👤 Natalia Nardelli

To summarize recent advances in therapeutic strategies targeting angiopoietin-like protein 3 (ANGPTL3), a central regulator of triglyceride and remnant lipoprotein metabolism, and to discuss the potential of emerging pharmacologic approaches. Several pharmacologic approaches have demonstrated robust lipid-lowering efficacy through ANGPTL3 inhibition. Monoclonal antibodies (evinacumab, SHR-1918) and RNA-based therapies (vupanorsen, zodasiran, solbinsiran) effectively reduce triglycerides, apoprotein B (apoB)-containing lipoproteins, and nonhigh-density lipoprotein cholesterol. The newest and most promising innovation is CRISPR-mediated disruption of ANGPTL3 (CTX310). ANGPTL3 inhibition represents one of the most powerful current strategies for lowering triglyceride-rich lipoproteins and residual cardiovascular risk. While monoclonal antibodies and RNA-based drugs offer effective, repeat-dose therapies, in vivo CRISPR editing could enable a one-time, lifelong correction of hypertriglyceridemia and mixed dyslipidemia. The main challenge ahead lies in ensuring safety, scalability, and equitable access if long-term efficacy and tolerability are confirmed in phase 3 trials. Show less

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in patients living with type 1 diabetes (T1D). Dyslipidemia is a frequent risk factor in this population. Although statin therapy has demonstrated cardiovascular (CV) benefits in diabetes overall, specific evidence in T1D remains limited. This systematic review aims to evaluate the impact of statins on clinical and surrogate atherosclerosis-related outcomes in patients with T1D without established ASCVD. Statin use was associated with a significant reduction in the risk of major adverse cardiovascular events (MACE), with a pooled hazard ratio (HR) of 0.77 (95% CI: 0.70-0.84; low certainty), and a mean low-density lipoprotein cholesterol (LDL-C) reduction of 30.3 mg/dL (95% CI: -47.02 to -13.58; moderate certainty). Reductions in ApoB and non-HDL cholesterol were also reported. We conducted a systematic review following PRISMA guidelines. Searches were performed in PubMed, EMBASE, and Epistemonikos from inception to June 2025 using terms related to T1D, statins, and primary prevention. Eleven studies were included-nine randomized controlled trials (RCTs) and two cohort studies. Six (four RCTs and two cohorts) were eligible for meta-analysis of two primary outcomes; the remaining were summarized narratively. Statin use in T1D patients without ASCVD was associated with improved lipid profiles and reduced MACE. These findings support considering statins as a preventive strategy in this population, although prospective studies with hard outcomes are needed to better identify patients most likely to benefit. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor. Despite its clinical relevance, data on Lp(a) prevalence and impact in Latin America are limited. We aimed to assess the prevalence of elevated Lp(a) and its association with cardiovascular outcomes in a large, multicenter Argentine registry. The GAELp(a) registry included 3000 adults from six Argentine regions. Lp(a) levels were measured using standardized assays; elevated Lp(a) was defined as >50 mg/dL or >125 nmol/L. Clinical, biochemical, and imaging data were collected retrospectively and prospectively. Associations between Lp(a) and major adverse cardiovascular events (MACE) were evaluated with logistic regression in the overall population and stratified by statin use. Elevated Lp(a) was present in 31.4 % of participants, with no sex difference. It was associated with family history of cardiovascular disease, subclinical atherosclerosis, and familial hypercholesterolemia. Patients with elevated Lp(a) had a higher prevalence of coronary artery disease (18.4 % vs. 12.5 %, p < 0.001), peripheral artery disease (4.8 % vs. 2.5 %, p = 0.001), and MACE (21.3 % vs. 14.8 %, p < 0.001). Elevated Lp(a) independently predicted MACE (OR 1.53, 95 % CI: 1.24-1.90, p < 0.001), with stronger associations in statin-naïve individuals (OR 2.18, 95 % CI: 1.17-4.07). ROC analysis showed modest discrimination (AUC 0.57 in nmol/L, 0.59 in mg/dL). Elevated Lp(a) is frequent in Argentina and strongly linked to cardiovascular disease and events. Its predictive value appears greater in statin-naïve patients, highlighting its role as a marker of residual risk. These findings support routine Lp(a) measurement in cardiovascular risk assessment, particularly in regions with high ASCVD burden. Show less