UNASSIGNED: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets.
UNASSIGNED: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression.
UNASSIGNED: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk.
UNASSIGNED: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.

Abnormal glucose metabolism is a common disease of the endocrine system. The effects of drugs on glucose metabolism have been reported frequently in recent years, and since abnormal glucose metabolism increases the risk of microvascular and macrovascular complications, metabolic disorders, and infection, clinicians need to pay close attention to these effects. A variety of common drugs can affect glucose metabolism and have different mechanisms of action. Hypertension is a common chronic cardiovascular disease that requires long-term medication. Studies have shown that various antihypertensive drugs also have an impact on glucose metabolism. Among them, α-receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers can improve insulin resistance, while β-receptor blockers, thiazides and loop diuretics can impair glucose metabolism. The aim of this review was to discuss the mechanisms underlying the effects of various antihypertensive drugs on glucose metabolism in order to provide reference information for rational clinical drug use.

UNASSIGNED: Blood pressure variability has been found to be a predictor of a stroke, heart failure, and ischemic heart disease that is independent of blood pressure control. This study used the variability independent of the mean (VIM) to evaluate the visit-to-visit blood pressure variability in patients previously undergoing catheter ablation (CA) of paroxysmal atrial fibrillation (PAF), and its relationship with AF recurrence was examined.
UNASSIGNED: The subjects were 274 consecutive PAF patients who underwent CA at our hospital. Finally, 237 subjects were included in the analysis. The mean follow-up period was 29.6 months, during which 37 subjects had recurrences, and 200 did not. During the outpatient blood pressure examinations, the VIM of the systolic blood pressure (VIM SBP) was significantly higher in the recurrence group, suggesting that blood pressure variability is associated with recurrence. The Cox proportional hazards ratio of the VIM SBP was significantly higher in the recurrence (4.839) than no-recurrence group, even after an adjustment, suggesting that the extent of the variability was a risk factor of recurrence post-CA. In addition, the Cox proportional hazard ratio for recurrence was significantly lower in the patients taking dihydropyridine calcium channel blockers, suggesting that the risk of recurrence may differ depending on the type of antihypertensive drug.
UNASSIGNED: Blood pressure variability may be a risk for AF recurrence after CA.

Elderly patients are prone to develop hyper- or hypokalemia, since they are susceptible to drugs or diets that affect the urinary or fecal potassium (K+) excretion. In aging mouse kidneys, in addition to glomerulosclerosis, proximal tubular atrophy, and atherosclerosis in renal arterioles, there was diffuse tubulointerstitial fibrosis with a number of inflammatory leukocytes infiltrating into the cortical interstitium. Since these pathological features greatly influence renal K+ handling, slowing the progression of kidney aging would fundamentally reduce the risk of developing hyper- or hypokalemia. Immunohistochemistry demonstrated the overexpression of K+ channels (Kv1.3) in leukocytes within the cortical interstitium, which was strongly associated with \"chronic inflammation\" in aging kidneys and the subsequent progression of renal fibrosis. In our basic studies, antihypertensive drugs (benidipine, nifedipine, verapamil, diltiazem) and anticholesterol drugs (lovastatin, simvastatin, pravastatin) strongly suppressed the leukocyte Kv1.3 channels and thus exerted anti-inflammatory effects. Given such pharmacological properties of these drugs, they may also be useful in slowing the progression of tubulointerstitial fibrosis in aging kidneys and reducing the risk of hyper- or hypokalemia in elderly patients.

BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension.
METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice.
CONCLUSIONS: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults.
BACKGROUND: PACTR202107579572114.

Hypertension treatment and blood pressure (BP) control reduce cardiovascular disease burden. However, prevalence of controlled BP is overall insufficient and lack of adherence to treatment is a suggested major contributor. This prospective, randomized clinical trial was designed to evaluate whether a specific 3-month (m) action plan to improve therapeutic adherence results in a decrease in BP. Patients with ambulatory 24 h-BP ≥ 130/80 mmHg despite receiving ≥2 antihypertensive drugs and with therapeutic non-compliance confirmed by antihypertensive drugs analyzed in urine were randomized (1:1) to receive a specific 3 m program to improve adherence (INT = intervention) or routine follow-up (C = control). Antihypertensive treatment was not modified and knowledge of non-adherence was only notified to patients randomized to the intervention group. Before randomization and at 3 m all patients underwent urinary screening for antihypertensive drugs and 24 h-ambulatory-BP monitoring. Forty-five patients (36% women, mean age: 58 ± 13 yr) were randomized. At 3 m, mean (95% CI) BP differences (INT vs. C) were 12.2 mmHg (4.3-20.8), adjusted-p = 0.032 and 8.7 mmHg (2.5-14.8), adjusted-p = 0.018 for 24 h-systolic and 24 h-diastolic BP, respectively. Differences (INT vs. C) for office SBP and DBP were 18.4 mmHg (6.8-30.1), adjusted-p = 0.005 and 15.7 mmHg (7.2-24.2), adjusted-p < 0.001. Non-detected antihypertensive drugs were median [IQR]: 40% [25-100] and 0% [0-20] at baseline and 3 m, respectively, in the INT group, and 33.3% [25-63.7] and 33.3% [23.8-57.9], in the C group (p < 0.001 for the 3-month between-group comparison). A combined action plan of notifying knowledge of non-adherence plus a 3-month specific nursing intervention to improve therapeutic adherence results in BP reduction in patients with inadequate therapeutic compliance.

OBJECTIVE: We estimated overall refill adherence to all antihypertensive [AHT] and/or lipid-lowering drugs in the treatment regimen and its association with cardiovascular disease (CVD) in adults with type 1 diabetes, taking kidney disease into account.
METHODS: This Finnish Diabetic Nephropathy Study involved 1,558 adults with type 1 diabetes who had purchased AHT and/or lipid-lowering drugs within ± 0.5 year from baseline and were followed until their first CVD event, death, or end of 2015. Proportion of days covered (PDC) method was used to calculate adherence. The adherence was classified as good (≥80 %), intermediate (≥50 and <80%) or poor (<50%).
RESULTS: Median adherence rate was 74% (IQR 63-84 %). Both good (OR 0.55 [95% CI 0.33, 0.92], P=0.02) and intermediate (0.47 [0.29, 0.77], P=0.003) adherence were associated with lower odds of CVD, compared to poor adherence. Moreover, the higher the adherence percentage point in those with moderate albuminuria, the lower was the odds for CVD (0.81 [0.67, 0.98], P=0.03, per 10 unit increase in adherence).
CONCLUSIONS: In adults with type 1 diabetes, refill adherence of 50% or more to cardio-protective medications is associated with lower odds of incident CVD. Our findings highlight the relevance of going beyond prescribing protective CVD drugs, ensuring, and improving medication adherence matters.

Resistant hypertension (RHTN) prevalence ranges from 4 to 19% in Africa. There is a paucity of data on the role of genetic variation on RHTN among Africans. We set out to investigate the role of polymorphisms in ABCB1, ADRB1, CYP3A4, CYP3A5, NEDD4L, and NR3C2, on RHTN susceptibility among South Africans. Using a retrospective matched case-control study, 190 RHTN patients (cases: blood pressure (BP) ≥ 140/90 mmHg on ≥3 anti-hypertensives or BP < 140/90 mmHg on >3 anti-hypertensives) and 189 non-RHTN patients (controls: <3 anti-hypertensives, BP < 140/90 or ≥140/90 mmHg), 12 single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), quantitative PCR and Sanger sequencing. Genetic association analyses were conducted using the additive model and multivariable logistic regression. Homozygosity for CYP3A5 rs776746C/C genotype (p = 0.02; OR: 0.44; CI: 0.22-0.89) was associated with reduced risk for RHTN. Homozygous ADRB1 rs1801252G/G (p = 0.02; OR: 3.30; CI: 1.17-10.03) and NEDD4L rs4149601A/A genotypes (p = 0.001; OR: 3.82; CI: 1.67-9.07) were associated with increased risk for RHTN. Carriers of the of ADRB1 rs1801252-rs1801253 G-C haplotype had 2.83-fold odds of presenting with RHTN (p = 0.04; OR: 2.83; CI: 1.05-8.20). These variants that are associated with RHTN may have clinical utility in the selection of antihypertensive drugs in our population.

Antihypertensive drugs are commonly used by older adults because of the high prevalence of cardiovascular disease and its risk factors, and the increased absolute benefit of blood pressure reduction with increasing age. Clinical trials of blood pressure reduction in older adults have generally excluded older adults with multimorbidity, frailty and limited life expectancy. In this population, the benefit-harm ratio of aggressive blood pressure lowering may become unfavourable; a more relaxed blood pressure target may be appropriate; and deprescribing (cessation or dose reduction) of one or more antihypertensive drugs can be considered. Before deprescribing an antihypertensive drug, it is important to consider other indications for which it may have been prescribed (e.g. heart failure with reduced ejection fraction, diabetic nephropathy, atrial fibrillation). Evidence from randomised controlled deprescribing trials indicates that it is possible to deprescribe antihypertensives in frail older people. However, some patients may experience an increase in blood pressure that warrants restarting the drug. There are limited data on long-term outcomes (follow-up in deprescribing trials ranged from 4 to 56 weeks). The risk of adverse outcomes associated with deprescribing, such as withdrawal effects, can be minimised through appropriate planning, patient engagement, dose tapering and monitoring.

[This corrects the article DOI: 10.3389/fphar.2023.1291900.].