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Abstract: Cardiovascular disease remains a leading cause of mortality despite major advances in lipid lowering and risk-factor control, highlighting the importance of residual cardiovascular risk. Inflammation is a central driver of atherosclerosis, while obesity promotes chronic low-grade inflammation, adipose tissue dysfunction, ectopic fat accumulation, and vascular injury. This narrative review focuses on obesity-associated inflammation as an upstream contributor to residual atherosclerotic risk and evaluates whether incretin-based therapies modify this pathway through weight loss, metabolic improvement, and additional inflammatory or vascular mechanisms. Data from mechanistic studies, biomarker analyses, vascular imaging studies, and cardiovascular outcome trials are reviewed. Anti-inflammatory trials support inflammation as a modifiable therapeutic pathway, although clinical benefit depends on the therapeutic target, timing, and patient selection. Glucagon-like peptide-1 receptor agonists reduce inflammatory and oxidative stress biomarkers and show anti-atherosclerotic effects in experimental models, but human vascular imaging data remain inconclusive. Cardiovascular outcome trials establish benefit with several GLP-1 receptor agonists, including semaglutide in selected patients with overweight or obesity without diabetes. However, direct human evidence for receptor-mediated anti-inflammatory or anti-atherosclerotic effects remains limited, and the relative contributions of weight loss, metabolic improvement, and additional mechanisms remain uncertain.
Keywords: atherosclerosis, inflammation, residual inflammatory risk, obesity, glucagon-like peptide-1 receptor agonists, semaglutide, tirzepatide, incretin-based therapy, cardiovascular prevention, adipose tissue inflammation
Published in DiRROS: 07.09.2026; Views: 123; Downloads: 80
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Abstract: Background: Juvenile-onset Huntington disease (JoHD) is a rare form of Huntington disease characterized by symptom onset at or before 20 years of age. Early manifestations are often non-choreic and may be attributed to developmental, psychiatric, movement, metabolic, or epileptic disorders. We described three molecularly confirmed cases and examined early manifestations, diagnostic pathways, and epilepsy. Methods: We conducted a retrospective case series and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review of PubMed, Scopus, and Web of Science Core Collection through 5 July 2026. The strict patient-level synthesis required attributable onset at or before 20 years, patient-specific molecular confirmation of a pathogenic HTT repeat expansion, and extractable clinical data. Complementary aggregate or linked reports using closely aligned JoHD criteria were retained for context but excluded from patient-level calculations. Results: The cases included childhood-onset JoHD with drug-resistant epilepsy, adolescent-onset JoHD with progressive motor-cognitive decline and epilepsy in a known Huntington disease pedigree, and childhood-onset JoHD without available family history, in whom status epilepticus prompted renewed diagnostic evaluation. Ninety-three reports were included; of these, 81 contributed 228 unique patients and 12 provided complementary data. Early manifestations were heterogeneous and broadly consistent with previously described childhood-onset JoHD phenotypes. Diagnostic delay was extractable in 180/228 patients; among 172 with point estimates, the median was 4.0 years. Definite epilepsy was reported in 60/145 patients with ascertainable seizure status and was descriptively more frequent in childhood-onset (<10 years) than adolescent-onset (10–20 years) JoHD (49/84 [58.3%] vs. 11/57 [19.3%]). Conclusions: JoHD should be considered in children and adolescents with progressive multisystem neurological involvement, particularly when epilepsy occurs with developmental regression, gait or speech deterioration, pyramidal or extrapyramidal signs, basal-ganglia abnormalities, or a compatible family history.
Keywords: juvenile-onset Huntington disease, epilepsy, HTT CAG repeat expansion, basal ganglia, systematic review, seizures
Published in DiRROS: 26.08.2026; Views: 127; Downloads: 103
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Abstract: Cardiac rehabilitation (CR) plays a crucial role in managing patients who have undergone coronary intervention (CI) following acute myocardial infarction. While water-based exercise is gaining recognition as an exercise modality in this patient population, its impact on the subgroup of older adults remains unexplored. In this post hoc analysis, we investigated the effects of water-based exercise on adults older than 60 years undergoing CR after CI, comparing it to land-based exercise and a control group. In total, 45 patients aged over 60 participated in 14-day exercise programs, featuring two daily 30-min sessions. We assessed exercise capacity (VO2peak), vascular function (flow-mediated vasodilation (FMD)), heart rate variability (HRV), and blood markers (Interleukins 6, 8, and 10, P-Selectin, ICAM, and High-sensitivity CRP) before and after CR. VO2peak in the water-based group improved significantly after CR in comparison with the land-based group: 1.35 kg/mL/min (95% CI [0.20–2.50], p = 0.022). The significant difference between water-based and land-based groups was observed in several HRV parameters: Total power −1129.20 ms2 (95% CI [−1951.92–−306.49], p = 0.008); peak LF 0.04 Hz (95% CI [0.00–0.08], p = 0.036); SD1 −9.02 millisecond (95% CI [−16.86–−1.18], p = 0.025); and SD2 −19.71 ms (95% CI [−35.08–−4.34], p = 0.013). FMD and blood markers did not vary significantly based on the exercise group. These findings suggest that short-term water-based CR may have potential as an alternative to traditional land-based CR, improving VO2peak and cardiorespiratory fitness among adults over 60 years undergoing CR after CI.
Keywords: cardiac rehabilitation, coronary artery disease, exercise training, water-based (aquatic) exercise
Published in DiRROS: 11.06.2026; Views: 371; Downloads: 187
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Abstract: Background and Aims: Randomized trials showed efficacious lipid-lowering with PCSK9 inhibitors (PCSK9i), but real-world treatment is often limited by statin-associated side effects (SASE). We quantified the effectiveness, safety and cardiovascular outcomes of alirocumab, evolocumab and inclisiran in a national prospective registry. Methods: This was a prospective registry-based study of patients initiating a PCSK9i. Lipid trajectories were assessed at 0, 3, 9, 21, and 33 months. The average treatment effect of PCSK9i on lipid trajectories and cardiovascular outcomes was estimated by inverse probability of treatment weighting (IPTW) using covariate balancing propensity scores. Results: 1,385 patients (median age 64 years; 52% women; median baseline low-density lipoprotein cholesterol [LDL-C] 4 mmol/L, 57% SASE) were included and followed for 2459 patient-years. In patients on alirocumab (N=598), evolocumab (N=693), or inclisiran (N=94), mean unadjusted LDL-C reductions were –58.2% (–1.98 mmol/L), –58.9% (–2.09 mmol/L), and –33.2% (–1.17 mmol/L), respectively (p<0.001). IPTW-adjusted LDL-C reductions remained numerically greater for monoclonal antibodies but were no longer significantly different long-term. Predictors of greater LDL-C reduction were longer treatment duration, male sex, higher age, statin co-therapy and first-line use (p<0.001). Adverse events occurred in 31% of patients. Major adverse cardiovascular events were infrequent (2.6 per 100 personyears) with no significant between-drug differences after IPTW. Conclusions: PCSK9i are safe in real-world practice. Alirocumab and evolocumab achieve trial-like LDL-C reductions, while inclisiran shows attenuated effectiveness without statins. Meaningful residual risk persists despite therapy.
Keywords: PCSK9 inhibitors, monoclonal antibodies, siRNA, real-world study, inclisiran, evolocumab, alirocumab, LDL-C, statin intolerance, cardiovascular outcomes
Published in DiRROS: 22.04.2026; Views: 541; Downloads: 383
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Abstract: Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, significantly increasing the risk of premature cardiac events and mortality. In Pakistan, despite the potential burden of FH, comprehensive studies evaluating its genetic characteristics, cascade screening significance, and lipoprotein (a) [Lp(a)] levels remain scarce. Understanding these factors is crucial for effective diagnosis, risk assessment, and management of FH in the Pakistani population. Methods: After the identification of index case with clinical homozygous FH, characterized by high LDL-C and high Lp(a) levels together with a positive personal and family history of cardiovascular disease, a cascade screening of 66 relatives from a consanguineous family was performed. Blood samples were obtained from all subjects for biochemical and genetic analysis. Simon Broome criteria was applied on children for clinical FH diagnosis. Dutch Lipid Clinic Network scores were calculated for individuals aged ≥16years. Genetic screening was performed using next-generation sequencing to analyse all coding regions and exon-intron borders of the following genes: ALMS1, APOA1, APOB, APOA5, APOC2, APOC3, APOE, ABCA1, ABCG5, ABCG8, CREB3L3, GPIHBP1, LDLR, LDLRAP1, LIPA, LMF1, LPL, and PCSK9. The identified variants were confirmed using Sanger sequencing. Results: Cascade screening identified seven homozygous and 25 heterozygous FH patients with pathogenic variant in the LDLR gene (NM_000527.5: c.2416dupG: p. Val806GlyfsTer11). Additionally, heterozygous variants of uncertain significance were identified in 4 other subjects. Conclusion: This study underscores the high effectiveness of cascade screening in consanguineous families and societies that could lead to early detection and prevention.
Keywords: cardiovascular disease, cascade screening, consanguineous, familial hypercholesterolemia, homozygous
Published in DiRROS: 09.04.2026; Views: 361; Downloads: 363
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