Renin-angiotensin Research Articles

Asymptomatic hyperuricemia: to treat or not a threat? A clinical and evidence-based approach to the management of hyperuricemia in the context of cardiovascular diseases.

Asymptomatic hyperuricemia is defined by serum uric acid levels above 6.2 mg/dl in women and 7 mg/dl in men. In the presence of monosodium urate crystal formation and articular inflammation, hyperuricemia may become symptomatic (namely nephrolithiasis and gout). Uric acid results from purine catabolism and is at the centre of a complex metabolic interplay that involves oxidative stress, inflammation, renin-angiotensin-aldosterone system (RAAS) activation and insulin resistance. Uric acid levels present a continuous relation with conditions like hypertension and chronic kidney disease (CKD) and are reported to have an impact on risk of cardiovascular events. However, whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain and matter of further investigation. Treating symptomatic hyperuricemia involves lowering uric acid drugs and controlling inflammation. Urate-lowering agents are well tolerated but show minimal impact on cardiovascular events in patients with gout. Use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, whereas addressing cardiovascular issues with guideline-recommended therapies lowers uric acid and reduces the occurrence of cardiovascular events. Regular assessment of uric acid and clinical symptoms is advised before starting and renewing a urate-lowering treatment.

The Combination of Valsartan and Spironolactone Mitigated Mitral Regurgitation-Induced Cardiac Dysfunction in a Novel Rat Model.

Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin-aldosterone system inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction, its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/d), spironolactone (80 mg/kg/d), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared with that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced heart failure.

Fat Embolism Does Not Alter Cardiac Structure or Induce Pathological Changes in a Rat Model

IntroductionFat embolism (FE) encompasses conditions in which fatty substance becomes embedded in a tissue/organ. Fat emboli most commonly affect the lungs in a trauma setting. This can lead to both significant pathology locally and systemically including changes in structure, inflammatory response, activation of the renin-angiotensin system, and subsequent hypoxia. In fact, changes in skin, brain, lungs, and kidneys have been noted in FE syndrome. Because there is an extensive record of pathology reports on this condition without evidence of direct cardiac involvement, as well as our studies showing apparent complete recovery after the acute embolism, we hypothesized that structural changes similar to the lung and at the same time course would not be observed in the heart. MethodsWe used a rat model of FE previously described by our group where we have documented significant lung pathology. In this study, we analyzed both pulmonary and cardiac structure, histology, and gene expression at 48 h and 10 wks post fat injection to mimic FE. ResultsDespite severe inflammatory evidence and structural changes to the lung and vasculature up to 10 wks after FE, we found no significant alterations to cardiovascular morphometry including lumen patency ratio, adventitia/media ratio, fibrosis content, and heart chamber/wall dimensions in stained histological sections. Additionally, genetic markers of cardiac pathological hypertrophy were not significantly elevated 48 h or 10 wks after fat treatment. Oil Red O staining showed increased fat droplet content within lung and aorta tissue, but not in the myocardium. ConclusionsOur study suggests that, in contrast to the lungs, the heart is more resistant to the inflammatory and remodeling responses that result from FE, possibly due to the organ-specific differences in fat retention.

Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy

IntroductionEndothelin A (ETA) receptor activation is a driver of proteinuria, kidney inflammation and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ETA receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss. MethodsEligibility criteria for the ALIGN main stratum included patients with biopsy-proven IgAN, total protein excretion ≥1g/d, eGFR ≥30 mL/min/1.73m2, receiving a maximally-tolerated stable dose of a renin-angiotensin system inhibitor (RASi). An exploratory stratum enrolled participants also receiving a stable dose of sodium glucose cotransporter-2 inhibitors (SGLT2i). Participants were randomized to 0.75 mg atrasentan or placebo orally daily for 132 weeks followed by a 4-week wash-out period. The primary outcome is proteinuria change from baseline (24h urine protein–creatinine ratio UPCR) to Week 36 in the main stratum. Key secondary endpoints include eGFR change from baseline to Week 136, safety and tolerability. ResultsEnrolment occurred across 20 countries; 404 patients are randomized: 340 in the main stratum and 64 in the SGLT2i stratum. At baseline in the main stratum, mean age was 44.7 years, 42.4% were female, mean eGFR and median UPCR were 58.9 mL/min/1.73 m2 and 1.4 g/g, respectively. ConclusionThe ongoing ALIGN trial evaluates the efficacy and safety of atrasentan in a representative global IgAN population at risk for disease progression despite optimized RASi therapy and includes an exploratory stratum evaluating atrasentan use in combination with an SGLT2i.

Effect of Cessation of Renin-Angiotensin System Inhibitors on Clinical Outcomes in AKI

Effect of Cessation of Renin-Angiotensin System Inhibitors on Clinical Outcomes in AKI

Impact of Age on Prescribing Patterns of Cardiovascular Medications in Older Japanese Patients with Non-Dialysis-Dependent Chronic Kidney Disease: A Cross-Sectional Study.

Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population. Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group. Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates. This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study.Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3–10. AT1 antagonist losartan or water was given orally postnatal days 8–10. Blood pressure, autonomic function, left ventricular sympathetic innervation, β-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats.Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased β1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in β1-adrenergic-receptor expression.In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

Digoxin Discontinuation in Patients with HFrEF on Beta-Blockers: Implication for Future “Knock-Out Trials” in Heart Failure

Background: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers. Methods: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated. Results: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85–1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85–1.25) or death (HR, 0.91; 95% CI, 0.72–1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25–2.04), 1.62 (1.18–2.22) and 1.43 (1.08–1.89). Conclusions: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy.

Decrease of Prolylcarboxypeptidase Dose of Aqueous Humor is Involved in the Pathogenesis of Primary Open-Angle Glaucoma via Finetuning of the Local Ocular Renin-Angiotensin System.

In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients. Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson' staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor. PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins. Our study found PRCP dose was decreased in POAG patients' aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

Vitamin D's Role in Cardiovascular Diseases.

This article explores the correlation between vitamin D levels and cardiovascular health, focusing on hypertension, atherosclerosis, and cardiac dysfunction. Cardiovascular diseases (CVDs) rank as the leading global cause of death, underscoring the significance of exploring vitamin D's potential role in maintaining a healthy cardiovascular system. It discusses vitamin D's mechanisms of action, including genomic and non-genomic pathways, and explores risk factors like smoking, obesity, and hypertension, linked to vitamin D deficiency. Additionally, it delves into its role in regulating the renin-angiotensin system, cardiac hypertrophy, and inflammation. The link between vitamin D supplementation and a lower risk of cardiovascular events, including hypertension, atherosclerosis, and heart failure, is considered. However, inconsistent results from supplementation trials call for further research to establish efficacy for cardiovascular health. In conclusion, the article emphasizes the importance of vitamin D for cardiovascular well-being and calls for comprehensive studies to explore its therapeutic potential in treating cardiovascular disease (CVD).

Kidney and Mortality Outcomes on Renin-Angiotensin System Inhibitors in Nonproteinuric CKD: Findings from the CRIC Study

Kidney and Mortality Outcomes on Renin-Angiotensin System Inhibitors in Nonproteinuric CKD: Findings from the CRIC Study

Hypertension and Left Ventricular Strain in Pediatric Chronic Kidney Disease.

Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited. Our objective was to describe LV GLS in the CKiD study (Chronic Kidney Disease in Children) and to examine the association between blood pressure (BP) and reduced LV GLS. A single apical 4-chamber view was used to estimate LV GLS. Our main analyses examined the association of clinic BP with the absolute value of LV GLS and LV GLS dichotomized at 16. Sensitivity analyses using 24-hour ambulatory BP monitoring data were also performed. Generalized estimating equations were used to account for within-person correlation and to estimate robust SEs for 95% CIs. Covariates in adjusted models included: age, sex, race, estimated glomerular filtration rate, urine protein, hemoglobin, left ventricular hypertrophy, and the use of renin-angiotensin system inhibitors. LV GLS was measured in 962 person-visits. A total of 77 assessments had an LV GLS <16. In adjusted models, both clinic systolic BP (odds ratio, 1.02 [95% CI, 1.01-1.03]) and diastolic BP (odds ratio, 1.02 [95% CI, 1.00-1.03]) percentiles were associated with LV GLS <16. Having awake or nighttime diastolic BP hypertension on ambulatory BP monitoring was significantly associated with a lower absolute value of LV GLS. Office systolic and diastolic hypertension was associated with diminished LV GLS. Only diastolic hypertension detected on ambulatory BP monitoring was associated with lower LV GLS.

Cardiac Effects of Renin-Angiotensin System Inhibitors in Nonproteinuric CKD.

In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications. Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up. A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86]). Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management.

Effects of a Low-Protein Diet in Patients with CKD Taking Renin-Angiotensin System Inhibitors: A Post Hoc Subanalysis of the RICE Study

Effects of a Low-Protein Diet in Patients with CKD Taking Renin-Angiotensin System Inhibitors: A Post Hoc Subanalysis of the RICE Study

Use of cardiac biomarkers to improve initiation of cardioprotective therapy in patients with breast cancer receiving cardiotoxic chemotherapy in a multidisciplinary cancer center.

344 Background: Treatment for breast cancer commonly includes anthracyclines and anti-Her2 directed therapy, both of which carry a known cardiovascular risk. In high-risk patients, ESMO guidelines recommend consideration of cardiac biomarker (hs-cardiac troponin) testing for patients undergoing potentially cardiotoxic chemotherapy. Prophylactic use of cardioprotective medications such as angiotensin converting enzyme (ACE) inhibitors, angiotensin renin blockers (ARBs) or beta-blockers (BBs) can be considered to reduce development of cardiotoxicity. We aimed to identify the rates of cardiac biomarker testing performed and rates of abnormalities in patients considered to be high risk for cardiovascular disease undergoing breast cancer treatment with potentially cardiotoxic medication in hope of improving prevention efforts. Methods: We performed a retrospective chart review of patients with breast cancer treated with either anthracycline or anti-Her2 based therapy at our ambulatory cancer center from 2020 to 2023. Pre-treatment cardiovascular risk score was determined based on initial cardiac assessment at time of consultation with cardio-oncology. Completion of troponin biomarker testing and initiation of cardioprotective medication therapy was assessed. Patients who were not established with cardio-oncology or not on active cardiotoxic chemotherapy were excluded. Results: A total of 172 patients (66 on anthracycline based therapy and 106 on anti-HER2 therapy) were assessed. The average age of all patients was 57 years. 47 patients were assessed as high risk for cardiovascular disease. Of these high-risk patients, troponin was checked in 42 of 47 (89.4%) and found to be elevated in 23 of 42 (55%). Rate of troponin elevation was statistically significant for high risk patients compared to all other patients (p&lt;0.05). Cardioprotective medications were utilized in 28 of the 47 patients considered to be high risk (59.6%). Conclusions: In patients with breast cancer who require treatment with a potentially cardiotoxic medication, a clinical risk assessment with cardiology can be utilized to select those who may benefit from additional cardiac biomarker monitoring and potential earlier initiation of cardioprotective therapy. This single center study reveals that the use of clinical assessment of high vs low/medium risk allows us to predict patients with increased risk of cardiotoxicity. Our population had cardiac biomarkers checked in nearly all high-risk patients and troponin was elevated 55% of the time. Further study is needed to investigate if biomarker directed initiation of cardio-protective therapy could reduce cardio-toxicity.

A multi-docking strategy for robotic LAR and deep pelvic surgery with the Hugo RAS system: experience from a tertiary referral center.

In June 2023, our institution adopted the Medtronic Hugo RAS system for colorectal procedures. This system's independent robotic arms enable personalized docking configurations. This study presents our refined multi-docking strategy for robotic low anterior resection (LAR) and deep pelvic procedures, designed to maximize the Hugo RAS system's potential in rectal surgery, and evaluates the associated learning curve. This retrospective analysis included 31 robotic LAR procedures performed with the Hugo RAS system using our novel multi-docking strategy. Docking times were the primary outcome. The Mann-Kendall test, Spearman's correlation, and cumulative sum (CUSUM) analysis were used to assess the learning curve and efficiency gains associated with the strategy. Docking times showed a significant negative trend (p < 0.01), indicating improved efficiency with experience. CUSUM analysis confirmed a distinct learning curve, with proficiency achieved around the 15th procedure. The median docking time was 6min, comparable to other robotic platforms after proficiency. This study demonstrates the feasibility and effectiveness of a multi-docking strategy in robotic LAR using the Hugo RAS system. Our personalized approach, capitalizing on the system's unique features, resulted in efficient docking times and streamlined surgical workflow. This approach may be particularly beneficial for surgeons transitioning from laparoscopic to robotic surgery, facilitating a smoother adoption of the new technology. Further research is needed to validate the generalizability of these findings across different surgical settings and experience levels.

Successful treatment of severe renal failure caused by malignant hypertension using a combination of renin-angiotensin-aldosterone system inhibitors: a case report.

Marked activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in malignant hypertension (MHT) by worsening hypertension and renal function. The rates of readmission for severe hypertension and cardiovascular disease in such emergencies are high, suggesting that suppression of the RAAS may be inadequate during the acute phase in some cases. This report presents a case of MHT complicated with renal insufficiency (creatinine 3.93mg/dL) and massive proteinuria, in which antihypertensive therapy, including an angiotensin receptor blocker, aliskiren, and spironolactone, normalized blood pressure (BP) and preserved renal function. Plasma renin activity was extremely high (131.9ng/mL/h) on admission but normalized within almost 2weeks. Although aliskiren and spironolactone were discontinued before discharge, BP was well controlled and renal function was further improved (creatinine 1.14mg/dL) at follow-up 24months later. This case of renal failure induced by MHT was successfully treated with a combination of RAAS inhibitors during the acute phase. The controlled BP and improved renal function in this patient suggest that adequate suppression of the RAAS cascade during the acute phase is potentially effective in terms of breaking the vicious cycle of MHT with hyperreninemia.

Renin-angiotensin blockade ameliorates the progression of glomerular injury in podocyte-specific Ctcf knockout mice.

Several studies have shown that the progression of proteinuria and renal tissue injury is associated with activation of the intrarenal renin-angiotensin system (RAS). CCCTC-binding factor (CTCF) is a DNA-binding factor that plays an essential role in the regulation of gene expression. In the present study, we aimed to investigate the phenotypic effects of CTCF deficiency in podocytes. Angiotensin II type 1 receptor blockers (ARBs) were administered to the podocyte-specific Ctcf knockout mice, and histological and biochemical analyzes were performed. We also investigated the changes in the expression of podocin in podocyte cell cultures with or without stimulation with angiotensin II from glomeruli isolated using magnetic beads from podocyte-specific Ctcf knockout mice. Mice in which Ctcf was deleted from podocytes developed glomerulopathy and mice developed severe progressive proteinuria, and impaired renal function. Moreover, ARBs suppressed the development of glomerulopathy in podocyte-specific Ctcf knockout mice. Both real-time polymerase chain reaction and western blotting showed that podocin expression was decreased in cell cultures stimulated with angiotensin II. Furthermore, RAS components gene expressions in podocyte cell cultures isolated from podocyte-specific Ctcf knockout mice were significantly increased. These results suggest that RAS is involved in the development of glomerulopathy in podocyte-specific Ctcf knockout mice. Elucidation of the pathophysiology of podocyte-specific Ctcf knockout mice may provide new insights into the relationship between podocyte injury and chronic glomerulonephritis.

IMPACT OF ANTIHYPERTENSIVE DRUGS ON C REACTIVE PROTEIN (HS-CRP) AND NEUTROPHIL LYMPHOCYTE RATIO (NLR)

Many studies showed the association between inflammation and Hypertension. Inflammatory markers may highlight the state of inflammation in hypertensive patients. This study aimed to investigate impact of antihypertensive drugs on high sensitive C-reactive protein (hsCRP) and neutrophil lymphocyte ratio (NLR). A comparative cross sectional study was conducted on 86 hypertensive patients attending cardiology outpatient clinic in Al-Gamhuoria Modern General Hospital, Aden, in the period from October to December 2023. Participants were divided into three groups: patients treated with mono-therapy from inhibitors of renin angiotensin aldosterone system (RAASI), patients treated with mono-therapy antihypertensive not acting on RAAS (NRAASI) and patients treed with combination of them (drug combination). Data on Age, Sex, BP level, BMI, duration of hypertension (HTN), family history of HTN, and medications used were collected. Blood samples for measuring HsCRP, neutrophils, lymphocytes were drawn. Descriptive statics and chi-square tests were used for data analysis. Almost equivalent distribution for males and females between groups, with a large proportion of the patients within each group laid in the age group 35-55 years. The median values of hypertension duration were 36, 48, and 54 months for RAASIs, NRAASIs and drug combination group, respectively. The target BP was obtained by 46.9% 45.5% and 50% of patients treated with RAASIs, NRAASIs and drug combination respectively. There was a statistically significant difference between SBP and DBP in patients with controlled BP and those with uncontrolled SBP levels and treated by different drug regimens (P=0.000 for each Bp level). There were significant differences between values of hs-CRP of patients with controlled (P=0.000) or uncontrolled (P=0.046) BP and treated with different modalities. The median differences in NLR between the groups were statistically significant; including groups of all patients P=.032, of patients having controlled BP P=0.014 as well as uncontrolled BP P=0.038. Comparing the uncontrolled of BP of the three groups we found the highest prevalence (9.3%)of patients with uncontrolled BP and had the lower level hsCRP (≤3mg /l) was in RAASIs group, while those with higher prevalence (11.6%) of uncontrolled BP and higher level of hs-CRP ( &gt;3mg/l) was in drug combination group. In conclusion, hypertensive patients treated with RAASI, NRAASI and drug combination and reached BP target showed significant reduction in hsCRP and NLR. Patients with uncontrolled BP treated with RAASIs revealed slightly lower hs-CRP than other groups. Careful selection of antihypertensive drugs may affect risks of CVD. This study recommends further prospective studies exploring the anti-inflammatory effect of antihypertensive drugs to ameliorate possible risks of cardiovascular disease.

Comparative evaluation of serum apelin, visfatin, and lipid levels in overweight hypertensive patients on enalapril versus telmisartan therapy

Objectives. Visfatin and apelin are two adipokines that recently gained a special interest in hypertension research as they may have a role in the pathogenesis of hypertension and are closely related to the renin-angiotensin system. This study aimed to evaluate the serum levels of apelin and visfatin in uncontrolled newly diagnosed hypertensive patients, controlled hypertensive patients managed by enalapril and controlled hypertensive patients managed by telmisartan. Patients and methods. The study population included 126 participants, who were divided into four groups established as healthy participants, newly diagnosed hypertensive patients, hypertensive patients managed by enalapril and hypertensive patients managed by telmisartan. Outcomes. Serum apelin levels reduced significantly in newly diagnosed hypertensive patients, with a significant increase in visfatin levels compared with control group. Enalapril-treated patients expressed significantly higher apelin levels with a significant reduction in visfatin levels compared with newly diagnosed. Apelin levels were significantly increased in enalapril-treated patients compared telmisartan-treated group. Additionally, a significant reduction in visfatin levels were found in telmisartan group compared with newly diagnosed hypertensive patients. Moreover, a significant positive correlation was found between HDL and visfatin in patients receiving treatment. Additionally, visfatin was negatively correlated with triglycerides and VLDL in the same patient group. Conclusions. In light of the data collected so far, whether visfatin and apelin play roles in the pathophysiology of hypertension remains unclear and further research is still required to fully understand its relevance. Nevertheless, high visfatin and low apelin levels appear to be intrinsic characteristics of uncontrolled hypertension, indicating that these adipokines could be potential biomarkers for this disease.