Background: Olpasiran and pelacarsen are gene-silencing therapies that lower lipoprotein(a). Cardiovascular outcome trials are ongoing. Mendelian randomisation studies estimated clinical benefits from lipoprotein(a) lowering.
Objective: Our study estimated prices at which olpasiran and pelacarsen, in addition to standard-of-care, would be deemed cost-effective in reducing risk of recurrent coronary heart disease (CHD) events in the Australian healthcare system.
Methods: We developed a decision tree and lifetime Markov model. For olpasiran, participants had CHD and lipoprotein(a) 260 nmol/L at baseline and three-monthly injections, profiled on OCEAN(a) Outcomes trial (NCT05581303). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a) from treatment. Mendelian randomisation study data were used to estimate downstream clinical benefits. Annual discounting was 5 %. For pelacarsen, participants had CHD and lipoprotein(a) 226 nmol/L at baseline and one- monthly injections, profiled on Lp(a) HORIZON (NCT04023552) trial.
Results: Olpasiran in addition to standard-of-care saved 0.87 discounted quality-adjusted life years (QALYs) per person. Olpasiran in addition to standard-of-care would be cost- effective at annual prices of AU$1867 (AU$467 per dose) at threshold AU$28,000 per QALY. Pelacarsen would be cost-effective at annual prices of AU$984 (AU$82 per dose). For ICER threshold AU$50,000 per QALY, olpasiran and pelacarsen would be cost-effective at annual prices AU$4207 and AU$2464 respectively.
Conclusion: This early health technology assessment model used inclusion criteria from clinical trials. Olpasiran and pelacarsen would be cost-effective if annual treatment prices were AU$1867 and AU$984 respectively, from the Australian healthcare perspective.
Background: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear.
Objective: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS.
Methods: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups.
Results: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02).
Conclusion: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.
Background: Although direct measurement of LDL cholesterol (LDL-C) in blood is possible, there are several formulas for its estimation. The performance and concordance of these formulas have not been evaluated in Colombia.
Objective: To determine the concordance between LDL-C directly measured using the enzymatic technique and existing methods to calculate it.
Methods: Study of diagnostic tests, and concordance. We analyzed complete lipid profile samples, which included direct measurement of LDL-C, from 2014 to 2022 at Hospital Universitario San Ignacio (Bogotá, Colombia). The direct LDL-C measurements were compared with estimations using the DeLong, Sampson, Friedewald, extended Martin/Hopkins, Anandaraja, and Cordova methods. Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were employed, conducting subgroup analyses based on triglycerides (TG), and LDL-C levels. Kappa coefficients assessed agreement in LDL-C risk categories according to dyslipidemia guidelines.
Results: A total of 2144 samples were evaluated. The formulas with the best CCC were DeLong (0.971) and Sampson (0.969), with no relevant differences. The extended Martin/Hopkins formula (0.964) and the Friedewald formula (0.964) also performed well. The Anandaraja (0.921) and Cordova (0.881) equations exhibited inferior performance. For all formulas, a decrease in concordance was observed when triglycerides were ≥400 mg/dL or when LDL-C was <100 mg/dL. Most formulas demonstrated optimal agreement when assessed using risk categories according to dyslipidemia guidelines, except for Anandaraja and Cordova.
Conclusions: The DeLong, Sampson, extended Martin/Hopkins, and Friedewald formulas show the best concordance with directly measured LDL-C, so in most cases the results can be considered interchangeable. However, the Anandaraja and Cordova formulas are not recommended.
Aim: The aim of this study was to examine the clinical, laboratory and demographic characteristics of patients diagnosed with cerebrotendinous xanthomatosis.
Materials and methods: This study included 11 patients followed up in the Paediatric Metabolism Polyclinic for a diagnosis of CTX. The diagnosis of CTX was made from high blood cholestanol level and CYP27A1 gene analysis. All the cases diagnosed with CTX for whom clinical and laboratory findings were evaluated were included in the study.
Results: Evaluation was made of 11 patients from 5 different families. The diagnosis was established 25 years after the symptoms first appeared. The diagnosis was made because of bilateral cataracts in 2 patients, tendon xanthomas in 2, and as a result of family screening in 7. Tendon xanthomas were present in 36.3 % of the patients, and there was a history of cataract in 54.5 %. In the current study, mental retardation was determined in 72 % of the patients, psychiatric findings in 36 %, epilepsy in 36 %, pyramidal-extrapyramidal findings in 45 %, and postural tremor in 54 %. In addition, neuropsychiatric symptoms were seen at different rates in patients with different gene alleles. No tendon xanthomas were determined in the cases with c.1263 + 4A>T and c.808C>T mutations. Cataract was determined in all the cases with homozygote c.1263 + 4A>T mutation.
Conclusion: In this study, it was determined that the cases were diagnosed late despite the onset of symptoms providing clues for diagnosis at an early age. It was determined that the delay in diagnosis was 25 years.
Background and aims: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients.
Methods: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities.
Results: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group.
Conclusions: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.