Clinical Research in Cardiology最新文献

Background: The association between high levels of lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD) is influenced by clinical characteristics. We aimed to explore the heterogeneity in high Lp(a) population with different clinical phenotypes and their relationship with atherosclerosis cardiovascular disease (ASCVD) risk.

Methods and results: We included 11,629 participants with Lp(a) measurement in RED-CARPET Study (ChiCTR2000039901) from the First Affiliated Hospital of Sun Yat-Sen University. The primary outcome was the occurrence of ASCVD events. The k-means clustering method was performed for baseline variables in participants with high Lp(a) levels (Lp(a) ≥ 50 mg/dL). Multivariate logistic regression model was used to assess the association between high Lp(a) level and ASCVD across clusters, with the low-Lp(a) group (Lp(a) < 50 mg/dL) serving as reference. Propensity score matching (PSM) was used to validate thefindings. High-Lp(a) group was categorized into four clusters: cluster 1 (dyslipidemia); cluster 2 (aged females); cluster 3 (males with an unhealthy lifestyle) and cluster 4 (anemia, renal insufficiency and hypercoagulability). Patients in different clusters exhibited differences in ASCVD risk. Patients with high-Lp(a) had significantly highest risk for ASCVD in cluster 3 (OR 2.12, 95% CI 1.62-2.76, p < 0.001) after adjusting for traditional risk factors. However, no significant association was observed in cluster 4 (OR 0.82, 95% CI 0.58-1.16, p = 0.233). These findings remained consistent after PSM.

Conclusions: Using a data-driven approach, high-Lp(a) patients can be stratified into four phenotypically distinct subgroups with different ASCVD risk.

Background: This study investigated the relationship between apolipoprotein B (apoB), "excess apoB" (apoB beyond low-density lipoprotein cholesterol (LDL-C)), and apoB/apolipoprotein A1 (apoA1) ratio with 20-year atherosclerotic cardiovascular disease (ASCVD) incidence, using an age- and sex-specific approach.

Methods: In 2002, a cohort of 3042 adults, free of cardiovascular disease (CVD) residing in the greater Athens area (Greece) was recruited. A 20-year follow-up was conducted in 2022, comprising of 2169 participants, of whom 1988 had complete data for CVD incidence. Cox proportional hazards models were used to assess the association of apoB, excess apoB, and apoB/apoA1 with 20-year ASCVD risk and residual risk (events not predicted by standard factors).

Results: Older participants and males had higher levels of apoB, excess apoB, and apoB/apoA1. In the overall cohort, only apoB was significantly associated with ASCVD risk (hazard ratio (HR), 1.006; p = 0.003). However, age- and sex-dependent associations were observed as apoB, excess apoB, and apoB/apoA1 significantly predicted increased ASCVD incidence only in males under 40 years (HR 1.025, p = 0.005; 1.052, p = 0.003; 1.396, p = 0.002; respectively). Significant associations were observed with residual ASCVD risk in the overall cohort, with the most pronounced associations seen in males under 40 (HR 1.023, p = 0.001; 1.039, p < 0.001; 1.285, p = 0.002; respectively).

Conclusions: The association of apoB, excess apoB, and apoB/apoA1 with long-term ASCVD incidence and residual risk demonstrates age- and sex-dependent variations, with younger males showing elevated risk, highlighting the value of these markers beyond traditional risk factors and emphasizing the need for age- and sex-specific considerations in ASCVD risk assessment.

Background: Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyze the effect of evolocumab on endothelial function in patients with cardiovascular disease.

Methods: This was a prospective, double-blinded, randomized, controlled, single center study including patients with cardiovascular disease and treated with statins. Patients were consecutively randomized (1:1) to either evolocumab treatment or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G). Parameters of endothelial function were flow-mediated vasodilation (FMD), low flow-mediated vasoconstriction (L-FMC) and vasoactive range (VAR).

Results: Hundred three patients with a mean age of 66.2 ± 7.7 years and a mean LDL-cholesterol of 98 ± 19.1 mg/dl completed the study. The change in VAR from baseline to week 8 was significantly different with evolocumab compared to placebo (p = 0.045). Moreover, VAR increased after 8 weeks of treatment with evolocumab compared to baseline (p = 0.034). No change has been noticed in FMD and L-FMC after 8 weeks of treatment with evolocumab. In subgroup analyses, VAR improved in patients with age ≤ 67 years, lower systolic blood pressure (≤ 125 mmHg) and higher baseline LDL-cholesterol (> 95 mg/dl), (p = 0.006, p = 0.049 and p = 0.042, respectively) after 8 weeks of evolocumab treatment. No serious adverse event related to study medication occurred during the study.

Conclusion: Our data indicate that endothelial function improved with evolocumab treatment in high-risk patients on statin therapy with preexisting cardiovascular disease. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

Background: Despite the availability of effective LDL cholesterol (LDL-C)-lowering drugs, only a minority of patients achieves the guideline-recommended treatment targets. This analysis describes treatment pathways of lipid-lowering therapy (LLT) in Germany.

Methods: Health claims data were used to identify patients at high or very-high cardiovascular risk who received a LLT prescription 2016-2022. Treatment pathways and the time to switch or discontinue LLT were analysed for statins, ezetimibe, bempedoic acid (BA), and PCSK9 inhibitors (PCSK9i).

Results: Out of 3,487,827 insured persons, 247,529 met the inclusion criteria. The most frequent first-line LLT were statins in 96.3%. Ezetimibe, BA, and PCSK9i were first-line LLT in only 0.9%, 0.061%, and 0.046%, respectively. Only few patients experienced a change in their treatment regimen following LLT initiation. Prescriptions of BA and PCSK9i were mainly second-, third-, or fourth-line add-on treatment. Termination of treatment with BA and PCSK9i was less frequent compared to statins and ezetimibe. The median time to treatment discontinuation was 1.45, 1.04, 0.60, and 2.45 years for statins, ezetimibe, BA, and PCSK9i, respectively, and the median time to switch therapy was 4.81 and 4.87 years for ezetimibe and PCSK9i, respectively (median not reached for statins and BA).

Conclusions: Changes in LLT were only observed in a minority of patients. BA and PCSK9i were switched more frequently than statins and ezetimibe. BA was discontinued earlier, and PCSK9i later than the other agents. Continued efforts to maintain long-term adherence and overcome therapeutic inertia are needed to realise the potential of available LLT with proven cardiovascular benefit.

Dyslipidaemia, especially elevated low-density lipoprotein cholesterol (LDL-C), is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Dyslipidaemia remains underdiagnosed and undertreated. Dyslipidemia is highly prevalent in Germany. Even among patients with high- and very-high cardiovascular risk, LDL-C targets are often not achieved. This paper highlights key lipid parameters beyond LDL-C, such as triglycerides and lipoprotein(a), which contribute to residual cardiovascular risk. Practical guidance to address diagnostic challenges and cardiovascular risk assessment, especially in younger adults and those with risk modifiers, is provided. Lifestyle interventions are the basis of therapy. Statins remain the first-line treatment, with additional options including ezetimibe, bempedoic acid, and PCSK9 inhibitors, alone or in combination. Novel lipid-lowering therapies are currently in development and may offer more individualized treatment options in the future. The most important messages from the 2025 Focused Update of the 2019 ESC/EAS guidelines for the management of dyslipidaemias have been incorporated into the paper. While LDL-C targets remain unchanged, important novel recommendations encompass consideration of cardiovascular risk modifiers such as lipoprotein(a) and CRP/inflammatory diseases. A second important new recommendation is the use of potent early combination therapy after an acute coronary syndrome. Improved awareness, early diagnosis, and evidence-based lipid management are critical for reducing ASCVD burden. This paper is aimed at supporting clinicians in optimizing lipid diagnostics and therapy in daily practice.

Aims: Lipoprotein(a) [Lp(a)] is a novel biomarker for Atherosclerotic cardiovascular disease prediction. Yet, given the scarcity in high-quality evidence, its use in routine primary prevention screening is lacking. For this reason, we aimed to assess Lp(a) prognostic utility during routine screening.

Methods: A retrospective cohort of adults with available Lp(a) measurement, taken during a screening program (2008-2024) in a tertiary care center. Major adverse cardiovascular events (MACE) was the study primary outcome. The optimal Lp(a) threshold was evaluated using spline curve analysis and validated by Cox regression models adjusted for clinical and laboratory covariates. Subgroup analyses were performed in patients with SCORE2 and PCE data.

Results: 3052 people were included with a median (IQR) follow-up of 6.4 (3.5-12) years. Lp(a) threshold of 50 mg/dL was identified as a risk inflection point. High Lp(a) (> 50 mg/dL) was associated with increased MACE risk, independent of clinical data (HR 1.55, 95% CI 1.10-2.17, p = 0.011) or different laboratory variables (HR 1.62, 95% CI 1.07-2.46). High Lp(a) remained a predictor for MACE in models incorporating the SCORE2 and PCE scores, and its incorporation into these scores improved their performance in high-risk patients. In people with cardiovascular comorbidities, the optimal Lp(a) threshold for MACE prediction was 61 mg/dL, while it was 48.4 mg/dL in those without (n = 2778).

Conclusions: In a large ambulatory and mostly healthy cohort, Lp(a) showed a strong predictive utility for cardiovascular events. These findings support the integration of Lp(a) into primary cardiovascular risk assessment and role in guiding emerging targeted therapies.

Objective: To systematically evaluate the causal effect of lipoproteins to the risk of coronary artery disease (CAD) by systematic review and meta-analysis of the associated Mendelian randomization (MR) studies.

Methods: This systematic review was registered in PROSPERO (ID CRD42023465430). Searches from the databases (e.g., PubMed, Embase, Cochrane, Web of Science) and non-database sources to collect MR studies. The search time frame was from the database inception to August 2023. After data extraction, quality evaluation was performed, and the meta-analysis with bias evaluation was carried out with RevMan software.

Results: A total of 5,828,409 participants from 21 records were included. Quality and bias assessment was performed by evaluating the internal three assumptions of MR studies. Meta-analysis for the causal association between non-HDL lipoproteins and CAD showed a significantly positive association between LDL and CAD (OR 1.37, 95% CI 1.26-1.49; P < 0.001, I² = 95%), apoB and CAD (OR 1.38, 95% CI 1.11-1.71; P = 0.003, I² = 98%), and Lp(a) and CAD (OR 1.21, 95% CI 1.12-1.31; P < 0.001, I² = 99%). Interestingly, although there was no statistical significance in the association between VLDL/apoA1 and CAD (both P > 0.05), the pooled non-HDL lipoproteins showed a significantly positive association with CAD (OR 1.28, 95% CI 1.22-1.34; P < 0.001, I² = 99%). For the HDL lipoproteins, the pooled OR showed a significantly negative association with CAD (OR 0.84, 95% CI 0.72-0.98; P = 0.002, I² = 72%). However, the protective effect of HDL on CAD diminished when analyzed together with apoA1 and/or apoB (both P > 0.05). The funnel plot did not show serious publication bias, and sensitivity analysis performed relatively well robustness of the causal association of LDL, apoB, Lp(a), and total cholesterol with CAD.

Conclusion: The present meta-analysis suggests an overall effect of causal association between lipoproteins and CAD. Most of the non-HDL lipoproteins (LDL, apoB, Lp(a)) promote CAD, while the protective effect of HDL in CAD still needs to be verified in the future.

Background: Intravascular lithotripsy (IVL) emerged for the treatment of coronary artery calcification with encouraging safety and effectiveness rates in previous trials. Knowledge about the in-hospital safety of IVL in comparison to frequently used plaque modification techniques remains limited.

Objectives: The aim of this study was to assess the in-hospital outcomes of IVL in comparison to rotational atherectomy (RA) and cutting/scoring balloons (C/S).

Methods: A total of 51,921 isolated PCI procedures of patients who underwent planned coronary angiography with IVL, RA or C/S between 2019 and 2023 were extracted from a German nationwide registry. Analyses of the average treatment effect were carried out employing a double-robust estimator using machine learning algorithms.

Results: Compared to IVL, adjusted procedural relative risk of in-hospital mortality was significantly higher for RA (RR 1.72; 95% CI: 1.24 - 2.38, p = 0.001) and C/S (RR 1.50; 95% CI: 1.08 - 2.08, p = 0.015), while safety parameters such as stroke, severe bleeding and acute kidney injury were comparable. The adjusted risk of shock (RR 1.57; 95% CI: 1.20 - 2.04, p = 0.001) and pericardial drainage (RR 1.95; 95% CI: 1.23 - 3.07, p = 0.004) was lower for IVL compared to RA but not to C/S. Further, IVL use was associated with a shorter adjusted length of hospitalization compared to RA (- 0.75 days, p < 0.001) and C/S (- 0.22 days, p = 0.047).

Conclusion: IVL is associated with a favorable safety profile compared to RA and C/S and a more timely discharge of patients.