Optimal Low-density Lipoprotein Cholesterol Research Articles

Intraindividual Discordance Between Remnant Cholesterol and Low-Density Lipoprotein Cholesterol Associated With Incident Stroke: Results From 2 National Cohorts.

The atherogenic effect of remnant cholesterol is being increasingly acknowledged. This study aimed to explore the association of discordance between remnant cholesterol and low-density lipoprotein cholesterol with stroke onset using 2 Chinese national cohorts. We studied 11 139 participants from CHARLS (China Health and Retirement Longitudinal Study) and 5993 participants from CHNS (China Health and Nutrition Survey) aged 45 years or older. The discordance between remnant cholesterol and low-density lipoprotein cholesterol was defined using the difference in percentile units (>15 units). There were 988 (8.9%) and 128 (2.1%) stroke events reported during follow-up in the 2 cohorts. Elevated remnant cholesterol was significantly associated with a higher risk of total stroke in 2 cohorts. After adjusting for remnant cholesterol level, the discordantly high remnant cholesterol group was significantly associated with an increased stroke risk (CHARLS: subdistribution hazard ratio [sHR], 1.31 [95 CI, 1.10-1.55]; CHNS: sHR, 1.84 [95 CI, 1.15-3.08]) compared with the discordantly low group. Consistent results were shown even among those with optimal low-density lipoprotein cholesterol level. The discordance between remnant cholesterol and low-density lipoprotein cholesterol, representing the intraindividual discrepancy, is significantly associated with stroke onset among Chinese adults.

The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up.

Despite the availability of statins and lifestyle modifications, many patients with Dyslipidemia struggle to achieve optimal low-density lipoprotein cholesterol (LDL-C) control. PCSK9 inhibitors offer a promising new therapeutic option with superior LDL-C lowering efficacy compared to statins. However, data on their real-world use, particularly in Iran, is limited. This study aims to address this gap by investigating the one-year effects of evolocumab on lipid profiles and potential cardiovascular outcomes in Iranian patients with Familial Hypercholesterolemia (FH).This single-center, prospective study evaluated evolocumab effectiveness in lowering LDL-C in 50 Iranian adults with FH. Participants with a documented LDL-C > 190 mg/dL on existing cholesterol medications (excluding PCSK9 inhibitors) and a clinical FH diagnosis was included. After baseline assessments (medical history, demographics, lipid profile), evolocumab was administered subcutaneously every two weeks for one year. Follow-up assessments at year one measured changes in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The study enrolled 50 participants with an average age of 55 years old (range 35-80 years).Treatment with evolocumab led to significant improvements in lipid profiles at all follow-up points compared to baseline. On average, LDL-C levels decreased by 105.24 mg/dL, triglycerides decreased by 59.20 mg/dL, and HDL-C levels increased by a modest but significant 4.5 mg/dL after one year(p<0.001). Subgroup analysis revealed no statistically significant interactions between baseline demographics (age, sex, BMI) or lifestyle habits (smoking, alcohol) and changes in lipid levels(p>0.05). However, a significant interaction emerged between baseline lipid levels and their corresponding reductions, suggesting greater improvement in patients with higher baseline values(p<0.05). It is noteworthy that no new cardiovascular events were reported during the study period. This study demonstrates the effectiveness of evolocumab in improving lipid profiles in Iranian patients with FH. The observed reductions in LDL-C and triglycerides, along with a modest increase in HDL-C, suggest potential benefits for cardiovascular risk reduction. The absence of new cardiovascular events during the study is encouraging, but further research with larger and longer-term follow-up is needed to confirm these findings and assess the long-term safety and impact on quality of life.

Efficacy and safety of bempedoic acid in acute coronary syndrome. Design of the clinical trial ES-BempeDACS

Introduction and objectivesOnly about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. MethodsAn independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. ResultsThe results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. ConclusionsEarly intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). Identification numberEudraCT 2021-006550-31.

Remnant Cholesterol and Carotid Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasonography in Patients With Ischemic Stroke.

We investigated the relationship between remnant cholesterol and carotid intraplaque neovascularization (IPN) assessed by contrast-enhanced ultrasonography (CEUS) in patients with ischemic stroke. This was a single-center study. Remnant cholesterol is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). All patients underwent CEUS. IPN is graded according to the presence and location of microbubbles within each plaque. The cohort included 110 patients with ischemic stroke. Patients with an IPN grading of 2 had higher triglyceride (TG), non-HDL-C, and remnant cholesterol concentrations than those with an IPN grading of < 2 (TG: 1.45 ± 0.69 vs. 0.96 ± 0.24 mmol/L, P < 0.001; non-HDL-C: 2.63 ± 0.85 vs. 2.31 ± 0.64 mmol/L, P = 0.037; remnant cholesterol: 0.57 ± 0.23 vs. 0.44 ± 0.07 mmol/L, P < 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for remnant cholesterol was 27.728 (2.714 - 283.253) for an IPN grading of 2 in the subset of patients with an optimal LDL-C concentration. The remnant cholesterol concentration is significantly associated with carotid IPN on CEUS in patients with ischemic stroke with an optimal LDL-C concentration. Remnant cholesterol may be an important indicator of risk stratification in patients with ischemic stroke.

Eficacia y seguridad del ácido bempedoico en el síndrome coronario agudo. Diseño del ensayo clínico ES-BempeDACS

Introduction and objectivesOnly about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. MethodsAn independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. ResultsThe results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. ConclusionsEarly intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). Identification numberEudraCT 2021-006550-31.

Lipid-Lowering Therapy after Acute Coronary Syndrome.

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.

New approaches to triglyceride reduction: Is there any hope left?

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

Effects of bempedoic acid on markers of inflammation and Lp(a).

To study the effect of bempedoic acid on markers of inflammation and lipoprotein (a) to help determine if the drug would be useful to treat patients with elevated cardiovascular risks and residual cardiovascular risk despite optimal low-density lipoprotein cholesterol (LDL-C) levels. Bempedoic acid is found to cause significant reduction in LDL-C and high-sensitivity C-reactive protein (hs-CRP) in various randomized clinical trials. Multiple meta-analyses have also found that bempedoic acid therapy leads to reduction in non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC) and apolipoprotein B (ApoB) levels. However, it has minimal effect on lipoprotein (a) (Lp(a)) level. Bempedoic acid is a new lipid-lowering agent that inhibits enzyme ATP-citrate lyase in the cholesterol biosynthesis pathway. Major risk of cardiovascular events and its associated morbidity and mortality are proportional to LDL-C and inflammatory markers levels. It was found that bempedoic acid significantly lowers LDL-C, hs-CRP and other inflammatory markers levels. This drug could potentially be used in patients with elevated cardiovascular risk, in patients with residual cardiovascular risk despite attaining LDL-C goal and in statin intolerant patients.

Mild untreated hypercholesterolaemia affects mechanical properties of the Achilles tendon but not gastrocnemius muscle

Tendon xanthoma and altered mechanical properties have been demonstrated in people with familial hypercholesterolaemia. However, it is unclear whether mild, untreated hypercholesterolaemia alters musculotendinous mechanical properties and muscle architecture. We conducted a case-control study of adults aged 50 years and over, without lower limb injury or history of statin medication. Based on fasting low-density lipoprotein (LDL) cholesterol levels, 6 participants had borderline high LDL (>3.33 mmol/L) and 6 had optimal LDL cholesterol (<2.56 mmol/L). Using shear wave elastography, shear wave velocity (SWV) of the Achilles tendon and gastrocnemius medialis muscle (a proxy for stiffness), along with muscle fascicle length and pennation angle were measured under four passive tensile loads (0, 0.5, 1.0, 1.5 kg) applied via a pulley system. Differences between groups were found for tendon SWV but not muscle SWV, fascicle length or pennation angle. Participants with hypercholesterolaemia showed greater SWV (mean difference, 95 % CI: 2.4 m/s, 0.9 to 4.0, P = 0.024) compared to the control group across all loads. These findings suggest that adults with mild hypercholesterolaemia have increased tendon stiffness under low passive loads, while muscle was not affected. Future research is needed to confirm findings in a larger cohort and explore the impact of hypercholesterolaemia on tendon fatigue injury and tendinopathy.

Assessment of Low-density Lipoprotein Cholesterol Levels and Non-invasive Vascular Health in School-aged Children: A Study in Ogasa District, Shizuoka Prefecture.

The present study assessed low-density lipoprotein cholesterol (LDL-C) levels in school-aged children from the Ogasa District of Shizuoka Prefecture and evaluated the utility of non-invasive vascular tests, namely flow-mediated dilation (FMD) and intima-media thickness (IMT), in pediatric patients with familial hypercholesterolemia (FH). We analyzed the lipid test results of 8,568 students screened for prevention of lifestyle-related diseases and 78 children under 15 years old with cholesterol levels exceeding 220 mg/dL who visited Chutoen General Medical Center. We examined the LDL-C distribution from school-age screenings and conducted FMD and IMT assessments on those meeting the 2022 Pediatric FH Guidelines criteria. Among the screened students, 186 (2.2%) exhibited LDL-C levels above 140 mg/dL, including 123 fourth-graders (2.8%) and 63 first-year junior high students (1.5%). The mean LDL-C level across all students was 90.0 mg/dL (standard deviation: 21.3 mg/dL), with the 95th percentile at approximately 125.0 mg/dL. Of the 78 children who visited the hospital, 65 met the FH diagnostic criteria. In children ≥ 10 years old, no significant IMT differences were observed between the Definitive and Probable FH groups and the Possible FH group; however, a significant difference in the FMD percentage was noted between these groups (9.9% [8.1%-11.9%] vs. 14.2% [11.6%-16.3%], P=0.003). Our findings highlight the LDL-C distribution in FH screening and suggest a potential reduction in FMD in pediatric FH patients ≥ 10 years old. These results emphasize the importance of initiating pharmacological interventions in school-aged children to maintain optimal LDL-C levels for lifelong cardiovascular health.

Statin therapy in individuals with intermediate cardiovascular risk

BackgroundAs intermediate cardiovascular risk group accounts for a large part of the total population, determining appropriate cholesterol target in this population is critical. Herein, we investigated the optimal low-density lipoprotein cholesterol (LDL-C) level in individuals with intermediate cardiovascular risk after statin therapy. MethodsThis was a nationwide observational and validation cohort study (median duration of follow-up: 7.5 and 8.7 years, respectively), using data from the Korean National Health Insurance Service and a tertiary hospital database. Among individuals who underwent regular health examinations, those with ≥2 cardiovascular risk factors except diabetes mellitus, LDL-C 100–189 mg/dL, and newly used statins were enrolled. Of the 358,694 screened people, 57,594 met the inclusion criteria, of whom 27,793 were finally analyzed. The study population was stratified according to post-treatment LDL-C levels as follows: <100, 100–119, 120–139, and ≥ 140 mg/dL. The primary outcome variable was composite cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke). From the patients screened of Severance Hospital cohort, 1859 meeting inclusion criteria were used for validation. ResultsThe rates of composite events ranged from 7.74 to 9.10 (mean 8.38)/1000 person-years in the three lower LDL-C groups. Adjusted hazard ratios (aHRs) ranged from 0.78 to 0.95 in the three groups with lower LDL-C, and a lower event risk was more evident in the groups that achieved LDL-C levels <120 mg/dL (p = 0.001–0.009). The total mortality risk did not differ between groups. In the validation cohort, the mean rate of composite events was 10.83/1000 person-years. aHRs ranged from 0.52 to 0.78 in the groups with lower LDL-C, and a lower risk was more obvious in patients who achieved LDL-C levels <100 mg/dL (p = 0.006–0.03). ConclusionsIndividuals with intermediate cardiovascular risk who achieved LDL-C levels <120 mg/dL after statin therapy had lower event risk. This result provides clinically useful evidence on target LDL-C levels in this population.

Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Incremental Benefit of Lipid Lowering in a Large Chinese Population Aged 75 Years and Older With Established Atherosclerotic Cardiovascular Disease

ObjectiveTo explore the optimal low-density lipoprotein cholesterol (LDL-C) level in patients aged 75 years and older with established atherosclerotic cardiovascular disease (ASCVD). Patients and MethodsWe conducted a retrospective multicenter cohort study of veterans aged 75 years and older with ASCVD who were regularly hospitalized or medically examined in 15 medical institutions in southern China from January 1, 2006, to December 31, 2013. Follow-up continued through October 1, 2021. The time-weighted average (TWA) LDL-C level represented the average LDL-C level during follow-up. Participants were divided into TWA LDL-C groups of 55.0 mg/dL or lower, 55.1 to 70.0 mg/dL, 70.1 to 85.0 mg/dL, 85.1 to 100.0 mg/dL, and greater than 100.0 mg/dL. The subgroup with LDL-C levels lower than 55.0 mg/dL was further subdivided into groups with LDL-C levels from 40.1 to 55.0 mg/dL and 40.0 mg/dL or less. The association of TWA LDL-C levels with outcomes was evaluated with Cox proportional hazards models. ResultsOverall, 6387 patients aged 75 years or older with ASCVD were included (mean age, 79.4 years). In total, 4267 major adverse cardiovascular events, 1518 stroke events, and 515 myocardial infarction events occurred during a mean follow-up of 12.7 years. Generally, lower TWA LDL-C level was associated with a lower risk of cardiovascular events but was not associated with a higher risk of adverse events in elderly individuals with ASCVD, with the lowest cardiovascular risk observed for LDL-C levels of less than 55.0 mg/dL. After multivariable adjustment, the risk of a major adverse cardiovascular event was 1.30 (95% CI, 1.26 to 1.34; P<.001) for a per SD increment in TWA LDL-C level. Compared with TWA LDL-C levels of 40.1 to 55.0 mg/dL, TWA LDL-C levels of 40.0 mg/dL or less were associated with an increased risk of hemorrhagic stroke (hazard ratio, 3.71; 95% CI, 1.89 to 7.26). ConclusionLow-density lipoprotein cholesterol levels from 40.1 to 55.0 mg/dL exhibited the maximum cardiovascular benefit in patients aged 75 years and older who had ASCVD. Lowering LDL-C levels to 40.0 mg/dL or less might increase the risk of hemorrhagic stroke.

Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

Lipoprotein(a) as a Higher Residual Risk for Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus than without.

Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level. This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People's Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation. There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12-3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36-4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C<1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L). Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.

Optimal lipid-lowering therapy in patients who were functionally deferred percutaneous coronary intervention

Deferral of percutaneous coronary intervention (PCI) for functionally insignificant stenosis, defined as fractional flow reserve (FFR) > 0.80, is associated with favorable long-term prognoses. The lower-the-better strategy for low-density lipoprotein cholesterol (LDL-C) management is an established non-angioplasty therapy to improve the clinical outcomes of patients undergoing PCI. We examined the optimal LDL-C management in cases of intermediate coronary stenosis with deferred PCI on the basis of FFR values. This observational study included 273 consecutive patients with a single target vessel and deferred PCI with an FFR > 0.80. Patients with an FFR of 0.81–0.85 (n = 93) and those with FFR > 0.85 (n = 180) were classified into the lower (< 100 mg/dL) and higher (≥ 100 mg/dL) LDL-C groups. The endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, non-fatal myocardial infarction, ischemic stroke, heart failure hospitalization, and unplanned revascularization. Patients with an FFR of 0.81–0.85 had a significantly higher MACCE rate than those with an FFR > 0.85 (log-rank, p = 0.003). In patients with an FFR of 0.81–0.85, the lower LDL-C group showed a significantly lower MACCE rate than the higher LDL-C group (log-rank, p = 0.006). However, the event rate did not differ significantly between the two groups in patients with FFR > 0.85 (log-rank, p = 0.84). Uncontrolled LDL-C levels were associated with higher MACCE rates in cases with deferred PCI due to an FFR of 0.81–0.85. This high-risk population for adverse cardiovascular events should receive strict LDL-C-lowering therapy.

Association of Multitrajectories of Lipid Indices With Premature Cardiovascular Disease: A Cohort Study.

Background The multitrajectory model can identify joint longitudinal patterns of different lipids simultaneously, which might help better understand the heterogeneous risk of premature cardiovascular disease (CVD) and facilitate targeted prevention programs. This study aimed to investigate the associations between multitrajectories of lipids with premature CVD. Methods and Results The study enrolled 78 526 participants from the Kailuan study, a prospective cohort study in Tangshan, China. Five distinct multitrajectories of triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol over 6-year exposure were identified on the basis of Nagin's criteria, using group-based multitrajectory modeling. During a median follow-up of 6.75 years (507 645.94 person-years), 665 (0.85%) premature CVDs occurred. After adjustment for confounders, the highest risk of premature CVD was observed in group 4 (the highest and increasing triglyceride, optimal and decreasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (hazard ratio [HR], 2.13 [95% CI, 1.36-3.32]), followed by group 5 (high and decreasing triglyceride, optimal and increasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (HR, 2.07 [95% CI, 1.45-2.98]), and group 3 (optimal and increasing triglyceride, borderline high and increasing LDL-C, optimal and decreasing high-density lipoprotein cholesterol) (HR, 1.90 [95% CI, 1.32-2.73]). Conclusions Our results showed that the residual risk of premature CVD caused by increasing triglyceride levels remained high despite the fact that LDL-C levels were optimal or declining over time. These findings emphasized the importance of assessing the joint longitudinal patterns of lipids and undertaking potential interventions on triglyceride lowering to reduce the residual risk of premature CVD, even among individuals with optimal LDL-C levels.

Preoperative serum low-density lipoprotein cholesterol is an independent prognostic factor in patients with renal cell carcinoma after nephrectomy

BackgroundLittle is known about the association between the preoperative low-density lipoprotein cholesterol (LDL-C) level and prognosis in patients with renal cell carcinoma (RCC) after nephrectomy, and its prognostic value needs to be elucidated.MethodsThe clinical and follow-up data of 737 RCC patients who underwent nephrectomy were retrospectively analyzed. The optimal cut-off LDL-C level was determined using X-tile, and then patients were divided into low and high LDL-C groups. The association between LDL-C levels and survival of RCC patients was assessed using the Kaplan-Meier method and Cox regression analysis.ResultsThe optimal cut-off LDL-C level was 1.93 mmol/L, and patients were divided into the low (≤ 1.93 mmol/L) and high LDL-C (> 1.93 mmol/L) groups. The Kaplan-Meier analysis showed that patients in the low LDL-C group had significantly shorter overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) than those in the high LDL-C group (P = 0.001, P = 0.001, and P = 0.003, respectively). The COX univariate analysis showed that the preoperative LDL-C level was closely associated with OS, CSS, and RFS in RCC patients (P = 0.002, P = 0.003, and P = 0.005, respectively). The multivariate analysis showed that the preoperative LDL-C level was an independent factor for predicting survival (OS, CSS and RFS) in RCC patients after nephrectomy. The low preoperative LDL-C levels predicted worse OS (hazard ratio [HR]: 2.337; 95% confidence interval [CI]: 1.192–4.581; P = 0.013), CSS (HR: 3.347; 95% CI: 1.515–7.392; P = 0.003), and RFS (HR: 2.207; 95% CI: 1.178–4.132; P = 0.013).ConclusionsThe preoperative LDL-C level is an independent factor for the prognosis of RCC patients after nephrectomy, and low preoperative LDL-C levels predict worse survival (OS, CSS, and RFS).

Type 1 diabetes management: Room for improvement.

Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Longitudinal association of remnant cholesterol with joint arteriosclerosis and atherosclerosis progression beyond LDL cholesterol

BackgroundArteriosclerosis and atherosclerosis are closely related with cardiovascular disease (CVD) risk. Remnant cholesterol (RC) could predict CVD. However, its effect on joint arteriosclerosis and atherosclerosis progression remains unclear. This study aims to evaluate the association of RC with joint arteriosclerosis and atherosclerosis progression trajectories in the general population.MethodsThis study collected data across five biennial surveys of the Beijing Health Management Cohort from 2010 to 2019. Multi-trajectory model was used to determine the joint arteriosclerosis and atherosclerosis progression patterns by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). We also performed discordance analyses for RC vs. low density lipoprotein cholesterol (LDL-C) using ordinal logistics model.ResultsA total of 3186 participants were included, with three clusters following distinct arteriosclerosis and atherosclerosis progression patterns identified using a multi-trajectory model. In the multivariable-adjusted ordinal logistics analyses, RC was significantly associated with baPWV and ABI progression (OR: 1.20; 95% CI: 1.13–1.28, per 10 mg/dL). For the discordance analyses, the discordant low RC group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60–0.89). People with a high RC level were at an increased risk of joint arteriosclerosis and atherosclerosis progression, even with optimal LDL-C.ConclusionsRC is independently associated with joint arteriosclerosis and atherosclerosis progression beyond LDL-C. RC could be an earlier risk factor than LDL-C of arteriosclerosis and atherosclerosis in the general population.