Background The aim of this study was to investigate the association of serum lipoprotein(a) [Lp(a)] concentrations with the angiographic extent of coronary artery disease and selected angiographic findings in patients hospitalized with acute coronary syndromes (ACS). Methods This retrospective, single-center study included 1009 consecutive patients hospitalized with ACS, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), between November 2022 and February 2025. Serum Lp(a) concentrations were measured routinely within the first 24 hours of hospitalization. Associations between Lp(a) concentrations and angiographic findings were evaluated using multivariable logistic regression adjusted for major cardiovascular risk factors. Results The median Lp(a) concentration was 23.8 nmol/L, and elevated Lp(a) concentrations (≥105 nmol/L) were observed in 24.9% of patients. Higher Lp(a) concentrations were associated with a greater angiographic extent of coronary artery disease, including an increased prevalence of three-vessel disease and chronic total occlusions (CTO). In multivariable analyses, each 50 nmol/L increase in Lp(a) was associated with higher odds of three-vessel disease (OR 1.16, 95% CI 1.08–1.24; p<0.001) and CTO (OR 1.17, 95% CI 1.06–1.29; p=0.003). Using the clinically recommended threshold of ≥105 nmol/L, elevated Lp(a) remained independently associated with three-vessel disease (OR 1.51, 95% CI 1.12–2.03; p=0.008) and CTO (OR 1.84, 95% CI 1.17–2.90; p=0.009). Patients with premature STEMI exhibited the highest Lp(a) concentrations among all ACS subgroups. Among routinely measured lipid parameters, Lp(a) demonstrated the highest discriminatory performance for identifying CTO, although the overall discriminatory ability was modest. Conclusions Elevated Lp(a) concentrations were independently associated with the angiographic extent of coronary artery disease in patients with acute coronary syndromes, including multivessel disease and chronic total occlusions. These findings demonstrate a cross-sectional association between a single Lp(a) measurement obtained during the index hospitalization and selected angiographic findings. Further prospective studies are required to confirm these associations and determine their clinical significance.
Background Familial hypercholesterolemia (FH) is most frequently caused by pathogenic variants in LDLR, but phenotypic variability suggests the influence of genetic modifiers. Methods We investigated a large multigenerational family with FH, combining clinical data, lipid profiles, and genetic analysis with functional studies. LDLR and PCSK9 variants were characterized according to ACMG/ClinGen guidelines. Functional assays in CHO-ldlA7 cells assessed LDLR activity, while plasma PCSK9 levels were quantified by ELISA. Results The LDLR c.2479G>A variant was associated with the FH phenotype in the family and showed borderline functional impairment in vitro. The presence of the established loss-of-function PCSK9 c.137G>T variant, together with the rare PCSK9 c.2023del variant with a predicted deleterious effect, was identified in a normocholesterolemic carrier of the LDLR variant who showed markedly low circulating PCSK9 levels. Conclusions These findings suggest the potential relevance of investigating gene–gene interactions and variants with opposing effects on the lipid phenotype in FH. Integrating clinical, biochemical, genetic, and functional data may help explain intrafamilial variability and support more precise interpretation of inherited dyslipidemias.
Aims Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality globally. While it impacts both sexes, women are frequently underdiagnosed and undertreated, particularly in lipid management. This study aimed to evaluate sex differences, and the gender-related factors potentially underlying them, in lipid control, the utilization of lipid-lowering therapy (LLT), and related perceptions within a large real-world cohort. Methods We analyzed 1,482 patients with established ASCVD from the nationwide, multicenter EPHESUS registry, conducted in 40 cardiology outpatient clinics across Turkey. Differences between women and men in risk profiles, LLT use, low density lipoprotein-cholesterol (LDL-C) goal attainment, and perceptions from both patients and physicians were assessed. Women and men were compared before and after 1:1 propensity score matching for age and education; covariate balance was quantified with standardized mean differences (SMD). Results Women showed a greater burden of cardiometabolic conditions such as hypertension, diabetes, and obesity, yet were less often prescribed statins. Total cholesterol, HDL-C, non-HDL-C and on-treatment LDL-C were higher in women than in men, whereas triglycerides were similar between the sexes; on-treatment LDL-C was significantly higher in women (115 mg/dL vs. 100 mg/dL, p < 0.001). Women also met LDL-C targets less frequently according to the 2016 ESC/EAS guidelines (14.9% vs. 19.6%, p = 0.017), while the difference for the 2019 target was not significant (6.3% vs. 8.3%, p = 0.186). After matching, 924 patients (462 women and 462 men) remained; age and education were well balanced (SMD < 0.05), whereas cardiometabolic covariates remained imbalanced by design. Differences in lipid levels were no longer apparent, and among patients receiving high-intensity statins women more frequently achieved the 2016 LDL-C target (26.0% vs. 13.6%, p = 0.017), whereas the corresponding difference for the 2019 target did not reach statistical significance (10.7% vs. 4.5%, p = 0.072). Media influence was the most common physician-reported reason for LLT cessation; side effects and physician-advised discontinuation were reported more often for women, although these differences were not statistically significant. Conclusion Age and education accounted for a substantial part of the observed differences between women and men in ASCVD care, whereas lower statin prescription in women persisted after matching. Studies addressing sex differences should incorporate gender-related demographic factors into their design and analysis.
Atherosclerosis is traditionally viewed as a lipid-driven inflammatory disease; however, this model does not fully explain acute coronary events arising from non-obstructive lesions or the persistence of residual cardiovascular risk despite lipid-lowering therapy. Emerging evidence implicates infectious agents as contributors to plaque instability rather than primary initiators of disease. Epidemiological studies demonstrate temporal associations between infections and myocardial infarction, while molecular analyses have identified bacterial components within atherosclerotic plaques. Recent findings suggest that microorganisms exist within plaques as biofilms, structured communities embedded in an extracellular matrix that permits immune evasion and long-term persistence. Under host-derived physiological triggers, including inflammatory surges and metabolic stress, biofilm dispersion may expose bacterial products that amplify inflammation and contribute to plaque destabilization. This biofilm-centered framework complements the lipid-centric model by identifying microbial factors as amplifiers of plaque vulnerability. It also highlights potential diagnostic and therapeutic targets aimed at reducing residual inflammatory cardiovascular risk.
Aims:Vitamin K antagonists (VKAs) may promote vascular calcification through inhibition of vitamin K-dependent proteins. We aimed to examine the association between long-term anticoagulant therapy with VKA or direct oral anticoagulants (DOACs) and progression of coronary artery calcification (CAC) in a large, population-based cohort. Methods:We included men and women (<75 years) with two non-contrast CT scans for CAC ≥4 years apart, categorized into VKA, DOAC, mixed anticoagulant, and control groups. Cumulative treatment duration was calculated from prescription data. CAC progression was analysed using zero-inflated negative binomial and multinomial logistic regression, adjusting for traditional cardiovascular risk factors, baseline CAC and follow-up time. Sensitivity analyses excluded participants predisposed to vascular mineralization (statin use, mechanical valve, renal impairment). Results:7365 participants with similar risk profile were included. VKA therapy was significantly associated with CAC progression (incidence rate ratio (IRR) = 1.004 per month of treatment (95% CI: 1.000-1.007)), showing a duration-response relationship. Long-term VKA therapy (>48months) was independently associated with higher CAC progression (IRR = 1.43 (95% CI: 1.076-1.908)), and an increased risk of having severe CAC (CAC score ≥400) at follow-up (relative risk ratio (RRR) = 1.012 per month of treatment (95% CI: 1.001-1.023)). In contrast, DOAC therapy was not associated with CAC progression. Sensitivity analyses confirmed that the association with VKA was not driven by high-risk subgroups. Conclusion:In this large, real-world cohort, VKA - but not DOAC - therapy was associated with accelerated, duration-dependent CAC progression. These findings suggest that choice of anticoagulant may influence CAC, yet the clinical implications remain to be determined.
Background In atherosclerotic cardiovascular disease (ASCVD), acute systemic inflammatory insults such as infections or major surgery are known to trigger cardiovascular events. However, it remains unclear whether such systemic triggers also modulate local inflammatory and degenerative processes within the aortic valve (AV). We therefore investigated the effect of orthopedic surgery on AV remodeling in an atherosclerosis-prone setting. Methods ApoE-/- mice subjected to orthopedic surgery, ApoE-/- controls, and non-atherosclerotic controls were analyzed at 5 and 15 days post-intervention. AVs were assessed for valve thickness, fibrosis, glycosaminoglycans (GAGs), lipid accumulation, calcification, iron deposition, and inflammatory cell infiltration. Results Atherosclerotic mice exhibited degenerative AV changes compared to non-atherosclerotic controls. Orthopedic surgery did not affect valve thickness or inflammatory cell infiltration, but induced compositional changes, including increased GAG content at day 5 (56.7 vs. 27.3; p=0.016), a a higher fibrotic area at day 15 that did not reach statistical significance (41.3 vs. 24.9; p=0.068), and reduced estimated lipid-rich area at day 5 (11.3 vs. 37.3; p=0.008). No differences were observed in calcification or iron deposition. Conclusion Orthopedic surgery induces early compositional remodeling of atherosclerotic aortic valves without increasing inflammatory cell infiltration or valve thickening. These findings suggest that orthopedic surgery induces compositional remodeling of the AV in an atherosclerotic setting. Although inflammatory cell infiltration was not increased at the examined time points, the underlying molecular mechanisms were not investigated. Therefore, systemic inflammatory mediators may contribute to these changes, but this remains to be established.
Background and aims:Muscle symptoms are common with statin therapy, and reduced plasma coenzyme Q10 (CoQ10) has been proposed as a potential mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are widely used in patients with statin intolerance or severe hypercholesterolemia, including familial hypercholesterolemia (FH), but their effects on plasma CoQ10 remain unclear. Methods:We evaluated serum lipid profiles and plasma CoQ10 baseline and 4 weeks after adding evolocumab in patients with heterozygous FH receiving rosuvastatin 10-20 mg/day and ezetimibe 10 mg/day (N = 10; mean age, 52 years; 6 men). Plasma CoQ10 concentrations were determined by high-performance liquid chromatography. Results:Evolocumab markedly reduced LDL cholesterol and lipoprotein(a) [Lp(a)] (121 mg/dL to 64 mg/dL, -50.0%, p < 0.001; 51.8 nmol/L to 39.1 nmol/L, -23.6%, p = 0.002), whereas median CoQ10 levels were unchanged (1028.5 nmol/L to 1002.5 nmol/L, -0.2%, p = 0.33). Changes in CoQ10 did not correlate with reductions in LDL cholesterol or Lp(a). Conclusions:These findings indicate that evolocumab lowers atherogenic lipoproteins without reducing plasma CoQ10, suggesting a potential advantage for patients susceptible to statin-associated muscle symptoms.
Background and aims:Cardiovascular disease (CVD) remains a leading cause of death in China. Systemic inflammation (SI) is an emerging risk factor in atherosclerotic CVD (ASCVD) and chronic kidney disease (CKD). High-sensitivity C-reactive protein (hsCRP) is increasingly recognised for prognostication. The SPARK-CVD China survey assessed Chinese cardiologists' and nephrologists' awareness and perceptions of SI and hsCRP in patients with both ASCVD and CKD. Methods:A nationwide cross-sectional survey was conducted (September to December 2024) across 31 provinces in China mainland among physicians with ≥3 years of clinical experience and managing ≥20 adult patients with both ASCVD and CKD per month. Descriptive and comparative statistics were used. Results:Among 1500 respondents, SI was used more to aid treatment than diagnosis (65.2% vs 45.5%). Although 73.3% viewed SI as a key determinant of cardiovascular events, only 35.2% discussed SI as a risk factor with patients. Non-testers cited no expected impact on decisions (71.3%), lack of guideline direction (44.0%), and limited treatments (37.2%). A knowledge-practice gap for hsCRP was observed: 29.7% identified hsCRP unprompted versus 87.7% when prompted; perceived diagnostic thresholds varied widely. Fewer than 1/4 of ASCVD and/or CKD patients would be prescribed colchicine; barriers included limited experience (55.2%), potential contraindications (54.1%), and side effects (47.1%). Cardiorenal benefits of GLP-1 receptor agonists were widely recognised (97.9%), with 76.5% attributing benefits partly to anti-inflammatory effects. Conclusion:SI is acknowledged but inconsistently operationalised domestically. Targeted professional education, explicit guideline recommendations, and further evidence for risk-stratified, inflammation-guided care may help refine treatment pathways for ASCVD with CKD.
Low-density lipoprotein cholesterol (LDL-C) is causal in atherosclerotic cardiovascular disease (ASCVD), still the leading causes of global morbidity and mortality. The 2025 update of the ESC/EAS guidelines for the management of dyslipidemia recommends increasingly stringent, risk-based LDL-C targets. Beyond achieved LDL-C targets, cumulative exposure over time has emerged as a key determinant of ASCVD risk. Accordingly, treatment strategies should evolve from a traditional stepwise approach toward a more proactive, personalized, and target-oriented model; the recognized impact of cumulative LDL-C exposure further reinforces the importance of early, intensive, and sustained lipid lowering therapies (LLT). Despite this awareness and the availability of effective therapies, LDL-C control in clinical practice remains suboptimal. This gap is largely driven by the so called "therapeutic inertia", involving physician-related factors, patient barriers, and healthcare system constraints; accordingly, fewer than one-third of patients in secondary prevention achieve recommended LDL-C goals. A significant improvement in this situation requires structured treatment algorithms, multidisciplinary care, improved patient education, and integration of digital decision-support tools. A pragmatic framework to improve goal attainment is the estimation of "distance to target", which enables selection of LLT based on the required percentage reduction from baseline LDL-C levels. This approach facilitates alignment between the expected efficacy of available treatments and individual patient needs. While statins remain first-line therapy, combination regimens are frequently required-particularly in very high-risk patients-including ezetimibe, bempedoic acid, PCSK9 inhibitors, and inclisiran.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss. In addition to the different pathogenic mechanisms, in recent years, increasing attention has been directed toward the role of lipid metabolism in ALS pathogenesis, although the clinical relevance of lipid alterations in ALS may differ from their well-established role in cardiovascular disease. This review critically examines the multifactorial relationship between cholesterol and ALS through three perspectives: (1) as a risk factor for disease onset, (2) as a prognostic biomarker of disease progression, and (3) as a potential therapeutic target. Epidemiological and genetic studies suggest a complex and sometimes contradictory association between lipid profile and ALS risk. Elevated LDL-cholesterol and total cholesterol have been linked to increased disease susceptibility in some cohorts, with Mendelian randomization studies supporting a potential causal role. Conversely, evidence regarding HDL-cholesterol remains conflicting and may be influenced by sex-specific and metabolic factors. As a prognostic biomarker, hyperlipidemia has been variably associated with prolonged survival in ALS patients; however, these findings often lose significance after adjusting for body mass index and nutritional status, suggesting that lipid levels may reflect systemic metabolic reserve rather than directly modulating disease progression. Pharmacological modulation of cholesterol reveals further complexity. While statins are generally not associated with increased ALS risk in clinical studies, preclinical models show divergent effects: some statins accelerate disease progression, while others like lovastatin may be protective. Other lipidlowering drugs, including fibrates and PCSK9 inhibitors, may also influence ALS-related pathways beyond cholesterol lowering, although their potential role remains to be clarified.
Background and aims Commonly measured cardiometabolic biomarkers have not been systematically characterized across the long-term continuum of the postprandial and postabsorptive phases. The aim of the present study was to evaluate how the exact time since last meal impacts test results for lipoprotein particles and inflammatory biomarkers. Methods We used data from a trial where 34 normal-weighted males and females aged 20-30 y were included. Subjects fasted 12 h, had blood sampled at baseline, then consumed a standardized, habitual breakfast meal, and had blood sampled 13 more times over the next 24 h. NMR metabolomics was used to quantify lipoprotein subclasses and various biomarkers, and ELISA to analyze VCAM-1, ICAM-1, E-selectin, and IL-6. We characterized the postprandial and postabsorptive responses using visualizations and non-linear mixed effects models. Results Six VLDL subclasses increased by 11-429% within 2-4 h postprandially before returning to baseline levels, followed by another increase 8-10 h after intake of the breakfast meal. IDL and three LDL subclasses increased around 10-12% over 24 h. Four HDL subclasses showed an inverse association with VLDL subclasses, reaching their lowest levels about 1 h after the meal and peaking after 8-10 h with a 5-15% increase from baseline. Participants had an average increase of 325% in IL-6 10 h after breakfast, while other inflammatory biomarkers showed little change over time. For most biomarkers, males generally exhibited higher baseline concentrations compared to females, however the responses over time remained similar. Conclusions Baseline levels and time of return to baseline varied between individuals, with some sex-specific differences in responses. TG-rich lipoproteins and VLDL increased postprandially and normalized by 12-24 h, whereas IDL and LDL showed minor early changes but increased by 24 h. IL-6 increased markedly during the first 10 h and returned to baseline by 12-24 h, while other inflammatory markers changed little.
Background and aims: Patients with familial hypercholesterolemia (FH) have elevated LDL-C levels from birth and increased risk of cardiovascular disease due to atherosclerosis, mostly affecting larger arteries. Less is known about effects of elevated LDL-cholesterol on smaller arteries. Retinal arterioles are prone to damage in the form of stiffening and thickening. We therefore explored the occurrence of retinal arteriolosclerosis in patients with genetically verified FH, and in a control group. Associations between retinal arteriolosclerosis and current serum lipid values, sex, age, statin treatment, and years on lipid-lowering treatment were also investigated. Methods: Eligible patients were 40 to 70 years of age, normotensive, and non-smokers. Exclusion criteria were diabetes and vascular retinal disease. Control subjects had to have normal lipid levels and no history of cardiovascular disease. Lipid measurements were collected prior to the visit, and at the visit retinal fundus photographs of both eyes were taken. The fundus photographs were graded by two ophthalmologists according to the Scheie classification for retinal arteriolosclerosis. Results: Fifty patients with FH and 30 control subjects participated. Mean duration of lipid-lowering medication for the patient group was 17.0 years. The control group had higher total cholesterol, LDL-C and HDL-C, ApoB and ApoA1 levels than the patient group. There were no differences in the occurrence of retinal arteriolosclerosis between the two groups, and no associations were found between current lipid levels, age, sex, statin treatment, years on LLT and retinal arteriolosclerosis. Conclusion: Patients with FH did not have increased prevalence of retinal arteriolosclerosis compared to controls.
Introduction:Peripheral artery disease (PAD) is a common yet underrecognized consequence of systemic atherosclerosis, affecting over 200 million adults worldwide and one in five older adults in the United States. PAD carries substantial morbidity, increasing the risk of major cardiovascular and limb events and contributing to declines in quality of life. Inflammation and metabolic dysfunction are key drivers of atherosclerosis. The C-reactive protein-triglyceride-glucose index (CTI) integrates these pathways. We examined whether CTI is associated with PAD in U.S. adults. Methods:National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 were analyzed. Adults aged ≥20 years with available ankle-brachial index (ABI), fasting glucose, triglycerides, and C-reactive protein (CRP) were included. PAD was defined as ABI <0.90; individuals with ABI ≥1.40 were excluded. CTI was calculated as 0.412 × ln(CRP [mg/L]) + ln(triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Logistic regression models evaluated CTI continuously and quartiles, adjusting for demographic, metabolic, and clinical covariates. Multinomial models assessed associations across ABI categories, including borderline ABI (0.90-0.99). Results:Among 5869 adults, 420 (7%) had PAD. Each 1-unit increase in CTI was associated with higher odds of PAD (aOR 1.47; 95% CI 1.25-1.75; p < 0.001). Higher CTI levels were associated with increased odds of PAD, with the strongest association observed in the highest quartile (aOR 2.07; 95% CI 1.41-3.06; p < 0.001). CTI was also linked to both borderline ABI and clinical PAD in multinomial analyses. Conclusion:Higher CTI is independently associated with PAD and may provide complementary information for vascular risk evaluation.
Background Multiple familial hypercholesterolemia (FH) screening strategies are recommended, but how they work together within a population remains poorly understood. Here, we aimed to compare the characteristics of children diagnosed through a universal screening program with those of adults identified through opportunistic screening. Methods In this retrospective cross-sectional study, we analyzed the clinical and genetic characteristics of children and adults with genetically confirmed heterozygous FH (HeFH). Results Out of 442 children and 299 adults with a definite or probable FH based on clinical criteria, 39 (13.0%) adults and 197 (44.6%) children had also a genetic HeFH. FH causative variants were present in low-density lipoprotein receptor (LDLR) in 159 (67.4%) patients and in apolipoprotein B (APOB) in 77 (32.6%) patients. The combined screening approach identified 44 disease-causing variants, of which 2 and 25 were unique to the adult and pediatric cohort, respectively. The proportion of children with missense variants was significantly higher (172 [87.3%] vs. 27 [69.2%]; p = 0.005), whereas the proportion of termination variants was significantly lower (20 [10.2%] vs. 11 [28.2%]; p = 0.002) compared to the adult group. Adults had higher adjusted low-density lipoprotein cholesterol compared to children. Conclusions Our study suggests that opportunistic adult screening identifies more severe FH phenotypes, while universal pediatric screening detects milder cases.
Aims:Autoantibodies against apolipoprotein A-1 (AAA1) are independent cardiovascular risk factor in the general population. Genetic factors and viral infections have been linked to AAA1 occurrence. We studied the association between environmental pollution and AAA1 response and their relationship with years of life lost or gained (YPLLG). Methods:We conducted a cross-sectional study involving 1867 individuals recruited between 2016 and 2018 in Geneva, Switzerland, characterized for serum AAA1 levels. Exploratory and confirmatory geospatial analyses of AAA1, air pollution (NO2, PM2.5, PM10), proximity to polluted sites, and YPLLG were performed. Associations with AAA1 were adjusted for premature mortality risk factors using Systemic Coronary Risk Evaluation 2 (SCORE2), while associations with YPLLG were adjusted for income, nationality, NO2 levels, and proximity to polluted sites. Results:Significant geographic clustering of high AAA1 serum levels (hotspots) were identified in urban areas with heavy traffic, associated with higher air pollutant levels (median NO2 26.90 μg/m3 in hotspots vs. 23.70 μg/m3 in non-hotspots, p < 0.001), and greater density of polluted sites (median weighted pollution score 66.8 vs. 52.1, p = 0.008). AAA1 geographic hotspots corresponded to areas showing a median reduction of four years in population life expectancy, based on mortality records (2009-2016) (p < 0.001), even after adjustments. Conclusions:While causal inference cannot be drawn due to the cross-sectional design, AAA1 hotspots overlapped regions of higher air and soil pollution and reduced life expectancy. Determining causality and whether specific pollutants amplify the AAA1 response will be key to validate these hypothesis-generating findings.
Background:Lipoprotein(a) [Lp(a)] is increasingly recognized as an independent and causal risk factor for atherosclerotic cardiovascular (CV) disease including aortic valve stenosis, myocardial infarction, stroke, peripheral arterial disease and CV death. Despite growing global awareness, significant gaps in diagnosis, risk stratification, and management persist in Gulf countries. Objective:To develop regionally tailored consensus statements on the clinical management of elevated Lp(a) in Gulf countries using a modified Delphi-based methodology. Methods:A multidisciplinary panel, mostly of Gulf-based experts in cardiology, lipidology, and endocrinology evaluated 64 evidence-based statements across six thematic domains, including pathophysiology, risk assessment, therapeutic strategies, and implementation challenges. Consensus was defined by ≥ 80% agreement, and relevant literature was reviewed to support each statement. Results:Strong consensus supported the inclusion of Lp(a) in routine CV risk assessment, especially for high-risk individuals. The panel endorsed early detection and aggressive management of modifiable risk factors, including LDL-C, apoB, and non-HDL-C. Areas of partial agreement highlighted practical challenges, including variability in insurance coverage and the need for clearer referral pathways, imaging protocols, and outcome-driven treatment guidance and particularly the current unavailability of specific Lp(a) lowering drugs. Conclusion:These expert recommendations provide a pragmatic framework for integrating Lp(a) into CV care pathways in Gulf countries. By aligning practice with emerging evidence, the consensus has the potential to shape national guidelines, inform payer policies, promote regional research on the epidemiology of Lp(a), and support equitable access to future Lp(a)-targeted therapies, ultimately improving long-term CV outcomes in the region.
Background The triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance. However, its clinical relevance in individuals with strictly normal fasting glucose and triglyceride levels remains unclear. We aimed to investigate the sex-specific associations of the TyG index with systemic inflammation and arterial stiffness among adults with normal fasting glucose and triglyceride levels. Methods This cross-sectional study included 2,574 apparently healthy adults (1,300 males and 1,274 females) with fasting plasma glucose <100 mg/dL and triglycerides <150 mg/dL. Elevated systemic inflammation was defined as high-sensitivity C-reactive protein (hsCRP) >3.0 mg/L, and increased arterial stiffness as brachial-ankle pulse wave velocity (baPWV) ≥1,400 cm/s. Sex-stratified multivariable logistic regression was used to evaluate these associations across TyG quartiles. Results In females, higher TyG quartiles were independently associated with both outcomes. Compared with the lowest quartile (Q1), adjusted odds ratios (AORs) in females for elevated hsCRP were 2.44 (95% CI, 1.36–4.39) for Q3 and 2.95 (1.65–5.29) for Q4. For increased arterial stiffness, AORs in females were 2.46 (1.34–4.53), 2.39 (1.31–4.36) and 2.44 (1.34–4.45) for Q2–Q4, respectively. Conversely, no significant independent associations were identified in males across all quartiles. A significant sex-interaction was observed for elevated hsCRP (p <0.001). Conclusion Among adults with normal fasting glucose and triglyceride levels, a higher TyG index is independently associated with subclinical inflammation and arterial stiffness, predominantly in females. These findings suggest that the TyG index may help identify early cardiometabolic vulnerability in women even within conventionally normal metabolic ranges.
Lipoprotein(a) [Lp(a)] is a useful marker for cardiovascular risk stratification. Previous studies have shown higher Lp(a) levels in women than in men and sex differences in its association with atherosclerosis. The aim of this study was to assess associations between Lp(a) levels and cardiovascular disease (CVD) in men and women with suspected familial hypercholesterolemia (FH).The study included 220 hypercholesterolemic patients (110 men) treated at an outpatient lipid clinic. Clinical data, anthropometric measurements, and laboratory tests were collected. Lipid concentrations were measured enzymatically and Lp(a) by latex-enhanced immunonephelometry. Coronary artery disease (CAD) was present in 27.3% of men and 14.5% of women; 30.9% were current smokers and 84.5% received statin therapy. Median Lp(a) levels were significantly higher in women with CAD than without CAD, whereas no significant difference was observed in men. After age standardization, mean Lp(a) levels did not differ by CAD status in either sex. In age-adjusted logistic regression, CAD in men was associated with smoking and hypertension, while in women it was associated with LDL-C, Lp(a), and smoking.These findings support sex-specific differences in the role of Lp(a) in CAD development and identify Lp(a) as a CVD risk factor in hypercholesterolemic women.
Atherosclerosis (AS) is a complex pathophysiological process. Evidence has demonstrated that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role in AS. Calponin 3 (CNN3) is implicated in the pathogenesis of various diseases by modulating cell proliferation and migration. However, the roles of CNN3 in VSMCs and AS remains elusive. Experiments were performed in tissues and in vitro to investigate the role of CNN3 in the pathophysiology of AS. The expression of CNN3 in aortic plaques was determined using immunohistochemistry, and the serum CNN3 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The diagnostic potential of CNN3 was evaluated by receiver operating characteristic (ROC) curve analysis. To in vitro functions of CNN3 were analyzed by EdU assays, CCK-8 assays, scratch wound assays, transwell assays, qRT-PCR and western blotting analyses. In this study, we demonstrated CNN3 was significantly upregulated in plaques compared to normal intima tissue. Patients with coronary artery disease were found to have higher CNN3 levels than healthy individuals and was positively correlated with the SYNTAX score of patients. The ROC curve for CNN3 as a diagnostic biomarker reached 0.787. In vitro experiments showed that CNN3 promoted VSMCs proliferation and migration by β-catenin signaling pathway. All the data indicated that CNN3 promoted VSMCs proliferation and migration by modulating the β-catenin signaling to accelerate the AS process. Serum level of CNN3 serves as a promising diagnostic biomarker for AS.
Background Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in inflammatory pathways beyond lipid metabolism. The effects of PCSK9 inhibition on monocyte subset distribution in high-risk coronary artery disease patients remain unclear. Objective To assess the effects of lipoprotein fractions and PCSK9 inhibitor (PCSK9i) therapy on monocyte subset distribution in patients with stable coronary artery disease and highly elevated Lp(a) levels. Methods We followed 100 statin-treated patients in the stable phase after myocardial infarction with highly elevated Lp(a), randomized to PCSK9i or placebo for six months. Biochemical, genetic, and cellular analyses were performed at baseline and follow-up. Results At baseline, IM levels correlated with total cholesterol (ρ=−0.202, p=0.044), triglycerides (ρ=−0.324, p<0.001), apolipoprotein A1 (ρ=0.241, p=0.016), and PCSK9 concentrations (ρ=−0.282, p=0.006). PCSK9 levels were positively associated with CC-motif chemokine ligand 2 (CCL2) (ρ=0.298, p =0.005), a marker of monocyte recruitment. PCSK9i therapy did not alter monocyte subset distribution. After treatment, only the association between IM and Lp(a) remained significant (ρ=−0.258, p=0.041). KIV-2 repeat number inversely correlated with CCL2 levels (ρ=−0.319, p=0.011). Conclusion In high-risk patients, PCSK9 inhibition modulates monocyte–lipoprotein interactions without affecting the monocyte subset distribution. PCSK9 may promote vascular inflammation through CCL2 regulation, which appears more closely related to Lp(a) composition than its circulating concentration. Clinical trial registration NCT04613167; https://www.clinicaltrials.gov/study/NCT04613167, date of registration: 6th of October 2020
