Low-density Lipoprotein Cholesterol Target Research Articles

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 using linked health-care 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% and non-high-intensity statin therapy decreased from 59.6% to 38.2%. The prescribing 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% to 21.6%) or PAD (3.9% to 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. Prescribing of LLT, including HI-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 Global Perspective on Cardiovascular Risk Factors by Educational Level in CHD Patients: SURF CHD II

Background: Clinical guidelines recommend lifestyle modifications and medication use to control cardiovascular risk factors in coronary heart disease (CHD) patients. However, risk factor control remains challenging especially in patients with lower educational level. Objective: To assess inequalities by educational level in the secondary prevention of CHD in the Survey of Risk Factors in Coronary Heart Disease (SURF CHD II). Methods: SURF CHD II is a cross-sectional clinical audit on secondary prevention of CHD, conducted during routine clinical visits in 29 countries. The easy-to-perform design of the survey facilitates its implementation in settings with limited resources. We reported risk factor recording, attainment of guideline-defined risk factor targets, and treatment in CHD patients. Differences by educational level in target attainment and treatment were assessed with logistic regression stratified for high- (HIC), upper middle- (UMIC), and lower middle-income (LMIC) countries. Results: SURF CHD II included 13,884 patients from 2019 to 2022, of which 25.0% were female and 18.6% had achieved only primary school level. Risk factor recording ranged from 22.2% for waist circumference to 95.6% for smoking status, and target attainment from 15.9% for waist circumference to 78.7% for smoking. Most patients used cardioprotective medications and 50.5% attended cardiac rehabilitation. Patients with secondary or tertiary education were more likely to meet targets for smoking, LDL cholesterol and physical activity in HICs and LMICs; for physical activity and triglycerides in UMICs; but less likely to meet targets for blood pressure in HICs and LDL &lt;1.4mmol/L in UMICs. Higher education was positively associated with medication use and cardiac rehabilitation participation. Conclusion: CHD patients generally have poor attainment of risk factor targets, but patients with a higher educational level are generally more likely to participate in cardiac rehabilitation, use medication, and meet targets. Main messages Target attainment and participation in cardiac rehabilitation are poor in CHD patients globally. Patients with higher education are more likely to meet risk factor targets, showing health inequities in secondary prevention of CHD. The association between education and risk factor target attainment and treatment varies with country income level.

Safety and efficacy of PCSK9 inhibitor (evolocumab) in patients with non-ST segment elevation acute coronary syndrome and non-culprit artery critical lesions: a randomised controlled trial protocol (SPECIAL study)

IntroductionPatients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify...

Cardiovascular risk assessment using SCORE2 in a population with hypertension – The reality at a primary health care unit

Introduction and objectivesCardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal, thus it is important to identify individuals at risk. Patients with hypertension have an increased risk of adverse cardiovascular (CV) events. The role of LDL cholesterol (LDL-C) in atherosclerotic CVD is well-established. SCORE2, a new CV risk calculation tool, is used to predict the 10-year risk of fatal or non-fatal CVD. The aim of this study was to understand the impact of SCORE2 on CV risk assessment in a population with hypertension from a moderate risk country, compared to the previously used SCORE. MethodsThis observational cross-sectional study analyzed a population census of 3146 patients diagnosed with hypertension without complications (K86). After applying inclusion and exclusion criteria, 654 patients were included. Data from medical records were collected to calculate and compare SCORE and SCORE2 categories and LDL-C targets. ResultsPatients were classified into SCORE categories: 188 (28.75%) low, 448 (68.5%) moderate, 17 (2.6%) high and 1 (0.15%) very high risk. Using SCORE2, individuals in the SCORE low risk category were reclassified, requiring new targets: 149 individuals (80%) as low to moderate and 39 (20%) as high risk. These differences became more evident when considering SCORE moderate and high-risk categories, where 358 patients (77%) received a higher CV risk categorization, and therefore a lower LDL-C target. There was a significant increase in individuals failing to meet the target when using SCORE2, compared to SCORE (p<0.001). ConclusionThese findings support the importance of CV risk assessment using SCORE2 algorithm in patients with hypertension.

Emerging therapies for refractory hypercholesterolemia: a narrative review.

Refractory hypercholesterolemia (RH) is characterized by the failure of patients to achieve therapeutic targets for low-density lipoprotein-cholesterol (LDL-C) despite receiving maximal tolerable doses of standard lipid-lowering treatments. It predominantly impacts individuals with familial hypercholesterolemia (FH), thereby elevating the risk of cardiovascular complications. The prevalence of RH is now recognized to be substantially greater than previously thought. This review provides a comprehensive insight into current and emerging therapies for RH patients, including groundbreaking genetic-based therapeutic approaches. The review places emphasis on the dependency of therapies on low-density lipoprotein receptors (LDLRs) and highlights the critical role of considering LDLR activity in RH patients for individualization of the treatment.

Lipid Levels and Risk of Diabetic Polyneuropathy in 2 Danish Type 2 Diabetes Cohorts.

Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM). We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression. We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users. High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.

Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis.

Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis.

Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

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.

Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial.

Recent changes in national and international lipid guidelines for reducing cardiovascular events recommend additional drugs, greater reductions, and lower targets for low-density lipoprotein cholesterol (LDL-C) if not attained with statins. The achievement of these targets with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has not yet been evaluated in a randomized clinical trial. To evaluate the 52-week safety and efficacy of lerodalcibep, a small anti-PCSK9-binding protein, in patients with cardiovascular disease (CVD) or who are at very high or high risk of CVD and requiring addition LDL-C-lowering treatment. This was a randomized, double-blind, placebo-controlled phase 3 trial. The trial was conducted at 66 clinics in 11 countries between April 23, 2021, and November 15, 2023. Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD were included. Patients were randomized 2:1 to monthly 1.2-mL subcutaneous lerodalcibep, 300 mg, or placebo for 52 weeks. The safety analysis included all randomized patients. The co-primary efficacy end points were percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52. Secondary efficacy outcomes included additional lipid apolipoprotein measures and achievement of guideline-recommended LDL-C targets. Of 922 randomized participants (mean [range] age, 64.5 [27-87] years; 414 [44.9%] female; mean [SD] baseline LDL-C, 116.2 [43.5] mg/dL), 811 (88%) completed the trial. The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all). With lerodalcibep, 555 of 615 participants (90%) achieved both a reduction in LDL-C of 50% or greater and recommended LDL-C targets during the study. Treatment-emergent adverse events were similar between lerodalcibep and placebo, except for injection site reactions. These occurred in 42 of 613 participants receiving lerodalcibep (6.9%) compared to 1 of 307 receiving placebo (0.3%), were graded mild or moderate, and did not result in higher discontinuation of treatment, at 26 of 613 (4.2%) and 14 of 307 (4.6%), respectively. Sporadic in vitro antidrug antibodies were detected, which had no impact on free PCSK9 or LDL-C-lowering efficacy. In this trial, lerodalcibep, a novel anti-PCSK9 small binding protein, dosed monthly and stable at ambient temperatures significantly reduced LDL-C in patients with CVD or at high risk of atherosclerotic cardiovascular disease with a safety profile similar to placebo. These results support long-term use of lerodalcibep in patients with CVD or at high risk of CVD who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone. ClinicalTrials.gov Identifier: NCT04806893.

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.

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.

Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond

There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.

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.

Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75years), yet their use in very-old adults (> 75years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65years (n = 152), 65-74years (n = 104), and ≥ 75years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70mg/dL compared to patients < 65years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55mg/dL. Low LLT uptake (16%) among older adults aged 64-74years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70mg/dL and < 55mg/dL, respectively. Oldest adults (≥ 75years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia.

A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups. Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study

BackgroundDefining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. MethodsA community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. ResultsSpearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. ConclusionBased on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

Effect and safety of PCSK9 inhibitor in-hospital use on blood lipid level in the ACS patients: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): none Aims To evaluate the effect and safety of in-hospital use of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor on blood lipid levels in the acute coronary syndrome (ACS) patients. Methods We searched the PubMed, MEDLINE, Web of Science, Ovid and Cochrane Library electronic databases through July 2023 to identify randomized controlled trials (RCTs) and cohort studies using PCSK9 inhibitors during ACS hospitalization. Then we compared the PCSK9 inhibitor group with a placebo or a blank control group with the same background of lipid-lowering therapy. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias for the included studies. A software was used to analyze the changes in overall lipids from baseline and the adverse event rates. Results A total of 15 studies enrolling 3891 patients with ACS were eligible, including 10 RCTs (n = 1406) and 5 cohort studies (n = 2485). Treatment with PCSK9 inhibitors showed a greater reduction in low-density lipoprotein cholesterol (LDLC) (SMD=1.46, 95% CI: 1.16-1.76, P&amp;lt;0.01). The cumulative meta-analysis of follow-up time showed that the degree of LDLC reduction stabilized after 12 weeks (SMD=1.42 at 12 weeks, 95% CI: 1.06-1.79, P&amp;lt;0.01), and thus, PCSK9 inhibitors dramatically decreased LDLC levels in comparison to controls at both ≤12 weeks and 12–72 weeks. The LDLC levels with PCSK9 inhibitors that reached the recommended standards of AHA/ACC (≤1.8mmol/l) and ESC (≤1.4mmol/l) were 95% and 80% respectively, which were significantly higher than those of the control group (58% and 22%). PCSK9 inhibitors can also reduce the total cholesterol, triglycerides, apolipoprotein B, and lipoprotein (a), while increasing the high-density lipoprotein cholesterol, but they have no statistical significance in reducing apolipoprotein A1. Compared with placebo or blank control, the addition of PCSK9 inhibitor did not increase the occurrence of adverse events (RR =-0.01,95% CI:-0.19-0.18, P = 0.95) and serious adverse events (RR =-0.03, 95% CI:-0.48-0.43, P=0.91). Conclusion In-hospital use of PCSK9 inhibitors can significantly improve the blood lipid levels of ACS patients and increase the target LDLC attainment rate, with satisfactory safety and good tolerance.

Assessment of post-myocardial infarction lipid levels and management: Results from a tertiary care hospital of Pakistan.

Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention. To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan. In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at < 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at < 55 mg/dL. Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% vs 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% vs 11.7%). Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.