3%), fourth-line therapy in 4 cases (7.3%). Overall, 35 patients assumed bosutinib as a second-line TKI: 22 of them were from the 1L-imatinib group (62.9%), while 13 were from the 2nd generation TKI-1L group (37.1%). Of the 22 1L-imatinib and 2L-bosutinib patients, 56.1% reached MR3 or deeper during bosutinib treatment and 38.1% reached MR4.5 or deeper. Of the 13 patients in 1L-2genTKI 2L-bosutinib group, 61.5% reached at least MR3, while 15.4% reached MR4.5 or MR5. Drop-out rate was similar between the two groups. Conclusion Bosutinib revealed to be safe in patients with CML in 2 nd and further lines of treatment, especially in terms of cardiotoxicity, even in subjects with a high CV risk at treatment initiation. Furthermore, our data revealed as most patients are currently treated with a lower dose of bosutinib than standard (median dosage 302 vs 500 mg a day), obtaining good response rates in 2 nd and further lines. Subsequent eventual dose increase is evaluated on the basis of the molecular response.

Triglyceride level as a potential marker of residual cardiovascular risk and its relation to HeartScore.

Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in Bosnia and Herzegovina. Elevated LDL-cholesterol is established as a strong marker of cardiovascular risk. Some researchers believe that measuring triglyceride levels gives a good assessment of the residual risk for ASCVD besides the measurement of LDL-cholesterol. The aim of this study was to evaluate the overall prevalence of major risk factors for ASCVD, lipid profile and 10-year fatal cardiovascular risk using the HeartSCORE scoring system. Further, we want to evaluate the prevalence and relationship between elevated triglyceride levels and high 10-year fatal cardiovascular risk calculated as a HeartSCORE. This is a cross-sectional study conducted on 832 volunteers aged between 40 and 65 years without a diagnosis of diabetes and without known preexisting cardiovascular disease, as a part of the preventive program conducted at the Family Medicine office. Data were collected for ASCVD risk factors and lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides). 10-year fatal cardiovascular risk was calculated using the HeartSCORE scoring system for countries with high CV risk. Among 832 participants included, 565 (67.9%) were female, and 267 (32.1%) were male. We found high prevalence of hypertension (27.7%), obesity (32.2%), and smoking (36.2%). All lipid parameters, except HDL-C, were not optimal. Only 17.4% of participants had normal estimated HeartSCORE risk, while more than one-third (33.9%) had high or very high estimated HeartSCORE risk. Although we found a higher percentage of participants with elevated triglycerides in groups with higher HeartSCORE, there was a very weak positive correlation between values of triglycerides and the 10-year risk of a fatal cardiovascular event (r= 0.249, p= 0.000). The high prevalence of major known risk factors and high estimated HeartSCORE risk indicate a high overall risk for ASCVD in the sample. The proportion of participants with elevated triglycerides was increased in patients with high HeartSCORE risk what implicates importance of triglyceride measurement.