Target Low-density Lipoprotein Cholesterol Levels Research Articles

Safety and efficacy of moderate-intensity statin with ezetimibe in elderly patients with atherosclerotic cardiovascular disease.

High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins. To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy. In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5mg with ezetimibe 10mg) or high-intensity statin monotherapy (rosuvastatin 20mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70mg/dL) within 6 months. The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p=0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels. Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.

Effectiveness of Lower Range of High-intensity Statin Therapy in Lowering LDL-C among STEMI Patients

Background: Lipid-lowering is an important intervention to reduce cardiovascular morbidity and mortality after ST-Elevation myocardial infarction. This study aimed to assess the proportion of such patients achieving guideline-directed therapeutic low-density lipoprotein cholesterol targets while on lower-range high-intensity statin treatment.Methods: This is a cross-sectional study conducted in Shahid Gangalal National Heart Centre, a tertiary cardiac center in Kathmandu, Nepal, from November 2021 to July 2022 among admitted acute ST-Elevation myocardial infarction patients who were prescribed a lower range of high-intensity statin therapy, Atorvastatin 40mg and Rosuvastatin 20 mg. Clinical characteristics were collected, including lipid parameters at baseline during admission and three months after the treatment. The proportion attaining the guideline-recommended levels was calculated and compared between each statin group. Results: A total of 240 patients were included in this study. The target low-density lipoprotein cholesterol level of less than 1.4mmol/L was noted only in 16.3% and the target reduction by ≥50% from baseline only in 7.1%. Just 3.3 % achieved a target of &lt;1.4 mmol/L and ≥50% reduction from baseline. However, 40.8% of the participants in our study met the 2012 European Society of Cardiology guidelines’ target achievement of less than 1.8 mmol/L. Conclusions: The overall proportion of patients attaining recommended low-density lipoprotein cholesterol levels after recent ST-Elevation myocardial infarction was low when patients were prescribed with a lower range of high-intensity statin, reflecting the need for rigorous follow up including monitoring of lipid levels and intensification of statin dose and type as recommended by international guidelines.Keywords: Low-Density Lipoprotein Cholesterol; secondary prevention; statin; statin intensity; ST-Elevation myocardial infarction.

Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials.

Cardiovascular disease is a leading cause of mortality, especially in individuals with type 2 diabetes mellitus and dyslipidemia. Despite adequate statin therapy, some patients fail to achieve the target low-density lipoprotein-cholesterol levels. Trials have compared doubling the statin dose with the addition of ezetimibe. A systematic literature search was performed using various databases. Forest plots were constructed for pooled analysis with statistical significance set at P < 0.05. Seven trials were included. Monotherapy showed no significant difference compared with dual therapy for low-density lipoprotein-cholesterol levels [mean difference (MD): -5.03; P = 0.37], high-density lipoprotein-cholesterol levels (MD: 0.01; P = 0.95), total cholesterol (MD: -2.38; P = 0.66), and triglycerides (MD: 5.37; P = 0.67) at follow-up compared to baseline. Monotherapy significantly reduced serious clinical adverse events (risk ratio: 0.21; P = 0.04), with no difference in treatment-related adverse effects, discontinuation due to treatment-related or overall adverse events.

PCSK9 Inhibitors: Focus on Evolocumab and Its Impact on Atherosclerosis Progression.

This paper investigates the therapeutic use of PCSK9 inhibitors, particularly Evolocumab, as monoclonal antibodies for the treatment of atherosclerosis based on recent literature reviews. PCSK9 is an outstanding example of a breakthrough in medical science, with advancements in understanding its biological function driving substantial progress in atherosclerosis treatment. Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, imposing substantial financial burdens on healthcare systems. Elevated low-density lipoprotein cholesterol (LDL-C), a modifiable risk factor, plays a pivotal role in the development of ASCVD. Emerging treatments such as PCSK9 inhibitors are now being introduced to combat this issue, with the goal of reducing ASCVD risk by directly targeting LDL-C levels. This discovery highlighted the potential of monoclonal antibodies to inhibit PCSK9, thereby enhancing LDL-C receptor activity. This breakthrough led to the development of Alirocumab and Evolocumab inhibitors, which typically reduce LDL-C levels by approximately 50%. This research underscores the importance of PCSK9 inhibitors in treating ASCVD, drawing on evidence from various randomized controlled trials such as FOURIER, ODYSSEY OUTCOMES, and VESALIUS-CV. These trials have also shown that PCSK9 inhibitors are effective and safe for the treatment of several cardiovascular disorders. PCSK9 inhibitors are therefore useful in patients who do not reach their target LDL-C levels when on the highest doses of statins or patients with very high cardiovascular risk who cannot tolerate statins at all.

Controlled low-density lipoprotein cholesterol attenuates cardiovascular risk mediated by elevated lipoprotein(a) after percutaneous coronary intervention.

Lipoprotein(a) [Lp(a)] is an independent, causal risk factor for cardiovascular disease. However, it is still unclear whether controlling low-density lipoprotein cholesterol (LDL-C) to optimal levels can attenuate cardiovascular risk mediated by elevated Lp(a), especially in the setting of secondary prevention. Adult patients with a baseline Lp(a) measurement who underwent percutaneous coronary intervention (PCI) and reached their LDL-C target levels (<70 mg/dl) at Mayo Clinic sites between 2006 and 2017 were included. Primary outcomes included major adverse cardiovascular events (MACE) and all-cause mortality. Kaplan-Meier curves were created to compare the survival probabilities among patients with Lp(a) ≥ 50 mg/dl compared with Lp(a) < 50 mg/dl. Multivariable Cox regression analyses were performed to quantify the association of elevated Lp(a) with our relevant outcomes and to control for possible confounders. In total, 878 patients (median age: 68 years, and 74% males) who underwent PCI were included for analysis. Of them, 29.7% had elevated Lp(a) ≥ 50 mg/dl. Kaplan-Meier curves did not reveal any significant difference in survival probabilities for elevated Lp(a) for any outcome including MACE (P = 0.91), all-cause mortality (P = 0.26), or the separate MACE components. Similarly, the multivariable analysis showed no significant association for MACE (hazard ratio: 1.07, 95% confidence interval: 0.84-1.37) or all-cause mortality (hazard ratio: 0.98, 95% confidence interval: 0.74-1.30). In patients who underwent PCI and have their LDL-C controlled below 70 mg/dl, no significant association was found between elevated Lp(a) ≥ 50 mg/dl and risk for MACE or all-cause mortality.

LDL-C target attainment and statin use in patients with ASCVD, familial hypercholesterolaemia, and those otherwise at moderate/high-risk of ASCVD in australian general practice (SCOPE-GP)

Abstract Background The proportion of Australian general practice patients not attaining low-density lipoprotein cholesterol (LDL-C) goals is not well described. The SCOPE-GP study evaluated duration of LDL-C exceeding treatment goals, statin use and discontinuation rates in patients with atherosclerotic cardiovascular disease (ASCVD), without ASCVD events but at moderate/high-risk, and familial hypercholesterolemia (FH). Methods This population-based retrospective cohort study used de-identified medical records of adult patients captured in the IQVIA GP-EMR database. Patients were indexed at the earliest date of ASCVD, FH, or hyperlipidemia diagnosis from January 1, 2010 to June 30, 2022, with a variable follow-up period from index to June 30, 2022. Ascertainment of study cohort was based on the 2021 ESC/EAS guidelines and Framingham Risk Equation. LDL-C test result levels were extracted per patient, summarised and analysed. Patients were stratified based on their test results at latest results/closest to censor date. Average time above target levels is the proportion of number of days above LDL-C target levels over total number of follow-up days for each patient. A Poisson distribution was fitted to estimate 95% confidence interval. Lipid lowering therapies (LLT) were stratified by (ASCVD, FH and moderate/high risk of CVD) at last visit/censor date. Combination of LLT were defined as prescriptions for fixed dose combinations or ≥2 separate scripts of LLT from different classes within 180 days from last visit/censor date (look back period). Discontinuation is defined as no statins were prescribed again after the last script for 270 days or more, limited to the first occurrence. Results The average time with LDL-C levels above target was 1077.5 days in ASCVD patients (n=2,688), 938.6 days in moderate-risk ASCVD (n=37,003), 980.9 days in high-risk ASCVD (n=85,199), and 900.8 days in FH (n=279). The proportion of days above target level for all four cohorts is described in Figure 1. Among 107,552 patients with recorded LDL-C levels ≥1.8mmol/L at their last visit/censor date, 30.9% were on statin monotherapy and 1.0% were on statin+ezetimibe. Statin use was highest in ASCVD patients (65.4%), followed by FH (49.5%), high risk (40.0%) and moderate risk subjects (29.5%) (Table 1). Statin discontinuation rates were 60.3%, 76.3, 66.1%, and 65.8% in these groups, respectively. The predominant reason for statin discontinuation was non-specific adverse drug reactions (12.2% ASCVD, 11.7% moderate-risk, 13.2% high-risk and 17.9% FH). The proportion of subjects contraindicated to statins was highest in moderate risk subjects (0.05%). Conclusions Prolonged periods of elevated LDL-C and high statin discontinuation rates were prevalent among at-risk individuals in Australian primary care. This underscores a significant ASCVD burden that could be prevented with more active lipid management.

Impact of Lp(a) on lipid control in patients with acute coronary syndrome

Abstract Background The lipoprotein(a) (Lp[a]) is a genetically determined low-density lipoprotein (LDL)-like particle. Lp(a) levels above 50mg/dl have been correlated to an increased risk of atherosclerosis and major adverse cardiovascular events. Thus, treatments designed to reduce Lp(a) levels are currently under investigation. However, it is unknown how high Lp(a) concentrations affect the control of lipid profile. Purpose The purpose of this project is to investigate how Lp(a) impacts lipid profile control in individuals with acute coronary syndromes (ACS). Methods We designed a single-center prospective registry including consecutive patients admitted for ACS. Lp(a) levels were obtained from all enrolled patients during hospitalization; lipid profile (total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides) was obtained at admission and at the 6-month follow-up (6MFU). Patients were stratified according Lp(a) concentration (low-Lp(a): Lp(a) &amp;lt; 50 mg/dL; high-Lp(a): Lp(a) ≥ 50 mg/dL). LDL-cholesterol (LDLcorr) levels corrected for concentration of Lp(a) were calculated as LDLcorr= LDLmeasured – 30%Lp(a). At discharge cholesterol lowering drugs were introduced or titrated as standard of care. The primary endpoint was the percentage of patients reaching target LDL and LDLcorr (&amp;lt;55 mg/dL) at 6MFU. The secondary endpoints were the correlations between Lp(a) levels and lipid profile, both at baseline and at 6MFU, as well as the correlation between Lp(a) levels and the total number of traditional cardiovascular risk factors in the study population. Results From February 2020 through September 2023, a total of 409 patients were included: 305 (74.6%) with Lp(a) &amp;lt; 50 mg/dL; 104 (25.4%) with Lp(a) ≥ 50 mg/dL (Table 1). High-Lp(a) patients showed a lower prevalence of diabetes (14.2% vs 27.87%, P = 0.0055), an overall lower number of traditional cardiovascular risk factors (&amp;gt;2 in 25.9% vs 38.1%, P=0.0244). High-Lp(a) patients showed higher level of LDL-cholesterol compared to the low-Lp(a) population both at baseline (124±52 mg/dL vs 110.4±44 mg/dL, P= 0.0263) and at 6MFU (70.5±21 vs 63.8±29, P= 0.0208) with fewer patients achieving the target LDL cholesterol levels (21.57% vs 40.13%, P=0.0184). Estimating the true LDL concentration (LDLcorr) the percentage of patients reaching target LDL cholesterol levels at FU significantly increased in the high-Lp(a) group (from 21.57% to 76.5%), with a minimal increase noticeable in the low-Lp(a) population (from 40.13% to 48.41%, p 0,1870). Conclusions In ACS population, patients with high Lp(a) concentrations have fewer traditional CV risk factors and a lower prevalence of diabetes. High-Lp(a) patients, furthermore, seem more challenging to meet LDL target at 6 month follow up, but not when the LDL values are adjusted for Lp(a).

Evaluation of Lipid Profile Management in Coronary Artery Disease Patients on Statin Therapy: A Single-Centre, Retrospective, Observational Study.

Lipid control is crucial in managing coronary artery disease (CAD) to reduce cardiovascular risk. This study aimed to evaluate the effectiveness of lipid-lowering therapy, particularly statins, in achieving target lipid levels in patients with CAD. This single-center, retrospective, observational study was conducted at the Cardiology Outpatient Department of Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharastra, India. A sample size of 72 patients was included in this study. Adult patients receiving treatment for acute coronary syndrome (ACS), chronic stable angina (CSA), or unstable angina (UA) were included. Exclusion criteria were comorbidities affecting clinical decisions, HIV-positive status, pregnancy, or breastfeeding. Data on lipid profiles, including low-density lipoprotein (LDL) cholesterol (LDL-C), were collected, with LDL-C calculated using the Friedewald equation or measured directly. The primary outcome was the proportion of patients achieving LDL-C targets as per the 2019European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. Statistical analysis was performed using chi-square tests, with significance set at p < 0.05. Of the enrolled patients, a substantial proportion did not achieve target LDL-C levels, with LDL-C remaining above the recommended thresholds in a significant number of patients. Despite ongoing statin therapy, lipid control was suboptimal in many cases, particularly among those with elevated LDL-C levels. A detailed analysis of lipid profiles and the achievement of target levels was done, highlighting areas where current treatment strategies may fall short. The study reveals that a significant number of patients with CAD on statin therapy do not achieve optimal lipid control, particularly in LDL-C management. This underscores the need for more aggressive or tailored lipid-lowering strategies to reduce residual cardiovascular risk in this high-risk population. Further studies are needed to explore the factors contributing to suboptimal lipid control and to develop interventions that can enhance the effectiveness of current therapies.

Coronary artery disease risk prediction by combined stratification of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels across different glucose statuses.

To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

Is Liver Transplantation Alone an Effective Treatment for Homozygotic Familial Hypercholesterolemia in Children?

To examine the long-term results and treatment effectiveness of liver transplantation (LT) in the treatment of homozygous familial hypercholesterolemia (HoFH) in children and adolescents. Patients who underwent LT due to HoFH between 2007 and 2023 were included in the study. The patients' demographic data, clinical findings, preoperative and postoperative laboratory examinations, transplantation complications, and postoperative disease courses were evaluated. There were five boys with an average age of 6.2 (median: 6, range 4-10) years in the study. The average total cholesterol level of the patients before transplantation was 923 (median: 950, range: 780-1002) mg/dL and the average LDL-cholesterol level was 864 (median: 852, range: 770-957) mg/dL. No patients died of transplant-related complications. After an average follow-up of 9.2 (median: 9, range: 1.5-16) years, the average total cholesterol level of the patients was 197 (median: 164, range: 137-359) mg/dL, and the average LDL-cholesterol level was 138 (median: 92, range: 85-313) mg/dL. Four (80%) patients developed atherosclerotic cardiovascular disease during follow-up, and two (40%) died of this cause. LT in the treatment of HoFH did not help our patients reach the target LDL-cholesterol level after transplantation and did not prevent the development of cardiovascular disease. Therefore, LT alone is not curative in the treatment of HoFH.

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.

Association Between Patient Sex and Familial Hypercholesterolemia and Long-Term Cardiovascular Risk Factor Management 5 Years After Acute Coronary Syndrome.

Long-term control of cardiovascular risk factors after acute coronary syndrome (ACS) is the cornerstone for preventing recurrence. We investigated the extent of cardiovascular risk factor management in males and females with and without familial hypercholesterolemia (FH) 5 years after ACS. We studied patients hospitalized for ACS between 2009 and 2017 in a Swiss multicenter prospective cohort study. FH was defined based on clinical criteria from the Dutch Lipid Clinic Network and Simon Broome definitions. Five years post-ACS, we assessed low-density lipoprotein-cholesterol (LDL-c) levels, lipid-lowering therapy (LLT), and other cardiovascular risk factors, comparing males to females with and without FH using generalized estimating equations. A total of 3139 patients were included; mean age was 61.4 years (SD, 12.1), 620 (19.8%) were female, and 747 (23.5%) had possible FH. Compared with males at 5-years post-ACS, females were more likely to not use statins (odds ratio, 1.61 [95% CI, 1.28-2.03]) and less likely to have combination LLT (odds ratio, 0.72 [95% CI, 0.55-0.93]), without difference between patients with FH and without FH. Females in both FH and non-FH groups less frequently reached LDL-c values ≤1.8 mmol/L (odds ratio, 0.78 [95% CI, 0.78-0.93]). Overall, patients with FH were more frequently on high-dose statins compared with patients without FH (51.0% versus 42.9%; P=0.001) and presented more frequently with a combination of 2 or more LLT compared with patients without FH (33.8% versus 17.7%; P<0.001), but less frequently reached LDL-c targets of ≤1.8 mmol/L (33.5% versus 44.3%; P<0.001) or ≤2.6 mmol/L (70.2% versus 78.1%; P=0.001). Five years after ACS, females had less intensive LLT and were less likely to reach target LDL-c levels than males, regardless of FH status. Males and females with FH had less optimal control of LDL-c despite more frequently taking high-dose statins or combination LLT compared with patients without FH. Long-term management of patients with ACS and FH, especially females, warrants optimization.

Trends in atherosclerotic cardiovascular disease and lipid management: a population-level observational cohort study in Wales.

European clinical guidelines recommend that patients with atherosclerotic cardiovascular disease (ASCVD), including ischaemic heart disease (IHD), stroke, and peripheral arterial disease (PAD), are prescribed lipid lowering treatment (LLT) and treated to target low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to document trends in ASCVD, including treatment, monitoring, and achievement of target LDL-C. A retrospective observational population study was performed using linked healthcare data (2010-22). Over the study period, the number of patients with ASCVD increased from 181 153 to 207 747 (8882 to 9398 per 100 000). The proportion of patients prescribed LLT decreased from 75.3% in 2010 to 67.1% in 2022; high-intensity statin therapy increased from 9.4 to 25.2%, while non-high-intensity statin therapy decreased from 59.6 to 38.2%. The prescription of high-intensity statin therapy was consistently higher amongst patients with IHD (10.9% in 2010 increasing to 28.0% in 2022) than in patients with stroke (4.7-21.6%) or PAD (3.9-10.6%).The proportion of cases with documented LDL-C decreased from 58.0% in 2010 to 49.3% in 2022. Of those with documented LDL-C in 2022, 44.0% achieved LDL-C < 1.8 mmol/L, including 45.2% of those with IHD, 42.0% of those with stroke, and only 32.8% of those with PAD. Prescription of LLT, including high-intensity statin therapy, documentation of LDL-C, and achievement of target LDL-C levels was relatively low, especially in PAD patients. Although target achievement in 'tested patients' increased over time, the proportion of patients undergoing lipid testing declined. More rigorous lipid management requires prioritisation, especially for PAD and stroke patients.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.

Cholesterol Lowering in Older Adults: Should We Wait for Further Evidence?

Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies. The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

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.

Efficacy of single-dose evolocumab injection in early-phase acute myocardial infarction: a retrospective single-center study.

Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI. A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups. The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001). Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Effectiveness of inclisiran lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Moscow healthcare

Aim. To evaluate the effectiveness of PCSK9-targeted therapy (inclisiran, alirocumab, and evolocumab) in patients with atherosclerotic cardiovascular disease (ASCVD) and who did not achieve the target low-density lipoprotein cholesterol (LDL-C) level on basic therapy (statins in maximum tolerated doses and/or ezetimibe).Material and methods. This observational study included 50 patients receiving the inclisiran and 30 patients of the control group with ASCVD treated with PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29). In all participants, we assessed medical history data and initially performed electrocardiography, echocardiography, Doppler ultrasound of extracranial and lower limb arteries, and laboratory tests (complete blood count, biochemical and lipid profile). Three Moscow public health facilities took part in the study.Results. Data on achievement of primary and secondary endpoints by the 12th month are presented. The study groups were comparable in basic clinical characteristics. In inclisiran group, a significant decrease in LDL-C level was found from 2,53±0,7 mmol/l initially to 1,29±0,5 mmol/l (by 49%), p=0,0002; the target LDL-C &lt;1,4 mmol/l was achieved by 73,9% of the subjects. Alirocumab/ evolocumab showed significant lipid-lowering effect with a LDL-C decrease from 2,4±0,9 mmol/l to 1,32±0,7 mmol/l (by 45%), p&lt;0,0001.Conclusion. The final results are consistent with the intermediate data and indicate not only the possibility of early achievement of target LDL-C levels in PCSK9targeted combination therapy, but their maintenance with a favorable tolerability and safety profile.

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases

WEIGHT LOSS IN HYPERTENSIVE PATIENTS WITH OBESITY UNDER THE INFLUENCE OF LIRAGULTIDE IS ASSOCIATED WITH A REDUCTION IN INSULIN RESISTANCE AND INCREASED EFFECTIVENESS OF THERAPY

Objective: One of the most important areas of treatment for patients with arterial hypertension (AH) with abdominal obesity (AO) is reduction of body weight (BW), which can be achieved using the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Objective: to study the relationship between the degree of weight loss under the influence of liraglutide and the effectiveness of antihypertensive and lipid-lowering therapy in hypertensive patients with AO. Design and method: 42 patients with AH of 2-3 degrees and AO of I-II degrees (24 men) aged from 46 to 60 years were examined using standard methods. Insulin resistance (IR) was determined by HOMA-IR. All patients received three-component antihypertensive therapy (a fixed combination of perindopril, indapamide and amlodipine) and, due to elevated low-density lipoprotein-cholesterol (LDL-C), atorvastatin in optimal doses. Liraglutide was administered as daily subcutaneous injections at a daily dose of 0.6 mg, with a gradual weekly dose increase of 0.6 mg to reach 3.0 mg/day. The duration of observation was 16 weeks. Results: After 16 weeks of treatment with liraglutide, 30 patients (71%) (the first subgroup) experienced a decrease in BW of 5% or more compared to baseline. At the same time, in 13 patients (29%) (second subgroup) BW decreased by less than 5% compared to the initial level or did not decrease. In the first subgroup of patients, a significant decrease in IR was detected from (5.06 ± 1.14) to (2.40 ± 1.22), p&lt;0.05), whereas in the second subgroup the IR indicator did not change significantly. Among patients of the first subgroup, a significantly higher frequency of achieving target levels of “office” blood pressure (in 100% of patients) and target levels of LDL-C (in 73% of patients) was found in comparison with patients of the second subgroup (in 69% of patients, p&lt;0.05) and in 39% of patients, p&lt;0.05), respectively). Conclusions: A pronounced decrease in BW in hypertensive patients with AO under the influence of liraglutide is associated with a significant decrease in IR and also with a significant increase in the effectiveness of both antihypertensive and lipid-lowering therapy.