Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial.

Importance: Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective: To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions: Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures: Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results: There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. Conclusions and Relevance: These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02774460.

The antihypertensive potential of flavonoids from Chinese Herbal Medicine: A review.

With the coming of the era of the aging population, hypertension has become a global health burden to be dealt with. Although there are multiple drugs and procedures to control the symptoms of hypertension, the management of it is still a long-term process, and the side effects of conventional drugs pose a burden on patients. Flavonoids, common compounds found in fruits and vegetables as secondary metabolites, are active components in Chinese Herbal Medicine. The flavonoids are proved to have cardiovascular benefits based on a plethora of animal experiments over the last decade. Thus, the flavonoids or flavonoid-rich plant extracts endowed with anti-hypertension activities and probable mechanisms were reviewed. It has been found that flavonoids may affect blood pressure in various ways. Moreover, despite the substantial evidence of the potential for flavonoids in the control of hypertension, it is not sufficient to support the clinical application of flavonoids as an adjuvant or core drug. So the synergistic effects of flavonoids with other drugs, pharmacokinetic studies, clinical trials and the safety of flavonoids are also incorporated in the discussion. It is believed that more breakthrough studies are needed. Overall, this review may shed some new light on the explicit recognition of the mechanisms of anti-hypertension actions of flavonoids, pointing out the limitations of relevant research at the current stage and the aspects that should be strengthened in future researches.

Cost effectiveness of antihypertensive drugs and treatment guidelines.

PURPOSE: Arterial hypertension (AH) is associated with a high economic burden for the individual patient and for society in general. The study evaluates antihypertensives and their cost-effectiveness, comparing diuretics (D), beta-blockers (B), angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers (A) and calcium channel blockers (C) with no intervention (NI). METHODS: The study included five health states in a Markov model. Cost values included average cost of the drugs used, treatment in hospital and treatment in general practice (collected from Croatian Health Insurance Fund). The study was conducted separately for 65-year old men and women, with an initial probability of cardiovascular death risk of 2% and heart failure risk of 1%. The results were presented in terms of increase in QALYs and associated financial savings or costs in euros (€). RESULTS: Results for men (compared with NI): treatment with D resulted in a QALY increase of 0.76 and €886 in savings, treatment with C in an increase of 0.74 QALYs and €767 in savings, treatment with A in an increase of 0.69 QALYs and €834 in savings, treatment with B resulted in an increase of 0.40 QALYs, but with an additional cost of €41. Results for women (compared with NI): treatment with D resulted in an increase of 0.93 QALYs and €987 in savings, treatment with C in an increase of 0.89 QALYs and savings of €855, treatment with A in an increase of 0.86 QALYs and savings of €991, treatment with B in an increase of 0.48 QALYs, but with an additional cost of €148. CONCLUSIONS: Treatment of AH with D, C and A is cost effective compared with the no-intervention scenario. Diuretics are the most cost-effective first-line treatment. The scenario with beta-blockers resulted in additional QALY when compared with no intervention, but also additional costs; therefore, based on our results, this therapy would not be recommended as first-line treatment.

Research on Beers Criteria and STOPP/START Criteria based on the FDA FAERS database.

PURPOSE: Inappropriate medication criteria for the elderly have played an important role in ensuring the safety of medications for the elderly. Too few drugs included in the criteria cannot guarantee the safety of medication for the elderly. Too many drugs included in the criteria will result in less selective medication for the elderly. This paper uses real-world data to evaluate the relationship between antihypertensive drugs and falls, so as to provide references for experts and scholars to revise the criteria of potentially inappropriate medications for the elderly and clinical safe medication. METHOD: We use the US Food and Drug Administration Adverse Event Reporting System (FDA FAERS) to evaluate the association between specific antihypertensive drugs in six categories (alpha-1 receptor blockers (α-1 blockers), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-receptor blockers (ß-blockers), and diuretics) and falls by data mining algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), Medicines and Healthcare Products Regulatory Agency (MHRA), and the empirical Bayes geometric mean (EBGM) and compared with the relevant drugs included in the Beers Criteria and STOPP/START Criteria. RESULT: There are a total of 5,157,172 co-occurrences found in 973,447 reports aged 65 years or older from 2016 to 2019 in the FDA FAERS database, and the number of co-occurrences of falls is 5917 for the six categories of 51 antihypertensive drugs. Four kinds of mining methods overlap detection of 12 kinds of positive signal drugs, none of which are not included in the Beers Criteria and 7 drugs are included in the STOPP/START Criteria; 1-3 kinds of mining methods overlap detection of positive signal drugs, a total of 12 kinds, and one drug is included in the Beers Criteria and 5 drugs are included in the STOPP/START Criteria; 22 drugs have fall adverse events, but no positive signal is detected, and 13 drugs are included in STOPP/START Criteria; and 5 drugs have no fall adverse events and 3 drugs are included in the STOPP/START Criteria. CONCLUSION: The FAERS database was used to confirm the potential connection between some antihypertensive drugs and fall adverse events through data mining algorithms. The Beers Criteria did not clearly indicate the antihypertensive drugs that caused falls, and the antihypertensive drugs included in the STOPP/START Criteria were too extensive and did not include ß-blockers and diuretics. It is recommended that experts and scholars use real-world data (such as FAERS, EudraVigilance, WHO VigiBase, and so on) to further explore the relationship between specific antihypertensive drugs and falls in the elderly, so as to revise and improve the criteria for inappropriate medications for the elderly.

Comparison of Antihypertensive Drug Classes for Dementia Prevention.

BACKGROUND: Hypertension in midlife is associated with increased risk of Alzheimer disease and vascular dementia late in life. In addition, some antihypertensive drugs have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose antihypertensive drugs for the prevention of dementia. This study systematically compared seven antihypertensive drug classes for this purpose, using the Clinical Practice Research Datalink. METHODS: We assessed treatments for hypertension in an instrumental variable analysis to address potential confounding and reverse causation. We used physicians' prescribing preference as an ordinal instrument, defined by the physicians' last seven prescriptions. Participants considered were new antihypertensive users between 1996 and 2016, aged 40 and over. RESULTS: We analyzed 849,378 patients, with total follow up of 5,497,266 patient-years. We estimated that ß-adrenoceptor blockers and vasodilator antihypertensives conferred small protective effects-for example, ß-adrenoceptor blockers were associated with 13 (95% confidence interval = 6, 20) fewer cases of any dementia per 1000 treated compared with other antihypertensives. CONCLUSIONS: We estimated small differences in the effects of antihypertensive drug classes on dementia outcomes. We also show that the magnitude of the differences between drug classes is smaller than that previously reported. Future research should look to implement other causal analysis methods to address biases in conventional observational research, with the ultimate aim of triangulating the evidence concerning this hypothesis.

Add-on aliskiren treatment can decrease blood pressure but requires attention to risks of renal impairment and hyperkalemia Chikushi Anti-Hypertension Trial-Rasilez® (CHAT-Ras).

BACKGROUND: Renin is the starting point of the renin angiotensin (RA) system cycle. Aliskiren (AL), which is a direct renin inhibitor, suppressed the entire RA cycle. In the present study, the efficacy of add-on of AL treatment in patients with essential hypertension (HT) was investigated. METHODS: This study was a multi-center, open-label, prospective, observational study. Study subjects were patients with essential HT and poor blood pressure (BP) control, who had received calcium channel blocker monotherapy or angiotensin II receptor blocker monotherapy or had not received any BP lowering drugs. Following add-on of AL for 12 months, BP and additional laboratory findings were analyzed. RESULTS: A total of 150 subjects were enrolled. There were 50 dropout subjects including discontinuation. Dropouts were the highest in the ARB combination therapy group at 9 subjects due to adverse events, and 3 of them were due to hyperkalemia. A significantly higher number of patients with chronic kidney disease (CKD) dropped out compared to patients without CKD (φ = 0.166, p < .05). BP before add-on of AL was 155/88 mmHg. After add-on of AL, BP was significantly improved and this lowering was sustained for 3 months (136/78 mmHg, p < .001), 6 months (136/77 mmHg, p < .001) and 12 months (134/78 mmHg, p < .001). In contrast, add-on of AL increased the potassium level and decreased the estimated glomerular filtration rate. CONCLUSION: While add-on AL treatment achieved a favorable and sustained decrease of BP in this study, caution is necessary with regard to elevation of potassium levels and renal impairment.

Effect of Different Classes of Antihypertensive Drugs on Endothelial Function and Inflammation.

Hypertension is characterized by structural and functional changes in blood vessels that travel with increased arterial stiffness, vascular inflammation, and endothelial dysfunction. Some antihypertensive drugs have been shown to improve endothelial function and reduce levels of inflammatory markers regardless of the effect of blood pressure lowering. Third-generation ß-blockers, such as nebivolol and carvedilol, because they have additional properties, have been shown to improve endothelial function in patients with hypertension. Calcium channel antagonists, because they have antioxidant effects, may improve endothelial function and vascular inflammation.The Angiotensin Receptor Blocker (ARBs) are able to improve endothelial dysfunction and vascular inflammation in patients with hypertension and other cardiovascular diseases. Angiotensin converting enzyme (ACE) inhibitors have shown beneficial effects on endothelial function in patients with hypertension and other cardiovascular diseases, however there are few studies evaluating the effect of treatment with this class on the reduction of C-reactive protein (CRP) levels. Further studies are needed to assess whether treatment of endothelial dysfunction and vascular inflammation may improve the prognosis of patients with essential hypertension.

Heart Failure and Changes in Kidney Function: Focus on Understanding, Not Reacting.

The kidney is a regulatory organ and accommodates changes in cardiac function. There is cross-talk between the kidney and the heart. In heart failure, the kidney acts as a bystander but also contributes to several maladaptive processes. The pathophysiology of worsening kidney function and its association with prognosis are discussed, as are other aspects of how worsening kidney function contributes to increased cardiovascular risk. Data suggest that morbidity and mortality reduction in people with heart failure and kidney disease requires use of a renin angiotensin system blocker, beta blocker, and mineralocorticoid receptor antagonist, as well as an SGLT 2 inhibitor.

Diagnosis and Prevention of Hypertensive Heart Failure.

Elevated blood pressure (BP) has a strong and continuous association with Stage B and C heart failure (HF) and carries the highest attributable risk for HF. Intensive treatment of hypertension is crucial, as progression from hypertension (Stage A HF) to left ventricular hypertrophy (LVH) or other structural damage (Stage B HF) is common despite therapy. Echo cardiography is the modality of choice to detect Stage B HF. Ideally, Stage B HF should be prevented. However, regression of established LVH and other structural damage is feasible and improves prognosis. Despite differences among antihypertensive agents, control of BP remains the most important goal.

Intraclass differences among antihypertensive drugs.

The four major classes of antihypertensive drugs­diuretics, ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)­have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other ß-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.

Treatment of Hypertension in Chronic Kidney Disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines. RECENT FINDINGS: For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80 mmHg. Blood pressure level above 130/80 mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed. In patients with CKD, an intensive BP goal < 130/80 mmHg has been recommended. We review current treatment options.

Resistant Hypertension in Pregnancy: How to Manage?

PURPOSE OF REVIEW: The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium. RECENT FINDINGS: The main cause of severe hypertension in pregnancy is preeclampsia, and differential diagnosis must be done with secondary or primary hypertension. Women with preexisting resistant hypertension may need pharmacological therapy adjustment. Several drugs can be used to treat severe hypertension, with exception of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. The most used drugs are methyldopa, beta-blockers, and calcium channel antagonists. There is a general agreement that severe hypertension must be treated, but there are still debates over the goals of the treatment. Delivery is indicated in viable pregnancies in which blood pressure control is not achieved with three drugs in full doses. Resistant hypertension may arise in postpartum. The management of resistant hypertension in pregnancy must regard the possible etiology, the fetal well-being, and the mother's risk. Good care is mandatory to reduce maternal mortality risk.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PURPOSE OF REVIEW: Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. RECENT FINDINGS: Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

Polymorphic and Quantum Chemistry Characterization of Candesartan Cilexetil: Importance for the Correct Drug Classification According to Biopharmaceutics Classification System.

The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2-6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System.

Family hyperaldosteronism type I: a clinical case and review of literature.

Family hyperaldosteronism type I (glucocorticoids-remediable hyperaldosteronism) is a rare form of symptomatic arterial hypertension (AH), which often leads to the development of cerebrovascular complications. The disease is caused by the formation of the chimeric gene CYP11B2/CYP11B1.  Expression of the chimeric gene is regulated by adrenocorticotropic hormone, and glucocorticoid therapy leads to a decrease in aldosterone secretion and normalization of blood pressure. The article presents the first clinical case of this monogenic disease diagnosed by us in Russia. The features of clinical course and treatment of the patient have been traced in the dynamics for 40 years of observation. Modern approaches to the diagnosis and treatment of this rare family form of hypertension are discussed.

Randomized controlled trials of blood pressure lowering in hypertension: a critical reappraisal.

Sixty-eight blood pressure (BP)-lowering randomized controlled trials (defined as randomized controlled trials comparing active treatment with placebo, or less active treatment, achieving a BP difference, performed between 1966 and end 2013 in cohorts with ≥ 40% hypertensive patients, and exclusive of trials in acute myocardial infarction, heart failure, acute stroke, and dialysis) were identified and meta-analyzed grouping the randomized controlled trials on the basis of clinically relevant questions: (1) does BP lowering reduce all types of cardiovascular outcome? (2) Is prevention of all outcomes proportional to the extent of systolic, diastolic, and pulse BP? (3) Have all classes of BP-lowering drugs been shown capable of reducing all types of cardiovascular outcome? (4) Is BP lowering beneficial when intervention is initiated at any grade (or stage) of hypertension? (5) Do BP-lowering randomized controlled trials provide evidence about systolic BP and diastolic BP targets of treatment? (6) Should BP-lowering treatment be preferentially addressed to patients in higher risk categories promising larger absolute treatment benefits? The results of these meta-analyses provide further support to current hypertension treatment guidelines by showing that BP lowering can significantly reduce major cardiovascular outcomes largely independent of the agents used, significant risk reduction is found at all hypertension grades (stages), and when systolic BP is lowered below a cut off of 140 mm Hg with some further reduction limited to stroke at systolic BP values just <130 mm Hg. Absolute risk reduction progressively increases higher is total cardiovascular risk, but this greater benefit is associated with a progressively higher residual risk, ie, higher treatment failures.

Antihypertensive Therapies and Left Ventricular Hypertrophy.

PURPOSE OF REVIEW: It is widely accepted that successful lowering of blood pressure (BP) in patients with hypertension leads to regression of left ventricular hypertrophy (LVH). However, whether differences exist among pharmacological BP-lowering therapies is debated. In this report, we discuss these differences in light of recent literature and the position of extant practice guidelines. RECENT FINDINGS: Studies comparing the effects of antihypertensive classes on LVH regression reached different conclusions, but the overall direction which is reflected in current society guidelines is that successful lowering of BP is more important than selection of an individual antihypertensive class. Nevertheless, some practice guidelines added statements about considering a specific antihypertensive class for its potential benefit such as angiotensin-converting enzyme inhibitors and/or excluding a class such as direct vasodilators. On the other hand, reports have been consistent about the more favorable effect of intensive BP-lowering strategy (target systolic BP < 120 mmHg) compared to standard BP lowering (target systolic BP > 140 mmHg), which is not yet discussed in the current practice guidelines. Successful lowering of BP leads to LVH regression. While reports have been inconsistent about differences among antihypertensive classes, lowering BP beyond currently recommended levels has consistently showed a greater effect on LVH regression.

Effect of antihypertensive treatment on the long-term outcome of patients discharged after acute ischemic stroke.

We aimed to evaluate the effects of the five main classes of antihypertensive agents on the long-term outcome of 313 consecutive patients discharged after acute ischemic stroke (36.4% males, age 78.5 ± 6.3 years). One year after discharge, the functional status [evaluated with the modified Rankin scale (mRS)], the occurrence of cardiovascular events, and vital status were recorded. Patients prescribed angiotensin receptor blockers (ARBs) had lower mRS than patients not prescribed ARBs (1.7 ± 2.0 vs. 2.9 ± 2.5, respectively; p = 0.006). The rates of adverse outcome (mRS 2-6) and cardiovascular events did not differ between patients prescribed each one of the major classes of antihypertensive agents and those not prescribed the respective class. Patients who were prescribed ARBs had lower risk of death during follow-up than patients who did not receive ARBs (9.4 and 26.9%, respectively; p < 0.05). In binary logistic regression analysis, the only independent predictor of all-cause mortality during follow-up was the mRS at discharge (relative risk 1.69, 95% confidence interval 1.25-2.28; p < 0.001). In conclusion, in patients discharged after acute ischemic stroke, administration of ARBs appears to have a more beneficial effect on long-term functional outcome and all-cause mortality than treatment with other classes of antihypertensive agents.

[Clinical evaluation of the effectiveness of cholinesterase inhibition with neuromidin in the treatment of primary glaucoma patients]. / Klinicheskaia otsenka éffektivnosti ingibitora kholinésterazy neĭromedina v lechenii bol'nykh s pervichnoĭ glaukomoĭ.

AIM: to investigate neuromidin effectiveness in the treatment of patients with primary glaucoma and compensated intraocular pressure (IOP). MATERIAL AND METHODS: A total of 40 patients (80 eyes) were examined. Of them, 10 eyes with early glaucoma, 36 eyes with moderate-stage glaucoma, 33 eyes with advanced glaucoma, and 1 eye with end-stage glaucoma. In 19 eyes, IOP was controlled through beta-blockers, in 11 eyes - through carbonic anhydrase inhibitors, in 10 eyes - through prostaglandin analogues, and in 39 eyes - through combination drugs. Twenty-six eyes had received glaucoma surgery some time earlier. Ipidacrine was prescribed in tablets at 20 mg 2 times daily for 25 days. Treatment effectiveness was judged by visual functions, hydrodynamics, and morphometric parameters of the optic disc. RESULTS: In moderate-stage eyes, visual acuity improved in 66.6% of cases and remained unchanged in 33.3%. In advanced-stage eyes, visual acuity improved in 51.5% of cases and remained unchanged in 48.5%. Visual field broadened in all cases. Moreover, under the neuromidin therapy, the number of scotomas in early-stage eyes decreased, while the number of areas with normal sensitivity of the retina increased by 14.9%. In advanced-stage glaucoma, the effect was less pronounced: the number of type 1 and type 2 scotomas decreased by 3.0±0.6% and 2.9±0.8%, respectively; the number of absolute scotomas did not change; the number of areas with normal sensitivity of the retina increased by 7.4±2.0%. Also, P0 was found to be reduced and intraocular fluid outflow - activated. In early and moderate glaucoma, there was a significant reduction in the cup area as well as an increase in the neuroretinal rim area and retinal nerve fiber layer thickness. In advanced-stage cases, it was only the retinal nerve fiber layer thickness that changed. CONCLUSION: Neuromidin has a positive impact on visual function, hydrodynamics, and morphometric parameters of the optic disc.

Hypertension, use of antihypertensive medications, and risk of epithelial ovarian cancer.

Few studies have examined the associations of hypertension and antihypertensive medications with ovarian cancer. In particular, beta-blockers, one of the most commonly prescribed medications to treat hypertension, may reduce ovarian cancer risk by inhibiting beta-adrenergic signaling. We prospectively followed 90,384 women in the Nurses' Health Study (NHS) between 1988-2012 and 113,121 NHSII participants between 1989-2011. Hypertension and use of antihypertensive medications were self-reported biennially. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 948 ovarian cancer cases during follow-up. Similar results were observed in the two cohorts. While hypertension was not associated with ovarian cancer risk (Pooled HR = 1.01; 95% CI = 0.88, 1.16), current use of any antihypertensive medication was associated with slightly increased risk compared to never users (Pooled HR = 1.18; 95% CI: 1.02, 1.37). This increased risk was primarily due to use of thiazide diuretics (Pooled HR = 1.37; 95% CI: 1.13, 1.68). No associations were observed for beta-blockers or angiotensin-converting-enzyme inhibitors. Calcium channel blockers (CCBs) were associated with suggestively reduced risk (NHS HR = 0.73; 95% CI: 0.53, 1.01), after adjusting for all antihypertensive medications. Associations were similar among hypertensive women and stronger for longer use of thiazide diuretics and CCBs. In conclusion, our results provided no evidence that beta-blockers were associated with reduced ovarian cancer risk. In contrast, we observed an increased risk for use of thiazide diuretics that should be confirmed in other studies.