Adherence to antihypertensives in the United States: A comparative meta-analysis of 23 million patients.

Adherence to antihypertensives is crucial for control of blood pressure. This study analyzed factors and interventions that could affect adherence to antihypertensives in the US. PubMed, Scopus, Web of Science, and Embase were searched on January 21, 2022 and December 25, 2023 for studies on the adherence to antihypertensives in the US. Nineteen studies and 23 545 747 patients were included in the analysis, which showed that adherence to antihypertensives was the highest among Whites (OR: 1.47, 95% CI 1.34-1.61 compared to African Americans). Employment status and sex were associated with insignificant differences in adherence rates. In contrast, marital status yielded a significant difference where unmarried patients demonstrated low adherence rates compared to married ones (OR: 0.8, 95% CI 0.67-0.95). On analysis of comorbidities, diabetic patients reported lower adherence to antihypertensives (OR: 0.95, 95% CI 0.92-0.97); furthermore, patients who did not have Alzheimer showed higher adherence rates. Different BMIs did not significantly affect the adherence rates. Patients without insurance reported significantly lower adherence rates than insured patients (OR: 3.93, 95% CI 3.43-4.51). Polypill users had higher adherence rates compared with the free-dose combination (OR: 1.21, 95% CI 1.2-1.21), while telepharmacy did not prove to be as effective. Lower adherence rates were seen among African Americans, uninsured, or younger patients. Accordingly, interventions such as fixed-dose combinations should be targeted at susceptible groups. Obesity and overweight did not affect the adherence to antihypertensives.

Acute cholesterol-induced anti-natriuretic effects: role of epithelial Na+ channel activity, protein levels, and processing.

The epithelial Na(+) channel (ENaC) is modulated by membrane lipid composition. However, the effect of an in vivo change of membrane composition is unknown. We examined the effect of a 70-day enhanced cholesterol diet (ECD) on ENaC and renal Na(+) handling. Rats were fed a standard chow or one supplemented with 1% cholesterol and 0.5% cholic acid (ECD). ECD animals exhibited marked anti-diuresis and anti-natriuresis (40 and 47%), which peaked at 1-3 weeks. Secondary compensation returned urine output and urinary Na(+) excretion to control levels by week 10. During these initial changes, there were no accompanying effects on systolic blood pressure, serum creatinine, or urinary creatinine excretion, indicating that the these effects of ECD preceded those which modify renal filtration and blood pressure. The effects of ECD on ENaC were evaluated by measuring the relative protein content of α, ß, and γ subunits. α and γ blots were further examined for subunit cleavage (a process that activates ENaC). No significant changes were observed in α and ß levels throughout the study. However, levels of cleaved γ were elevated, suggesting that ENaC was activated. The changes of γ persisted at week 10 and were accompanied by additional subunit fragments, indicating potential changes of γ-cleaving proteases. Enhanced protease activity, and specifically that which could act on the second identified cleavage site in γ, was verified in a newly developed urinary protease assay. These results predict enhanced ENaC activity, an effect that was confirmed in patch clamp experiments of principal cells of split open collecting ducts, where ENaC open probability was increased by 40% in the ECD group. These data demonstrate a complex series of events and a new regulatory paradigm that is initiated by ECD prior to the onset of elevated blood pressure. These events lead to changes of renal Na(+) handling, which occur in part by effects on extracellular γ-ENaC cleavage.