Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated “game-changer” trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.
Background Despite the implementation in the use of primary percutaneous coronary intervention (pPCI) and in secondary preventive measures, the risk of recurrence of myocardial infarction (MI) in patients who underwent ST-elevation myocardial infarction (STEMI) remains high. The prognostic role of old and emerging cardiovascular risk factors for MI recurrence, such as Lipoprotein(a) [Lp(a)] levels, in this very high-risk population is still not fully understood. Purpose To identify the baseline predictors of MI recurrence in a cohort of patients admitted for STEMI and treated with pPCI. Methods Single-center, observational, retrospective analysis of consecutive patients admitted for STEMI who underwent pPCI from February 2013 to April 2019 at our Insitution. Baseline demographic, clinical, echocardiographic and laboratory data were prospectively collected. Only patients with available Lp(a) values were included in the analysis. The study outcome was the recurrence of MI at three years follow-up. Univariable and multivariable Cox regression analysis was performed to identify the baseline variables correlated to the study outcome. Results The study population included 560 patients (mean age = 60.6±13.7 years; 79.5% males). Hypertension was observed in 351 patients (62.7%), diabetes in 134 (23.9%), dyslipidemia in 266 (47.5%), smoking status in 316 (56.4%), history of coronary artery disease (CAD) in 76 (13.6%), prior MI in 69 (12.3%), prior PCI in 62 (11.1%). Multivessel disease (MVD) was reported in 211 (37.7%) cases. The infarct-related artery was the left anterior descending in 310 patients (55.4%), the right coronary artery in 179 (32.0%), the left circumflex 60 (10.7%) and the left main in 11 (2.0%). Total cholesterol mean value was 187.7±48.8 mg/dl; LDL cholesterol was 112.2±41.3 mg/dl and Lp(a) was 26.5±27.2 mg/dl. At three-year follow-up, MI occurred in 58 (10.4%) patients. At multivariable analysis, Lp(a) (HR 1.015 95% CI: 1.008–1.022 p<0.001) and MVD (HR 1.994; 95% CI 1.179–3.372 p=0.010) emerged as the only two independent predictors of MI recurrence up to three years. The Kaplan-Meier analysis showed a significantly lower survival free from MI in patients with Lp(a) ≥50 mg/dl as compared to the subgroups with levels ≥30 and <50 mg/dL, or <30 mg/dL (Log-Rank=0.001). Also, MVD was able to identify patients with significantly lower survival free from MI for up to three years (Log-Rank=0.004). The Kaplan-Meier analysis combining these two parameters identified patients with both MVD and Lp(a) ≥50 mg/dl as the highest risk cohort for MI recurrence up to three years (MI incidence rate=22.2%; Log-Rank=0.002). Conclusions Among patients with STEMI who underwent pPCI, high Lp(a) level and MVD predict the recurrence of MI at long-term follow-up. Funding Acknowledgement Type of funding source: None
Aims The aim is to describe the baseline clinical, laboratory, and angiographic characteristics of patients with acute myocardial infarction (MI) according to the presence or not of diabetes mellitus (DM), and to evaluate if DM may influence the effect of lipoproteina [Lpa] serum level on long-term outcome in this very high-risk population. Methods and results This was a retrospective, single-centre, study including consecutive patients admitted with MI diagnosis between 1 January 2017 and 31 December 2020. The availability of data on baseline Lpa serum level was considered as an inclusion criterion. The study population was divided into two groups according to the presence or not of DM. The Lpa value of 50 mg/dl was used to test the hypothesis of a different effect of Lpa on the clinical outcome of patients with or without DM. The primary study outcome was all-cause death at 3-year follow-up. The study population included 997 patients (mean age 63.7 ± 13.5 years; 75.7% were males). Diabetes was reported in 280 (28.1%) patients. DM patients were older than those without DM (67.8 ± 12.1 vs. 62.0 ± 13.7 years, P < 0.001) and showed a significantly higher prevalence of dyslipidaemia, hypertension, obesity, prior MI, and prior coronary revascularization (P < 0.001). DM patients showed higher SYNTAX score value (19.8 vs. 15.1, P < 0.001) and a higher prevalence of left main involvement (6.3 vs. 3.1, P = 0.023). At Kaplan–Meier analysis, in the group without DM, patients with Lpa ≥ 50 mg/dl showed a significantly lower long-term survival compared with those with Lpa < 50 mg/dl (Log-Rank = 0.004). In DM patients, conversely, no survival difference was found between patients with Lpa ≥ 50 mg/dl vs. those with Lpa < 50 mg/dl. At multivariable Cox regression analysis, in patients without DM, Lpa serum level (HR: 2.68, 95% CI: 1.23–5.83; P = 0.013) and age (HR: 1.06, 95% CI: 1.04–1.09; P < 0.001) were independent predictors of mortality at 3-year follow-up. Among DM patients, only age was independently associated with 3-year mortality (HR: 1.07, 95% CI: 1.03–1.10; P < 0.001) (Table). Conclusions In this MI population, Lpa was independently associated with long-term mortality in patients without DM, but not in patients with DM. Whether DM can modify the effect of Lpa on clinical outcome after MI requires confirmation by larger prospective studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.