Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option.

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)-Lp(a)-lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.

Hyperuricemia in Cardiac Rehabilitation Patients: Prevalence and Association with Functional Improvement and Left Ventricular Ejection Fraction.

INTRODUCTION: The role of uric acid (UA) and Hyper Uricemia (HU) in cardiac rehabilitation (CR) patients have been very little studied. AIM: To evaluate the prevalence of HU and if it is associated to the functional improvement obtained or the left ventricular Ejection Fraction (EF) in CR patients after Acute or Chronic Coronary Syndrome (ACS and CCS respectively). METHODS: We enrol 411 patients (62.4 ± 10.2 years; males 79.8%) enrolled in the CR program at Niguarda Hospital (Milan) from January 2012 to May 2023. HU was defined both as the classic cut-off (> 6 for females, > 7 mg/dL for males) and with the newly identified one by the URRAH study (> 5.1 for females, > 5.6 mg/dL for males). All patients performed a 6MWT and an echocardiography at the beginning and at the end of CR program. RESULTS: Mean UA values were within the normal range (5.6 ± 1.4 mg/dL) with 19.5% (classic cut-off) HU patients with an increase to 47.4% with the newer one. Linear regression analysis showed no role for UA in determining functional improvement, while UA and hyperuricemia (classic cut-off) were associated to admission and discharge EF. The same was not with the URRAH cut-off. CONCLUSIONS: HU is as frequent in CR patients as in those with ACS and CCS. UA didn't correlate with functional recovery while it is associated with admission and discharge EF as also is for HU (classic cut-off). Whit the URRAH cut-off HU prevalence increases significantly, however, it doesn't show any significant association with EF.

[Lipoprotein(a): relationships with atherosclerosis and valvular heart disease, and emerging therapies]. / Lipoproteina(a): associazione con la malattia aterosclerotica e valvolare e terapie emergenti.

Lipoprotein(a) [Lp(a)] is a well-established cardiovascular risk factor, whose relationship with atherosclerotic disease has been confirmed by epidemiological, genome-wide association, Mendelian randomization, and meta-analysis studies. This association is determined by its pro-atherogenic, pro-thrombotic and pro-inflammatory properties. Lp(a) is the most common monogenic risk factor for atherosclerosis, with a prevalence of about 1 in 5 people. Recently, its etiopathogenetic relationship with calcific and degenerative valvular heart diseases, particularly with aortic and mitral stenosis, has been suspected. It has not yet been demonstrated whether its reduction translates into a lower risk of cardiovascular events. Up to now, Lp(a) has been considered a non-modifiable risk factor, as current lipid-lowering drugs have limited effects on its levels. New specific lipid-lowering therapies with high efficacy in reducing circulating Lp(a) levels are being investigated in randomized trials; however, the effects of this reduction on cardiovascular outcomes are still being studied.

Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study.

Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED.