Revisión sistemática: papel de la dieta cetogénica y de los componentes de la dieta mediterránea en la función cognitiva y la influencia de APOE4

Treball Final de Grau en Medicina. Codi: MD1758. Curs acadèmic: 2022/2023La incapacidad y deterioro de la calidad de vida que provoca la enfermedad de Alzheimer (EA) sumado a la inefectividad de los tratamientos actuales, hace necesario definir y trasladar a la clínica estrategias efectivas de prevención y tratamiento de la enfermedad, como es la dieta. Esta revisión tiene por objetivo primario explorar el beneficio tanto de diferentes componentes de la dieta mediterránea (AOVE y carotenos), como el de la dieta cetogénica en la mejora de la función cognitiva y como objetivos secundarios conocer la influencia de la dieta dependiendo del genotipo APOE de los pacientes y la influencia en la calidad de vida y actividades de la vida diaria en los pacientes. Para llegar a estos objetivos, se ha realizado una búsqueda exhaustiva en bases de datos y se ha realizado el análisis pormenorizado de la calidad metodológica y evidencia arrojada por los ensayos clínicos aleatorizados. En general, y con una calidad metodológica adecuada, los estudios analizados determinan que ciertos componentes de la dieta mediterránea como el aceite de oliva virgen extra, sobre todo alto y moderado fenólico y los α-caroteno, luteína y Zeaxantina mejoran la función cognitiva en pacientes con deterioro cognitivo leve o función cognitiva normal pero con riesgo de EA en presencia (APOE4+) o ausencia del alelo APOE4 (APOE4-). Además, también se concluye que la cetosis y la dieta cetogénica tienen la capacidad de mejorar la función cognitiva, en pacientes APOE4- con deterioro cognitivo leve y EA de leve a moderada, aunque con mayores riesgos que la dieta mediterránea.The disability and deterioration of quality of life caused by Alzheimer's disease (AD) and the ineffectiveness of current treatments, makes necessary to define and transfer to the clinic effective strategies for prevention and treatment of the disease, such as the diet. This review has as a primary aim to explore the benefit of both the Mediterranean diet and its variations, as well as the ketogenic diet in improving cognitive function and as secondaries aims its influence depending on the APOE genotype of patients and the influence in the quality of life and the improving of the daily life activities. To reach this objective, an exhaustive search in databases and a systematic review has been carried out to analyse in detail the methodological quality and evidence provided by six randomized clinical trials. In general, and with an adequate methodological quality, the studies analysed determine that certain components of the Mediterranean diet such as the extra virgin olive oil, especially high and moderate phenolic, and high content of α-carotene, lutein and Zeaxanthin improve cognitive function in patients with mild cognitive impairment and patients at risk of AD but normal cognitive function, in both APOE4+ and APOE4-. In addition, it is also concluded that ketosis and ketogenic diet could improve cognitive function only in APOE4- patients with mild cognitive impairment and in mild to moderate AD, but with more risk of complications than the mediterranean diet

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Iron deficiency and short-term adverse events in patients with decompensated heart failure

Background: For patients with heart failure (HF), iron deficiency (ID) is a common therapeutic target. However, little is known about the utility of transferrin saturation (TSAT) or serum ferritin for risk stratification in decompensated HF (DHF) or the European Society of Cardiology's (ESC) current definition of ID (ferritin < 100 μg/L or TSAT < 20% if ferritin is 100–299 μg/L). We evaluated the association between these potential markers of ID and the risk of 30-day readmission for HF or death in patients with DHF. Methods: We retrospectively included 1701 patients from a multicenter registry of DHF. Serum ferritin and TSAT were evaluated 24–72 h after hospital admission, and multivariable Cox regression was used to assess their association with the composite endpoint. Results: Participants' median (quartiles) age was 76 (68–82) years, 43.8% were women, and 51.7% had a left ventricular ejection fraction > 50%. Medians for NT-proBNP, TSAT, and ferritin were 4067 pg/mL (1900–8764), 14.1% (9.0–20.3), and 103 ug/L (54–202), respectively. According to the current ESC definition, 1,246 (73.3%) patients had ID. By day 30, there were 177 (10.4%) events (95 deaths and 85 HF readmission). After multivariable adjustment, lower TSAT was associated with outcome (p = 0.009) but serum ferritin was not (HR 1.00; 95% confidence interval 0.99–1.00, p = 0.347). Conclusions: Lower TSAT, but not ferritin, was associated with a higher risk of short-term events in patients with DHF. Further research is needed to confirm these findings and the utility of serum ferritin as a marker of ID in DHF