Inhibitors of apolipoprotein C3, triglyceride levels, and risk of pancreatitis: a systematic review and meta-analysis.

In recent years, novel apoC3 inhibitor therapies for the treatment of hypertriglyceridemia have been developed and assessed through phase II and III clinical trials. The objective of this study was to perform an updated meta-analysis on the impact of new apoC3 inhibitor drugs on triglyceride and apoC3 levels, as well as on the incidence of pancreatitis. We conducted a meta-analysis of randomized, placebo-controlled studies assessing the effects of apoC3 inhibitors therapy (antisense oligonucleotides and small interfering RNA) on triglyceride levels, apoC3 levels, and the occurrence of acute pancreatitis. This meta-analysis was performed according to PRISMA guidelines. The random-effects model was performed. Nine randomized clinical trials (n = 717 patients) were considered eligible for this systematic review. ApoC3 inhibitor drugs were consistently associated with decreased triglyceride levels (MD -57.0%; 95% CI -61.9 to -52.1, I2 82%) and lowered apoC3 values (MD -76; 95% CI -80.1 to -71.8, I2 77%) when compared to placebo. Furthermore, the use of apoC3 inhibitor drugs demonstrated a reduction in the risk of acute pancreatitis (OR 0.11; 95% CI 0.04 to 0.27, I2 0%). The present updated meta-analysis of randomized clinical trials demonstrated that the utilization of apoC3 inhibitors in patients with hypertriglyceridemia correlated with reduced apoC3 and triglyceride levels, along with a decreased risk of acute pancreatitis compared to the placebo.

Dyslipidemia in adults with congenital heart disease: A systematic review and meta-analysis.

AIMS: Several particular characteristics of patients with congenital heart disease could affect lipid levels. The objectives of this study were: a) to analyze the prevalence of dyslipidemia in congenital heart disease patients; 2) to compare lipid levels between congenital heart disease patients and a control group. DATA SYNTHESIS: This systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO CRD42023432041). A literature search was performed to detect studies that have reported lipid levels or the prevalence of dyslipidemia in congenital heart disease patients. We performed a qualitative analysis (studies that reported dyslipidemia prevalence) and quantitative analysis (studies that compared lipid values between congenital heart disease patients and controls). In total, 29 observational studies involving 22,914 patients with congenital heart disease and 641,086 controls were eligible for this review. The reported presence of "hyperlipidemia" or "dyslipidemia" ranged from 14.3% to 69.9%. When studies analyzed lipid variables dichotomously between congenital heart disease patients and controls, the results were conflicting. The quantitative analysis showed that patients with congenital heart disease have lower levels of total cholesterol (MD: -18.9 [95% CI: -22.2 to -15.7]; I2 = 93%), LDL-C (MD: -10.7 [95% CI: -13.1 to -8.3]; I2 = 90%) and HDL-C (MD: -6.3 [95% CI: -7.7 to -4.9]; I2 = 95%) compared to controls. CONCLUSIONS: The qualitative analysis showed some concerns, but the quantitative analysis indicates that congenital heart disease patients showed lower levels of total cholesterol, LDL-C, and HDL-C compared to controls. New research should be developed to clarify this relevant topic.

Lipoprotein(a) and heart failure: a systematic review.

The role of lipoprotein(a) [Lp(a)] as a possible causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information on the association between Lp(a) levels and heart failure (HF) is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and HF. This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between Lp(a) levels and HF. Eight studies, including 73,410 patients, were eligible for this research. Seven prospective or retrospective cohorts and one cross-sectional study were analyzed. Five studies analyzed populations without HF; another three included patients with HF or left ventricular dysfunction. The endpoints evaluated varied according to the study analyzed, including incident HF, HF hospitalizations, and decreased left ventricular ejection fraction. Lp(a) levels were also analyzed in different ways, including analysis of Lp(a) as a continuous or categorical variable (distinct cut-off points or percentiles). Globally, the studies included in this review found predominantly positive results. Data on some relevant subgroups, such as HF of ischemic or non-ischemic etiology or HF with or without left ventricular dysfunction, was poorly reported. This systematic review suggests that there would be a positive relationship between Lp(a) levels and HF. Given the complexity and heterogeneity of HF, new studies should be developed to clarify this topic.

Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies. RECENT FINDINGS: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

High lipoprotein(a) levels and mitral valve disease: A systematic review.

AIMS: The role of lipoprotein(a) [Lp(a)] as a possibly causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information available on the association between Lp(a) levels and mitral valve disease is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and mitral valve disease. DATA SYNTHESIS: This systematic review was performed according to PRISMA guidelines (PROSPERO CRD42022379044). A literature search was performed to detect studies that evaluated the association between Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and mitral valve disease, including mitral valve calcification and valve dysfunction. Eight studies including 1,011,520 individuals were considered eligible for this research. The studies that evaluated the association between Lp(a) levels and prevalent mitral valve calcification found predominantly positive results. Similar findings were reported in two studies that evaluated the SNPs related to high levels of Lp(a). Only two studies evaluated the association of Lp(a) and mitral valve dysfunction, showing contradictory results. CONCLUSIONS: This research showed disparate results regarding the association between Lp(a) levels and mitral valve disease. The association between Lp(a) levels and mitral valve calcification seems more robust and is in line with the findings already demonstrated in aortic valve disease. New studies should be developed to clarify this topic.

Effect of Yerba Mate (Ilex paraguariensis) on Lipid Levels: A Systematic Review and Meta-Analysis.

Several studies have evaluated the lipid-lowering properties of yerba mate, although the results were conflicting. The objective of this systematic review was to assess the effect of yerba mate consumption on lipid levels. A literature search was performed to detect observational and experimental studies that evaluated the association between yerba mate consumption and lipid levels. A quantitative analysis was performed with the subgroup of experimental studies. A meta-regression was performed considering the difference in baseline lipid values between the intervention and control groups as a covariate. Thirteen studies were considered eligible for this systematic review and seven studies (378 patients) were selected for quantitative analysis. In the qualitative analysis, the results were conflicting, both in the observational and in the experimental studies. In quantitative analysis, we found no differences in total cholesterol [mean difference 6.4 (CI 95% -2.2 to 15.0)], LDL-C [mean difference 5.5 (CI 95% - 1.5 to 12.6)], HDL-C [mean difference 0.4 (CI 95% -2.8 to 3.7)] and triglycerides [mean difference 5.7 (CI 95% 0.0 to 11.4)] levels when comparing the yerba mate and control groups. According to meta-regression, differences between baseline levels could influence the findings on total cholesterol and LDL-C but not on HDL-C or triglycerides. In conclusion, this research showed that yerba mate consumption was not associated with a significant change in lipid levels. Since the results are based on small inconclusive studies, more research is needed to confirm these findings.

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

OBJECTIVE: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). CONCLUSIONS: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.

Pharmacological lipid-modification therapies for prevention of ischaemic heart disease: current and future options.

Atherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle interventions and subsequently with pharmacological therapy. Statins are the recommended first-line pharmacological treatment. Some individuals might require further lowering of LDL cholesterol or be unable to tolerate statins. Additional therapies targeting different pathways in cholesterol metabolism are now available, ranging from small molecules taken orally, to injectable therapies. Examples include ezetimibe, which targets Niemann-Pick C1-like protein, and monoclonal antibodies that target PCSK9. Phase 3 trials have also been completed for bempedoic acid (targeting ATP-citrate lyase) and inclisiran (an interference RNA-based therapeutic targeting hepatic PCSK9 synthesis). In addition to LDL cholesterol, mendelian randomisation studies support a causal role for lipoprotein(a) and triglycerides in ischaemic heart disease. In this Series paper, we appraise currently available and emerging therapies for lowering LDL cholesterol, lipoprotein(a), and triglycerides for prevention of ischaemic heart disease.

A Low-Cost IEEE 802.15.7 Communication System Based on Organic Photodetection for Device-to-Device Connections.

In this article, we compare two different kinds of commercial light-emitting diodes (LEDs) in transmission and organic photodetectors based on poly(3-hexylthiophene) (P3HT) and a phenyl-C61-butyric acid methyl ester (PCBM) blend used as active layer in reception. Photovoltaic cells based on massive heterojunctions of semiconductor polymers have focused the attention of researchers due to their several potential advantages over their inorganic counterparts, such as their simplicity, low cost, and ability to process large area devices, even on flexible substrates. Furthermore, in logistics, storage management systems require the implementation of technological solutions that allow the control of merchandise in real time by means of light-emitting diode signals that send information about the product. However, the slow response time of these organic photodetectors should not be critical for this application, where the light intensity changes are very slow, which limits the speed of data transmission compared to inorganic based systems that use wireless optical communications. Finally, we show a low-cost visible light communication system based on organic photodetectors with a frame based on on-off keying with Manchester encoding to support device-to-device connections.

Radio-frequency low-coherence interferometry.

A method for retrieving low-coherence interferograms, based on the use of a microwave photonics filter, is proposed and demonstrated. The method is equivalent to the double-interferometer technique, with the scanning interferometer replaced by an analog fiber-optics link and the visibility recorded as the amplitude of its radio-frequency (RF) response. As a low-coherence interferometry system, it shows a decrease of resolution induced by the fiber's third-order dispersion (ß3). As a displacement sensor, it provides highly linear and slope-scalable readouts of the interferometer's optical path difference in terms of RF, even in the presence of third-order dispersion. In a proof-of-concept experiment, we demonstrate 20-µm displacement readouts using C-band EDFA sources and standard single-mode fiber.

Association between lipid markers in childhood/adolescence and cardiovascular events in adulthood: A systematic review. / Asociación entre los marcadores lipídicos en la infancia/adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Applicability of Artificial Intelligence in the Field of Clinical Lipidology: A Narrative Review.

The development of advanced technologies in artificial intelligence (AI) has expanded its applications across various fields. Machine learning (ML), a subcategory of AI, enables computers to recognize patterns within extensive datasets. Furthermore, deep learning, a specialized form of ML, processes inputs through neural network architectures inspired by biological processes. The field of clinical lipidology has experienced significant growth over the past few years, and recently, it has begun to intersect with AI. Consequently, the purpose of this narrative review is to examine the applications of AI in clinical lipidology. This review evaluates various publications concerning the diagnosis of familial hypercholesterolemia, estimation of low-density lipoprotein cholesterol (LDL-C) levels, prediction of lipid goal attainment, challenges associated with statin use, and the influence of cardiometabolic and dietary factors on the discordance between apolipoprotein B and LDL-C. Given the concerns surrounding AI techniques, such as ethical dilemmas, opacity, limited reproducibility, and methodological constraints, it is prudent to establish a framework that enables the medical community to accurately interpret and utilize these emerging technological tools.

Impact of Lipoprotein(a) Levels on Cardiovascular Risk Estimation.

INTRODUCTION: A new cardiovascular risk (CVR) calculator that incorporates Lipoprotein(a) [Lp(a)] levels has recently been designed. AIMS: To estimate CVR using the new score and to identify the reduction in low-density lipoprotein cholesterol (LDL-C) or systolic blood pressure (SBP) necessary to balance the risk attributable to Lp(a). METHODS: CVR throughout life and at 10 years was estimated with the new score in patients in primary prevention, both considering and not considering the value of Lp(a). When the estimated risk considering Lp(a) levels exceeded the baseline risk, the reduction in LDL-C levels or SBP necessary to balance the risk attributable to Lp(a) was calculated. RESULTS: In total, 671 patients (mean age 54.2 years, 47.2% women) were included. Globally, 22.7% of the population had high Lp(a) values (> 50 mg/dL or > 125 nmol/L). When calculating CVR throughout life and considering the Lp(a) value, the global risk increased in 66.7% of cases (median 19.3%). Similar results were observed when we assessed the 10-year risk. The risk associated with Lp(a) could be completely compensated by decreasing LDL-C (average 21 mg/dL) or SBP (average 6.3 mmHg) in 79.2% and 74.7% of cases, respectively. CONCLUSION: When calculating the CVR with the new score, two-thirds and one-third of the population were bidirectionally recategorized as 'up' or 'down,' respectively. The decrease in LDL-C or SBP mitigated the increased risk caused by Lp(a) levels across a substantial proportion of patients.

Temporal variability of Lp(a) in clinically stable patients: Implications for cardiovascular risk assessment.

OBJECTIVES: Lipoprotein(a) [Lp(a)] is a significant risk factor for cardiovascular disease, yet it is often overlooked in routine clinical assessments. As a primarily genetically determined risk factor, the traditional recommendation is to assess its level once in a lifetime, as the variability of Lp(a) over time is considered to be minimal. This study aims to evaluate the potential variability of Lp(a) in clinically stable patients and investigate factors contributing to the lack of stable levels. METHODS: A retrospective analysis was conducted on a sample of adult patients attending a lipid clinic. Participants with at least two Lp(a) measurements taken with a minimum interval of four months were included. Lp(a) measurements were performed using the immunoturbidimetric assay. Variability in Lp(a) values was calculated as a percentage change from baseline, with participants exceeding a 25% change classified as having hypervariable Lp(a) levels. Additional clinical and biochemical variables were assessed. RESULTS: 61 participants with 171 Lp(a) determinations were included. Thirty-four percent exhibited a variability of 25% or higher (hypervariable). Men showed slightly greater variability than women. Changes in Lp(a) categories were observed among hypervariable patients, with some participants experiencing an increase while others showed a decrease. Menopause was present in all the women with hypervariable levels. CONCLUSION: Our study suggests reconsidering the reliance on a single Lp(a) measurement for assessing cardiovascular risk. Repeat measurements, particularly in borderline cases, may be beneficial.

Ethnic/Racial and Geographic Disparities on Major Cardiovascular Events in Glucagon Like Peptide-1 receptor Agonists Trials: A Meta-Analysis.

Higher rates of type 2 diabetes mellitus (T2D) are found among racial and ethnic minorities in the United States. These groups also experience a higher rate of cardiovascular and renal complications. Despite the previously mentioned high risk, these minority groups are usually underrepresented in clinical trials. The purpose of this study was to report the effect of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on major cardiovascular events (MACE) in subgroup analysis along different ethnic/racial and geographical groups in patients with T2D included in cardiovascular outcomes trials (CVOTs). A meta-analysis of randomized studies that evaluated the use of GLP-1 RAs in patients with T2D and reporting MACE across ethnic/race and geographical regions groups was performed after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar, and Cochrane Controlled Trials databases. This meta-analysis was performed according to PRISMA guidelines. Measures of the effect size were expressed as odds ratios (ORs). Fixed or random effects models were used. Seven trials, including 58,294 patients, were identified and considered eligible for the analyses. GLP-1 RAs were associated with a reduction in MACE incidence in Europe (OR 0.77, 95% CI: 0.65-0.91) and Asia/Pacific (OR 0.70, 95% CI: 0.55-0.90) regions with no significant reduction observed in North America (OR 0.95, 95% CI: 0.86-1.05) and Latin America (OR 0.87, 95%CI: 0.63-1.21) MACE reduction was observed in all ethnic/race groups evaluated with exception to black patients. In this meta-analysis, we observed ethnic/racial and geographic disparities in MACE reduction with GLP-1 RAs in CVOTs. Consequently, we believe it is essential to systematically include and assess ethnic/racial minorities in clinical studies.

Relationship Between Lipoprotein(a) Levels and Cardiovascular Outcomes in Postmenopausal Women: A Systematic Review.

Elevated lipoprotein(a) [Lp(a)] levels are independently associated with atherosclerotic cardiovascular disease, although this association is less explored in postmenopausal women. The main objective of this systematic review was to analyze the association between elevated Lp(a) levels and cardiovascular outcomes in posmenopausal women. Studies that evaluated this association were searched in the current literature. Ten studies including 157.690 women were considered eligible for this study. In total, 4 prospective cohorts, 3 cross-sectional studies, 2 nested case-control studies, and one post-hoc analysis from a randomized clinical trial were analyzed. The included studies showed different results regarding the association between Lp(a) levels and cardiovascular outcomes: a positive association (4 studies), no association (2 studies), or different results depending on the subgroups or outcomes evaluated (4 studies). The results were robust when evaluating coronary events. The reduction in coronary events attributed to a hormone replacement therapy-associated decrease in Lp(a) levels was controversial.

Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

INTRODUCTION: The polycystic ovary syndrome (PCOS) may represent an important model of lipid alterations. Lipoprotein(a) [Lp(a)] has emerged as a new marker of cardiovascular risk. AIM: The main objective of this meta-analysis was to analyze the available evidence on Lp(a) levels in patients with PCOS compared to a control group. METHODS: This meta-analysis was performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified Lp(a) levels in women with PCOS compared to a control group. The primary outcome was Lp(a) levels expressed in mg/dL. Random effects models were used. RESULTS: Twenty-three observational studies including 2,337 patients were identified and considered eligible for this meta-analysis. In the overall analysis, the quantitative analysis showed that patients with PCOS have a higher Lp(a) levels (SMD: 1.1 [95% CI: 0.7 to 1.4]; I2=93%) compared to the control group. The results were similar in the analysis of the subgroups of patients according to body mass index (normal weight group: SMD: 1.2 [95% CI: 0.5 to 1.9], I2=95%; overweight group: SMD: 1.2 [95% CI: 0.5 to 1.8], I2=89%). Sensitivity analysis showed that the results were robust. CONCLUSIONS: This meta-analysis shows that women with PCOS had higher levels of Lp(a) compared to healthy women used as a control group. These findings were observed in both overweight and non-overweight women.

Relationship between lipoprotein(a) levels, cardiovascular outcomes and death in patients with chronic kidney disease: a systematic review of prospective studies.

INTRODUCTION AND AIM: In the general population, high levels of lipoprotein(a) (Lp(a)) are an independent risk factor for atherosclerotic cardiovascular diseases. However, the information available in patients with chronic kidney disease (CKD) is less robust. The main objective of this updated systematic review of prospective studies was to analyze the association between elevated Lp(a) levels and cardiovascular outcomes or death in patients with CKD. METHODS: The PRISMA guidelines were used to carry out this systematic review. Randomized clinical trials or prospective observational studies that evaluated the association between Lp(a) levels and cardiovascular outcomes or death in CKD patients were searched in the current literature. RESULTS: Fifteen studies including 12,260 individuals were identified and considered eligible for this systematic review. In total, 14 prospective cohorts and one post-hoc analysis of a randomized clinical trial were analyzed. Eight studies evaluated hemodialysis patients, one study analyzed patients on peritoneal dialysis, while six studies evaluated subjects with different stages of CKD. Median follow-up duration ranged from 1 to 8.6 years. Our findings showed that elevated Lp(a) values were associated with a higher risk of cardiovascular events or death in most studies, despite adjusting for traditional risk factors. CONCLUSION: The findings of this systematic review show that there is a positive association between Lp(a) levels and fatal and non-fatal cardiovascular events in patients with CKD.

Elevated Lipoprotein(a) Levels and Atrial Fibrillation: A Systematic Review.

Objective: The role of lipoprotein(a) (Lp[a]) as a possibly causal risk factor for atherosclerotic cardiovascular disease has been well established. However, the clinical evidence regarding the association between Lp(a) levels and atrial fibrillation (AF) remains limited and inconsistent. This study aimed to analyze the association between elevated Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and AF. Methods: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed to identify studies that evaluated the association between Lp(a) levels or SNPs related to high levels of Lp(a) and AF. Observational studies with a cross-sectional, case-control, or cohort design were included in this systematic review, without limitations according to language, country, or publication type. Results: Eleven observational studies including 1,246,817 patients were eligible for this systematic review. Two cross-sectional studies, 5 prospective/retrospective cohort studies, and 4 Mendelian randomization studies were analyzed. Two cross-sectional studies that compared Lp(a) levels between patients with and without AF showed conflicting results. Cohort studies that evaluated the incidence of AF according to Lp(a) levels showed different results: no association (3 studies), a positive association (1 study), and an inverse relationship (1 study). Finally, Mendelian randomization studies also showed heterogeneous results (positive association: 2 studies; inverse association: 1 study; no association: 1 study). Conclusion: Although there could be an association between Lp(a) levels and AF, the results of the studies published to date are contradictory and not yet definitive. Therefore, further research should clarify this issue.

New Therapies for Primary Hyperlipidemia.

Primary hyperlipidemias include a heterogeneous set of monogenic and polygenic conditions characterized by a strong family aggregation, severe forms of hypercholesterolemia and/or hypertriglyceridemia, appearance early on life, and a high risk of cardiovascular events and/or recurrent pancreatitis. In real life, a small proportion of the primary hyperlipidemia cases is recognized and treated properly. Our goal is to present an update of current and upcoming therapies for patients with primary hyperlipidemia. Recently, new lipid-lowering medications have obtained authorization from the U.S. Food and Drug Administration and the European Medicines Agency. These drugs target metabolic pathways, including (adenosine 5'-triphosphates)-citrate lyase (bempedoic acid), proprotein convertase subtilisin/kexin 9 (inclisiran), apolipoprotein CIII (volanesorsen), and angiopoietin-like 3 (volanesorsen), that have additive effects with the actions of the currently available therapies (i.e., statins, ezetimibe or fibrates). We discuss the potential clinical indications for the novel medications. To conclude, the addition of these new medications to the therapeutic options for primary hyperlipidemia patients may increase the likelihood of achieving the treatment targets. Also, it could be a safer alternative for patients with side effects for the currently available drugs.