Use Of Lipid-lowering Therapy Research Articles

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.

Efficacy of combination lipid lowering therapy in achieving low density lipoprotein cholesterol targets after one month of event in patients with acute coronary syndrome

Abstract Introduction Rapid reduction in low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of recurrent events in patients with acute coronary syndrome (ACS) with benefits proportional to LDL-C reduction. Early use of combination lipid-lowering therapy (LLT) is therefore recommended. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-intensity statins (HIS) improve LDL-C goal attainment but are unaffordable for many patients in India and worldwide. Purpose We share our experience with the use of dual RE (rosuvastatin plus ezetimibe) and triple REB (rosuvastatin plus ezetimibe and bempedoic acid) combination LLT in patients admitted with ACS. Methods All ACS patients admitted to our institute over one year (January 2023 to December 2023) were considered in this retrospective analysis. Those with unavailable lipid profile reports, either at the time of ACS or at 1-month follow-up, were excluded. Clinical and laboratory details were obtained from hospital records. The primary objective was to assess the percentage change in LDL-C levels from index event to 4 weeks follow-up. Results A total of 299 patients were included, out of which 60 were on HIS alone, 71 were on RE, and 168 were on REB (Figure). The majority (99%) of patients in the REB group were statin naïve, compared to the other two groups. The baseline mean LDL-C levels at the time of the index event were 95.3+30.5, 103.2+39.6, and 115.6+32.9 mg/dl, respectively (p<0.001) (Table). The mean LDL-C levels at four weeks post-ACS reduced to 52.9+21.2, 45.9+20.5, and 43.7+15.4 mg/dl, respectively (p<0.01). The percentage reduction in LDL-C level was 44.4%, 55.5%, and 62.2%, respectively (p<0.001). REB enabled 70.8% and 95.2% of patients to achieve the Lipid Association of India, and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 4 weeks. These target levels were achieved in 67.6% and 88.7% of patients on the dual RE therapy and 50% and 81.6% of patients, respectively, on HIS alone. Conclusion Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen compared to costly PCSK9i therapy.Figure.Lipid lowering strategies usedComparison of study groups

Burden of systemic inflammation and associated health outcomes in adults with atherosclerotic cardiovascular disease managed in routine care

Abstract Background The burden and outcomes of inflammation in people with atherosclerotic cardiovascular disease (ASCVD) are poorly defined, particularly beyond the controlled settings of trials and research cohorts. Methods We conducted a longitudinal observational study of adults with ASCVD undergoing C-reactive-protein (CRP) testing in routine healthcare in Stockholm, Sweden. After excluding CRP tests associated with acute illness and patients with medications/conditions that bias CRP interpretation, the systemic inflammation of participants was defined over a 3-month ascertainment window. Baseline determinants of CRP≥2 mg/L were explored with logistic regression, and baseline CRP categories were compared via Poisson and Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events (MACE), heart failure hospitalization, and all-cause death. Result After applying inclusion/exclusion criteria, we identified 84,399 adults with ASCVD with a mean age of 71 years and of which 54% were men. In total, 60% had CRP≥2 mg/L. At baseline, female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anemia, were associated with CRP≥2 mg/L. Conversely, the use of RASi, antiplatelets, and lipid-lowering therapy were associated with lower odds. Over a median follow-up of 6.4 years and compared to people with CRP <2 mg/L, those with CRP≥2 mg/L had a higher rate of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications during follow-up (P<0.05 for all). They also had a higher rate of MACE [adjusted hazard ratio (HR), 1.30; 95% CI, 1.27–1.33], heart failure hospitalization [1.24; 1.20–1.39], and all-cause death [1.35; 1.20–1.30]. Results were consistent across subgroups and more granular CRP categories, and robust to the exclusion of extreme CRP values or early events. Conclusions Two in three adults with ASCVD have systemic inflammation. A CRP≥2 mg/L is associated with excess healthcare resource utilization as well as increased rates of MACE, heart failure, and death.

Lipid-lowering therapy with Inclisiran in the real-world setting: initial data from a national health care service

Abstract Introduction Inclisiran, a first-in-class siRNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in randomized clinical trials. Challenges for real-life use of inclisiran include limited access to therapy, injections by medical staff, lack of cardiovascular outcome data, and concern from adverse effects considering the novel mechanism and long-term activity. Real-life data on the potential to attain lipid-goals and reduce treatment gaps is lacking. We investigated the implementation of inclisiran in real-world clinical setting in Israel. Methods Data from a nationwide healthcare organization on patients initiating inclisiran therapy during the period of 3/2022-11/2023. Patients’ characteristics, efficacy, use of combination lipid-lowering therapies, and attainment of low-density lipoprotein cholesterol (LDL-C) goals, were evaluated. Results Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Atherosclerotic cardiovascular disease was present in 54%, and peak historical LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Follow-up lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n=254), median LDL-C reduction from peak historical levels was 57% (IQR, 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant oral lipid-lowering therapies (n=143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%) (Figure). LDL-C <70 mg/dL was attained by 39% and LDL-C <55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C <55 mg/dL. Overall, 6.5% did not persist with inclisiran therapy after initial injection. Conclusions In real-life practice, inclisiran showed good efficacy with positive short-term adherence. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.Waterfall Plot of LDL-C (%) Reduction

The difference between guideline based lipid optimisation and real-world practice in a very high risk population

Abstract Background Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor for the progression of cardiovascular disease and early optimisation of lipid lowering therapy following an acute coronary syndrome (ACS) or stroke is associated with improved outcomes. Recent guidelines have advocated the use of combination lipid-lowering therapy and achieving very low LDL-C concentrations.Purpose To identify if optimal lipid management in high risk patients has occurred. Methods A retrospective analysis of high-risk patients with a prior history of ACS or stroke presenting with a further subsequent ACS/stroke from January 2022 to December 2022 in a UK District General Hospital was performed. Lipid lowering therapy in primary care in the 18 months leading up admission, inpatient admission and subsequent 12 month post admission (delivered through the cardiac rehabilitation service post ACS and via primary care post stroke) was compared to our regional secondary prevention lipid lowering pathway. This patient group, with recurrent events, was selected as represents the "very high risk group" and had been through various clinicians multiple times increasing the opportunity to treat to guidance. Results 102 very high risk patients were admitted within the 12 month period. Only 79/102 patients had lipid profile in preceding 18 months and only 19% were compliant with the standard secondary prevention guidelines (20/102 patients high intensity statins), mainly due to reduced intensity statin doses (60%) and no lipid lowering medications (15%). A significant proportion of patients did not have any lipid blood tests during their index admission (no lipid profile 21% in stroke group vs 77% in ACS group) and whilst there was a significant inpatient escalation in lipid therapy this was mainly confined to high dose statins, and seen more clearly in the ACS group (ACS 65% vs stroke 21%). During the 12 months following admission a significant number of patients had no further lipid profiles (21% ACS vs 57% stroke) and minimal further optimisation of lipid management. Further escalation following high intensity statins were rare with only 5 / 102 patients receiving high intensity statin plus ezetimibe, 1 patient receiving statin/ ezetimibe/ PCSK9 inhibitor. Only 45% of patients achieved the guideline target of LDL < 1.8 mmol/L and only 18% achieved the ESC target of LDL <1.4 during 1 year follow up. Conclusion Although lipid guidelines have changed in recent year’s clinical real-world practice locally has not reflected these important developments, even in a very high-risk group patients are not benefiting from established evidence-based interventions. A majority of our ACS patients did not have a lipid profile blood test during their admission highlighting the fact that whilst guidelines have progressed significantly over the last few years the clinical importance of lipid optimisation in practice has not been appreciated by many of the cliniciansResults

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease.

The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts. This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein ≥ 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death. A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein ≥ 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein ≥ 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein ≥ 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events. Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

Lipid-lowering therapy use and LDL-C goal attainment in France: Results from 1-year follow-up of the European observational Santorini study

Lipid-lowering therapy use and LDL-C goal attainment in France: Results from 1-year follow-up of the European observational Santorini study

Calcified carotid artery atheroma on standard dental radiographs: A public health opportunity for cardiovascular risk reduction

ObjectiveCalcified carotid artery atheroma (CCAA) can be identified incidentally on standard dental panoramic radiographs (DPRs). We sought to (1) determine the prevalence of CCAA on DPRs in a general dental population and (2) establish the proportion of patients in whom this would represent a new statin-indicated condition. MethodsWe identified patients aged ≥30 with DPRs from 2019 to 2021 from the University of British Columbia Dental Clinic. Patient charts were reviewed for use of lipid-lowering therapies (LLT) and existing statin-indicated conditions. DPRs for each patient were evaluated for the presence and characteristics of CCAA. ResultsOf 921 patients with a DPR and documented medical history, 548 (59.5 %) were diagnostic for evaluation of CCAA. Although 116/548 (21.2 %) of these patients had evidence of CCAA, only 25.9 % (30/116) were already on LLT; another 20.7 % (24/116) of patients with CCAA had a pre-existing statin-indicated condition but were not on LLT. Therefore, in 53.4 % (62/116) of patients with CCAA-positive DPRs, this constituted a new diagnosis of atherosclerosis not yet treated with LLT, representing 6.7 % (62/921) of the clinic population and 11.3 % of individuals with DPRs of diagnostic quality (62/548). Dyslipidemia, hypertension, coronary artery disease, diabetes, atrial fibrillation, stroke/transient ischemic attack, older age, and male sex were all found to be significant predictors of CCAA. ConclusionCCAA is a common finding among patients with DPRs and in over half of cases, the presence of CCAA represents a new diagnosis of atherosclerosis. The high prevalence of new, untreated atherosclerosis in this population indicates an opportunity for risk factor modification and collaboration between dentists and physicians to optimize patient care.

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.

Causal Relationships between Lipid-Lowering Drug Target and Aortic Disease and Calcific Aortic Valve Stenosis: A Two-Sample Mendelian Randomization.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesteryl ester transfer protein (CETP) and apolipoprotein C3 (APOC3) are pivotal regulators of lipid metabolism, with licensed drugs targeting these genes. The use of lipid-lowering therapy via the inhibition of these genes has demonstrated a reduction in the risk of cardiovascular disease. However, concerns persist regarding their potential long-term impact on aortic diseases and calcific aortic valve disease (CAVS). This study aims to investigate causal relationships between genetic variants resembling these genes and aortic disease, as well as calcific aortic valve disease using Mendelian randomization (MR). We conducted drug-target Mendelian randomization employing summary-level statistics of low-density lipoprotein cholesterol (LDL-C) to proxy the loss-of-function of PCSK9, HMGCR, CETP and APOC3. Subsequently, we investigated the association between drug-target genetic variants and calcific aortic valve stenosis and aortic diseases, including thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic dissection (AD). The genetically constructed variants mimicking lower LDL-C levels were associated with a decreased risk of coronary artery disease, validating their reliability. Notably, HMGCR inhibition exhibited a robust protective effect against TAA (odds ratio (OR): 0.556, 95% CI: 0.372-0.831, p = 0.004), AAA (OR: 0.202, 95% CI: 0.107-0.315, p = 4.84 10-15), and AD (OR: 0.217, 95% CI: 0.098-0.480, p = 0.0002). Similarly, PCSK9, CETP and APOC3 inhibition proxies reduced the risk of AAA (OR: 0.595, 95% CI: 0.485-0.730, p = 6.75 10-7, OR: 0.127, 95% CI: 0.066-0.243, p = 4.42 10-10, and OR: 0.387, 95% CI: 0.182-0.824, p = 0.014, respectively) while showing a neutral impact on TAA and AD. Inhibition of HMGCR, PCSK9, and APOC3 showed promising potential in preventing CAVS with odds ratios of 0.554 (OR: 0.554, 95% CI: 0.433-0.707, p = 2.27 10-6), 0.717 (95% CI: 0.635-0.810, p = 9.28 10-8), and 0.540 (95% CI: 0.351-0.829, p = 0.005), respectively. However, CETP inhibition did not demonstrate any significant benefits in preventing CAVS (95% CI: 0.704-1.544, p = 0.836). The consistency of these findings across various Mendelian randomization methods, accounting for different assumptions concerning genetic pleiotropy, enhances the causal inference. Our MR analysis reveals that genetic variants resembling statin administration are associated with a reduced risk of AAA, TAA, AD and CAVS. HMGCR, PCSK9 and APOC3 inhibitors but not CETP inhibitors have positive benefits of reduced CAVS. Notably, PCSK9, CETP and APOC3 inhibitors exhibit a protective impact, primarily against AAA, with no discernible benefits extending to TAA or AD.

Real-world evidence evaluation of LDL-C in hospitalized patients: a population-based observational study in the timeframe 2021–2022

AimsEuropean registries and retrospective cohort studies have highlighted the failure to achieve low-density lipoprotein-cholesterol (LDL-C) targets in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause and cardiovascular mortality. The aim of this study is to evaluate LDL-C levels in a real-world inpatient setting, identifying cardiovascular risk categories and highlighting treatment gaps in the implementation of LDL-C management.MethodsThis retrospective, observational study included all adult patients admitted to an Italian hospital between 2021 and 2022 with available LDL-C values during hospitalization. Disease-related real-world data were collected from Hospital Information System using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). We performed assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines, and use of lipid-lowering therapies (LLT).Results13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of on-target patients was progressively lower towards the worst categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients, 28.48% were on-target in VH category, 47.60% in H, 69.12% in M and 68.47% in L. We also analyzed the impact of monotherapies and combination therapies on target achievement.ConclusionsWe found relevant gaps in LDL-C management in the population of inpatients, especially in the VH category. Future efforts should be aimed at reducing cardiovascular risk in these subjects.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

The Dynamics of Cardiovascular Risk-An Analysis of the Prospective Urban Rural Epidemiology (PURE) Poland Cohort Study.

Background: The purpose of this study was to analyze the major cardiovascular risk (CVR) factors and their trends in the study population. Methods: The results of subjects in the Polish Prospective Urban and Rural Epidemiological Study (PURE) study group were interpreted. CVR was calculated for each participant according to the Systematic Coronary Risk Evaluation (SCORE2) scale or the Systematic Coronary Risk Evaluation-Older Persons (SCORE2-OP) scale. Data from the beginning of the analysis (2013) and nine years later (2022) were included. In addition, the use of lipid-lowering therapy (LLT) and meeting the low-density lipoprotein cholesterol (LDL-c) target criterion at the beginning and end of the study were analyzed. Results: Patients in the high and very high CVR groups who had abnormal LDL-c results accounted for 64% and 91% of their group in 2013 and 70% and 92% in 2022, respectively. Conclusions: Regardless of age, patients using LLT at the start of the analysis had a greater increase in future CVR, especially if they had lipid abnormalities at the start of the study. This may be due to reverse causality and multimorbidity in these patients, highlighting the importance of appropriate treatment of lipid abnormalities.

Use of combination therapy is associated with improved LDL-cholesterol management: 1-year follow-up results from the European observational SANTORINI study.

To assess whether implementation of the 2019 ESC/EAS dyslipidaemia guidelines observed between 2020-2021 improved between 2021-2022 in the SANTORINI study. High- or very-high cardiovascular (CV) risk patients were recruited across 14 European countries from March 2020-February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. . Of 9559 patients enrolled, 9136 (2626 high risk, 6504 very high risk) had any follow-up data, and 7210 (2033 high risk, 5173 very high risk) had baseline and follow-up LDL-C data. LLT was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6% and 25.6% to 57.1% and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 mmol/L to 2.0 mmol/L. Goal attainment improved from 21.2% to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs 25.5%). LLT use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal, hence strategies are needed to improve implementation of combination LLT.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

#1212 Trends in real-world lipid lowering therapy use among adult patients with chronic kidney disease: 5-year single center experience in the Philippines

Abstract Background and Aims Patients with chronic kidney disease (CKD) carry an extremely high burden for atherosclerotic cardiovascular disease (ASCVD), which worsens as CKD progresses. Several international guidelines, including the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, have recommended the use of lipid-lowering therapy (LLT) in this high-risk population. To evaluate the implementation of these recommendations in real-world practice, we assessed patterns of dyslipidemia management among patients with CKD. Specific objectives include describing the prevalence and intensity of LLT prescription [stratified by estimated glomerular filtration rate (GFR) and whether requiring renal replacement therapy or not] as well as adherence to guideline recommendations on LLT use. Method We conducted a single-center, cross-sectional study covering the period of January 2019 to December 2023. A review of inpatient and outpatient medical records of the Department of Medicine, University of the Philippine—Philippine General Hospital was done. Eligible patients were at least 18 years of age, and diagnosed with CKD. Exclusion criteria included having a concomitant diagnosis of Acute Kidney Injury, and being pregnant or breastfeeding at any point in the study period. Sociodemographic, clinical, and laboratory data were based off the latest entry in each patient's medical record. No clinical data were collected beyond those that were available on the records. Classification of statin intensity was based on the 2019 American Heart Association/American College of Cardiology Guidelines on the Management of Blood Cholesterol as well as the 2020 Philippine Clinical Practice Guidelines on the Management of Dyslipidemia. All analyses were descriptive and done using STATA 18. Categorical variables were summarized as frequencies and percentages. Continuous variables were reported as measures of central tendency [i.e. mean (SD) or median (IQR), as appropriate]. Results Of the 3845 patients included in the study, 2922 (76%) were prescribed LLT. The most common LLT were statins (92%), followed by statin/ezetimibe combinations (6%), then statin/fibrate combinations (2%). None were prescribed PCKS9 inhibitors, niacin, omega-3 fatty acids, or bile acid sequestrants. Among non-dialytic patients, the distribution of LLT use was as follows: a) eGFR ≥ 60 ml/min/1.73 m2: 40% (173/431) b) eGFR 30-60 ml/min/1.73 m2: 76% (1198/1576) c) eGFR &amp;lt;30 ml/min/1.73 m2: 84% (1551/1838). Among dialytic patients, 68% (601/884) were already on LLT prior to initiation of dialysis while 35% (283/884) were started on LLT after dialysis initiation. Notably, 89% (786/884) of these dialytic patients were still on moderate-to-high-intensity statin doses. Based on recommendations from the 2013 KDIGO guidelines, only 78% (2610/3334) of eligible patients were prescribed on LLT, while 61% (312/511) of ineligible patients were prescribed on LLT. Similar rates of adherence were seen to other international guideline recommendations on the management of dyslipidemia in CKD (e.g. 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol, 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemias, 2020 Clinical Practice Guidelines for the management of dyslipidemia in the Philippines). Conclusion Real-world LLT use among CKD patients remains high, even at lower eGFRs. More importantly, a large proportion of patients remain under- and over-treated, highlighting significant gaps between guideline recommendations and real-world clinical practice. Further investigation regarding the underlying reasons for these practice variations is necessary to improve quality of care, and safely reduce the burden of dyslipidemia and ASCVD among CKD patients.

Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults.

Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed. The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences. Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98]). In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.

Prevalence of Dysbetalipoproteinemia in the UK Biobank According to Different Diagnostic Criteria

Abstract Context Dysbetalipoproteinemia (DBL) is a multifactorial disorder that disrupts the normal metabolism of remnant lipoproteins, causing increased risk of cardiovascular disease. However, establishing a proper diagnosis is difficult, and the true prevalence of the disease in the general population remains unknown. Objective The objectives were to study the prevalence of the disease and to validate the performance of different clinical diagnostic criteria in a large population-based cohort. Methods This study included 453 437 participants from the UK Biobank. DBL was established in participants having an ε2ε2 genotype with mixed dyslipidemia or lipid-lowering therapy use (n = 964). The different diagnostic criteria for DBL were applied in individuals without lipid-lowering medication (n = 370 039, n = 534 DBL), to compare their performance. Results Overall, 0.6% of participants had an ε2ε2 genotype, of which 36% were classified as DBL, for a disease prevalence of 0.2% (1:469). The prevalence of DBL was similar between the different genetic ancestries (≤0.2%). Several diagnostic criteria showed good sensitivity for the diagnosis of DBL (&amp;gt;90%), but they suffered from a very low positive predictive value (0.6-15.4%). Conclusion This study reported for the first time the prevalence of DBL in the UK Biobank according to genetic ancestry. Furthermore, we provided the first external validation of different diagnostic criteria for DBL in a large population-based cohort and highlighted the fact that these criteria should not be used to diagnose DBL alone but should rather be used as a first screening step to determine which individuals may benefit from genetic testing to confirm the diagnosis.