High Cardiovascular Risk Patients Research Articles

Ezetimibe: Integrating Established Use with New Evidence - A Comprehensive Review.

To consolidate key information on the efficacy and safety of ezetimibe, with a focus on the latest evidence. While ezetimibe has long been used alongside statins to help achieve lipid goals when statins are insufficient or in statin-intolerant patients, recent studies confirm and extend its benefits. Ezetimibe, when added to statins, is now recognized as an effective option for high-risk cardiovascular patients. Additionally, for those intolerant to statins, it can be combined with bempedoic acid, offering significant LDL cholesterol reduction. Ezetimibe's favourable tolerability, with fewer side effects than statins, along with the availability of fixed-dose combinations, enhances both treatment efficacy and patient adherence. Overall, this review underscores ezetimibe's evolving role in lipid management, providing valuable guidance for optimizing cardiovascular risk reduction strategies.

Uric Acid-HDL Ratio as Predictor of Major Cardiovascular Events in Very High Cardiovascular Risk Patients Treated with High-Intensity Statin Therapy

Introduction: Uric acid levels are positively correlated with cardiovascular disease. High Density Lipoprotein (HDL) cholesterol plays a role in suppressing blood oxidation reactions and protecting vascular endothelial cells. The combination of these two metabolic parameters, the Uric Acid-HDL Ratio (UHR) makes it a very useful predictor marker for metabolic disorders. Statins are known to be the gold standard for raising HDL cholesterol. Some types of statins are also known to reduce serum uric acid levels by involving pleiotropic actions. The aim of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Objectives: The Objective of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Methods: This study was conducted at the cardiac center of Dr Zainal Abidin Regional General Hospital. This study is an observational study with a prospective cohort design. The target population was patients classified as patients with very high cardiovascular risk and using consecutive sampling techniques.Results: During the study period, a total of 82 patients with ischemic heart disease with very high cardiovascular risk met the inclusion and exclusion criteria. Of these, 49 patients (59.8%) were identified as having major cardiovascular events (MACE) while the remaining 33 patients (40.2%) did not had MACE. The results of this study are that statin therapy may not significantly affect the uric acid-HDL ratio in the context of major cardiovascular events.Conclusions: The uric acid-HDL ratio had no significant predictive ability for major cardiovascular events in patients with very high cardiovascular risk who were treated with high-intensity statin therapy.

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Abstract 4138269: The Association Between Automatically Assessed Broad P-wave and Cardiovascular Events in Patients with Cardiovascular Risks

Background: A broad P wave in electrocardiography reflects atrial remodeling and is associated with cardiovascular events. Although there are several reports on the association between a broad P wave and cardiovascular events, the association between automatically assessed P-wave duration and cardiovascular events in cardiovascular high-risk patients has not been clarified. Hypothesis: We hypothesized that a greater automatically assessed P-wave duration would be associated with cardiovascular events in patients with cardiovascular risk factors. Methods: We included 4,654 patients with access to automated electrocardiography (ECG) analysis of those in the Cardiovascular Prognostic Coupling Study in Japan (a registry of subjects with one or more cardiovascular risk factors, excluding patients with atrial fibrillation). Twelve-lead ECG was conducted, and the P-wave duration in each lead was analyzed automatically using the 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). We selected the maximum P wave duration (Pmax) among the 12 leads. The primary endpoint was a composite endpoint (cardiovascular death, nonfatal myocardial infarction/stroke), and the secondary endpoint was heart failure hospitalization. We assessed two P-wave cut-offs (Pmax ≥ 140, 150 msec) in relation to cardiovascular events. Results: There were 218 patients with Pmax ≥140 ms and 123 patients with Pmax ≥150 ms. N-Terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with Pmax ≥140 ms than in those with Pmax <140 ms (median 134.0 vs. 65.7 pg/mL, p<0.001). NT-ProBNP was also higher in patients with Pmax ≥150 ms than in those with Pmax <150 ms (median 192.0 vs. 66.9 pg/mL, p<0.001). The mean follow-up period was 53 ± 17 months. The primary endpoint occurred in 180 cases and the secondary endpoint in 73 cases. A broad P-wave defined as Pmax ≥140 ms was independently associated with the primary endpoint (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.04–2.70, p=0.034) but not with the secondary endpoint (HR 1.96, 95% CI 0.99–3.90, p=0.055) after adjustment for covariates including NT-proBNP. A broad P-wave defined as Pmax ≥150 ms was independently associated with both the primary endpoint (HR 2.08, 95% CI 1.06–4.09, p=0.034) and the secondary endpoint (HR 3.22, 95% CI 1.38–7.52, p=0.007). Conclusions: Automatically assessed P-wave duration of Pmax ≥ 150 ms was a significant predictor of cardiovascular events and heart failure.

Abstract 4120785: Differential Cardiovascular Impact of ω-3 Fatty Acid in Patients at High Cardiovascular Risk in Asians versus non-Asians: Sub-analysis of the STRENGTH Randomized Clinical Trial

Background: Racial differences in lipid and cardiovascular risk profiles are well-established including for Asians. The STRENGTH trial found that ω-3 carboxylic acid (CA) formulation of eicosapentaenoic acid and docosahexaenoic acid did not result in significant changes in cardiovascular event rates compared with corn oil in statin-treated patients at high cardiovascular risk, however drug efficacy may vary by race. We evaluated and compared the cardiovascular treatment effect of ω-3 CA between Asians and non-Asians in this sub-analysis of the STRENGTH trial. Methods: The STRENGTH trial was a double-blinded 1:1 randomized controlled trial of 13,078 high cardiovascular risk patients enrolled during 10/30/2014-6/14/2017 at 675 centers. Efficacy of ω-3 CA for Asians (n=1,355) and non-Asians (n=11,723) and interactions between race and treatment effect were assessed. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stroke, coronary revascularization and unstable angina hospitalizations. Results: Key differences in baseline characteristics include Asians having significantly higher prevalence of men, secondary prevention, and lower total cholesterol, LDL, apoB100, and hsCRP. In Asians, ω-3 CA was associated with significantly lower primary endpoint during follow-up, with 81/698 events [Kaplan-Meier (KM) Estimate: 14.8%] in the ω-3 CA group, 103/657 events (KM Estimate: 20.4%) in the corn oil group, and hazard ratio (HR) 0.72, 95% CI 0.54-0.96, P=0.026 (Figure A). In non-Asians, there was not a significant difference in primary endpoint rates between the two groups, with 704/5841 events (KM Estimate: 15.6%) in the ω-3 CA group, 692/5882 events (KM Estimate: 15.9%) in the corn oil group, and HR 1.03 95% CI 0.93-1.14, P=0.60 (Figure B). There were significant interactions between race (Asian versus non-Asian) and treatment group for the primary endpoint (P=0.021) and non-fatal stroke (P=0.016) and remained significant after adjusting for other covariates. Conclusion: ω-3 CA was associated with significant reduction in major adverse cardiovascular events compared with corn oil in Asians but not in non-Asian patients with high cardiovascular risk. Further research is necessary to elucidate the mechanisms for potentially beneficial effects of ω-3 CA unique to Asian race.

PCSK9 Inhibitors: The Evolving Future.

PCSK9 inhibitors are a novel class of medications that lower LDL cholesterol (LDL-C) by increasing LDL receptor activity, promoting clearance of LDL-C from the bloodstream. Over the years, PCSK9 inhibitors have been explored as adjunct therapies to statins or as monotherapy in high-risk cardiovascular patients. This review aims to provide an updated perspective on PCSK9 inhibitors, assessing their clinical efficacy, safety, and significance, especially in light of recent clinical trials. The review examines the role of PCSK9 in cholesterol regulation and summarizes the results of major cardiovascular trials, including FOURIER, SPIRE-1, SPIRE-2, and ODYSSEY Outcomes. It also discusses emerging treatments like small interfering RNA (siRNA) therapies and evaluates PCSK9 inhibitor effects on LDL-C and lipoprotein(a) levels. Clinical trials have shown PCSK9 inhibitors reduce LDL-C by up to 60%. In the FOURIER trial, evolocumab reduced LDL-C by 59% and major cardiovascular events by 15%-20%. The SPIRE-2 trial, despite early termination, showed a 21% risk reduction in the primary composite endpoint with bococizumab. The ODYSSEY Outcomes trial reported a 57% LDL-C reduction with alirocumab, alongside a 15% reduction in adverse events. Emerging treatments like Inclisiran offer long-term LDL-C control with fewer doses. PCSK9 inhibitors are generally well-tolerated, with the most common side effect being injection site reactions. PCSK9 inhibitors significantly lower LDL-C and reduce cardiovascular events, offering promising therapies for high-risk patients, including those with familial hypercholesterolemia (FH) and those who cannot tolerate statins. Future research will focus on optimizing these inhibitors, integrating complementary therapies, and exploring gene-editing technologies to improve patient outcomes.

Prevalence, type, severity and determinants of sleep disordered breathing in acute myocardial infarction patients: the AMI-Sleep study

Abstract Background Sleep Disordered Breathing (SDB) is highly prevalent in patients with ischemic heart disease and often remains undiagnosed. Purpose We aimed to assess the prevalence, type, severity and determinants of SDB in patient hospitalized for acute myocardial infarction (AMI). Methods We prospectively enrolled a subset of patients hospitalized for AMI of the French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry included from January 2019 and December 2022 in the 16 AMI-Sleep-trained centers. Baseline and in-hospital information were collected through the FRENCHIE registry. A simplified polygraphy through ApneaLink Air+ was performed overnight during the initial hospitalization before discharge. Data were scored in centralized manner at a single center where trained physicians ascertained SDB characteristics (central or obstructive) and severity based on Apnea-Hypopnea index (AHI). SDB was defined by an AHI≥15/h. Multivariable logistic regression (adjusted for age, sex, diabetes, hypertension, smoking, body mass index, severity of the coronary artery disease, left ventricular ejection fraction [LVEF] at admission [or at discharge if missing] and use of Ticagrelor) was used to analyze the associations between characteristics of the patients at inclusion and SDB. Results Among 1752 patients, 955 (54.5 [52.1;56.9] %) had an AHI≥15/h. The prevalences of mild (AHI= 5-14.9), moderate (AHI=15-29.9) and severe (AHI≥30) SDB were 30.9%, 24.2% and 30.3% respectively. SDB characterization was technically possible in 712 patients (74.6%), and was found central in 72.2% of cases, obstructive in 12.9% and mixed in 15.4%. Male sex, age, BMI, diabetes, degree of severity of CAD, LVEF≤40% and treatment with Ticagrelor were independently associated with SDB. Conclusion More than half of the patients hospitalized for AMI had at least moderate SDB with a majority of them characterized as central. SDB diagnosis should be considered in this setting and particularly in very high cardiovascular risk patients with severe CAD.SDB determinants in AMI patients

Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study

Abstract Background Middle aged women have a faster increase in atherosclerotic cardiovascular disease (ASCVD) events than men over time. Undertreatment with guideline-recommended therapy in women may be one of the drivers for this burden. Purpose To compare high- or very high-risk male and female patients regarding contemporary 1-year low-density lipoprotein cholesterol (LDL-C) goal attainment, lipid-lowering therapy (LLT) intensity, and major adverse cardiovascular event (MACE) rate. Methods SANTORINI is an observational, prospective study that enrolled high- and very high-cardiovascular risk patients between March 2020 and Feb 2021, across 623 sites and 14 countries in Europe from primary & secondary care settings, with a further 1-year prospective follow-up. We included all patients with an LDL-C measurement at baseline and 1-year follow up (1yFU) for the current analysis. LDL-C goal attainment was defined separately for high and very-high risk categories according to 2019 ESC/EAS guidelines. Results Overall, 5197 males with a mean age of 65 years, and 2013 females with a mean age 66 years were included. At baseline, male patients had higher prevalence of pre-existing ASCVD (81.6% vs. 63.5%), and a lower prevalence of familial hypercholesterolaemia (8.7% vs. 17.2%) than female patients (Table 1). The proportion of patients reaching LDL-C goal improved from baseline to 1yFU, but was greater in males (22.9% and 33.3%, respectively) than females (16.9% and 24.6%, respectively). Similarly, the proportion of patients receiving no LLT decreased from baseline to 1yFU for both sexes, however, more females than males received no LLT at 1yFU (male: 20.7% to 2.7%; female: 23.9% to 3.9%). High intensity statin use increased for both sexes but was higher for males (22.2% to 27.3%) than for females (15.5% to 19.5%) at 1yFU. By contrast, PCSK9i use at baseline and 1yFU was lower for males (6.6% to 9.3%) than for females (9.8% to 13.4%). Nevertheless, the use of combination LLT at 1yFU was lower among females than males (male: 27.8% to 42.2%; female: 26.7% to 40.2%). During follow-up, MACE-4 was higher in males (5.31/100 patient years [PY]; 95% confidence interval [CI]: 4.68–5.95) than in females (3.63/100PY; 95% CI: 2.79–4.47). Similar results were observed for MACE-3 (Table 2). Conclusions Despite similar guideline recommendations, use of combination LLT and high intensity statin therapy was lower in female patients at high or very high cardiovascular risk than in male patients over one year of follow-up. Accordingly, female patients had lower LDL-C goal attainment both at baseline and at one-year. Nevertheless, due to intrinsic risk factors, female patients had lower rates of MACE-4 and MACE-3 than male patients.

Arterial stiffness for predicting major adverse cardiovascular events in post-infarcted patients

Abstract Introduction According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity –PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance in different patient population (hypertension, diabetes, chronic kidney disease), however in post-infarcted, very high cardiovascular risk population the exact prognostic value for PWV and Aix needs to be clarify. Purpose We evaluated PWV and Aix cut-off values for MACE prediction and validated the prognostic relevance of high stiffness parameters in post-infarcted patients. Methods Oscillometric based pulse wave analysis method (Arteriograph) was applied for calculating arterial stiffness. We aimed to evaluate PWV and Aix cut-off values for predicting MACE (comprising all-cause death, non-fatal myocardial infarction, ischemic stroke, hospitalization for heart failure and coronary revascularization) in post-infarcted, very high cardiovascular risk patient population. 114 patients (89 male, average age: 62,5±10,5 years) were investigated in this long term, median 16,2 (IQR: 6,5-17,4) years follow-up study. Results Strong, significant correlation was found between PWV and Aix values (Spearman rho: 0,648, p<0,001). Totally 140 MACE events occurred during the 16,2 years follow-up period. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWV: 9,84 m/s, AUC: 0,754 (95% CI: 0,66-0,85), p<0,001; Aix: 34,8 %, AUC: 0,67 (95% CI: 0,57-0,77), p<0,05) by ROC analysis (Figure 1.). Kaplan-Meier analysis in both parameters showed a significantly lower event-free survival in case of high PWV and Aix values (p<0,05; Figure 2.). Multivariate Cox regression analysis revealed PWV and Aix as an independent predictor of MACE (PWV HR: 1,32 (95% CI: 1,15-1,53), p<0,001; Aix HR:1,04 (95% CI: 1,01-1,08), p<0,05). Conclusions Arterial stiffness, particularly elevated PWV predicts MACE in post-infarcted, very high cardiovascular risk patient population. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improve individual risk stratification in patients after myocardial infarction.ROC analysis for the prediction of MACEKaplan-Meier curves for MACE

Global burden of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - preliminary results from Germany

Abstract Background Clinical trial data has shown that low-density lipoprotein cholesterol (LDL-C) lowering with PCSK9-inhibitors reduced cardiovascular (CV) endpoints in patients with established atherosclerotic cardiovascular disease (ASCVD). Intervening early in patients with high CV risk prior to myocardial infarction (MI) or stroke, while perceived to be less urgent, may result in larger public health benefits. The effect of evolocumab in this population is investigated in a phase-3 clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]). This observational study examines the global burden of VESALIUS-CV-like population in the REAL-World ("VESALIUS-REAL") in eight regions (Germany, Hong Kong, Japan, South Korea, Sweden, Taiwan, UK and US) using a unified protocol across multiple databases. The multi-database study is ongoing, and the current analysis focuses on characteristics of VESALIUS-CV like patients in Germany. Methods Eligibility criteria are shown in the Figure. Data were obtained from the German Disease Analyzer (2013-2022), a representative claims database from Germany. Criteria were aligned with the clinical trial, and real-world definitions were created using diagnosis and procedure codes. Results A total of 195,621 patients were included in the present analysis (Table). At baseline, the median age was 71 years (Q1-Q3: 64-79) and 48% of patients were women. Approximately two-thirds of patients had atherosclerosis (48.5% had coronary artery disease, 13.8% had cerebrovascular disease and 13.8% had peripheral artery disease) and 33.7% had high-risk diabetes mellitus (DM), defined as DM with microvascular complications or chronic insulin use. The median baseline LDL-C was 139 (Q1-Q3: 113-166) mg/dL [3.6 (2.9 - 4.3) mmol/L] and 110,867 patients (57%) had an LDL-C ≥130 mg/dL (≥3.4 mmol/L). Overall, 69% of VESALIUS-CV like patients were receiving no background LLT. Conclusions Despite having atherosclerosis and/or high-risk DM and LDL-C exceeding target thresholds, a large proportion of VESALIUS-CV like patients were not on any LLT in Germany. Final results from VESALIUS-REAL will be able to report if this treatment gap is also observed in other countries.

PCSK9 Monoclonal Antibodies Have Come a Long Way.

This review examines the pivotal role of monoclonal antibodies against PCSK9 in lipid-lowering therapy, emphasizing their biological and clinical impact. Randomized controlled trials have validated that PCSK9 monoclonal antibodies (Mabs) effectively reduce LDL-c levels by approximately 50%, even when added to maximal statin therapy. They moreover produce a notable 15-20% relative decrease in major cardiovascular events, with a greater reduction among high-risk patients and no evidence for serious adverse effects, assuaging previous concerns. This review highlights the benefits of PCSK9 Mabs in high cardiovascular risk patients. Despite their efficacy and safety, these therapies are hindered by limited access, and require broader integration into clinical practice to optimize therapeutic outcomes.

Evaluating the Efficacy of a Pre-Established Lipid-Lowering Algorithm in Managing Hypercholesterolemia in Patients at Very High Cardiovascular Risk.

Recent data from European studies (EUROASPIRE V, DA VINCI, SANTORINI) indicate that achieving the LDL cholesterol (LDL-C) target in patients at very high cardiovascular risk is uncommon. Additionally, using a combination therapy involving statins and ezetimibe remains infrequent. A single-center assessment of a pre-defined lipid lowering treatment algorithm's effectiveness at achieving the LDL-C target in patients at very high cardiovascular risk one month and one year after hospitalization. 81 patients were included, all in secondary prevention. The average age of the patient was 66.9 years, and the main cardiovascular risk factors included hypertension, diabetes mellitus, and smoking history. Following the predefined lipid-lowering algorithm specific to our study, which involves initiating high-intensity statin therapy or a combination of statin and ezetimibe depending on initial LDL-C levels and patient history; 30 (37%) patients initiated high-intensity statin therapy (Atorvastatin (40 mg, 80 mg) or Rosuvastatin (20 mg, 40 mg)), while 51 (63%) started combination therapy with high-intensity statin and ezetimibe 10 mg. After one year, 57 (70.4%) remained adherent to their initial treatment, achieving a mean LDL-C of 49.5 ± 16.9 mg/dL, with 36 (63.2%) of them reaching the LDL-C target of <55 mg/dL. A total of 13 patients discontinued treatment, and 9 were lost to follow-up, withdrew from the study, or died. Initiating dual statin and ezetimibe therapy or high-intensity statin therapy early, based on the expected treatment efficacy, holds the potential to more rapidly and effectively achieve LDL-C targets in a larger proportion of very high-risk cardiovascular patients.

HABITUAL COFFEE CONSUMPTION AND RISK OF CARDIOVASCULAR AND ALL-CAUSE MORTALITY IN THE PAMELA HYPERTENSIVE POPULATION.

Background and aimsEvidence has been provided that in the normotensive population chronic coffee consumption does not adversely affect cardiovascular and total mortality. Whether and to what extent this is the case also in high risk cardiovascular patients such as those with elevated blood pressure (BP) is largely debated. Methods and resultsWe analyzed data collected in 943 hypertensive patients belonging to the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, which were classified as coffee consumers and non-consumers (self report). Cardiovascular and total mortality were evaluated at the 25 year follow-up taking into account a number of variables including office and 24-hour ambulatory BP. When data were analyzed as unadjusted values no significant difference in hazard ratios for cardiovascular and total mortality was detected in coffeee consumers and non-consumers considering office (0.85 and 0.83 respectively, P=NS) or 24-hour (1.08 vs 0.80 respectively, P=NS) BP. This was the case also when the data were adjusted for confounders (age, sex, BP, lipid profile, plasma glucose and cholesterol levels, renal function, previous cardiovascular events) or when analyzed according to presence or absence of antihypertensive treatment. ConclusionsThus in mild-to-moderate hypertensive patients chronic coffee consumption does not exert deleterious long-term effects on cardiovascular and total mortality. This is the case in both genders and in treated and untreated hypertensive patients.

Prevalence, incidence, and treatment of dyslipidemia in patients with high or very high cardiovascular risk in Germany

Background2019 ESC/EAS guidelines on management of dyslipidemia outline treatment goals of LDL-C reduction in patients with high and very high cardiovascular (CV) risk. ObjectiveTo describe the proportion, clinical characteristics, and treatment practices of adult patients with dyslipidemia and high or very high CV risk in Germany. MethodsBased on German claims data from 2010-2019, a retrospective cross-sectional study on prevalence, incidence, and treatment pathways in patients with dyslipidemia and high and very high CV risk is performed. ResultsBetween 2010 and 2019, there were 213 to 233 adult patients per 1,000 with prevalent dyslipidemia based on ICD 10 codes. Annual incidence ranged from 31.7 to 40.2 per 1,000. In 2019, 1.2% and 22.8% of the prevalent patients are classified to high or very high CV risk. Out of these patients, 61.7% and 78.5% received lipid lowering treatments (LLT). Among incidence patients, prescription rates are further apart between high-risk and very-high-risk patients, at 56.6% and 79.2%. Cross-sectional analysis showed that in 2019 statin monotherapy is the most common LLT (87.2%) administered mainly at moderate dose (59.9%). In that year, 2.7% and 8.4% of the patients received ezetimibe as monotherapy or in combination with statins. The proportion of treatment pause, or discontinuation was 56.6% over time, with subsequent re-initiation for 42.0% of patients. ConclusionsAnalysis indicates that despite recommendations, intensive treatment therapies are underutilized in clinical practice even in high and very high CV risk patients with primary hypercholesterolemia/mixed dyslipidemia, who may have benefited from LLT optimization.

Balancing Relief and Pain: Effects of COX-2 Inhibitor Valdecoxib

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, was initially acclaimed for its gastrointestinal safety and effectiveness in managing chronic inflammatory conditions and pain. It reduced gastrointestinal complications compared to other anti-inflammatory drugs, benefiting patients with complex medication regimens. The injectable form, parecoxib, was seen as promising for acute post-surgery pain management. However, clinical trials in high-risk cardiovascular patients, particularly those undergoing coronary artery bypass grafting, revealed increased risks when using higher doses of parecoxib. These findings led to the re-evaluation of valdecoxib’s safety profile and its subsequent market withdrawal due to cardiovascular concerns and reports of serious skin reactions. Despite its withdrawal, valdecoxib has garnered interest for repurposing in other conditions. Its pharmacodynamic and pharmacokinetic properties suggest potential in qualifying palmitate-induced insulin resistance in type 2 diabetes and inhibiting matrix metalloproteinases for wound healing. Its efficacy against SARS-CoV-2 highlights drug repurposing strategies for health crises like COVID-19. Valdecoxib's established success in arthritis, dysmenorrhea, and postoperative pain, along with its potential in treating glaucoma, underscores the value of repurposing existing drugs for new therapeutic purposes. In conclusion, valdecoxib exemplifies the balance between drug safety, clinical utility, and innovative repurposing. The aim of this study is to fully harness drug potential in medical science through a concerted effort made by the scientific community, regulatory bodies, and industry stakeholders to navigate the technological and regulatory hurdles.

Coronary Artery Disease, Family History, and Screening Perspectives: An Up-to-Date Review.

Family history for CAD (coronary artery disease) is an established cardiovascular (CV) risk factor and it is progressively acquiring importance in patients' CV risk stratification. Numerous studies have demonstrated that individuals with a first-degree relative affected by CAD have a significantly higher risk of developing the condition themselves; in particular, when CAD occurs at an early age in relatives. Indeed, recently published CCS (chronic coronary syndrome) ESC (European Society of Cardiology) guidelines include family history (FH) as a risk factor to consider when calculating pre-test risk for CAD. ESC guidelines on preventive cardiology (2021) only suggested CV risk assessment in the presence of a positive FH for CV disease, not considering it in the actual risk scores. Evidence suggests that positive anamnesis for relatives affected by CAD correlates with ACS (acute coronary syndrome) and CAD, with slight differences in relative risk as far as the degree of kinship is concerned. Genetic factors contribute to this correlation by influencing key processes that affect heart health, such as cholesterol metabolism, blood pressure regulation, and inflammatory responses. New technologies in the genetics field are increasing the availability of genome sequencing, and new polymorphism panels are being tested as predictive for CAD, objectifying familiarity. Advances in imaging techniques allow the assessment of coronary atherosclerosis and its composition, and these are acquiring strength in evidence and recommendations in ESC guidelines as a way to define coronary disease in low and low-to-intermediate risk patients and to guide medical therapy and interventional procedures. Use of these emerging tools to guide screening is likely to be extended, beyond high CV risk patients, to individuals with FH for early CAD and/or specific genetic profiles, as recent evidence in the literature is suggesting.

Refractory case of amiodarone-induced thyrotoxicosis in a high cardiovascular risk patient

Refractory case of amiodarone-induced thyrotoxicosis in a high cardiovascular risk patient

Mechanisms of high cardiovascular risk in patients with nonalcoholic fatty liver disease

Aim. To optimise the curation of patients with a comorbid course of nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) to explore pathogenetically-based targets of high cardiovascular risk (CVR) formation. Materials and methods. An open comparative study was conducted with the formation of a cohort of 126 patients with comorbid course of NAFLD and CVD with different stages of liver fibrosis, who were divided into comparison groups according to SCORE-2 and SCORE-2-OR. Collection of complaints, medical and life history, examination, general laboratory investigations and examination of hormonal status, abdominal ultrasound, EchoCG and liver elastometry to assess the severity of fibrosis were performed. Work with the study data and graphical analysis was performed using Microsoft Office 2019 software package statistical analysis using STATISTICA 12.0. Results. SCORE-2 risk increased with increasing age of patients (z=-5.29; p0.01). The most common non-cardiovascular co-morbidities in the study sample were cholelithiasis in 35 (66.78%) patients. Soluble leptin receptor levels were lower (z=-8.60; p0.01) and leptin resistance index was higher (z=-5.95; p0.01) in the higher cardiovascular group. Corresponding data were also obtained when the changes in insulin resistance index were calculated and analysed (z=-2.15; p0.01). Fibrosis stage was higher, in patients with higher CVR (z=-3.488; p0.01), while no statistically significant difference in steatosis level was recorded. According to transient elastometry, patients taking statins had lower levels of fibrosis (z=-3.747; p0.01) and hepatic steatosis (z=-3.379; p0.01). Conclusions. The most common pathology is arterial hypertension. Gallstone disease and type 2 diabetes mellitus are often found in patients with a comorbid course. The risk of comorbid pathology and CVD increases with age. Formation of advanced stages of liver fibrosis, hyperinsulinaemia and leptin resistance phenomenon are associated with higher CVR according to SCORE-2 and SCORE-2-OR. The syndrome of increased intestinal permeability is a possible mechanism of increased CVD in patients with NAFLD.

White-coat effect and masked hypertension in patients with high-normal office blood pressure: results of the Hungarian ABPM Registry.

Blood pressure (BP) lowering therapy in hypertension can markedly reduce the risk of cardiovascular diseases. In case of high-normal office blood pressure (oBP), the initiation of antihypertensive medication is recommended by guidelines in patients with very high cardiovascular risk. The aims of this study were to evaluate the presence of white-coat high-normal BP (WhHNBP) and masked hypertension in high-normal oBP and to explore the prevalence of untreated very high cardiovascular risk patients. Data of the Hungarian Ambulatory Blood Pressure Monitoring (ABPM) Registry between September 2020 and November 2023 were used in our analysis. From 38 720 uploaded ABPM curves with clinical data, 4300 individuals were categorized as having high-normal oBP. Among those, 3285 (76.4%) were on antihypertensive treatment. Based on the ABPM recordings, high-normal BP was confirmed in 20.5% ( n = 881), while WhHNBP was present in 27.6% ( n = 1188) and masked hypertension in 51.9% ( n = 2231). Similar results were found in treated and untreated subjects or patients as well. Independent predictors of WhHNBP were age [odds ratio (OR) 1.02 (95% confidence interval, 95% CI: 1.01-1.02), P < 0.001], female sex [OR: 1.59 (1.32-1.92), P < 0.001] and snoring [OR: 0.70 (0.57-0.86), P < 0.001]. Independent predictors of masked hypertension were male sex [OR: 1.31 (1.12-1.54), P < 0.001] and obesity [OR: 1.71 (1.39-2.09), P < 0.001]. Five hundred and two individuals had very high cardiovascular risk with high-normal oBP and only 25 of them were untreated. In high-normal oBP, WhHNBP or masked hypertension is present in three out of four individuals. Most of the patients with high-normal oBP and very high cardiovascular risk are already treated with antihypertensive drugs.

Laterality of Radiation Therapy in Breast Cancer is Not Associated With Increased Risk of Coronary Artery Disease in the Contemporary Era

BackgroundExternal beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesize there is no difference the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left vs right sided radiation. MethodsFor the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022. CAD was identified using a homogenous metric across multiple studies included. We computed the risk ratio (RR) for included studies using a random effects model. For the institutional cohort portion of our study, we selected high cardiovascular risk patients diagnosed with BC between 2010-2022 if they met our inclusion criteria. We performed a Cox proportional hazards model with stepwise adjustment. ResultsA pooled random effects model with 9 studies showed that patients with left-sided BC receiving EBRT had a 10% increased risk of CAD when compared to patients with right-sided BC receiving EBRT (RR: 1.10, 95% CI: 1.02 - 1.18, p = 0.01). However, subgroup analysis of 6 studies that included patients diagnosed after 1980 did not show a significant difference in CAD based on BC laterality (RR: 1.07, 95% CI: 0.95 – 1.20, p = 0.27). For the institutional cohort portion of the study, we found that patients with left-sided BC who received EBRT did not have a significantly higher risk for CAD when compared to their right-sided counterparts (HR = 0.73, 95% CI: 0.34 - 1.54, p = 0.402). ConclusionOur study suggests a historical trend of increased CAD in BC patients receiving left-sided EBRT. Data from patients diagnosed after 2010 in our institutional cohort did not show a significant difference, emphasizing that modern EBRT regimens are safe, and laterality of BC does not affect CAD outcomes in the short term after a breast cancer diagnosis.