LDL-C Levels Research Articles

Gender-differences in Polyvascular disease: implications for lipid-lowering management and cardiovascular outcomes

Abstract Background Polyvascular disease (PolyVD) exhibits extensive atherosclerotic disease in multiple vascular beds. Despite lowering LDL-C with a statin, patients with PolyVD still present elevated risks of subsequent atherosclerotic cardiovascular events, suggesting the need to better understand pathophysiology of PolyVD. Female gender has been reported to mitigate severity of atherosclerotic disease and future events’ risks. However, whether this gender-difference exists in patients with PolyVD remains to be fully elucidated yet. Purpose To characterize gender-differences in cardiovascular outcomes in patients with and without PolyVD, respectively. Methods The on-going multi-center registry enroll patients with CAD receiving intravascular imaging-guided PCI. The current study included 679 patients with CAD. PolyVD was defined as the concomitance of other atherosclerotic cardiovascular disease (stroke and/or LEAD). In patients with PolyVD (n=185) and Non-PolyVD (n=494), clinical characteristics and major cardiovascular outcomes (MACE) were compared between men and women, respectively. MACE was defined as a composite of cardiovascular death, non-fatal MI, ischemic stroke, LEAD and coronary revascularization. Results The proportion of women was 21% and 18% in Non-PolyVD and PolyVD subjects, respectively. In patients with non-PolyVD, women were more likely to be older (75 vs. 68 years, p<0.001) and exhibit a lower BMI (22.3 vs. 24.0 kg/m2, p<0.001) with a lower frequency of previous myocardial infarction (13.5 vs. 24.9%, p=0.01). LDL-C levels did not differ between the two groups [102 (76-130) vs. 93 (71-120) mg/dL, p=0.06). However, during the observational period (median=3 years), women were associated with a lower frequency of MACE compared to men (HR=0.31, 95%CI=0.13-0.78, p=0.012, Figure, Table). In patients with PolyVD, BMI, and the frequency of established risk factors and previous myocardial infarction were comparable between men and women. Despite the use of high-intensity statin in over 40% of study subjects (44 vs. 36%, p=0.41), women still exhibited an elevated level of LDL-C [103 (74-122) vs. 82 (64-103) mg/dL, p=0.04]. Furthermore, in contrast to Non-PolyVD patients, similar cardiovascular outcomes were observed in both men and women with PolyVD (Figure). On multivariate analysis adjusting clinical characteristics, women were not a significant factor associated with a reduced risk of MACE (Table). Conclusion 18% of PolyVD were women who presented a higher LDL-C level. While women with Non-PolyVD exhibited better cardiovascular outcomes compared to men, this gender-difference did not exist in patients with PolyVD. Our findings indicate that female PolyVD did not necessarily show better outcomes but similar cardiovascular event’s risks compared to men. Further intensified anti-atherosclerotic managements are required in both men and women with PolyVD.

Apolipoprotein B and the regression of lipidic plaque in statin-treated type 2 DM patients with coronary artery disease: the pre-specified sub-analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Type 2 diabetic mellitus (T2DM) patients more likely present vulnerable form of diseases. Despite lowering LDL-C level with a statin, their on-going cardiovascular risks still exist, which indicates the need to identify additional therapeutic targets in T2DM patients. Apolipoprotein B (ApoB) is a proatherogenic lipoprotein. Atherosclerosis is promoted via the influx of ApoB into vessel wall. The current ESC guideline recommends ApoB levels as a secondary therapeutic target under control of LDL-C levels with a statin. However, it remains to be fully determined about the association of ApoB levels with plaque vulnerability in statin-treated T2DM patients. Purpose To elucidate whether serial change in ApoB levels affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL randomized controlled trial compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in 94 statin-treated T2DM patients with CAD. Serial NIRS/IVUS imaging was conducted at baseline and week 48 to monitor non-culprit lesions. The current study included 71 patients with serial ApoB levels at both baseline and week 48. Clinical demographics and NIRS/IVUS-derived measures were compared in those with and without any reduction of ApoB levels. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, 60.6% of study subjects exhibited any reduction of ApoB levels, accompanied by a greater reduction of LDL-C levels. Patients with any reduction of ApoB levels were more likely to be older (67.4±10.0 vs. 71.7±7.3 years, p=0.03), whereas there were no significant differences in the proportion of established risk factors between the two groups. Baseline NIRS/IVUS-derived PAV (47.1±12.9 vs. 44.8±15.4%, p=0.54) and maxLCBI4mm [290.5 (205.5, 338.7) vs. 270.0 (97.0, 416.0), p=0.76] were comparable in patients with and without any reduction of ApoB. On serial NIRS/IVUS imaging analysis, the progression rate of atheroma volume did not differ between the two groups (-0.4±0.2 vs. -0.3±0.2mm3, p=0.77). However, patients with any reduction of ApoB more frequently presented a regression of maxLCBI4mm (27.6±0.1 vs. 61.5±0.1%, p=0.01). Multivariate analysis adjusting age, female and high-intensity statin use demonstrated change in ApoB as an independent factor associated with regression of maxLCBI4mm (OR=0.94, 95%CI=0.91-0.98, p=0.002). Conclusion In statin-treated T2DM patients with CAD, any reduction of ApoB levels was associated with a greater regression of NIRS-derived maxLCBI4mm. The current findings indicate a potential anti-atherosclerotic effect of lowering ApoB levels, which induces delipidation of diabetic coronary atheroma. ApoB may be an important therapeutic target to modulate lipidic plaque materials in T2DM patients receiving a statin.

Serum lipid profiles and uptake of lipid-lowering therapy in patients with premature atherosclerotic cardiovascular disease (ASCVD) in comparison to older patients with ASCVD

Abstract Background Serum lipid levels are well-established risk factors for developing atherosclerotic cardiovascular disease (ASCVD). There are multiple guideline-supported treatments for managing dyslipidaemia for secondary prevention of ASCVD events. Lipid profiles and uptake of guideline-directed lipid-lowering therapy (GDLLT) is poorly characterised in patients with premature ASCVD compared to their older counterparts. Purpose To investigate serum lipid profiles and GDLLT uptake in patients with premature ASCVD in comparison to older patients with ASCVD. Methods Consecutive patients who underwent inpatient invasive coronary angiography at our institution between January 2019-December 2021 were examined. Patients with confirmed ASCVD on coronary angiography were stratified into two groups based on the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias definition of premature ASCVD: Group 1 comprised of younger patients (<55 years for men, <60 years for women) and Group 2 comprised of older patients (≥55 years for men, ≥60 years for women). Demographics, clinical and biochemical parameters (including lipid profiles) and medications were obtained from the electronic medical record and compared between groups to identify differences in risk factor profiles. Results A total of 1437 patients (980 [68.2%] male, mean age 62.4±13.9 years) underwent coronary angiography. 916 patients (63.7%) had confirmed ASCVD, of which 225 were classified as premature ASCVD (24.6%, mean age 47.8±10.1 years) vs 691 older patients with ASCVD (75.4%, mean age 69.5±8.7 years). Group 1 patients had significantly higher mean BMI (31.7±8.1 vs 69.5±8.7; p=0.001) and lower prevalence of hypertension (54.2% vs 69.5%; p<0.001) or chronic kidney disease (5.3% vs 12.6%; p=0.002) compared to Group 2. There were no significant differences in sex, diabetes mellitus, or smoking history. Lipid profiles were significantly different between the two groups: Group 1 had higher levels of total cholesterol (TC), LDL-C, triglycerides, and TC/HDL-C ratio, but lower HDL-C levels (all p<0.001). A lower proportion of Group 1 patients were on GDLLT (42.7% vs. 60.3%; p<0.001). Amongst patients on GDLLT, there were similar rates in the use of high-intensity statins between groups, but Group 1 patients were significantly more likely to have an LDL-C level ≥1.8mmol/L (p=0.003). Multivariable models for individual lipid subfractions, accounting for gender, cardiovascular risk factors, and LLT use, showed that all lipid parameters remained significantly different between groups (all p<0.001). Conclusion Patients with premature ASCVD have significantly different lipid profiles compared to older ASCVD patients. They also have lower uptake of guideline-directed LLT and are less likely to meet recommended LDL-C targets for high-risk ASCVD despite therapy. These findings highlight the need for tailored risk factor evaluation and management in this population.

Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Abstract Introduction Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Methods This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients are primary prevention patients and among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non-contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by immunonephelometric method. Results The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin usage to %32 and statin usage to %96) within the population. 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study highlights the influence of subclinical atherosclerosis on treatment approaches, as demonstrated by the notable rise in statin and aspirin utilization observed after screening.Clinical and biochemical characteristicsSubclinical Atherosclerosis Rates

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) >250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level <1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P<0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target <1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C >1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

Hyperlipidemia interferes with the behavior of variant NKT cells

Abstract Background NKT cells significantly influence atherosclerosis development. However, inconsistent findings on the function of the NKT cells and the invariant subset in atherosclerosis remains a challenge. Moreover, there is no clarity on the role and phenotype of the variant (vNKT) subset in atherosclerosis. Purpose To understand the role of the vNKT subsets in HFD-induced atherosclerosis. Methods We extracted the data for meta-analysis to understand the role of the whole NKT and iNKT cells in atherosclerosis. PRISMA guidelines were followed for the meta-analysis. In addition, C57BL/6 mice (WT) were fed with HFD for 20 weeks from 6-8 weeks of age. vNKTs were identified as CD3+NK1.1+CD1d-tetramer- within the CD3+NK1.1+ NKT cell population in both liver and spleen by flow cytometry. Intracellular cyotkines staining was performed. Statistical differences inthe means of two groups are calculated by two-tailed Student’s t-test with nonparametric Mann-Whitney tests. P-value<0.05 was considered significant. All data represented as mean±SEM. Results The NKT cell numbers increased significantly in the spleen, lymph nodes, blood, and liver in the HFD-fed mice fed from 1.5 to 24 weeks in Apoe-/-, Ldlr-/- in comparison to wild-type mice (SMD, 2.51 [95% CI, 1.42, 3.61]). Contrary to this, the iNKT cell numbers and the iNKT TCR gene expression levels, decreased significantly in the HFD-fed mice (SMD, -2.04 [95% CI, -3.34, -0.75]). The reduction in iNKT cell numbers is also supported by the clinical data from the AMI patients when compared to healthy controls [SMD = -1.81, 95% CI = -2.89, -0.74] (Figure 1). In HFD-fed C57BL/6 hyperlipidemic mice, significantly increased levels of total cholesterol (HFD vs Chow; 226.5±29.66 vs 118.5±10.56 mg/dL, n=4) and LDLc (44.56±11.96 vs 16.69±1.13 mg%, n=4) was observed. The number of vNKTs in the liver was significantly increased by 46% (HFD vs Chow 28.35±2.28 vs 19.41±1.36, n=6-7) (Figure 2A). However, the CD8+ vNKTs were significantly decreased by 68.6% in the liver (4.72±0.99 vs 15.06±0.96) and the CD4+ vNKTs decreased more than two times in the HFD-fed WT liver (7.39±0.76 vs 18.28±0.36) (Figure 2B). Also, the intracellular IFN-γ+ vNKT cells doubled in their numbers in the HFD-fed spleen (14.31±1.39 vs 6.367±0.87) compared to the chow-fed mice (Figure 2C). Conclusion(s) Meta-analysis revealed dual nature of the NKT cells and its invariant subsets in atherosclerosis, since the whole NKTs increase whereas the iNKTs decrease in number. The vNKT subset actively participates in immune modulation in the HFD-induced hyperlipidemia by increasing their number, as well as by differentially regulating CD8 and CD4 co-receptors between chow and HFD. HFD induced a pro-inflammatory nature in the splenic vNKTs but not in liver vNKTs, that in turn may aggravate other immune cells. This data confirms the dual nature of the NKT subsets and reveals a crucial systemic involvement of vNKT cells in the progression of dyslipidemia.

Impact of allogenic Fecal Microbiota Transplantation (FMT) on lipid parameters in patients with metabolic syndrome (MetS): a meta-analysis

Abstract Background Metabolic Syndrome (MetS) has long been considered a formidable global health concern, and impaired lipid metabolism has been one of its crucial clinical manifestations. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapeutic strategy for MetS, nevertheless, prior meta-analyses have not only yielded conflicting outcomes, but as well predominantly centered on glycemic parameters, leaving the potential impact of FMT on lipid metabolism remained unexplored. Purpose This meta-analysis systematically assessed the influence of allogenic FMT on lipid parameters in MetS patients, unraveling its potential as an innovative therapeutic modality for MetS. Methods A meta-analysis was performed to explore the impact of allogenic FMT on lipid parameters (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TCHO] and triglycerides [TG]) in patients with MetS. Terms regarding FMT and metabolic syndrome were searched in PubMed/Medline, EMBASE, Web of Science, the Cochrane Library, and Scopus from the inception of the databases until 31 August 2023. Ten randomized controlled trials (RCTs) were included and mean difference (MD) of parameters were pooled using a fixed effects model. Subgroup analyses according to follow-up durations were performed, and this study was registered in PROSPERO. Results A total of 532 patients in 10 studies were included. Patients undergoing allogenic FMT manifested significantly higher HDL-c level compared with control group (receiving placebo or autologous FMT, pooled MD 0.06 [95% CI: 0.02, 0.10]), and the result remained consistent in the subgroup with 4 to 6 weeks of follow-up (MD 0.07 [95% CI: 0.02, 0.10]). Though overall pooled result did not manifest a significant LDL lowering effect (MD -0.08 [95% CI: -0.21, 0.05]), in subgroup analyses, a significantly lowered LDL level was observed at 12 weeks of follow-up (MD -0.34 [95% CI: -0.60, -0.08]). No significant difference was observed between allogenic FMT and control group concerning TCHO ant TG levels regardless of lengths of follow-up. Conclusions An overall higher level of HDL-C and lowered LDL-C at 12 weeks of follow-up was observed in MetS patients receiving allogenic FMT. The results indicated that gut microbiota from lean, healthy donors may display a beneficial effect on modulating lipid metabolism in patients with MetS. Allogenic FMT manifested promising therapeutic impact and could serve as a viable intervention for MetS patients. Future large-scale RCTs are required for further validation.

Association between achieved cholesterol levels and the risk of major adverse cardiovascular events after acute coronary syndromes

Abstract Background European guidelines recommend reducing lipid levels to defined targets to lower cardiovascular risk after acute coronary syndromes (ACS). Purpose This study aims to evaluate the association of achieved and reduced lipid levels one year post-ACS with the risk of subsequent major adverse cardiovascular events (MACE) in a real-world setting. Methods Data from SPUM-ACS, a Swiss multicentric cohort of patients hospitalized with ACS between 2007 and 2021, were used to assess the association between lipid levels (LDL-C, non-HDL-C, HDL-C, triglycerides), relative difference from baseline lipid levels, and lipid targets achievement (LDL-C <1.8 and ≥50% reduction from baseline, non-HDL-C <2.2 and triglycerides <1.7mmol/l) one year after ACS with the risk of MACE (myocardial infarction, stroke, coronary revascularization, and cardiovascular death). The observation period for MACE started after a follow-up visit one year post-ACS, during which lipid levels were measured, extending over a median duration of 5.5 years. Cox proportional hazards models, adjusted age, sex, BMI, smoking status, statin therapy intensity, diabetes, systemic inflammatory disease, and creatinine were used. Predicted adjusted hazard ratios (HR) were represented graphically for continuous exposures. Analyses were repeated with interaction terms for predefined subgroups. Results 2579 ACS survivors (mean age 62 years; 80% male), primarily undergoing percutaneous revascularization, attended a follow-up visit one year after ACS and were followed up for a median of 5.5 years. 98% were prescribed statin therapy (59% high-intensity) at discharge. During the first year post-ACS, median LDL-C decreased from 3.7 to 2.4 mmol/l (-34%, p<0.001), non-HDL-C from 3.9 to 2.6 mmol/l (-32%, p<0.001), and triglycerides from 1.21 to 1.16 mmol/l (-6%, p<0.001); HDL-C increased from 1.1 to 1.2 mmol/l (+6%, p<0.001). 92% of patients were on statin therapy (50% high-intensity) one year after ACS. In log-linear models, one year after ACS, a 1 mmol/l reduction of LDL-C, non-HDL-C, and triglycerides levels to the target was associated with a lower risk of subsequent MACE by 23%, 24%, and 14%, respectively (p values <0.001). A 10% relative reduction from baseline levels of LDL-C, non-HDL-C and triglycerides was associated with a lower risk of MACE by 8%, 9%, and 4%, respectively (p values <0.001). Achieving LDL-C <1.8 mmol/l (21%, HR=0.71 [0.54, 0.93]), LDL-C reduction ≥50% from baseline (26%, HR=0.63 [0.48, 0.84]), non-HDL-C <2.2 mmol/l (30%, HR=0.65 [0.51, 0.83]), and triglycerides <1.7 mmol/l (76%, HR=0.76 [0.62, 0.94]) were all associated with a reduction in the risk of MACE. Neither age, sex, BMI, diabetes, or smoking status affected the results (p for interaction ≥0.05). Conclusion These findings affirm current recommendations and underscore lipid reduction and targets achievement as critical strategies for mitigating residual cardiovascular risk in patients with ACS.

Systemic inflammation in patients with atherosclerotic cardiovascular and chronic kidney disease in Spain: a population-based study using electronic medical records from a primary care database

Abstract Background Systemic inflammation (SI) is recognized as a critical driver of atherosclerotic cardiovascular disease (ASCVD), and it is frequently observed in ASCVD patients with comorbid chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels, a common biomarker for SI, have been associated with poor prognosis in ASCVD and CKD patients, increased risk of major adverse cardiovascular events and renal disease progression, as well as greater mortality. Purpose To estimate the prevalence of SI in patients with ASCVD in Spain overall and by CKD status, and to describe patients’ clinical characteristics. Methods In this population-based observational study, data from THIN Spain, a database of electronic medical records from a large network of general practitioners, were used to identify adult patients with a diagnosis code of ASCVD (atherosclerotic coronary or cerebrovascular event, peripheral arterial disease, or other atherosclerotic vascular event) and ≥1 eligible CRP measurement between January 1st 2014 to July 31st 2023 (latest data available at time of data extraction).[Figure] SI was defined as CRP ≥ 2mg/L. Point prevalence of SI at the end of the study (among patients alive with ≥1 CRP in the prior 18 months) and the proportion of patients with evidence of SI during the study period (2014-2023) were estimated overall and by CKD status (defined as CKD stage 3+, or eGFR <60 mL/min/1.73m², or urinary albumin-to-creatinine ratio ≥30 mg/g). Patients’ comorbidities (defined using primary care diagnoses), and laboratory values were reported by SI status at first CRP measurement during the study period. Results Among 76,423 patients with ASCVD diagnosis, 15,798 patients (20.7%) were included in the study (mean age: 71.1 years; 43% females), of whom 5,111 (34%) had CKD at first eligible CRP (n=975 with unknown CKD status). Mean CRP in ASCVD patients with CKD was 24% higher than in those without CKD (4.36 vs 3.53 mg/L, p<0.001). The proportion of ASCVD patients with SI at first CRP measurement was 58% overall (65% among CKD patients; 55% among patients without CKD; p<0.001). The point prevalence of SI at the end of the study was 56% among ASCVD patients overall (62% among CKD patients; 52% among patients without CKD; p<0.001), while 64% of ASCVD patients had evidence of SI at any time during the study period (72% among CKD patients; 59% among patients without CKD; p<0.001). Compared to ASCVD patients without SI, higher proportion of SI patients were smokers and with comorbidities. Also, ASCVD patients with SI had lower baseline eGFR levels and higher levels of LDL-C and triglycerides than ASCVD patients without SI.[Table] Conclusions SI prevalence is high among patients with ASCVD in Spain, especially among patients with comorbid CKD. Strategies to target SI may have beneficial effects in prevention of cardiovascular events and mortality in ASCVD patients.

Angioprotein-like 3 and atheroma progression in statin-treated type 2 diabetic patients with coronary artery disease: the pre-specified analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Despite guideline-recommended control of LDL-C with a statin, type 2 diabetic patients more likely cause cardiovascular events. This indicates the need to identify additional therapeutic targets in those patients. Angioprotein-like 3 (ANGPTL3) is an inhibitor of lipoprotein and endothelial lipase, which increases the levels of LDL-C and other atherogenic lipoproteins. These properties suggest ANGPTL3 as a potential driver associated with diabetic atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring-guided versus HbA1c-guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic patients by using serial intravascular ultrasound (IVUS) imaging. This pre-specified analysis of the OPTIMAL study was designed to evaluate whether ANGPTL3 affects progression of coronary atheroma in statin-treated type 2 diabetic patients. Purpose To elucidate the association of serial change in ANGPTL3 with the degree of atheroma progression in statin-treated type 2 diabetic patients. Methods 59 patients (59 lesions) with serial ANGPTL3 levels at baseline and week 48 were included into the current analysis. Clinical demographics and IVUS-derived measure were compared in patients with and without any increase in ANGPTL3. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, any increase in ANGPTL3 levels at week 48 was observed in 52.5% of study participants. Patients with any increase in ANGPTL3 were more likely to have a history of hypertension (90.0% vs. 64.3%, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels between the two groups (1.8 ± 0.4 vs. 1.6 ± 0.6 mmol/L, p=0.25) (Table). On IVUS imaging analysis, baseline percent atheroma volume (PAV) did not differ in those with and without any increase in ANGPTL3. However, patients with any increase in ANGPTL3 presented a greater progression of PAV (0.08 ± 0.28 vs. -0.74 ± 0.29, p=0.04). There was a trend toward a lower frequency of PAV regression in those exhibiting any increase in ANGPTL3 (48.4% vs. 57.1%), but this comparison did not meet statistical significance (p=0.50) (Figure). Multivariate analysis adjusting clinical characteristics demonstrated that any increase in ANGPTL3 level was not independently associated with PAV progression (β=0.16, 95%CI=-0.01 – 0.18, p=0.27). Conclusion Over 50% of statin-treated type 2 diabetic patients with coronary atherosclerosis showed any increase in ANGPTL3 levels at week 48. Serial IVUS imaging revealed that patients with any increase in ANGPTL3 more likely presented a greater atheroma progression. However, this relationship did not exist after adjusting clinical characteristics. Our findings suggest that ANGPTL3 may not be a pivotal driver associated with atheroma progression in statin-treated type 2 diabetic patients.

Metabolomic profiling of the entire UK Biobank enables interpretation of familial hypercholesterolemia mutations and prediction of severe cardiovascular outcomes

Abstract Background Familial hypercholesterolemia (FH) is an inherited disorder resulting in high levels of LDL-C from birth. Premeature coronary heart disease occurs in half of affected men by age 50 years(1). While many genetic variants that cause FH are well understood, there are also many variants in FH genes that are of uncertain clinical significance. Furthermore, the variability in residual cardiovascular risk of FH carriers after statin treatment is not fully understood. We here investigate whether metabolomic and genomic data from the 500,000 person UK Biobank cohort can aid in interpretation of candidate pathogenic variants for FH, and characterise future risk of severe cardiac events in the carriers of such variants. Methods We have quantified 249 metabolomic parameters in 490,830 blood samples from UK Biobank cohort. Among 186,483 participants with exome sequence data we identified 896 who carried known pathogenic FH variants and 405 who carried variants of unknown significance in an established FH gene. We fitted a logistic predictive model to identify pathogenic mutations using LDL levels, statin use and 17 principal components of the metabolomic parameters. We further tested whether metabolomic and genomic scores for predicting future risk of myocardial infarction (MI), that were trained in the general population (i.e. individuals without FH), could predict risk in FH carriers. Results A model including all metabolites had a higher accuracy at identifying known pathogenic FH variants (36/56 at FDR < 0.05), compared to LDL and statin use alone (30/56). Our model also identified 8 FH variants marked as uncertain significance in ClinVar with significant (FDR < 0.05) evidence of predicted pathogenicity. We found that our metabolomic risk score predicted 10-year risk of MI among FH carriers (HR=1.96 per SD, p = 0.0011). This was indeed stronger than the effect in the general population (HR = 1.64 per SD, p = 2.5e-168). A combined metabolomic and polygenic risk score had an even larger effect at predicting MI in FH carriers (HR = 3.06 per SD, p = 2.0e-6), and this score was significantly better at predicting MI in FH carriers than in non-carriers (HR = 3.06 vs 1.88 per SD, interaction p = 0.042). Conclusion Familial hypercholesterolemia is an important source of risk for early cardiovascular disease. Population-scale metabolomics can help distinguish pathogenic from benign variants that have not yet been characterised. Metabolomic and genomic scores can also identify individuals at most elevated risk, and provide even more information to FH individuals than in the general population.

Sex differences in atherogenic lipid profile following acute coronary syndrome

Abstract Background Despite significant advancements in lipid-lowering therapy, the management of dyslipidemia remains challenging in patients with acute coronary syndrome (ACS). Significant differences are shown in lipid panels and management between different sexes following ACS. Objective To shed light on the alterations and characteristics of atherogenic lipoproteins and the characteristics of patients who achieve LDL-C targets after statin treatment, harnessing real-world data from electronic health records of patients with ACS after their discharge between sexes. Methods The data in the present study were derived from the iHeart program sponsored by the Chinese Cardiovascular Association. Eligible patients with a diagnosis of ACS from January 2014 to December 2021 during hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed the control of atherogenic lipid profiles between sexes. The primary outcome was the achievement of the LDL-C target, defined as LDL-C <1.8 mmol/L. A multivariable logistic regression model was used to assess the associations between patient characteristics and LDL-C achievement. Results Between 2012 and 2021, 4861 patients (1299 [26.7%] women) were hospitalised with a primary diagnosis of ACS (49.2% STEMI, 13.8% NSTEMI, and 33.8% UA). The mean age was 64.9 (12.4) years. In contrast to a higher proportion of AMI in men, more prevalence of UA was observed in women. Women had more cardiovascular comorbidities than men and were more likely to receive lipid-lowering therapies, blood pressure-lowering therapies, glucose-lowering therapies, and antiplatelet medications at discharge. In both men and women, TC, TG, LDL-C, ApoB, and non-HDL-C levels significantly decreased within 12 months (P<0.05). Women had less reduction in atherogenic lipid profile than men. The rate of LDL-C <1.8 mmol/L was similar between sexes (14.3% vs16.1%; P=0.136) at baseline, whereas within 12 months after discharge, women had a much lower achievement rate of LDL-C target than men (34.6% vs 45.6%; P<0.001). The risk factors for non-achievement of the LDL-C target in men were revascularisation, history of MI, atrial fibrillation, newly diagnosed MI, and high baseline LDL-C levels. For women, the risk factor was hypertension and diabetes. Conclusion Substantial sex disparities were observed in the management of atherogenic lipids. Despite a higher likelihood of receiving guideline-recommended medical therapy at discharge, women had poorer lipid control compared to men, especially among those with NSTEMI.

Factors influencing low-density-lipoprotein cholesterol after acute coronary syndrome and effectiveness of intensive teleconsultation monitoring, the teleobjectif cohort study

Abstract Context: Low-density lipoprotein cholesterol (LDL-c) plays a key role in the development and progression of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective lipid-lowering treatments, patients who have experienced an acute coronary syndrome (ACS) continue to face a high risk of recurrent cardiovascular events and mortality. Achieving the recommended LDL-c target of <0.55 g/L in secondary cardiovascular prevention remains a significant challenge, with fewer than 30% of patients reaching this goal. Aim To investigate the factors influencing LDL-c control after ACS and the effectiveness of intensive teleconsultation monitoring to control LDL-c, even in sub-groups where control is poorest. Methods This bi-centric prospective cohort study conducted between december 2019 and december 2021 compared a group that received standard follow-up after an ACS with an interventional group that received regular follow-up by teleconsultation in addition of usual care to optimize lipid-lowering treatment. A subgroup analysis was carried out to examine the effect of teleconsultation in subpopulations known to be significantly associated with better or worse LDL-c control in the usual care group or described in the literature. Results 1602 patients met the inclusion criteria for our study (814 in the usual care group and 788 in the teleconsultation group). Baseline characteristics were similar between groups. In the usual care group, factors influencing lipid control included gender, diabetes, cardiology consultation, distance to the nearest cardiologist, social deprivation and initial LDL-C levels. Teleconsultation significantly improved LDL-C target attainment compared to usual care (74.7% vs. 26.6%, p<0.001 with multivariate analysis OR 5.06 [4.21 ; 6.07]), particularly benefiting geographically and socially disadvantaged patients. Conclusion Teleconsultation significantly improves lipid control in acute coronary syndrome patients compared to usual care. This universal intervention, particularly beneficial for geographically and socially disadvantaged patients, highlights the potential of telemedicine in enhancing cardiovascular management.analysis in usual care groupTeleconsultation effect in sub-groups

Correlation of coronary and carotid atheroma volume in patients with severe and familial hypercholesterolemia (VOCCA-3D HF)

Abstract Background Stratifying the risk of CV event of familial hypercholesterolemia (FH) patients is not always simple, as they usually are excluded from CV disease risk estimation scores. It has become increasingly clear over the last several years that the heterogeneity in risk among patients with FH is far greater than previously appreciated. To that end, not all patients with FH will require the use of PCSK9 inhibitors. Aim We described the type of coronary artery disease (CAD) in patients with severe and familial hypercholesterolemia and without known atherosclerotic cardiovascular disease and searched for the best determinants of CAD. We searched for correlation between epicardial adipose tissue and CAD. Methods We evaluated the atherosclerosis burden with a combination of calcium score (CAC), computed tomography angiography, and the quantification of coronary atheroma volume and the analysis of the composition of the plaques, alongside with the use of ultrasonography of supra-aortic trunks with 3D quantification of atheroma volume. We also evaluated epicardial adipose tissue volume with CT. Results We analyzed 89 individuals with LDL-c > 190 mg/dL, with a mean age of 56,7 years. LDL-c burden was high (maximal LDL-c level across life of 2.77 g/L in mean, duration of hypercholesterolemia of 21.5 years in mean). Forty percent of the individuals had a CAC score of zero, and only one patient had non-calcified atheroma despite a CAC score of zero. Among patients with CAD, 50% had a CAC > 100 AU, 9% had a stenosis > 50%. Coronary atheroma volume amounted to a median of 50.9 mm3 in patients with CAD, representing 4% of the analyzed coronary lumen volume, and was mainly made of calcified and non-calcified fibrous plaques. At-risk plaques were not frequent (9% of low-attenuation plaques, 15.2% of positive remodeling and 2% of napkin-ring sign) in patients with CAD. Fifty percent of the individuals had no carotid plaque. Among various clinical and biological risk factors (LDL-year-score, age, blood pressure, smoking, familial history, diabetes), the carotid atheroma volume was the only variable to be independently correlated with both CAC (t=3.1, p=0.006) and coronary atheroma volume (t=4.9, p<0.001). Epicardial adipose tissue was not associated with CAD. Conclusion A significant part of the patients with severe and familial hypercholesterolemia has no CAD, however half of the patients with CAD have an important atherosclerosis burden, which can be well predicted by the carotid atheroma volume. Such a screening could help identify the individuals who would benefit the most from intensive cholesterol-lowering drugs.CAC categoriesType of coronary plaques

Characterization of plaque hemorrhage with optical coherence tomography imaging in statin-treated patients with coronary artery disease: comparison with noncontrast T1-weighted MRI

Abstract Background Plaque hemorrhage is a phenotypic feature of coronary lesions associated with future coronary events. Noncontrast T1-weighted MRI has a potential to non-invasively identify plaque hemorrhage. Plaque to myocardium ratio (PMR) evaluated by noncontrast T1-weighted MRI has been shown to pathohistologically correspond to plaque hemorrhage. In several case reports comparing OCT images with coronary specimens, low intensity area without its attenuation was observed at lesions presenting plaque hemorrhage. However, whether the association of this OCT-derived feature with PMR remains to be elucidated yet. Purpose To characterize plaque hemorrhage in vivo by comparing with OCT and noncontrast T1-weighted MRI. Methods The current study prospectively enrolled 80 statin-treated patients with coronary artery disease requiring elective PCI. A total of 103 target lesions were imaged by both noncontrast T1-weighted MRI and OCT prior to PCI. Plaque hemorrhage on noncontrast T1-weighted MRI was defined as PMR>1.0. On OCT imaging analysis, low intensity area without attenuation (LIA) was defined according to the following criteria; (1) area presenting homogeneous low intensity signals, (2) clear border and (3) no signal attenuation behind its area. The maximum arc of LIA was manually measured. OCT-derived plaque features were compared in lesions with and without PMR>1.0. Results PMR>1.0 was observed at 49.5% of analyzed lesions. Patients with PMR>1.0 were more likely older (72 vs. 66 years, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels (median: 80 vs. 77 mg/dL, p=0.62) (Table). On lesion-based analysis, while fibrous cap thickness was similar between the two groups (80 vs. 100um, p=0.10), a larger lipid arc (270 vs. 230º, p=0.02) and a greater frequency of macrophage (90.2 vs. 53.9%, p<0.01), layered plaque (62.8 vs. 32.7%, p=0.003) and cholesterol crystal (70.6 vs. 30.8%, p<0.001) were observed at lesions with PMR>1.0. Furthermore, lesions with PMR>1.0 more frequently exhibited LIA (66.7 vs. 19.2%, p<0.001) and its greater maximum arc (33 vs. 0º, p<0.001) (Figure). Of note, PMR was significantly correlated to the maximum arc of LIA (r=0.51, p<0.001) (Figure). Multivariate analysis demonstrated LIA and cholesterol crystal as independent OCT-derived features associated with PMR>1.0 (Table). Conclusion In statin-treated patients, 49.5% of analyzed lesions presented PMR>1.0. Coronary lesions with PMR>1.0 more frequently harbored LIA and cholesterol crystals, in addition to other vulnerable OCT features. Our findings suggest OCT-derived LIA as a potential signature of plaque hemorrhage. Given that cholesterol crystal was another feature of PMR>1.0, plaque inflammation driven by cholesterol crystallization may exist at plaque hemorrhage despite statin use. Whether anti-inflammation agent could modulate plaque hemorrhage requires future investigation.

Predictive factors and gender insights into abnormal myocardial flow reserve in non-obstructive coronary artery disease: a CZT-SPECT analysis

Abstract Background Dynamic myocardial perfusion imaging (D-MPI) using cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT has emerged as a valuable method for assessing coronary microcirculation, particularly compared to conventional SPECT. Additionally, gender-specific disparities in microvascular dysfunction require further investigation. Objective This study aims to identify predictive factors for abnormal myocardial flow reserve (MFR) in non-obstructive coronary artery disease (CAD) using CZT-SPECT, with a focus on gender differences in MFR dysfunction. Methods A retrospective analysis was conducted on clinical data from 393 patients presenting with symptoms of "chest pain and/or tightness," all of whom were confirmed to lack obstructive CAD by coronary angiography or CT angiography. MFR was measured using CZT-SPECT, with values ≥2.5 considered normal and values <2.5 considered abnormal. Results Of the patients, 49.1% (193/393) demonstrated abnormal MFR, with females representing 56.7% (223/393). Females with abnormal MFR exhibited higher averages in age, total cholesterol, LDL-C, creatinine, left atrial diameter, left ventricular posterior wall (LVPW) thickness in diastole, and E/e’ ratio (P < 0.05). Additionally, MDRD-eGFR and mitral annular septal velocity e’ were lower in the abnormal MFR cohort (P < 0.05). Multivariate logistic regression analysis identified elevated LDL-C levels (OR = 1.513, 95%CI: 1.122–2.041, P = 0.007) and increased LVPW thickness (OR = 1.717, 95%CI: 1.140–2.585, P = 0.010) as independent predictors of abnormal MFR in females. ROC analysis suggested optimal cutoff for LDL-C at 3.68 mmol/L (sensitivity 31%, specificity 84%, AUC = 0.586; 95%CI: 0.511–0.661) and LVPW thickness at 9.5 mm (sensitivity 62%, specificity 52%, AUC = 0.576; 95%CI: 0.501–0.652). A combined ROC analysis of LDL-C and LVPW thickness showed a sensitivity of 50% and specificity of 73% (AUC = 0.632, 95%CI: 0.559–0.705). In males, greater left ventricular end-diastolic diameter (LVEDD) was significantly associated with abnormal MFR (P = 0.014), with LVEDD identified as a predictor (OR = 1.130, 95%CI: 1.016–1.258, P = 0.025) and an optimal cutoff at 44.5 mm (sensitivity 88%, specificity 37%, AUC = 0.609; 95%CI: 0.524–0.694). No significant gender differences were observed in overall left ventricular resting myocardial blood flow (MBF) among patients with abnormal MFR (P = 0.072); however, female patients exhibited higher resting MBF in specific territories supplied by the left circumflex and right coronary arteries, and higher E/e’ ratios (P < 0.05). Furthermore, a negative correlation was found between resting MBF in the territory supplied by the right coronary artery and E/e’ in females (r = -0.210, P = 0.030). Conclusion Predictors of abnormal MFR in non-obstructive CAD show gender disparities, implicating an association with left ventricular diastolic function.

Absence of coronary artery disease in high-risk sickle cell anemia patients: a new illustration supporting the protective effect of Bilirubin against atherosclerosis?

Abstract Background Sickle cell anemia (SCA) is associated with both cardiac and systemic vascular disorders, which are the leading cause of morbi-mortality. Although these patients cumulate multiple cardiovascular (CV) risk factors, along with chronic inflammation and endothelial activation, some pre-clinical studies underlined a paradoxical protection against atherosclerosis. Purpose The aim of this study was to evaluate the prevalence of coronary artery disease in a high-risk SCA population. Methods From January 2019 to December 2023, consecutive adult patients with SCA were prospectively included in the DREPACOEUR registry to specifically analyze cardiac structure and function. They all had a comprehensive CV evaluation at steady-state in day-hospital including clinical exam, cardiac imaging, rhythm monitoring along with biology analysis. Only patients that underwent coronary imaging (CT coronary angiogram) were included in this study. Results Ninety patients were included. Mean age was 44±12, 50% were male with a high prevalence of systemic hypertension (57%), obstructive sleep apnea (21%) and 10% smokers. Only one patient had history of diabetes while no dyslipidemia (or lipid lowering therapy) was reported. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 58±5%. Expectedly, patients showed low hemoglobin level 8,7±1.4g/dL with high hemolysis markers. Glomerular filtration rate was 109 [62; 122] mL/min/m² with 21% having chronic kidney disease. Plasmatic LDLc level was low (0.7±0.3g/L, with 20% <0.5g/l) while triglycerides (TG) were highly variable (1.1±0.7mg/dL). Strikingly, no patient showed signs of significant coronary artery disease, with 87% presenting a calcium score of 0, 77% had a CAD-RADS of 0 while no patient was higher than 2. Correlation and linear regression analysis were performed to find independent parameters associated with LDLc and TG. Total bilirubin was the only variable that correlated with both LDLc and TG (R= -0.37, p<0.001 and R= -0.33, p=0.001 respectively). Conclusion Despite systemic vasculopathy and chronic inflammation, ageing SCA patients showed no significant coronary artery disease. These data are in line with pre-clinical studies suggesting a lipid-lowering role of bilirubin and its protective effect against atherosclerosis.

The effectiveness and barrier of reverse cascade screening for paediatric familial hypercholesterolaemia

Abstract Background Familial Hypercholesterolaemia (FH) is an autosomal dominant genetic disorder that is prevalent in one out of every 300 individuals in the general population. Recognized as an actionable condition, early diagnosis of FH in children is crucial to prevent the onset of atherosclerosis, and equally important is the identification of parents before the development of coronary artery disease events. Therefore, the significance of universal FH screening during childhood combined with reverse cascade screening has been increasingly acknowledged. To achieve these objectives, in our region, universal lipid screening is conducted in elementary schools for children aged 9 or 10 years, annually screening approximately 8,000 individuals, with those identified being referred through a three-step process to four major healthcare facilities within the prefecture. However, the effectiveness of reverse-cascade screening remains unclear. Purpose Our study aimed to assess the effectiveness of and identify barriers to implementing reverse cascade screening in conjunction with universal lipid screening. Methods We conducted a single-center, retrospective observational study from January 2018 to July 2023 and evaluated the utility of reverse cascade screening for children genetically diagnosed with FH following universal screening. This study analysed prevalent barriers and identified families with suspected FH through reverse cascade screening, counting those with Potential FH among second-degree relatives. Beyond successful identification, we categorized the frequently encountered barriers into five distinct categories: bereavement, prior cardiovascular events, dyslipidaemia with unspecified LDL-C levels, incomplete family history information, and inadequate disease awareness of FH. Reverse FH diagnosis adhered to current guidelines. Results and Discussion Of 151 paediatric patients referred to our facility, 67 were genotypically confirmed to have FH. Excluding 8 cases of divorce and 4 cases of tracking challenges, 55 patients were finally analysed. 62 patients were diagnosed with reverse FH, and appropriate treatment was initiated. Notably, 158 cases of Potential FH were identified. (25 first-degree and 133 second-degree relatives). While a higher number of reverse FH diagnoses were observed in first-degree relatives (55 cases), the diagnostic yield was lower among second-degree relatives (seven cases). Common barriers for second-degree relatives included dyslipidaemia with unspecified LDL-C levels (42 cases) and incomplete family history information (66 cases). Conclusion Integrating universal screening with reverse cascade screening facilitates the identification of new FH cases. A comprehensive strategy for diagnosing reverse FH is paramount, raising disease awareness, genetic testing, the development of a family-based care plan, and enhancing access to information and communication technologies.

Clinical Deep Data Accumulation System (CLIDAS) reveals a "Lipid paradox" of hypertriglyceridemia in Japanese patients

Abstract Background The association between triglycerides (TG), HDL cholesterol (HDL-C) and the prognosis of cardiovascular disease has not been established. Purpose The aim of this study was to elucidate the relationships between the combination of TG and HDL-C levels and the risk of a major adverse cardiac and cerebral events (MACCE) and to verify the usefulness of TG and HDL-C as a risk stratification factor using the Clinical Deep Data Accumulation System (CLIDAS) database. Methods CLIDAS is a database that accumlates electronic medical records in seven tertiary hospitals in Japan including patient characteristics, medications, laboratory test, physiological test, cardiac catheterization, and PCI treatment. We analyzed 9,690 patients who underwent PCI between April 2014 and March 2020. These patients were stratified into the acute coronary syndrome (ACS) group (N=4,135; 43%) and the chronic coronary syndrome (CCS) group (N=5,555; 57%). Furthermore, patients were divided into four groups based on mean serum TG levels (175 mg/dL) and HDL-C levels (40 mg/dL) as cutoff values: high TG/low HDL-C, low TG/low HDL-C, high TG/high HDL-C, and low TG/high HDL-C, and compared for major adverse cardiac and cerebrovascular events (MACCE). The median follow-up duration was 2.5 years. Results The patients with high TG/low HDL-C showed the highest event rates in myocardial infarction among the ACS group. The hazard ratio for high TG/low HDL-C versus low TG/high HDL-C was 1.76 (95% CI, 1.08 to 2.87, P < 0.05) after adjustment for age, sex, eGFR, and mean LDL-C levels, while we observed no risk stratification by the combination of TG and HDL-C levels in the CCS group (Figure 1). In contrast, the patients with low TG levels showed the paradoxically higher event rates of MACCE in both the ACS and CCS groups, as well as cardiovascular death in the CCS group, compared to those with high TG levels (Figure 2). The hazard ratio for low TG/low HDL-C versus high TG/low HDL-C was 3.21 (95% CI, 1.44 to 7.13, P <0.005), and the hazard ratio for low TG/high HDL-C versus high TG/high HDL-C was 2.23 (95% CI, 1.03 to 4.84, P < 0.05) in the CCS group after adjustment for age, sex, eGFR, and mean LDL-C levels. Conclusion In the CLIDAS database, while high TG and low HDL-C levels stratified the risk of ACS, low TG levels showed worsening prognosis for CV death, suggesting a "Lipid paradox" in the real world.Figure 1Figure 2

Body mass index as a contributor to the accumulation of lipidic plaque materials in statin-treated type 2 diabetic patients with coronary artery disease: sub-analysis from the OPTIMAL randomized study

Abstract Background Patients with type 2 diabetes mellitus more likely exhibit obesity. Pathophysiologically, obesity promotes a range of metabolic disturbances including insulin resistance, dyslipidemia and hypertension, in addition to the secretion of adipokines and pro-inflammatory cytokines from excessive fat accumulation. These atherogenic features may promote instability of atherosclerotic plaques, which ultimately result in elevating a risk of atherosclerotic cardiovascular disease. However, it remains to be fully elucidated how obesity affects atherosclerotic plaque features in type 2 diabetic patients with coronary artery disease (CAD). Near-infrared spectroscopy (NIRS) imaging enables to quantitatively visualize lipidic plaque materials in vivo. This imaging modality provides insights into lipidic plaque features in obese patients with type 2 diabetes mellitus. Purpose To elucidate the association of body mass index (BMI, kg/m2) with lipidic plaque materials in type 2 diabetic patients. Methods The OPTIMAL study was a prospective randomized controlled trial to evaluate the efficacy of continuous glucose monitoring (CGM) guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic participants with CAD requiring PCI. 94 patients were randomized into CGM-guided or HbA1c-guided glycemic control. Serial NIRS imaging was conducted to monitor non-culprit lesions at baseline and week 48. The current sub-analysis included 78 patients with both baseline BMI data and evaluable baseline NIRS/IVUS images. Results All of study subjects received a statin (high-intensity statin use=36%), and the averaged LDL-C level was 86.7±26.3 mg/dL. The average BMI and HbA1c level were 24.7±3.1 kg/m2 and 7.5±0.9%, respectively (Table 1). On NIRS imaging analysis, maxLCBI4mm at non-culprit lesions was 286.2±167.0, and 21.8% of study subjects exhibited maxLCBI4mm >400 (Table 2). BMI was associated with maxLCBI4mm (p<0.001). Multivariate analysis adjusting clinical characteristics and LDL-C demonstrated that BMI was an independent contributor to maxLCBI4mm [estimate=17.15 (12.88-21.42), p<0.001] (Table 2). Even in patients receiving high-intensity statin, BMI was still associated with maxLCBI4mm (p<0.001). Conclusions A greater accumulation of lipidic plaque materials was observed in association with BMI in statin-treated type 2 diabetic patients with CAD. This presence of enhanced plaque vulnerability at non-culprit lesions, in the setting of obesity, may contribute to an increased risk of cardiovascular events in type 2 diabetic patients with CAD. The current finding suggests the need to adopt further therapeutic approaches to favourably modify plaque vulnerability in type 2 diabetic patients exhibiting obesity.Table 1:Clinical DemographicsTable 2:Factors Associated with maxLCBI