Background: Cardiac autonomic neuropathy (CAN) is a serious but sometimes underdiagnosed complications of Diabetes Mellitus (DM). Because of the subtle onset and non-specific symptoms that can be mistaken for other conditions, CAN is frequently underdiagnosed despite the serious consequences that can appear. Its significance as an independent risk factor for cardiovascular events, including arrhythmias, sudden cardiac death, and silent myocardial ischemia, is being demonstrated by recent studies. The objective of this review article is to highlight the reasons why CAN is underdiagnosed and its association with decreased cardiovascular risk and promote clinical awareness. This review article summarizes the epidemiology, influence on the cardiovascular system and diagnostic methods of CAN, and the clinical implications of diabetic neuropathy. This review analyzes available data from papers relevant to the topic of diabetic neuropathy, cardiac autonomic neuropathy, and cardiovascular system implications. Conclusions: CAN is still underdiagnosed despite its clinical impact because routine screening is lacking, and healthcare providers are not aware of it. To improve outcomes for people with DM, it is necessary to introduce standardized diagnostic procedures into clinical practice and increase the knowledge about CAN.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a common but also underdiagnosed complication of diabetes mellitus (DM), associated with high cardiovascular risk and mortality. Sudomotor dysfunction can serve as an early indicator of autonomic dysfunction. This study evaluated the association between sudomotor dysfunction and the severity of CAN in patients with type 2 diabetes (T2D). Materials and Methods: In this cross-sectional study, 109 patients with T2D were evaluated for diabetic peripheral neuropathy, cardiovascular autonomic dysfunction, and sudomotor dysfunction. Additionally, clinical and biochemical data were collected from patients’ medical records. Results: Sudomotor dysfunction (SUDO+) was present in 59.6% of patients. The presence of SUDO+ was associated with a higher age, longer duration of diabetes, lower eGFR (estimated glomerular filtration rate) values, and more severe signs of peripheral neuropathy. SUDO+ patients showed significantly greater orthostatic systolic and diastolic BP (blood pressure) changes, lower RR interval ratios, and lower feet ESC (electrochemical skin conductance) values. ROC (receiver operating characteristic) analysis for feet ESC in identifying pathological RR ratio showed an AUC of 0.689 (95% CI: 0.593–0.774, p = 0.0022), with a sensitivity of 46.7% and a specificity of 94.7% at a cutoff of ≤68 µS. For orthostatic hypotension and QTc prolongation, the ESC values had limited discriminative power. Chi-squared analysis showed a significant association between feet sudomotor impairment and pathological RR ratio (χ² = 6.521, p = 0.0107). Conclusions: Sudomotor dysfunction is associated with indicators of CAN. SUDOSCAN can be used as a complementary tool for early CAN detection in clinical practice.

Lipoprotein(a) [Lp(a)] is a highly heritable apoB-containing lipoprotein and a causal contributor to atherosclerotic cardiovascular disease that may contribute to residual cardiovascular risk after myocardial infarction (MI), while the clinical benefit of selective pharmacological Lp(a) lowering remains unresolved. This narrative review examines Lp(a) as a determinant of residual and recurrent cardiovascular risk after MI, integrating molecular biology, human genetics, coronary imaging, post-MI observational studies, measurement considerations, current management, and emerging therapies. Elevated Lp(a) has been associated with coronary plaque progression, high-risk plaque features, oxidized-phospholipid-related inflammatory pathways, recurrent ischemic events, and repeat revascularization, although prognostic associations vary across populations and endpoints. Because concentrations measured during acute MI may underestimate the stable Lp(a) phenotype in some patients, selective repeat measurement after clinical stabilization may be appropriate when classification could influence management or trial eligibility. Contemporary treatment remains centered on intensive control of LDL-C and other modifiable risk factors, while antisense oligonucleotides, small interfering RNAs, and oral particle-assembly inhibitors can produce profound Lp(a) reductions. According to sponsor-reported topline data released in September 2026, pelacarsen lowered Lp(a) but did not significantly reduce the prespecified primary cardiovascular endpoint in the overall Lp(a)HORIZON population; complete peer-reviewed results are not yet available. The sponsor-reported neutral HORIZON topline result raises unresolved questions regarding baseline Lp(a) and absolute reduction, timing of intervention and disease stage, and endpoint composition. Full peer-reviewed HORIZON data and ongoing cardiovascular outcome trials will be required to determine whether and under what conditions selective Lp(a) lowering translates into cardiovascular benefit.

Background/Objectives: Oxidative stress and galectin-3-related fibro-inflammatory processes contribute to heart failure pathophysiology, but their concurrent relationships with natriuretic peptides and structural/cardiorenal parameters remain incompletely characterized. We evaluated baseline associations of serum peroxide burden and galectin-3 with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and related phenotypic parameters in chronic heart failure. Methods: This cross-sectional analysis included 57 patients from a prospective single-center cohort. Serum peroxides were quantified using the ferrous oxidation–xylenol orange assay and expressed as nmol H₂O₂ equivalents/mL. Associations were assessed using Spearman correlation and linear regression with ln-transformed NT-proBNP. Benjamini–Hochberg correction was applied to eight secondary/exploratory correlations. Results: Serum peroxide burden correlated with NT-proBNP (ρ = 0.387, p = 0.0095; n = 44) and remained significantly associated after adjustment for age, sex, and left ventricular ejection fraction (B = 0.1756, p = 0.0420; n = 43). After additional estimated glomerular filtration rate (eGFR) adjustment, the effect estimate remained similar, although statistical significance was not reached (B = 0.1646, p = 0.0525; n = 39). Galectin-3 correlated with NT-proBNP, left ventricular end-diastolic volume index (LVEDVi), and serum uric acid; all associations remained significant after false-discovery-rate correction. Serum peroxide burden and galectin-3 were not significantly correlated. In an exploratory joint model (n = 29), both biomarkers remained significantly associated with ln(NT-proBNP) (adjusted R² = 0.4294). Conclusions: Serum peroxide burden and galectin-3 showed different cross-sectional association patterns with NT-proBNP and selected structural/cardiorenal parameters. Given the limited sample size, missing data, and exploratory nature of the joint model, these findings should be considered hypothesis-generating and do not establish biological independence or incremental clinical value.

Background/Objectives: Cardiovascular autonomic dysfunction in type 2 Diabetes Mellitus (T2DM) is heterogeneous, and individual autonomic measures may identify distinct clinical profiles. This study assessed the clinical, neuropathic, metabolic, and vascular correlates of three cardiovascular autonomic measures: the expiratory-to-inspiratory (E:I) R–R interval ratio, orthostatic blood pressure response, and corrected QT interval (QTc). Methods: This secondary cross-sectional analysis included 109 patients with T2DM from a previously characterized cohort. Cardiovagal function was assessed using the E:I R–R interval ratio during deep breathing. Orthostatic hypotension (OH) was defined according to systolic and diastolic blood pressure changes after standing, while QTc was calculated using Bazett’s formula. Peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument (MNSI) and Toronto Clinical Neuropathy Score (TCNS), and peripheral vascular status using the ankle–brachial pressure index (ABI). Group comparisons, chi-square or Fisher exact tests as appropriate, odds ratios (OR) with 95% confidence intervals (CI), Spearman correlation analyses, and multivariable linear regression analyses were performed. Exploratory families of comparisons and correlations were controlled using the Benjamini–Hochberg false discovery rate procedure. Results: A pathological E:I R–R interval ratio was identified in 90 patients (82.6%), prolonged QTc in 23 (21.1%), and orthostatic hypotension in 40 (36.7%). Categorical OH was not associated with the evaluated clinical, neuropathic, or vascular parameters. In contrast, continuous systolic blood pressure change after standing (ΔSBP) was independently associated with peripheral neuropathy severity, assessed using the MNSI and TCNS. The nominal univariable association between ΔSBP and HbA1c did not remain significant after false-discovery-rate correction or multivariable adjustment. QTc prolongation showed no consistent association pattern with the other evaluated autonomic-related measures. Conclusions: The evaluated cardiovascular autonomic measures showed partially distinct cross-sectional association patterns in patients with T2DM. Continuous ΔSBP was independently associated with peripheral neuropathy severity, whereas categorical orthostatic hypotension showed no significant associations. The E:I R–R interval ratio and QTc prolongation showed limited overlap with the other evaluated measures. These findings are hypothesis-generating and do not establish the diagnostic utility of individual measures for cardiovascular autonomic neuropathy.