RESUMEN
OBJECTIVE: Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V). METHODS: A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments. RESULTS: Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83-1.18), ASCVD event (aHR 0.97, 95% CI 0.84-1.12), and heart failure (aHR 1.06, 95% CI 0.87-1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52-0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups. CONCLUSIONS: There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke.
Asunto(s)
Amlodipino , Antihipertensivos , Bisoprolol , Quimioterapia Combinada , Hipertensión , Humanos , Femenino , Masculino , Bisoprolol/administración & dosificación , Bisoprolol/uso terapéutico , Persona de Mediana Edad , Amlodipino/administración & dosificación , Amlodipino/uso terapéutico , Amlodipino/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/complicaciones , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Resultado del Tratamiento , Valsartán/administración & dosificación , Valsartán/uso terapéutico , Taiwán/epidemiología , Adulto , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Estudios de CohortesRESUMEN
Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.
RESUMEN
High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.
Asunto(s)
Ezetimiba , Accidente Cerebrovascular Hemorrágico , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Quinolinas , Humanos , Masculino , Ezetimiba/uso terapéutico , Ezetimiba/efectos adversos , Ezetimiba/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Femenino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Anciano , Accidente Cerebrovascular Hemorrágico/epidemiología , Factores de Riesgo , Taiwán/epidemiología , AdultoRESUMEN
We aim to clarify the relationship between low skeletal muscle mass and varying levels of adiposity and to identify the types of physical function impairments associated with sarcopenic obesity (SO). This study examined cross-sectional data from the National Health and Nutrition Examination Survey with whole-body dual-energy X-ray absorptiometry (DXA) scans. The data included age, gender, DXA-assessed body composition, and physical functional activity with performing daily tasks by questionnaire. We subdivided the data by body composition into a non-SO group and a SO group (ASMI 0-49.99% and FMI of 50-100%), after which the SO data were subdivided into three classes. A higher class indicated higher adiposity and lower muscle mass. The physical function impairment of the two groups was compared. Our study examined 7161 individuals, of which 4907 did not have SO and 2254 had SO, and their data were further divided into three classes (i.e., class I, 826 individuals; class II, 1300 individuals; and class III, 128 individuals). Significant differences in demographics and DXA parameters were identified between the non-SO and SO groups (P < 0.001); the individuals with SO were older, included more women, and exhibited high adiposity and less lean muscle mass. The individuals with class III SO exhibited greater differences and reported more difficulty in performing daily activities. The individuals with class III SO exhibited the most severe physical function impairment. Our study highlights the considerable difficulties encountered by individuals with SO in performing daily activities. Given this finding, customized rehabilitation strategies should be implemented to improve the quality of life of individuals with SO.