BACKGROUND: Protection against vascular inflammation in endothelial cells represents a pivotal atheroprotective attribute of high-density lipoproteins (HDL). OBJECTIVE: The present study sought to assess the predictive v...BACKGROUND: Protection against vascular inflammation in endothelial cells represents a pivotal atheroprotective attribute of high-density lipoproteins (HDL). OBJECTIVE: The present study sought to assess the predictive value of the HDL anti-inflammatory property for major adverse cardiovascular events (MACE). METHODS: The anti-inflammatory property of HDL was evaluated by its ability to suppress vascular cell adhesion molecule-1 mRNA expression stimulated by tumor necrosis factor α in endothelial cells in a prospective study of patients with coronary artery disease from South China (n = 466, median follow-up of 2.3 years). The primary endpoint was MACE, encompassing nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS: Within the study population (mean age 64.0 years, 77.9% male), 12.7% experienced recurrent MACE. After multivariable adjustment, higher HDL anti-inflammatory property was independently linked to lower residual cardiovascular risk (adjusted hazard ratio [aHR]: 0.96, 95% CI: 0.92-0.99; P = .022), with a linear inverse relationship (P for nonlinearity = .128). When divided into tertiles, patients with the highest HDL anti-inflammatory property showed significantly reduced MACE risk compared with the reference group in the multivariable-adjusted model (aHR: 0.48, 95% CI: 0.24-0.97; P = .040). Mediation analysis revealed that estimated glomerular filtration rate mediated 36.6% (P < .001) of the observed association. Moreover, subgroup analysis revealed a stronger protective effect in female patients (aHR: 0.73, 95% CI: 0.55-0.97). CONCLUSION: Our findings indicate that better HDL anti-inflammatory function was linked to reduced recurrent MACE risk, independent of HDL cholesterol levels and statin treatment. Kidney function partially mediated this association. These findings underscore the prognostic relevance of HDL functional assessment in secondary cardiovascular prevention.
The 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline marks a defining moment for lipidology with the reinstatement of low-density lipoprotein cholesterol (LDL‑C) and non-...The 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline marks a defining moment for lipidology with the reinstatement of low-density lipoprotein cholesterol (LDL‑C) and non-high-density lipoprotein cholesterol treatment goals and a decisive endorsement of combination lipid‑lowering therapy. Although statins remain foundational, statin monotherapy often fails to achieve sufficient LDL‑C lowering, particularly in high-risk patients or patients with statin intolerance or refusal. These realities elevate nonstatin therapies from secondary considerations to core components of evidence‑based care. This commentary reviews the expanded role of currently available nonstatin agents across all guideline‑defined treatment groups. New outcomes data further strengthen the rationale for greater LDL‑C reduction in high‑risk primary prevention populations and reinforce the "lower is better" principle central to lipidology. Finally, we explore the rapidly evolving pipeline of next‑generation LDL‑C-lowering therapies, including long‑acting injectables and oral proprotein convertase subtilisin/kexin type 9 inhibitors, that promise to further individualize care and address longstanding barriers to adherence and goal attainment. These advances underscore a new lipid‑lowering paradigm that includes combination therapy to achieve and sustain optimal LDL‑C levels and meaningfully reduce atherosclerotic cardiovascular disease risk.
BACKGROUND: Remnant cholesterol (RC) is a known contributor to cardiovascular disease, but its role in gestational diabetes mellitus (GDM) remains insufficiently characterized. OBJECTIVE: To examine the association betwe...BACKGROUND: Remnant cholesterol (RC) is a known contributor to cardiovascular disease, but its role in gestational diabetes mellitus (GDM) remains insufficiently characterized. OBJECTIVE: To examine the association between first-trimester RC levels and GDM risk, and to quantify the mediating effects of prepregnancy body mass index (BMI) and insulin sensitivity. METHODS: This prospective cohort study included 877 pregnant women in Southeastern China. RC was calculated from first-trimester fasting lipid profiles. GDM was diagnosed via a 75 g oral glucose tolerance test at 24 to 28 weeks. Binary logistic regression, restricted cubic splines, and serial mediation models were employed for analysis. RESULTS: Among all participants, 160 (18.2%) developed GDM. After full adjustment for confounders, women in the highest quartile of first-trimester RC had a significantly higher risk of GDM (odds ratio = 2.850, 95% CI: 1.679-4.836) compared with those in the lowest quartile. A significant positive dose-response relationship was observed (P for overall < .001). Serial mediation analysis indicated that the association between RC and GDM was partially mediated through the sequential pathway of prepregnancy BMI → Matsuda index, accounting for 13.50% of the total effect. RC also showed modest predictive performance for GDM (area under the curve = 0.673) compared with conventional lipid parameters. CONCLUSION: Elevated first-trimester RC is independently associated with increased GDM risk. This association is partially mediated by prepregnancy BMI and subsequent insulin resistance. Measuring RC in early pregnancy may improve the identification of women at high risk for GDM.
BACKGROUND: Combined dyslipidemia of overweight/obesity (CDO) is prevalent in youth and is associated with an increased risk of early cardiovascular disease. OBJECTIVE: We sought to determine the impact and safety of sta...BACKGROUND: Combined dyslipidemia of overweight/obesity (CDO) is prevalent in youth and is associated with an increased risk of early cardiovascular disease. OBJECTIVE: We sought to determine the impact and safety of statin therapy for CDO in adolescents. METHODS: A double-blind, randomized trial was performed across 18 North American sites. Participants aged 10 to 19 years with body mass index ≥85th percentile and CDO defined as non-high-density lipoprotein cholesterol (non-HDL-C) ≥120 mg/dL (3.10 mmol/L) and either low HDL-C or high triglyceride:HDL-C ratio were randomized centrally to receive either pitavastatin calcium 4 mg/d or placebo for 2 years. The primary outcome was change in carotid-femoral pulse wave velocity (PWV), assessed at baseline, 6, 12, 18, and 24 months. Secondary outcomes included safety and lipid measures. RESULTS: The intention-to-treat analysis included 59 participants (33 males) who received pitavastatin calcium and 60 who received placebo (32 males), enrolled from June 2018 to April 2021. There were no significant changes or trends for PWV in either group. Compared with placebo, at 24 months, pitavastatin was associated with significantly reduced low-density lipoprotein cholesterol (from 134 ± 23 mg/dL [3.47 ± 0.60 mmol/L] to 105 ± 25 mg/dL [2.72 ± 0.65 mmol/L] pitavastatin vs 130 ± 25 mg/dL [3.37 ± 0.65 mmol/L] to 126 ± 27 mg/dL [3.26 ± 0.70 mmol/L] placebo; P < .001). There was 1 serious adverse event (placebo), and no significant differences in liver enzymes, muscle toxicity, glucose homeostasis, or linear growth. CONCLUSION: Over 2 years, treatment with pitavastatin calcium of CDO for adolescents resulted in no changes in vascular measures. Statin therapy safely lowered atherogenic lipid particles, potentially reducing cardiovascular risk.
BACKGROUND: The incidence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is rising and is prone to a poor prognosis. Low molecular weight heparin (LMWH) has garnered attention in acute pancreatitis treatment...BACKGROUND: The incidence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is rising and is prone to a poor prognosis. Low molecular weight heparin (LMWH) has garnered attention in acute pancreatitis treatment due to its anti-inflammatory, microcirculation-improving effects, but evidence for its efficacy and safety specifically in HTG-AP is limited. OBJECTIVE: To evaluate the impact of early LMWH administration (within 48 hours of admission) on in-hospital mortality and other clinical outcomes in patients with HTG-AP. METHODS: Based on a single-center database (2005-2023), 2862 patients with HTG-AP were included (LMWH group: 960; non-LMWH group: 1902). LMWH treatment was administered within 48 hours of admission (mean duration: 7 days). The primary outcome was in-hospital mortality. Secondary outcomes included persistent organ failure and bleeding complications. Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were used to adjust for baseline differences and evaluate LMWH efficacy. RESULTS: After adjustment with PSM, IPTW, and OW, mortality was significantly lower in the LMWH group compared with the non-LMWH group (adjusted hazard ratio 0.44-0.47, all P < .05). LMWH significantly reduced the risk of persistent organ failure (P < .01) and the need for continuous renal replacement therapy (5.3% vs 8.3%, P = .01), without increasing bleeding risk (gastrointestinal bleeding: 0.3% vs 0.7%; abdominal bleeding: 1.0% vs 0.6%, all P > .05). Subgroup analysis showed more pronounced benefits in patients aged <60 years, those with diabetes, or those with Acute Physiology and Chronic Health Evaluation II ≥8. CONCLUSION: Early application of LMWH was associated with a significant reduction in mortality and organ failure risk in patients with HTG-AP without increasing bleeding complications. Patients with severe disease, diabetes, or high inflammatory burden may derive greater benefit, but further mechanistic studies are needed to guide patient selection.
BACKGROUND: Severe hypertriglyceridemia (sHTG) has a causal role in acute pancreatitis (AP), whereas the relationship between triglyceride (TG) levels and risk of cardiovascular (CV) events is less well-known. OBJECTIVE:...BACKGROUND: Severe hypertriglyceridemia (sHTG) has a causal role in acute pancreatitis (AP), whereas the relationship between triglyceride (TG) levels and risk of cardiovascular (CV) events is less well-known. OBJECTIVE: To assess the incidence, risk, and odds of AP and CV events among US adults with sHTG and hypertriglyceridemia (HTG) compared to those with normal TG levels. METHODS: The Optum Research Database identified 4 cohorts of adults with a TG test between January 1, 2017, and March 31, 2021. sHTG (500 ≤ TG <880 mg/dL) and extreme HTG (eHTG; TG ≥880 mg/dL) were identified first, followed by random identification of normal TG (35 ≤ TG <150 mg/dL) and HTG (150 ≤ TG <500 mg/dL) cohorts. Primary outcomes included incidence, adjusted risk, and adjusted odds of AP and CV events. RESULTS: A total of 134,116 patients were included: 46,676 (34.8%) with normal TG, 54,090 (40.3%) with HTG, 28,556 (21.3%) with sHTG, and 4994 (3.7%) with eHTG. Incidents of both outcomes were significantly higher for HTG, sHTG, and eHTG, compared with normal TG (P < .001). Adjusted hazard ratios (HRs) of AP were 1.491, 2.586, and 4.695 for HTG, sHTG, and eHTG, respectively (all P < .001). Adjusted HRs of CV events were 1.163 and 1.206 for sHTG and eHTG, respectively (both P < .001). CONCLUSION: In this cohort study, patients with sHTG and eHTG had significantly higher incidence of AP and CV events, compared with those with normal TG. The adjusted risk of AP and CV events increased stepwise with TG level; the association was stronger for AP.
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a severe, life-threatening genetic disorder resulting from pathogenic variants in genes involved in lipoprotein lipase (LPL) function, including LPL, APOC2, APOA5, G...BACKGROUND: Familial chylomicronemia syndrome (FCS) is a severe, life-threatening genetic disorder resulting from pathogenic variants in genes involved in lipoprotein lipase (LPL) function, including LPL, APOC2, APOA5, GPIHBP1, and LMF1. OBJECTIVE: This study aimed to assess the quality of life (QoL) of patients with FCS and explore the relationship between clinical symptoms, comorbidities, and QoL. METHODS: The study was conducted over 12 months and involved genetically confirmed patients with FCS and healthy controls in Saudi Arabia. Data were collected using a structured questionnaire and the validated Arabic version of the PedsQL 4.0 Generic Core Scale. Statistical analyses included descriptive statistics, the Mann-Whitney U test for comparisons between patients with FCS and healthy controls, and Fisher's exact test for categorical variables. A P value of <.05 was considered statistically significant. RESULTS: Twenty-eight patients with FCS and 142 controls participated. Commonly reported symptoms among patients with FCS included stomach bloating (25%), persistent stomach pain (21%), nausea (18%), xanthomas (21%), and anxiety related to pancreatitis (39%). Comorbidities such as chronic pancreatitis (29%), vision problems (18%), weakness (14%), and eating disorders (11%) were also observed. Patients with frequent stomach pain (P = .002), bloating (P = .016), and nausea (P = .044) were significantly more likely to have comorbidities. In addition, xanthomas (P = .038) and anxiety related to pancreatitis (P = .049) were more prevalent in patients with comorbidities. QoL was significantly lower in patients with FCS with comorbidities (median score 86) compared with those without (median 92, P = .019), particularly in the physical health domain (P = .006). CONCLUSION: FCS significantly affects QoL, especially when comorbidities are present. Symptom burden, particularly gastrointestinal symptoms, is closely linked to comorbidities and poorer QoL. These findings highlight the need for symptom-focused care and early comorbidity management to improve patient outcomes.
BACKGROUND: Existing evidence regarding the effect of leptin on low-density lipoprotein cholesterol (LDL-C) is inconsistent. One possible explanation for this inconsistency is sleep-disordered breathing (SDB), a common c...BACKGROUND: Existing evidence regarding the effect of leptin on low-density lipoprotein cholesterol (LDL-C) is inconsistent. One possible explanation for this inconsistency is sleep-disordered breathing (SDB), a common condition associated with both leptin and dyslipidemia. OBJECTIVE: This study aimed to clarify the role of leptin in the regulation of LDL-C in humans and to examine whether SDB modifies this association. METHODS: We analyzed data from the Toon Health Study. Among those who completed baseline examinations, leptin and LDL-C measurements were available for 1113 participants. Follow-up examinations were conducted 5 years later. SDB was assessed using overnight pulse oximetry. Longitudinal changes in LDL-C were evaluated using linear mixed-effects models. Serum leptin levels were analyzed in sex-specific quartiles; for stratified analyses, high leptin was defined as above the sex-specific 75th percentile. RESULTS: Over the 5-year follow-up period, upper-quartile baseline leptin levels were associated with a pronounced decline in LDL-C compared with the lowest quartile. Comparison of the high and low leptin groups revealed that this association was evident only among participants without SDB (n = 149 and 570, respectively). When a stricter cutoff of oxygen desaturation index (<2) was applied, the association remained significant (n = 79 and 347, respectively). Moreover, the 3-way interaction term (leptin × time × SDB status) reached statistical significance. CONCLUSION: Higher baseline leptin levels were associated with a statistically significant decline in LDL-C over 5 years, particularly among individuals without SDB. These results suggest that SDB modifies the longitudinal association between leptin and LDL-C.
BACKGROUND: Autoimmune diseases are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk driven by chronic systemic inflammation and prothrombotic mechanisms. Lipoprotein(a) [Lp(a)] is a causal A...BACKGROUND: Autoimmune diseases are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk driven by chronic systemic inflammation and prothrombotic mechanisms. Lipoprotein(a) [Lp(a)] is a causal ASCVD risk factor with proinflammatory and antifibrinolytic properties; however, its role in autoimmune diseases and the impact of immunomodulatory therapies remain unclear. OBJECTIVE: To evaluate the consistency of Lp(a) elevation across autoimmune diseases and whether anti-inflammatory or immunomodulatory therapies modify circulating Lp(a) levels. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-guided systematic review registered in International Prospective Register of Systematic Reviews (PROSPERO)(CRD420251121143) was conducted. MEDLINE and Cochrane were searched for English-language studies (1990-2025) assessing Lp(a) in adults with autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, psoriasis, Behçet's disease, and Takayasu arteritis. Two reviewers independently screened studies and assessed quality using the Newcastle-Ottawa Scale. Findings were synthesized descriptively. RESULTS: Of 313 records, 13 studies met the inclusion criteria. Elevated Lp(a) was frequently observed, with variable outcome associations. In systemic lupus erythematosus, higher Lp(a) correlated with renal involvement and inflammatory activity, whereas cardiovascular associations were inconsistent. In rheumatoid arthritis, tumor necrosis factor inhibitor therapy did not significantly modify Lp(a). In psoriasis, Mendelian randomization supported a causal association between psoriasis and elevated Lp(a). In Takayasu arteritis and Behçet's disease, elevated Lp(a) was linked to vascular involvement. A population-based cohort demonstrated additive cardiovascular risk among individuals with autoimmune disease and elevated Lp(a). CONCLUSION: Lp(a) elevation is common across autoimmune diseases and may contribute to excess ASCVD risk. Evidence for modification with immunomodulatory therapy is limited. Prospective studies are needed.
Zubarioglu T, Yalçın-Çakmaklı G, Yıldız Y
… +15 more, Bulut FD, Kor D, Yıldız S, Kadıoğlu-Yılmaz B, Öztürk-Hi̇şmi̇ B, Genç E, Güneş D, Karaca M, Akgün A, Yıldız M, Teke-Kısa P, Arslan N, Eli̇bol B, Kıykım E, Aktuğlu-Zeybek Ç
BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a progressive neurometabolic disorder, and chenodeoxycholic acid (CDCA) is the primary treatment that effectively prevents disease progression. However, using CDCA duri...BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a progressive neurometabolic disorder, and chenodeoxycholic acid (CDCA) is the primary treatment that effectively prevents disease progression. However, using CDCA during pregnancy presents clinical challenges due to limited safety data and theoretical concerns about fetal teratogenicity. OBJECTIVE: This study aims to evaluate maternal and neonatal outcomes in genetically confirmed CTX pregnancies and to assess the safety profile of CDCA when used during pregnancy. METHODS: This retrospective, multicenter study included 19 pregnancies in 12 women with CTX. Data were collected on maternal neurological status, pregnancy outcomes, neonatal characteristics, and long-term offspring development. CDCA treatment status during pregnancy was documented, and outcomes were compared. RESULTS: Of the 19 pregnancies, 16 resulted in live births (84.2%), whereas 3 ended in spontaneous abortions-all in a single undiagnosed patient. Among the 5 pregnancies with a prior CTX diagnosis, 4 were treated with CDCA during gestation. No maternal neurological deterioration or fetal malformations were observed in CDCA-treated pregnancies. In contrast, adverse findings, including neurological decline in 1 mother, a case of spina bifida, and cognitive impairment in offspring, were limited to pregnancies without CDCA treatment. No fetal or neonatal complications suggestive of CDCA-related toxicity were detected. CONCLUSION: Our findings support evidence that continuing CDCA therapy during pregnancy in women with CTX is associated with favorable maternal and fetal outcomes, with no clear indications of teratogenicity. Maintaining CDCA treatment appears to contribute to maternal neurological stability.
BACKGROUND: Cardiovascular outcomes trials depend on adequate event accrual for statistical power. Patients with severe hypercholesterolemia (SH), defined as low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL, have e...BACKGROUND: Cardiovascular outcomes trials depend on adequate event accrual for statistical power. Patients with severe hypercholesterolemia (SH), defined as low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL, have elevated cardiovascular risk and frequently harbor undiagnosed familial hypercholesterolemia (FH). Lipid-lowering therapies mask diagnostic LDL-C levels at screening. OBJECTIVE: To determine whether pretreatment LDL-C calculation at trial enrollment could identify undiagnosed SH and facilitate opportunistic FH screening. METHODS: We applied correction factors to baseline LDL-C to calculate pretreatment LDL-C in ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Participants at a High Risk for Vascular Outcomes) participants (n = 11,993) and across 57 trials informing the 2018 Multisociety Blood Cholesterol Guideline. SH was defined as pretreatment LDL-C ≥190 mg/dL; clinically probable FH as SH plus family history of hypercholesterolemia in a first- or second-degree relative. The association between SH and major adverse cardiovascular events (MACE) was examined using multivariable Cox regression. RESULTS: In ACCELERATE, 15.1% (1809/11,993) had SH and 2.1% (255/11,993) met criteria for probable FH, 3- and 5-fold higher than population prevalences (∼5% and ∼0.4%). Across 57 guideline-informing trials, weighted SH prevalence was 14% (range 0%-77%). Pretreatment LDL-C ≥190 mg/dL was associated with higher MACE incidence among ACCELERATE participants (15.1% vs 13.5%; adjusted hazard ratio 1.19, 95% CI 1.03-1.38, P = .021). CONCLUSION: SH and probable FH are more prevalent in cardiovascular outcomes trial participants than in the general population, and SH was associated with increased MACE risk. Pretreatment LDL-C calculation at enrollment can enrich trials for higher-risk participants and enable opportunistic identification of probable FH for cascade screening. This dual approach may reduce trial costs whilst identifying a critically underdiagnosed condition.
BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor increasingly linked to calcific valvular disease. Although its role in aortic stenosis is well established, the association betwee...BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor increasingly linked to calcific valvular disease. Although its role in aortic stenosis is well established, the association between Lp(a) and mitral valve pathology, particularly mitral annular calcification (MAC), mitral stenosis (MS), and mitral regurgitation (MR), remains uncertain. OBJECTIVE: To evaluate the association between elevated Lp(a) levels and mitral valve disease in a large, real-world cohort. METHODS: We conducted a retrospective observational analysis using the TriNetX research network, including over 130,000 adults with available Lp(a) measurements. Patients with Lp(a) >50 mg/dL were propensity score matched 1:1 to those with Lp(a) <50 mg/dL across 54 demographic, clinical, and treatment variables. Valvular outcomes were defined using administrative codes. Kaplan-Meier survival estimates and log-rank tests were calculated in the matched cohorts. The primary outcome was MAC, with MR, MS, and mitral valve prolapse (MVP) as secondary outcomes. AS served as a positive control. RESULTS: Each matched cohort included 66,292 patients. Elevated Lp(a) was significantly associated with the primary outcome of MAC (hazard ratio [HR] 1.330, 95% CI 1.172-1.509, P < .001). The positive control outcome of AS(Aortic stenosis) was also significant (HR 1.313, 95% CI 1.175-1.466, P < .001). No significant associations were observed for the secondary outcomes of MR (HR 1.006, 95% CI 0.940-1.077, P = .856), MS (HR 1.178, 95% CI 0.875-1.587, P = .280), or MVP (HR 1.035, 95% CI 0.863-1.241, P = .710). CONCLUSION: In this large multicenter propensity-matched cohort, elevated Lp(a) was independently associated with MAC but not with MS, MR, or mitral valve prolapse. These findings support a potential role of Lp(a) in mitral annular calcification and highlight the need for prospective studies to clarify causality and clinical implications.
BACKGROUND: Chylomicronemia is associated with extreme hypertriglyceridemia and an increased risk of acute pancreatitis and cardiometabolic complications. Rarely, chylomicronemia persists despite control of secondary cau...BACKGROUND: Chylomicronemia is associated with extreme hypertriglyceridemia and an increased risk of acute pancreatitis and cardiometabolic complications. Rarely, chylomicronemia persists despite control of secondary causes and conventional treatments. The most severe form of persistent chylomicronemia (PC) is familial chylomicronemia syndrome (FCS). Diagnosis scoring systems have been developed to help clinicians differentiate FCS from other causes of chylomicronemia. OBJECTIVE: To assess the ability of FCS diagnosis scoring systems to discriminate FCS from other forms of PC. METHODS: This study included 413 Caucasians presenting a history of chylomicronemia, among whom 65 (15.7%) met the criteria of PC. The performance of 3 FCS diagnosis scoring systems (French Canadian, European, and North American) was evaluated. RESULTS: Among the 65 individuals with PC, 39 carried a biallelic combination of pathogenic variants (biallelic FCS). The 26 others were classified according to whether they presented a score above (clinical FCS) or below (multifactorial PC) the diagnosis threshold of FCS. Using the French Canadian system, 20/26 (76.9%) met FCS diagnosis criteria (clinical FCS) compared with 16/26 (61.5%) with the European system, 7/26 (26.9%) with the North American system at the threshold of 45 (FCS very likely), and 1 (3.8%) at the threshold of 60 (definite FCS). Among the 39 biallelic FCS, some scored below the clinical threshold of FCS. CONCLUSION: All diagnosis scoring systems, including the North American system at a threshold of 45, discriminate multifactorial PC from biallelic FCS and fairly identify people presenting characteristics of FCS without having the capacity of distinguishing biallelic FCS from clinical FCS. FCS clinical diagnosis systems might contribute to equitable access to precision medicine for patients affected by PC.
BACKGROUND: Despite extensive efforts to lower low-density lipoprotein cholesterol (LDL-C), cardiovascular disease remains highly prevalent. Remnant cholesterol (RC) has been proposed as a potentially more relevant thera...BACKGROUND: Despite extensive efforts to lower low-density lipoprotein cholesterol (LDL-C), cardiovascular disease remains highly prevalent. Remnant cholesterol (RC) has been proposed as a potentially more relevant therapeutic target. OBJECTIVE: To evaluate the association between RC reduction and cardiovascular outcomes in randomized controlled trials (RCTs) of cholesterol- and triglyceride-lowering therapies, assessing whether RC independently influences cardiovascular risk. METHODS: Cochrane Central and Embase were searched for RCTs with ≥1000 participants and ≥2 years' planned duration that assessed cholesterol- or triglyceride-lowering therapies vs placebo, usual care, or other lipid-lowering drugs in adults. Two reviewers independently extracted data and evaluated methodological quality. Meta-analysis and meta-regression were performed. RESULTS: Forty-three RCTs met the inclusion criteria; most had some risk of bias, and evidence certainty was moderate. Meta-analysis showed absolute risk reductions of 0.4% (95% CI 0.1%-0.6%) for all-cause mortality, 1.3% (95% CI 1.1%-1.6%) for myocardial infarction, and 0.4% (95% CI 0.2%-0.6%) for stroke in treatment vs control groups. Meta-regression demonstrated no association between RC reduction and any clinical outcome, whereas LDL-C and non-high-density lipoprotein cholesterol reductions were associated with risk reduction. CONCLUSION: RC reduction was not associated with cardiovascular benefit. This contrasts with observational and Mendelian randomization studies, likely reflecting methodological differences; MR estimates lifelong genetically mediated exposure and may not reliably predict the effects of short-term pharmacological lipid lowering. LAY SUMMARY: In a review of 43 large clinical trials, lowering "remnant cholesterol" did not reduce heart attacks, strokes, or deaths - unlike lowering LDL ("bad") cholesterol, which did - suggesting that remnant cholesterol may not be a useful treatment target despite earlier studies hinting otherwise.Summary sentence A review of 43 clinical trials found that lowering remnant cholesterol did not translate into fewer deaths, heart attacks, or strokes.
BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal contributor to atherosclerotic cardiovascular disease (ASCVD). While no therapies are currently approved solely for lowering Lp(a), subgroup analyses suggest that i...BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal contributor to atherosclerotic cardiovascular disease (ASCVD). While no therapies are currently approved solely for lowering Lp(a), subgroup analyses suggest that individuals with elevated Lp(a) may gain added benefit from intensive lipid-lowering strategies. No prior meta-analysis has compared evolocumab, alirocumab, inclisiran, lerodalcibep, and enlicitide in their Lp(a)-lowering efficacy. We aimed to determine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) targeted therapies differ significantly in Lp(a) reduction, or whether agent selection can be guided primarily by other factors such as dosing frequency, cost, and patient preference. SOURCES OF MATERIAL: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting percent change in Lp(a) following treatment with the 5 PCSK9-targeted agents. A random-effects model calculated pooled estimates of percentage Lp(a) change, and mixed-effects meta-regression assessed differences between agents. ABSTRACT OF FINDINGS: Thirty-one RCTs were included. PCSK9 inhibitors and inclisiran reduced Lp(a) by a pooled mean of -25.76% vs control (95% CI -29.54 to -21.99; P < .0001). Meta-regression revealed no significant differences between agents (alirocumab vs evolocumab: +3.3%, 95% CI -1.40 to 8.07, P = .16; inclisiran vs evolocumab: +4.9%, 95% CI -2.31 to 12.16, P = .18; inclisiran vs alirocumab: +1.6%, 95% CI -5.38 to 8.55, P = .65). Lerodalcibep and enlicitide demonstrated similar approximate 25% reductions; however, insufficient trial numbers precluded a powered head-to-head comparison. CONCLUSIONS: No statistically significant differences in Lp(a) reduction were observed between currently available PCSK9-targeting medications. Agent selection may reasonably be based on non-efficacy factors, including administration frequency, cost, and patient preference.
INTRODUCTION: mTOR (mechanistic target of rapamycin) inhibitors (eg, everolimus) are increasingly used post-transplant to reduce calcineurin inhibitor nephrotoxicity but can cause severe dyslipidemia, including marked hy...INTRODUCTION: mTOR (mechanistic target of rapamycin) inhibitors (eg, everolimus) are increasingly used post-transplant to reduce calcineurin inhibitor nephrotoxicity but can cause severe dyslipidemia, including marked hypertriglyceridemia with pancreatitis risk. CASE PRESENTATION: A 64-year-old man with type 2 diabetes and chronic obstructive pulmonary disease, with resected pleomorphic giant-cell carcinoma, underwent left single-lung transplantation in March 2023. Everolimus was introduced on April 9, 2025, to spare calcineurin inhibitors in the setting of worsening renal function requiring dialysis. Triglycerides rose from 256 mg/dL (March 24, 2022) to 2886 mg/dL (August 5, 2025) and 4960 mg/dL (September 16, 2025). Everolimus was replaced by mycophenolate mofetil on September 26, 2025, with triglycerides (TGs) falling to 2000 mg/dL (September 29, 2025) and 300 mg/dL (November 3, 2025). INTERVENTIONS: Discontinuation of everolimus and switch to mycophenolate mofetil; continuation of pravastatin; and dietary measures. OUTCOMES: Rapid reduction in TGs after stopping everolimus; no acute pancreatitis documented in the available data. CONCLUSION: This case highlights everolimus-associated hypertriglyceridemia in a lung transplant recipient and underscores the need for tight lipid monitoring and early immunosuppression adjustment when severe dyslipidemia emerges.
Essalmani R, Evagelidis A, Roubtsova A
… +9 more, Chong M, Pathan N, Pare G, Petrochenko EV, Reimund M, Remaley AT, Chalifour L, Schweitzer M, Seidah NG